HYDROGEL SILICONE LENSES WITH WATER RICH SURFACES

专利摘要:
silicone hydrogel lenses with water-rich surfaces the present invention relates to a hydrated silicone hydrogel contact lens having a layered structural configuration: a silicone hydrogel core with low water content (or bulk material) completely covered by a layer of water-rich hydrogel (for example, a water content greater than 80%), totally or substantially free of silicone. a hydrated hydrogel silicone contact lens of the invention has high oxygen permeability to maintain corneal health and a lubricated surface, rich in water and soft to offer comfort during use.
公开号:BR112013002179B1
申请号:R112013002179-9
申请日:2011-07-29
公开日:2020-12-15
发明作者:Yongxing Qiu；John Dallas Pruitt；Sibichen Thekveli；Robert Carey Tucker；Jared Nelson
申请人:Alcon Inc；
IPC主号:

专利说明:

[1] The present invention relates, in general, to an ophthalmic device, especially a silicone hydrogel contact lens that has a structural lens configuration that creates a water content gradient and comprises: a volumetric silicone hydrogel material which has a water content (called WCSiHy) from about 10% to about 70% by weight and an outer surface layer that has a thickness of about 0.1 to about 20 μm and completely covers the material volumetric silicone hydrogel and is produced from a hydrogel material that is totally or substantially silicone-free and has a higher water content characterized by a water expansion ratio of at least about 100% if WCSiHy = 45% or by a ratio of water expansion of at least about [120 • WCSiHy / (1-WCSffly)]% s and WCSiHy> 45%, as measured by AFM with a cross section of the silicone hydrogel contact lens in full state hydrated. BACKGROUND
[2] Silicone hydrogel (SiHy) contact lenses are widely used to correct many different types of visual impairments. They are produced from a hydrated cross-linked polymeric material that contains silicone and a certain amount of water within the equilibrium lens polymer matrix. According to the FDA classification for a contact lens, hydrogel contact lenses are generally classified into two main categories: low water contact lenses (which contain less than 50% water) and lenses high water content (containing more than 50% water). For SiHy contact lenses, the high oxygen permeability, which is necessary for a contact lens to have minimal adverse effects on corneal health, is achieved by incorporating silicone, and not by increasing the water content, in the material cross-linked polymeric. As a result, unlike conventional hydrogel contact lenses, SiHy contact lenses can have a low water content and, at the same time, have a relatively high oxygen permeability (Dk), for example, Focus®Night & Day® from CIBA Vision Corporation (approximately 23.5% H2O and Dk ~ 10.50E-16 m2 / s Pa (140 Barrers); Air Optix® from CIBA Vision Corporation (approximately 33% H2O and Dk ~ 110 Barrers) ); Bausch & Lomb PureVision® (approximately 36% H2O and Dk ~ 100 Barrers); Johnson & Johnson Acuvue®Oasys® (approximately 38% H2O, Dk ~ 7.88E-16 m2 / s Pa (105 Barrers )); Johnson & Johnson's Acuvue® Advance® (approximately 47% H2O, Dk ~ 65 Barrers); Johnson & Johnson's Acuvue®TruEye® (approximately 46% H2O, Dk ~ 100 Barrers); CooperVision Biofinity® ( approximately 48% H2O, Dk ~ 128 Barrers); Avaira® by CooperVision (approximately 46% H2O, Dk ~ 7.50E-16 m2 / s Pa (100 Barrers)); and PremiOTMda Menicon (approximately 40% d and H2O, Dk ~ 129 Barrers).
[3] The water in a SiHy contact lens can provide the desired softness that allows a SiHy lens to be used for sufficiently long periods of time and gives patients benefits that include adequate initial comfort (that is, immediately after placement) lens), relatively short adaptation time necessary for the patient to get used to them and / or appropriate fit. A higher water content would be desirable to give SiHy contact lenses biocompatibility and comfort. However, there is a limit to the amount of water (believed to be 80%) that a SiHy contact lens can contain and, at the same time, still have the sufficient mechanical strength and stiffness required for a contact lens , such as conventional hydrogel contact lenses. In addition, a high water content could also have unintended consequences. For example, the oxygen permeability of a SiHy contact lens can be compromised by increasing the water content. In addition, a high water content in a SiHy lens could result in greater dehydration in the eye and, consequently, discomfort in use induced by dehydration, since a SiHy contact lens with a high water content can deplete the supply of tears (water) limited from the eye. It is believed that dehydration in the eye can be derived from evaporation (ie, water loss) on the anterior surface of the contact lens and such water loss is mainly controlled by the diffusion of water through a lens from the posterior surface to the anterior surface and that the diffusion rate is strictly proportional to the water content of the volumetric material of the balanced lens (L. Jones et al., Contact Lens & Anterior Eye 25 (2002) 147156, incorporated herein by reference in its entirety).
[4] The incorporation of silicone in a contact lens material also has undesirable effects on the biocompatibility of the contact lens, since the silicone is hydrophobic and has a great tendency to migrate to the surface of the lens that is exposed to air . As a result, a SiHy contact lens, in general, will require a surface modification process to eliminate or minimize the exposure of the contact lens silicone and maintain a hydrophilic surface including, for example, various plasma treatments (for example , Focus®Night & Day®and Air Optix® by CIBA Vision Corporation; PureVision® by Bausch &Lomb; and PremiO® by Menicon); internal wetting agents physically and / or chemically incorporated into the polymeric matrix of SiHy (eg Acuvue®Oasys®, Acuvue®Advance® and Acuvue®TruEye® from Johnson &Johnson; Biofinity® and Avaira® from CooperVision). Although the surface modification techniques used in the production of a commercial SiHy lens may offer new (unused) SiHy lenses with suitably hydrophilic surfaces, SiHy lenses used in the eye may have dry spots and / or hydrophobic surface areas created in due to exposure to air, shear forces of the eyelids, migration of silicone and / or a partial failure to avoid exposure of the silicone. These dry spots and / or hydrophobic surface areas are not humectable and are susceptible to adsorbing lipids or proteins from the eye environment and can adhere to the eye, causing discomfort to the patient.
[5] Therefore, SiHy contact lenses with hydrophilic surfaces that have persistent hydrophilicity, wetting capacity and lubricity that can be maintained in the eye all day long are still needed. SUMMARY OF THE INVENTION
[6] The present invention can satisfy the needs of SiHy contact lenses that have hydrophilic surfaces with surface hydrophilicity, surface wetting capacity and surface lubricity persistent in the eye all day.
[7] In one aspect, the invention offers a hydrated hydrogel silicone contact lens comprising: an opposing anterior (convex) surface and a posterior (concave) surface; and a layered structural configuration from the front surface to the rear surface, wherein the layered structural configuration includes an outer hydrogel outer layer, an inner layer of a hydrogel silicone material and an outer hydrogel back layer, wherein the hydrogel silicone material has an oxygen permeability (Dk) of at least about 50, preferably at least about 60, more preferably at least about 70, even more preferably at least about 6.75E-16 m2 / s Pa (90 barrers), even more preferably at least about 110 Barrers, and a first water content (called WCSiHy) from about 10% to about 70%, preferably from about 10% to about 65%, more preferably from about 10% to about 60%, even more preferably from about 15% to about 55%, even more preferably from about 15% to about 50 % by weight, where the cam external front and rear hydrogel layers have a substantially uniform thickness and merge at the peripheral edge of the contact lens to completely surround the inner layer of the hydrogel silicone material, with the outer front and rear hydrogel layers having, independently of each other , a second water content greater than WCSiHy, as defined by having a swelling ratio in water (referred to as WSR) of at least about 100% (preferably at least about 150%, more preferably at least about 200% , even more preferably at least about 250%, even more preferably at least about 300%) if WCsiHy <45%, or because it has a water expansion ratio of at least about [120 • WCSiHy / (1-WCSiHy )]% (preferably [130 • WCSiHy / (1-WCSiHy)]%, more preferably [140 • WCSiHy / (1-WCSiHy)]%, even more preferably [150 • WCSiHy / (1-WCSiHy)]%) if WC> 45%, where the thickness of each of the front and rear outer layers of hydrogel ranges from about 0.1 μm to about 20 μm, preferably from about 0.25 μm to about 15 μm, more preferably from about 0.5 μm to about 12.5 μm, even more preferably from about 1 μm to about 10 μm (as measured with atomic force microscopy through a cross section from the posterior surface to the anterior surface of the hydrogel silicone contact lens in the fully hydrated state).
[8] In another aspect, the invention offers a hydrated silicone hydrogel contact lens. A hydrated silicone hydrogel contact lens of the invention comprises: a silicone hydrogel material as a volumetric material, an opposing front and rear surface; including and next contact lens has an oxygen transmissibility of at least about 40, preferably at least about 60, more preferably at least about 80, even more preferably at least about 110 barrers / mm and a module profile cross-sectional surface which comprises, along the shortest line between the anterior and posterior surfaces on the surface of a cross-section of the contact lens, an anterior outer zone including and close to the anterior surface, an inner zone including and around from the center of the shorter line and a posterior outer zone including and close to the posterior surface, where the anterior outer zone has a medium anterior surface module (designated SM ^ t), while the posterior outer area has a posterior surface module medium (called SMPost), in which the inner zone has an average internal surface module (called SM ^ o), in which at least one
it is at least about 20%, preferably at least about 25%, more preferably at least about 30%, even more preferably at least about 35%, even more preferably at least about 40%.
[9] In another aspect, the invention offers a hydrated silicone hydrogel contact lens. A hydrated silicone hydrogel contact lens of the invention comprises: a silicone hydrogel material as a volumetric material, an opposing front and rear surface; where the contact lens has (1) an oxygen transmissibility of at least about 40, preferably at least about 60, more preferably at least about 80, even more preferably at least about 110 barrers / mm, and ( 2) a surface lubricity characterized by having a critical friction coefficient (designated as CCOF) of about 0.046 or less, preferably about 0.043 or less, more preferably about 0.040 or less, where the front and rear surfaces have a low concentration on the surface of negatively charged groups, including carboxylic acid groups, as characterized by an attraction of at most about 200, preferably at most about 160, more preferably at most about 120, even more preferably at most about 90, even more preferably at most about 60 positively charged particles in the positively charged particle adhesion test.
[10] These and other aspects of the invention, including various preferred embodiments in any combination, will become apparent from the following description of presently preferred embodiments. The detailed description is merely illustrative of the invention and does not limit the scope of the invention, which is defined by the appended and equivalent claims thereof. As will be obvious to those skilled in the art, many variations and modifications of the invention can be made without departing from the spirit and scope of the innovative concepts of the invention. BRIEF DESCRIPTION OF THE DRAWINGS
[11] Figure 1 schematically represents a sectional view of the structural configuration of a SiHy contact lens according to a preferred embodiment of the invention.
[12] Figure 2 schematically represents a sectional view of the structural configuration of a SiHy contact lens according to another preferred embodiment of the invention.
[13] Figure 3 shows the fluorescence intensity profiles through the cross sections of a SiHy contact lens in a confocal laser fluorescence microscopy.
[14] Figure 4 shows SEM (electronic scanning microscopy) images of a SiHy contact lens of the invention in a lyophilized state.
[15] Figure 5 schematically illustrates the configuration of the inclined plate method according to a preferred embodiment.
[16] Figure 6 shows optical microscopy images of contact lenses that have different coatings on them after being immersed in a dispersion of positively charged particles (DOWEX®1x4 resins of 20-50 mesh).
[17] Figure 7 illustrates schematically how to mount vertically, on a metal clamp, a piece of the cross section of a SiHy contact lens of the invention for AFM testing.
[18] Figure 8 shows the AFM (atomic force microscopy) image of a portion of a cross section of a SiHy contact lens in the fully hydrated state (in phosphate buffered saline, pH ~ 7.3). according to a preferred embodiment of the invention.
[19] Figure 9 shows a profile of the cross-sectional surface module of a SiHy contact lens of the invention in the fully hydrated state (in phosphate buffered saline, pH ~ 7.3) along two shorter lines between the anterior and posterior surfaces on the surface of a cross section of a SiHy contact lens according to a preferred embodiment of the invention, as represented approximately by the cantilever deflection plots as a function of distance. DETAILED DESCRIPTION OF MODALITIES OF THE INVENTION
[20] Reference will now be made in detail to the modalities of the invention. It will be apparent to those skilled in the art that various modifications, variations and combinations can be made to the present invention without departing from the scope or spirit of the invention. For example, features illustrated or described as part of one modality can be used in another modality to result in yet another modality. Thus, it is intended that the present invention covers such modifications, variations and combinations that are within the scope of the appended claims and their equivalents. Other objectives, characteristics and aspects of the present invention are described or will be obvious from the detailed description below. It will be understood by those skilled in the art that the present discussion is only a description of exemplary modalities, and is not intended to limit the broader aspects of the present invention.
[21] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which the present invention belongs. In general, the nomenclature used here and laboratory procedures are well known and commonly used in the art. Conventional methods are used for these procedures, such as those provided in the literature and in several general references. Where a term is provided in the singular, the inventors also consider the plural of that term. The nomenclature used here and the laboratory procedures described below are well known and commonly used in the art.
[22] As used in the present application, the term "silicone hydrogel contact lens" refers to a contact lens that comprises a silicone hydrogel material.
[23] As used in the present application, the term "hydrogel" or "hydrogel material" refers to a cross-linked polymeric material which is not water-soluble and contains at least 10% by weight of water within its polymeric matrix when fully hydrated. .
[24] As used in the present application, the term "silicone-free hydrogel" refers to a hydrogel that is theoretically silicone-free.
[25] As used in the present application, the term "silicone hydrogel" refers to a hydrogel that contains silicone. A silicone hydrogel is typically obtained by copolymerizing a polymerizable composition comprising at least one vinyl monomer containing silicone or at least one vinyl macromer containing silicone or at least one prepolymer containing silicone having ethylenically unsaturated groups.
[26] As used in this application, the term "vinyl monomer" refers to a compound that has a single ethylenically unsaturated group and can be polymerized actinically or thermally.
[27] As used in this application, the term "olefinically unsaturated group" or "ethylenically unsaturated group" is used here in a broad sense and is intended to cover all groups that contain at least one group> C = C <. Exemplary ethylenically unsaturated groups include, without limitation, (meth) acryloyl
alila, vinyl
styrene or other groups that contain C = C.
[28] As used in this application, the term "(meth) acrylamide" refers to methacrylamide and / or acrylamide.
[29] As used in this application, the term "(meth) acrylate" refers to methacrylate and / or acrylate.
[30] As used in the present application, the term "hydrophilic vinyl monomer" refers to a vinyl monomer which, as a homopolymer, typically produces a polymer that is water-soluble or can absorb at least 10 weight percent water.
[31] As used in the present application, the term "hydrophobic vinyl monomer" refers to a vinyl monomer which, as a homopolymer, typically produces a polymer that is not water-soluble and can absorb less than 10 weight percent water. .
[32] As used in the present application, the term "macromer" or "prepolymer" refers to a compound or polymer of medium and high molecular weight that contains two or more ethylenically unsaturated groups. Medium and high molecular weight typically means molecular weights greater than 700 Daltons.
[33] As used in this application, the term "crosslinker" refers to a compound that has at least two ethylenically unsaturated groups. A "crosslinking agent" refers to a crosslinker that has a molecular weight of about 700 Daltons or less.
[34] As used in the present application, the term "polymer" means a material formed by polymerizing / crosslinking one or more monomers or macromers or prepolymers.
[35] As used in this application, the term "molecular weight" of a polymeric material (including monomeric or macromeric materials) refers to the weighted average molecular weight, unless otherwise specifically noted or unless the test conditions indicate the opposite.
[36] As used in the present application, the term "amino group" refers to a primary or secondary amino group of the formula -NHR ', where R'is hydrogen or a straight or branched, unsubstituted or substituted C1-C20 alkyl group , unless otherwise specifically noted.
[37] As used in this application, the term "epichlorohydrin-functionalized polyamine" or "epichlorohydrin-functionalized polyamidoamine" refers to a polymer obtained by reacting a polyamine or polyamidoamine with epichlorohydrin to convert all or a substantial percentage of the groups polyamine amine or polyamidoamine in azetidinium groups.
[38] As used in this application, the term "OHH ^ N © azetidinium group" refers to a positively charged group of

[39] As used in this application, the term "thermally crosslinkable", in reference to a polymeric material or a functional group, means that the polymeric material or the functional group may undergo a crosslinking (or coupling) reaction with another material or functional group at a relatively high temperature (from about 40 ° C to about 140 ° C), while the material or functional group may not undergo the same cross-linking reaction (or coupling reaction) with another material or functional group at room temperature (i.e., from about 22 ° C to about 28 ° C, preferably from about 24 ° C to about 26 ° C, in particular about 25 ° C) to a detectable extent (i.e., more than about 5%) over a period of about an hour.
[40] As used in this application, the term "phosphorylcholine" refers to a Zwitterionic group of
where n is an integer from 1 to 5 and R1, R2 and R3 are, independently of one another, C1-C8 alkyl or C1-C8 hydroxyalkyl.
[41] As used in the present application, the term "reactive vinyl monomer" refers to a vinyl monomer that has a carboxyl group or an amino group (i.e., a primary or secondary amino group).
[42] As used in the present application, the term "non-reactive hydrophilic vinyl monomer" refers to a hydrophilic vinyl monomer that is free from any carboxyl group or amino group (i.e., primary or secondary amino group). A non-reactive vinyl monomer can include a tertiary or quaternary amino group.
[43] As used in the present application, the term "water-soluble", in reference to a polymer, means that the polymer can be dissolved in water to an extent sufficient to form an aqueous solution of the polymer that has a concentration of up to about 30 % by weight at room temperature (defined above).
[44] As used in this application, the term "contact angle with water" refers to an average contact angle with water (that is, contact angles measured by the sessile drop method), which is obtained by calculate the average of contact angle measurements.
[45] As used in the present application, the term "ability to remain intact", in reference to a coating on a SiHy contact lens, is intended to describe the extent to which the contact lens can be stained with Black Sudan Black in a Sudan Black staining test described in Example 1. A good ability to remain intact from the coating on a SiHy contact lens means that there is virtually no Sudan Black staining of the contact lens.
[46] As used in this application, the term "durability", in reference to a coating on a SiHy contact lens, is intended to describe that the coating on the SiHy contact lens can survive a rub test between the fingers.
[47] As used in this application, the term "survive a finger rub test" or "survive a durability test" in reference to a coating on a contact lens means that after the lens is rubbed between the fingers according to a procedure described in Example 1, the angle of contact with water on the lens rubbed between the fingers is still about 100 degrees or less, preferably about 90 degrees or less, more preferably about 80 degrees or less, even more preferably about 70 degrees or less.
[48] The intrinsic "oxygen permeability", Dk, of a material is the rate at which oxygen will pass through a material. As used in this application, the term "oxygen permeability (Dk)", in reference to a hydrogel (silicone or non-silicone) or a contact lens, means a measured oxygen permeability (Dk) which is corrected for resistance from the surface to the flow of oxygen caused by the boundary layer effect according to the procedures shown in the Examples below. Oxygen permeability is conventionally expressed in units of barrers, where "barrer" is defined as [(cm3 of oxygen) (mm) / (cm2) (sec) (mm Hg)] x 10-10.
[49] The "oxygen transmissibility", Dk / t, of a lens or material is the rate at which oxygen will pass through a specific lens or material with an average thickness of t [in units of mm] over the area that is being measured. Oxygen transmissibility is conventionally expressed in units of barrers / mm, where "barrers / mm" is defined as [(cm3 of oxygen) / (cm2) (sec) (mm Hg)] x 10-9.
[50] "Ion permeability" through a lens is correlated to the Ionoflux Diffusion Coefficient. The Ionoflux Diffusion Coefficient, D (in units of [mm2 / min]), is determined by applying Fick's law, as follows: D = - n '/ (A x dc / dx) where:
[51] n '= ion transport rate [mol / min]; A = exposed lens area [mm2]; dc = concentration difference [mol / L]; dx = lens thickness [mm].
[52] As used in this application, the term "ophthalmically compatible" refers to a material or surface of a material which can be in close contact with the eye environment for an extended period of time without significantly damaging the eye environment and without cause significant discomfort to the user.
[53] As used in this application, the term "ophthalmically safe", in relation to a packaging solution to sterilize and store contact lenses, is intended to mean that a contact lens stored in the solution is safe for placement directly into the eye. without rinsing after autoclaving and that the solution is safe and comfortable enough for daily contact with the eye via a contact lens. An ophthalmically safe packaging solution after autoclaving has a tonicity and pH that are compatible with the eye and is substantially free of ocular irritating materials or ocular cytotoxic materials in accordance with international ISO standards and United States FDA regulations.
[54] As used in this application, the term "cross section" of a SiHy contact lens refers to a section of lens obtained by cutting through the lens with a knife or cutting instrument at an angle substantially normal to any one. the front and rear surfaces of the lens. Those skilled in the art know how to cut manually (that is, cut by hand), or with a Cryosta microtome or with a vise, a contact lens to obtain a cross section of the contact lens. A cross section resulting from a contact lens can be polished using reactive ion corrosion or similar techniques.
[55] The terms "surface modulus", "surface softness", "surface elastic modulus", "Young surface modulus" or "surface compression modulus" are used interchangeably in the present application to indicate a nanomechanical properties (elastic property) which is measured by atomic force microscopy (AFM) on a material surface or a cross-section of a contact lens in the fully hydrated state (in a phosphate buffered solution, pH ~ 7.3 ± 0.2) using the contact mode, the nanoindentation method, the Peakforce QNM method or the Harmonic Force method, known to those skilled in the art. Jan Domke and Manfred Radmacher reported that the elastic properties of thin films can be measured with AMF (Langmuir 1998, 14, 3320-3325, incorporated herein by reference in full). Nanoindentation by AFM can be performed according to the experimental protocol described by González-Méijome JM, Almeida JB & Parafita MA in Microscopy: Science, Technology, Applications and Education, "Analysis of Surface Mechanical Properties of Unworn and Worn Silicone Hydrogel Contact Lenses Using Nanoindentation with AFM ", pages 554-559, A. Méndez-Vilas & J. Díaz (Eds.), Formatex Research Center, Badajoz, Spain (2010), incorporated herein by reference in its entirety. It should be noted that the surface of a cross section of a contact lens, and not the anterior or posterior surface of a contact lens (as described by González-Méijome JM, Almeida JB & Parafita MA in his article), is analyzed using nanoindentation by AFM. The nanoindentation method, the Peakforce QNM method and the Harmonic Force method are described in the article by Kim Sweers, et al. in Nanoscale Research Letters 2011, 6: 270, entitled "Nanomechanical properties of a-synuclein amiloid fibrils: a comparative study by nanoindentation, harmonic force microscopy and Peakforce QNM" (hereby incorporated by reference in its entirety). It should also be understood that when measurements of the surface elastic modulus are performed with AFM through a cross section of a SiHy contact lens fully hydrated from the anterior surface to the volumetric material or from the volumetric material to the posterior surface (or vice -verse), a surface module profile through a cross section of a contact lens can be established along the shortest line between the anterior and posterior surfaces on the surface of the contact lens cross section. It should also be understood that, as a good approximation, any experimental and directly measured quantity can be used to represent the surface module, as long as the measured quantity is proportional to the surface module.
[56] As used in the present application, the term "outer hydrogel outer layer", in reference to a SiHy contact lens of the invention, means a hydrogel layer that includes the front surface of the contact lens, is substantially thick uniform (that is, the variation in thickness is at most about 10% of the average thickness of this layer) and has an average thickness of at least about 0.1 μm. The "average thickness" of an anterior hydrogel outer layer is simply referred to as "thickness of an anterior hydrogel outer layer" in the present application.
[57] As used in the present application, the term "hydrogel back outer layer", in reference to a SiHy contact lens of the invention, means a hydrogel layer that includes the back surface of the contact lens, is substantially thick uniform (that is, the variation in thickness is at most about 10% of the average thickness of this layer) and has an average thickness of at least about 0.1 μm. The "average thickness" of a rear outer hydrogel layer is simply referred to as "thickness of a rear outer hydrogel layer" in the present application.
[58] As used in this application, the term "inner layer", in reference to a SiHy contact lens of the invention, means a layer that includes a central curved plane (which divides the contact lens into two parts, one containing the anterior surface and the other containing the posterior surface) and presents a variable thickness.
[59] As used in the present application, the terms "crosslinked coating" or "hydrogel coating" are used interchangeably to describe a crosslinked polymeric material that has a three-dimensional network that can contain water when fully hydrated. The three-dimensional network of a cross-linked polymeric material can be formed by cross-linking two or more linear or branched polymers through cross-links.
[60] As used in the present application, the term "water expansion ratio", in reference to an anterior or posterior outer hydrogel layer of a SiHy contact lens hydrogel material of the invention, means a value determined with AFM according to
where WSR is the proportion of water expansion of one of the anterior and posterior outer layers of hydrogel, Lúmida is the average thickness of this external hydrogel layer of the SiHy contact lens in the fully hydrated state measured with AFM in a cross section of the SiHy contact in the fully hydrated state (ie, in a phosphate buffered solution, pH ~ 7.3 ± 0.2) and Lseca is the average thickness of this external hydrogel layer of the SiHy contact lens in the dry state measured with AFM in a cross section of the SiHy contact lens in the dry state (dry without preserving the porosity of the hydrogel material, for example, vacuum dried) and in a substantially dry atmosphere. It is believed that the water expansion ratio of each external hydrogel layer (of a SiHy contact lens of the invention) is proportional to the water content that each external hydrogel layer has and a water expansion ratio of at least about 100% or
(whichever is greater, WCSiHy is the water content of the volumetric material (or inner layer) of silicone hydrogel material of a SiHy contact lens of the invention) and can function as a good indicator of the nature of the external hydrogel layers that they have a higher water content in relation to the whole (or inner layer) of hydrogel silicone material of a SiHy contact lens of the invention.
[61] As used in the present application, the term "reduced surface modulus", in reference to one or both of the outer and anterior hydrogel layers of a SiHy contact lens of the invention, means a value calculated on the basis of the following equation:

[62] where RSM is the reduced modulus of the posterior or anterior outer layer of hydrogel in relation to the inner layer, SM is the average surface module of the posterior or anterior outer layer of hydrogel and SMtotemo is the average surface module of the inner layer. SM and SM are obtained from a cross-sectional surface module profile of the SiHy contact lens in a fully hydrated state (measured by analyzing the mechanical properties of the surface, ie surface modules of a lens cross section contact of SiHy fully hydrated using AFM), as described above. It is expected that the cross sectional surface module profile (ie, a graph of the surface module as a function of the distance from one of the anterior and posterior surfaces to the other surface along the shortest line between the anterior and posterior surfaces on the surface of a cross section of a SiHy lens in a fully hydrated state) has at least two outer zones (one including the front surface and the other including the back surface) and an inner zone (which corresponds to the volumetric silicone hydrogel material) . The average surface modulus for the outer zone (ie, the outer hydrogel layer) is obtained by averaging all surface modules in the outer zone, excluding a region of about 1 to about 2 microns between the zone outer and inner zone (ie, in and / or close to the border or transition zone).
[63] A "critical friction coefficient" is the tangent of the critical angle which is the most inclined angle of an inclined plate in which a lens begins to slide over the inclined plate after being pushed, but stops, or takes more than 10 seconds, before reaching the end. The procedures for determining the critical friction coefficient (CCOF) are described in Example 29. The critical friction coefficient (CCOF) of a contact lens is believed to correlate with the surface lubricity of this contact lens and can be used to quantify the surface lubricity of a contact lens.
[64] As used in the present application, the "positively charged particle adhesion test" refers to a test to characterize the surface concentration of negatively charged groups (eg, carboxylic acid groups) of a hydrated SiHy contact lens . The adhesion test of positively charged particles is carried out as follows. An aqueous dispersion of DOWEX® 1x4 resins 20-50 mesh, which are strong basic spherical resins of type I (styrene / divinylbenzene copolymers containing N + (CH3) 3Cl-and 4% divinylbenzene functional groups) is prepared by dispersing a given quantity of DOWEX® 1x4 resins 20-50 mesh in a phosphate-buffered saline solution (pH ~ 7.3) to have a resin concentration of 5% by weight and then mix well by shaking or shaking or vortexing at approximately 1000 rpm for 10 seconds. Hydrated silicone hydrogel contact lenses are immersed in the aqueous dispersion of DOWEX®1x4 20-50 mesh resins prepared above and vortexed at a rpm of about 1000-1100 for about 1 minute, followed by rinsing with DI water and vortex in DI water for about 1 minute. Then, the lenses are placed in glass Petri dishes and images of the lenses are taken with a Nikon optical microscope, using background lighting. The number of positively charged particles adhered to the surface of each lens can be counted. The number of positively charged particles adhered to the lens surface is proportional to the concentration on the surface of negatively charged groups of a contact lens.
[65] As used in the present application, the term "carboxylic acid content", in reference to the crosslinked coating or an outer hydrogel layer of a SiHy contact lens of the invention, means the weight percentage of carboxylic groups (COOH) based on the weight of the crosslinked coating or the outer hydrogel layer of the SiHy contact lens. The carboxylic acid content of a crosslinked coating or an outer layer of hydrogel can theoretically be estimated based on the composition of raw materials to make the crosslinked coating or outer layer of hydrogel and based on the carboxylic acid content of each one of the raw materials.
[66] The invention relates to a SiHy contact lens that features a layered structural configuration and a unique water gradient from inside to outside the SiHy contact lens: a silicone hydrogel core (or volumetric material) with a lower water content completely covered by an outer layer (surface) of hydrogel that has a higher water content and an adequate thickness (at least about 0.1 μm) and that is substantially silicone-free (preferably totally silicone-free) ); and the water content of the outer hydrogel layer being at least about 1.2 times (or 120%), preferably at least about 1.3 times (or 130%), more preferably at least about 1.4 times times (or 140%), even more preferably at least about 1.5 times (150%), even more preferably at least about 2 times (or 200%) the water content of the volumetric material. Figure 1 schematically illustrates a SiHy contact lens that has a layered structural configuration according to a preferred embodiment. According to this preferred embodiment of the invention, the SiHy 100 contact lens has an anterior surface (or curved or convex front surface) 101 and an opposite rear surface (or curved or concave base surface) 102 which remains at rest on the cornea of the eye when used by a user. The SiHy 100 contact lens comprises an inner (or intermediate) layer 110 and two outer layers 120. The inner layer 110 is the volumetric material of the SiHy 100 contact lens and has a three-dimensional shape very similar to that of the contact lens. SiHy 100. The inner layer 110 is preferably produced from a silicone hydrogel with a lower water content. The two outer layers 120, substantially identical to each other, have a substantially uniform thickness and are produced from a substantially silicone-free hydrogel material (preferably totally silicone-free) which has a higher water content than that of the inner layer 110. The two outer layers 120 merge at the peripheral edge 103 of the contact lens 100 and completely cover the inner layer 110.
[67] A SiHy contact lens with a layered structural configuration of the invention can offer several advantages over prior art contact lenses. First, such a SiHy contact lens may still have a high oxygen permeability, which is necessary to maintain the health of the eye's cornea. Second, since the inner layer (volumetric material) provides the volumetric mechanical strength and rigidity required for a contact lens, the outer layers of hydrogel may have no limits in terms of water content and may contain as much water as possible. As such, the outer layers of hydrogel can give the contact lens a super-enriched film in water or a gradient of water content in the structural configuration of the lens (higher water content in the region including and near the lens surface and lower water content. the lens core). Third, a SiHy contact lens with a layered structural configuration of the invention can have low dehydration in the eye, can cause less dryness in the eye and, consequently, can offer greater wearing comfort at the end of the day. It is believed that the inner layer (ie the volumetric material of the lens) with low water content will control (limit) the rate of water diffusion through a lens from the posterior surface to the anterior surface and, in turn, evaporation (water loss) on the front surface of the lens. It is also believed that a layered structural configuration of the invention can create an internal water concentration gradient (that is, the water content decreases as it advances from the anterior surface to the lens core), which is unfavorable for diffusion of water through a lens from the posterior surface to the anterior surface based on Fick's diffusion laws. Fourth, a SiHy contact lens with a layered structural configuration of the invention can impart a high biocompatibility, since water is highly biocompatible with tears and a high water content (for example, preferably> 75% H2O ) in the outer layers of hydrogel is located on and near the anterior and posterior surfaces with which the eye is in direct contact and where biocompatibility is most important. Fifth, a high water content in the hydrogel outer layers with adequate thickness can give a SiHy contact lens a very soft surface, that is, a "water mattress". Sixth, a SiHy contact lens with a layered structural configuration of the invention can have a highly lubricated surface. It is believed that the outer layer of hydrogel with a much higher water content and an adequate thickness will provide a "water-like" surface which can cause tears to spread on the lens surface. It is believed that the outer layer of hydrogel with a softness far superior to that of the volumetric material of the lens (the inner layer) can be very susceptible to deformation under pressure (ie, shear forces of the eyelids) and can confer elastohydrodynamic lubrication. when such a SiHy contact lens is placed on the eye. Seventh, a layered structural configuration on a SiHy contact lens of the invention can prevent exposure of the silicone. It is believed that the three-dimensional mesh network (ie, polymeric matrix) of the outer layers of hydrogel with a suitable thickness can protect the silicone and prevent the silicone from migrating to the lens surface. Eighth, a SiHy contact lens of the invention may have a low concentration on the surface of negatively charged groups (e.g., carboxylic acid groups) and is less susceptible to high residue adherence during patient handling and high protein adherence during use (most proteins in tears are believed to be positively charged).
[68] In one aspect, the invention offers a hydrated hydrogel silicone contact lens comprising: an opposing anterior (convex) surface and a posterior (concave) surface; and a layered structural configuration from the front surface to the rear surface, wherein the layered structural configuration includes an outer hydrogel outer layer, an inner layer of a hydrogel silicone material and an outer hydrogel back layer, wherein the hydrogel silicone material has an oxygen permeability (Dk) of at least about 50, preferably at least about 60, more preferably at least about 70, even more preferably at least about 90, even more preferably at least about 110 barrers, and a first water content (called WCSiHy) from about 10% to about 70%, preferably from about 10% to about 65%, more preferably from about 10% to about 60%, even more preferably from about 15% to about 55%, even more preferably from about 15% to about 50% by weight, where the outer and front layers are hydrogel outer layer has a substantially uniform thickness and fuses at the peripheral edge of the contact lens to completely envelop the inner layer of the hydrogel silicone material and in which the outer front and back layers of hydrogel have, independently of each other, a second content of water greater than WCSiHy, as defined by having a water expansion ratio of at least about 100% (preferably at least about 150%, more preferably at least about 200%, even more preferably at least about 250 %, even more preferably at least about 300%) if WCsiHy <45% or because it has a water expansion ratio of at least about
(preferably
more preferably
even more preferably
if WCSiHy> 45%, where the thickness of each external hydrogel layer is from about 0.1 µm to about 20 µm, preferably from about 0.25 µm to about 15 µm, more preferably from about 0.5 µm to about 12.5 µm, even more preferably from about 1 µm to about 10 µm (measured with atomic force microscopy through a cross section of the posterior surface to the anterior surface of the hydrogel silicone contact lens in a fully hydrated state). Preferably, the anterior and posterior surfaces show a low concentration on the surface of negatively charged groups (for example, carboxylic acid groups), as characterized by an attraction of at most about 200, preferably at most about 160, more preferably at maximum about 120, even more preferably at most about 90, even more preferably at most about 60 positively charged particles in the positively charged particle adhesion test. Also preferably, the hydrated hydrogel silicone contact lens has a surface lubricity characterized by having a critical friction coefficient (called CCOF) of about 0.046 or less, preferably about 0.043 or less, more preferably about 0.040 or any less.
[69] According to the invention, the inner layer of a SiHy contact lens is practically the volumetric material of the lens. It can be derived directly from a precast SiHy contact lens in a surface modification process where two outer layers of hydrogel are applied and bonded directly and / or indirectly to the precast SiHy contact lenses. A precast SiHy contact lens can be any commercial SiHy lens, such as one described above. Alternatively, a precast SiHy contact lens can be produced according to any method known to those skilled in the art. For example, preformed contact lenses can be produced in a "rotating fusion mold" as described, for example, in United States Patent No. 3,408,429 or through the process of total fusion molding in static form, as described United States Patent Nos. 4,347,198, 5,508,317, 5,583,463, 5,789,464, and 5,849,810, or by cutting around silicone hydrogel buttons used in the manufacture of custom contact lenses. In fusion molding, a lens formulation is typically distributed in molds and cured (i.e., polymerized and / or cross-linked) in molds to make contact lenses. For the production of precast SiHy contact lenses, a SiHy lens formulation for fusion molding or rotary fusion molding or for making SiHy sticks used in cutting around contact lenses generally comprises at least a component selected from the group consisting of a vinyl monomer containing silicone, a vinyl macromer containing silicone, a prepolymer containing silicone, a hydrophilic vinyl monomer, a hydrophobic vinyl monomer, a crosslinking agent (a compound that has a molecular weight of about 700 Daltons or less and containing at least two ethylenically unsaturated groups), a free radical initiator (photoinitiator or thermal initiator), a hydrophilic vinyl macromer / prepolymer, and combinations thereof, well known to those skilled in the art. technical. A SiHy contact lens formulation can also comprise other necessary components known to those skilled in the art such as, for example, a UV absorbing agent, a coloring agent for visibility (e.g., dyes, pigments, or mixtures thereof) , antimicrobial agents (for example, preferably silver nanoparticles), a bioactive agent, leachable lubricants, leachable tear stabilizers, and mixtures thereof, known to those skilled in the art. The resulting precast SiHy contact lenses can then be subjected to extraction with an extraction solvent to remove the unpolymerized components from the resulting lenses and for the hydration process, as known to those skilled in the art. In addition, a precast SiHy contact lens can be a colored contact lens (i.e., a SiHy contact lens that has at least one color pattern printed on it, as is well known to those skilled in the art. ).
[70] Any suitable vinyl monomers containing silicone can be used in the invention. Examples of preferred silicone-containing vinyl monomers include, without limitation, N- [tris (trimethylsiloxy) silylpropyl] - (meth) acrylamide, N- [tris (dimethylpropylsiloxy) - silylpropyl] - (meth) acrylamide, N- [tris (dimethylphenylsiloxy ) silylpropyl] - (meth) acrylamide, N- [tris (dimethylethylsiloxy) silylpropyl] - (met) acrylamide, N- (2-hydroxy-3- (3- (bis (trimethylsilyloxy) methylsilyl) propyloxy) propyl) -2- methyl acrylamide; N- (2-hydroxy-3- (3- (bis (trimethylsilyloxy) methylsilyl) propyloxy) propyl) -acrylamide; N, N-bis [2-hydroxy-3- (3- (bis (trimethylsilyloxy) methylsilyl) propyloxy) propyl] -2-methyl-acrylamide; N, N-bis [2-hydroxy-3- (3- (bis (trimethylsilyloxy) methylsilyl) propyloxy) propyl] -acrylamide; N- (2-hydroxy-3- (3- (tris (trimethylsilyloxy) silyl) propyloxy) propyl) -2-methyl-acrylamide; N- (2-hydroxy-3- (3- (tris (trimethylsilyloxy) silyl) propyloxy) propyl) acrylamide; N, N-bis [2-hydroxy-3- (3- (tris (trimethylsilyloxy) silyl) propyloxy) propyl] -2-methyl-acrylamide; N, N-bis [2-hydroxy-3- (3- (tris (trimethylsilyloxy) silyl) propyloxy) propyl] acrylamide; N- [2-hydroxy-3- (3- (t-butyldimethylsilyl) propyloxy) propyl] -2-methyl-acrylamide; N- [2-hydroxy-3- (3- (t-butyldimethylsilyl) propyloxy) propyl] acrylamide; N, N-bis [2-hydroxy-3- (3- (t-butyldimethylsilyl) propyloxy) propyl] -2-methyl-acrylamide; N, N-bis [2-hydroxy-3- (3- (t-butyldimethylsilyl) propyloxy) propyl] acrylamide; 3- methacryloxypropylpentamethyldisiloxane, tris (trimethylsilyloxy) silyl propyl methacrylate (TRIS), (3-methacryloxy-2-hydroxypropyloxy) propylbis (trimethylsiloxy) methylsilane), (3-methacryloxy-methylsily) methacryloxy-oxy-2- (2-hydroxyethoxy) -propyloxy) propylbis (trimethylsiloxy) methylsilane, N-2-methacryloxyethyl-O- (methyl-bis-trimethylsiloxy-3-propyl) silyl, 3- (trimethylsilyl) carbonate propylvinyl, 3- (vinyloxycarbonylthio) propyl-tris (trimethylsiloxy) silane, 3- [tris (trimethylsiloxy) silyl] propylvinyl, 3- [tris (trimethylsiloxy) silyl] propyl-allyl carbonate, 3- [ tris (trimethylsiloxy) silyl] propyl-vinyl, t-butyldimethyl-siloxyethyl-vinyl carbonate; trimethylsilylethyl-vinyl carbonate and trimethylsilylmethyl-vinyl carbonate). Most preferred (meth) acrylamide monomers containing siloxane of formula (1) are N- [tris (trimethylsiloxy) silylpropyl] acrylamide, TRIS, N- [2-hydroxy-3- (3- (t-butyldimethylsilyl) propyloxy) propyl ] acrylamide or combinations thereof.
[71] A preferred class of vinyl monomers or macromers that contain silicone is that of vinyl monomers or macromers that contain polysiloxane. Examples of such vinyl monomers or macromers that contain polysiloxane are monomethacrylated or monoacrylated polydimethylsiloxanes of various molecular weights (for example, mono-3-methacryloxypropyl terminated with mono-3-methacryloxypropyl and terminated with mono-3-methacryloxymethyloxy hydroxypropyloxy) propyl and terminated with mono-butyl); dimethacrylated or diacrylated polydimethylsiloxanes of various molecular weights; polydimethylsiloxanes terminated with vinyl carbonate; polydimethylsiloxane terminated with vinyl carbamate; vinyl-terminated polydimethylsiloxanes of various molecular weights; methacrylamide-terminated polydimethylsiloxanes; acrylamide-terminated polydimethylsiloxanes; acrylate-terminated polydimethylsiloxanes; methacrylate-terminated polydimethylsiloxanes; bis-3-methacryloxy-2-hydroxypropyloxypropyl-polydimethylsiloxane; N, N, N ', N'-tetrakis (3-methacryloxy-2-hydroxypropyl) - alpha, omega-bis-3-aminopropyl-polydimethylsiloxane; polysiloxanilalkyl (meth) acrylic monomers; macromers containing siloxane are selected from the group consisting of Macromere A, Macromere B, Macromere C and Macromere D described in United States Patent No. 5,760,100 (incorporated herein by reference in its entirety); the products of the reaction of glycidyl methacrylate with amino-functionalized polydimethylsiloxanes; vinyl monomers or macromers that contain hydroxyl-functionalized siloxanes; polymers containing polysiloxane described in United States Patent Nos. 4,136,250, 4,153,641, 4,182,822, 4,189,546, 4,343,927, 4,254,248, 4,355,147, 4,276,402, 4,327,203, 4,341,889, 4,486,577, 4,543,398, 4,605,712, 4,661,575, 4,684,538, 4,703,097, 4,833,218, 4,837,289, 4,954,586, 4,954,587, 5,010,141, 5,034,461, [1 ] 70,170, 5,079,319, 5039,761, 5,346,946, 5,358,995, 5,387,632, [2] 16,132, 5,451,617, 5,486,579, 5,962,548, 5,981,675, 6,039,913 and 6,762,264 ( incorporated herein by reference in full); polymers containing polysiloxane described in United States Patent Nos. 4,259,467, 4,260,725 and 4,261,875 (incorporated herein by reference in their entirety). Macromers in diblocks and triblocks that consist of polydimethylsiloxane and polyalkylene oxides can also be useful. For example, it is possible to use polyethylene oxide-block-polydimethylsiloxane-block-polyethylene oxide protected at the end with methacrylate to improve oxygen permeability. Suitable monofunctional hydroxyl-functionalized vinyl monomers / macromers and suitable multifunctional hydroxyl-functionalized vinyl monomers / macromers are commercially available from Gelest, Inc., Morrisville, PA.
[72] Another preferred class of silicone-containing macromers is that of silicone-containing prepolymers that comprise hydrophilic segments and hydrophobic segments. Any of the suitable silicone-containing prepolymers with hydrophilic segments and hydrophobic segments can be used in the invention. Examples of such silicone-containing prepolymers include those described in United States Patents commonly assigned Nos. 6,039,913, 7,091,283, 7,268,189 and 7,238,750, 7,521,519; United States Patent Application Publications commonly assigned No. 2008-0015315 A1, US 2008-0143958 A1, US 2008-0143003 A1, US 2008-0234457 A1, US 2008-0231798 A1 and Commonly assigned United States Patent Applications Nos61 / 180,449 and 61 / 180,453; all of which are incorporated by reference in full.
[73] Examples of preferred hydrophilic vinyl monomers are N, N-dimethylacrylamide (DMA), N, N-dimethylmethacrylamide (DMMA), 2-acrylamidoglycolic acid, 3-acryloylamino-1-propanol, N-hydroxyethyl acrylamide, N- [tris (hydroxymethyl) methyl] -acrylamide, N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5- methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, 1-n-propyl-3-methylene-2-pyrrolidone, 1-n-propyl- 5-methylene-2-pyrrolidone, 1-isopropyl-3-methylene-2-pyrrolidone, 1-isopropyl-5-methylene-2-pyrrolidone, 1-n-butyl-3-methylene-2-pyrrolidone, 1-tert- butyl-3-methylene-2-pyrrolidone, 2-hydroxyethyl methacrylate (HEMA), 2-hydroxyethyl acrylate (HEA), hydroxypropyl acrylate, hydroxypropyl methacrylate (HPMA), 2-hydroxy propyl trimethylammonium methacrylate, hydrochloride aminopropyl methacrylate, dimethylaminoethyl methacrylate (DMAEMA), glycerol methacrylate (GMA), N-vinyl-2-pyrrolidone (NVP), allyl alcohol, vinylpyridine, a C1-C4-alkoxy polyethylene glycol (meth) acrylate that has a weighted average molecular weight of up to 1500, methacrylic acid, N-vinyl formamide, N- vinyl acetamide, N-vinyl isopropylamide, N-vinyl-N-methyl acetamide, allyl alcohol, N-vinyl caprolactam, and mixtures thereof.
[74] Examples of preferred hydrophobic vinyl monomers include methylacrylate, ethyl acrylate, propyl acrylate, isopropyl acrylate, cyclohexyl acrylate, 2-ethylhexyl acrylate, methyl methacrylate, ethyl methacrylate, propyl methacrylate vinyl acetate, vinyl propionate, vinyl butyrate, vinyl valerate, styrene, chloroprene, vinyl chloride, vinylidene chloride, acrylonitrile, 1- butene, butadiene, methacrylonitrile, vinyl toluene, ethyl vinyl ether, perfluor-hexylethyl methacrylate -thiocarbonyl-aminoethyl, isobornyl methacrylate, trifluoroethyl methacrylate, hexafluoro-isopropyl methacrylate, hexafluorobutyl methacrylate.
[75] Examples of preferred crosslinking agents include, without limitation, tetraethylene glycol diacrylate, triethylene glycol diacrylate, ethylene glycol diacrylate, diethylene glycol diacrylate, tetraethylene glycol dimethacrylate, triethylene glycol dimethacrylate, dimethacrylate and ethyl acetate diethylene glycol, trimethylolpropane trimethacrylate, pentaerythritol tetramethacrylate, bisphenol A dimethacrylate, vinyl methacrylate, ethylenediamine dimethylacrylamide, diacrylamide methylethylacrylate, methylethylacrylate, triallycyl acrylate, triallycerate, trially ) -1,1,3,3-tetrakis (trimethylsiloxy) disiloxane, N, N'-methylenebisacrylamide, N, N'-methylenebismethacrylamide, N, N'-ethylenebisacrylamide, N, N'-ethylenebismetacrylamide, 1,3-bis ( N-methacrylamidopropyl) -1,1,3,3-tetrakis- (trimethylsiloxy) disiloxane, 1,3-bis (methacrylamidobutyl) -1,1,3,3-tetrakis (trimethylsiloxy) -disiloxane, 1,3- bis ( acrilami dopropyl) -1,1,3,3-tetrakis (trimethylsiloxy) disiloxane, 1,3-bis (methacryloxyethylureidopropyl) -1,1,3,3-tetrakis (trimethylsiloxy) disiloxane, and combinations thereof. A preferred cross-linking agent is tetra diacrylate (ethylene glycol), tri (ethylene glycol) diacrylate, ethylene glycol diacrylate, di (ethylene glycol) diacrylate, methylenebisacrylamide, trialyl isocyanurate or trialyl cyanide. The amount of crosslinking agent used is expressed by weight in relation to the total polymer and is preferably in the range from about 0.05% to about 4% and, more preferably, in the range from about 0.1% to about 2%.
[76] Examples of suitable thermal initiators include, but are not limited to, 2,2'-azobis (2,4-dimethylpentanonitrile), 2,2'-azobis (2-methylpropanonitrile), 2,2'-azobis (2-methylbutanonitrile) ), peroxides, such as benzoyl peroxide, among others. Preferably, the thermal initiator is 2,2'-azobis (isobutyronitrile) (AIBN).
[77] Suitable photoinitiators are benzoyl methyl ether, diethoxyacetophenone, a benzoylphosphine oxide, 1-hydroxycyclohexyl phenyl ketone and types Darocur and Irgacur, preferably Darocur 1173® and Darocur 2959®. Examples of benzoylphosphine based initiators include 2,4,6-trimethylbenzoyldiphenylphosphine oxide; bis- (2,6-dichlorobenzoyl) -4-N-propylphenylphosphine oxide; and bis- (2,6-dichlorobenzoyl) -4-N-butylphenylphosphine oxide. Reactive photoinitiators that can be incorporated into, for example, a macromer, or that can be used as a special monomer are also suitable. Examples of reactive photoinitiators are those described in EP 632 329, hereby incorporated by reference in their entirety. The polymerization can then be triggered by actinic radiation, for example light, in particular UV light of a suitable wavelength. Spectral requirements can be adequately controlled, if appropriate, by adding appropriate photosensitizers.
[78] Any suitable polymerizable UV absorbing agent can be used in the invention. Preferably, a polymerizable UV absorbing agent comprises a benzotriazole moiety or a benzophenone moiety. Examples of preferred polymerizable UV absorbers include, without limitation, 2- (2-hydroxy-oxy-5-vinylphenyl) -2H-benzotriazole, 2- (2-hydroxy-oxy-5-acrylyloxyphenyl) -2H-benzotriazole, 2- (2-hydroxy-oxy-3-methacrylamido-methyl-5-tert-octylphenyl) benzotriazole, 2- (2'-hydroxy-oxy-5'-methacrylamidophenyl) -5-chlorobenzotriazole, 2- (2'-hydroxy-oxy - 5'-methacrylamidophenyl) -5-methoxybenzotriazole, 2- (2'-hydroxy-oxy-5'-methacryloxypropyl-3'-t-butyl-phenyl) -5-chlorobenzotriazole, 2- (2'-hydroxy-oxy- 5'- methacryloxyethylphenyl) benzotriazole, 2- (2'-hydroxy-oxy-5'-methacryloxypropylphenyl) benzotriazole, 2-hydroxy-oxy-4-acryloxy-alkoxy-benzophenone, 2-hydroxy-oxy-4-methacryloxy-alkoxy-alkoxy benzophenone, allyl-2-hydroxybenzophenone, 2-hydroxy-oxy-4-methacryloxy-benzophenone.
[79] The bioactive agent is any compound that can prevent eye disease or reduce the symptoms of an eye disease. The bioactive agent can be a drug, an amino acid (for example, taurine, glycine, etc.), a polypeptide, a protein, a nucleic acid or any combination thereof. Examples of drugs useful in the present invention include, but are not limited to, rebamipide, ketotifen, olaptidine, chromoglycolate, cyclosporine, nedocromil, levocabastine, lodoxamide, ketotifen or a pharmaceutically acceptable salt or ester thereof. Other examples of bioactive agents include 2-pyrrolidone-5-carboxylic acid (PCA), alpha hydroxy acids (e.g., glycolic acid, lactic acid, malic acid, tartaric acid, mandelic acid and citric acid and salts thereof, etc.) , linoleic acid and gamma linoleic acid and vitamins (for example, B5, A, B6, etc.).
[80] Examples of leachable lubricants include, without limitation, mucin-like materials (eg, polyglycolic acid) and non-cross-linkable hydrophilic polymers (ie, without ethylenically unsaturated groups). Any hydrophilic polymer or copolymer without ethylenically unsaturated groups can be used as a leachable lubricant. Examples of preferred non-crosslinkable hydrophilic polymers include, but are not limited to, polyvinyl alcohols (PVAs), polyamides, polyimides, polylactone, a lactam vinyl homopolymer, a copolymer of at least one lactam vinyl in the presence or absence of one or more hydrophilic vinyl comonomers, an acrylamide or methacrylamide homopolymer, an acrylamide or methacrylamide copolymer with one or more hydrophilic vinyl monomers, polyethylene oxide (ie polyethylene glycol (PEG), a polyoxyethylene, polyethylene, polyethylene derivative, polyethylene, polyethylene polyacrylic acid, poly 2 ethyl oxazoline, heparin polysaccharides, polysaccharides and mixtures thereof. The weighted average molecular weight Mw of the non-crosslinkable hydrophilic polymer is preferably from 5,000 to 1,000,000.
[81] Examples of leachable tear stabilizing agents include, without limitation, phospholipids, monoglycerides, diglycerides, triglycerides, glycolipids, glyceroglycolipids, sphingolipids, sphingoglycolipids, fatty alcohols, fatty acids, mineral oils and mixtures thereof. Preferably, a tear stabilizing agent is a phospholipid, a monoglyceride, a diglyceride, a triglyceride, a glycolipid, a glyceroglycolipid, a sphingolipid, a sphingoglycolipid, a fatty acid that has 8 to 36 carbon atoms, a fatty alcohol that contains 8 to 36 carbon atoms or a mixture of them.
[82] According to the invention, a SiHy lens formulation can be a solution or a melt at a temperature from about 20 ° C to about 85 ° C. Preferably, a polymerizable composition is a solution of all desirable components in a suitable solvent or a mixture of suitable solvents.
[83] A SiHy lens formulation can be prepared by dissolving all desirable components in any suitable solvent, such as water, a mixture of water and one or more water-miscible organic solvents, an organic solvent, or a mixture of a or more organic solvents, as known to those skilled in the art.
[84] Examples of preferred organic solvents include, without limitation, tetrahydrofuran, tripropylene glycol methyl ether, dipropylene glycol methyl ether, ethylene glycol n-butyl ether, ketones (e.g., acetone, methyl ethyl ketone, etc.). ), diethylene glycol n-butyl ether, diethylene glycol methyl ether, ethylene glycol methyl ether, propylene glycol methyl ether, propylene glycol methyl ether acetate, dipropylene glycol methyl ether acetate, propylene n-propyl ether glycol, dipropylene glycol n-propyl ether, tripropylene glycol n-butyl ether, propylene glycol n-butyl ether, dipropylene glycol n-butyl ether, tripropylene glycol n-butyl ether, propylene glycol phenyl ether, dimethyl ether dipropylene glycol, polyethylene glycols, polypropylene glycols, ethyl acetate, butyl acetate, amyl acetate, methyl lactate, ethyl lactate, i-propyl lactate, methylene chloride, 2-butanol, 1-propan ol, 2-propanol, menthol, cyclohexanol, cyclopentanol and exonorborneol, 2-pentanol, 3-pentanol, 2-hexanol, 3-hexanol, 3-methyl-2-butanol, 2-heptanol, 2-octanol, 2- nonanol, 2-decanol, 3-octanol, norborneol, tert-butanol, tert-amyl alcohol, 2-methyl-2-pentanol, 2,3-dimethyl-2-butanol, 3-methyl-3-pentanol, 1-methylcycle -hexanol, 2-methyl-2-hexanol, 3,7-dimethyl-3-octanol, 1-chloro-2-methyl-2-propanol, 2-methyl-2-heptanol, 2-methyl-2-octanol, 2 -2-methyl-2-nonanol, 2-methyl-2-decanol, 3-methyl-3-hexanol, 3-methyl-3-heptanol, 4-methyl-4-heptanol, 3-methyl-3-octanol, 4 -methyl-4-octanol, 3-methyl-3-nonanol, 4-methyl-4-nonanol, 3-methyl-3-octanol, 3-ethyl-3-hexanol, 3-methyl-3-heptanol, 4-ethyl -4-heptanol, 4-propyl-4-heptanol, 4-isopropyl-4-heptanol, 2,4-dimethyl-2-pentanol, 1-methylcyclopentanol, 1-ethylcyclopentanol, 1-ethylcyclopentanol, 3-hydroxy-oxy-3 -methyl-1-butene, 4-hydroxy-oxy-4-methyl-1-cyclopentanol, 2-phenyl-2-propanol, 2-methoxy-oxy-2-methyl-2-propanol 2,3,4-trimethyl- 3-pentanol, 3,7-dimethyl-3-octanol, 2-phenyl-2-butanol, 2-methyl-1-phenyl-2-propanol and 3-ethyl-3-pentanol, 1-ethoxy-oxy-2-propanol, 1-methyl-2-propanol, t-amyl alcohol , isopropanol, 1-methyl-2-pyrrolidone, N, N-dimethylpropionamide, dimethylformamide, dimethyl acetamide, dimethyl propionamide, N-methyl pyrrolidinone and mixtures thereof.
[85] Numerous SiHy lens formulations have already been described in numerous patents and patent applications filed up to the filing date of the present application. All of them can be used to obtain a precast SiHy lens which, in turn, becomes the inner layer of a SiHy contact lens of the invention, as long as they produce a SiHy material that has a Dk and water content specified above. A SiHy lens formulation to produce commercial SiHy lenses, such as lotrafilcon A, lotrafilcon B, balafilcon A, galyfilcon A, senofilcon A, narafilcon A, narafilcon B, comfilcon A, enfilcon A, asmofilcon A, filcon II 3, too can be used to produce precast SiHy contact lenses (the inner layer of a SiHy contact lens of the invention).
[86] Lens molds for producing contact lenses are well known to those skilled in the art and are used, for example, in fusion molding or rotary molding. For example, a mold (for melt molding) generally comprises at least two mold sections (or portions) or mold halves, that is, first and second mold halves. The first mold half defines a first molding (or optical) surface and the second mold half defines a second molding (or optical) surface. The first and second mold halves are configured to receive one another, so that a lens-forming cavity is formed between the first molding surface and the second molding surface. The molding surface of a mold half is the cavity-forming surface of the mold and is in direct contact with the lens-forming material.
[87] Methods for making mold sections for melting molding a contact lens are generally known to those skilled in the art. The process of the present invention is not limited to any particular method of forming a mold. In fact, any method of forming a mold can be used in the present invention. The first and second mold halves can be formed using various techniques, such as injection molding or turning. Examples of suitable processes for forming the mold halves are described in United States Patent Nos. 4,444,711 issued to Schad; 4,460,534 granted to Boehm et al .; 5,843,346 granted to Morrill; and 5,894,002 granted to Boneberger et al., which are incorporated herein by reference.
[88] Virtually all materials known in the art for making molds can be used to make molds for making contact lenses. For example, polymeric materials such as polyethylene, polypropylene, polystyrene, PMMA, Topas®COC grade 8007-S10 (transparent amorphous copolymer of ethylene and norbornene from Ticona GmbH in Frankfurt, Germany and Summit, New Jersey), among others, can be used. Other materials that enable the transmission of UV light could be used, such as quartz glass and sapphire.
[89] In a preferred embodiment, reusable molds are used and the silicone hydrogel lens-forming composition is cured actinically under a spatial limitation of actinic radiation to form a SiHy contact lens. Examples of preferred reusable molds are those described in United States Patent Applications No. 08 / 274,942 filed on July 14, 1994, 10 / 732,566 filed on December 10, 2003, 10 / 721,913 filed on November 25, 2003, and United States Patent No. 6,627,124, which is incorporated herein by reference in its entirety. Reusable molds can be produced from quartz, glass, sapphire, CaF2, a cyclic olefin copolymer (such as, for example, Topas®COC grade 8007-S10 (transparent amorphous ethylene and norbornene copolymer) from Ticona GmbH in Frankfurt , Germany and Summit, New Jersey, Zeonex® and Zeonor® from Zeon Chemicals LP, Louisville, KY), polymethylmethacrylate (PMMA), DuPont polyethylene (Delrin), Ultem® (polyetherimide) from GE Plastics, PrimoSpire®, etc.
[90] According to the invention, the hydrogel silicone (volumetric material) of the inner layer has an oxygen permeability of at least about 50, preferably at least about 60, more preferably at least about 70, even more preferably at least about 90 barrers, even more preferably at least about 110 barrers. The hydrogel silicone material can also have a (first) WCSiHy water content from about 10% to about 70%, preferably from about 10% to about 65%, more preferably from about from 10% to about 60%; even more preferably from about 15% to about 55%, even more preferably from about 15% to about 50% by weight. The hydrogel silicone material may also have a volumetric elastic modulus or Young volumetric modulus (hereinafter, the terms "softness", "elastic modulus" and Young modulus "are used interchangeably in this application to indicate the volumetric elastic modulus if the term is not modified by the word "surface") from about 0.3 MPa to about 1.8 MPa, preferably from 0.4 MPa to about 1.5 MPa, more preferably from about 0.5 MPa to about 1.2 MPa. The oxygen permeability, elastic modulus and water content of the inner layer of the hydrogel silicone material of a SiHy contact lens of the invention can be determined by measuring the oxygen permeability, elastic modulus and water content of the precast SiHy lens from which the inner layer is derived. It should be understood that, as a reasonable approximation, the elastic modulus of a SiHy contact lens from invention can be considered the elastic modulus of the mat silicone hydrogel material of the inner layer due to the much thinner outer hydrogel layers. Those skilled in the art will know how to determine the elastic modulus and water content of a silicone hydrogel material or a SiHy contact lens. For example, all commercial SiHy contact lenses have reported values of elastic modulus and water content.
[91] The two outer hydrogel layers of a SiHy contact lens of the invention are preferably substantially identical to each other and are a cross-linked coating which is applied over a precast SiHy contact lens that has a Dk , a desired water content and volumetric elastic modulus.
[92] The structural layered configuration of a SiHy contact lens of the invention can be established through atomic force microscopy (AFM) analysis of a cross section of a SiHy contact lens in the fully hydrated state (ie, directly in water or in a buffered saline solution), as already described above and shown in the Examples. The surface modules of a cross section can be characterized (imaging) with AFM (for example, Force-Volume mode) in order to view all changes in the surface module from the side of the posterior surface to the side of the anterior surface through the cross section. A significant change (for example, about 20% or more, preferably about 30% or more) seen in the surface module (when examining the AFM image) over a thickness of about 0.04 μm, preferably about 0.03 μm, more preferably about 0.02 μm, even more preferably about 0.01 μm, along the shortest line between the anterior and posterior surfaces through a cross section of the SiHy contact lens in the state fully hydrated indicates a transition from one layer to another layer. The average thickness of each external hydrogel layer can be determined from the AFM image, as is well known to those skilled in the art.
[93] The two outer hydrogel layers of a SiHy contact lens of the invention have a substantially uniform thickness. They fuse at the peripheral edge of the contact lens to completely envelop the inner layer of the silicone hydrogel material. The thickness of each outer hydrogel layer varies from about 0.1 μm to about 20 μm, preferably from about 0.25 μm to about 15 μm, even more preferably from about 0 , 5 μm to about 12.5 μm, even more preferably from about 1 μm to about 10 μm. The thickness of the outer hydrogel layers (or reticulated coating) of a SiHy contact lens of the invention is determined by AFM analysis of a cross section of the SiHy contact lens in the fully hydrated state, as already described above. In a more preferred embodiment, the thickness of each outer hydrogel layer is preferably at most about 30% (i.e., 30% or less), preferably at most about 20% (20% or less), more preferably at most about 10% (10% or less) of the central thickness of the SiHy contact lens in the fully hydrated state.
[94] It should be understood that the structural layered configuration of a SiHy contact lens of the invention can also be established qualitatively by scanning electron microscopy (SEM) analysis of a cross section of the lyophilized SiHy contact lens, as shown in the Examples. SEM can show the different compositions and / or structures of each of the layers of a cross section of the SiHy contact lens in the lyophilized state. A significant change (for example, about 20% or more, preferably about 30% or more) observed in the compositions and / or significant (visually perceptible) changes in the structures (when examining the SEM image) over a thickness of about 0.04 μm, preferably about 0.03 μm, more preferably about 0.02 μm, even more preferably about 0.01 μm, through a cross section of the SiHy contact lens in the lyophilized state indicates a transition from one layer to another layer. However, the thickness value based on SEM analysis of a cross section of a SiHy lens in the lyophilized state is typically less than the actual value due to the collapse of the outer hydrogel layers, the transition layer if applicable, and of the inner layer after being lyophilized.
[95] In accordance with this aspect of the invention, the two outer layers of hydrogel (the front and rear outer layers of hydrogel) of a SiHy contact lens of the invention comprise a (second) water content that must be greater than ( first) water content (WCSiHy) of the inner layer of the hydrogel silicone material and, more specifically, it should be at least about 1.2 times (ie, 120%) the (first) water content (WCSiHy) of the layer internal hydrogel silicone material. It is believed that the proportion of water expansion of each external hydrogel layer is correlated to its water content and, as a good approximation, it can reasonably represent the water content of the external hydrogel layer. In alternative preferred embodiments, where the water content (WCSiHy) of the inner layer of the hydrogel silicone material is about 55% or less, the water swelling ratio of each outer hydrogel layer is at least about 150%; where the water content (WCSiHy) of the inner layer of the hydrogel silicone material is about 60% or less, the proportion of water expansion of each outer layer of hydrogel is at least about 200%; where the water content (WCSiHy) of the inner layer of the silicone hydrogel material is about 65% or less, the water swelling ratio of each outer hydrogel layer is at least about 250%; where the water content (WCSiHy) of the inner layer of the silicone hydrogel material is about 70% or less, the water swelling ratio of each outer hydrogel layer is at least about 300%.
[96] It should be understood that the water content of the front and rear outer layers of hydrogel (the cross-linked coating) can be more precisely determined according to the procedures described in Example 23. Alternatively, the water content of the two layers external hydrogel (the cross-linked coating) can be determined with an article comprising a thin non-absorbent water substrate and a cross-linked coating thereon, where the cross-linked coating is applied on the thin non-absorbent water substrate according to a coating process identical to that used for the SiHy contact lens under substantially identical conditions. The water content of each outer layer of hydrogel can then be determined based on the difference between the dry and hydrated weights of the article with the reticulated coating.
[97] According to the invention, each of the two outer hydrogel layers is substantially silicone-free, preferably totally silicone-free. However, it is known that when X-ray photoelectronic spectroscopy (XPS) is used to establish the presence or absence of silicone in an outer layer of hydrogel (usually a probing depth from 1.5 to 6 nm), inevitably samples are contaminated by silicone from the environment, as shown by XPS detection of silicone on the surface of samples that are theoretically free of any silicon atom such as, for example, a polyethylene blade, a DAILIES® AquaComfortPlus® contact lens from CIBA VISION Corporation or an ACUVUE® Moist from Johnson & Johnson (see Example 21 below). As such, the term "substantially silicone-free" is used in this application to indicate that the atomic percentage of silicon on the surface, measured by XPS, in a SiHy contact lens is less than about 200%, preferably less than about 175%, more preferably less than about 150%, even more preferably less than about 125% of the atomic percentage of silicon in a control sample known to be inherently (theoretically) silicone-free (for example, a polyethylene, a DAILIES® AquaComfortPlus® contact lens from CIBA VISION Corporation or an ACUVUE®Moist from Johnson & Johnson). Alternatively, each outer hydrogel layer of a SiHy contact lens of the invention is substantially silicone-free, as defined by having an atomic percentage of silicon of about 5% or less, preferably about 4% or less, even more preferably about 3% or less, of the total elemental percentage, as measured by XPS analysis of the dry contact lens. It should be understood that a small percentage of silicone can optionally (however, preferably not) be incorporated into the polymer network of the outer hydrogel layer, as long as this does not significantly impair the surface properties (hydrophilicity, wetting capacity and / or lubricity) of a SiHy contact lens.
[98] In a preferred embodiment, the front and back outer layers of hydrogel (the crosslinked coating) have a crosslinking density (or crosslinking density) sufficient to transmit to the crosslinked coating or the external hydrogel layers (i.e., the SiHy contact lens) a high resistance to digital friction, as characterized by having no crack lines on the surface visible in the dark field after the SiHy contact lens is rubbed between the fingers. It is believed that a crack on the surface induced by rubbing between the fingers may reduce the surface lubricity and / or may not be able to prevent the silicone from migrating to the surface (exposure). A crack in the surface can also indicate excessive crosslink density in the surface layers, which can affect the elastic surface modulus. Preferably, the non-silicone hydrogel material in the outer hydrogel layers (the crosslinked coating) comprises crosslinks derived from azetidinium groups in a thermally induced coupling reaction.
[99] In another preferred embodiment, the anterior and posterior surfaces have a low concentration on the surface of negatively charged groups, including carboxylic acid groups, as characterized by an attraction of at most about 200, preferably at most about 160, more preferably at most about 120, even more preferably at most about 90, even more preferably at most about 60 positively charged particles in the positively charged particles adherence test. It is desirable to have a minimum concentration on the surface of negatively charged groups (for example, carboxylic acid groups) in a SiHy contact lens of the invention, since contact lenses with a high concentration on the surface of negatively charged groups (for example, carboxylic acid groups) are susceptible to high adherence of residues during handling by the patient, high adherence of proteins during use (most tears are believed to be positively charged), high deposition and accumulation of antimicrobials, such as poly- biguanide hexamethylene (PHMB) present in contact lens care solutions. In order to have a low concentration on the surface of negatively charged groups (for example, carboxylic acid groups), the front and rear outer layers of hydrogel must have a relatively low carboxylic acid content. Preferably, the front and rear outer layers of hydrogel have a carboxylic acid content of about 20% by weight or less, preferably about 15% by weight or less, even more preferably about 10% by weight or less, even more preferably about 5% by weight or less.
[100] In another preferred embodiment, a SiHy contact lens of the invention has good surface lubricity characterized by having a critical friction coefficient (designated as CCOF) of about 0.046 or less, preferably about 0.043 or less, more preferably about 0.040 or less. Alternatively, a SiHy contact lens of the invention preferably has a better lubricity than that of ACUVUE OASYS or ACUVUE TruEye, as measured in a blind test according to the lubricity assessment procedures described in Example 1.
[101] In another preferred embodiment, a SiHy contact lens of the invention further comprises, in its layered structural configuration, two transition layers of polymeric materials, as illustrated schematically in Figure 2. Each of the two transition layers 115 is located between the inner layer 110 and one of the two outer layers of hydrogel 120. Each transition layer has a substantially uniform thickness. The thickness of each transition layer is at least about 0.05 μm, preferably from about 0.05 μm to about 10 μm, more preferably from about 0.1 μm to about 7, 5 μm, even more preferably from about 0.15 μm to about 5 μm. The transition layers fuse at the peripheral edge of the contact lens to completely envelop the inner layer of the hydrogel silicone material. The presence and thickness of the transition layers can preferably be determined by AFM analysis of a cross section of the SiHy contact lens in the fully hydrated state, as described above for the outer hydrogel layers and the inner layers .
[102] The two transition layers of a SiHy contact lens of the invention are essentially a base coat (or primer) which is applied over a precast SiHy contact lens that has a Dk, water content and a desired volumetric elastic modulus before the cross-linked coating (the outer layers of hydrogel) is applied to them. The transition layers (base coat) serve to anchor / fix the outer hydrogel layers. Preferably, the transition layers comprise a carboxyl-containing polymer (COOH), preferably a homopolymer or copolymer of acrylic acid or methacrylic acid or C2-C12 alkylacrylic acid. It should be understood that the carboxyl-containing polymer can penetrate the volumetric material and extend to the outer hydrogel layers. When such penetration into the inner layer of the silicone hydrogel material occurs, each transition layer will comprise the polymer containing carboxyl and the silicone hydrogel which are intertwined with each other. Also, it is believed that the presence of the transition layers, especially when comprising a polymer containing carboxyl, can impart a relatively high water content to the thicker layer and / or a water reservoir for the outer hydrogel layers due to the strong water-binding properties of the carboxyl groups. Furthermore, even if the transition layer may contain many carboxylic acid groups, this would have a minimal adverse impact on the surface concentration of SiHy contact lens carboxylic acid groups, since the surface concentration of carboxylic acid groups it is predominantly determined by the outer hydrogel layers that completely cover the transition layer. The outer layers of hydrogel with a low concentration on the surface of carboxylic acid groups can prevent the deposition of positively charged proteins from the tears of the patient using the lens.
[103] In another preferred embodiment, the outer front and rear hydrogel layers have, independently of each other, a reduced surface modulus of at least about 20%, preferably at least about 25%, more preferably at least about 30%, even more preferably at least about 35%, even more preferably at least about 40%, with respect to the inner layer.
[104] The front and rear outer layers of hydrogel are preferably made from the same materials or substantially identical materials (preferably totally silicone-free) and can be formed by applying and cross-linking a water-soluble, cross-linkable hydrophilic polymeric material a precast SiHy contact lens comprising amino and / or carboxyl groups on and / or close to the surface of the contact lens or a base coating comprising amino and / or carboxyl groups, wherein the contact lens of Precast SiHy becomes the inner layer after crosslinking.
[105] According to the invention, a precast SiHy contact lens can inherently comprise or be modified to comprise amino groups and / or carboxyl groups on and / or near its surface.
[106] Where a precast SiHy contact lens inherently comprises amino groups and / or carboxyl groups on and / or near its surface, it is obtained by polymerizing a silicone hydrogel lens formulation comprising a monomer reactive vinyl.
[107] Examples of preferred reactive vinyl monomers include, without limitation, (meth) acrylate of C2-C6 alkyl, (meth) acrylate of C1-C6 alkylamino-C2-C6 alkyl, allylamine, vinylamine, amino-C2-C6 alkyl (meth) acrylamide, C1-C6 alkylamino-C2-C6 alkyl (meth) acrylamide, acrylic acid, C1-C12 alkylacrylic acid (e.g., methacrylic acid, ethylacrylic acid, propylacrylic acid, butylacrylic acid, pentylacrylic acid, etc.) , N, N-2-acrylamidoglycolic acid, beta methyl-acrylic acid (crotonic acid), alpha-phenyl acrylic acid, beta-acryloxy propionic acid, sorbic acid, angelic acid, cinnamic acid, 1-carboxy-4-phenyl- butadiene-1,3-itaconic, citraconic acid, mesaconic acid, glutaconic acid, aconitic acid, maleic acid, fumaric acid, tricarboxyethylene and combinations thereof. Preferably, the SiHy contact lens is produced from a lens formulation comprising at least one reactive vinyl monomer selected from the group consisting of (meth) acrylate-C2-C6 alkyl, (meth) acrylate of C1-C6 alkylamino-C2-C6 alkyl, allylamine, vinylamine, amino-C1-C6 alkyl (meth) acrylamide, C1-C6 alkylamino-C2-C6 alkyl (meth) acrylamide, acrylic acid, C1-C12 alkylacrylic acid, N, N-2-acrylamidoglycolic, and combinations thereof.
[108] The lens formulation preferably comprises from about 0.1% to about 10%, more preferably from about 0.25% to about 7%, even more preferably from about 0.5% to about 5%, even more preferably from about 0.75% to about 3%, by weight of a reactive vinyl monomer described above.
[109] A precast SiHy contact lens can also be subjected to a surface treatment to form a reactive base coat that has amino groups and / or carboxyl groups on the surface of the contact lens. Examples of surface treatments include, without limitation, an energy surface treatment (for example, a plasma source, static charge, radiation or other energy source), chemical treatments, chemical vapor deposition, grafting of monomers or hydrophilic vinyl macromers on the surface of an article, layer by layer coating ("LbL coating") obtained according to methods described in United States Patent Nos. 6,451,871, 6,719,929, 6,793,973, 6,811,805 and 6,896,926 and in United States Patent Application Publications Nos2007 / 0229758A1, 2008 / 0152800A1 and 2008 / 0226922A1, (incorporated herein by reference). "LbL coating", as used here, refers to a coating that is not covalently bonded to the polymer matrix of a contact lens and is obtained by a layer-by-layer ("LbL") deposition of charged materials or chargeable (through protonation or deprotonation) and / or not loaded on the lens. An LbL coating can be composed of one or more layers.
[110] Preferably, the surface treatment is an LbL coating process. In this preferred embodiment (i.e., the reactive LbL base coat modality), a resulting silicone hydrogel contact lens comprises a reactive LbL base coat (i.e., the two transition layers) that includes at least one layer of a reactive polymer (i.e., a polymer that has pendant amino groups and / or carboxyl groups), where the reactive LbL base coating is obtained by contacting the contact lens with a reactive polymer solution. Contact lens contact with a coating solution of a reactive polymer can occur by immersing it in the coating solution or spraying it with the coating solution. A contact process involves just immersing the contact lens in a bath of a coating solution for a period of time or, alternatively, immersing the contact lens sequentially in a series of baths of coating solutions for a fixed shorter period of time. for each bath. Another contact process involves just spraying a coating solution. However, numerous alternatives involve various combinations of spraying and dipping steps that can be designed by those skilled in the art. The contact time of a contact lens with a reactive polymer coating solution can last up to about 10 minutes, preferably from about 5 to about 360 seconds, more preferably from about 5 to about 250 seconds, even more preferably from about 5 to about 200 seconds.
[111] According to this modality of the reactive LbL base coat, the reactive polymer can be a linear or branched polymer that has pendant amino groups and / or carboxyl groups. Any polymer that has pendant amino groups and / or carboxyl groups can be used as the reactive polymer to form a base coat over silicone hydrogel contact lenses. Examples of such reactive polymers include, without limitation: a homopolymer of a reactive vinyl monomer; a copolymer of two or more reactive vinyl monomers; a copolymer of a reactive vinyl monomer with one or more non-reactive hydrophilic vinyl monomers (i.e., hydrophilic vinyl monomers free from any carboxyl or amino group (primary or secondary)); polyethyleneimine (PEI); polyvinyl alcohol with pendent amino groups; a carboxyl-containing cellulose (for example, carboxymethylcellulose, carboxyethylcellulose, carboxypropylcellulose); hyaluronate; chondroitin sulfate; (poly) glutamic acid; (poly) aspartic acid; and combinations thereof.
[112] Any preferred reactive vinyl monomers described above can be used in this embodiment to form a reactive polymer to form a reactive LbL base coating.
[113] Preferred examples of non-reactive hydrophilic vinyl monomers free of carboxyl or amino groups include, without limitation, acrylamide (AAm), methacrylamide, N, N-dimethylacrylamide (DMA), N, N-dimethylmethacrylamide (DMMA), N-vinylpyrrolidone (NVP), N, N-dimethylaminoethyl methacrylate (DMAEM), N, N-dimethylaminoethyl acrylate (DMAEA), N, N-dimethylaminopropylmethacrylamide (DMAPMAm), N, N-dimethylaminopropylacrylamide (DMAPAAm), acryloylamino-1-propanol, N-hydroxyethyl acrylamide, N- [tris (hydroxymethyl) methyl] -acrylamide, N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl -5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, (meth) acrylate 2- hydroxyethyl, hydroxypropyl (meth) acrylate, C1-C4-alkoxy polyethylene glycol which has a weighted average molecular weight of up to 1500 Daltons, N-vinyl formamide, N-vinyl acetamide, N-vinyl isopropyl ylamide, N-vinyl-N-methyl acetamide, allyl alcohol, vinyl alcohol (hydrolyzed form of vinyl acetate in the copolymer), a vinyl monomer containing phosphorylcholine (including (meth) acryloyloxyethyl phosphorylcholine and those described in United States Patent No. 5. 461,433, incorporated herein by reference in its entirety), and combinations thereof.
[114] Preferably, the reactive polymers to form a reactive LbL base coat are polyacrylic acid, polymethacrylic acid, (poly) C2-C12 alkylacrylic acid, (poly) acrylic-co-methacrylic acid, [acid (poly ) C2-C12 alkylacrylic-co-(meth) acrylic acid], (poly) -N, N-2-acrylamidoglycolic acid), [oly (met) acrylic-co-acrylamide acid], [oly (meth) acrylic acid- co-vinylpyrrolidone], [(poly) C2-C12 alkylacrylic-co-acrylamide acid], [(poly) C2-C12 alkylacrylic-co-vinylpyrrolidone acid], [(poly) (meth) acrylic-co-vinyl acetate ] hydrolyzate, [(poly) C2-C12 alkylacrylic acid-vinyl acetate] hydrolyzate, polyethyleneimine (PEI), homopolymer or copolymer of polyalylamine hydrochloride (PAH), homopolymer or copolymer of polyvinylamine, or combinations thereof.
[115] The weighted average molecular weight Mw of a reactive polymer to form a reactive LbL base coat is at least about 10,000 Daltons, preferably at least about 50,000 Daltons, more preferably from about 100,000 Daltons to 5,000 .000 Daltons.
[116] A reactive polymer solution to form a reactive LbL base coating on contact lenses can be prepared by dissolving one or more reactive polymers in water, a mixture of water and one or more water-miscible organic solvents, a solvent organic or a mixture of one or more organic solvents. Preferably, the reactive polymer is dissolved in a mixture of water and one or more organic solvents, an organic solvent or a mixture of one or more organic solvents. It is believed that a solvent system containing at least one organic solvent can expand a precast SiHy contact lens, so that a portion of the reactive polymer can penetrate the precast SiHy contact lens and increase durability of the reactive base coat. All of the organic solvents described above can be used in the preparation of a solution of the reactive polymer, as long as it can dissolve the reactive polymer.
[117] In another preferred embodiment, a precast SiHy contact lens inherently comprises amino groups and / or carboxyl groups on and / or near its surface and is further subjected to a surface treatment to form a base coat. Reactive LbL that contains amino groups and / or carboxyl groups in it.
[118] In another preferred embodiment (reactive plasma base coating), a precast SiHy contact lens is subjected to plasma treatment to form a reactive plasma base coating covalently attached to the contact lens, that is, polymerization of one or more reactive vinyl monomers (any of those already described) under the effect of plasma generated by electrical discharge (the so-called plasma-induced polymerization). The term "plasma" designates an ionized gas, for example, created by means of a bright electrical discharge that can be composed of electrons, ions of any polarity, atoms and gas molecules on earth or any higher state of any form of excitation, as well as photons. This is often referred to as "low temperature plasma". For a review of plasma polymerization and its uses reference is made to R. Hartmann "Plasma polymerisation: Grundlagen, Technik und Anwendung, Jahrb. Oberflachentechnik (1993) 49, pages 283-296, Battelle-Inst. EV Frankfurt / Main Germany; H. Yasuda, "Glow Discharge Polymerization", Journal of Polymer Science: Macromolecular Reviews, vol. 16 (1981), pages 199-293; H. Yasuda, "Plasma Polymerization", Academic Press, Inc. (1985); Frank Jansen , "Plasma Deposition Processes", in "Plasma Deposited Thin Films", edited by T. Mort & F. Jansen, CRC Press Boca Raton (19); O. Auciello et al. (Ed.) "Plasma-Surface Interactions and Processing of Materials "published by Kluwer Academic Publishers in NATO ASI Series; Series E: Applied Sciences, vol. 176 (1990), pages 377-399; and N. Dilsiz & G. Akovali" Plasma Polymerization of Selected Organic Compounds ", Polymer, vol 37 (1996) pages 333-341. Preferably, plasma-induced polymerization is a plasma-induced polymerization "p afterglow "as described in WO98028026 (hereby incorporated by reference in its entirety). For "post-shine" plasma-induced polymerization, the surface of a contact lens is first treated with a non-polymerizable plasma gas (for example, H2, He or Ar) and then, in a subsequent step, the surface thus activated is exposed to a vinyl monomer that has an amino group or carboxyl group (any reactive vinyl monomer described above), while the plasma energy has been deactivated. The activation results in the plasma-induced formation of radicals on the surface which, in the subsequent stage, initiate the polymerization of the vinyl monomer on it.
[119] According to the invention, the water-soluble and cross-linkable hydrophilic polymeric material to form the outer hydrogel layers (or cross-link coating) comprises cross-linkable groups, preferably thermally cross-linkable groups, more preferably azetidinium groups. Preferably, the water-soluble, cross-linkable hydrophilic polymeric material to form the outer hydrogel layers (or cross-linked coating) is a partially cross-linked polymeric material comprising a three-dimensional network and cross-linkable groups (preferably thermally cross-linkable), more preferably azetidinium groups, within the network. The term "partially crosslinked", in reference to a polymeric material, means that the crosslinkable groups of the raw materials to produce the polymer material in the crosslinking reaction have not been fully consumed. Examples of crosslinkable groups include, without limitation, azetidinium groups, epoxy groups, isocyanate groups, aziridine groups, azo-lactone groups, and combinations thereof.
[120] In a preferred embodiment, the water-soluble, crosslinkable hydrophilic polymeric material to form the outer hydrogel layers (or crosslinked coating) comprises (i) from about 20% to about 95% by weight of chains of the first polymer derived from a polyamine functionalized with epichlorohydrin or polyamidoamine, (ii) from about 5% to about 80% by weight of hydrophilic portions or chains of the second polymer derived from at least one hydrophilicity-enhancing agent having at least one group reactive functional selected from the group consisting of an amino group, carboxyl group, thiol group, and combinations thereof, in which the hydrophilic moieties or chains of the second polymer are covalently linked to the chains of the first polymer through one or more covalent bonds, each formed between an azetidinium group of the polyamine functionalized with epichlorohydrin or polyamidoamine and an amino group, carbox line or thiol of the hydrophilicity-enhancing agent, and (iii) azetidinium groups that form part of the chains of the first polymer or pendant or terminal groups covalently linked to the chains of the first polymer.
[121] With such a water-soluble and cross-linkable hydrophilic polymeric material, the outer layers of hydrogel (or cross-linked coating) can be formed by simply heating a pre-molded SiHy contact lens (which has amino and / or carboxyl groups in and / or close to the contact lens surface or a base coat comprising amino and / or carboxyl groups) in an aqueous solution in the presence of the hydrophilic polymeric material up to and at a temperature from about 40 ° C to about 140 ° C for a period of time sufficient to covalently bond the hydrophilic polymeric material to the contact lens surface via covalent bonds, each formed between an azetidinium group of the hydrophilic polymeric material and one of the amino and / or carboxyl groups in and / or close to the contact lens surface, thereby forming a crosslinked hydrophilic coating on the contact lens. It is to be understood that any water-soluble and cross-linkable hydrophilic polymeric material containing cross-linkable groups (for example, those described above) can be used in the invention to form the front and rear outer layers of hydrogel of a SiHy contact lens.
[122] A water-soluble, thermally cross-linkable hydrophilic polymeric material containing azetidinium groups comprises (i.e. has a composition which includes) from about 20% to about 95%, preferably from about 35% to about from 90%, more preferably from about 50% to about 85%, by weight of chains of the first polymer derived from a polyamine functionalized with epichlorohydrin or polyamidoamine and from about 5% to about 80%, of preferably from about 10% to about 65%, even more preferably from about 15% to about 50%, by weight of hydrophilic moieties or chains of the second polymer derived from at least one hydrophilicity-enhancing agent which it has at least one reactive functional group selected from the group consisting of an amino group, carboxyl group, thiol group and combinations thereof. The composition of the hydrophilic polymeric material is determined by the composition (based on the total reagent weight) of the reagent mixture used to prepare the thermally crosslinkable hydrophilic polymeric material according to the crosslinking reactions shown in Scheme I above. For example, if a reagent mixture comprises about 75% by weight of a polyamine functionalized with epichlorohydrin or polyamidoamine and about 25% by weight of at least one hydrophilicity-enhancing agent based on the total weight of the reactants, then the material The resulting hydrophilic polymer comprises about 75% by weight of chains of the first polymer derived from the polyamine functionalized with epichlorohydrin or polyamidoamine and about 25% by weight of hydrophilic portions or chains of the second polymer derived from said at least one hydrophilicity-enhancing agent. The azetidinium groups of the thermally crosslinkable hydrophilic polymeric material are those azetidinium groups (of the polyamine functionalized with epichlorohydrin or polyamidoamine) that do not participate in the crosslinking reactions to prepare the thermally crosslinkable hydrophilic polymeric material.
[123] A polyamine functionalized with epichlorohydrin or polyamidoamine can be obtained by reacting epichlorohydrin with a polyamine polymer or a polymer containing primary or secondary amino groups. For example, a (poly) alkylene imine or a (poly) amidoamine which is a polycondensate derived from a polyamine and a dicarboxylic acid (for example, adipic acid-diethylene triamine copolymers) can react with epichlorohydrin to form an epichlorohydrin functionalized polymer. . Similarly, an aminoalkyl (meth) acrylate, monoalkylaminoalkyl (meth) acrylate, aminoalkyl (meth) acrylamide or monoalkylaminoalkyl (meth) acrylamide homopolymer or copolymer can also react with epichlorohydrin to form a functionalized polyamine with epichlorohydrin. The reaction conditions for functionalization of a polyamine or polyamidoamine polymer with epichlorohydrin are taught in EP1465931 (hereby incorporated by reference in its entirety). A preferred epichlorohydrin-functionalized polymer is polyaminoamide-epichlorohydrin (PAE) (or polyamide-polyamine-epichlorohydrin or polyamide-epichlorohydrin) such as, for example, Kymene®or Policup® resins (adipic acid-diethylenetriamine copolymers of functionalized epichlorohydrin with epichlorohydrin) Hercules or the Servo / Delden Policup® or Servamina® resins.
[124] Any suitable hydrophilicity-enhancing agents can be used in the invention, as long as they contain at least one amino group, at least one carboxyl group and / or at least one thiol group.
[125] A preferred class of hydrophilicity-enhancing agents includes, without limitation: monosaccharides containing amino, carboxyl or thiol groups (eg, 3-amino-1,2-propanediol, 1-thiolglycerol, 5-keto-D- acid gluconic, galactosamine, glucosamine, galacturonic acid, gluconic acid, glucosaminic acid, mannosamine, 1,4-lactone saccharic acid, saccharide acid, ketodeoxynonulosonic acid, N-methyl-D-glucamine, 1-amino-1-de0xi-0xi- β-D-galactose, 1-amino-1-deoxysorbitol, 1-methylamino-1-deoxysorbitol, N-aminoethyl gluconamide); disaccharides containing amino, carboxyl or thiol groups (e.g., chondroitin disaccharide sodium salt, di (β-D-xylopyranosyl) amine, digalacturonic acid, heparin disaccharide, hyaluronic acid disaccharide, lactobionic acid); oligosaccharides containing amino, carboxyl or thiol groups (for example, sodium carboxymethyl-β-cyclodextrin, trigalacturonic acid); and combinations thereof.
[126] Another preferred class of hydrophilicity-enhancing agents is that of hydrophilic polymers having one or more amino, carboxyl and / or thiol groups. More preferably, the content of monomeric units having an amino group (-NHR 'with R' as defined above), carboxyl (-COOH) and / or thiol (-SH) in a hydrophilic polymer as a hydrophilicizing agent is lower to about 40%, preferably less than about 30%, more preferably less than about 20%, even more preferably less than about 10% by weight based on the total weight of the hydrophilic polymer.
[127] A preferred class of hydrophilic polymers as hydrophilicity enhancing agents is that of polysaccharides that contain amino or carboxyl groups, for example, such as carboxymethylcellulose (which has a carboxyl content of about 40% or less, which is estimated based on the composition of the repetitive units, - [C6H10-mO5 (CH2CO2H) m] -, where m ranges from 1 to 3), carboxyethylcellulose (which has a carboxyl content of about 36% or less, which is estimated based on the composition of the repetitive units, - [C6H10-mO5 (C2H4CO2H) m] -, where m ranges from 1 to 3), carboxypropylcellulose (which has a carboxyl content of about 32% or less, which is estimated based on the composition of the repetitive units, - [C6H10-mO5 (C3H6CO2H) m] -, where m varies from 1 to 3), hyaluronic acid (which has a carboxyl content of about 11%, which is estimated based on the composition of the repetitive units, - (C13H20O9NCO2H) -), chondroitin sulfate a (which has a carboxyl content of about 9.8%, which is estimated based on the composition of the repetitive units, - (C12H18O13NS CO2H) -), or combinations thereof.
[128] Another preferred class of hydrophilic polymers as hydrophilicity enhancing agents includes, without limitation: (poly) ethylene glycol (PEG) with a monoamino, carboxyl or thiol group (for example, PEG-NH2, PEG-SH, PEG- COOH); H2N-PEG-NH2; HOOC-PEG-COOH; HS-PEG-SH; H2N-PEG-COOH; HOOC-PEG-SH; H2N-PEG-SH; Multiple-arm PEG with one or more amino, carboxyl or thiol groups; PEG dendrimers with one or more amino, carboxyl or thiol groups; a homopolymer or copolymer terminated with diamino or dicarboxyl of a non-reactive hydrophilic vinyl monomer; a monoamino or monocarboxyl-terminated homopolymer or copolymer of a non-reactive hydrophilic vinyl monomer; a copolymer which is a product of the polymerization of a composition comprising (1) about 60% by weight or less, preferably from about 0.1% to about 30%, more preferably from about 0.5% to about 20%, even more preferably from about 1% to about 15% by weight of one or more reactive vinyl monomers and (2) at least one non-reactive hydrophilic vinyl monomer and / or at least least one vinyl monomer containing phosphorylcholine; and combinations thereof. Reactive vinyl monomers and non-reactive hydrophilic vinyl monomers are those already described above.
[129] More preferably, a hydrophilic polymer as a hydrophilicity-enhancing agent is PEG-NH2; PEG-SH; PEG-COOH; H2N-PEG-NH2; HOOC-PEG-COOH; HS-PEG-SH; H2N-PEG-COOH; HOOC-PEG-SH; H2N-PEG-SH; Multiple-arm PEG with one or more amino, carboxyl or thiol groups; PEG dendrimers with one or more amino, carboxyl or thiol groups; a monoamino, monocarboxyl, diamino or dicarboxyl-terminated homopolymer or copolymer of a non-reactive hydrophilic vinyl monomer selected from the group consisting of acrylamide (AAm), N, N-dimethylacrylamide (DMA), N-vinylpyrrolidone (NVP), N -vinyl-N-methyl acetamide, (meth) glycerol acrylate, (meth) hydroxyethyl acrylate, N-hydroxyethyl (meth) acrylamide, (meth) C1-C4-alkoxy polyethylene glycol which has a weighted average molecular weight up to 400 Daltons, vinyl alcohol, N-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, N (meth) acrylate, N-dimethylaminoethyl, N, N-dimethylaminopropyl- (meth) acrylamide, (meth) acryloyloxyethyl phosphorylcholine, and combinations thereof; a copolymer which is a product of the polymerization of a composition comprising (1) from about 0.1% to about 30%, preferably from about 0.5% to about 20%, more preferably from about 1% to about 15% by weight of (meth) acrylic acid, C2-C12 alkylacrylic acid, vinylamine, allylamine and / or (meth) acrylate of C2-C4 alkyl and (2) ( met) acryloyloxyethyl phosphorylcholine and / or at least one non-reactive hydrophilic vinyl monomer selected from the group consisting of acrylamide, N, N-dimethylacrylamide, N-vinylpyrrolidone, N-vinyl-N-methyl acetamide, (glycerol acrylate) , hydroxyethyl (meth) acrylate, N-hydroxyethyl (meth) acrylamide, (C1-C4-alkoxy polyethylene glycol) acrylate with a weighted average molecular weight of up to 400 Daltons, vinyl alcohol, and combinations thereof.
[130] More preferably, the hydrophilicity-enhancing agent as a hydrophilicity-enhancing agent is PEG-NH2; PEG-SH; PEG-COOH; polyvinylpyrrolidone terminated with monoamino, monocarboxyl, diamino or dicarboxyl; monoamino, monocarboxyl, diamino or dicarboxyl-terminated polyacrylamide; monoamino-, poly (DMA) terminated with monocarboxyl, diamino or dicarboxyl; poly (DMA-co-NVP) terminated with monoamino or monocarboxyl, diamino or dicarboxyl; (meth) acrylate) of (poly) NVP-co- N, N-dimethylaminoethyl terminated with monoamino, monocarboxyl, diamino or dicarboxyl; (poly) vinyl alcohol terminated with monoamino, monocarboxyl, diamino or dicarboxyl; homopolymer or copolymer of poly [(meth) acryloyloxyethyl phosphorylcholine] terminated with monoamino, monocarboxyl, diamino or dicarboxyl; homopolymer or copolymer of (poly) NVP-vinyl alcohol terminated with monoamino, monocarboxyl, diamino or dicarboxyl; homopolymer or copolymer of (poly) DMA-vinyl alcohol terminated with monoamino, monocarboxyl, diamino or dicarboxyl; [oly (meth) acrylic-co-acrylamide acid] from about 0.1% to about 30%, preferably from about 0.5% to about 20%, more preferably from about preferably from 1% to about 15% by weight of (meth) acrylic acid; [oly (meth) acrylic acid-co-NVP) from about 0.1% to about 30%, preferably from about 0.5% to about 20%, more preferably from about 1 % to about 15% by weight of (meth) acrylic acid; a copolymer which is a product of the polymerization of a composition comprising (1) (meth) acryloyloxyethyl phosphorylcholine and (2) from about 0.1% to about 30%, preferably from about 0.5 % to about 20%, more preferably from about 1% to about 15% by weight of a vinyl monomer containing carboxylic acid and / or a vinyl monomer containing amino, and combinations thereof.
[131] PEGs with functional groups and PEGs with multiple arms with functional groups can be purchased from several commercial suppliers, for example, Poliscience and Shearwater Polimers, Inc., etc.
[132] Homopolymers or copolymers terminated with monoamino, monocarboxyl, diamino or dicarboxyl of one or more non-reactive hydrophilic vinyl monomers or of a vinyl monomer containing phosphorylcholine can be prepared according to procedures described in United States Patent No. 6,218,508, incorporated herein by reference in its entirety. For example, to prepare a diamino or dicarboxyl-terminated homopolymer or copolymer of a non-reactive hydrophilic vinyl monomer, the non-reactive vinyl monomer, a chain transfer agent with an amino or carboxyl group (for example, 2-aminoethanethiol, 2-acid -mercaptopropinic, thioglycolic acid, thiolactic acid or other hydroxy mercaptans, aminomercaptanes or mercaptans containing carboxyl), and optionally another vinyl monomer, are copolymerized (thermally or actinically) with a reactive vinyl monomer (which has an amino or carboxyl group) in the presence of free radical initiator. In general, the molar ratio of the chain transfer agent to that of all vinyl monomers other than the reactive vinyl monomer varies from about 1: 5 to about 1: 100, while the molar ratio of the chain transfer agent chain for the reactive vinyl monomer is 1: 1. In such a preparation, the chain transfer agent with amino or carboxyl group is used to control the molecular weight of the resulting hydrophilic polymer and forms a terminal end of the resulting hydrophilic polymer, so as to provide the resulting hydrophilic polymer with an amino or carboxyl end group. , while the reactive vinyl monomer provides the other carboxyl or amino terminal group to the resulting hydrophilic polymer. Similarly, to prepare a monoamino or monocarboxyl-terminated homopolymer or copolymer of a non-reactive hydrophilic vinyl monomer, the non-reactive vinyl monomer, a chain transfer agent with an amino or carboxyl group (for example, 2-aminoethanethiol, 2- mercaptopropinic, thioglycolic acid, thiolactic acid or other hydroxy-mercaptan, aminomercaptan or mercaptan containing carboxyl), and optionally other vinyl monomers, are copolymerized (thermally or actinically) in the absence of any reactive vinyl monomer.
[133] As used in the present application, a copolymer of a non-reactive hydrophilic vinyl monomer refers to a polymerization product of a non-reactive hydrophilic vinyl monomer with one or more additional vinyl monomers. Copolymers comprising a non-reactive hydrophilic vinyl monomer and a reactive vinyl monomer (for example, a carboxyl-containing vinyl monomer) can be prepared according to any well-known radical polymerization method or purchased from commercial suppliers. Copolymers containing methacryloyloxyethyl phosphorylcholine and vinyl monomer containing carboxyl can be purchased from NOP Corporation (for example, LIPIDURE® -A and -AF).
[134] The weighted average molecular weight Mw of the hydrophilic polymer having at least one amino, carboxyl or thiol group (as a hydrophilicity-enhancing agent) is preferably from about 500 to about 1,000,000, more preferably from about 1,000 to about 500,000.
[135] According to the invention, the reaction between a hydrophilicity-enhancing agent and a polyamine functionalized with epichlorohydrin or polyamidoamine is carried out at a temperature from about 40 ° C to about 100 ° C for a sufficient period of time (from about 0.3 hour to about 24 hours, preferably from about 1 hour to about 12 hours, even more preferably from about 2 hours to about 8 hours) to form a water-soluble and thermally crosslinkable hydrophilic polymeric material containing azetidinium groups.
[136] According to the invention, the concentration of a hydrophilicity-enhancing agent in relation to a polyamine functionalized with epichlorohydrin or polyamidoamine must be chosen so as not to leave a resulting hydrophilic polymeric material that is not water-soluble (that is, a solubility less than 0.005 g per 100 ml of water at room temperature) and consume no more than about 99%, preferably about 98%, more preferably about 97%, even more preferably about 96% of the polyamine azetidinium groups functionalized with epichlorohydrin or polyamidoamine.
[137] According to the invention, heating is preferably carried out by autoclaving a precast SiHy contact lens comprising amino and / or carboxyl groups on and / or close to the surface of the contact lens or a base coat comprising amino and / or carboxyl groups and immersed in a packaging solution (ie, a buffered aqueous solution) that includes a thermally crosslinkable, water-soluble hydrophilic polymeric material in a sealed lens package at a temperature at from about 118 ° C to about 125 ° C for approximately 20-90 minutes. According to this embodiment of the invention, the packaging solution is an aqueous buffered solution which is ophthalmically safe after autoclaving. Alternatively, heating is preferably carried out by autoclaving a pre-molded SiHy contact lens which comprises a base coat and a layer of a thermally cross-linkable, water-soluble hydrophilic polymeric material on the base coat immersed in a packaging solution (i.e., a buffered aqueous solution) in a sealed lens pack at a temperature from about 118 ° C to about 125 ° C for approximately 20-90 minutes.
[138] Lens packs (or containers) are well known to those skilled in the art for autoclaving and storing a soft contact lens. Any lens packaging can be used in the invention. Preferably, a lens pack is a blister pack comprising a base and a cap, where the cap is removably sealed to the base, where the base includes a cavity for receiving a sterile packaging solution and the lens contact.
[139] The lenses are packed in individual packages, sealed and sterilized (for example, by autoclaving at about 120 ° C or more for at least 30 minutes) before being distributed to users. Those skilled in the art will understand how to seal and sterilize lens packaging.
[140] According to the invention, a packaging solution contains at least one buffering agent and one or more of other ingredients known to those skilled in the art. Examples of other ingredients include, without limitation, tonicity agents, surfactants, antibacterial agents, preservatives and lubricants (or water-soluble viscosity builders) (for example, cellulose derivatives, polyvinyl alcohol, polyvinylpyrrolidone).
[141] The packaging solution contains a buffering agent in an amount sufficient to maintain the pH of the packaging solution in the desired range, for example, preferably in a physiologically acceptable range of about 6 to about 8.5. Any known physiologically compatible buffering agent can be used. Buffering agents suitable as a constituent of the contact lens care composition according to the invention are known to those skilled in the art. Examples are boric acid, borates, for example, sodium borate, citric acid, citrates, for example, potassium citrate, bicarbonates, for example, sodium bicarbonate, TRIS (2-amino-2-hydroxymethyl-1,3-propanediol ), Bis-Tris (Bis- (2-hydroxyethyl) - imino-tris- (hydroxymethyl) -methane), bis-aminopolyols, triethanolamine, ACES (N- (2-hydroxyethyl) -2-aminoethanesulfonic acid), BES (acid N, N-Bis (2-hydroxyethyl) -2-aminoethanesulfonic acid), HEPES (4- (2-hydroxyethyl) -1-piperazine ethanesulfonic acid), MES (2- (N-morpholino) ethanesulfonic acid), MOPS (3- [N-morpholino] - propanesulfonic), PIPES (piperazine-N, N'-bis (2-ethanesulfonic acid), TES (N- [Tris (hydroxymethyl) methyl] -2-aminoethanesulfonic acid), salts thereof, phosphate, for example, Na2HPO4, NaH2PO4, and KH2PO4 or mixtures thereof A preferred bis-aminopoliol is 1,3-bis (tris [hydroxymethyl] -methylamino) propane (bis-TRIS-propane). buffering in a packaging solution is preferably from 0.001% to 2%, preferably from 0.01% to 1%; even more preferably from about 0.05% to about 0.30% by weight.
[142] The packaging solution has a tonicity from about 200 to about 450 milliosmol (mOsm), preferably from about 250 to about 350 mOsm. The tonicity of a packaging solution can be adjusted by adding organic or inorganic substances that affect tonicity. Ocularly suitable tonicity agents include, but are not limited to, sodium chloride, potassium chloride, glycerol, propylene glycol, polyols, mannitols, sorbitol, xylitol and mixtures thereof.
[143] A packaging solution of the invention has a viscosity from about 1 centipoise to about 20 centipoise, preferably from about 1.2 centipoise to about 10 centipoise, more preferably from about 1 , 5 centipoises to about 5 centipoises, at 25 ° C.
[144] In a preferred embodiment, the packaging solution preferably comprises from about 0.01% to about 2%, more preferably from about 0.05% to about 1.5% , even more preferably from about 0.1% to about 1%, even more preferably from about 0.2% to about 0.5%, by weight of a water-soluble and thermally crosslinkable hydrophilic polymeric material of the invention.
[145] A packaging solution of the invention may contain a viscosity-enhancing polymer. Preferably, the viscosity-enhancing polymer is non-ionic. Increasing the viscosity of the solution results in a film on the lens that can facilitate comfortable use of the contact lens. The viscosity-enhancing component also serves to cushion the impact on the surface of the eye during placement and also serves to relieve irritation in the eye.
[146] Preferred viscosity-enhancing polymers include, but are not limited to, water-soluble cellulose ethers (for example, methyl cellulose (MC), ethyl cellulose, hydroxymethylcellulose, hydroxyethyl cellulose (HEC), hydroxypropylcellulose (HPC), hydroxypropylmethyl cellulose (HPMC), or a mixture thereof, water-soluble polyvinyl alcohols (PVAs), high molecular weight (poly) ethylene oxide with a molecular weight greater than about 2000 (up to 10,000,000 Daltons), polyvinylpyrrolidone with a molecular weight from about from 30,000 daltons to about 1,000,000 daltons, a copolymer of N-vinylpyrrolidone and at least one dialkylaminoalkyl (meth) acrylate with 7-20 carbon atoms, and combinations thereof. Water-soluble cellulose ethers and vinylpyrrolidone copolymers and dimethylaminoethyl methacrylate are the most preferred viscosity-enhancing polymers, copolymers of N-vinylpyrrolidone and dimethylaminoethyl methacrylate are c commercially available, for example, Copolymer 845 and Copolymer 937 from ISP.
[147] The viscosity-enhancing polymer is present in the packaging solution in an amount from about 0.01% to about 5% by weight, preferably from about 0.05% to about 3% by weight, even more preferably from about 0.1% to about 1% by weight, based on the total amount of the packaging solution.
[148] A packaging solution can further comprise a polyethylene glycol having a molecular weight of about 1200 or less, more preferably 600 or less, even more preferably from about 100 to about 500 Daltons.
[149] Where at least one of the crosslinked coating and the packaging solution contains a polymeric material that has polyethylene glycol segments, the packaging solution preferably comprises a sufficient amount of a-oxo-multi-acid or salt thereof to obtain a reduced susceptibility to oxidative degradation of the polyethylene glycol segments. A commonly assigned copending patent application (United States Patent Application Publication No. 2004/0116564 A1, hereby incorporated in its entirety) describes that oxo-multi-acid or salt thereof can reduce the susceptibility to oxidative degradation of a polymeric material that contains PEG.
[150] a-oxo-multi-acids or biocompatible salts of the same examples include, without limitation, citric acid, 2-ketoglutaric acid or malic acid or biocompatible (preferably ophthalmically compatible) salts thereof. More preferably, an α-oxo-multi-acid is citric or malic acid or biocompatible (preferably ophthalmically compatible) salts thereof (for example, sodium, potassium, among others).
[151] According to the invention, the packaging solution can also comprise mucin-like materials, ophthalmically beneficial and / or surfactant materials. The exemplary mucin type materials described above, the exemplary ophthalmically beneficial materials described above, the exemplary surfactants described above can be used in this embodiment.
[152] In a preferred embodiment, a SiHy contact lens of the invention has a relatively long break-through time (WBUT). WBUT is the time required for the water film to break (dehydrate), exposing the underlying lens material under visual examination. A SiHy contact lens that has a longer WBUT can keep the water film (tears) on its surface for a relatively longer period of time when used on the eye. It is less likely to develop dry spots between eye blinks and can provide greater comfort during use. WBUT can be measured according to the procedures described in the Example below. Preferably, a SiHy contact lens of the invention has a surface hydrophilicity characterized by having a break time in water of at least about 10 seconds.
[153] In a preferred embodiment, a SiHy contact lens of the invention has a surface wetting capability characterized by having an average water contact angle of about 90 degrees or less, preferably about 80 degrees or less , more preferably about 70 degrees or less, even more preferably about 60 degrees or less, even more preferably about 50 degrees or less.
[154] In a preferred embodiment, a SiHy contact lens has an oxygen transmissibility of at least about 40, preferably at least about 60, more preferably at least about 80, even more preferably at least about 100 , even more preferably at least about 120 barrers / mm.
[155] It will be understood that, although in this aspect of the invention several modalities, including preferred embodiments of the invention, can be separately described above, they can be combined and / or used together in any desirable way to arrive at different modalities of a contact lens silicone hydrogel of the invention.
[156] In another aspect, the invention offers a hydrated silicone hydrogel contact lens. A hydrated silicone hydrogel contact lens of the invention comprises: a silicone hydrogel material as a volumetric material, an opposing front and rear surface; wherein the contact lens has an oxygen transmissibility of at least about 40, preferably at least about 60, more preferably at least about 80, even more preferably at least about 110 barrers / mm, and a profile of cross sectional surface module comprising, along the shortest line between the anterior and posterior surfaces on the surface of a cross section of the contact lens, an anterior outer zone including and close to the anterior surface, an inner zone including and around from the center of the shorter line and a posterior outer zone including and close to the posterior surface, where the anterior outer zone has a medium anterior surface module (designated SM ^ t), while the posterior outer area has a posterior surface module medium (called SMPost), in which the inner zone presents a medium internal surface module (called SMtotemo), where at least one of
is by the SM Internal SM less than about 20%, preferably at least about 25%, more preferably at least about 30%, even more preferably at least about 35%, even more preferably at least about 40%. Preferably, the front and rear outer zones cover a range of at least about 0.1 μm, preferably from about 0.1 μm to about 20 μm, more preferably from about 0.25 μm at about 15 μm, even more preferably from about 0.5 μm to about 12.5 μm, even more preferably from about 1 μm to about 10 μm.
[157] In a preferred embodiment, the hydrated hydrogel silicone contact lens may have an elastic modulus (or Young's modulus) from about 0.3 MPa to about 1.8 MPa, preferably from about from 0.4 MPa to about 1.5 MPa, more preferably from about 0.5 MPa to about 1.2 MPa; a water content from about 10% to about 75%, preferably from about 10% to about 70%, more preferably from about 15% to about 65%; even more preferably from about 20% to about 60%, even more preferably from about 25% to about 55% by weight; a surface wetting ability characterized by having an average angle of contact with water of about 90 degrees or less, preferably about 80 degrees or less, more preferably about 70 degrees or less, even more preferably about 60 degrees or less, even more preferably about 50 degrees or less; a surface hydrophilicity characterized by having a WBUT of at least about 10 seconds; or combinations thereof.
[158] In another preferred embodiment, the anterior and posterior surfaces exhibit a low concentration on the surface of negatively charged groups (for example, carboxylic acid groups), as characterized by an attraction of at most about 200, preferably at most about 160, more preferably at most about 120, even more preferably at most about 90, even more preferably at most about 60 positively charged particles in the positively charged particle adhesion test. To have a low concentration on the surface of negatively charged groups (for example, carboxylic acid groups), the outer front and rear layers of hydrogel must have a relatively low carboxylic acid content. Preferably, the front and rear outer layers of hydrogel have a carboxylic acid content of about 20% by weight or less, preferably about 15% by weight or less, even more preferably about 10% by weight or less, even more preferably about 5% by weight or less.
[159] In another preferred embodiment, a SiHy contact lens of the invention has good surface lubricity characterized by a critical friction coefficient (designated as CCOF) of about 0.046 or less, preferably about 0.043 or less, more preferably about 0.040 or less. Alternatively, a SiHy contact lens of the invention preferably has a better lubricity than that of ACUVUE OASYS or ACUVUE TruEye, as measured in a blind test according to the lubricity assessment procedures described in Example 1.
[160] In another preferred embodiment, the hydrated SiHy contact lens preferably has a high resistance to digital friction, as characterized by not having visible surface crack lines in the dark field after the SiHy contact lens is rubbed between the fingers. It is believed that surface cracks induced by rubbing the fingers may reduce surface lubricity and / or may not be able to prevent the migration of the silicone to the surface (exposure).
[161] In another preferred embodiment, a hydrated SiHy contact lens of the invention comprises an inner layer of the hydrogel silicone material, an outer layer of hydrogel and an outer outer layer of hydrogel, wherein the outer front and rear layers of hydrogels have a substantially uniform thickness and fuse at the peripheral edge of the contact lens to completely envelop the inner layer of the hydrogel silicone material. It should be understood that the first and second outer zones in the cross sectional surface module profile correspond to the two outer hydrogel layers, while the inner zone corresponds to the inner layer of the silicone hydrogel material. All of the various modalities of the outer hydrogel layers (crosslinked coating) described above for the other aspect of the invention can be used, alone or in any combination, in this aspect of the invention as the outer hydrogel layers. All of the various embodiments of the inner layer of a silicone hydrogel material described above for another aspect of the invention can be used, alone or in any combination, in this aspect of the invention as the inner layer of the silicone hydrogel material.
[162] According to this aspect of the invention, the outer layers of hydrogel have a substantially uniform thickness and have a thickness of at least about 0.1 μm, preferably from about 0.1 μm to about 20 μm, more preferably from about 0.25 μm to about 15 μm, even more preferably from about 0.5 μm to about 12.5 μm, even more preferably from about 1 μm to about 10 μm. The thickness of each outer hydrogel layer of a SiHy contact lens of the invention is determined by AFM analysis of a cross section of the SiHy contact lens in the fully hydrated state, as already described above. In a more preferred embodiment, the thickness of each outer hydrogel layer is at most about 30% (i.e., 30% or less), preferably at most about 20% (20% or less), more preferably at most about 10% (10% or less) of the central thickness of the SiHy contact lens in the fully hydrated state. In addition, each of the two outer hydrogel layers is substantially silicone-free (as defined by having an atomic percentage of silicon of about 5% or less, preferably about 4% or less, even more preferably about 3% or less, of the total elemental percentage, measured by XPS analysis of the contact lens in the dry state), preferably totally silicone-free. It should be understood that a small percentage of silicone can optionally (however, preferably not) be incorporated into the polymeric network of the external hydrogel layer, as long as it does not significantly deteriorate the surface properties (hydrophilicity, wetting capacity and / or lubricity) of a SiHy contact lens.
[163] In another preferred embodiment, the two outer hydrogel layers of a hydrated SiHy contact lens of the invention comprise a water content higher than the water content (called WCLente) of the hydrated hydrogel silicone contact lens and, more especially, it should be at least about 1.2 times (ie, 120%) of WCLente. It is believed that the proportion of water expansion of each outer layer of hydrogel may represent approximately the water content of the outer layer of hydrogel, as already discussed above. Where WCLente is about 45% or less, the water swelling ratio of each outer layer of hydrogel is preferably at least about 150%, more preferably at least about 200%, more preferably at least about 250 %, even more preferably at least about 300%. Where WCLente is greater than 45%, the proportion of water expansion of each outer layer of hydrogel is at least about
preferably about
more preferably about
even more preferably about
In alternative preferred embodiments, where WCLente is about 55% or less, the water swelling ratio of each outer hydrogel layer is at least about 150%; where WCLente is about 60% or less, the proportion of water expansion of each outer layer of hydrogel is at least about 200%; where WCLente is about 65% or less, the proportion of water expansion of each outer layer of hydrogel is at least about 250%; where WCLente is about 70% or less, the water expansion ratio of each outer layer of hydrogel is at least about 300%.
[164] Preferably, the SiHy contact lens further comprises a transition layer located between the hydrogel silicone material and the outer hydrogel layer. All of the various modalities of the transition layer already described for the previous aspect of the invention can be used, alone or in any combination, in this aspect of the invention.
[165] A hydrated SiHy contact lens of the invention can be prepared according to the methods described above. All of the various modalities of the inner layer (i.e., silicone hydrogel material) described above can be used, alone or in any combination, in this aspect of the invention as the silicone hydrogel core. All of the various embodiments already described above for the previous aspect of the invention can be used, alone or in any combination, in this aspect of the invention.
[166] It will be understood that, although in this aspect of the invention several modalities, including preferred embodiments of the invention, can be separately described above, they can be combined and / or used together in any desirable manner to arrive at different modalities of a contact lens silicone hydrogel of the invention. All of the various embodiments described above for the prior aspect of the invention can be used alone or in combination in any desirable manner in this aspect of the invention.
[167] In another aspect, the invention offers a hydrated silicone hydrogel contact lens. A hydrated silicone hydrogel contact lens of the invention comprises: a silicone hydrogel material as a volumetric material, an opposing front and rear surface; wherein the contact lens has (1) an oxygen transmissibility of at least about 40, preferably at least about 60, more preferably at least about 80, even more preferably at least about 110 barrers / mm and ( 2) a surface lubricity characterized by having a critical friction coefficient (designated as CCOF) of about 0.046 or less, preferably about 0.043 or less, more preferably about 0.040 or less, where the front and rear surfaces have a low concentration on the surface [of negatively charged groups, including carboxylic acid groups, as characterized by an attraction of at most about 200, preferably at most about 160, more preferably at most about 120, even more preferably at most about from 90, even more preferably at most about 60 positively charged particles in the positively charged particle adhesion test.
[168] In a preferred embodiment, the hydrated hydrogel silicone contact lens has an elastic modulus (or Young's modulus) from about 0.3 MPa to about 1.8 MPa, preferably from about 0.4 MPa to about 1.5 MPa, more preferably from about 0.5 MPa to about 1.2 MPa; a water content from about 10% to about 75%, preferably from about 10% to about 70%, more preferably from about 15% to about 65%; even more preferably from about 20% to about 60%, even more preferably from about 25% to about 55% by weight; a surface wetting ability characterized by having an average angle of contact with water of about 90 degrees or less, preferably about 80 degrees or less, more preferably about 70 degrees or less, even more preferably about 60 degrees or less, even more preferably about 50 degrees or less; a surface hydrophilicity characterized by having a WBUT of at least about 10 seconds; or combinations thereof.
[169] In another preferred embodiment, the hydrated SiHy contact lens preferably has a high resistance to conforming digital friction, characterized by having no visible surface crack lines in the dark field after the SiHy contact lens is rubbed between your fingers. It is believed that surface cracks induced by rubbing the fingers may reduce surface lubricity and / or may not be able to prevent the migration of the silicone to the surface (exposure).
[170] In another preferred embodiment, a hydrated SiHy contact lens of the invention comprises an inner layer of the hydrogel silicone material, an outer layer of hydrogel and an outer outer layer of hydrogel, with the outer front and rear layers of hydrogel have a substantially uniform thickness and fuse at the peripheral edge of the contact lens to completely envelop the inner layer of the silicone hydrogel material. It will be understood that the first and second outer zones in the cross sectional surface module profile correspond to the two outer hydrogel layers, while the inner zone corresponds to the inner layer of the hydrogel silicone material. All of the various modalities of the hydrogel outer layers (crosslinked coating) described above for another aspect of the invention can be used, alone or in any combination, in this aspect of the invention as the outer hydrogel layers. All of the various embodiments of the inner layer of a silicone hydrogel material described above for another aspect of the invention can be used, alone or in any combination, in this aspect of the invention as the inner layer of the silicone hydrogel material.
[171] According to this aspect of the invention, the outer layers of hydrogel have a substantially uniform thickness and have a thickness of at least about 0.1 μm, preferably from about 0.1 μm to about 20 μm, more preferably from about 0.25 μm to about 15 μm, even more preferably from about 0.5 μm to about 12.5 μm, even more preferably from about 1 μm to about 10 μm. The thickness of each outer hydrogel layer of a SiHy contact lens of the invention is determined by AFM analysis of a cross section of the SiHy contact lens in the fully hydrated state, as already described above. In a more preferred embodiment, the thickness of each outer hydrogel layer is preferably at most about 30% (i.e., 30% or less), preferably at most about 20% (20% or less), more preferably at most about 10% (10% or less) of the central thickness of the SiHy contact lens in the fully hydrated state. In addition, each of the two outer hydrogel layers is substantially silicone-free (as defined by having an atomic percentage of silicon of about 5% or less, preferably about 4% or less, even more preferably about 3% or less, of the total elemental percentage, as measured by XPS analysis of the contact lens in the dry state), preferably completely silicone-free. It should be understood that a small percentage of silicone can optionally (however, preferably not) be incorporated into the polymeric network of the external hydrogel layer, as long as it does not significantly deteriorate the surface properties (hydrophilicity, wetting capacity and / or lubricity) of a SiHy contact lens. To have a low concentration on the surface of negatively charged groups (for example, carboxylic acid groups), the outer front and rear layers of hydrogel must have a relatively low carboxylic acid content. Preferably, the front and rear outer layers of hydrogel have a carboxylic acid content of about 20% by weight or less, preferably about 15% by weight or less, even more preferably about 10% by weight or less, even more preferably about 5% by weight or less.
[172] In another preferred embodiment, the two outer hydrogel layers of a hydrated SiHy contact lens of the invention comprise a water content greater than the water content (referred to as WCLente) of the hydrated hydrogel silicone contact lens and, more specifically, it should be at least about 1.2 times (ie, 120%) the water content (WCLente) of the hydrated hydrogel silicone contact lens. It is believed that the proportion of water expansion of each outer layer of hydrogel may represent approximately the water content of the outer layer of hydrogel, as already discussed above. Where WCLente is about 45% or less, the water swelling ratio of each outer layer of hydrogel is preferably at least about 150%, more preferably at least about 200%, more preferably at least about 250 %, even more preferably at least about 300%. Where WCLente is greater than 45%, the proportion of water expansion of each outer layer of hydrogel is at least about
preferably about
more preferably about
even more preferably about
In alternative preferred embodiments, where WCLente is about 55% or less, the water swelling ratio of each outer hydrogel layer is at least about 150%; where WCLente is about 60% or less, the proportion of water expansion of each outer layer of hydrogel is at least about 200%; where WCLente is about 65% or less, the proportion of water expansion of each outer layer of hydrogel is at least about 250%; where WCLente is about 70% or less, the water expansion ratio of each outer layer of hydrogel is at least about 300%.
[173] In another preferred embodiment, the outer front and back layers of hydrogel have, independently of each other, a reduced surface modulus of at least about 20%, preferably at least about 25%, more preferably at least about 30%, even more preferably at least about 35%, even more preferably at least about 40%, with respect to the inner layer.
[174] Preferably, the SiHy contact lens further comprises a transition layer located between the hydrogel silicone material and the outer hydrogel layer. All of the various transition layer modalities described for the previous aspect of the invention can be used, alone or in any combination, in this aspect of the invention.
[175] A hydrated SiHy contact lens of the invention can be prepared according to the methods described above. All of the various modalities of the inner layer (i.e., hydrogel silicone material) described above can be used, alone or in any combination, in this aspect of the invention as the silicone core. All of the various embodiments already described above for the previous aspect of the invention can be used, alone or in any combination, in this aspect of the invention.
[176] It will be understood that, although in this aspect of the invention several modalities, including preferred embodiments of the invention, can be separately described above, they can be combined and / or used together in any desirable manner to arrive at different modalities of a contact lens silicone hydrogel of the invention. All of the various embodiments described above for the foregoing aspect of the invention can be used alone or in combination in any desirable manner in this aspect of the invention.
[177] The description above will allow those skilled in the art to put the invention into practice. Various modifications, variations and combinations can be made in the various modalities described here. To enable the reader to better understand the specific modalities and their advantages, we suggest that you consult the following examples. It is intended that the descriptive report and the examples are considered as exemplary.
[178] Although various aspects and modalities of the invention have been described using specific terms, devices and methods, such description is for illustrative purposes only. The words used are descriptive and not limiting words. It will be understood that changes and variations can be made by those skilled in the art without departing from the spirit or scope of the present invention, which is presented in the claims below. Furthermore, it will be understood that the aspects of the various modalities can be alternated either totally or partially or can be combined in any way and / or used together. Therefore, the spirit and scope of the appended claims will not be limited to the description of the preferred versions contained herein. Example 1 Oxygen Permeability Measurements
[179] The apparent oxygen permeability of a lens and the oxygen transmissibility of a lens material are determined according to a technique similar to that described in United States Patent No. 5,760,100 and in an article by Winterton et al. (The Cornea: Transactions of the World Congress on the Cornea 111, H.D. Cavanagh Ed., Raven Press: New York 1988, pages 273280), both of which are incorporated herein by reference in their entirety. Oxygen flows (J) are measured at 34 ° C in a wet cell (ie gas streams are maintained at about 100% relative humidity) using a Dk1000 instrument (available from Applied Design and Development Co ., Norcross, GA) or similar analytical instrument. A stream of air, which has a known percentage of oxygen (for example, 21%), is passed through one side of the lens at a rate of about 10 to 20 cm3 / min, while a stream of nitrogen is passed through the opposite side of the lens at a rate of about 10 to 20 cm3 / min. A sample is equilibrated in a test medium (ie, saline or distilled water) at the prescribed test temperature for at least 30 minutes before measurement, but not more than 45 minutes. Any test medium used as the top layer is equilibrated at the established test temperature for at least 30 minutes before measurement, however, not more than 45 minutes. The speed of the agitation motor is set to 1200 ± 50 rpm, which corresponds to an indicated setting of 400 ± 15 on the stepper motor controller. The barometric pressure surrounding the system, Pmeasured, is measured. The thickness (t) of the lens in the area being exposed for testing is determined by measuring about 10 positions with a VL-50 Mitotoya micrometer, or similar instrument, and averaging the measurements. The oxygen concentration in the nitrogen stream (that is, the oxygen that diffuses through the lens) is measured using the DK1000 instrument. The apparent oxygen permeability of the lens material, Dkap, is determined from the following formula: Dkap = Jt / (Poxigen) where: J = oxygen flow [microliters of O2 / cm2- minute] Poxigen = (Pmeasure -Vapor) of water) = (% of O2 in the air stream) [mm Hg] = partial pressure of oxygen in the air stream Pmed = barometric pressure (mm Hg) P water vapor = 0 mm Hg at 34 ° C (in a dry cell ) (mm Hg) P water vapor = 40 mm Hg at 34 ° C (in a wet cell) (mm Hg) t = average lens thickness across the exposed test area (mm) Dkap is expressed in units of barrers.
[180] The apparent oxygen transmittance (Dk / t) of the material can be calculated by dividing the apparent oxygen permeability (Dkap) by the average thickness (t) of the lens.
[181] The measurements described above are not corrected for the so-called boundary layer effect, which is attributable to the use of an aqueous or saline solution on the contact lens during oxygen flow measurement. The boundary layer effect causes the reported value for the apparent Dk of a silicone hydrogel material to be lower than the true intrinsic Dk value. In addition, the relative impact of the border layer effect is greater for thinner lenses than for thicker lenses. The net effect is that the reported Dk appears to vary depending on the thickness of the lens when it should remain constant.
[182] The intrinsic Dk value of a lens can be estimated based on the corrected Dk value for the surface resistance to oxygen flow caused by the boundary layer effect as follows.
[183] Measure the apparent oxygen permeability values (single point) of the lotrafilcon A (Focus®N & D® from CIBA VISION CORPORATION) or lotrafilcon B (AirOptix® from CIBA VISION CORPORATION) lenses using the same equipment. Reference lenses have an optical power similar to that of test lenses and are measured concurrently with test lenses.
[184] Measure the oxygen flow through a series of thicknesses of the lotrafilcon A or lotrafilcon B (reference) lenses using the same equipment according to the procedure described for apparent Dk measurements described above to obtain the intrinsic Dk value (Dki ) of the reference lens. A thickness series should cover a thickness range of approximately 100 μm or more. Preferably, the thickness range of the reference lens will include the thicknesses of the test lens. The Dkap of these reference lenses should be measured with the same equipment as the test lenses and, ideally, should be measured concomitantly with the test lenses. The equipment configuration and measurement parameters must be kept constant throughout the experiment. Individual samples can be measured several times, if desired.
[185] Determine the residual oxygen resistance value, Rr, from the results of the reference lens using equation 1 in the calculations.
where t is the thickness of the test lens (that is, the reference lens as well) and n is the number of measured reference lenses. Plot the residual oxygen resistance graph, Rr, as a function of the data to fit a curve of the form Y = a + bX where, for the jth lens, Yj = (ΔP / J) je X = tj. Resistance to residual oxygen, Rr is equal to.
[186] Use the residual oxygen resistance value determined above to calculate the correct oxygen permeability Dkc (estimated intrinsic Dk) for the test lenses based on equation 1. Dkc = t / [(t / Dka) - Rr] (two)
[187] The estimated intrinsic Dk of the test lens can be used to calculate what the apparent Dk (Dka_standard) would have been for a standard thickness lens in the same test environment based on equation 3. The standard thickness (standard) for lotrafilcon A = 85 μm. The standard thickness for lotrafilcon B = 60 μm. Dka_pattern = tpattern / [(tpattern / Dkc) + Rr_pattern] (3)
[188] Ion permeability measurements. The ionic permeability of a lens is measured according to the procedures described in United States Patent No. 5,760,100 (hereby incorporated by reference in its entirety). The ion permeability values reported in the examples below are relative ion flux diffusion coefficients (D / Dref) in relation to a lens material, Alsacon, as a reference material. Alsacon has an ion flow diffusion coefficient of 0.314 x 10-3mm2 / minute.
[189] Lubricity Assessment. The lubricity grade is a qualitative rating scheme where 0 is assigned to control lenses coated with polyacrylic acid, 1 is assigned to commercial Oasys® / TruEye®e lenses and 4 is assigned to commercial Air Optix® lenses. The samples are rinsed with an excess of DI water at least three times and then transferred to PBS before being evaluated. Before evaluation, hands are washed with a soap solution, rinsed with DI water in abundance and then dried with KimWipe® paper towels. The samples are manipulated between the fingers and a numerical value is assigned to each sample in relation to the standard lenses described above. For example, if it is determined that the lenses are only slightly better than Air Optix® lenses, then they are assigned the number 3. For the sake of consistency, all graduations are independently collected by the same two operators in order to avoid distortions and the data show good qualitative correspondence and consistency in the assessment.
[190] Surface Moisture Capability Tests. The angle of contact with water on a contact lens is a generic measure of the surface wetting capacity of the contact lens. In particular, a low contact angle with water corresponds to a more moisturizing surface. The average contact angles (sessile drop) of contact lenses are measured using a VCA 2500 XE contact angle meter from AST, Inc., based in Boston, Massachusetts. This equipment is capable of measuring advanced or recessed contact angles or sessile (static) contact angles. Measurements are made on fully hydrated contact lenses and immediately after blot drying as follows. A contact lens is removed from the bottle and washed 3 times in ~ 200 mL of fresh DI water to remove loosely attached packaging additives from the surface of the lens. The lens is then placed over the top of a clean, lint-free fabric (Alpha Wipe TX1009), securely fastened with the cloth to remove water from the surface, mounted on the contact angle measurement pedestal, blown dry with a jet of dry air and finally the contact angle of the sessile drop is automatically measured using the software provided by the manufacturer. The DI water used to measure the contact angle has a resistivity> 18 MQcm and the drop volume used is 2 μl. Typically, uncoated silicone hydrogel lenses (after autoclaving) have a sessile drop contact angle of around 120 degrees. The tweezers and pedestal are thoroughly washed with isopropanol and rinsed with DI water before coming into contact with the contact lenses.
[191] Water Break Time Tests (WBUT). The surface hydrophilicity of the lenses (after autoclaving) is assessed by determining the time required for the water film to break on the lens surface. In summary, the lenses are removed from the bottle and washed 3 times in ~ 200 mL of fresh DI water to remove loosely attached packaging additives from the surface of the lenses. The lens is then removed from the solution and held with forceps against a source of bright light. The time it takes for the water film to break (dehydrate) exposing the underlying lens material is observed visually. Typically, uncoated lenses break instantly when removed from DI water and a 0 second WBUT is assigned. Lenses that exhibit a WBUT = 5 seconds are considered to be lenses with good hydrophilicity and are believed to have an adequate capacity to support the tear film when used in the eye.
[192] Testing the Coating's Ability to Stay Intact. The ability to remain intact on a coating on the surface of a contact lens can be tested according to the Sudan Negro staining test, as described below. Contact lenses with a coating (an LbL coating, a plasma coating or any other coating) are immersed in a solution of Sudan Black dye (Sudan Black in vitamin E oil) and then rinsed thoroughly with water. Sudan Black dye is hydrophobic and exhibits a great tendency to be absorbed by a hydrophobic material or on the surface of a hydrophobic lens or hydrophobic spots on a partially coated surface of a hydrophobic lens (for example, silicone hydrogel contact lens) . If the coating on a hydrophobic lens is intact, no stain will be seen on the lens. All lenses under test are fully hydrated.
[193] Coating Durability Tests. The lenses are rubbed between your fingers 30 times with the Solo-care® multi-purpose lens care solution and then rinsed with saline. The above procedure is repeated for a given number of times, for example, from 1 to 30 times, (that is, the number of consecutive rubbing tests between the fingers that mimic cleaning and dipping cycles). The lenses are then subjected to the Sudan Negro test (that is, a test of the ability to remain intact from the above coating) to examine whether the coating is still intact. To survive the rubbing test between fingers, there should be no significantly increased dye stains (for example, dye stains that cover a maximum of about 5% of the total lens surface). The angles of contact with water are measured to determine the durability of the coating.
[194] Determination of Azetidinium Content. The azetidinium content in PAE can be determined according to one of the tests below.
[195] PPVS trials. The charge density of PAE (ie azetidinium content) can be determined according to the PPVS test, a colorimetric titration test where the titrating agent is vinyl potassium sulfate (PPVS) and toluidine blue is the indicator . See S-K Kam & J. Gregory, "Charge determination of synthetic cationic polielectrolytes by colloid titration," in Colloid & Surface A: Physicochem. Eng. Aspect, 159: 165-179 (1999). PPVS binds to positively charged species, for example, toluidine blue and the PAE azetidinium groups. Reductions in the absorbance intensities of toluidine blue are indicative of proportional PAE charge density (azetidinium content).
[196] PES-Na assay. The PES-Na assay is another colorimetric titration assay to determine the charge density of PAE (azetidinium content). In this test, the titrating agent is sodium polyethylene sulfonate (PES-Na), instead of PPVS. The assay is identical to the PPVS assay described above.
[197] PCD assays. The PCD assay is a potentiometric titration assay to determine the charge density of PAE (azetidinium content). The titrating agent is sodium polyethylene sulfonate (PES-Na), PPVS or other titrating agent. The PAE charge is detected by an electrode, for example, using the Mütek PCD-04 particle charge detector from BTG. The measurement principle for this detector can be found on the BTG website http://www.btg.com/products.asp langage=1&appli=5&numProd=357& cat = prod).
[198] NMR method. The positively charged portion active in the PAE is the azetidinium group (AZR). The NMR proportion method is a proportion of the number of specific protons for the AZR group as a function of the number of protons associated with non-AZR groups. This proportion is an indicator of the load or density of AZR for PAE.
[199] Waste Adhesion Test. Contact lenses with a highly charged surface may be susceptible to greater residue adherence during handling by the patient. A paper towel is rubbed against your hands using gloves, and then the two sides of the lens are rubbed with your fingers to transfer debris to the surface of the lens. The lens is quickly rinsed and then viewed under a microscope. A qualitative rating scale from 0 (no residue adhesion) to 4 (residue adhesion equivalent to a PAA-coated control lens) is used to rate each lens. Lenses with a score of "0" or "1" are considered acceptable. Example 2 Preparation of the CE-PDMS Macromere
[200] In the first step, α, ®-bis (2-hydroxyethoxypropyl) - polydimethylsiloxane (Mn = 2000, Shin-Etsu, KF-6001a) is capped with isophorone diisocyanate (IPDI) by means of a reaction of 49, 85 g of a, ®-bis (2-hydroxyethoxypropyl) -polidimethylsiloxane with 11.1 g of IPDI in 150 g of dry ethyl ethyl ketone (MEK) in the presence of 0.063 g of dibutyltin dilaurate (DBTDL). The reaction is maintained for 4.5 hours at 40 ° C, forming IPDI-PDMS-IPDI. In the second step, a mixture of 164.8 g of a, ®-bis (2-hydroxyethoxypropyl) -polidimethylsiloxane (Mn = 3000, Shin-Etsu, KF-6002) and 50 g of dry MEK is added dropwise to the solution of IPDI-PDMS-IPDI to which an additional 0.063 g of DBTDL was added. The reactor is maintained for 4.5 hours at about 40 ° C, forming HO-PDMS-IPDI-PDMS-IPDI-PDMS-OH. MEK is then removed under reduced pressure. In the third stage, the hydroxyl terminal groups are capped with methacryloyloxyethyl groups in a third stage by adding 7.77 g of isocyanatoethyl methacrylate (IEM) and an additional 0.063 g of DBTDL, forming IEM-PDMS- IPDI-PDMS-IPDI-PDMS -IEM (ie CE-PDMS terminated with methacrylate groups). Alternative Preparation of the Macromer of CE-PDMS with Methacrylate End Groups
[201] 240.43 g of KF-6001 are added to a 1 l reactor equipped with a stir bar, a thermometer, a cryostat, a dropper funnel and a nitrogen / vacuum inlet adapter and then dry when applying a high vacuum (2 x 10-2mBar). Then, under an atmosphere of dry nitrogen, 320 g of distilled MEK are added to the reactor and the mixture is stirred vigorously. 0.235 g of DBTDL are added to the reactor. After the reactor is heated to 45 ° C, 45.86 g of IPDI is added to the reactor through an addition funnel for 10 minutes with moderate stirring. The reaction is maintained for 2 hours at 60 ° C. 630 g of KF-6002 dissolved in 452 g of distilled MEK are then added and stirred to form a homogeneous solution. About 0.235 g of DBTDL is added and the reactor is kept at about 55 ° C overnight under a blanket of dry nitrogen. The next day, MEK is removed by rapid distillation. The reactor is cooled and 22.7 g of EMI are then loaded into the reactor, followed by about 0.235 g of DBTDL. After about 3 hours, an additional 3.3 g of EMI is added and the reaction is allowed to proceed overnight. The following day, the reaction mixture is cooled to about 18 ° C to obtain the CE-PDMS macromer with methacrylate end groups. Example 3 Preparation of Lens Formulations
[202] A lens formulation is prepared by dissolving the components in 1-propanol to have the following composition: 33% by weight of the CE-PDMS macromer prepared in Example 2, 17% by weight of N- [tris ( trimethylsiloxy) -silylpropyl] acrylamide (TRIS-Am), 24% by weight of N, N-dimethylacrylamide (DMA), 0.5% by weight of N- (carbonyl-methoxypolyethylene glycol-2000) -1,2-diestearoyl- sn-glycero-3-phosphoethanolamine, sodium salt) (L-PEG), 1.0% by weight of Darocur 1173 (DC1173), 0.1% by weight of Visitint (5% copper phthalocyanine blue pigment dispersion) in tris (trimethylsiloxy) silylpropyl methacrylate, TRIS), and 24.5% by weight of 1-propanol. Lens Preparation
[203] The lenses are prepared by melting molding the lens formulation prepared above into a reusable mold, similar to the mold shown in Figures 1-6 of United States Patent Nos. 7,384,590 and 7,387,759 (Figures 1-6) . The mold comprises a female mold half made of CaF2 and a male mold half made of PMMA. The source of UV radiation is a Hamamatsu lamp with the cut filter WG335 + TM297 at an intensity of about 4 mW / cm2. The lens formulation in the mold is irradiated with UV radiation for about 25 seconds. Fusion-shaped lenses are extracted with isopropanol (or methyl ethyl ketone, MEK), rinsed with water, coated with polyacrylic acid (PAA) by immersing the lenses in a PAA solution (0.1% by weight, acidified with formic acid to a pH of about 2.5) in propanol and hydrated in water. It was determined that the resulting lenses that have a reactive PAA-LbL base coating on them have the following properties: ion permeability of about 8.0 to about 9.0 with respect to the Alsacon lens material; Apparent Dk (single point) of about 90 to 100; a water content of about 30% to about 33%; and a volumetric elastic modulus of about 0.60 MPa to about 0.65 MPa. Example 4
[204] A wrapping saline solution (IPC) is prepared by adding 0.2% polyamidoamine-epichlorohydrin (PAE) (Ashland's Kymene as an aqueous solution and used as received, 0.46 azetidinium content tested with NMR) in phosphate buffered saline (hereinafter PBS) (about 0.044% w / w NaH2PO4 ^ H2O, about 0.388% w / w Na2HPO4 ^ 2H2O, about 0.79% w / w of NaCl) and the pH is then adjusted to 7.2-7.4.
[205] The lenses of Example 3 are placed in a polypropylene lens packaging bag with 0.6 mL of the IPC saline solution (half of the IPC saline solution is added prior to placing the lens). The blister is then sealed with an aluminum foil and autoclaved for about 30 minutes at 121 ° C, forming crosslinked coatings (PAA-x-PAE coating) on the lenses.
[206] Next, the lenses are evaluated for residue adhesion, cracks on the surface, lubricity, contact angle and break time in water (WBUT). The test lenses (packaged / autoclaved in the IPC saline solution, that is, the lenses with the PAA-x-PAE coating on them) do not show residue adhesion after being rubbed with a paper towel, whereas the lenses control (packaged / autoclaved in PBS, that is, the lenses with a PAA-LbL base coating on them) show severe residue adherence. The water contact angle (WCA) of the test lens is low (~ 20 degrees), however, the WBUT is less than 2 seconds. When viewed under a dark field microscope, severe crack lines are visible after manipulation of the lens (inversion of the lens and rubbing between the fingers). Test lenses are much less lubricated than control lenses, as assessed by a qualitative rubbing test between the fingers. Example 5
[207] Partial sodium salt of poly (acrylamide-co-acrylic acid) (or PAAm-PAA or poly (AAm-co-AA) or p (AAm-co-AA)) (solids content ~ 80%, Poly ( AAm-co-AA) (80/20), Mw. 520,000, Mn 150,000) is purchased from Aldrich and used as received.
[208] An IPC solution is prepared by dissolving 0.02% Poly (AAm-co-AA) (80/20) and 0.2% PAE (Ashland's Kymene as an aqueous solution and used as received, azetidinium content of 0.46 tested with NMR) in PBS. The pH is adjusted to 7.2 ~ 7.4. PBS is prepared by dissolving 0.76% NaCl, 0.044% NaH2PO4 ^ O and 0.388% Na2HPO4 ^ 2H2O in water.
[209] Lenses with a PAA-LbL base coating prepared in Example 3 are placed in a polypropylene lens packaging bag containing 0.6 mL of the IPC solution (half of the saline is added before lens placement). The blister is then sealed with aluminum foil and autoclaved for about 30 minutes at about 121 ° C. A crosslinked coating composed of three layers of PAA-x-PAE-x-poly (AAm-co-AA) is believed to be formed on the lenses during autoclaving.
[210] The test lenses (packaged / autoclaved in the IPC solution, that is, the lenses with the PAA-x-PAE-x-poly (AAm-co-AA) reticulated coating on them) do not show adhesion of residues after being rubbed with a paper towel. The test lenses have a WBUT of more than 10 seconds. When viewed under a dark field microscope, crack lines are visible after the test lenses are rubbed. The test lenses are much more lubricated than the test lenses of Example 4, however, not as lubricated as the control lenses packaged in PBS. Example 6
[211] An IPC saline solution is prepared by dissolving 0.02% poly (AAm-co-AA) (80/20) and 0.2% PAE (Ashland's Kymene as an aqueous solution and used as received, azetidinium content of 0.46 tested with NMR) in PBS and pH adjustment to 7.2 ~ 7.4. Then, the saline solution is then treated by heating to about 70 ° C for 4 hours (pre-heat treatment). During this heat pretreatment, poly (AAm-co-AA) and PAE are partially cross-linked (that is, not consuming all the PAE azetidinium groups) to form a water-soluble and thermally crosslinkable hydrophilic polymeric material that contains azetidinium groups in the branched polymeric network in the IPC solution. After pre-heat treatment, the final IPC saline solution is filtered using a 0.22 micron polyether sulfone (PES) membrane filter and cooled to room temperature.
[212] Lenses with a PAA-LbL base coating prepared in Example 3 are placed in a polypropylene lens packaging bag containing 0.6 mL of the IPC solution (half of the saline is added before lens placement). The blister is then sealed with an aluminum foil and autoclaved for about 30 minutes at about 121 ° C, forming a cross-linked coating (PAA-x-hydrophilic polymeric material) on the lenses.
[213] Test lenses (packaged in thermally treated IPC saline, ie lenses with a coating of PAA-x-hydrophilic polymeric material) do not show residue adhesion after being rubbed with a paper towel, while control lenses (packaged in PBS, that is, lenses with a non-covalently bonded PAA layer on them) show severe residue adherence. The test lenses have a WBUT of more than 10 seconds. When viewed under a dark field microscope, no crack lines are visible after the test lenses are rubbed. Test lenses are heavily lubricated in a rubbing test between fingers equivalent to control lenses.
[214] A series of experiments is carried out to study the effects of the conditions (duration and / or temperature) of the thermal pretreatment of the IPC solution on the surface properties of the resulting lenses coated with the IPC solution. A heat treatment time of about 6 hours or more at about 70 ° C results in lenses that are susceptible to adhesion of debris in the same way as control lenses. It is believed that a longer heat pretreatment should consume most of the azetidinium groups and, thus, the number of azetidinium groups left on the branched polymeric network of the resulting water-soluble polymeric material will be insufficient to bind the polymeric material to the PAA coating . A heat treatment of just 4 hours at 50 ° C results in lenses that show crack lines on the surface under the dark field microscope after being rubbed between the fingers in the same way as the test lenses in Example 5, where the IPC solution it is not thermally pretreated. It is believed that a shorter heat pretreatment should consume a small amount of azetidinium groups and, thus, the number of azetidinium groups left on the branched polymeric network of the resulting water-soluble polymeric material will be high, so that the resulting cross-linked coating ( PAA-x-hydrophilic polymeric material) on the lenses may have too high a crosslink density. Example 7
[215] Partial sodium sodium of poly (acrylamide-co-acrylic acid) (solids content ~ 90%, poly (AAm-co-AA) 90/10, Mw 200,000) is purchased from Polisciences, Inc. and used as received.
[216] An IPC solution is prepared by dissolving 0.07% PAAm-PAA (90/10) and 0.2% PAE (Ashland Kymene as an aqueous solution and used as received, azetidinium content of 0, 46 tested with NMR) in PBS and pH adjustment to 7.2-7.4. Then, the saline solution is thermally pretreated for about 4 hours at about 70 ° C (heat pretreatment). During this heat pretreatment, poly (AAm-co-AA) and PAE are partially cross-linked (that is, not consuming all the PAE azetidinium groups) to form a water-soluble, thermally crosslinkable hydrophilic polymeric material that contains azetidinium groups in the branched polymeric network in the IPC solution. After thermal pretreatment, the IPC solution is filtered using a 0.22 micron polyether sulfone (PES) membrane filter and cooled to room temperature.
[217] Lenses with a PAA-LbL base coating prepared in Example 3 and Lotrafilcon B uncoated lenses (from CIBA VISION CORPORATION) that are immersed in a solution of PAA in acid propanol (about 0, 1%, pH ~ 2.5) are placed in polypropylene lens packaging wrappers with 0.6 mL of the thermally pretreated IPC saline solution (half of the IPC solution is added before lens placement). The blister is then sealed with an aluminum foil and autoclaved for approximately 30 minutes at 121 ° C, forming a cross-linked coating (PAA-x-hydrophilic polymeric material) on the lenses.
[218] The test lenses (both the Lotrafilcon B lenses and the lenses of Example 3 which have a coating of PAA-x hydrophilic polymer on them) do not show residue adhesion after being rubbed with a paper towel. The test lenses have a WBUT of more than 10 seconds. When viewed under a dark field microscope, crack lines are not visible after the lens is rubbed between the fingers. The lenses are extremely lubricated in the qualitative rubbing test between fingers. Example 8
[219] In the design of experiments (DOE), IPC saline solutions are produced in order to contain between about 0.05% and about 0.09% PAAm-PAA and about 0.075% to about 0.19% PAE (Ashland's Kymene as an aqueous solution and used as received, 0.46 azetidinium content tested with NMR) in PBS. The IPC solutions are heat treated for 8 hours at 60 ° C and the lenses of Example 3 are packaged in the thermally treated IPC saline solution. No difference was observed in the final surface properties of the lens and all lenses showed excellent lubricity, resistance to residue adhesion, excellent wetting capacity and no evidence of surface cracking. Example 9
[220] In the design of experiments (DOE), IPC saline solutions are produced to contain about 0.07% PAAm-PAA and PAE sufficient to provide an initial azetidinium content of approximately 8.8 millimolar equivalents / liter (~ 0.15% PAE). The pre-heat treatment conditions vary in a central composite design from 50 ° C to 70 ° C and the pre-reaction time varies from about 4 to about 12 hours. A pre-treatment time of 24 hours at 60 ° C is also tested. 10 ppm of hydrogen peroxide is then added to the saline solutions to prevent the growth of biological charges and the IPC solutions are filtered using a 0.22 micron polyether sulfone (PES) filter.
[221] The lenses of Example 3 are packaged in heat-treated IPC saline solutions and the blisters are then autoclaved for 45 minutes at 121 ° C. All lenses have excellent lubricity, wetting capacity and resistance to cracking on the surface. Some of the lenses show adhesion of paper towel residues, as shown in Table 1. Table 1
Example 10
[222] Copolymers of methacryloyloxyethyl phosphorylcholine (MPC) with a vinyl monomer containing carboxyl (CH2 = CH (CH3) C (O) OC2H4OC (O) C2H4COOH (MS), methacrylic acid (MA)) in the absence or presence of methacrylate butyl (BMA) are evaluated in internal packaging coating systems in combination with PAE.
[223] PBS containing NaCl (0.75% by weight), NaH2PO4 ^ H2O (0.0536% by weight), Nθ2HPO <2H2O (0.3576% by weight) and DI water (97.59% by weight) is prepared and 0.2% PAE (Policup 3160) is added. The pH is adjusted to about 7.3.
[224] 0.25% of one of several MPC copolymers are then added to form an IPC solution and the IPC solution is thermally pretreated at 70 ° C for 4 hours (heat pretreatment). During this heat pretreatment, MPC and PAE are partially cross-linked (that is, not consuming all the PAE azetidinium groups) to form a water-soluble and thermally crosslinkable hydrophilic polymeric material that contains azetidinium groups on the branched polymeric network in the solution CPI. After 4 hours, the thermally pretreated IPC saline solution is filtered through 0.22 micron polyether sulfone (PES) membrane filters (Fisher Scientific catalog # 09-741-04, Thermo Scientific Nalgene # 568-0020 ( 250 mL).
[225] Lenses with a PAA-LbL base coating prepared in Example 3 are packaged in thermally treated IPC saline and autoclaved for about 30 minutes at 121 ° C. Table 2 shows that all lenses have excellent surface properties. Table 2
* Numbers are molar percentages of monomer units in the copolymer. DA = residue adhesion. The WBUT is more than 10 seconds. Example 11
[226] PAA coated lenses. Lenses molded by melting a lens formulation prepared in Example 3 according to the molding process described in Example 3 are extracted and dipped in the following series of baths: 3 baths of MEK (22, 78 and 224 seconds); DI water bath (56 seconds); 2 baths of PAA coating solution (prepared by dissolving 3.6 g of PAA (MW: 450kDa, from Lubrizol) in 975 ml of 1-propanol and 25 ml of formic acid) for 44 and 56 seconds separately; and 3 DI water baths, each for 56 seconds.
[227] PAE / PAA coated lenses. The lenses prepared above with a PAA base coating on them are successively immersed in the following baths: 2 baths of PAE coating solution, which is prepared by dissolving 0.25% by weight of PAE (Policup 172, from Hercules) in DI water and adjust the pH to about 5.0 using sodium hydroxide and, finally, filter the resulting solution using a 5 μm filter, for 44 and 56 seconds, respectively; and 3 DI water baths, each for 56 seconds. After this treatment, the lenses have a PAA layer and a PAE layer.
[228] Lenses with PAA-x-PAE-x-CMC coatings. A batch of lenses with a PAA layer and a PAE layer is packed in 0.2% sodium carboxymethyl cellulose (CMC, Product # 7H 3SF PH, Ashland Aqualon) in phosphate buffered saline (PBS) and the pH is, then, adjusted to 7.2 - 7.4. The blisters are then sealed and autoclaved for about 30 minutes at 121 ° C, forming crosslinked coatings (PAA-x-PAE-x-CMC) on the lenses.
[229] Lenses with PAA-x-PAE-x-HA coatings. Another batch of lenses with a PAA layer and a PAE layer on top of it is packed in 0.2% hyaluronic acid (HA, Product # 6915004, Novozymes) in phosphate buffered saline (PBS) and the pH is, then, adjusted to 7.2 - 7.4. The blisters are then sealed and autoclaved for about 30 minutes at 121 ° C, forming crosslinked coatings (PAA-x-PAE-x-HA) on the lenses.
[230] The resulting lenses, either with PAA-x-PAE-x-CMC coating or PAA-x-PAE-x-HÁ coating, do not show Sudan Black stains, residue adhesion, or cracks under microscopic examination. PAA-x-PAE-x-CMC coated lenses have an average contact angle of 30 ± 3 degrees, while PAA-x-PAE-x-HA coated lenses have an average contact angle of 20 ± 3 degrees. Example 12
[231] Preparation of the IPC Solution. A reaction mixture is prepared by dissolving 2.86% by weight of mPEG-SH 2000 (Methoxy-oxy-Poly (Ethylene Glycol) -Tiol, average MW 2000, Product # MPEG-SH- 2000, Laysan Bio Inc.) together with 2% by weight of PAE (Ashland's Kymene as an aqueous solution and used as received, azetidinium content of 0.46 tested with NMR) in PBS and the final pH was adjusted to 7.5. The solution is thermally treated for about 4 hours at 45 ° C (pre-heat treatment). During this heat pretreatment, mPEG-SH 2000 and PAE are reacted together to form a hydrophilic, hydrophilic polymeric material that is thermally crosslinkable which contains chemically grafted azetidinium groups and polymeric polyethylene glycol chains. After heat treatment, the solution is diluted 1:10 with PBS containing 0.25% sodium citrate, the pH is adjusted to 7.2-7.4 and then the solution is filtered using a filter with a 0.22 micron polyether sulfone (PES) membrane. The final IPC saline solution contains 0.286 wt% hydrophilic polymeric material (consisting of about 59 wt% MPEG-SH-2000 chains and about 41 wt% PAE chains) and di sodium citrate -0.25% hydrate. PBS is prepared by dissolving 0.74% NaCl, 0.053% NaH2PO4.H2O and 0.353% Na2HPO4.2H2O in water.
[232] Lenses with Reticulated Coatings. The PAA-coated lenses of Example 11 are packaged in the above IPC saline solution in polypropylene lens packaging wrappers and then autoclaved for about 30 minutes at about 121 ° C, forming a cross-linked coating on the lenses.
[233] The lenses show no adhesion of debris or crack lines after being rubbed. The lenses are heavily lubricated in a finger rub test comparable to PAA-coated control lenses.
[234] A series of experiments is carried out to study the effects of conditions (reaction time and concentration of the mPEG-SH2000 solution (with a constant PAE concentration of 2%) on the surface properties of the resulting lenses coated with the solution of The results are shown in Table 3. Table 3
DA = residue adhesion; WCA = contact angle with water. 1. PAE concentration: 2% by weight.
[235] As the concentration of the mPEGSH2000 solution increases, the lubricity of the lens increases accordingly. It is believed that the increase in the contact angle of the surface may be due to the increasing density of methyl terminal groups on the surface with the increasing density of grafting. At high grafting densities, which correspond to a 0.6% solution concentration, the contact angle approaches the measurements obtained on flat substrates grafted with a polyethylene glycol (PEG) monolayer (Reference: Langmuir 2008, 24, 10646-10653). Example 13
[236] A series of experiments is carried out to study the effects of the molecular weight of mPEG-SH. The IPC solution is prepared in a similar manner to the procedure described in Example 12. However, the following mPEG-SH are used to prepare the saline solution: mPEG-SH 1000, mPEG-SH 2000, mPEG-SH 5000 and mPEG-SH 20000. All saline solutions are subjected to heat treatment at 45 ° C for 4 hours and a 1:10 dilution. The results and reaction conditions are shown below:
DA = residue adhesion; WCA = contact angle with water. * The initial concentration of MPEG-SH in the IPC solution with 2% PAE before thermal pretreatment and 1:10 dilution. Example 14
[237] A reaction mixture is prepared by dissolving 2.5% mPEG-SH 2000, 10% PAE (Ashland Kymene as an aqueous solution and used as received, 0.46 azetidinium content tested with NMR) in PBS and 0.25% sodium citrate dihydrate. The pH of this solution is then adjusted to 7.5 and also degassed with bubbling nitrogen gas through the container for 2 hours. This solution is subsequently heat treated for about 6 hours at 45 ° C, forming a thermally crosslinkable hydrophilic polymeric material containing mPEG-SH-2000 groups chemically grafted into the polymer by reaction with the azetidinium groups in the PAE. After heat treatment, the solution is diluted 1:50 using PBS containing 0.25% sodium citrate, the pH is adjusted to 7.2-7.4 and then the solution is filtered using a filter with a 0.22 micron polyether sulfone (PES) membrane. The final IPC saline solution contains about 0.30% by weight of the polymeric material (which consists of about 17% by weight of mPEG-SH-2000 and about 83% by weight of PAE) and di sodium citrate -0.25% hydrate.
[238] The PAA-coated lenses of Example 11 are packed in the IPC saline solution above in polypropylene lens packaging wrappers and then autoclaved for about 30 minutes at about 121 ° C, forming a cross-linked coating over the lenses.
[239] The final lenses do not show residue adherence, nor crack lines after being rubbed. The test lenses are heavily lubricated in a finger rub test comparable to PAA coated control lenses. Example 15
[240] A reaction mixture is prepared by dissolving 3.62% mPEG-NH2 550 (methoxy-oxy- (poly) ethylene glycol-amine, MW ~ 550 (Product # MPEG-NH2-550, Laysan Bio Inc.) together with 2% PAE (Kymene from Ashland as an aqueous solution and used as received, azetidinium ratio 0.46 tested with NMR) in PBS and the final pH was adjusted to 10. The solution is heat treated for about for 4 hours at 45 ° C, forming a thermally crosslinkable hydrophilic polymeric material containing MPEG-NH2-550 groups chemically grafted into the polymer by reaction with the azetidinium groups in the PAE. After heat treatment, the solution is diluted 1:10 with PBS containing 0.25% sodium citrate, the pH is adjusted to 7.2-7.4 and then the solution is filtered using a 0.22 micron polyether sulfone (PES) membrane filter The final IPC saline solution contains about 0.562% by weight of polymeric material (which consists of 64% by weight of MPEG-SH-2000 and about 36 % by weight of PAE) and 0.25% sodium citrate dihydrate. PBS is prepared by dissolving 0.74% NaCl, 0.053% NaH2PO4.H2O and 0.353% Na2HPO4.2H2O in water.
[241] The PAA-coated lenses of Example 11 are packaged in the above IPC saline solution in polypropylene lens wrappers and then autoclaved for about 30 minutes at about 121 ° C, forming a cross-linked coating over the lenses.
[242] The final lenses show no adhesion of debris and no crack lines are seen when the lenses are rubbed between the fingers. Example 16
[243] Poloxamer 108 (sample) and Nelfilcon A (CIBA VISION) are used in the state as received. Nelfilcon A is a polymerizable polyvinyl alcohol obtained by modifying a polyvinyl alcohol (for example, Nippon Gohsei Gohsenol KL-03 or similar) with N- (2,2-dimethoxyethyl) acrylamide under reaction conditions to form cyclic acetal (Bühler et al., CHIMIA, 53 (1999), 269-274, incorporated herein by reference in its entirety). About 2.5% of the vinyl alcohol units in Nelfilcon A are modified by N- (2,2-dimethoxyethyl) acrylamide.
[244] IPC saline is prepared by dissolving 0.004% poloxamer 108, 0.8% Nelfilcon A, 0.2% PAE (Kymene, Policup 3160), 0.45% NaCl and 1.1% of disodium hydrogen phosphate (dihydrate) in DI water. The saline solution is thermally pretreated by stirring for 2 hours at about 65 - 70 ° C. After pre-heat treatment, the saline solution is allowed to cool to room temperature and then filtered using a 0.2 μm PES filter.
[245] The lenses prepared in Example 3 are placed in a polypropylene lens packaging bag with 0.6 mL of the IPC solution (half of the saline is added before placing the lens). The blister is then sealed with aluminum foil and autoclaved for approximately 30 minutes at 121 ° C.
[246] The test lenses do not show residue adhesion after being rubbed with paper towels. The lenses had a WBUT of more than 10 seconds. When viewed under a dark field microscope, no crack line was visible after the lenses were rubbed between the fingers. The lens is much more lubricated than the lenses of Example 4, but still not as lubricated as the PAA-coated control lenses packaged in PBS. Example 17 A. Synthesis of 80% ethylenically functionalized extended-chain polysiloxane
[247] KF-6001A (α, ®-bis (2-hydroxyethoxypropyl) -polidimethylsiloxane, Mn = 2000, from Shin-Etsu) and KF-6002A (α, ®-bis (2-hydroxyethoxypropyl) - polydimethylsiloxane, Mn = 3400 , from Shin-Etsu) are separately dried at about 60 ° C for 12 hours (or overnight) under high vacuum in a single necked flask. The OH molar equivalent weights of KF-6001A and KF-6002A are determined to the holder the hydroxyl groups and are used to calculate the millimolar equivalent to be used in the synthesis.
[248] A one-liter reaction vessel is evacuated overnight to remove moisture and the vacuum is broken with dry nitrogen. 75.00 g (75 meq) of dry KF6001A is loaded into the reactor and then 16.68 g (150 meq) of freshly distilled IPDI is added to the reactor. The reactor is purged with nitrogen and heated to 45 ° C with stirring and then 0.30 g of DBTDL is added. The reactor is sealed and a positive nitrogen flow is maintained. An exotherm occurs, after which the reaction mixture is allowed to cool and stirred at 55 ° C for 2 hours. After the exotherm is reached, 248.00 g (150 meq) of dry KF6002A are loaded into the reactor at 55 ° C and then 100 μL of DBTDL is added. The reactor is stirred for four hours. Heating is stopped and the reactor is allowed to cool overnight. The nitrogen bubbling is stopped and the reactor is opened to the atmosphere for 30 minutes with moderate agitation. A hydroxyl-terminated extended-chain polysiloxane with 3 polysiloxane segments, HO-PDMS-IPDI-PDMS-IPDI-PDMS-OH (or HO-CE-PDMS-OH) is formed.
[249] For 80% ethylenically functionalized polysiloxane, 18.64 g (120 meq) of EMI are added to the reactor, along with 100 μL of DBTDL. The reactor is stirred for 24 hours, and then the product (CE-PDMS 80% capped with EMI) is decanted and stored under refrigeration. B: Synthesis of non-UV absorbing amphiphilic branched polysiloxane prepolymer
[250] A jacketed 1 l reactor is equipped with a 500 mL addition funnel, a suspended stir bar, a reflux condenser with a nitrogen / vacuum inlet adapter, a thermometer and a sample collection adapter. The reactor is loaded with 45.6 g of CE-PDMS 80% capped with EMI prepared above and sealed. A solution of 0.65 g of hydroxyethyl methacrylate (HEMA), 25.80 g of DMA, 27.80 g of (tris (trimethylsilyl)) - siloxypropyl (TRIS) methacrylate in 279 g of ethyl acetate is loaded into the addition funnel. The reactor is degassed at <1 mbar for 30 minutes at room temperature with a high vacuum pump. The monomer solution is degassed at 100 mbar and at room temperature for 10 minutes for three cycles, the vacuum being broken with nitrogen between the degassing cycles. The monomer solution is then charged to the reactor, and then the reaction mixture is stirred and heated to 67 ° C. During heating, a solution of 1.50 g of mercaptoethanol (chain transfer agent, CTA) and 0.26 g of azoisobutyronitrile dissolved in 39 g of ethyl acetate is loaded into the addition funnel and deoxygenated three times at 100 mbar at room temperature for 10 minutes. When the reactor temperature reaches 67 ° C, the CTA initiator / solution is added to the PDMS / monomer solution in the reactor. The reaction is allowed to proceed for 8 hours and then heating is stopped and the temperature in the reactor is brought to room temperature within 15 minutes.
[251] The resulting reaction mixture is then siphoned into a flask with a single dry neck with airtight lid and 4.452 g of EMI are added with 0.21 g of DBTDL. The mixture is stirred for 24 hours at room temperature, forming a non-UV absorbing amphiphilic branched polysiloxane prepolymer. To this mixing solution, 100 μL of a solution of hydroxy-oxy-tetramethylene piperonyloxy in ethyl acetate (2 g / 20 mL) is added. The solution is then concentrated to 200 g (~ 50%) using a rotary vaporizer at 30 ° C and filtered through a filter paper with a pore size of 1 μm. After the solvent is exchanged for 1-propanol, the solution is further concentrated to the desired concentration. C. Synthesis of UV-absorbing amphiphilic branched polysiloxane prepolymer
[252] A 1 liter jacketed reactor is equipped with a 500 mL addition funnel, a suspended stir bar, a reflux condenser with a nitrogen / vacuum inlet adapter, a thermometer and a sample collection adapter. The reactor is then loaded with 45.98 g of the 80% CE-PDMS capped with EMI prepared above and the reactor is sealed. A solution of 0.512 g of HEMA, 25.354 g of DMA, 1.38 g of Norbloc methacrylate, 26.034 g of TRIS, in 263 g of ethyl acetate is loaded into the addition funnel. The reactor is degassed at <0.1kPa (1 mbar) for 30 minutes at room temperature with a high vacuum pump. The monomer solution is degassed at 10 kPa (100 mbar) and at room temperature for 10 minutes for three cycles, the vacuum being broken with nitrogen between the degassing cycles. The monomer solution is then charged to the reactor, and then the reaction mixture is stirred and heated to 67 ° C. During heating, a solution of 1,480 g of mercaptoethanol (chain transfer agent, CTA) and 0.260 g of azoisobutyronitrile dissolved in 38 g of ethyl acetate is loaded into the addition funnel and deoxygenated three times at 100 mbar at room temperature during 10 minutes. When the reactor temperature reaches 67 ° C, the CTA initiator / solution is added to the PDMS / monomer solution in the reactor. The reaction is allowed to proceed for 8 hours and then heating is stopped and the reactor temperature is brought to room temperature within 15 minutes.
[253] The resulting reaction mixture is then siphoned into a flask with a single dry neck with airtight lid and 3,841 g of isocyanatoethyl acrylate are added with 0.15 g of DBTDL. The mixture is stirred for 24 hours at room temperature, forming a UV absorbing branched amphiphilic polysiloxane prepolymer. To this mixing solution, 100 μL of a solution of hydroxy-oxy-tetramethylene piperonyloxy in ethyl acetate (2 g / 20 ml) is added. The solution is then concentrated to 200 g (~ 50%) using a rotary vaporizer at 30 ° C and filtered through a filter paper with a pore size of 1 μm. D-1: Lens formulation with non-UV absorbing polysiloxane prepolymer
[254] In a 100 mL amber flask, 4.31 g of the synthesized macromer solution (82.39% in 1-propanol) prepared above is added. In a 20 mL flask, 0.081 g of TPO and 0.045 g of 1,2-dimiristoyl-sn-glycero-3-phosphocholine (DMPC) are dissolved in 10 g of 1-propanol and then transferred to the macromer solution . After the mixture is concentrated to 5.64 g using a rotary vaporizer at 30 ° C, 0.36 g of DMA is added and the formulation is homogenized at room temperature. 6 g of the D-1 clear lens formulation are obtained. D-2: Lens formulation with UV-absorbing polysiloxane prepolymer (4% DMA)
[255] In a 100 ml amber flask, 24,250 g of the macromer solution prepared above (43.92% in ethyl acetate) are added. In a 50 mL flask, 0.15 g of TPO and 0.75 g of DMPC are dissolved in 20 g of 1-propanol and then transferred to the macromer solution. 20 g of solvent are extracted using a rotary vaporizer at 30 ° C, followed by the addition of 20 g of 1-propanol. After two cycles, the mixture is concentrated to 14.40 g. 0.6 g of DMA is added to this mixture and the formulation is homogenized at room temperature. 15 g of the D-2 clear lens formulation are obtained. D-3: Lens formulation with UV-absorbing polysiloxane prepolymer (2% DMA / 2% HEA)
[256] In a 100 ml amber flask, 24,250 g of the macromer solution prepared above (43.92% in ethyl acetate) are added. In a 50 mL flask, 0.15 g of TPO and 0.75 g of DMPC are dissolved in 20 g of 1-propanol and then transferred to the macromer solution. 20 g of solvent are extracted using a rotary vaporizer at 30 ° C, followed by the addition of 20 g of 1-propanol. After two cycles, the mixture is concentrated to 14.40 g. 0.3 g of DMA and 0.3 g of HEA are added to this mixture and the formulation is homogenized at room temperature. 15 g of the D-3 clear lens formulation are obtained. Example 18 Example E: Covalent Bonding of Modified PAE Coating Polymers
[257] Monomers containing amine groups, N- (3-aminopropyl) methacrylamide hydrochloride (APMAA-HCl) or N- (2-aminoethyl) methacrylamide hydrochloride (AEMAA-HCl) were purchased from Polisciences and used as received . Poly (amidoamine epichlorohydrin) (PAE) was received from Ashland as an aqueous solution and used as received. Poly (acrylamide-co-acrylic acid) (poly (AAm-co-AA) (90/10) from Polisciences, mPEG-SH from Laysan Bio, and poly (MPC-co-AeMA) (ie, a methacryloyloxyethyl copolymer) phosphorylcholine (MPC) and aminoethyl methacrylate (AeMA)) from NOF were used in the state as received.
[258] The APMAA-HCl monomer is dissolved in methanol and added to the lens formulations D-1, D-2 and D-3 (prepared in Example 17) until reaching a concentration of 1% by weight.
[259] Reactive packaging saline is prepared by dissolving the components listed in Table 4 together with appropriate buffer salts in DI water. The saline solution is thermally pretreated by stirring for 8 hours at about 60 ° C. After thermal pretreatment, the saline solution is allowed to cool to room temperature and then filtered using a 0.2 μm PES filter. Table 4

[260] The D-1 lens formulation prepared in Example 17 is modified by adding the APMAA-HCl monomer (APMMA-HCL stock solution in methanol: 1: 1 propanol) and cured at 16 mW / cm2 with a filter 330 nm. The lens formulations D-2 and D-3 prepared in Example 17 are modified by adding the APMAA-HCl monomer and cured at 4.6 mW / cm2 with a 380 nm filter.
[261] DSM lenses. Female portions of polypropylene lens molds are filled with about 75 microliters of a lens formulation prepared in the manner described above and the molds are closed with the male portion of the polypropylene lens molds (basic curved molds). Contact lenses are obtained by curing the closed molds for about 5 minutes with a source of UV radiation (Hamamatsu lamp with a 330 nm cut filter at an intensity of about 16 mW / cm2.
[262] LS lenses. LS lenses are prepared by melt molding a lens formulation prepared in the manner described above in a reusable mold, similar to the mold shown in Figures 1-6 of United States Patent Nos. 7,384,590 and 7,387,759 (Figures 1- 6). The mold comprises a female mold half made from CaF2 and a male mold half made from PMMA. The source of UV radiation is a Hamamatsu lamp with a 380 nm cut filter at an intensity of about 4.6 mW / cm2. The lens formulation in the mold is irradiated with UV radiation for about 30 seconds.
[263] The APMAA-HCl modified D-1 lens formulation is cured according to the DSM and LS methods described above, while the D-2 or D-3 lens formulation is cured according to the LS method described. above.
[264] Molded lenses are extracted in methyl ethyl ketone, hydrated, and packed in one of the saline solutions described in Table 4. The lenses are placed in a polypropylene lens packaging case with 0.6 mL of the IPC solution ( half of the saline solution is added before placing the lens). The blister is then sealed with aluminum foil and autoclaved for 30 minutes at 121 ° C.
[265] Evaluation of the surface of the lenses shows that all test lenses did not exhibit residue adhesion after being rubbed with a paper towel. When viewed under a dark field microscope, no crack line was visible after the lenses were rubbed between the fingers.
[266] The lens surface wetting capacity (WBUT), lubricity and contact angle were measured and the results are summarized in Table 5. The lenses are produced according to the DSM method, unless otherwise specified. Lubricity is rated on a qualitative scale from 0 to 5 where smaller numbers indicate greater lubricity. In general, all properties were better after the application of the internal packaging coating. Table 5
1. The number is the saline packaging number shown in Table 4. 2. LS lenses Example 19
[267] Preparation of lens formulations. A lens formulation is prepared by dissolving the components in 1-propanol to have the following composition: about 32% by weight of the CE-PDMS macromer prepared in Example 2, about 21% by weight of TRIS-Am, about 23% by weight of DMA, about 0.6% by weight of L-PEG, about 1% by weight of DC1173, about 0.1% by weight of Visitint (dispersion of the blue copper phthalocyanine pigment at 5% in TRIS), about 0.8% by weight of DMPC, about 200 ppm H-time and about 22% by weight of 1-propanol.
[268] Preparation of the lenses. The lenses are prepared by fusing molding the lens formulation prepared above into a reusable mold (half of the quartz female mold and half of the glass male mold), similar to the mold shown in Figures 1-6 of United States Patent Nos7 .384,590 and 7,387,759 (Figures 1-6). The lens formulation in the molds is irradiated with UV radiation (13.0 mW / cm2) for about 24 seconds.
[269] PAA coating solution. A PAA coating solution is prepared by dissolving an amount of PAA (MW: 450kDa, from Lubrizol) in a given volume of 1-propanol in order to have a concentration of about 0.36% by weight and the pH is adjusted with formic acid to about 2.0.
[270] PAA coated lenses. Fusion-shaped contact lenses as described above are extracted and coated by immersion in the following series of baths: DI water bath (about 56 seconds); 6 baths of MEK (about 44, 56, 56, 56, 56, and 56 seconds, respectively); DI water bath (about 56 seconds); a bath of PAA coating solution (about 0.36% by weight acidified with formic acid to a pH of about 2.0) in 100% 1-propanol (about 44 seconds); a bath of a 50% water / 1-propanol / 50% mixture (about 56 seconds); 4 DI water baths, each for about 56 seconds; a bath of PBS for about 56 seconds; and a DI water bath for about 56 seconds.
[271] IPC saline solution. Partial poly (AAm-co-AA) sodium salt (90/10) (solids content ~ 90%, poly (AAm-co-AA) 90/10, Mw 200,000) is purchased from Polisciences, Inc. and used as received. PAE (Kymene, azetidinium content of 0.46 analyzed by NMR) is purchased from Ashland as an aqueous solution and used as received. A solution of IPC is prepared by dissolving about 0.07% w / w of poly (AAm-co-AA) (90/10) and about 0.15% PAE (an initial millimolar equivalent of azetidinium of about 8.8 millimoles) in PBS (about 0.044% w / w NaH2PO <H2O, about 0.388% w / w Na2HPO <2H2O, about 0.79% w / w NaCl) and adjust the pH to 7 , 2-7.4. Then, the IPC solution is thermally pretreated for about 4 hours at about 70 ° C (heat pretreatment). During this thermal pretreatment, poly (AAm-co-AA) and PAE are partially cross-linked (that is, not consuming all the PAE azetidinium groups) to form a water-soluble, thermally crosslinkable hydrophilic polymeric material that contains azetidinium groups on the branched polymeric network in the IPC solution. After heat pretreatment, the IPC solution is filtered using a 0.22 micron PES membrane filter and cooled again to room temperature. 10 ppm of hydrogen peroxide is then added to the final IPC saline solution to prevent biological charge growth and the IPC solution is filtered using a 0.22 micron PES membrane filter.
[272] Application of the reticulated coating. Lenses with a PAA-LbL base coating prepared above are placed in polypropylene lens packaging cases (one lens per case) with 0.6 mL of the IPC solution (half of the saline solution is added before placing the lens ). The blisters are then sealed with an aluminum foil and autoclaved for about 30 minutes at about 121 ° C, forming SiHy contact lenses with cross-linked coatings (PAA-x-hydrophilic polymeric material) applied on them.
[273] Characterization of SiHy lenses. The resulting SiHy contact lenses with reticulated coatings (PAA-x-hydrophilic polymeric material) do not show residue adhesion after being rubbed with a paper towel, while the control lenses (packaged in PBS, that is, lenses that present a non-covalently bonded PAA layer) show severe residue adherence. The lenses have an oxygen permeability (Dkc or estimated intrinsic Dk) of 146 barrers, a volumetric elastic modulus of 0.76 MPa, a water content of about 32% by weight, a relative ionic permeability of about 6 (in relative to the Alsacon lens), a contact angle of about 34 to 47 degrees, a WBUT of more than 10 seconds. When viewed under a dark field microscope, no crack lines are visible after the test lenses are rubbed. The lenses are heavily lubricated in a rubbing test between fingers and equivalent to control lenses. Example 20
[274] SiHy lenses and IPC saline solutions in lens packs after autoclaving, which are prepared in Examples 6, 14 and 19, are subjected to the following biocompatibility studies.
[275] In vitro cytotoxicity assessment. SiHy lenses are evaluated using the USP Direct Contact Material assay. The lens extracts are evaluated using the CEN ISO Cell Growth Inhibition and MEM USP Elution Assay ("USP MEM Elution and ISO CEN Cell Growth Inhibition Assay") and the IPC solution in the packages after autoclaving is evaluated using of a modified elution test. All lenses and lens extracts evaluated meet the acceptance criteria for each test and no unacceptable cytotoxicity is observed.
[276] In vivo testing. ISO systemic toxicity in mice shows that there is no evidence of systemic toxicity in mice with lens extracts. The ISO eye irritation study in rabbits shows that lens extracts are not considered to be irritating to rabbit eye tissue. The ISO eye irritation study shows that the IPC solution in packaging after autoclaving is not considered an irritant to rabbit eye tissue. Lenses used in a disposable daily wear mode for 22 consecutive days are not irritating to the rabbit model and the eyes treated with the test lenses are similar to the eyes treated with the control lenses. The ISO sensitization study (test for maximizing packaging solutions in guinea pigs) shows that the IPC solution after autoclaving does not cause delayed skin contact sensitization in guinea pigs. The ISO sensitization study (test for maximizing lens extracts in guinea pigs) shows that sodium chloride and sesame oil extracts from the lenses do not cause delayed skin contact sensitization in guinea pigs.
[277] Genotoxicity test. When the IPC saline solutions from the lens packaging and the SiHy lens extracts are tested in the Bacterial Reverse Mutation Assay (Ames test), it was found that the IPC lens extracts and saline solutions are considered non-mutagenic for the test strains of Salmonella typhimurium TA98, TA100, TA1535 and TA1537 and for Escherichia coli WPuvrA. When SiHy lens extracts are tested in the Mammalian Erythrocyte Micronucleus Assay, they did not exhibit clastogenic activity and are negative in the Mouse Bone Marrow Micronucleus Assay. When the IPC saline solutions of the lens packaging are tested according to the Chinese Hamster Ovary Chromosomal Abnormality Assay, the IPC solutions are negative for induction in structural and numerical chromosomal abnormality assays using CHO cells in both not activated as well as in test systems activated with S9. When SiHy lens extracts are tested according to the Cell Gene Mutation Test (Mouse Lymphoma Mutagenesis Assay), lens extracts are negative in the Mouse Lymphoma Mutagenesis Assay. Example 21
[278] The surface compositions of the precast SiHy contact lenses (ie SiHy contact lens without any coating and prior to the application of PAA base coat), of SiHy contact lenses with PAA coating (that is, the lenses before being sealed and autoclaved in packaging for lenses with the IPC solution) and SiHy contact lenses with a reticulated coating, all of which are prepared according to the procedures described in Example 19, are determined by characterizing vacuum-dried contact lenses with X-ray photoelectronic spectroscopy (XPS). XPS is a method for measuring the surface composition of lenses with a sampling depth of about 10 nm. The surface compositions of three types of lenses are provided in Table 6. Table 6
*: Fluorine is detected, most likely from surface contamination during the vacuum drying process and XPS analysis.
[279] Table 6 shows that when a PAA coating is applied over a SiHy lens (precast without coating), the atomic composition of silicon is substantially reduced (from 12.1% to 4.5% ) and the atomic composition of nitrogen is also reduced (from 6.2% to 1.6%). When a cross-linked coating is still applied over the PAA coating, the surface composition is predominated by carbon, nitrogen and oxygen, which are the three atomic compositions (excluding hydrogen, since XPS does not consider hydrogen in the composition of surface). Such results indicate that the outermost layer of the SiHy contact lens with reticulated coating possibly consists essentially of the hydrophilic polymeric material which is the product of the poly (AAm-co-AA) reaction (90/10) (60% C , 22% O and 18% N) and PAE.
[280] The following commercial SiHy lenses, which are vacuum dried, are also subjected to XPS analysis. The surface compositions of these commercial SiHy contact lenses are provided in Table 7. Table 7
*: Fluorine is also detected in Advance, Oasys and TruEye lenses, most likely from surface contamination during the vacuum drying process and XPS analysis.
[281] A SiHy contact lens of the invention was found to have a nominal silicon content, about 1.4%, in the surface layer, much lower than that of commercial SiHy lenses without plasma coatings (Acuvue®Advance ®, Acuvue® Oasys®, TruEye®, Biofinity®, Avaira®) and PureVision® (with plasma oxidation) and Premio® (with unknown plasma treatment), and even lower than SiHy lenses with a coating deposited by plasma that has a thickness of about 25 nm (N & D®Aqua® and Air Optix®Aqua®). This very low Si% value is equivalent to an atomic percentage of silicon from a Goodfellow polyethylene control sample (LDPE, d = 0.015 mm; LS356526 SDS; ET31111512; 3004622910). These results indicate that the very low value in the XPS analysis of the vacuum dried SiHy contact lens of the invention may be due to the contaminants introduced during the preparation process, including the vacuum drying process and XPS analysis, similar to fluoride content observed in lenses that do not contain fluoride. The silicone was successfully protected in XPS analysis on the SiHy contact lenses of the invention.
[282] XPS analysis of the SiHy contact lenses of the invention (prepared according to the procedures described in Example 19), of commercial SiHy contact lenses (CLARITITM1 Day, ACUVUE®TruEye® (Narafilcon A and Narafilcon B) ), Goodfellow's polyethylene lenses (LDPE, d = 0.015 mm; LS356526 SDS; ET31111512; 3004622910), DAILIES® (polyvinyl alcohol hydrogel lenses, ie non-silicone hydrogel lenses), ACUVUE®Moist (lenses) hydroxyethyl (poly) methacrylate hydrogel, i.e., non-silicone hydrogel lenses) is also performed. All lenses are vacuum-dried. Polyethylene lenses, DAILIES® and ACUVUE®Moist are used as controls, as they do not contain silicon. The atomic compositions of silicon in the surface layers of the test samples are as follows: 1.3 ± 0.2 (polyethylene lens); 1.7 ± 0.9 (DAILIES®); 2.8 ± 0.9 (ACUVUE®Moist); 3.7 ± 1.2 (three SiHy lenses prepared according to the procedures described in Example 19); 5.8 ± 1.5 (CLARITI®1 Day); 7.8 ± 0.1 (ACUVUE® TruEye® (Narafilcon A)); and 6.5 ± 0.1 (ACUVUE®TruEye® (Narafilcon B)). The results for the SiHy contact lens of the invention are closer to those for traditional hydrogels than those for silicone hydrogels. Example 22
[283] Fluorescein-labeled PAA (PAA-F). PAA-F is synthesized internally by covalently binding 5-aminofluorescein to PAA (Mw 450k). The level of fluorescein labeling is a few%, for example, about 2 mol% (or n / (m + n) = 2% in the formula shown below)
Fluorescein-labeled PAA (PAA-F) X: fluorescein portion
[284] Preparation of the lenses. The lenses are prepared by melting molding the lens formulation prepared above in Example 19 into a reusable mold (half of the quartz female mold and half of the glass male mold), similar to the mold shown in Figures 1-6 of the US Patents. United States Nos 7,384,590 and 7,387,759 (Figures 1-6). The lens formulation in the molds is irradiated with UV radiation (13.0 mW / cm2) for about 24 seconds.
[285] PAA-F coating solution. A PAA-F coating solution is prepared by dissolving an amount of PAA-F prepared above in a given volume of the solvent mixture 1-PrOH / water (95/5) so as to have a concentration of about 0.36 % by weight and the pH is adjusted with formic acid to about 2.0. About 5% water is used to dissolve PAA-F.
[286] PAA coated lenses. Fusion-shaped contact lenses are extracted and coated by immersion in the following series of baths: DI water bath (about 56 seconds); 6 baths of MEK (about 44, 56, 56, 56, 56, and 56 seconds, respectively); DI water bath (about 56 seconds); a bath of PAA-F coating solution (about 0.36% by weight acidified with formic acid to a pH of about 2.0) in the solvent mixture 1-PrOH / water (95/5) (about 44 seconds); a bath of a 50% water / 1-propanol / 50% mixture (about 56 seconds); 4 DI water baths, each for about 56 seconds; a bath of PBS for about 56 seconds; and a DI water bath for about 56 seconds.
[287] Application of the reticulated coating. Lenses having a base coat of PAA-LbL base prepared above are placed in polypropylene lens packaging cases (one lens per housing) with 0.6 ml of the IPC solution prepared according to the procedures described in Example 19 ( half of the saline solution is added before placing the lens). The blisters are then sealed with an aluminum foil and autoclaved for about 30 minutes at about 121 ° C, forming SiHy contact lenses with reticulated coatings (PAA-x-hydrophilic polymeric material) on them.
[288] Confocal fluorescence microscopy by laser scanning. A cross section of a hydrated SiHy lens with a reticulated coating (prepared above) is cut and placed between two glass coverslips and the image is captured in a confocal fluorescence microscope by laser scanning (model # Zeiss LSM 510 Vis). Scanning is performed from the front curved side of the lens to the base curved side of the lens, or vice versa. The presence of PAA-F is shown by green fluorescence and confocal microscopic images of fluorescence by laser scanning can be obtained. Examination of confocal fluorescence microscopic images by laser scanning reveals that the PAA-F-rich layer is present on both lens surfaces (anterior and posterior surfaces) and at the peripheral edge, while PAA-F is not observed in the volumetric material of the hydrated lens.
[289] The fluorescence intensity profiles are examined through the lens cross section along a line that crosses both the posterior and anterior surfaces and is normal to the posterior surface. Figure 3 shows two representative fluorescence intensity profiles along two lines across the lens cross section, one at the point where the lens thickness is about 100 μm (panel A) and the other at the point where the thickness the lens is about 200 μm (panel B). the original points in Figure 3 are the central points between the anterior and posterior surfaces along the lines. It can be seen in Figure 3 that there is a layer rich in PAA-F close to the outer surfaces of the SiHy lens with reticulated coating, PAA-F is not present in the volumetric material of the lens and the coating thickness is similar in these two sections. transversal regardless of the thickness of the cross sections.
[290] The thickness of the PAA-F-rich layer (that is, the sum of the infusion depth in the outer hydrogel layer and the depth of penetration of the PAA-F into the volumetric material (ie, the inner layer)) or the transition layer (for a schematic illustration see Figure 2, the transition layer 115), can be estimated from the fluorescence intensity profile shown in Figure 3. The possible thickness of the transition layer (layer rich in PAA-F ) is estimated by the distance from the zero intensity after crossing the peak intensity to the zero intensity again. Considering that there is a possible contribution of unknown factors (such as dispersion) to the fluorescence intensity, the minimum layer thickness is the thickness at which a fluorescent intensity of at least 10% of the maximum peak intensity is preserved. Based on this estimate, the minimum thickness of the PAA-F rich layer could be at least about 5 microns. Note that the thickness for the PAH-coated SiHy lenses from the previous examples could be greater, considering that the PAA concentration used is 10 times greater than the PAA-F concentration used in the present experiments. A thicker coated lens can also be prepared using an immersion coating time that is greater than 44 seconds, 44 seconds was the immersion coating time for PAA-F used in this experiment. A thicker coated lens can also be prepared using a PAA of different molecular weight. Example 23
[291] This example illustrates how to determine the water content of the crosslinked coating (the two outer layers of hydrogel) in a SiHy of the invention). In an effort to determine the potential water content of the crosslinked coating on the SiHy lenses of Example 19, polymer samples consisting of the coating components are prepared for evaluation. The resulting gels are then hydrated and tested to determine the water content.
[292] Solutions are prepared using the two polymeric components of a crosslinked coating formed in Example 19: poly (AAm-co-AA) (90/10) and PAE, to have the following composition: 12.55% w / w of PAE, 6.45% w / w of poly (AAm-co-AA) (90/10), and 81% w / w of water. The ratio of PAE / poly (AAm-co-AA) is identical to that in the IPC solution of Example 19, however, the individual concentrations of the components are higher to ensure the formation of a gel during autoclaving.
[293] The solution is then autoclaved for about 45 minutes at 121 ° C, after which the sample gels. The gel samples are then prepared to determine the water content by testing the samples after hydration (n = 3). Hydrated samples are prepared by immersing the gel sample in the SoftWear saline solution for at least about 6 hours (ie, hydrated overnight).
[294] The hydrated samples are dried with a blotter and the mass in the hydrated state is recorded via mass balance. Subsequent to mass recording in the hydrated state, all samples are placed in a vacuum oven set at a temperature of approximately 50 ° C and dried in a vacuum of <2.54 cm (1 inch) Hg overnight.
[295] The dried samples are removed from the vacuum oven after drying overnight and are then measured to record the dry mass. The water content is calculated using the following ratio: Water content = (wet mass - dry mass) / wet mass x 100%
[296] The water content was determined and was 84.6 ± 0.4% w / w.
[297] This water content of this PAE / poly (AAm-co-AA) hydrogel is believed to represent the outer hydrogel layer (reticulated coating) of the SiHy contact lenses of Example 19 for the following reasons. First, it is reasonably assumed that polymers of volumetric hydrophobic lenses (silicone hydrogel) are not present in the outer surface layer. This appears to be a good assumption based on the XPS data. According to the XPS data from Example 21, there is no silicon content or very low silicon content on the SiHy lens surface with the reticulated coating, indicating that the outer surface layer is composed almost entirely of the polymers coating (PAE and PAAm-PAA). Second, the polyacrylic acid (PAA) base coating (the transition layer) presumably has a minimal impact on the water content of the surface layer. This assumption may not be valid. However, if a little loaded PAA is present in the outer surface layer, this will further increase the water content beyond 84.6%. Third, a concentration of PAE and PAAm-PAA is required to produce the PAE / poly hydrogel (AAm-co-AA) much higher than that used in the IPC solution of Example 19. This can result in a higher crosslink density for the PAE / poly hydrogel (AAm-co-AA), which can provide an artificially low water content result. It is believed that both the presence of PAA in the outer layer of hydrogel and the lower crosslinking density due to the lower concentration of polymeric materials during crosslinking (in Example 19) can result in a surface layer (outer layer of hydrogel) that presents a water content that is even higher than that measured in the tests in this example. We can assume that the outer coating layer of the SiHy contact lenses of Example 19 comprises at least 80% water and this content can be even higher when fully hydrated. Example 24
[298] An Abbe refractometer is typically used to measure the refractive index of contact lenses. The difference in the refractive index between a test lens and the instrument's prism creates a unique angle of total internal reflectance that results in a visible dark shadow line. The angle at which this shadow line appears is directly related to the refractive index of the test lens. Most contact lenses (including the uncoated SiHy contact lenses prepared in Example 19) produce a distinct shadow line on the Abbe refractometer, but the reticulated coating SiHy (ie the outer hydrogel layers) of the Example 19 does not produce a distinct shadow line. It is believed that this phenomenon is due to a reduction in the refractive index of the lens on the surface compared to the volumetric material and the fact that the transition from the volumetric material to the surface is not abrupt. It is also believed that, close to the lens surface, the water content starts to increase, which results in a localized reduction in the lens refractive index. This, in reality, would create simultaneous shadow lines at various angles, resulting in a blurred image of the shadow line.
[299] Abbe data shows that the outer surface layer is characterized by an increase in water content close to the lens surface, consistent with the results described in Example 23. Example 25
[300] SiHy contact lenses with cross-linked coating (ie, the outer layers of hydrogel) prepared in Example 19 were desalted in ultrapure water, placed individually in a 50 ml disposable beaker with 50 ml of ultrapure water and frozen when placing the beaker in a bath with dry ice and isopropyl alcohol. The beakers are wrapped in aluminum foil and placed in a VirTis Freezemobile 35EL with a vacuum pressure = 30 μbar and a condenser temperature = -70 ° C. After 24 hours, the aluminum foil is removed to increase heat transfer and the balloons are left for an additional 24-48 hours to remove residual moisture. The balloons are capped to prevent the introduction of moisture from the air until analyzed. The lens samples are cut in half and two strips are then cut from the middle of each half and mounted on their edges for imaging the cross sections. The samples are then coated by spraying Au / Pd for ~ 1 minute and analyzed by SEM using a Bruker Quantax microanalysis system (JEOLJSM-800LV SEM). The sample plate is tilted at ~ 0-60 ° at the analyst's discretion to obtain the desired orientation of the sample.
[301] It is believed that when SiHy contact lenses are lyophilized, the hydrated surface structure of the lenses can be preserved or blocked to some extent. Figure 4, panel A, shows the top view of a SEM image of a surface of a lyophilized SiHy contact lens prepared in Example 19. It can be seen in Figure 4 that the lyophilized SiHy contact lens has a structure with a sponge-like surface, which would be expected for a hydrogel with a high water content. This result further confirms that a SiHy contact lens of the invention comprises the two outer hydrogel layers of a hydrogel with a high water content. Figure 4, panels B and C, show side views at two different angles of a cross section of the lyophilized SiHy contact lens shown in panel A. Panels B and C show the thick inner layer that presents a smooth surface, a layer transition layer (PAA layer) with a brighter color on the inner layer and an outer layer of hydrogel with sponge-like structures on the transition layer. Based on the data shown in panels B and C, it is estimated that the thickness of the lyophilized hydrogel outer layer is between about 2 μm and 2.5 μm. Example 26 Poly (AAm-co-AA) (90/10) labeled with fluorescein (called PAAm-PAA-F).
[302] PAAm-PAA-F is synthesized internally by covalently binding 5-aminofluorescein to PAAm-PAA (90/10) through a procedure similar to the preparation of PAA-F. Partial poly (AAm-co-AA) sodium salt (90/10) (solids content ~ 90%, poly (AAm-co-AA) 90/10, Mw 200,000) is purchased from Polisciences, Inc. and used as received. The level of fluorescein labeling is about 0.04 mol%. Modified IPC saline using PAAm-PAA-F.
[303] This saline solution is prepared using the same IPC preparation procedure, as described in Example 19, except that PAAm-PAA is replaced by PAAm-PAA-F. PAA coated lenses.
[304] Lenses are prepared by melting molding the lens formulation prepared above in Example 19 into a reusable mold (half of the quartz female mold and half of the glass male mold), similar to the mold shown in Figures 1-6 of United States Patents Nos 7,384,590 and 7,387,759 (Figures 1-6). The lens formulation in the molds is irradiated with UV radiation (13.0 mW / cm2) for about 24 seconds. Fusion-shaped contact lenses are extracted and coated by immersion in the following series of baths: DI water bath (about 56 seconds); 6 baths of MEK (about 44, 56, 56, 56, 56, and 56 seconds, respectively); DI water bath (about 56 seconds); a bath of PAA coating solution (about 0.36% by weight acidified with formic acid to a pH of about 2.0) in the 1-PrOH solvent (about 44 seconds); a bath of a 50% water / 1-propanol / 50% mixture (about 56 seconds); 4 DI water baths, each for about 56 seconds; a bath of PBS for about 56 seconds; and a DI water bath for about 56 seconds. Application of the reticulated coating.
[305] Lenses with a PAA base coat prepared above are placed in polypropylene lens packaging cases (one lens per case) with 0.6 mL of the modified IPC saline solution prepared above using PAAm-PAA-F ( half of the saline solution is added before placing the lens). The blisters are then sealed with an aluminum foil and autoclaved for about 30 minutes at about 121 ° C, forming SiHy contact lenses with cross-linked coatings (PAA-x-hydrophilic polymeric material) applied on them. Confocal fluorescence microscopy by laser scanning.
[306] A piece of a hydrated SiHy lens with a reticulated coating (prepared above) is placed between two glass coverslips and the image is captured in a confocal fluorescence microscope by laser scanning (model # Zeiss LSM 510 Vis). Scanning is performed from the front curved side of the lens to the base curved side of the lens, or vice versa. The presence of PAAm-PAA-F is shown by green fluorescence and confocal microscopic images of fluorescence by laser scanning can be obtained. Examination of confocal fluorescence microscopic images by laser scanning reveals that the PAAm-PAA-F-rich layer (ie, the outer hydrogel layers) is present on both lens surfaces (anterior and posterior surfaces) and at the edge peripheral, while PAAm-PAA-F is not observed in the volumetric material of the lens.
[307] Fluorescence intensity profiles are examined through the lens cross section along a line that crosses both the posterior and anterior surfaces and is normal to the posterior surface. The thickness of the PAAm-PAA-F-rich layer can be estimated from the fluorescence intensity profile through the lens. The possible thickness of the outer hydrogel layer (layer rich in PAAm-PAA-F) is estimated by the distance from zero intensity after crossing the peak intensity to zero intensity again. Considering that there is a possible contribution of unknown factors (such as dispersion) to the fluorescence intensity, the minimum layer thickness is the thickness to which a fluorescent intensity of at least 10% of the maximum peak intensity is preserved. Based on this estimate, the minimum thickness of the PAAm-PAA-F rich layer (hydrated hydrogel outer layer) could be at least about 5 microns. Example 27
[308] Lenses are manufactured using the D-2 lens formulation (Example 17) to which the APMAA monomer has been added at a concentration of 1%. LS lenses are prepared by fusing molding a lens formulation prepared above into a reusable mold, similar to the mold shown in Figures 1-6 of United States Patent Nos. 7,384,590 and 7,387,759 (Figures 1-6). The mold comprises a female mold half made from glass and a male mold half made from quartz. The source of UV radiation is a Hamamatsu lamp with a 380 nm cut filter at an intensity of about 4.6 mW / cm2. The lens formulation in the mold is irradiated with UV radiation for about 30 seconds.
[309] Fusion-shaped lenses are extracted with methyl ethyl ketone (MEK), rinsed with water, coated with polyacrylic acid (PAA) by immersing the lenses in a solution of PAA in propanol (0.0044% acidified weight) with formic acid to a pH of about 2.5), and hydrated in water.
[310] IPC saline is prepared according to the composition described in Example 9 under 8 hour pre-reaction conditions at approximately 60 ° C. The lenses are placed in a polypropylene lens packaging bag containing 0.6 mL of the IPC solution (half of the saline is added before placing the lens). The blister is then sealed with aluminum foil and autoclaved for 30 minutes at 121 ° C.
[311] Evaluation of the lens surface shows that all test lenses did not exhibit residue adhesion. When viewed under a dark field microscope, no crack line was visible after the lenses were rubbed between the fingers. The lens surface wetting capacity (WBUT) is more than 10 seconds, the lubricity is rated "1" and the contact angle is approximately 20 °. Example 28
[312] SiHy fusion-molded contact lenses (without any coating) prepared in Example 9 are used. All lenses are extracted in MEK overnight to ensure that any residual monomer is removed. The first group of lenses (lenses with a hydrated reticulate coating) is immersed overnight in a PAA coating solution (0.36% by weight of PAA in 1-propanol, pH 1.7 - 2 , 3 adjusted with formic acid), while the second group of lenses (control) is immersed in 1-propanol for the same period. Both groups of lenses are packed in the IPC solution prepared in Example 19 and autoclaved. The lenses after autoclaving are tested (in groups of 5) using the gravimetric analysis technique to determine the weights of dry and wet contact lenses (N = 14 for the first group of contact lenses; N = 18 for the second group of contact lenses) contact lenses). The results are shown in Table 8. Table 8

[313] There is a statistically significant difference (7 mg) in wet weight between the first and second groups of contact lenses due to the presence of the hydrated reticulate coating on the contact lenses compared to the control lenses (uncoated). However, the difference in dry weight between the first and second contact lens groups is about 0.3 mg and is not statistically significant. The water content of the lens for the coated lens can be estimated at ~ 96% according to the following calculation
It should be understood that the water content estimated here for the reticulated coating on a contact lens may not be accurate, since the difference in wet and dry weight between the first and second contact lens groups is too small and even lower standard deviation. Example 29
[314] This example illustrates how to quantify the lubricity of SiHy contact lenses according to the angled plate method ("Derby friction test"). The inclined plate method is a simple test to assemble, as shown in Figure 5. The inclined plate method assembly is composed of a 501 plastic reservoir or tank that is filled with phosphate buffered saline (PBS, pH ~ 7.3) 502, a borosilicate glass plate 503 and a shim 506 with an adjustable height between 5 mm and 20 mm high. Both the borosilicate glass plate 503 and the shim 506 are immersed in phosphate buffered saline 502 in the plastic tank or tank 501. In one test, a contact lens 504 is placed on the borosilicate glass plate and then , a stainless steel rim (to provide physiologically relevant F pressure). The critical friction coefficient = —L = tan θ, FN where θ is the critical angle, FN is the normal force, and Ft is the tangent force. The largest angle at which a lens continues to slide after being pushed, but stops, or takes more than 10 seconds before reaching the end, is defined as the "critical angle θ". The critical friction coefficient (CCOF) is the tangent of the critical angle θ. A lens that does not move will be below the CCOF, while a lens that does not stop during the travel distance will be above the CCOF. Angles above or below the CCOF are removed from the analysis. The Derby friction test can be a direct way to measure the kinematic friction coefficient.
[315] In tests according to the inclined plate method, all lenses are stored in PBS solution for at least one night (> 6 hours) before being tested to remove any residual conditioning solution. The glass plate (6 "x 4" borosilicate glass) is rubbed with a soap solution (1% Micro-90) and wiped (AlphaWipe TX1009). Each plate is rinsed vigorously in DI water, about 2 minutes. A friction section of the plate is tested by rubbing your finger to ensure that all soap solution has been removed. The water is dried with paper towels (KimTech Kimwipe # 34705) and inspected under the light to ensure that no foreign particles have remained on the glass. The glass plate is placed on shims of various heights in a plastic reservoir or tank and the height of this plane is measured with a micrometer and recorded. The reservoir is filled with phosphate buffered saline (PBS) to ensure that the lens is completely immersed (28 mm deep).
[316] Each lens is placed on the "starting line" and a 0.79 g ring (0.635 cm (1/4 "stainless steel) to provide physiologically relevant pressure) is dropped onto the lens surface. the plate is allowed to slide down and the time it takes the lens to travel the 96 mm is recorded.
[317] The lens is then brought to the initial position with the weight removed before being tested again. This "preload" effect should be minimized for better repeatability. The lens can be tested at different angles to obtain the ideal CCOF.
[318] Sixteen commercial contact lenses and the silicone hydrogel contact lenses prepared in Example 19 are tested for CCOF and the results are provided in Table 9. The results show that a SiHy contact lens of the invention (prepared in Example 19 in order to have a reticulated coating) has the smallest CCOF of any class of silicone hydrogel lenses that are commercially available and tested, thus having the highest lubricity. Table 9

CH: critical height; AC: critical angle Example 30
[319] This example illustrates how to characterize the negatively charged surface of a SiHy contact lens according to the positively charged particle adhesion test.
[320] The surface charge of a contact lens can be detected indirectly via its interaction with charged particles or spheres. A negatively charged surface will attract positively charged particles. A surface free of negative charges or substantially free of negative charges will not attract positively charged particles or attract few positively charged particles.
[321] Uncoated SiHy contact lenses (ie, melt molded and extracted with MEK as described in Example 19), PAA coated SiHy contact lenses (prepared in Example 19), and SiHy contact lenses with a cross-linked coating (prepared in Examples 14 and 19) are tested as follows. The PAA coating of PAA-coated contact lenses has a surface concentration of carboxylic groups of about 62.5% by weight
where MCOOH is the mass of carboxylic acid groups and MAA is the mass of acrylic acid). The crosslinked coating of the contact lenses of Example 14 is theoretically free of carboxylic acid groups, while the crosslinked coating of the contact lenses of Example 19 may contain a low concentration on the surface of carboxylic acid groups (must be less than
by weight). The lenses are immersed in a dispersion with positively charged particles and, after appropriate rinsing, the number of particles adhered to the lens is visualized and estimated or counted.
[322] DOWEX® 1x4 resins of 20-50 mesh are purchased from Sigma-Aldrich and used as received. DOWEXTM1x4 resins of 20-50 mesh are spherical type I strong basic anionic resins and are a styrene / divinylbenzene copolymer containing N + (CH3) 3Cl- and 4% divinylbenzene functional groups. 5% of 1x4 resins of 20-50 mesh are dispersed in PBS and mixed well by shaking or vortexing at approximately 1000 rpm for 10 seconds. The lenses are immersed in this dispersion and agitated between 1000-1100 rpm for 1 minute, followed by rinsing with DI water and vortexing for 1 minute. The lenses are then placed in water in glass Petri dishes and images of the lenses are taken with a Nikon optical microscope, using background lighting. As shown in Figure 6, almost the entire surface of the PAA-coated lenses is covered with positively charged particles adhered to (Figure 6a), while a total of about 50 positively charged particles are adhered to the lenses with the reticulated coating prepared in Example 19 (Figure 6B) and no positively charged particles are adhered to the lenses with the crosslinked coating prepared in Example 14 (Figure 6C). Some loosely attached particles can fall off the lens surface and can also be found in the water around the lens.
[323] It should be understood that when positively charged particles of a larger size (ie DOWEX® monosphere ion exchange resins, cross-linked polystyrene spheres, chloride form, ~ 590 micron size, from Sigma-Aldrich) are used in tests, the number of particles adhered to the particles can be reduced. About 30% of these DOWEX monosphere resins are dispersed in PBS. The lenses are immersed in this dispersion for ~ 1 minute, followed by rinsing with DI water. The lenses are then placed in water in glass Petri dishes and images of the lenses are taken with a Nikon optical microscope, using background lighting. It was found that there are many particles (about 200 particles) adhered to the PAA-coated lenses and no particles adhered to the lenses with a cross-linked coating. Some commercially available contact lenses have also been tested. No particles were observed in the following lenses: Acuvue®TruEyeTM, Acuvue®Advance®, Acuvue®Oasys®, Avaira®, Biofinity®, Air Optix®, and Focus®Night & Day®. Particles were observed in the following 4 types of lenses (in order of increasing particle number): PureVision®, 1 Day Acuvue®Moist®, Proclear 1 Day, Acuvue® (Etafilcon A). Virtually the entire surface of the Acuvue® lens (Etafilcon A) was covered with positively charged particles adhered to.
[324] Negatively charged resins (Amberlite CG50) are purchased from Sigma and used as received. 5% of this Amberlite CG50 resin in beads are dispersed in PBS and stirred at about 1000 rpm for 10 seconds. The PAA-coated lenses are immersed in this dispersion and agitated between 1000-1100 rpm for 1 minute, followed by rinsing with DI water and vortexing for 1 minute. The lenses are then placed in water in glass Petri dishes and images of the lenses are taken with a Nikon optical microscope using background lighting. No Amberlite particles (negatively charged) were found in the PAA-coated lenses.
[325] Negatively charged spheres (Amberlite CG50), which are coated with polyethyleneimine (PEI, a positively charged electrolyte), are used in this experiment. The PEI coating procedure is done as follows. PEI (Lupasol SK, 24% in water, Mw of ~ 2,000,000) is purchased from BASF and used as received. Prepare a 1% aqueous dispersion of Amberlite particles and 5% PEI. Adjust the pH to 7 and make sure that the solution is mixed well (for example, by stirring for 30 minutes). Then, suspend the dispersion in a large amount of water 2 to 3 times and filter 2 to 3 times before the particles are collected (PEI coated Amberlite). 5% particles of Amberlite CG50 coated with PEI are dispersed in PBS and stirred at about 1000 rpm for 10 seconds. The lenses are immersed in this dispersion and agitated between 1000-1100 rpm for 1 minute, followed by rinsing with DI water and vortexing for 1 minute. The lenses are then placed in water in glass Petri dishes and images of the lenses are taken with a Nikon optical microscope using background lighting. It can be seen that there are many particles of Amberlite coated with PEI (particles positively charged due to the presence of PEI) adhered to the lenses coated with PAA (Example 19). However, there is virtually no PEI-coated Amberlite particle adhered to uncoated SiHy contact lenses (Example 19), crosslinked SiHy contact lenses (Example 19) or PAExPAA coated lenses (Example 4). Example 31 Sample preparation:
[326] AFM studies were conducted on SiHy contact lenses (prepared in Example 19) in the hydrated and dry state. A lens is removed from its blister pack (sealed and autoclaved) and a cross section is cut (for example, with a razor blade). The lens cross-section piece is mounted vertically on a metal clamp, as shown in Figure 7. A small piece of the lens protrudes from the top of the bracket to allow the AFM tip (above the lens cross section on the Figure 7) explore it. Experiment with AFM:
[327] Two distinct AFM instruments are used to characterize the cross section of the lens. In both cases (except for dry samples), the AFM is scanned under a phosphate buffered solution (PBS with or without NaCl, however, having an osmolarity substantially identical to that of the physiological saline) to maintain the fully hydrated state of the hydrogel sample.
[328] The first AFM instrument is the Veeco BioScope AFM with a Nanoscope IV controller. Data are collected using triangular silicon cantilevers with a spring constant of 0.58 N / m and a nominal tip radius with a curvature of 20-60 nm. Scans are made in constant contact mode (force-volume) with a probe speed of 30 microns / second and a force-volume scan rate of 0.19 Hz. Topographic data and force-volume data are collected simultaneously. Each strength curve consisted of about 30 data points. The lens is fully immersed in PBS during the AFM scan. Normally, a scan size of a maximum of 20 microns is used to obtain a resolution high enough for the force-volume image. Force schemes of 128 x 128 pixels are collected for approximately 3 hours per image.
[329] An AFM image of a cross section of a SiHy contact lens with reticulated coating (Example 19) in the fully hydrated state is obtained via the Force-Volume method and is shown in Figure 8. In the image, the region of darker color 420 indicates the coating and the lighter color region 410 indicates the volumetric material of the lens. The average thickness of the reticulated coating (ie, the anterior and posterior outer layers) of the SiHy contact lens (Example 19) is determined to be about 5.9 μm (0.8 μm standard deviation) obtained from 7 images, 4 lenses.
[330] The AFM technique allows the determination of the surface modulus (smoothness of the surface) at specific locations in the cross section of the lens. Figure 9 shows the cross sectional surface module profile of a SiHy contact lens with a crosslinked coating (prepared in Example 19) in the fully hydrated state. Since the surface modulus of a material is proportional to the deflection of the cantilever, a cross sectional surface modulus profile of a contact lens can be obtained approximately by plotting the deflection values of the cantilevers (measured for the surface modulus) of a material at a specific location on the lens cross section) as a function of the distance from the side (front or back surface) of the cross section along two lines through the cross section shown in Figure 8. As shown in Figure 9, the cross-linked coating (the front and back outer layers of the contact lens of Example 19) is softer than the volumetric material (inner layer) of the silicone hydrogel lens. When moving the two lines apart, the surface modulus first remains constant with an average cantilever deflection of about 52 nm (ie, average surface modulus) in the range between 0 and about 5.9 microns and then gradually increases at the innermost locations of the lens until it reaches a maximum and thereafter remains approximately constant (plateau) with an average cantilever deflection of about 91 (ie, average surface modulus) in the zone above about 7 microns. The transition from the softer crosslinked coating to the harder volumetric SiHy material, which occurs gradually over the range of a few microns, suggests that a gradient in morphology or composition (water content) may be present between the surface of the coating and the material volume of the lens. Surface modules in the area between 5.9 microns and about 7 microns, that is, a region around the edge between the outer layer of hydrogel and the inner layer of silicone hydrogel material, are not used in calculating the modulus of medium surface. It can be calculated that the outer front and rear hydrogel layers (reticulated coating) of the SiHy contact lens (Example 19) have a reduced surface modulus
, in which SMInterno is the average surface modulus of the posterior or anterior hydrogel layer and SMtotemo is the average surface modulus of the inner layer) of about 43%.
[331] SiHy contact lenses (prepared in Example 19) are studied with the second AFM instrument. The scan is performed using an AFM Bruker Icon in "Quantitative Nanomechanical Measurements" mode (PeakForce QNM) using lenses in the fully hydrated state (PBS without NaCl, however, with glycerol to achieve a similar osmolarity) or in the dry state. The lens cross section is mounted on a metal clamp, as described above. The test conditions include a spring constant of 1.3 N / m, a tip radius of 33.3 nm, a sensitivity of 31 nm / V, a scan rate of 0.4 Hz and a scan resolution of 512 x 512.
[332] AFM images of a cross section of the SiHy contact lens (Example 19) in the fully hydrated and dry state are obtained according to the PeakForce QNM method. When analyzing the images obtained, the thickness of the crosslinked coating in the fully hydrated state is determined to be about 4.4 microns, while the thickness of the crosslinked coating in the dry state is determined to be about 1.2 microns for a dry sample. vacuum, about 1.6 microns for an oven dried sample. The proportion of water expansion
where L ^ a is the average thickness of the outer layer of hydrogel of the SiHy contact lens in the fully hydrated state and Lseca is the average thickness of this outer layer of hydrogel of the SiHy contact lens in the dry state) of the reticulated coating of the SiHy contact lenses (prepared in Example 19) are calculated to be about 277% (oven dried sample) or about 369% (vacuum dried sample). Example 32 Preparation of lens formulations
[333] Formulation I is prepared by dissolving the components in 1-propanol to have the following composition: 33% by weight of the CE-PDMS macromer prepared in Example 2, 17% by weight of N- [tris (trimethylsiloxy) - silylpropyl] acrylamide (TRIS-Am), 24% by weight of N, N-dimethylacrylamide (DMA), 0.5% by weight of N- (carbonylmethoxy-polyethylene glycol 2000) -1,2-diestearoil-sn-glycerol- 3-phosphoethanolamine, sodium salt) (L-PEG), 1.0% by weight of Darocur 1173 (DC1173), 0.1% by weight of Visitint (5% dispersion of blue copper phthalocyanine pigment in tris methacrylate (trimethylsiloxy) silylpropyl, TRIS) and 24.5% by weight of 1-propanol.
[334] Formulation II is prepared by dissolving the components in 1-propanol in order to have the following composition: about 32% by weight of the CE-PDMS macromer prepared in Example 2, about 21% by weight of TRIS- Am, about 23% by weight of DMA, about 0.6% by weight of L-PEG, about 1% by weight of DC1173, about 0.1% by weight of Visitint (5% dispersion of the pigment copper phthalocyanine blue in TRIS), about 0.8 wt% DMPC, about 200 ppm H-time and about 22 wt% 1-propanol. Lens Preparation
[335] The lenses are prepared by melting molding a lens formulation prepared above into a reusable mold (half of the quartz female mold and half of the glass male mold), similar to the mold shown in Figures 1-6 of the Patents United States Nos 7,384,590 and 7,387,759 (Figures 1-6). The source of UV radiation is a Hamamatsu lamp with a cut filter WG335 + TM297 at an intensity of about 4 mW / cm2. The lens formulation in the mold is irradiated with UV radiation for about 25 seconds. Fusion-shaped lenses are extracted with methyl ethyl ketone (MEK) (or propanol or isopropanol). Application of PAA base coat to SiHy contact lenses
[336] A polyacrylic acid (PAA-1) coating solution is prepared by dissolving an amount of PAA (MW: 450 kDa, from Lubrizol) in a given volume of 1-propanol in order to have a concentration of about 0 , 36% by weight and the pH is adjusted with formic acid to about 2.0.
[337] Another PAA coating solution (PAA-2) is prepared by dissolving an amount of PAA (MW: 450 kDa, from Lubrizol) in a given volume of an organic solvent (50/50 1-propanol / H2O) ) in order to have a concentration of about 0.39% by weight and the pH is adjusted with formic acid to about 2.0.
[338] The SiHy contact lenses obtained above are subjected to one of the immersion processes shown in Tables 10 and 11. Table 10

[339] PrOH represents 100% 1-propanol; PBS means phosphate buffered saline; MEK means methyl ethyl ketone; 50/50 means a 50/50 1-PrOH / H2O solvent mixture. Table 11

[340] PrOH represents 100% 1-propanol; PBS means phosphate buffered saline; MEK means methyl ethyl ketone; 50/50 means a 50/50 1-PrOH / H2O solvent mixture. Application of cross-linked hydrophilic coating
[341] Partial (poly) acrylamide-co-acrylic acid sodium salt, Poly (AAm-co-AA) (90/10) (solids content ~ 90%, poly (AAm-co-AA) 90/10, 200,000 Mw) is purchased from Polisciences, Inc. and used as received. PAE (Kymene, azetidinium content of 0.46 analyzed by NMR) is purchased from Ashland as an aqueous solution and used as received. A saline solution for internal packaging lining (IPC) is prepared by dissolving about 0.07% w / w of poly (AAm-co-AA) (90/10) and about 0.15% PAE (an equivalent initial millimolar azetidinium of about 8.8 millimoles) in phosphate buffered saline (PBS) (about 0.044% w / w NaH2PO-H2O, about 0.388% w / w Na2HPO <2H2O, about 0, 79% w / w NaCl) and pH adjustment to 7.2- 7.4. Then, the IPC solution is thermally pretreated for about 4 hours at about 70 ° C (heat pretreatment). During this thermal pretreatment, poly (AAm-co-AA) and PAE are partially cross-linked (that is, not consuming all the PAE azetidinium groups) to form a water-soluble, thermally crosslinkable hydrophilic polymeric material that contains azetidinium groups on the branched polymeric network in the IPC solution. After thermal pretreatment, the IPC solution is filtered using a 0.22 micron polyether sulfone (PES) membrane filter and cooled to room temperature. 10 ppm of hydrogen peroxide is then added to the final IPC saline solution to prevent growth of biological charge and the IPC solution is filtered using a 0.22 micron polyether sulfone (PES) filter.
[342] Lenses with a PAA base coating prepared above are placed in polypropylene lens packaging cases (one lens per case) with 0.6 mL of the IPC solution (half of the saline is added before placing the lens). The blisters are then sealed with aluminum foil and autoclaved for about 30 minutes at about 121 ° C, forming SiHy contact lenses with cross-linked hydrophilic coatings on them. Characterization of SiHy lenses
[343] The resulting SiHy contact lenses with crosslinked hydrophilic coatings and a central thickness of about 0.95 microns present an oxygen permeability (estimated intrinsic Dkc or Dk) from about 142 to about 150 barrers, a volumetric elastic modulus from about 0.72 to about 0.79 MPa, a water content from about 30% to about 33% by weight, a relative ionic permeability of about 6 ( relative to the Alsacon lens) and a contact angle from about 34 to about 47 degrees. Characterization of the Nanotextured Surfaces of the Contact Lens
[344] Differential Transmission Interference Contrast (TDIC) method. _The contact lenses are placed on a glass slide and flattened by compressing the lens between the blade and a glass cover slip. The surfaces of contact lenses are located and examined by focusing through the lens using a Nikon ME600 microscope with differential transmission interference contrast optics using a 40x objective lens. The TDIC images obtained are then evaluated to determine the presence of wrinkled patterns on the surface (for example, random and / or wormlike patterns, among others).
[345] Differential Reflection Interference Contrast (RDIC) method. The contact lenses are placed on a glass slide and flattened by making 4 radial cuts every ~ 90 degrees. Excess saline is removed by blowing the surface using compressed air. The lens surface is then examined using a Nikon Optiphot-2 with differential reflection interference contrast optics for the presence of wrinkled patterns on the surface of a contact lens using 10x, 20x and 50x objective lenses. A representative image on each side is obtained using a 50x objective lens. The contact lens is then turned, the excess saline solution is removed and the other side of the contact lens is inspected in the same way. The obtained RDIC images are then evaluated to determine the presence of wrinkled patterns on the surface (for example, random and / or wormlike patterns, among others).
[346] Dark Field Optical Microscopy (DFLM). DFLM is based, in general, on dark field lighting, which is a method to improve the contrast in the observed samples. This technique consists of a light source outside the observer's field of view or blocked in the observer's field of view to illuminate a sample at an angle relative to normal transmitted light. Since the non-scattered light from the source is not captured by the objective lens, it is not part of the image and the background of the image looks dark. Since the light source illuminates the sample at a certain angle, the light observed in the sample image is that which is scattered by the sample towards the observer, thus creating a contrast between this scattered light from the sample and the dark background of image. This contrast mechanism makes dark lighting especially useful for observing dispersion phenomena, such as turbidity.
[347] DFLM is used to assess the turbidity of contact lenses as follows. It is believed that, since the dark-field configuration involves scattered light, dark-field data offers the worst estimated case of turbidity. In 8-bit grayscale digital images, each image pixel is assigned a grayscale intensity value (GSI) in the range 0-255. Zero represents a pixel that is perfectly black, 255 represents a pixel that is perfectly white. An increase in the scattered light captured in the image will produce pixels with higher GSI values. This GSI value can then be used as a mechanism to quantify the amount of scattered light observed in a darkfield image. Turbidity is expressed by averaging the GSI values of all pixels in an area of interest (AOI) (for example, an entire lens or the lenticular or optical zone of a lens). The experimental environment consists of a microscope or equivalent optical instrument, an associated digital camera and a dark field support with an annular light source and a light source of varying intensity. The optical instrument is designed / positioned so that the entire contact lens to be observed fills the field of view (typically a field of view of ~ 15 mm x 20 mm). The lighting is adjusted to an appropriate level to observe the desired changes in the relevant samples. The light intensity is adjusted / calibrated at the same level for each group of samples using a density / light scattering pattern known to those skilled in the art. For example, a pattern is made up of two overlapping plastic coverslips (identical or light or moderately matte). Such a pattern consists of areas with three different average GSI that include two areas with intermediate levels in the gray scale and saturated white (borders). The black areas represent the empty dark field. The black and saturated white areas can be used to check the camera's gain and retreat (contrast and brightness) settings. The intermediate gray levels can provide three points for checking the linear response of the camera. The light intensity is adjusted so that the average GSI of the empty dark field approaches 0 and that of an AOI defined in a digital image of the standard is the same all the time within ± 5 GSI units. After calibrating the light intensity, a contact lens is immersed in a phosphate-buffered saline solution filtered through a 0.2 μm filter in a quartz Petri dish or a plate or similar clarity that is placed in the DFLM holder. An 8-bit gray scale digital image is then acquired as viewed using the calibrated lighting and the average GSI of an AOI defined within the portion of the image containing the lens is determined. This procedure is repeated for a group of contact lens samples. Calibration of light intensity is periodically reassessed during the course of the test to ensure consistency. The turbidity level when evaluating a DFLM exam refers to a turbidity

[348] SiHy contact lenses, whose PAA base coating is obtained according to any of the 20-0 and 80-0 immersion processes, have been determined to have an average DFLM turbidity of about 73% and shows wrinkled patterns on the surface (random patterns similar to an earthworm) that can be visually observed when examining the contact lens in the hydrated state according to the RDIC or TDIC method already described above. However, the wrinkled patterns on the surface have virtually no adverse effects on the light transmissibility of contact lenses.
[349] SiHy contact lenses, whose PAA base coating is obtained according to any of the 20-1 to 20-4 immersion processes, have been determined to have a low average turbidity per DFLM of about 26% (probably due to the presence of particles from the Visitint pigment) and do not exhibit noticeable wrinkled patterns on the surface (random patterns similar to an earthworm) when examined by RDIC or TDIC already described above.
[350] It has been determined that a large percentage of SiHy contact lenses, whose PAA base coating is obtained according to the 20-5 immersion process, have a moderate DFLM turbidity of about 45% and exhibit patterns wrinkles on the surface slightly noticeable when examined by RDIC or TDIC already described above. However, the wrinkled patterns on the surface have virtually no adverse effects on the light transmissibility of contact lenses.
[351] SiHy contact lenses, whose PAA base coating is obtained according to any of the 80-1, 80-2, 80-3, 80-5 and 80-6 immersion processes, do not exhibit patterns noticeable wrinkles on the surface when examined under RDIC or TDIC, as described above. However, SiHy contact lenses, whose PAA base coating is obtained according to any of the 80-0 and 80-4 immersion processes, exhibit noticeable wrinkled patterns on the surface when examined under RDIC or TDIC, as described above . However, the wrinkled patterns on the surface have practically no adverse effects on the light transmissibility of contact lenses. Example 33 Synthesis of Amphiphilic Branched Prepolymer UV Absorbent
[352] A jacketed reactor of 1 l is equipped with a 500 mL addition funnel, a suspended stir bar, a reflux condenser with a nitrogen / vacuum inlet adapter, a thermometer and a sample collection adapter. 89.95 g of 80% partially ethylenically functionalized polysiloxane prepared in Example 17, A, is loaded into the reactor and then degassed under a vacuum of less than 1 mbar at room temperature for about 30 minutes. The monomer solution prepared by mixing 1.03 g of HEMA, 50.73 g of DMA, 2.76 g of Norbloc methacrylate, 52.07 g of TRIS and 526.05 g of ethyl acetate is loaded into the addition funnel. 500 mL, followed by degassing under a vacuum of 100 mbar at room temperature for 10 minutes and then refilled with nitrogen gas. The monomer solution is degassed under the same conditions for two more cycles. The monomer solution is then loaded into the reactor. The reaction mixture is heated to 67 ° C with adequate stirring. During heating, a solution composed of 2.96 g of mercaptoethanol (chain transfer agent, CTA) and 0.72 g of 2,2'-azobis (dimethyl 2-methylpropionate) (initiator V-601) and 76, 90 g of ethyl acetate is loaded into the addition funnel, followed by the same degassing process depending on the monomer solution. When the reactor temperature reaches 67 ° C, the initiator / CTA solution is also added to the reactor. The reaction is carried out at 67 ° C for 8 hours. After copolymerization is completed, the reactor temperature is cooled to room temperature. Synthesis of Amphiphilic Branched Prepolymer UV Absorbent
[353] The copolymer solution prepared above is ethylenically functionalized to form an amphiphilic branched prepolymer by adding 8.44 g of IEM (or 2-isocyanatoethyl methacrylate in the desired molar equivalent amount) in the presence of 0.50 g of DBTDL. The mixture is stirred at room temperature under a sealed condition for 24 hours. The prepared prepolymer is then stabilized with 100 ppm of hydroxy-tetramethylene piperonyloxy before the solution is concentrated to 200 g (~ 50%) and filtered through a filter paper with a pore size of 1 μm. After the reaction solvent is exchanged for 1-propanol through several evaporation and dilution cycles, the solution is ready to be used for formulation. The solids content is measured by removing the solvent in a vacuum oven at 80 ° C. Lens Formulation Preparation
[354] A lens formulation is prepared to have the following composition: 71% by weight of the prepolymer prepared above; 4% by weight of DMA; 1% by weight of TPO; 1 wt% DMPC; 1% by weight of Brij 52 (from Sigma-Aldrich), and 22% by weight of 1PrOH. Lens Preparation
[355] Lenses are manufactured by fusing molding the lens formulation prepared above using a reusable mold, similar to the mold shown in Figures 1-6 of United States Patent Nos. 7,384,590 and 7,387,759 (Figures 1-6) under spatial limitation of UV radiation. The mold comprises a female mold half made from glass and a male mold half made from quartz. The source of UV radiation is a Hamamatsu lamp with a 380 nm cut filter at an intensity of about 4.6 mW / cm2. The lens formulation in the mold is irradiated with UV radiation for about 30 seconds.
[356] Fusion-shaped lenses are extracted with methyl ethyl ketone (MEK), rinsed with water, coated with polyacrylic acid (PAA) by immersing the lenses in a solution of PAA in propanol (0.004% by weight acidified with acid formic to a pH of about 2.0) and hydrated in water.
[357] IPC saline is prepared from a composition containing about 0.07% PAAm-PAA and PAE sufficient to provide an initial azetidinium content of approximately 8.8 millimolar equivalents / liter (~ 0.15 % PAE) under 6 hour pre-reaction conditions at approximately 60 ° C. 5 ppm of hydrogen peroxide is then added to the IPC solutions to prevent the growth of biological charge and the IPC solutions are filtered using a 0.22 micron polyether sulfone (PES) filter. The lenses are placed in a polypropylene lens packaging bag containing 0.6 mL of the IPC solution (half of the saline is added before placing the lens). The blister is then sealed with aluminum foil and autoclaved for 30 minutes at 121 ° C. Lens Characterization
[358] The obtained lenses have the following properties: E '~ 0.82 MPa; DKc ~ 159.4 (using lotrafilcon B as the reference lens, an average center thickness of 80 μm and an intrinsic Dk of 110); IP ~ 2.3; % water ~ 26.9; and UVA / UVB% T ~ 4.6 / 0.1. When viewed under a dark field microscope, no crack line was visible after the lens rub test. The lenses are heavily lubricated in a rubbing test between fingers and equivalent to control lenses.

权利要求:
Claims (64)
[0001]
1. Hydrated hydrogel silicone contact lens (100), characterized by the fact that it comprises: an opposite front surface (101) and an opposite rear surface (102); and a layered structural configuration from the front surface (101) to the rear surface (102), the layered structural configuration including an outer front layer of hydrogel (120), an inner layer (110) of a hydrogel silicone and a hydrogel back outer layer (120), with the hydrogel silicone material having an oxygen permeability, Dk, of at least 50 Barrers and a first water content, designated as WCSiHy, from 10% to 70% by weight, with the outer front and rear hydrogel layers (120) having a substantially uniform thickness and fusing at the peripheral edge (103) of the contact lens to completely envelop the inner layer (110) of the silicone hydrogel material, being that the anterior and posterior external hydrogel layers (120) have, independently of each other, a second water content higher than WCSiHy, as characterized (a) by presenting a swelling ratio o in water, WSR, of at least 100% if WCsH <45% or (b) because it has a dilation ratio in water of at least
[0002]
2. Hydrated hydrogel silicone contact lens (100), according to claim 1, characterized by the fact that the outer front and rear hydrogel layers of hydrogel have, independently of each other, a proportion of hair water expansion minus 150% if WCsiHy <55%.
[0003]
3. Hydrated hydrogel silicone contact lens (100) according to claim 1, characterized by the fact that the outer front and rear hydrogel layers of hydrogel have, independently of each other, a proportion of hair water expansion minus 200% if WCSiHy <60%.
[0004]
4. Hydrated hydrogel silicone contact lens (100) according to claim 1, characterized by the fact that the outer front and rear hydrogel layers of hydrogel have, independently of each other, a proportion of hair water expansion minus 250% if WCSiHy <65%.
[0005]
5. Hydrated hydrogel silicone contact lens (100), according to claim 1, characterized by the fact that the external anterior and posterior hydrogel layers have, at least 300%, a water expansion ratio of at least 300 %.
[0006]
6. Hydrated silicone hydrogel contact lens (1 00), according to claim 1, characterized by the fact that the silicone hydrogel material has an oxygen permeability, Dk, of at least 70 and a first water content ( WCSiHy) from 15% to 55% by weight, with the thickness of each of the anterior and posterior external hydrogel layers (120) being from 0.25 μm to 15 μm.
[0007]
7. Hydrated hydrogel silicone contact lens (100) according to claim 1, characterized by the fact that the outer anterior and posterior hydrogel layers (120) have, independently of each other, a reduced surface module of at least 20% less than the inner layer (110).
[0008]
8. Hydrated hydrogel silicone contact lens (100), according to claim 7, characterized by the fact that the thickness of each of the anterior and posterior external hydrogel layers (120) presents from 0.5 μm to 12.5 μm.
[0009]
9. Hydrated hydrogel silicone contact lens (100), according to claim 7, characterized by the fact that the hydrogel silicone material has an elasticity module from 0.4 MPa to 1.5 MPa.
[0010]
10. Hydrated hydrogel silicone contact lens (100), according to claim 1, characterized by the fact that the anterior (101) and posterior (102) surfaces have a low concentration on the surface of negatively charged groups, as defined by an attraction of a maximum of 200 positively charged particles in the positively charged particle adhesion test.
[0011]
11. Hydrated hydrogel silicone contact lens (100), according to claim 1, characterized by the fact that the outer anterior and posterior hydrogel layers (120) have a thickness of 1 μm to 10 μm.
[0012]
12. Hydrated hydrogel silicone contact lens (100), according to claim 1, characterized by the fact that it also comprises, in its layered structural configuration, two transition layers (115) of polymeric material (s) ), where each of the two transition layers (115) is located between the inner layer (110) and one of the front and back outer hydrogel layers (120) and has a substantially uniform thickness, with the thickness of each layer transition (115) is at least 0.05 μm.
[0013]
13. Hydrated hydrogel silicone contact lens (100), according to claim 1, characterized by the fact that it presents a high resistance to digital friction, as characterized by not having superficial crack lines visible under a dark field after the lens contact pad be rubbed between your fingers.
[0014]
14. Hydrated hydrogel silicone contact lens (100), according to claim 1, characterized by the fact that it has good surface lubricity, as defined by having a critical friction coefficient of 0.046 or less.
[0015]
15. Hydrated hydrogel silicone contact lens (100), according to claim 1, characterized by the fact that it has a surface hydrophilicity as defined by having a break time in water of at least 10 seconds; a surface wetting capacity as defined by having an average water contact angle of 80 degrees or less; or combinations thereof.
[0016]
16. Hydrated hydrogel silicone contact lens (100) according to claim 12, characterized in that the transition layers (115) comprise a polymer containing carboxyl (COOH).
[0017]
17. Hydrated hydrogel silicone contact lens (100) according to claim 1, characterized by the fact that the anterior and posterior external hydrogel layers (120) are formed by applying and cross-linking a water-soluble, cross-linkable hydrophilic polymeric material over a precast silicone hydrogel contact lens, wherein the precast silicone hydrogel contact lens comprises amino and / or carboxyl groups at and / or near the surface of the contact lens or a base coat comprising amino groups and / or carboxyl; where the pre-molded hydrogel silicone contact lens becomes the inner layer after crosslinking.
[0018]
18. Hydrated hydrogel silicone contact lens (100) according to claim 17, characterized in that the water-soluble and cross-linkable hydrophilic polymeric material is a partially cross-linked polymeric material comprising a three-dimensional network and cross-linkable groups within the network.
[0019]
19. Hydrated hydrogel silicone contact lens (100) according to claim 17, characterized by the fact that the water-soluble and cross-linkable hydrophilic polymeric material comprises (i) from 20% to 95% by weight of first polymer chains derived from a polyamine or polyamidoamine functionalized with epichlorohydrin; (ii) from 5% to 80% by weight of hydrophilic moieties or second polymer chains derived from at least one hydrophilicity-enhancing agent that has at least one reactive functional group selected from the group consisting of an amino group, group carboxyl, thiol group and combination thereof, in which the hydrophilic moieties or second polymer chains are covalently linked to the first polymer chains through one or more covalent bonds, each formed between a polyamine azetidinium group or polyamidoamine functionalized with epichlorohydrin and an amino, carboxyl or thiol group of the hydrophilicity-enhancing agent; and (iii) azetidinium groups that are part of the first polymer chains or pendant or terminal groups covalently linked to the first polymer chains.
[0020]
20. Hydrated hydrogel silicone contact lens (100), according to claim 19, characterized by the fact that the hydrophilic polymer as a hydrophilicity-enhancing agent is: PEG-NH2; PEG-SH; PEG-COOH; H2N-PEG-NH2; HOOC-PEG-COOH; HS-PEG-SH; H2N-PEG-COOH; HOOC-PEG-SH; H2N-PEG-SH; Multiple-arm PEG with one or more amino, carboxyl or thiol groups; PEG dendrimers with one or more amino, carboxyl or thiol groups; a diamino, dicarboxyl, monoamino or monocarboxyl-terminated homo- or copolymer of a non-reactive hydrophilic vinyl monomer; a copolymer which is a polymerization product of a composition comprising (1) 60% by weight or less by weight of at least one reactive vinyl monomer and (2) at least one non-reactive hydrophilic vinyl monomer; or combinations thereof, in which PEG is a segment of polyethylene glycol, in which the reactive vinyl monomer is selected from the group consisting of (meth) acrylate-C1-C6 alkyl, (meth) C1- acrylate C6 alkylamino C1-C6 alkyl, allylamine, vinylamine, amino-C1-C6 alkyl (meth) acrylamide, C1-C6 alkylamino-C1-C6 alkyl (meth) acrylamide, acrylic acid, C1-C4 alkyl acrylic acid, N, N acid -2-acrylamidoglycolic acid, beta-methyl-acrylic acid, alpha-phenyl acrylic acid, beta-acryloxy propionic acid, sorbic acid, angelic acid, cinnamic acid, 1- carboxy-4-phenylbutadiene-1,3-itaconic acid, citraconic acid , mesaconic acid, glutaconic acid, aconitic acid, maleic acid, fumaric acid, tricarboxyethylene and meso combinations, in which the non-reactive vinyl monomer is selected from the group consisting of acrylamide, methacrylamide, N, N-dimethylacrylamide, N, N-dimethylmethacrylamide, N-vinylpyrrolidone, N methacrylate, N-dimethylaminoethyl, N, N acrylate -dimethylaminoethyl, N, N-dimethylaminopropylmethacrylamide, N, N-dimethylaminopropylacrylamide, glycerol methacrylate, 3-acryloylamino-1-propanol, N-hydroxyethylacrylamide, N- [tris (hydroxymethyl) methyl-3-methyl] -acrylamide -2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2 -pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, (meth) 2-hydroxyethyl acrylate, (meth) hydroxypropyl acrylate, a vinyl monomer containing phosphorylcholine, (meth) C1-C4-alkoxy polyethylene glycol acrylate which has a weighted average molecular weight of up to 1500 Daltons, N-vinyl formamide, N-vinyl acetamide, N-vinyl isopropylamide, N-vinyl-N-methyl acetamide, allyl alcohol, vinyl alcohol (hydrolyzed form of vinyl acetate in the copolymer ), and combinations thereof.
[0021]
21. Hydrated hydrogel silicone contact lens (100) according to claim 1, characterized by the fact that the front and rear outer hydrogel layers (120) comprise cross-linkages derived from azetidinium groups in a thermally induced coupling reaction .
[0022]
22. Hydrated silicone hydrogel contact lens (100) according to claim 1, characterized in that the silicone hydrogel material is obtained from a silicone hydrogel lens formulation comprising at least one component selected from from the group consisting of a vinyl monomer containing silicone, a vinyl macromer containing silicone, a prepolymer containing silicone, a hydrophilic vinyl monomer, a hydrophobic vinyl monomer, a crosslinking agent, a free radical initiator, a macromer / hydrophilic vinyl prepolymer and combinations thereof.
[0023]
23. Hydrated silicone hydrogel contact lens (100) according to claim 22, characterized in that the silicone hydrogel lens formulation comprises: (1) a hydrophilic vinyl monomer selected from the group consisting of N , N-dimethylacrylamide, N, N-dimethylmethacrylamide, N-vinylpyrrolidone, N-vinyl-N-methyl-acetamide, 1-methyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, methacrylate hydroxyethyl, hydroxyethyl acrylate and meso combinations; and (2) a vinyl monomer containing silicone, a vinyl monomer or macromer containing polysiloxane and / or a prepolymer containing silicone.
[0024]
24. Hydrated silicone hydrogel contact lens (100), characterized by the fact that it comprises: a silicone hydrogel material as a volumetric material, an anterior surface (101) and an opposite posterior surface (102), the contact lens being (100) has an oxygen transmissibility of at least 40 barrers / mm and a cross sectional surface module profile, with the cross sectional surface module profile comprising, along a shorter line between the anterior surfaces (101 ) and posterior (102) on the surface of a cross-section of the contact lens (100), an anterior outer zone including and close to the anterior surface (101), an inner zone that includes and is around the center of the shorter line and a posterior outer zone including and close to the posterior surface (102), the anterior outer zone having an average anterior surface module, designated SM ^ t, while the posterior outer zone or has an average posterior surface module, called SMPost, and the inner area has an average internal surface module, called SM ^ o, with at least one of
[0025]
25. Hydrated hydrogel silicone contact lens (100) according to claim 24, characterized by the fact that the anterior (101) and posterior (102) surfaces have a low concentration on the surface of negatively charged groups, as characterized by an attraction of a maximum of 200 positively charged particles in a positively charged particle adhesion test.
[0026]
26. Hydrated silicone hydrogel contact lens (100) according to claim 24, characterized in that the hydrated hydrogel silicone contact lens (100) comprises an inner layer (110) of the silicone hydrogel material, a layer of anterior external hydrogel (120) and a posterior external hydrogel layer (120), the anterior and posterior external hydrogel layers (120) being substantially uniform in thickness and merging at the peripheral edge (103) of the contact lens to completely surround the inner layer (110) of the silicone hydrogel material, where the outer anterior, outer posterior and inner zones in the cross sectional surface module profile represent the outer outer hydrogel (120), outer outer (120) and internal (110), respectively, in which the hydrated hydrogel silicone contact lens (100) has a water content of 10% to 70% by weight, in which the external hydrogel layers anterior and posterior (120) have a thickness from 0.1 μm to 20 μm, in which the external anterior and posterior hydrogel layers (120) present, independently of each other, a water expansion rate of at least 100 % if the water content, called WCLente, of the hydrated hydrogel silicone contact lens (100) is 45% or less or a water expansion rate of at least
[0027]
27. Hydrated hydrogel silicone contact lens (100) according to claim 26, characterized by the fact that the outer anterior and posterior hydrogel layers (120) exhibit, independently of each other, a rate of water expansion of at least 150% if WCLente <55%.
[0028]
28. Hydrated silicone hydrogel contact lens (100), according to claim 26, characterized by the fact that the outer anterior and posterior hydrogel layers (120) exhibit, independently of each other, a rate of water expansion of at least 200% if WCLente <60%.
[0029]
29. Hydrated silicone hydrogel contact lens (100) according to claim 26, characterized by the fact that the outer anterior and posterior hydrogel layers (120) exhibit, independently of each other, a rate of water expansion of at least 250% if WCLente <65%.
[0030]
30. Hydrated silicone hydrogel contact lens (100), according to claim 26, characterized by the fact that the outer anterior and posterior hydrogel layers (120) have, independently of each other, a proportion of water expansion of at least 300%.
[0031]
31. Hydrated hydrogel silicone contact lens (100), according to claim 26, characterized by the fact that the outer anterior and posterior hydrogel layers (120) have a thickness from 1 μm to 10 μm.
[0032]
32. Hydrated silicone hydrogel contact lens (100) according to claim 26, characterized by the fact that the silicone hydrogel contact lens also includes, in its layered structural configuration, two transition layers (115) of polymeric material (s), where each of the two transition layers (115) is located between the inner layer (110) and one of the front and back outer layers (120) of hydrogel and have a substantially uniform thickness, where the thickness of each transition layer is at least 0.05 μm.
[0033]
33. Hydrated hydrogel silicone contact lens (100), according to claim 24, characterized by the fact that it presents a high resistance to digital friction, as characterized by not having lines of superficial cracks visible under a dark field after the lens contact pad be rubbed between your fingers.
[0034]
34. Hydrated hydrogel silicone contact lens (100) according to claim 24, characterized by the fact that it has good surface lubricity, as defined by having a critical friction coefficient of 0.046 or less.
[0035]
35. Hydrated hydrogel silicone contact lens (100), according to claim 24, characterized by the fact that it has a surface hydrophilicity as defined by having a break time in water of at least 10 seconds; a surface wetting capacity as defined by having an average water contact angle of 80 degrees or less; or combinations thereof.
[0036]
36. Hydrated hydrogel silicone contact lens (100) according to claim 32, characterized in that the transition layers (115) comprise a carboxyl-containing polymer (COOH).
[0037]
37. Hydrated hydrogel silicone contact lens (100) according to claim 26, characterized by the fact that the anterior and posterior external hydrogel layers (120) are formed by applying and cross-linking a water-soluble, cross-linkable hydrophilic polymeric material over a precast silicone hydrogel contact lens, wherein the precast silicone hydrogel contact lens comprises amino and / or carboxyl groups at and / or near the surface of the contact lens or a base coat comprising amino groups and / or carboxyl; wherein the precast hydrogel silicone contact lens becomes the inner layer (110) after crosslinking.
[0038]
38. Hydrated hydrogel silicone contact lens (100) according to claim 37, characterized in that the water-soluble and cross-linkable hydrophilic polymeric material is a partially cross-linked polymeric material comprising a three-dimensional network and cross-linkable groups within the network.
[0039]
39. Hydrated hydrogel silicone contact lens (100) according to claim 37, characterized in that the water-soluble and crosslinkable hydrophilic polymeric material comprises (i) from 20% to 95% by weight of first polymer chains derived from a polyamine or polyamidoamine functionalized with epichlorohydrin; (ii) from 5% to 80% by weight of hydrophilic moieties or second polymer chains derived from at least one hydrophilicity-enhancing agent that has at least one reactive functional group selected from the group consisting of an amino group, group carboxyl, thiol group and combination thereof, in which the hydrophilic moieties or second polymer chains are covalently linked to the first polymer chains through one or more covalent bonds, each formed between a polyamine azetidinium group or polyamidoamine functionalized with epichlorohydrin and an amino, carboxyl or thiol group of the hydrophilicity-enhancing agent; and (iii) azetidinium groups that are part of the first polymer chains or pendant or terminal groups covalently linked to the first polymer chains.
[0040]
40. Hydrated hydrogel silicone contact lens (100) according to claim 39, characterized by the fact that the hydrophilic polymer as a hydrophilicity-enhancing agent is: PEG-NH2; PEG-SH; PEG-COOH; H2N-PEG-NH2; HOOC-PEG-COOH; HS-PEG-SH; H2N-PEG-COOH; HOOC-PEG-SH; H2N-PEG-SH; Multiple-arm PEG with one or more amino, carboxyl or thiol groups; PEG dendrimers with one or more amino, carboxyl or thiol groups; a diamino, dicarboxyl, monoamino or monocarboxyl-terminated homo- or copolymer of a non-reactive hydrophilic vinyl monomer; a copolymer which is a polymerization product of a composition comprising (1) 60% by weight or less by weight of at least one reactive vinyl monomer and (2) at least one non-reactive hydrophilic vinyl monomer; or combinations thereof, in which PEG is a segment of polyethylene glycol, in which the reactive vinyl monomer is selected from the group consisting of (meth) acrylate-C1-C6 alkyl, (meth) C1- acrylate C6 alkylamino C1-C6 alkyl, allylamine, vinylamine, amino-C1-C6 alkyl (meth) acrylamide, C1-C6 alkylamino-C1-C6 alkyl (meth) acrylamide, acrylic acid, C1-C4 alkyl acrylic acid, N, N acid -2-acrylamidoglycolic acid, beta-methyl-acrylic acid, alpha-phenyl acrylic acid, beta-acryloxy propionic acid, sorbic acid, angelic acid, cinnamic acid, 1- carboxy-4-phenylbutadiene-1,3-itaconic acid, citraconic acid , mesaconic acid, glutaconic acid, aconitic acid, maleic acid, fumaric acid, tricarboxyethylene and meso combinations, in which the non-reactive vinyl monomer is selected from the group consisting of acrylamide, methacrylamide, N, N-dimethylacrylamide, N, N-dimethylmethacrylamide, N-vinylpyrrolidone, N methacrylate, N-dimethylaminoethyl, N, N acrylate -dimethylaminoethyl, N, N-dimethylaminopropylmethacrylamide, N, N-dimethylaminopropylacrylamide, glycerol methacrylate, 3-acryloylamino-1-propanol, N-hydroxyethylacrylamide, N- [tris (hydroxymethyl) methyl-3-methyl] -acrylamide -2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2 -pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, (meth) 2-hydroxyethyl acrylate, (meth) hydroxypropyl acrylate, a vinyl monomer containing phosphorylcholine, (meth) C1-C4-alkoxy polyethylene glycol acrylate which has a weighted average molecular weight of up to 1500 Daltons, N-vinyl formamide, N-vinyl acetamide, N-vinyl isopropylamide, N-vinyl-N-methyl acetamide, allyl alcohol, vinyl alcohol (hydrolyzed form of vinyl acetate in the copolymer ) and combinations of the same-N-methyl acetamide, allyl alcohol, vinyl alcohol (hydrolyzed form of vinyl acetate in the copolymer) and their combinations.
[0041]
41. Hydrated silicone hydrogel contact lens (100) according to claim 26, characterized in that the outer front and rear hydrogel layers (120) comprise crosslinked bonds derived from azetidinium groups in a thermally induced coupling reaction .
[0042]
42. Hydrated silicone hydrogel contact lens (100) according to claim 26, characterized in that the silicone hydrogel material is obtained from a silicone hydrogel lens formulation comprising at least one component selected from from the group consisting of a vinyl monomer containing silicone, a vinyl macromer containing silicone, a prepolymer containing silicone, a hydrophilic vinyl monomer, a hydrophobic vinyl monomer, a crosslinking agent, a free radical initiator, a macromer / hydrophilic vinyl prepolymer and combinations thereof.
[0043]
43. Hydrated silicone hydrogel contact lens (100) according to claim 42, characterized in that the silicone hydrogel lens formulation comprises: (1) a hydrophilic vinyl monomer selected from the group consisting of N , N-dimethylacrylamide, N, N-dimethylmethacrylamide, N-vinylpyrrolidone, N-vinyl-N-methyl-acetamide, 1-methyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, methacrylate hydroxyethyl, hydroxyethyl acrylate and meso combinations; and (2) a vinyl monomer containing silicone, a vinyl monomer or macromer containing polysiloxane and / or a prepolymer containing silicone.
[0044]
44. Hydrated silicone hydrogel contact lens (100), characterized by the fact that it comprises: a silicone hydrogel material as a volumetric material, an opposite front surface (101) and a rear surface (102); and the contact lens has an oxygen transmissibility of at least 40 barrers / mm and good surface lubricity, as defined by having a critical friction coefficient, designated as CCOF, of 0.046 or less, where the anterior surfaces ( 101) and later (102) have a low concentration on the surface of negatively charged groups, such as carboxylic acid groups, as characterized by an attraction of at most 200 positively charged particles in a positively charged particle adhesion test.
[0045]
45. Hydrated hydrogel silicone contact lens (100) according to claim 44, characterized in that it comprises an inner layer (110) of the hydrogel silicone material, an outer outer layer (120) of hydrogel and a layer rear outer (120) of hydrogel, the outer outer and rear outer layers (120) of hydrogel having a substantially uniform thickness and fusing at the peripheral edge (103) of the contact lens to completely envelop the inner layer (110) of the hydrogel silicone material, with the outer front, outer back and inner zones in the cross sectional surface module profile representing the outer outer hydrogel (120), outer outer hydrogel (120) and inner (110) layers, the hydrated hydrogel silicone contact lens (100) has a water content (WCLente) from 10% to 70% by weight, the outer and front hydrogel layers (120) being approx. have a thickness from 0.1 μm to 20 μm, in which the anterior and posterior external hydrogel layers (120) show, at least 100%, an expansion ratio in water of at least 100% if WCLente is 45% or less, or a water expansion ratio of at least
[0046]
46. Hydrated hydrogel silicone contact lens (100) according to claim 45, characterized by the fact that the front and rear outer hydrogel layers (120) have, independently of each other, a water expansion ratio of at least 150% if WCLente <55%.
[0047]
47. Hydrated hydrogel silicone contact lens (100) according to claim 45, characterized by the fact that the front and rear outer hydrogel layers (120) have, independently of each other, a proportion of water expansion of at least 200% if WCLente <60%.
[0048]
48. Hydrated hydrogel silicone contact lens (100) according to claim 45, characterized by the fact that the outer anterior and posterior hydrogel layers (120) have, independently of each other, a proportion of water expansion of at least 250% if WCLente <65%.
[0049]
49. Hydrated hydrogel silicone contact lens (100) according to claim 45, characterized by the fact that the outer anterior and posterior hydrogel layers (120) have, independently of each other, a proportion of water expansion of at least 300%.
[0050]
50. Hydrated silicone hydrogel contact lens, according to claim 45, characterized by the fact that the external anterior and posterior hydrogel layers (120) have, independently, a thickness from 0.25 μm to 15 μm.
[0051]
51. Hydrated hydrogel silicone contact lens (100) according to claim 45, characterized by the fact that the front and rear outer hydrogel layers (120) have a thickness from 0.5 μm to 12.5 μm.
[0052]
52. Hydrated hydrogel silicone contact lens (100) according to claim 45, characterized by the fact that the outer anterior and posterior hydrogel layers (120) have a thickness from 1 μm to 10 μm.
[0053]
53. Hydrated hydrogel silicone contact lens (100) according to claim 45, characterized by the fact that it also includes, in its layered structural configuration, two transition layers (115) of polymeric material (s) ), where each of the two transition layers (115) is located between the inner layer (110) and one of the outer (120) and back (120) outer layers of hydrogel and have a substantially uniform thickness, where the thickness of each transition layer (115) is at least 0.05 μm.
[0054]
54. Hydrated hydrogel silicone contact lens (100), according to claim 44, characterized by the fact that it presents a high resistance to digital friction, as characterized by not having lines of superficial cracks visible under a dark field after the lens contact pad be rubbed between your fingers.
[0055]
55. Hydrated hydrogel silicone contact lens (100) according to claim 44, characterized by the fact that it has good surface lubricity, as defined by having a critical friction coefficient, designated as CCOF, of 0.043 or less .
[0056]
56. Hydrated hydrogel silicone contact lens (100), according to claim 44, characterized by the fact that it has a surface hydrophilicity as defined by having a break time in water of at least 10 seconds; a surface wetting capacity as defined by having an average water contact angle of 80 degrees or less; or combinations thereof.
[0057]
57. Hydrated silicone hydrogel contact lens (100) according to claim 53, characterized in that the transition layers (115) comprise a carboxyl-containing polymer (COOH).
[0058]
58. Hydrated hydrogel silicone contact lens (100) according to claim 45, characterized by the fact that the anterior and posterior external hydrogel layers (120) are formed by applying and cross-linking a water-soluble, cross-linkable hydrophilic polymeric material over a precast silicone hydrogel contact lens, wherein the precast silicone hydrogel contact lens comprises amino and / or carboxyl groups at and / or near the surface of the contact lens or a base coat comprising amino groups and / or carboxyl; wherein the precast hydrogel silicone contact lens becomes the inner layer (110) after crosslinking.
[0059]
59. Hydrated hydrogel silicone contact lens (100) according to claim 58, characterized in that the water-soluble and cross-linkable hydrophilic polymeric material is a partially cross-linked polymeric material comprising a three-dimensional network and cross-linkable groups within the network.
[0060]
60. Hydrated hydrogel silicone contact lens (100) according to claim 58, characterized in that the water-soluble and cross-linkable hydrophilic polymeric material comprises (i) from 20% to 95% by weight of first polymer chains derived from a polyamine or polyamidoamine functionalized with epichlorohydrin; (ii) from 5% to 80% by weight of hydrophilic moieties or second polymer chains derived from at least one hydrophilicity-enhancing agent that has at least one reactive functional group selected from the group consisting of an amino group, group carboxyl, thiol group and combination thereof, in which the hydrophilic moieties or second polymer chains are covalently linked to the first polymer chains through one or more covalent bonds, each formed between a polyamine azetidinium group or polyamidoamine functionalized with epichlorohydrin and an amino, carboxyl or thiol group of the hydrophilicity-enhancing agent; and (iii) azetidinium groups that are part of the first polymer chains or pendant or terminal groups covalently linked to the first polymer chains.
[0061]
61. Hydrated hydrogel silicone contact lens (100) according to claim 60, characterized by the fact that the hydrophilic polymer as a hydrophilicity-enhancing agent is: PEG-NH2; PEG-SH; PEG-COOH; H2N-PEG-NH2; HOOC-PEG-COOH; HS-PEG-SH; H2N-PEG-COOH; HOOC-PEG-SH; H2N-PEG-SH; Multiple-arm PEG with one or more amino, carboxyl or thiol groups; PEG dendrimers with one or more amino, carboxyl or thiol groups; a diamino, dicarboxyl, monoamino or monocarboxyl-terminated homo- or copolymer of a non-reactive hydrophilic vinyl monomer; a copolymer which is a polymerization product of a composition comprising (1) 60% by weight or less by weight of at least one reactive vinyl monomer and (2) at least one non-reactive hydrophilic vinyl monomer; or combinations thereof, in which PEG is a segment of polyethylene glycol, in which the reactive vinyl monomer is selected from the group consisting of (meth) acrylate-C1-C6 alkyl, (meth) C1- acrylate C6 alkylamino C1-C6 alkyl, allylamine, vinylamine, amino-C1-C6 alkyl (meth) acrylamide, C1-C6 alkylamino-C1-C6 alkyl (meth) acrylamide, acrylic acid, C1-C4 alkyl acrylic acid, N, N acid -2-acrylamidoglycolic acid, beta-methyl-acrylic acid, alpha-phenyl acrylic acid, beta-acryloxy propionic acid, sorbic acid, angelic acid, cinnamic acid, 1- carboxy-4-phenylbutadiene-1,3-itaconic acid, citraconic acid , mesaconic acid, glutaconic acid, aconitic acid, maleic acid, fumaric acid, tricarboxyethylene and meso combinations, in which the non-reactive vinyl monomer is selected from the group consisting of acrylamide, methacrylamide, N, N-dimethylacrylamide, N, N-dimethylmethacrylamide, N-vinylpyrrolidone, N methacrylate, N-dimethylaminoethyl, N, N acrylate -dimethylaminoethyl, N, N-dimethylaminopropylmethacrylamide, N, N-dimethylaminopropylacrylamide, glycerol methacrylate, 3-acryloylamino-1-propanol, N-hydroxyethylacrylamide, N- [tris (hydroxymethyl) methyl-3-methyl] -acrylamide -2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2 -pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone, (meth) 2-hydroxyethyl acrylate, (meth) hydroxypropyl acrylate, a vinyl monomer containing phosphorylcholine, (meth) C1-C4-alkoxy polyethylene glycol acrylate which has a weighted average molecular weight of up to 1500 Daltons, N-vinyl formamide, N-vinyl acetamide, N-vinyl isopropylamide, N-vinyl-N-methyl acetamide, allyl alcohol, vinyl alcohol (hydrolyzed form of vinyl acetate in the copolymer ) and combinations thereof.
[0062]
62. Hydrated hydrogel silicone contact lens (100) according to claim 45, characterized in that the outer anterior and posterior hydrogel layers (120) comprise crosslinked bonds derived from azetidinium groups in a thermally induced coupling reaction .
[0063]
63. Hydrated silicone hydrogel contact lens (100) according to claim 45, characterized in that the silicone hydrogel material is obtained from a silicone hydrogel lens formulation comprising at least one component selected from from the group consisting of a vinyl monomer containing silicone, a vinyl macromer containing silicone, a prepolymer containing silicone, a hydrophilic vinyl monomer, a hydrophobic vinyl monomer, a crosslinking agent, a free radical initiator, a macromer / hydrophilic vinyl prepolymer and combinations thereof.
[0064]
64. Hydrated silicone hydrogel contact lens (100) according to claim 63, characterized in that the silicone hydrogel lens formulation comprises: (1) a hydrophilic vinyl monomer selected from the group consisting of N , N-dimethylacrylamide, N, N-dimethylmethacrylamide, N-vinylpyrrolidone, N-vinyl-N-methyl-acetamide, 1-methyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone, methacrylate hydroxyethyl, hydroxyethyl acrylate and meso combinations; and (2) a vinyl monomer containing silicone, a vinyl monomer or macromer containing polysiloxane and / or a prepolymer containing silicone.

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TW201938712A|2019-10-01|

---

KR101800059B1|2017-11-21|

---

BR122020017237B1|2021-02-02|

---

CN105334640A|2016-02-17|

---

JP2013190822A|2013-09-26|

---

CN103293707B|2014-12-31|

---

EP2705808A2|2014-03-12|

---

JP2020098354A|2020-06-25|

---

JP6326115B2|2018-05-16|

---

US20160097938A1|2016-04-07|

---

US10513628B2|2019-12-24|

---

KR102266815B1|2021-06-18|

---

BR122013012250A2|2019-10-01|

---

KR102009137B1|2019-08-08|

---

US20150099822A1|2015-04-09|

---

RU2013125115A|2014-12-10|

---

RU2571747C2|2015-12-20|

---

TW201610508A|2016-03-16|

---

CN103038699A|2013-04-10|

---

CN103038699B|2015-03-18|

---

MY154750A|2015-07-15|

---

CN103052364B|2015-12-02|

---

KR20210075210A|2021-06-22|

---

EP2598938A4|2018-01-24|

---

EP2461767B1|2013-05-08|

---

JP2016122203A|2016-07-07|

---

TWI708093B|2020-10-21|

---

CN104678462B|2019-11-05|

---

US20200339836A1|2020-10-29|

---

KR101413390B1|2014-06-27|

---

US9507173B2|2016-11-29|

---

TW201535009A|2015-09-16|

---

TWI567443B|2017-01-21|

---

EP2638879A3|2018-05-16|

---

TW201738625A|2017-11-01|

---

US20200017713A1|2020-01-16|

---

RU2739355C1|2020-12-23|

---

SG2014007348A|2014-07-30|

---

SG10201505892WA|2015-09-29|

---

US8939577B2|2015-01-27|

---

BR112013002150B1|2020-11-17|

---

EP2638878A2|2013-09-18|

---

JP2013533518A|2013-08-22|

---

KR101724984B1|2017-04-07|

---

JP2016118797A|2016-06-30|

---

CA2802337A1|2012-02-02|

---

JP5930221B2|2016-06-08|

---

JP2018139002A|2018-09-06|

---

SI2461767T1|2013-08-30|

---

RU2619715C1|2017-05-17|

---

JP5882322B2|2016-03-09|

---

JP2020008873A|2020-01-16|

---

KR20150118200A|2015-10-21|

---

AU2011282602B2|2014-06-26|

---

EP2705808A3|2018-01-24|

---

US9816009B2|2017-11-14|

---

BR112013002179A2|2019-08-06|

---

RU2754524C1|2021-09-02|

---

RU2540655C2|2015-02-10|

---

RU2644349C1|2018-02-09|

---

KR101819873B1|2018-01-17|

---

EP2461767A1|2012-06-13|

---

TWI599813B|2017-09-21|

---

PT2638878T|2019-12-05|

---

TWI519845B|2016-02-01|

---

US20180044549A1|2018-02-15|

---

MY174013A|2020-03-04|

---

KR20140017706A|2014-02-11|

---

US8480227B2|2013-07-09|

---

KR101958162B1|2019-03-13|

---

KR20180006487A|2018-01-17|

---

JP6664081B2|2020-03-13|

---

KR20170038193A|2017-04-06|

---

RU2675109C1|2018-12-17|

---

KR101889246B1|2018-08-16|

---

KR20190140108A|2019-12-18|

---

US20160091734A1|2016-03-31|

---

JP2013533517A|2013-08-22|

---

KR102104222B1|2020-04-24|

---

RU2691047C1|2019-06-07|

---

TWI707926B|2020-10-21|

---

SG187237A1|2013-03-28|

---

TW201335660A|2013-09-01|

---

NZ610544A|2014-08-29|

---

KR101795983B1|2017-11-08|

---

KR102139022B1|2020-07-29|

---

TWI507764B|2015-11-11|

---

KR20200091498A|2020-07-30|

---

JP6982640B2|2021-12-17|

---

HK1207689A1|2016-02-05|

---

WO2012016098A1|2012-02-02|

---

KR20190026973A|2019-03-13|

---

US9411171B2|2016-08-09|

---

US20170037276A1|2017-02-09|

---

WO2012016096A1|2012-02-02|

---

US9244200B2|2016-01-26|

---

MY156626A|2016-03-15|

---

RU2714143C1|2020-02-12|

---

US20120026457A1|2012-02-02|

---

US10131815B2|2018-11-20|

---

CN103293707A|2013-09-11|

---

US9239409B2|2016-01-19|

---

KR20200111273A|2020-09-28|

---

RS52882B|2014-02-28|

---

KR20190069619A|2019-06-19|

---

KR102057814B1|2019-12-19|

---

CA2802793A1|2012-02-02|

---

KR20180083954A|2018-07-23|

---

JP6295281B2|2018-03-14|

---

KR20180093097A|2018-08-20|

---

PL2461767T3|2013-09-30|

---

TW201207466A|2012-02-16|

---

CA2802793C|2014-10-21|

---

CN103052364A|2013-04-17|

---

MX2013001189A|2013-02-21|

---

US10308835B2|2019-06-04|

---

RU2015148819A|2017-05-19|

---

US20190055427A1|2019-02-21|

---

KR20130086607A|2013-08-02|

---

US10563090B2|2020-02-18|

---

JP6076199B2|2017-02-08|

---

JP2018106189A|2018-07-05|

---

KR20190095500A|2019-08-14|

---

PT2461767E|2013-08-26|

---

TWI524110B|2016-03-01|

---

TWI587032B|2017-06-11|

---

EP2638878B1|2019-10-23|

---

AU2011282604A1|2013-02-28|

---

TW201812394A|2018-04-01|

---

RU2728781C1|2020-07-31|

---

US10781340B2|2020-09-22|

引用文献:

---

公开号 | 申请日 | 公开日 | 申请人 | 专利标题

---

---

US2296891A|1940-11-09|1942-09-29|Celanese Corp|Cement|

---

US2926154A|1957-09-05|1960-02-23|Hercules Powder Co Ltd|Cationic thermosetting polyamide-epichlorohydrin resins and process of making same|

---

US3161935A|1959-04-28|1964-12-22|Carl W Chanlund|Tamping mechanism|

---

US3224986A|1962-04-18|1965-12-21|Hercules Powder Co Ltd|Cationic epichlorohydrin modified polyamide reacted with water-soluble polymers|

---

US3171502A|1962-07-26|1965-03-02|Jean K Kamphere|Expansible rotary drill bits|

---

NL128305C|1963-09-11|

---

SE306597B|1964-12-17|1968-12-02|Incentive Ab|

---

US3434984A|1966-04-25|1969-03-25|Owens Illinois Inc|Thermosetting cationic resin and method of making same|

---

US3598790A|1966-07-01|1971-08-10|Roehm & Haas Gmbh|Azlactone copolymers|

---

US3617344A|1966-08-05|1971-11-02|Us Health Education & Welfare|Nonthrombogenic plastic surfaces and preparation thereof|

---

GB1218394A|1967-03-08|1971-01-06|Toho Kagaku Kogyo Kabushiki Ka|Process for producing water-soluble thermosetting polymer|

---

US3488327A|1967-06-30|1970-01-06|Roehm & Haas Gmbh|Preparation of coating materials|

---

DE1745348A1|1967-12-01|1971-09-09|Roehm Gmbh|Copolymers containing azlactone groups|

---

US3566874A|1968-08-13|1971-03-02|Nat Patent Dev Corp|Catheter|

---

US3639141A|1968-09-16|1972-02-01|Cordis Corp|Heparinization of plastic|

---

JPS4813341B1|1969-06-13|1973-04-26|

---

US3663288A|1969-09-04|1972-05-16|American Cyanamid Co|Physiologically acceptible elastomeric article|

---

US3772076A|1970-01-26|1973-11-13|Hercules Inc|Reaction products of epihalohydrin and polymers of diallylamine and their use in paper|

---

US3616935A|1970-02-05|1971-11-02|Dow Chemical Co|Preparation of antithrombogenic surfaces|

---

US3925178A|1970-04-17|1975-12-09|Hymie D Gesser|Contact lenses|

---

US3700623A|1970-04-22|1972-10-24|Hercules Inc|Reaction products of epihalohydrin and polymers of diallylamine and their use in paper|

---

US3695921A|1970-09-09|1972-10-03|Nat Patent Dev Corp|Method of coating a catheter|

---

US3844989A|1971-12-23|1974-10-29|Toray Industries|Shampooer with rotary foam generating means anti-thrombogenic polymer compositions with internally bound heparin|

---

US3892696A|1972-05-12|1975-07-01|Grace W R & Co|Polyureas and preparation thereof|

---

US3975350A|1972-08-02|1976-08-17|Princeton Polymer Laboratories, Incorporated|Hydrophilic or hydrogel carrier systems such as coatings, body implants and other articles|

---

US3813695A|1973-02-21|1974-06-04|D Podell|Surgical glove|

---

US3900672A|1973-04-04|1975-08-19|Hoya Lens Co Ltd|Process for coating an optical material and the resulting product|

---

US3861396A|1973-08-08|1975-01-21|Hydro Med Sciences Inc|Drainage tube|

---

US4099859A|1974-12-02|1978-07-11|High Voltage Engineering Corporation|Contact lens having a smooth surface layer of a hydrophilic polymer|

---

SE400173B|1975-03-20|1978-03-20|Aminkemi Ab|PROCEDURE FOR STABILIZING A HEPARINIZED SURFACE CONTAINING FOR BLOOD CONTACT RELEASE HEPARIN|

---

FR2306243B1|1975-04-03|1978-11-03|Asahi Dow Ltd|

---

DE2614662C2|1975-04-07|1988-08-25|The Dow Chemical Co., Midland, Mich., Us|

---

US4154898A|1976-09-27|1979-05-15|The Dow Chemical Company|Absorbent articles and methods for their preparation|

---

US4143949A|1976-10-28|1979-03-13|Bausch & Lomb Incorporated|Process for putting a hydrophilic coating on a hydrophobic contact lens|

---

US4343927A|1976-11-08|1982-08-10|Chang Sing Hsiung|Hydrophilic, soft and oxygen permeable copolymer compositions|

---

US4182822A|1976-11-08|1980-01-08|Chang Sing Hsiung|Hydrophilic, soft and oxygen permeable copolymer composition|

---

JPS5650581B2|1977-07-01|1981-11-30|

---

US4136250A|1977-07-20|1979-01-23|Ciba-Geigy Corporation|Polysiloxane hydrogels|

---

US4189546A|1977-07-25|1980-02-19|Bausch & Lomb Incorporated|Polysiloxane shaped article for use in biomedical applications|

---

US4153641A|1977-07-25|1979-05-08|Bausch & Lomb Incorporated|Polysiloxane composition and contact lens|

---

DE2839249C2|1977-09-12|1991-09-12|Toray Industries, Inc., Tokio/Tokyo, Jp|

---

US4168112A|1978-01-05|1979-09-18|Polymer Technology Corporation|Contact lens with a hydrophilic, polyelectrolyte complex coating and method for forming same|

---

US4298715A|1978-03-01|1981-11-03|Monsanto Company|Polyamine/epihalohydrin reaction products|

---

US4217038A|1978-06-05|1980-08-12|Bausch & Lomb Incorporated|Glass coated polysiloxane contact lens|

---

US4191596B1|1978-09-06|1990-06-26|Amchem Prod|

---

US4280970A|1979-01-19|1981-07-28|Puropore Inc.|Polyoxyethylene grafted membrane materials with grafting links derived from a diisocyanate|

---

US4261875A|1979-01-31|1981-04-14|American Optical Corporation|Contact lenses containing hydrophilic silicone polymers|

---

US4298639A|1979-03-19|1981-11-03|Monsanto Company|Wet strength polymers|

---

JPS5836604B2|1979-04-18|1983-08-10|Hitachi Seisakusho Kk|

---

US4263188A|1979-05-23|1981-04-21|Verbatim Corporation|Aqueous coating composition and method|

---

US4276402A|1979-09-13|1981-06-30|Bausch & Lomb Incorporated|Polysiloxane/acrylic acid/polcyclic esters of methacrylic acid polymer contact lens|

---

US4254248A|1979-09-13|1981-03-03|Bausch & Lomb Incorporated|Contact lens made from polymers of polysiloxane and polycyclic esters of acrylic acid or methacrylic acid|

---

US4312575A|1979-09-18|1982-01-26|Peyman Gholam A|Soft corneal contact lens with tightly cross-linked polymer coating and method of making same|

---

US4260725A|1979-12-10|1981-04-07|Bausch & Lomb Incorporated|Hydrophilic contact lens made from polysiloxanes which are thermally bonded to polymerizable groups and which contain hydrophilic sidechains|

---

US4259467A|1979-12-10|1981-03-31|Bausch & Lomb Incorporated|Hydrophilic contact lens made from polysiloxanes containing hydrophilic sidechains|

---

US4293642A|1980-05-13|1981-10-06|Gaf Corporation|In photographic emulsion adhesion to a polyester film base|

---

JPH0260696B2|1980-10-28|1990-12-18|Mitsui Petrochemical Ind|

---

US4462665A|1981-01-29|1984-07-31|The Kendall Company|Composite hydrogel-forming lens and method of making same|

---

US4327203A|1981-02-26|1982-04-27|Bausch & Lomb Incorporated|Polysiloxane with cycloalkyl modifier composition and biomedical devices|

---

US4355147A|1981-02-26|1982-10-19|Bausch & Lomb Incorporated|Polysiloxane with polycyclic modifier composition and biomedical devices|

---

US4341889A|1981-02-26|1982-07-27|Bausch & Lomb Incorporated|Polysiloxane composition and biomedical devices|

---

US4495313A|1981-04-30|1985-01-22|Mia Lens Production A/S|Preparation of hydrogel for soft contact lens with water displaceable boric acid ester|

---

US4373009A|1981-05-18|1983-02-08|International Silicone Corporation|Method of forming a hydrophilic coating on a substrate|

---

US4379893A|1981-08-26|1983-04-12|Diamond Shamrock Corporation|Surface-treated soft contact lenses|

---

DE3135830A1|1981-09-10|1983-03-24|Basf Ag, 6700 Ludwigshafen|METHOD FOR THE PRODUCTION OF WATER-SOLUBLE, NITROGEN-CONDENSING PRODUCTS AND THE USE THEREOF IN PAPER PRODUCTION|

---

US4444711A|1981-12-21|1984-04-24|Husky Injection Molding Systems Ltd.|Method of operating a two-shot injection-molding machine|

---

US4416729A|1982-01-04|1983-11-22|The Dow Chemical Company|Ammonium polyamidoamines|

---

US4661575A|1982-01-25|1987-04-28|Hercules Incorporated|Dicyclopentadiene polymer product|

---

SE8200751L|1982-02-09|1983-08-10|Olle Larm|PROCEDURE FOR COVALENT COUPLING FOR MANUFACTURE OF CONJUGATE AND REQUIRED PRODUCTS|

---

SE456347B|1982-02-09|1988-09-26|Ird Biomaterial Ab|SURFACE MODIFIED SOLID SUBSTRATE AND PROCEDURES FOR PRODUCING THEREOF|

---

US4487808A|1982-04-22|1984-12-11|Astra Meditec Aktiebolag|Medical article having a hydrophilic coating|

---

US4499154A|1982-09-03|1985-02-12|Howard L. Podell|Dipped rubber article|

---

US4460534A|1982-09-07|1984-07-17|International Business Machines Corporation|Two-shot injection molding|

---

US4973493A|1982-09-29|1990-11-27|Bio-Metric Systems, Inc.|Method of improving the biocompatibility of solid surfaces|

---

US5217492A|1982-09-29|1993-06-08|Bio-Metric Systems, Inc.|Biomolecule attachment to hydrophobic surfaces|

---

US5002582A|1982-09-29|1991-03-26|Bio-Metric Systems, Inc.|Preparation of polymeric surfaces via covalently attaching polymers|

---

US4486577A|1982-10-12|1984-12-04|Ciba-Geigy Corporation|Strong, silicone containing polymers with high oxygen permeability|

---

US4479312A|1983-04-11|1984-10-30|Valley Engineering, Inc.|Foldable snow compactor with side wings pivotable behind central blade|

---

US4543398A|1983-04-28|1985-09-24|Minnesota Mining And Manufacturing Company|Ophthalmic devices fabricated from urethane acrylates of polysiloxane alcohols|

---

US4527293A|1983-05-18|1985-07-09|University Of Miami|Hydrogel surface of urological prosthesis|

---

US4689374A|1983-06-09|1987-08-25|W. R. Grace & Co.|Water soluble polyamidoaminepolyamine having weight average molecular weight of at least 5×105|

---

US4521564A|1984-02-10|1985-06-04|Warner-Lambert Company|Covalent bonded antithrombogenic polyurethane material|

---

US4695608A|1984-03-29|1987-09-22|Minnesota Mining And Manufacturing Company|Continuous process for making polymers having pendant azlactone or macromolecular moieties|

---

EP0166998B1|1984-06-04|1991-05-08|TERUMO KABUSHIKI KAISHA trading as TERUMO CORPORATION|Medical instrument and method for making|

---

US4959074A|1984-08-23|1990-09-25|Gergory Halpern|Method of hydrophilic coating of plastics|

---

US4605712A|1984-09-24|1986-08-12|Ciba-Geigy Corporation|Unsaturated polysiloxanes and polymers thereof|

---

AT380897B|1984-12-10|1986-07-25|Koller Anton|MIXTURE FOR THE CARE AND CLEANING OF CONTACT LENSES|

---

US4833218A|1984-12-18|1989-05-23|Dow Corning Corporation|Hydrophilic silicone-organic copolymer elastomers containing bioactine agent|

---

US4546123A|1984-12-28|1985-10-08|Alcon Laboratories, Inc.|Polymer hydrogels adapted for use as soft contact lenses, and method of preparing same|

---

JPH0674369B2|1985-03-14|1994-09-21|大日本インキ化学工業株式会社|Method for producing aqueous dispersion of vinyl copolymer resin|

---

DE3517615C2|1985-05-15|1987-04-09|Titmus Eurocon Kontaktlinsen Gmbh, 8750 Aschaffenburg, De|

---

US4684538A|1986-02-21|1987-08-04|Loctite Corporation|Polysiloxane urethane compounds and adhesive compositions, and method of making and using the same|

---

US4786556A|1986-03-24|1988-11-22|Becton, Dickinson And Company|Polymeric articles having enhanced antithrombogenic activity|

---

US4720512A|1986-03-24|1988-01-19|Becton, Dickinson And Company|Polymeric articles having enhanced antithrombogenic activity|

---

DE3708308A1|1986-04-10|1987-10-22|Bayer Ag|CONTACT OPTICAL ITEMS|

---

US4791175A|1986-08-04|1988-12-13|Ciba-Geigy Corporation|Particulate hydroperoxidized poly-n-vinyl lactam, its preparation and use thereof|

---

DE3778446D1|1986-08-18|1992-05-27|Mueller Lierheim Wolfgang G K|CONTACT LENS.|

---

US4979959A|1986-10-17|1990-12-25|Bio-Metric Systems, Inc.|Biocompatible coating for solid surfaces|

---

US5263992A|1986-10-17|1993-11-23|Bio-Metric Systems, Inc.|Biocompatible device with covalently bonded biocompatible agent|

---

US4734475A|1986-12-15|1988-03-29|Ciba-Geigy Corporation|Wettable surface modified contact lens fabricated from an oxirane containing hydrophobic polymer|

---

US5712327A|1987-01-07|1998-01-27|Chang; Sing-Hsiung|Soft gas permeable contact lens having improved clinical performance|

---

US5290548A|1987-04-10|1994-03-01|University Of Florida|Surface modified ocular implants, surgical instruments, devices, prostheses, contact lenses and the like|

---

US5108776A|1987-04-10|1992-04-28|University Of Florida|Ocular implants and methods for their manufacture|

---

JP2551580B2|1987-04-30|1996-11-06|ホ−ヤ株式会社|How to make contact lenses hydrophilic|

---

US4837289A|1987-04-30|1989-06-06|Ciba-Geigy Corporation|UV- and heat curable terminal polyvinyl functional macromers and polymers thereof|

---

US5059659A|1987-05-29|1991-10-22|Harry P. Gregor|Surface treatments to impart hydrophilicity|

---

US4978713A|1987-12-16|1990-12-18|Ciba-Geigy Corporation|Polyvinyl alcohol derivatives containing pendant vinylic monomer reaction product units bound through ether groups and hydrogel contact lenses made therefrom|

---

US4943460A|1988-02-19|1990-07-24|Snyder Laboratories, Inc.|Process for coating polymer surfaces and coated products produced using such process|

---

US5070170A|1988-02-26|1991-12-03|Ciba-Geigy Corporation|Wettable, rigid gas permeable, substantially non-swellable contact lens containing block copolymer polysiloxane-polyoxyalkylene backbone units, and use thereof|

---

AU629203B2|1988-03-23|1992-10-01|E.I. Du Pont De Nemours And Company|Low coefficient of friction surface|

---

JP2561309B2|1988-03-28|1996-12-04|テルモ株式会社|Medical material and manufacturing method thereof|

---

EP0335308B1|1988-03-31|1993-12-08|W.R. Grace & Co.-Conn.|Protein non-adsorptive polyurea-urethane polymer coated devices|

---

US5061738A|1988-04-18|1991-10-29|Becton, Dickinson And Company|Blood compatible, lubricious article and composition and method therefor|

---

US4954587A|1988-07-05|1990-09-04|Ciba-Geigy Corporation|Dimethylacrylamide-copolymer hydrogels with high oxygen permeability|

---

US5019393A|1988-08-03|1991-05-28|New England Deaconess Hospital Corporation|Biocompatible substance with thromboresistance|

---

KR900701332A|1988-08-09|1990-12-01|마에다 카쓰노스케|Active Medical Materials and Manufacturing Method Thereof|

---

JPH0651795B2|1988-09-16|1994-07-06|信越化学工業株式会社|Methacryl functional dimethyl polysiloxane|

---

US5053048A|1988-09-22|1991-10-01|Cordis Corporation|Thromboresistant coating|

---

US5270046A|1988-09-27|1993-12-14|Ube Industries, Ltd.|Heparin bound anti-thrombotic material|

---

US4983702A|1988-09-28|1991-01-08|Ciba-Geigy Corporation|Crosslinked siloxane-urethane polymer contact lens|

---

EP0362137A3|1988-09-28|1991-09-04|Ciba-Geigy Ag|Molded polymers with hydrophilic surfaces, and process for making them|

---

US5510418A|1988-11-21|1996-04-23|Collagen Corporation|Glycosaminoglycan-synthetic polymer conjugates|

---

US5039459A|1988-11-25|1991-08-13|Johnson & Johnson Vision Products, Inc.|Method of forming shaped hydrogel articles including contact lenses|

---

AT117699T|1988-12-19|1995-02-15|Ciba Geigy Ag|HYDROGELS BASED ON FLUORINE AND SACCHARID MONOMERS.|

---

US5214452A|1988-12-19|1993-05-25|Ciba-Geigy Corporation|Hydrogels based on fluorine-containing and saccharide monomers|

---

US4973359A|1989-01-04|1990-11-27|Nippon Paint Co., Ltd.|Surface treatment chemical and bath for forming hydrophilic coatings and method of surface-treating aluminum members|

---

US4978481A|1989-01-13|1990-12-18|Ciba-Geigy Corporation|Process for the encapsulation of preformed substrates by graft copolymerization|

---

US4968532A|1989-01-13|1990-11-06|Ciba-Geigy Corporation|Process for graft copolymerization on surfaces of preformed substrates to modify surface properties|

---

US4954586A|1989-01-17|1990-09-04|Menicon Co., Ltd|Soft ocular lens material|

---

US5091205A|1989-01-17|1992-02-25|Union Carbide Chemicals & Plastics Technology Corporation|Hydrophilic lubricious coatings|

---

US5262484A|1989-04-10|1993-11-16|Minnesota Mining And Manufacturing Company|Azlactone graft copolymers|

---

DK0393532T3|1989-04-14|1996-08-19|Jessen Wesley Corp|Method of dyeing contact lenses|

---

US5080924A|1989-04-24|1992-01-14|Drexel University|Method of making biocompatible, surface modified materials|

---

US4990357A|1989-05-04|1991-02-05|Becton, Dickinson And Company|Elastomeric segmented hydrophilic polyetherurethane based lubricious coatings|

---

US5034461A|1989-06-07|1991-07-23|Bausch & Lomb Incorporated|Novel prepolymers useful in biomedical devices|

---

US5272012A|1989-06-23|1993-12-21|C. R. Bard, Inc.|Medical apparatus having protective, lubricious coating|

---

WO1991004283A1|1989-09-14|1991-04-04|Chang Sing Hsiung|Soft gas permeable contact lens having improved clinical performance|

---

JPH03102313A|1989-09-18|1991-04-26|Seiko Epson Corp|Contact lens|

---

US5049403A|1989-10-12|1991-09-17|Horsk Hydro A.S.|Process for the preparation of surface modified solid substrates|

---

US5010141A|1989-10-25|1991-04-23|Ciba-Geigy Corporation|Reactive silicone and/or fluorine containing hydrophilic prepolymers and polymers thereof|

---

US5079319A|1989-10-25|1992-01-07|Ciba-Geigy Corporation|Reactive silicone and/or fluorine containing hydrophilic prepolymers and polymers thereof|

---

US5135516A|1989-12-15|1992-08-04|Boston Scientific Corporation|Lubricious antithrombogenic catheters, guidewires and coatings|

---

GB9004881D0|1990-03-05|1990-05-02|Biocompatibles Ltd|Method of improving the ocular of synthetic polymers haemo and biocompatibility|

---

GB9009097D0|1990-04-23|1990-06-20|Lrc Products|Method of making dipped rubber articles|

---

DE4026978A1|1990-08-25|1992-02-27|Bayer Ag|Coated substrates for electro=optical applications, etc.|

---

JPH0783761B2|1990-10-04|1995-09-13|テルモ株式会社|Medical equipment|

---

US5160790A|1990-11-01|1992-11-03|C. R. Bard, Inc.|Lubricious hydrogel coatings|

---

US5132108A|1990-11-08|1992-07-21|Cordis Corporation|Radiofrequency plasma treated polymeric surfaces having immobilized anti-thrombogenic agents|

---

US5135297A|1990-11-27|1992-08-04|Bausch & Lomb Incorporated|Surface coating of polymer objects|

---

WO1992009639A2|1990-11-27|1992-06-11|Bausch & Lomb Incorporated|Surface-active macromonomers|

---

US5407715A|1990-11-28|1995-04-18|Tactyl Technologies, Inc.|Elastomeric triblock copolymer compositions and articles made therewith|

---

US5112900A|1990-11-28|1992-05-12|Tactyl Technologies, Inc.|Elastomeric triblock copolymer compositions and articles made therewith|

---

AU649287B2|1990-12-19|1994-05-19|Novartis Ag|Process for rendering contact lenses hydrophilic|

---

US5270415A|1990-12-21|1993-12-14|Allergan Inc.|Balanced charge polymer and hydrophilic contact lens manufactured therefrom|

---

JPH04316013A|1991-04-16|1992-11-06|Seiko Epson Corp|Manufacture of contact lens|

---

US5739236A|1991-04-24|1998-04-14|Biocompatibles Limited|Biocompatible zwitterion polymers|

---

US6225431B1|1991-07-05|2001-05-01|Biocompatibles Limited|Biocompatibilizing process|

---

US6284854B1|1991-07-05|2001-09-04|Biccompatibles Limited|Polymeric surface coatings|

---

US5397848A|1991-04-25|1995-03-14|Allergan, Inc.|Enhancing the hydrophilicity of silicone polymers|

---

US5443907A|1991-06-18|1995-08-22|Scimed Life Systems, Inc.|Coating for medical insertion guides|

---

GB9113875D0|1991-06-27|1991-08-14|Biointeractions Ltd|Polymer coatings|

---

US6087462A|1995-06-07|2000-07-11|Biocompatibles Limited|Polymeric surface coatings|

---

US6743878B2|1991-07-05|2004-06-01|Biocompatibles Uk Limited|Polymeric surface coatings|

---

US5705583A|1991-07-05|1998-01-06|Biocompatibles Limited|Polymeric surface coatings|

---

AU666485B2|1991-07-05|1996-02-15|Biocompatibles Uk Limited|Polymeric surface coatings|

---

US6090901A|1991-07-05|2000-07-18|Biocompatibles Limited|Polymeric surface coatings|

---

US5210111A|1991-08-22|1993-05-11|Ciba-Geigy Corporation|Crosslinked hydrogels derived from hydrophilic polymer backbones|

---

BR9206601A|1991-09-12|1995-10-17|Bausch & Lob Inc|Method for making a wettable hydrogel composition containing silicone, hydrogel composition containing silicone, biomedical device and contact lens|

---

WO1993005825A1|1991-09-20|1993-04-01|Baxter International Inc.|Processes for reducing the thrombogenicity of biomaterials|

---

EP0537972B1|1991-10-14|1996-07-10|Nof Corporation|Treating solution for contact lenses|

---

JP3093375B2|1991-11-01|2000-10-03|株式会社東海メディカルプロダクツ|Immobilization method of antithrombotic substance|

---

US5352714A|1991-11-05|1994-10-04|Bausch & Lomb Incorporated|Wettable silicone hydrogel compositions and methods for their manufacture|

---

JP3354571B2|1991-11-05|2002-12-09|ボシュ・アンド・ロム・インコーポレイテッド|Wettable silicone hydrogel composition and method for producing the same|

---

GB9124353D0|1991-11-15|1992-01-08|Albright & Wilson|Immobilisation of metal contaminants from a liquid to a solid metal|

---

US6314199B1|1991-12-18|2001-11-06|Novartis Ag|Process and apparatus for examining optical components, especially optical components for the eye and device for illuminating clear-transparent|

---

JPH06506019A|1991-12-18|1994-07-07|

---

IL100443A|1991-12-20|1995-03-30|Dotan Gideon|Inspection system for detecting surface flaws|

---

EP0585436B1|1992-02-13|2000-05-03|SurModics, Inc.|Immobilization of chemical species in crosslinked matrices|

---

US5470944A|1992-02-13|1995-11-28|Arch Development Corporation|Production of high molecular weight polylactic acid|

---

JPH05285164A|1992-04-03|1993-11-02|Unitika Ltd|Antithrombotic intraocular lens|

---

US5358995A|1992-05-15|1994-10-25|Bausch & Lomb Incorporated|Surface wettable silicone hydrogels|

---

US5805264A|1992-06-09|1998-09-08|Ciba Vision Corporation|Process for graft polymerization on surfaces of preformed substates to modify surface properties|

---

JPH0649251A|1992-06-09|1994-02-22|Ciba Geigy Ag|Method of grafting onto surface of premolded substrate to modify surface property|

---

DK172393B1|1992-06-10|1998-05-18|Maersk Medical As|Process for producing an article having friction-reducing surface coating, coating material for use in the manufacture of such article, and using an osmolality-increasing compound in slurry or emulsified form in the coating material|

---

US5292514A|1992-06-24|1994-03-08|Minnesota Mining And Manufacturing Company|Azlactone-functional substrates, corneal prostheses, and manufacture and use thereof|

---

JP3195662B2|1992-08-24|2001-08-06|株式会社メニコン|Ophthalmic lens materials|

---

JP2774233B2|1992-08-26|1998-07-09|株式会社メニコン|Ophthalmic lens materials|

---

US5310571A|1992-09-01|1994-05-10|Allergan, Inc.|Chemical treatment to improve oxygen permeability through and protein deposition on hydrophilic and rigid gas permeable contact lenses|

---

IL106922A|1992-09-14|1998-08-16|Novartis Ag|Composite materials with one or more wettable surfaces and process for their preparation|

---

KR0122741B1|1992-09-23|1997-11-17|배순훈|Memory having parallel architecture|

---

US5480950A|1992-09-28|1996-01-02|Kabi Pharmacia Ophthalmics, Inc.|High refractive index hydrogels and uses thereof|

---

US5316704B1|1992-09-28|1996-05-21|Kabi Pharmacia Ophthalmics Inc|Process for fabricating full sized expansible hydrogel intraocular lenses|

---

US5409731A|1992-10-08|1995-04-25|Tomei Sangyo Kabushiki Kaisha|Method for imparting a hydrophilic nature to a contact lens|

---

AU5733594A|1992-11-30|1994-06-22|Bulk Chemicals, Inc.|A method and composition for treating metal surfaces|

---

IL107601A|1992-12-21|1997-09-30|Johnson & Johnson Vision Prod|Illumination and imaging subsystems for a lens inspection system|

---

IL107605A|1992-12-21|1998-01-04|Johnson & Johnson Vision Prod|Lens inspection system|

---

US5995213A|1995-01-17|1999-11-30|Johnson & Johnson Vision Products, Inc.|Lens inspection system|

---

NZ250042A|1992-12-21|1997-01-29|Johnson & Johnson Vision Prod|Robotic inspection of ophthalmic lenses|

---

IL107602D0|1992-12-21|1994-02-27|Johnson & Johnson Vision Prod|Method of inspecting ophthalmic lenses|

---

IL107603A|1992-12-21|1997-01-10|Johnson & Johnson Vision Prod|Ophthalmic lens inspection method and apparatus|

---

GB9226791D0|1992-12-23|1993-02-17|Biocompatibles Ltd|New materials|

---

US5350800A|1993-01-19|1994-09-27|Medtronic, Inc.|Method for improving the biocompatibility of solid surfaces|

---

US5308641A|1993-01-19|1994-05-03|Medtronic, Inc.|Biocompatibility of solid surfaces|

---

DE69403445T2|1993-01-29|1997-12-18|Minnesota Mining & Mfg|AZLACTON MEMBRANE WITH THERMALLY INDUCED PHASE SEPARATION|

---

CA2114697C|1993-02-08|2006-06-13|Kenichi Shimura|Medical tool having lubricious surface in a wetted state and method for production thereof|

---

JPH08507715A|1993-03-18|1996-08-20|シーダーズサイナイメディカルセンター|Drug-inducing and releasable polymeric coatings for bioartificial components|

---

US5531715A|1993-05-12|1996-07-02|Target Therapeutics, Inc.|Lubricious catheters|

---

TW328535B|1993-07-02|1998-03-21|Novartis Ag|Functional photoinitiators and their manufacture|

---

US5578675A|1993-07-21|1996-11-26|Basf Corporation|Non-isocyanate basecoat/clearcoat coating compositions which may be ambient cured|

---

TW325744U|1993-07-21|1998-01-21|Ciba Geigy Ag|Two-sided contact lens mold|

---

AU7473894A|1993-07-29|1995-02-28|Wesley-Jessen Corporation|Inspection system for optical components|

---

TW272976B|1993-08-06|1996-03-21|Ciba Geigy Ag|

---

TW253849B|1993-08-09|1995-08-11|Ciba Geigy|

---

US5408002A|1993-09-09|1995-04-18|Minnesota Mining And Manufacturing Company|Azlactone-functional polymer blends, articles produced therefrom and methods for preparing both|

---

FR2709756B1|1993-09-10|1995-10-20|Essilor Int|Hydrophilic, transparent material with high oxygen permeability, based on a polymer with interpenetrating networks, its method of preparation and manufacture of soft contact lenses with high oxygen permeability.|

---

US5514478A|1993-09-29|1996-05-07|Alcan International Limited|Nonabrasive, corrosion resistant, hydrophilic coatings for aluminum surfaces, methods of application, and articles coated therewith|

---

US5723145A|1993-09-30|1998-03-03|Takiron Co., Ltd.|Transdermal absorption preparation|

---

US5936703A|1993-10-13|1999-08-10|Nof Corporation|Alkoxysilane compound, surface processing solution and contact lens|

---

GB9321714D0|1993-10-21|1993-12-15|Sandoz Ltd|Improvements in or relating to organic compounds|

---

US5446090A|1993-11-12|1995-08-29|Shearwater Polymers, Inc.|Isolatable, water soluble, and hydrolytically stable active sulfones of poly and related polymers for modification of surfaces and molecules|

---

US6342570B1|1994-11-14|2002-01-29|Novartis Ag|Cross-linkable copolymers and hydrogels|

---

US5712356A|1993-11-26|1998-01-27|Ciba Vision Corporation|Cross-linkable copolymers and hydrogels|

---

US5894002A|1993-12-13|1999-04-13|Ciba Vision Corporation|Process and apparatus for the manufacture of a contact lens|

---

JP3734512B2|1993-12-27|2006-01-11|株式会社メニコン|Contact lens appearance inspection method and appearance inspection apparatus|

---

HUT72406A|1994-03-14|1996-04-29|Seikagaku Kogyo Co Ltd|Material to be worn on the eyeball|

---

JPH10500712A|1994-04-11|1998-01-20|ヘキストセラニーズコーポレーション|Superabsorbent polymer and products obtained therefrom|

---

US5476665A|1994-04-13|1995-12-19|Minnesota Mining And Manufacturing Company|Azlactone functional particles incorporated in a membrane formed by solvent phase inversion|

---

KR100383303B1|1994-05-19|2003-07-18|미네소타 마이닝 앤드 매뉴팩춰링 캄파니|Polymeric articles with improved hydrophilicity and methods of making them|

---

US5500732A|1994-06-10|1996-03-19|Johnson & Johnson Vision Products, Inc.|Lens inspection system and method|

---

US5626000A|1994-06-10|1997-05-06|Johnson & Johnson Vision Products, Inc.|Packaging arrangement|

---

US5843346A|1994-06-30|1998-12-01|Polymer Technology Corporation|Method of cast molding contact lenses|

---

US5670558A|1994-07-07|1997-09-23|Terumo Kabushiki Kaisha|Medical instruments that exhibit surface lubricity when wetted|

---

US6800225B1|1994-07-14|2004-10-05|Novartis Ag|Process and device for the manufacture of mouldings and mouldings manufactured in accordance with that process|

---

US5922249A|1995-12-08|1999-07-13|Novartis Ag|Ophthalmic lens production process|

---

TW393498B|1995-04-04|2000-06-11|Novartis Ag|The preparation and use of Polysiloxane-comprising perfluoroalkyl ethers|

---

DE29624309U1|1995-04-04|2002-01-03|Novartis Ag|Duration supporting lenses|

---

US7468398B2|1994-09-06|2008-12-23|Ciba Vision Corporation|Extended wear ophthalmic lens|

---

TW585882B|1995-04-04|2004-05-01|Novartis Ag|A method of using a contact lens as an extended wear lens and a method of screening an ophthalmic lens for utility as an extended-wear lens|

---

US5760100B1|1994-09-06|2000-11-14|Ciba Vision Corp|Extended wear ophthalmic lens|

---

DE69636460T2|1995-12-08|2007-03-29|Novartis Ag|PLASMA-INDUCED POLYMER COATINGS|

---

US5509899A|1994-09-22|1996-04-23|Boston Scientific Corp.|Medical device with lubricious coating|

---

IT1270125B|1994-10-05|1997-04-28|Spherilene Srl|PROCESS FOR THE POLYMERIZATION OF OLEFINE|

---

US5681510A|1994-10-13|1997-10-28|Bausch & Lomb Incorporated|Method for treating plastic mold pieces|

---

US5665840A|1994-11-18|1997-09-09|Novartis Corporation|Polymeric networks from water-soluble prepolymers|

---

US5507804A|1994-11-16|1996-04-16|Alcon Laboratories, Inc.|Cross-linked polyethylene oxide coatings to improve the biocompatibility of implantable medical devices|

---

JP3647093B2|1994-11-17|2005-05-11|株式会社メニコン|Hydrophilized oxygen permeable contact lens and method for producing the same|

---

US5510004A|1994-12-01|1996-04-23|Hercules Incorporated|Azetidinium polymers for improving wet strength of paper|

---

SE503711C2|1994-12-14|1996-08-12|Medicarb Ab|Multistage procedure for coating an intraocular lens|

---

US5700559A|1994-12-16|1997-12-23|Advanced Surface Technology|Durable hydrophilic surface coatings|

---

TW353086B|1994-12-30|1999-02-21|Novartis Ag|Method for multistep coating of a surface|

---

US5532311A|1995-02-01|1996-07-02|Minnesota Mining And Manufacturing Company|Process for modifying surfaces|

---

TW349967B|1995-02-03|1999-01-11|Novartis Ag|Process for producing contact lenses and a cross-linkable polyvinylalcohol used therefor|

---

AU4620596A|1995-02-03|1996-08-21|Novartis Ag|Crosslinked polymers containing ester or amide groups|

---

US5599576A|1995-02-06|1997-02-04|Surface Solutions Laboratories, Inc.|Medical apparatus with scratch-resistant coating and method of making same|

---

WO1996024392A1|1995-02-07|1996-08-15|Fidia Advanced Biopolymers, S.R.L.|Process for the coating of objects with hyaluronic acid, derivatives thereof, and semisynthetic polymers|

---

US5702754A|1995-02-22|1997-12-30|Meadox Medicals, Inc.|Method of providing a substrate with a hydrophilic coating and substrates, particularly medical devices, provided with such coatings|

---

US6179817B1|1995-02-22|2001-01-30|Boston Scientific Corporation|Hybrid coating for medical devices|

---

US5869127A|1995-02-22|1999-02-09|Boston Scientific Corporation|Method of providing a substrate with a bio-active/biocompatible coating|

---

JPH08239639A|1995-03-02|1996-09-17|Sekisui Chem Co Ltd|Pressure-sensitive adhesive composition and article coated therewith|

---

US5633504A|1995-03-30|1997-05-27|Wesley-Jessen Corporation|Inspection of optical components|

---

US5674942A|1995-03-31|1997-10-07|Johnson & Johnson Vision Products, Inc.|Interpenetrating polymer networks for contact lens production|

---

US5688855A|1995-05-01|1997-11-18|S.K.Y. Polymers, Inc.|Thin film hydrophilic coatings|

---

AU5630796A|1995-05-25|1996-12-11|Minnesota Mining And Manufacturing Company|Process for producing biocompatible surfaces|

---

US5583463A|1995-05-30|1996-12-10|Micron Technology, Inc.|Redundant row fuse bank circuit|

---

US5731087A|1995-06-07|1998-03-24|Union Carbide Chemicals & Plastics Technology Corporation|Lubricious coatings containing polymers with vinyl and carboxylic acid moieties|

---

US5620738A|1995-06-07|1997-04-15|Union Carbide Chemicals & Plastics Technology Corporation|Non-reactive lubicious coating process|

---

AUPN354595A0|1995-06-14|1995-07-06|Ciba-Geigy Ag|Novel materials|

---

TW428018B|1995-06-29|2001-04-01|Ciba Sc Holding Ag|Aminosilane salts and silanamides of carboxylic acids as corrosion inhibitors|

---

CN1085990C|1995-06-30|2002-06-05|联邦科学及工业研究组织|Improved surface treatment of polymers|

---

CN1189774A|1995-07-03|1998-08-05|伊兰公司Plc|Controlled release formulations for poorly soluble drugs|

---

US5874127A|1995-08-16|1999-02-23|Ciba Vision Corporation|Method and apparatus for gaseous treatment|

---

US5672638A|1995-08-22|1997-09-30|Medtronic, Inc.|Biocompatability for solid surfaces|

---

DE69617637T2|1995-09-06|2002-07-18|Menicon Co Ltd|METHOD FOR THE PRODUCTION OF CONTACT LENSES AND THE CONTACT LENSES PRODUCED IN THIS PROCESS|

---

EP0763754B1|1995-09-13|2003-01-08|Seikagaku Kogyo Kabushiki Kaisha |Photocured crosslinked-hyaluronic acid contact lens|

---

US5849222A|1995-09-29|1998-12-15|Johnson & Johnson Vision Products, Inc.|Method for reducing lens hole defects in production of contact lens blanks|

---

SG75101A1|1995-09-29|2000-09-19|Johnson & Johnson Vision Prod|Laminated barrier materials for the packaging of contact lens|

---

US5674557A|1995-09-29|1997-10-07|Johnson & Johnson Vision Products, Inc.|Method for transiently wetting lens molds in production of contact lens blanks to reduce lens hole defects|

---

AU698522B2|1995-09-29|1998-10-29|Johnson & Johnson Vision Products, Inc.|Lens parameter measurement using optical sectioning|

---

US6007526A|1995-10-12|1999-12-28|Hollister Incorporated|Male external catheter with short annular sealing flap|

---

US5804318A|1995-10-26|1998-09-08|Corvita Corporation|Lubricious hydrogel surface modification|

---

US6509098B1|1995-11-17|2003-01-21|Massachusetts Institute Of Technology|Poly coated surfaces|

---

US5710302A|1995-12-07|1998-01-20|Bausch & Lomb Incorporated|Monomeric units useful for reducing the modules of silicone hydrogels|

---

US6169127B1|1996-08-30|2001-01-02|Novartis Ag|Plasma-induced polymer coatings|

---

EP0876165B1|1995-12-18|2006-06-21|Angiotech BioMaterials Corp.|Crosslinked polymer compositions and methods for their use|

---

EP0780419A1|1995-12-22|1997-06-25|Holland Biomaterials Group B.V.|Multi-functional site containing polymers, and applications thereof|

---

WO1997023532A1|1995-12-22|1997-07-03|Novartis Ag|Polyurethanes made from polysiloxane/polyol macromers|

---

AU2259197A|1996-02-09|1997-08-28|Surface Solutions Laboratories, Inc.|Water-based hydrophilic coating compositions and articles prepared therefrom|

---

US5792531A|1996-02-20|1998-08-11|Tactyl Technologies, Inc.|Readily donned, powder free elastomeric article|

---

US5779943A|1996-03-19|1998-07-14|Johnson & Johnson Vision Products, Inc.|Molded polymeric object with wettable surface made from latent-hydrophilic monomers|

---

US5786429A|1996-04-18|1998-07-28|Hercules Incorporated|Highly branched polyamidoamines and their preparation|

---

US5811151A|1996-05-31|1998-09-22|Medtronic, Inc.|Method of modifying the surface of a medical device|

---

EP0814116A1|1996-06-19|1997-12-29|Hüls Aktiengesellschaft|Hydrophilic coating of polymeric substrate surfaces|

---

US5807944A|1996-06-27|1998-09-15|Ciba Vision Corporation|Amphiphilic, segmented copolymer of controlled morphology and ophthalmic devices including contact lenses made therefrom|

---

US6174326B1|1996-09-25|2001-01-16|Terumo Kabushiki Kaisha|Radiopaque, antithrombogenic stent and method for its production|

---

US5800412A|1996-10-10|1998-09-01|Sts Biopolymers, Inc.|Hydrophilic coatings with hydrating agents|

---

IL129393D0|1996-10-21|2000-02-17|Novartis Ag|Crosslinkable polymers|

---

US6639007B2|1996-11-15|2003-10-28|Tactyl Technologies, Inc.|Elastomeric copolymer compositions and articles made therewith|

---

AR009439A1|1996-12-23|2000-04-12|Novartis Ag|AN ARTICLE THAT INCLUDES A SUBSTRATE WITH A PRIMARY POLYMERIC COATING THAT CARRIES REACTIVE GROUPS PREDOMINANTLY ON ITS SURFACE, A METHOD FOR PREPARING SUCH AN ARTICLE, AN ARTICLE THAT HAS A HYBRID-TYPE COATING AND A CONTACT LENS|

---

US6306514B1|1996-12-31|2001-10-23|Ansell Healthcare Products Inc.|Slip-coated elastomeric flexible articles and their method of manufacture|

---

US5882687A|1997-01-10|1999-03-16|Allergan|Compositions and methods for storing contact lenses|

---

US6018001A|1997-01-23|2000-01-25|Menicon Co., Ltd.|Process for producing contact lens with hydrophilic surface and contact lens obtained thereby|

---

US5997517A|1997-01-27|1999-12-07|Sts Biopolymers, Inc.|Bonding layers for medical device surface coatings|

---

EP0867456A1|1997-02-04|1998-09-30|Novartis AG|Ophthalmic moulded part|

---

US5818573A|1997-02-06|1998-10-06|Pbh, Inc.|Opthalmic lens inspection system|

---

US5801822A|1997-02-06|1998-09-01|Pbh, Inc.|Ophthalmic lens inspection system|

---

JP4144902B2|1997-02-21|2008-09-03|ノバルティスアクチエンゲゼルシャフト|Ophthalmic molding|

---

US6096138A|1997-04-30|2000-08-01|Bausch & Lomb Incorporated|Method for inhibiting the deposition of protein on contact lens|

---

US5879697A|1997-04-30|1999-03-09|Schneider Usa Inc|Drug-releasing coatings for medical devices|

---

US6221467B1|1997-06-03|2001-04-24|Scimed Life Systems, Inc.|Coating gradient for lubricious coatings on balloon catheters|

---

GB9711818D0|1997-06-06|1997-08-06|Bausch & Lomb|Contact lens packing solutions and methods for improving the comfort of disposable contact lenses|

---

US6866938B2|1997-07-22|2005-03-15|Nissha Printing Co., Ltd.|Foil-detecting sheet and method of producing a foil-decorated resin article using the same|

---

DE19732587A1|1997-07-29|1999-02-04|Huels Chemische Werke Ag|Bioactive coating with a low-friction surface|

---

US6165322A|1997-07-29|2000-12-26|Hercules Incorporated|Polyamidoamine/epichlorohydrin resins bearing polyol sidechains as dry strength agents|

---

AU9627298A|1997-09-23|1999-04-12|Novartis Ag|Method for hydrogel surface treatment and article formed therefrom|

---

US5858653A|1997-09-30|1999-01-12|Surmodics, Inc.|Reagent and method for attaching target molecules to a surface|

---

TW429327B|1997-10-21|2001-04-11|Novartis Ag|Single mould alignment|

---

US6054504A|1997-12-31|2000-04-25|Hydromer, Inc.|Biostatic coatings for the reduction and prevention of bacterial adhesion|

---

HU0100553A2|1998-01-09|2001-06-28|Novartis Ag.|Coating of polymers|

---

JPH11223901A|1998-02-06|1999-08-17|Fuji Photo Film Co Ltd|Heat-developable recording material|

---

US6943203B2|1998-03-02|2005-09-13|Johnson & Johnson Vision Care, Inc.|Soft contact lenses|

---

US5962548A|1998-03-02|1999-10-05|Johnson & Johnson Vision Products, Inc.|Silicone hydrogel polymers|

---

US6367929B1|1998-03-02|2002-04-09|Johnson & Johnson Vision Care, Inc.|Hydrogel with internal wetting agent|

---

US5998498A|1998-03-02|1999-12-07|Johnson & Johnson Vision Products, Inc.|Soft contact lenses|

---

US6096726A|1998-03-11|2000-08-01|Surface Solutions Laboratories Incorporated|Multicomponent complex for use with substrate|

---

US6410616B1|1998-04-09|2002-06-25|Nippon Shokubai Co., Ltd|Crosslinked polymer particle and its production process and use|

---

US6686054B2|1998-04-22|2004-02-03|Sri International|Method and composition for the sizing of paper using azetidinium and/or guanidine polymers|

---

TW473488B|1998-04-30|2002-01-21|Novartis Ag|Composite materials, biomedical articles formed thereof and process for their manufacture|

---

US6348507B1|1998-05-05|2002-02-19|Bausch & Lomb Incorporated|Surface treatment of silicone hydrogel contact lenses|

---

US6193369B1|1998-05-05|2001-02-27|Bausch & Lomb Incorporated|Plasma surface treatment of silicone hydrogel contact lenses|

---

US6106889A|1998-06-11|2000-08-22|Biocoat Incorporated|Method of selective coating of articles|

---

US6500481B1|1998-06-11|2002-12-31|Johnson & Johnson Vision Care, Inc.|Biomedical devices with amid-containing coatings|

---

US6087415A|1998-06-11|2000-07-11|Johnson & Johnson Vision Care, Inc.|Biomedical devices with hydrophilic coatings|

---

JP2000010055A|1998-06-19|2000-01-14|Seed Co Ltd|Hydrophilic lens for eye and its production|

---

US6039913A|1998-08-27|2000-03-21|Novartis Ag|Process for the manufacture of an ophthalmic molding|

---

US6099852A|1998-09-23|2000-08-08|Johnson & Johnson Vision Products, Inc.|Wettable silicone-based lenses|

---

US6149842A|1998-11-12|2000-11-21|Novartis Ag|Methods and compositions for manufacturing tinted ophthalmic lenses|

---

US6207796B1|1998-11-18|2001-03-27|Nippon Shokubai Co., Ltd.|Production process for hydrophilic polymer|

---

EP1002807A1|1998-11-20|2000-05-24|Novartis AG|Functionalized resin derived from polyallylamine|

---

US6451871B1|1998-11-25|2002-09-17|Novartis Ag|Methods of modifying surface characteristics|

---

US5981675A|1998-12-07|1999-11-09|Bausch & Lomb Incorporated|Silicone-containing macromonomers and low water materials|

---

US6537614B1|1998-12-18|2003-03-25|Kimberly-Clark Worldwide, Inc.|Cationically charged coating on hydrophobic polymer fibers with poly assist|

---

TW480246B|1998-12-18|2002-03-21|Kimberly Clark Co|Cationically charged coating on glass fibers and method for making the same|

---

US6550915B1|1998-12-21|2003-04-22|Bausch & Lomb Incorporated|Surface treatment of fluorinated contact lens materials|

---

US6465602B2|2000-01-20|2002-10-15|Kimberly-Clark Worldwide, Inc.|Modified condensation polymers having azetidinium groups and containing polysiloxane moieties|

---

US6896769B2|1999-01-25|2005-05-24|Kimberly-Clark Worldwide, Inc.|Modified condensation polymers containing azetidinium groups in conjunction with amphiphilic hydrocarbon moieties|

---

US6340465B1|1999-04-12|2002-01-22|Edwards Lifesciences Corp.|Lubricious coatings for medical devices|

---

JP2000351862A|1999-04-30|2000-12-19|Novartis Ag|Neutral coating film|

---

US6440571B1|1999-05-20|2002-08-27|Bausch & Lomb Incorporated|Surface treatment of silicone medical devices with reactive hydrophilic polymers|

---

US6630243B2|1999-05-20|2003-10-07|Bausch & Lomb Incorporated|Surface treatment of silicone hydrogel contact lenses comprising hydrophilic polymer chains attached to an intermediate carbon coating|

---

AU770880B2|1999-07-08|2004-03-04|Armstrong World Industries, Inc.|Compositions for imparting desired properties to materials|

---

US7344607B2|1999-07-08|2008-03-18|Ge Betz, Inc.|Non-chromate conversion coating treatment for metals|

---

JP2003505728A|1999-07-27|2003-02-12|ボシュ・アンド・ロム・インコーポレイテッド|Contact lens material|

---

CA2381424C|1999-09-02|2010-06-08|Alcon Universal Ltd.|Covalently-bound, hydrophilic coating compositions for surgical implants|

---

US6632905B2|1999-09-02|2003-10-14|Alcon Universal Ltd.|Covalently-bound, hydrophilic coating compositions for surgical implants|

---

US6723815B2|1999-09-02|2004-04-20|Alcon, Inc.|Covalently-bound, hydrophilic coating compositions for surgical implants|

---

JP2001075060A|1999-09-03|2001-03-23|Seiko Epson Corp|Contact lens and its production|

---

WO2001020997A1|1999-09-20|2001-03-29|Menicon Co., Ltd.|Liquid preparation for contact lenses|

---

AU778102B2|1999-10-12|2004-11-18|Johnson & Johnson Vision Care, Inc.|Contact lens coating selection and manufacturing process|

---

US6478423B1|1999-10-12|2002-11-12|Johnson & Johnson Vison Care, Inc.|Contact lens coating selection and manufacturing process|

---

JP2001117054A|1999-10-19|2001-04-27|Nof Corp|Surface treated contact lens and method for manufacturing the same|

---

AU1387401A|1999-10-27|2001-05-08|Commonwealth Scientific And Industrial Research Organisation|Coating process|

---

JP2001163932A|1999-10-27|2001-06-19|Novartis Ag|Method for modifying surface of material|

---

JP2001163933A|1999-10-27|2001-06-19|Novartis Ag|Method for moldifying surface of material|

---

JP2001158813A|1999-10-27|2001-06-12|Novartis Ag|Method for covering surface of material|

---

WO2001034700A1|1999-11-09|2001-05-17|Nof Corporation|Composition for hydrogel, hydrogel, and use thereof|

---

CN1177972C|1999-11-24|2004-12-01|赫尔克里士公司|Creping adhesives|

---

AU779729B2|1999-12-16|2005-02-10|Coopervision International Limited|Soft contact lens capable of being worn for a long period|

---

US6517678B1|2000-01-20|2003-02-11|Kimberly-Clark Worldwide, Inc.|Modified polysaccharides containing amphiphillic hydrocarbon moieties|

---

US6719929B2|2000-02-04|2004-04-13|Novartis Ag|Method for modifying a surface|

---

AR027348A1|2000-02-04|2003-03-26|Novartis Ag|PROCESS TO COVER A SURFACE|

---

JP3929014B2|2000-02-24|2007-06-13|Ｈｏｙａヘルスケア株式会社|Contact lens material comprising a macromer having a polysiloxane structure in the side chain|

---

US7521519B1|2000-03-14|2009-04-21|Novartis Ag|Organic compounds|

---

GB0006891D0|2000-03-23|2000-05-10|Arjobex Ltd|Coating composition|

---

AU6014301A|2000-03-24|2001-10-03|Novartis Ag|Novel polymers|

---

CN100510847C|2000-03-31|2009-07-08|库柏维景国际控股公司|Contact lens|

---

US6467903B1|2000-03-31|2002-10-22|Ocular Sciences, Inc.|Contact lens having a uniform horizontal thickness profile|

---

US6599559B1|2000-04-03|2003-07-29|Bausch & Lomb Incorporated|Renewable surface treatment of silicone medical devices with reactive hydrophilic polymers|

---

JP4834916B2|2000-05-10|2011-12-14|東レ株式会社|Surface-treated plastic molded product|

---

US6689480B2|2000-05-10|2004-02-10|Toray Industries, Inc.|Surface-treated plastic article and method of surface treatment|

---

JP4776863B2|2000-05-30|2011-09-21|ノバルティスアーゲー|Covered product|

---

US6589665B2|2000-05-30|2003-07-08|Novartis Ag|Coated articles|

---

US6428839B1|2000-06-02|2002-08-06|Bausch & Lomb Incorporated|Surface treatment of medical device|

---

US6923538B2|2000-07-06|2005-08-02|Coopervision, Inc.|Method for cast moulding contact lenses with a rounded edge form|

---

US6364934B1|2000-07-31|2002-04-02|Bausch & Lomb Incorporated|Method of making ocular devices|

---

US6482221B1|2000-08-21|2002-11-19|Counter Clockwise, Inc.|Manipulatable delivery catheter for occlusive devices |

---

WO2002015911A1|2000-08-22|2002-02-28|Nof Corporation|Lubricating agent and insertion aid solution for contact lens|

---

US6852353B2|2000-08-24|2005-02-08|Novartis Ag|Process for surface modifying substrates and modified substrates resulting therefrom|

---

WO2002024793A1|2000-09-19|2002-03-28|Bausch & Lomb Incorporated|Method for applying polymeric lens coating|

---

US6551267B1|2000-10-18|2003-04-22|Becton, Dickinson And Company|Medical article having blood-contacting surface|

---

US20020182315A1|2000-11-01|2002-12-05|Heiler David J.|Surface treatment of non-plasma treated silicone hydrogel contact lenses|

---

DE10055762A1|2000-11-10|2002-06-06|Woehlk Contact Linsen Gmbh|Hydrogel contact lenses with high biocompatibility|

---

US6861123B2|2000-12-01|2005-03-01|Johnson & Johnson Vision Care, Inc.|Silicone hydrogel contact lens|

---

US6531432B2|2000-12-07|2003-03-11|Johnson & Johnson Vision Care, Inc.|Contact lens packaging solutions|

---

GB0030177D0|2000-12-11|2001-01-24|Unilever Plc|Textile care composition|

---

JP4043789B2|2001-01-24|2008-02-06|ノバルティスアクチエンゲゼルシャフト|Method for modifying a surface|

---

RU2196784C2|2001-03-30|2003-01-20|Кемеровский государственный университет|Method of modifying polydimethylsiloxane rubber|

---

US6835410B2|2001-05-21|2004-12-28|Novartis Ag|Bottle-brush type coatings with entangled hydrophilic polymer|

---

JP2003066381A|2001-05-23|2003-03-05|Novartis Ag|System and method for processing object with liquid|

---

US6815074B2|2001-05-30|2004-11-09|Novartis Ag|Polymeric materials for making contact lenses|

---

US6811805B2|2001-05-30|2004-11-02|Novatis Ag|Method for applying a coating|

---

US7879267B2|2001-08-02|2011-02-01|J&J Vision Care, Inc.|Method for coating articles by mold transfer|

---

US6822016B2|2001-09-10|2004-11-23|Johnson & Johnson Vision Care, Inc.|Biomedical devices containing internal wetting agents|

---

US7461937B2|2001-09-10|2008-12-09|Johnson & Johnson Vision Care, Inc.|Soft contact lenses displaying superior on-eye comfort|

---

US20070138692A1|2002-09-06|2007-06-21|Ford James D|Process for forming clear, wettable silicone hydrogel articles|

---

US20080299179A1|2002-09-06|2008-12-04|Osman Rathore|Solutions for ophthalmic lenses containing at least one silicone containing component|

---

US7052131B2|2001-09-10|2006-05-30|J&J Vision Care, Inc.|Biomedical devices containing internal wetting agents|

---

US6891010B2|2001-10-29|2005-05-10|Bausch & Lomb Incorporated|Silicone hydrogels based on vinyl carbonate endcapped fluorinated side chain polysiloxanes|

---

TW200407367A|2001-11-13|2004-05-16|Novartis Ag|Method for modifying the surface of biomedical articles|

---

US7402318B2|2001-11-14|2008-07-22|Novartis Ag|Medical devices having antimicrobial coatings thereon|

---

TWI255224B|2002-01-09|2006-05-21|Novartis Ag|Polymeric articles having a lubricious coating and method for making the same|

---

GB0201165D0|2002-01-18|2002-03-06|Unilever Plc|Azetidinium modidfied poymers and fabric treatment composition|

---

US6936641B2|2002-06-25|2005-08-30|Johnson & Johnson Vision Care, Inc.|Macromer forming catalysts|

---

US7270678B2|2002-06-28|2007-09-18|Bausch & Lomb Incorporated|Surface modification of functional group-containing medical devices with catalyst-containing reactive polymer system|

---

AU2002950469A0|2002-07-30|2002-09-12|Commonwealth Scientific And Industrial Research Organisation|Improved biomedical compositions|

---

WO2004011970A1|2002-07-30|2004-02-05|Nitto Denko Corporation|Optical film and its manufacturing method|

---

EP1534767B1|2002-08-14|2007-11-28|Novartis AG|Radiation-curable prepolymers|

---

US6896926B2|2002-09-11|2005-05-24|Novartis Ag|Method for applying an LbL coating onto a medical device|

---

US6926965B2|2002-09-11|2005-08-09|Novartis Ag|LbL-coated medical device and method for making the same|

---

US6740336B2|2002-10-04|2004-05-25|Mirus Corporation|Process for generating multilayered particles|

---

US20040116564A1|2002-11-27|2004-06-17|Devlin Brian Gerrard|Stabilization of poly containing polymeric materials|

---

US8172395B2|2002-12-03|2012-05-08|Novartis Ag|Medical devices having antimicrobial coatings thereon|

---

US7032251B2|2002-12-10|2006-04-25|Kimberly-Clark Worldwide, Inc.|Crosslinking agent for coated elastomeric articles|

---

US7387759B2|2002-12-17|2008-06-17|Novartis Ag|System and method for curing polymeric moldings having a masking collar|

---

US7384590B2|2002-12-17|2008-06-10|Novartis Ag|System and method for curing polymeric moldings|

---

AT507501T|2003-01-10|2011-05-15|Menicon Co Ltd|HIGHLY SAFE SILICONE-CONTAINING MATERIAL FOR AN OKULAR LENS AND MANUFACTURING PROCESS THEREFOR|

---

ES2531326T3|2003-02-28|2015-03-13|Biointeractions Ltd|Polymeric network systems for medical devices and methods of use|

---

JP5047613B2|2003-04-24|2012-10-10|クーパーヴィジョンインターナショナルホウルディングカンパニーリミテッドパートナーシップ|Hydrogel contact lenses and packaging systems and methods for their production|

---

CN1207326C|2003-07-18|2005-06-22|清华大学|Preparation method of natural high-molecular microsphere whose surface has loaded functional group|

---

US20050070688A1|2003-09-26|2005-03-31|3M Innovative Properties Company|Reactive hydrophilic oligomers|

---

GB0322640D0|2003-09-26|2003-10-29|1800 Contacts|Process|

---

JP4369194B2|2003-09-30|2009-11-18|Ｈｏｙａ株式会社|Plastic lens and manufacturing method thereof|

---

US7977430B2|2003-11-25|2011-07-12|Novartis Ag|Crosslinkable polyurea prepolymers|

---

US7084188B2|2003-12-05|2006-08-01|Bausch & Lomb Incorporated|Surface modification of contact lenses|

---

US7214809B2|2004-02-11|2007-05-08|Johnson & Johnson Vision Care, Inc.|acrylamide monomers containing hydroxy and silicone functionalities|

---

US20060052306A1|2004-05-10|2006-03-09|Nastech Pharmaceutical Company Inc.|GRAS composition for enhanced mucosal delivery of parathyroid hormone|

---

AT484766T|2004-05-28|2010-10-15|Menicon Co Ltd|CONTACT LENS|

---

CN101163991A|2004-08-27|2008-04-16|旭化成爱目股份有限公司|Silicone hydrogel contact lens|

---

SG155241A1|2004-08-27|2009-09-30|Asahikasei Aime Co Ltd|Silicone hydrogel contact lenses|

---

JP4782508B2|2004-09-30|2011-09-28|株式会社シード|High oxygen permeation hydrous ophthalmic lens|

---

US7247692B2|2004-09-30|2007-07-24|Johnson & Johnson Vision Care, Inc.|Biomedical devices containing amphiphilic block copolymers|

---

US20060065138A1|2004-09-30|2006-03-30|Tucker Robert C|Pad printing method for making colored contact lenses|

---

US7249848B2|2004-09-30|2007-07-31|Johnson & Johnson Vision Care, Inc.|Wettable hydrogels comprising reactive, hydrophilic, polymeric internal wetting agents|

---

US7556858B2|2004-09-30|2009-07-07|3M Innovative Properties Company|Substrate with attached dendrimers|

---

EP1802357B2|2004-10-01|2013-09-18|Menicon Singapore Pte Ltd.|Method for sterilising contact lens with package solution|

---

US7857447B2|2004-10-05|2010-12-28|The Board Of Trustees Of The Leland Stanford Junior University|Interpenetrating polymer network hydrogel contact lenses|

---

US20060100113A1|2004-11-05|2006-05-11|Pegram Stephen C|Methods of inhabiting the adherence of lenses to surfaces during their manufacture|

---

AT514491T|2004-11-29|2011-07-15|Dsm Ip Assets Bv|METHOD FOR REDUCING THE AMOUNT OF MIGRATABLE COMPONENTS OF POLYMER COATINGS|

---

SE0403092D0|2004-12-20|2004-12-20|Amo Groningen Bv|Amphiphilic block copolymers and their use|

---

RU2269552C1|2004-12-23|2006-02-10|Институт Катализа Им. Г.К. Борескова Сибирского Отделения Российской Академии Наук|Polymer composition for prolonged-use soft contact lenses and a method for preparation thereof|

---

CN101094878B|2004-12-29|2011-04-13|博士伦公司|Polysiloxane prepolymers for biomedical devices|

---

EP1838748B1|2004-12-29|2009-03-11|Bausch & Lomb Incorporated|Polysiloxane prepolymers for biomedical devices|

---

EP1861069B2|2005-02-09|2013-07-03|Safilens S.R.L.|Contact lens, method for producing same, and pack for storage and maintenance of a contact lens|

---

JP5154231B2|2005-02-14|2013-02-27|ジョンソン・アンド・ジョンソン・ビジョン・ケア・インコーポレイテッド|Comfortable ophthalmic device and its manufacturing method|

---

US20060193894A1|2005-02-28|2006-08-31|Jen James S|Methods for providing biomedical devices with hydrophilic antimicrobial coatings|

---

US7426993B2|2005-08-09|2008-09-23|Coopervision International Holding Company, Lp|Contact lens package|

---

WO2007017243A1|2005-08-10|2007-02-15|Novartis Ag|Silicone hydrogels|

---

MY141143A|2005-08-11|2010-03-15|Coopervision Int Holding Co Lp|Contact lenses and methods for reducing conjunctival pressure in contact lens wearers|

---

EP1754731A1|2005-08-16|2007-02-21|Nederlandse Organisatie voor Toegepast-Natuuurwetenschappelijk Onderzoek TNO|Method of modifying materials surfaces|

---

US20070087113A1|2005-10-19|2007-04-19|Bausch & Lomb Incorporated|Surface-modified medical devices and method of making|

---

CN101360764B|2005-11-14|2011-12-14|西巴控股公司|Preparation of functionalized cationic polymers and their preparation and application in personal care|

---

WO2007064594A2|2005-11-29|2007-06-07|Bausch & Lomb Incorporated|New coatings on ophthalmic lenses|

---

US20070149428A1|2005-12-14|2007-06-28|Bausch & Lomb Incorporated|Method of Packaging a Lens|

---

JP2009521013A|2005-12-20|2009-05-28|ジョンソン・アンド・ジョンソン・ビジョン・ケア・インコーポレイテッド|Method and system for leaching and releasing silicone hydrogel ophthalmic lenses using an alcohol solution|

---

US7825273B2|2006-01-06|2010-11-02|Bausch & Lomb Incorporated|Process for making cationic hydrophilic siloxanyl monomers|

---

US8790678B2|2006-03-03|2014-07-29|Washington University|Biomaterials having nanoscale layers and coatings|

---

US8044112B2|2006-03-30|2011-10-25|Novartis Ag|Method for applying a coating onto a silicone hydrogel lens|

---

WO2007121513A1|2006-04-20|2007-11-01|Aortech Biomaterials Pty Ltd|Gels|

---

US7789509B2|2006-06-01|2010-09-07|Advanced Vision Science, Inc.|Non- or reduced glistenings intraocular lens and method of manufacturing same|

---

US7858000B2|2006-06-08|2010-12-28|Novartis Ag|Method of making silicone hydrogel contact lenses|

---

US8231218B2|2006-06-15|2012-07-31|Coopervision International Holding Company, Lp|Wettable silicone hydrogel contact lenses and related compositions and methods|

---

US7540609B2|2006-06-15|2009-06-02|Coopervision International Holding Company, Lp|Wettable silicone hydrogel contact lenses and related compositions and methods|

---

US7572841B2|2006-06-15|2009-08-11|Coopervision International Holding Company, Lp|Wettable silicone hydrogel contact lenses and related compositions and methods|

---

TWI443116B|2006-06-15|2014-07-01|Coopervision Int Holding Co Lp|Wettable silicone hydrogel contact lenses and related compositions and methods|

---

US20080002146A1|2006-06-28|2008-01-03|Stachowski Mark J|Biocompatible, surface modified materials|

---

US20080003259A1|2006-06-30|2008-01-03|Salamone Joseph C|Modification of surfaces of polymeric articles by Michael addition reaction|

---

US7960465B2|2006-06-30|2011-06-14|Johnson & Johnson Vision Care, Inc.|Antimicrobial lenses, processes to prepare them and methods of their use|

---

PT2038310E|2006-07-12|2010-08-25|Novartis Ag|Actinically crosslinkable copolymers for manufacturing contact lenses|

---

US8459445B2|2006-07-21|2013-06-11|Menicon, Co., Ltd.|Colored contact lens primary packaging|

---

EP2067797B1|2006-09-29|2020-11-04|Toray Industries, Inc.|Silicone polymer, ocular lenses, and contact lens|

---

HUE027342T2|2006-10-30|2016-09-28|Novartis Ag|Method for applying a coating onto a silicone hydrogel lens|

---

CN101534793A|2006-11-06|2009-09-16|诺瓦提斯公司|Ocular devices and methods of making and using thereof|

---

US20080110770A1|2006-11-10|2008-05-15|Bausch & Lomb Incorporated|Packaging solutions|

---

GB0623299D0|2006-11-22|2007-01-03|Sauflon Cl Ltd|Contact lens|

---

EP2087397A1|2006-11-29|2009-08-12|Procornea Holding B.V.|Hydrogel contact lens comprising a polymer comprising a carboxy betaine ester monomer|

---

TWI434926B|2006-12-11|2014-04-21|Alcon Res Ltd|Use of peo-pbo block copolymers in ophthalmic compositions|

---

AR064286A1|2006-12-13|2009-03-25|Quiceno Gomez Alexandra Lorena|PRODUCTION OF OPHTHALMIC DEVICES BASED ON POLYMERIZATION BY PHOTOINDUCIDED SCALE GROWTH|

---

CA2671740C|2006-12-13|2015-08-11|Novartis Ag|Actinically curable silicone hydrogel copolymers and uses thereof|

---

US20080141628A1|2006-12-15|2008-06-19|Bausch & Lomb Incorporated|Packaging Solutions|

---

EP2091585B1|2006-12-15|2010-12-15|Bausch & Lomb Incorporated|Surface treatment of biomedical devices|

---

US20080142038A1|2006-12-15|2008-06-19|Bausch & Lomb Incorporated|Surface treatment of medical devices|

---

US20080148689A1|2006-12-20|2008-06-26|Bausch & Lomb Incorporated|Packaging solutions|

---

US7832856B2|2006-12-20|2010-11-16|Bausch & Lomb Incorporated|Coatings and solutions for contact lenses|

---

US8158192B2|2006-12-21|2012-04-17|Novartis Ag|Process for the coating of biomedical articles|

---

US20080152540A1|2006-12-22|2008-06-26|Bausch & Lomb Incorporated|Packaging solutions|

---

US8101702B2|2007-01-12|2012-01-24|Dow Corning Corporation|Silicone-containing composition|

---

EP2122390B1|2007-02-09|2011-11-02|Novartis AG|Cross-linkable polyionic coatings for contact lenses|

---

MX2009010116A|2007-03-22|2009-10-12|Novartis Ag|Prepolymers with dangling polysiloxane-containing polymer chains.|

---

BRPI0809151A2|2007-03-22|2014-09-16|Novartis Ag|PREPOLYMERS CONTAINING SILICON WITH PENDING HYDROPHILIC POLYMER CHAINS|

---

JP5217240B2|2007-05-21|2013-06-19|星光Ｐｍｃ株式会社|Paper additive and paper making method using the same|

---

US7691917B2|2007-06-14|2010-04-06|Bausch & Lomb Incorporated|Silcone-containing prepolymers|

---

US20080314767A1|2007-06-22|2008-12-25|Bausch & Lomb Incorporated|Ophthalmic Solutions|

---

KR101231181B1|2007-06-25|2013-02-07|남택인|Silicone-hydrogel compound for soft contact lens and soft contact lens produced using the compound|

---

US7868071B2|2007-07-30|2011-01-11|Georgia-Pacific Chemicals Llc|Method of stabilizing aqueous cationic polymers|

---

US20090033864A1|2007-07-30|2009-02-05|Shone Thomas R|Multifocal contact lenses and methods for improving vision and for producing multifocal contact lenses|

---

TWI419719B|2007-08-31|2013-12-21|Novartis Ag|Contact lens products|

---

WO2009032122A1|2007-08-31|2009-03-12|Novartis Ag|Contact lens packaging solutions|

---

TW200918983A|2007-10-22|2009-05-01|mo-wei Hong|Forming method of a silicone gel contact lens and its structure|

---

US8490782B2|2007-10-23|2013-07-23|Bausch & Lomb Incorporated|Packaging solutions|

---

US20090111942A1|2007-10-25|2009-04-30|Bausch & Lomb Incorporated|Method for Making Surface Modified Biomedical Devices|

---

WO2009070429A1|2007-11-29|2009-06-04|Bausch & Lomb Incorporated|Process for making biomedical devices|

---

WO2009070443A1|2007-11-29|2009-06-04|Bausch & Lomb Incorporated|Process for making biomedical devices|

---

US7934830B2|2007-12-03|2011-05-03|Bausch & Lomb Incorporated|High water content silicone hydrogels|

---

US20090145091A1|2007-12-11|2009-06-11|Richard Connolly|Method for treating ophthalmic lenses|

---

US20090145086A1|2007-12-11|2009-06-11|Reynolds Ger M|Method for treating ophthalmic lenses|

---

BRPI0821158A2|2007-12-20|2015-06-16|Novartis Ag|Method for Making Contact Lenses|

---

CN103969706B|2008-12-18|2017-08-25|诺华股份有限公司|Lens forming composition suitable for manufacturing silicone hydrogel contact lens|

---

US20090171049A1|2007-12-27|2009-07-02|Linhardt Jeffrey G|Segmented reactive block copolymers|

---

US20090173643A1|2008-01-09|2009-07-09|Yu-Chin Lai|Packaging Solutions|

---

US20090173045A1|2008-01-09|2009-07-09|Yu-Chin Lai|Packaging Solutions|

---

US7837934B2|2008-01-09|2010-11-23|Bausch & Lomb Incorporated|Packaging solutions|

---

US8011784B2|2008-01-14|2011-09-06|Coopervision International Holding Company, Lp|Polymerizable contact lens formulations and contact lenses obtained therefrom|

---

US8142835B2|2008-01-23|2012-03-27|Novartis Ag|Method for coating silicone hydrogels|

---

WO2009094368A1|2008-01-25|2009-07-30|Bausch & Lomb Incorporated|Contact lens|

---

US20090200692A1|2008-02-07|2009-08-13|Jame Chang|Method for manufacturing a silicone contact lens having a hydrophilic surface|

---

US7781554B2|2008-03-05|2010-08-24|Bausch & Lomb Incorporated|Polysiloxanes and polysiloxane prepolymers with vinyl or epoxy functionality|

---

WO2009115477A2|2008-03-18|2009-09-24|Novartis Ag|Coating process for ophthalmic lenses|

---

US20090244479A1|2008-03-31|2009-10-01|Diana Zanini|Tinted silicone ophthalmic devices, processes and polymers used in the preparation of same|

---

US8470906B2|2008-09-30|2013-06-25|Johnson & Johnson Vision Care, Inc.|Ionic silicone hydrogels having improved hydrolytic stability|

---

US8246168B2|2008-11-10|2012-08-21|Bausch & Lomb Incorporated|Methacrylate-based bulky side-chain siloxane cross linkers for optical medical devices|

---

EP2356497B8|2008-11-13|2020-03-11|Alcon Inc.|Silicone hydrogel materials with chemically bound wetting agents|

---

TWI506333B|2008-12-05|2015-11-01|Novartis Ag|Ophthalmic devices for delivery of hydrophobic comfort agents and preparation method thereof|

---

US20100149482A1|2008-12-12|2010-06-17|Ammon Jr Daniel M|Contact lens|

---

US8534031B2|2008-12-30|2013-09-17|Bausch & Lomb Incorporated|Packaging solutions|

---

WO2010077708A1|2008-12-30|2010-07-08|Bausch & Lomb Incorporated|Packaging solutions|

---

JP5240520B2|2009-01-15|2013-07-17|星光Ｐｍｃ株式会社|Paper making method for applying creping adhesive to dryer|

---

CA2761218C|2009-05-22|2016-06-28|Novartis Ag|Actinically-crosslinkable siloxane-containing copolymers|

---

WO2010133680A1|2009-05-22|2010-11-25|Novartis Ag|Actinically-crosslinkable siloxane-containing copolymers|

---

WO2011005937A2|2009-07-09|2011-01-13|Bausch & Lomb Incorporated|Mono ethylenically unsaturated polymerizable group containing polycarbosiloxane monomers|

---

US7915323B2|2009-07-09|2011-03-29|Bausch & Lamb Incorporated|Mono ethylenically unsaturated polycarbosiloxane monomers|

---

CN102597856B|2009-11-04|2014-07-23|诺华股份有限公司|A silicone hydrogel lens with a grafted hydrophilic coating|

---

TWI483996B|2009-12-08|2015-05-11|Novartis Ag|A silicone hydrogel lens with a covalently attached coating|

---

KR102057814B1|2010-07-30|2019-12-19|노파르티스 아게|A silicone hydrogel lens with a crosslinked hydrophilic coating|

---

BR112013002154A2|2010-07-30|2016-05-31|Novartis Ag|amphiphilic polysiloxane prepolymers and their uses|

---

EP2637847B1|2010-11-10|2014-07-23|Novartis AG|Method for making contact lenses|

---

EP2718751B1|2011-06-09|2015-07-22|Novartis AG|Silicone hydrogel lenses with nano-textured surfaces|JPH06122238A|1992-08-28|1994-05-06|Mitsubishi Electric Corp|Sheet carrying equipment|

---

JP3947575B2|1994-06-10|2007-07-25|Ｈｏｙａ株式会社|Conductive oxide and electrode using the same|

---

TW385375B|1996-07-26|2000-03-21|Asahi Glass Co Ltd|Transparent conductive film and forming method for transparent electrode|

---

US9322958B2|2004-08-27|2016-04-26|Coopervision International Holding Company, Lp|Silicone hydrogel contact lenses|

---

US20150219928A1|2006-02-10|2015-08-06|Johnson & Johnson Vision Care, Inc.|Comfortable ophthalmic device and methods of its production|

---

JP5154231B2|2005-02-14|2013-02-27|ジョンソン・アンド・ジョンソン・ビジョン・ケア・インコーポレイテッド|Comfortable ophthalmic device and its manufacturing method|

---

TWI506333B|2008-12-05|2015-11-01|Novartis Ag|Ophthalmic devices for delivery of hydrophobic comfort agents and preparation method thereof|

---

US9522980B2|2010-05-06|2016-12-20|Johnson & Johnson Vision Care, Inc.|Non-reactive, hydrophilic polymers having terminal siloxanes and methods for making and using the same|

---

KR102057814B1|2010-07-30|2019-12-19|노파르티스 아게|A silicone hydrogel lens with a crosslinked hydrophilic coating|

---

US8524215B2|2010-08-02|2013-09-03|Janssen Biotech, Inc.|Absorbable PEG-based hydrogels|

---

EP2681613B1|2011-02-28|2018-10-24|CooperVision International Holding Company, LP|Silicone hydrogel contact lenses|

---

US9170349B2|2011-05-04|2015-10-27|Johnson & Johnson Vision Care, Inc.|Medical devices having homogeneous charge density and methods for making same|

---

US20130203813A1|2011-05-04|2013-08-08|Johnson & Johnson Vision Care, Inc.|Medical devices having homogeneous charge density and methods for making same|

---

EP2780748B1|2011-11-15|2016-01-13|Novartis AG|A silicone hydrogel lens with a crosslinked hydrophilic coating|

---

US8798332B2|2012-05-15|2014-08-05|Google Inc.|Contact lenses|

---

US20130313733A1|2012-05-25|2013-11-28|Ivan Nunez|Method of making a fully polymerized uv blocking silicone hydrogel lens|

---

US8807745B2|2012-05-25|2014-08-19|Bausch & Lomb Incorporated|Fully polymerized UV blocking silicone hydrogel lens|

---

EP3296334A1|2012-05-25|2018-03-21|Johnson & Johnson Vision Care Inc.|Polymers and nanogel materials and methods for making and using the same|

---

US9297929B2|2012-05-25|2016-03-29|Johnson & Johnson Vision Care, Inc.|Contact lenses comprising water soluble N- acrylamide polymers or copolymers|

---

US9244196B2|2012-05-25|2016-01-26|Johnson & Johnson Vision Care, Inc.|Polymers and nanogel materials and methods for making and using the same|

---

US9075187B2|2012-05-25|2015-07-07|Bausch & Lomb Incorporated|Fully polymerized UV blocking silicone hydrogel lens|

---

US10073192B2|2012-05-25|2018-09-11|Johnson & Johnson Vision Care, Inc.|Polymers and nanogel materials and methods for making and using the same|

---

AU2013266649B2|2012-05-25|2016-04-14|Bausch & Lomb Incorporated|Fully polymerized UV blocking silicone hydrogel lens|

---

US20130323291A1|2012-05-31|2013-12-05|Biocoat Incorporated|Hydrophilic and non-thrombogenic polymer for coating of medical devices|

---

CA2870333C|2012-06-14|2016-10-04|Novartis Ag|Azetidinium-containing copolymers and uses thereof|

---

US9523865B2|2012-07-26|2016-12-20|Verily Life Sciences Llc|Contact lenses with hybrid power sources|

---

US8857981B2|2012-07-26|2014-10-14|Google Inc.|Facilitation of contact lenses with capacitive sensors|

---

US9158133B1|2012-07-26|2015-10-13|Google Inc.|Contact lens employing optical signals for power and/or communication|

---

US9298020B1|2012-07-26|2016-03-29|Verily Life Sciences Llc|Input system|

---

US8919953B1|2012-08-02|2014-12-30|Google Inc.|Actuatable contact lenses|

---

US9696564B1|2012-08-21|2017-07-04|Verily Life Sciences Llc|Contact lens with metal portion and polymer layer having indentations|

---

US8971978B2|2012-08-21|2015-03-03|Google Inc.|Contact lens with integrated pulse oximeter|

---

US9111473B1|2012-08-24|2015-08-18|Google Inc.|Input system|

---

US9395468B2|2012-08-27|2016-07-19|Ocular Dynamics, Llc|Contact lens with a hydrophilic layer|

---

US8820934B1|2012-09-05|2014-09-02|Google Inc.|Passive surface acoustic wave communication|

---

US20140192315A1|2012-09-07|2014-07-10|Google Inc.|In-situ tear sample collection and testing using a contact lens|

---

US9398868B1|2012-09-11|2016-07-26|Verily Life Sciences Llc|Cancellation of a baseline current signal via current subtraction within a linear relaxation oscillator-based current-to-frequency converter circuit|

---

US10010270B2|2012-09-17|2018-07-03|Verily Life Sciences Llc|Sensing system|

---

US9326710B1|2012-09-20|2016-05-03|Verily Life Sciences Llc|Contact lenses having sensors with adjustable sensitivity|

---

US8960898B1|2012-09-24|2015-02-24|Google Inc.|Contact lens that restricts incoming light to the eye|

---

US8870370B1|2012-09-24|2014-10-28|Google Inc.|Contact lens that facilitates antenna communication via sensor impedance modulation|

---

US8979271B2|2012-09-25|2015-03-17|Google Inc.|Facilitation of temperature compensation for contact lens sensors and temperature sensing|

---

US8989834B2|2012-09-25|2015-03-24|Google Inc.|Wearable device|

---

US20140088372A1|2012-09-25|2014-03-27|Google Inc.|Information processing method|

---

US8960899B2|2012-09-26|2015-02-24|Google Inc.|Assembling thin silicon chips on a contact lens|

---

US9884180B1|2012-09-26|2018-02-06|Verily Life Sciences Llc|Power transducer for a retinal implant using a contact lens|

---

US8821811B2|2012-09-26|2014-09-02|Google Inc.|In-vitro contact lens testing|

---

US8985763B1|2012-09-26|2015-03-24|Google Inc.|Contact lens having an uneven embedded substrate and method of manufacture|

---

US9063351B1|2012-09-28|2015-06-23|Google Inc.|Input detection system|

---

US8965478B2|2012-10-12|2015-02-24|Google Inc.|Microelectrodes in an ophthalmic electrochemical sensor|

---

US9176332B1|2012-10-24|2015-11-03|Google Inc.|Contact lens and method of manufacture to improve sensor sensitivity|

---

US9757056B1|2012-10-26|2017-09-12|Verily Life Sciences Llc|Over-molding of sensor apparatus in eye-mountable device|

---

CN104837612B|2012-12-11|2017-08-25|诺华股份有限公司|The method that coating is put on silicone hydrogel lens|

---

SG11201504763UA|2012-12-17|2015-07-30|Novartis Ag|Method for making improved uv-absorbing ophthalmic lenses|

---

US9161598B2|2012-12-21|2015-10-20|Coopervision International Holding Company, Lp|Ophthalmic devices for delivery of beneficial agents|

---

US20140178327A1|2012-12-21|2014-06-26|Coopervision International Holding Company, Lp|Antimicrobial Ophthalmic Devices|

---

US8874182B2|2013-01-15|2014-10-28|Google Inc.|Encapsulated electronics|

---

US10441676B2|2013-01-15|2019-10-15|Medicem Institute s.r.o.|Light-adjustable hydrogel and bioanalogic intraocular lens|

---

WO2014111769A1|2013-01-15|2014-07-24|Medicem OphthalmicLimited|Bioanalogic intraocular lens|

---

US9289954B2|2013-01-17|2016-03-22|Verily Life Sciences Llc|Method of ring-shaped structure placement in an eye-mountable device|

---

US20140209481A1|2013-01-25|2014-07-31|Google Inc.|Standby Biasing Of Electrochemical Sensor To Reduce Sensor Stabilization Time During Measurement|

---

US9636016B1|2013-01-25|2017-05-02|Verily Life Sciences Llc|Eye-mountable devices and methods for accurately placing a flexible ring containing electronics in eye-mountable devices|

---

US9250357B2|2013-03-15|2016-02-02|Johnson & Johnson Vision Care, Inc.|Silicone-containing contact lens having reduced amount of silicon on the surface|

---

US9161712B2|2013-03-26|2015-10-20|Google Inc.|Systems and methods for encapsulating electronics in a mountable device|

---

US9113829B2|2013-03-27|2015-08-25|Google Inc.|Systems and methods for encapsulating electronics in a mountable device|

---

JP2016524178A|2013-04-30|2016-08-12|クーパーヴィジョン インターナショナル ホウルディング カンパニー リミテッド パートナーシップ|Primary amine-containing silicone hydrogel contact lenses and related compositions and methods|

---

SG2013035662A|2013-05-08|2014-12-30|Menicon Singapore Pte Ltd|Systems and methods for printing on a contact lens|

---

US9950483B2|2013-05-29|2018-04-24|Novartis Ag|Method for determining the surface concentration of carboxyl groups on a lens|

---

US20140371560A1|2013-06-14|2014-12-18|Google Inc.|Body-Mountable Devices and Methods for Embedding a Structure in a Body-Mountable Device|

---

US9084561B2|2013-06-17|2015-07-21|Google Inc.|Symmetrically arranged sensor electrodes in an ophthalmic electrochemical sensor|

---

US9948895B1|2013-06-18|2018-04-17|Verily Life Sciences Llc|Fully integrated pinhole camera for eye-mountable imaging system|

---

US9685689B1|2013-06-27|2017-06-20|Verily Life Sciences Llc|Fabrication methods for bio-compatible devices|

---

US9492118B1|2013-06-28|2016-11-15|Life Sciences Llc|Pre-treatment process for electrochemical amperometric sensor|

---

US9814387B2|2013-06-28|2017-11-14|Verily Life Sciences, LLC|Device identification|

---

US9028772B2|2013-06-28|2015-05-12|Google Inc.|Methods for forming a channel through a polymer layer using one or more photoresist layers|

---

US9307901B1|2013-06-28|2016-04-12|Verily Life Sciences Llc|Methods for leaving a channel in a polymer layer using a cross-linked polymer plug|

---

JP5452756B1|2013-07-02|2014-03-26|Ｈｏｙａ株式会社|Method for producing silicone-containing copolymer molded article having hydrophilic surface and silicone hydrogel contact lens having hydrophilic surface|

---

EP3052534B1|2013-09-30|2019-05-01|Novartis AG|Method for making uv-absorbing ophthalmic lenses|

---

US9568645B2|2013-09-30|2017-02-14|Novartis Ag|Silicone hydrogel lenses with relatively-long thermal stability|

---

WO2015066255A1|2013-10-31|2015-05-07|Novartis Ag|Method for producing ophthalmic lenses|

---

CN104628943B|2013-11-15|2016-09-21|中国石油化工股份有限公司|A kind of acrylamide based copolymer and its preparation method and application|

---

CA2930552A1|2013-11-15|2015-05-21|Ocular Dynamics, Llc|Contact lens with a hydrophilic layer|

---

US9808966B2|2013-12-02|2017-11-07|Novartis Ag|Process for making molded devices|

---

EP3079888B1|2013-12-13|2018-01-31|Novartis AG|Method for making contact lenses|

---

HUE038809T2|2013-12-17|2018-11-28|Novartis Ag|A silicone hydrogel lens with a crosslinked hydrophilic coating|

---

US9654674B1|2013-12-20|2017-05-16|Verily Life Sciences Llc|Image sensor with a plurality of light channels|

---

US9572522B2|2013-12-20|2017-02-21|Verily Life Sciences Llc|Tear fluid conductivity sensor|

---

US9366570B1|2014-03-10|2016-06-14|Verily Life Sciences Llc|Photodiode operable in photoconductive mode and photovoltaic mode|

---

US9184698B1|2014-03-11|2015-11-10|Google Inc.|Reference frequency from ambient light signal|

---

US9789655B1|2014-03-14|2017-10-17|Verily Life Sciences Llc|Methods for mold release of body-mountable devices including microelectronics|

---

US9618773B2|2014-04-08|2017-04-11|Novartis Ag|Ophthalmic lenses with oxygen-generating elements therein|

---

JP6378359B2|2014-04-25|2018-08-22|ノバルティス アーゲー|Hydrophilized carbosiloxane vinyl monomer|

---

CN106716233B|2014-05-09|2019-11-05|茵洛有限公司|Hydrogel contact lens and preparation method thereof with wettable surfaces|

---

CN106999295A|2014-07-21|2017-08-01|实体科学有限责任公司|Contact lenses and the method for preparing contact lenses|

---

SG11201700278UA|2014-08-26|2017-03-30|Novartis Ag|Poly-epichlorohydrin copolymers and uses thereof|

---

HUE046948T2|2014-08-26|2020-03-30|Novartis Ag|Method for applying stable coating on silicone hydrogel contact lenses|

---

US10266656B2|2014-09-23|2019-04-23|Momentive Performance Materials Gmbh|Silicone compounds and compositions thereof for the treatment of amino acid based substrates|

---

MX2017003939A|2014-09-26|2017-06-26|Novartis Ag|Polymerizable polysiloxanes with hydrophilic substituents.|

---

US9408684B2|2014-10-03|2016-08-09|Soft Health Technologies, Llc|Systems and methods for incontinence control|

---

CN107003541B|2014-10-08|2020-11-17|印诺维嘉有限公司|Contact lens and method and system for constructing contact lens|

---

CN104406927B|2014-11-28|2017-09-29|华南理工大学|One kind generates monitoring method and system based on optical hydrate|

---

EP3229851A4|2014-12-09|2018-08-01|Tangible Science LLC|Medical device coating with a biocompatible layer|

---

US9981436B2|2014-12-17|2018-05-29|Novartis Ag|Reusable lens molds and methods of use thereof|

---

CN107000344B|2014-12-17|2019-06-07|诺华股份有限公司|The lens mold and its application method that can be reused|

---

CN104793349B|2015-01-29|2017-09-19|广州琦安琦视觉科技有限公司|One kind has antiultraviolet, diffraction light and blue light multi-functional contact lenses|

---

CA2978635A1|2015-03-11|2016-09-15|University Of Florida Research Foundation, Inc.|Mesh size control of lubrication in gemini hydrogels|

---

CN106033150B|2015-03-17|2019-04-05|专力国际开发股份有限公司|Composite contact lens|

---

HUE048048T2|2015-05-07|2020-05-28|Alcon Inc|Method for producing contact lenses with durable lubricious coatings thereon|

---

US10269670B2|2015-06-24|2019-04-23|Sumitomo Osaka Cement Co., Ltd.|Curable silicone resin composition, silicone resin composite, photosemiconductor light emitting device, luminaire and liquid crystal imaging device|

---

JP6791143B2|2015-07-31|2020-11-25|日産化学株式会社|Liquid crystal alignment agent, liquid crystal alignment film and liquid crystal display element|

---

JP6592189B2|2015-09-04|2019-10-16|ノバルティス アーゲー|Method for manufacturing a contact lens having a durable lubricious coating thereon|

---

JP6680870B2|2015-09-04|2020-04-15|アルコン インク．|Soft silicone medical device with a durable lubricious coating thereon|

---

CN108463323B|2015-11-11|2020-10-13|万福克斯视觉公司|Adjustable lens with cavity|

---

BR112018010180A2|2015-12-03|2018-11-21|Novartis Ag|contact lens packaging solutions|

---

EP3391101B1|2015-12-15|2020-07-08|Alcon Inc.|Method for applying stable coating on silicone hydrogel contact lenses|

---

US10227435B2|2015-12-15|2019-03-12|Novartis Ag|Polymerizable polysiloxanes with hydrophilic substituents|

---

SG11201803724TA|2015-12-15|2018-06-28|Novartis Ag|Method for producing contact lenses with a lubricious surface|

---

BR112018011867A2|2015-12-15|2018-11-27|Novartis Ag|hydrophilized polycarbonosiloxanes vinyl cross-linking agents and uses thereof|

---

EP3391100B1|2015-12-15|2020-08-12|Alcon Inc.|Amphiphilic branched polydiorganosiloxane macromers|

---

WO2017103705A1|2015-12-17|2017-06-22|Novartis Ag|Reusable lens molds and methods of use thereof|

---

RU2612121C1|2016-01-27|2017-03-02|Федеральное государственное бюджетное научное учреждение "Научно-исследовательский институт глазных болезней"|Silicone hydrogel therapeutic soft contact lens|

---

JP6807011B2|2016-02-15|2021-01-06|日油株式会社|Contact lenses with a phosphorylcholine group-containing hydrophilic polymer on the surface|

---

JP6606294B2|2016-02-22|2019-11-13|ノバルティスアーゲー|Soft silicone medical device|

---

US11045574B2|2016-02-22|2021-06-29|Toray Industries, Inc.|Device and production method for the same|

---

EP3395376A4|2016-02-22|2020-01-01|Toray Industries, Inc.|Device and production method for same|

---

EP3427104A4|2016-03-11|2019-11-20|Innovega Inc.|Contact lens|

---

TWI716586B|2016-04-28|2021-01-21|日商日油股份有限公司|Surface treatment agent for contact lens and contact lens|

---

WO2018055488A1|2016-09-20|2018-03-29|Novartis Ag|Method for producing a water-soluble thermally-crosslinkable polymeric material|

---

EP3516431B1|2016-09-20|2021-03-03|Alcon Inc.|Process for producing contact lenses with durable lubricious coatings thereon|

---

US10449739B2|2016-09-20|2019-10-22|Novartis Ag|Hydrogel contact lenses with lubricious coating thereon|

---

CN109690362A|2016-09-20|2019-04-26|诺华股份有限公司|On it with the coloured hydro-gel contact lens of lubricant coating|

---

US10850461B2|2016-09-27|2020-12-01|Coopervision International Holding Company, Lp|Method of manufacturing contact lenses|

---

JP6839295B2|2016-10-11|2021-03-03|アルコン インク．|Polymerizable Polydimethylsiloxane-Polyoxyalkylene Block Copolymer|

---

US10301451B2|2016-10-11|2019-05-28|Novartis Ag|Chain-extended polydimethylsiloxane vinylic crosslinkers and uses thereof|

---

HUE051063T2|2016-10-19|2021-03-01|Alcon Inc|Hydrophilic copolymer with one thiol-containing terminal group|

---

CA3034604C|2016-10-19|2021-03-09|Novartis Ag|Hydrophilic copolymer with pendant thiol groups|

---

WO2018078542A1|2016-10-26|2018-05-03|Novartis Ag|Soft contact lenses with a lubricious coating covalently-attached thereon|

---

CA3035490C|2016-10-26|2021-09-14|Novartis Ag|Amphiphilic branched polydiorganosiloxane macromers|

---

KR101910842B1|2016-10-27|2018-10-23|연세대학교 산학협력단|Ophthalmic composition with hydrophilic surface, and preparation method thereof|

---

HUE053839T2|2016-10-31|2021-07-28|Alcon Inc|Method for producing surface coated contact lenses with wearing comfort|

---

KR101872120B1|2016-11-21|2018-06-27|대구가톨릭대학교산학협력단|Contact lens with high-water-content surface layer and method for fabricating the same|

---

EP3587464A4|2017-02-21|2021-03-24|Mitsui Chemicals, Inc.|Polymerizable composition of optical materials, optical material obtained from said composition, and plastic lens|

---

TWI610802B|2017-04-10|2018-01-11|明基材料股份有限公司|Ophthalmic lens and manufacturing method thereof|

---

US10509238B2|2017-04-14|2019-12-17|Verily Life Sciences Llc|Electrowetting opthalmic optics including gas-permeable components|

---

KR20200003797A|2017-05-11|2020-01-10|도레이 카부시키가이샤|Method of manufacturing a medical device|

---

EP3928967A4|2017-06-07|2021-12-29|Alcon Inc|Silicone hydrogel contact lenses|

---

WO2018224975A1|2017-06-07|2018-12-13|Novartis Ag|Silicone hydrogel contact lenses|

---

HUE055667T2|2017-06-07|2021-12-28|Alcon Inc|Method for producing silicone hydrogel contact lenses|

---

CN107796674B|2017-07-04|2021-03-16|程树军|Method for evaluating eye irritation injury and repair by long-term culture of animal cornea|

---

TWI640557B|2017-07-05|2018-11-11|晶碩光學股份有限公司|Contact lens with surface modification and the method for its preparation|

---

EP3655446A1|2017-07-18|2020-05-27|Alcon Inc.|Polyacrylamide-based copolymers with carboxyl-terminated pendant chains|

---

CN110831991A|2017-07-18|2020-02-21|爱尔康公司|Copolymers based on polyacrylamide containing phosphorylcholine|

---

KR20200026294A|2017-08-01|2020-03-10|가부시키가이샤 시드|Endoscope Hood|

---

CN110944686B|2017-08-09|2021-12-28|东丽株式会社|Medical device and method of manufacturing the same|

---

EP3668447A4|2017-08-17|2021-05-12|The Trustees of Princeton University|Ultrathin interfacial layer on a hydrogel to direct its surface properties and cell adhesion|

---

US10809181B2|2017-08-24|2020-10-20|Alcon Inc.|Method and apparatus for determining a coefficient of friction at a test site on a surface of a contact lens|

---

EP3676082A1|2017-08-29|2020-07-08|Alcon Inc.|Cast-molding process for producing contact lenses|

---

KR101944008B1|2017-09-18|2019-01-30| 제이씨바이오|Transparent hydrogel membrane containing hyaluronic acid and contact lens using same|

---

US11029538B2|2017-10-25|2021-06-08|Coopervision International Limited|Contact lenses having an ion-impermeable portion and related methods|

---

US11067831B2|2017-10-30|2021-07-20|Coopervision International Limited|Methods of manufacturing coated contact lenses|

---

US20200385653A1|2017-12-04|2020-12-10|Nof Corporation|Soft contact lens treatment solution|

---

AU2018381954A1|2017-12-13|2020-05-14|Alcon Inc.|Weekly and monthly disposable water gradient contact lenses|

---

WO2019142132A1|2018-01-22|2019-07-25|Novartis Ag|Cast-molding process for producing uv-absorbing contact lenses|

---

WO2019162881A1|2018-02-26|2019-08-29|Novartis Ag|Silicone hydrogel contact lenses|

---

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---

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---

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---

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---

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---

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---

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---

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---

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---

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---

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---

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---

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---

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---

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---

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---

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---

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---

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---

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---

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---

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---

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---

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---

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---

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---

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---

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---

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---

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---

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---

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---

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法律状态:
2019-08-20| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|

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2019-09-03| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|

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2020-02-11| B25A| Requested transfer of rights approved|Owner name: ALCON INC. (CH) |

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2020-07-21| B06A| Patent application procedure suspended [chapter 6.1 patent gazette]|

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2020-09-24| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|

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2020-12-15| B16A| Patent or certificate of addition of invention granted [chapter 16.1 patent gazette]|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 29/07/2011, OBSERVADAS AS CONDICOES LEGAIS. |

优先权:

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申请号 | 申请日 | 专利标题

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US36910210P| true| 2010-07-30|2010-07-30|

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US61/369,102|2010-07-30|

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US201161448478P| true| 2011-03-02|2011-03-02|

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US61/448,478|2011-03-02|

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PCT/US2011/045808|WO2012016096A1|2010-07-30|2011-07-29|Silicone hydrogel lenses with water-rich surfaces|BR122020017237-1A| BR122020017237B1|2010-07-30|2011-07-29|hydrated silicone hydrogel lenses|

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BR122013012250-8A| BR122013012250B1|2010-07-30|2011-07-29|silicone hydrogel contact lenses featuring a layered structural configuration and a gradient of water content from the inside to the outside of the silicone hydrogel contact lens|

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BR122020017231-2A| BR122020017231B1|2010-07-30|2011-07-29|hydrated silicone hydrogel lenses|