METHOD FOR MANUFACTURING A HYDROGEL CONTACT LENS, HYDROGEL CONTACT LENS AND BATCH AND PACKAGING OF S

专利摘要:
phosphine-containing hydrogel contact lenses are described hydrogel contact lenses which are derived from a polymerizable composition including at least one hydrophilic monomer and at least one phosphine-containing component. the contact lens hydrogel can be a silicone hydrogel or a silicone-free hydrogel. the use of polymerizable compositions comprising a phosphine-containing component that can be cured under both inert and air atmospheres, and can be used to form hydrogel contact lenses having improved shape-keeping properties, having improved resistance to discoloration. batches of hydrogel contact lenses and methods of preparing hydrogel contact lenses are also described.
公开号:BR112013021486B1
申请号:R112013021486-4
申请日:2012-02-23
公开日:2021-06-22
发明作者:Guigui Wang；Yun Zhang；Yuwen Liu；Ye Hong；Charlie Chen；Peter Zhu
申请人:Coopervision International Holding Company, Lp；
IPC主号:

专利说明:

[0001] This application claims benefit under 35 USC §119(e) of prior US Provisional Patent Application No. 61/447,152, filed February 28, 2011, which is incorporated in its entirety by reference herein. . Field
[0002] The present disclosure is directed to hydrogel silicone contact lenses and related compositions and methods. Background
[0003] Hydrogel contact lenses, commercially and clinically, including silicone hydrogel contact lenses, currently dominate the contact lens market. The maturing market for hydrogel lenses puts pressure on lens manufacturers to increase quality while reducing cost.
[0004] Some documents describing silicone hydrogel contact lenses include: US4711943, US5712327, US5760100, US7825170, US6867245, US20060063852, US20070296914, US7572841, US20090299022, US20090234089, and US20100249356, each of which is incorporated in its entirety , by reference, in this document.
[0005] In the polymerization of polymerizable compositions via free radicals, an inhibition of the reaction may occur as a result of the presence of oxygen, in the form of dissolved oxygen gas present in the polymerizable composition, or in the form of oxygen gas present in the vapor space surrounding the mold before or during the healing process. Nitrogen purging and/or the use of vacuum conditions to remove unwanted oxygen from the polymerizable composition, mold cavity, and/or curing oven can be used to keep oxygen levels low before and during the curing process. cure. However, the use of nitrogen purging and vacuum conditions can significantly increase the cost of the manufacturing process, manufacturing equipment, and thus the final lens product.
[0006] Additionally, regardless of the type of atmosphere present during filling and curing, many polymerizable compositions do not result in hydrogel contact lenses that are ophthalmically acceptable, as lenses formed from these polymerizable compositions do not adequately preserve its molded shape after hydration or after autoclaving. In other words, many polymerizable compositions produce contact lenses having undesirable characteristics, such as being discolored, deformed, or crooked, or not retaining their molded shapes, etc., even when the polymerizable compositions are prepared and cured under conditions of low oxygen or an inert atmosphere. Thus, there continues to be a need for new hydrogel contact lens formulations and manufacturing methods, particularly lens formulations that do not require expensive inert atmospheres to be provided during curing, or that use inexpensive ingredients to improve. lens life, reduce lens deformation, or improve lens shape conservation. Summary
[0007] The present disclosure is directed to polymerizable compositions, hydrogel contact lenses that are formed by reaction of polymerizable compositions to form polymeric lens bodies, to batches of hydrogel contact lenses, to contact lens packaging of hydrogel, and to methods of making hydrogel contact lenses from polymerizable compositions.
[0008] The polymerizable compositions of the present disclosure comprise (a) at least one hydrophilic monomer, and (b) at least one phosphine-containing compound, where the phosphine-containing compound is present in an unoxidized form at the time it is combined with the at least one hydrophilic monomer in the polymerizable composition. The phosphine-containing compound, which is present in an unoxidized form when combined with the hydrophilic monomer of the polymerizable composition, may be a compound of structure (1):
where X1, X2, and X3 are the same or different and are an alkyl group or an aryl group, or a polymerizable group. As used herein, an aryl group is understood to refer to a functional group substituent derived from an aromatic ring. In one example, the phosphine-containing compound can be a polymerizable phosphine-containing compound. The structure of structure (1) can comprise one polymerizable group, or it can comprise more than one polymerizable group. The one or more polymerizable groups of structure (1) may comprise an acrylate group, such as, for example, a methacrylate group. The one or more polymerizable groups of structure (1) may comprise a non-acrylate vinyl-containing functional group, i.e., a functional group having a carbon-carbon double bond that is not part of an acrylate functional group. The phosphine-containing compound may comprise a tertiary phosphine-containing compound, that is, a compound having a tertiary phosphine group as part of its molecular structure. As used herein, a tertiary phosphine is understood to refer to an organophosphorus compound, where the phosphorus atom is bonded to three alkyl groups or three aryl groups or polymerizable groups or any combination of three groups selected from alkyl groups , aryl groups and polymerizable groups. The phosphine-containing compound can comprise triphenylphosphine. The phosphine-containing compound may comprise diphenyl(4-vinylphenyl)phosphine. The phosphine-containing compound comprises both triphenylphosphine and diphenyl(4-vinylphenyl)phosphine. The phosphine compound can be present in the polymerizable composition in an amount of 0.01 to 5 parts of the unit by weight.
[0009] The polymerizable composition may contain an amount of the phosphine-containing compound, which is present in an unoxidized form when combined with the hydrophilic monomer, that is effective to expel at least a portion of the oxygen present in the polymerizable composition during manufacture of a contact lens.
[00010] The polymerizable composition may contain an amount of the phosphine-containing compound, which is present in an unoxidized form when combined with the hydrophilic monomer, that is effective to produce a polymeric lens body having a reduced amount of lifting. axial edge (AEL), as compared to a second hydrogel contact lens body formed from a second polymerizable composition, substantially identical to the polymerizable composition, except without the phosphine-containing compound and using a manufacturing process substantially identical to the hydrogel contact lens manufacturing process.
[00011] The polymerizable composition may contain an amount of the phosphine-containing compound, which is present in an unoxidized form when combined with the hydrophilic monomer, that is effective in reducing the deformation of the hydrogel contact lens, as compared to a second hydrogel contact lens body formed from a second polymerizable composition substantially identical to the polymerizable composition, except without the phosphine-containing compound and using a manufacturing process substantially identical to the hydrogel contact lens manufacturing process.
[00012] The polymerizable composition may contain an amount of the phosphine-containing compound, which is present in an unoxidized form when combined with the hydrophilic monomer, that is effective to reduce contact lens discoloration for at least 1 year when stored at room temperature, as compared to a second contact lens formed from a second polymerizable composition substantially identical to the first polymerizable composition, except without the phosphine-containing compound and using a manufacturing process substantially identical to the process manufacturing hydrogel contact lens.
[00013] The polymerizable composition may optionally comprise at least one siloxane monomer. The polymerizable composition may optionally comprise at least one crosslinking agent. The polymerizable composition can further comprise at least one hydrophobic monomer. Optionally, the ingredients of the polymerizable composition can additionally include at least one initiator, or at least one organic diluent, or at least one surfactant, or at least one coloring agent, or at least one UV absorber, or at least one agent. transfer chain, or combinations thereof.
[00014] As discussed above, the polymerizable composition is reacted to form a polymeric lens body, which is further processed to prepare a hydrogel contact lens. A batch of hydrogel contact lenses can be prepared by preparing a plurality of hydrogel contact lenses. The lot of contact lenses may have lens properties that make them acceptable for use as contact lenses. For example, contact lenses can have adequate levels of shape conservation. In one example, the level of shape conservation of the hydrogel contact lens can be determined by measuring the axial edge elevation (AEL) exhibited by an individual lens, or by measuring the edge elevation variance axial (AEL) average for a lot of lenses. In a particular example, a batch of lenses may have an average axial edge elevation (AEL) variance of less than plus or minus 50% over a time period of two weeks to seven years when stored at room temperature. or, when stored under accelerated shelf life conditions, for a period of time and temperature equivalent to storage of two weeks to seven years at room temperature, as determined based on at least 20 individual lenses in the batch, the percentage variance of the AEP determined for each of the individual lenses by the following equation (A): ((AELFinal - AELInitial) / AELInitial) x 100 (A).
[00015] The present disclosure is also directed to hydrogel contact lens packaging. The hydrogel contact lens package may comprise a polymeric lens body which is the reaction product of a polymerizable composition, the polymerizable composition comprising (a) at least one hydrophilic monomer, and (b) at least one phosphine-containing compound, wherein the phosphine-containing compound is present in an unoxidized form at the time it is combined with the at least one hydrophilic monomer in the polymerizable composition; a conditioning solution comprising a lens hydrating agent; and a contact lens package base element having a cavity configured to hold the contact lens body and packaging solution, and a seal joined to the base element configured to hold the contact lens and the packaging solution. conditioning in a sterile condition for a duration of time equivalent to the service life at room temperature of the contact lens.
[00016] The present disclosure is also directed to a method of manufacturing a hydrogel contact lens. The method may comprise providing a polymerizable composition comprising (a) at least one hydrophilic monomer, and (b) at least one phosphine-containing compound, wherein the phosphine-containing compound is present in an unoxidized form at the time it is combined with the at least one hydrophilic monomer in the polymerizable composition; and reacting the polymerizable composition to form a polymeric lens body. In one example, the polymerizable composition reaction is conducted in an atmosphere comprising air. In another example, the polymerizable composition reaction is conducted in an atmosphere consisting essentially of air. In another example, the polymerizable composition reaction is conducted in an atmosphere comprising an inert gas in a concentration greater than that found in air. In another example, the reaction comprises casting molding the polymerizable composition in a contact lens molding unit to form a polymeric lens body.
[00017] The present method may further comprise contacting the polymeric lens body with a washing liquid to remove extractable material from the polymeric lens body. In some examples, contacting removes a portion of the at least one phosphine compound from the polymeric lens body.
[00018] The present method may further comprise oxidizing at least a part of the phosphine-containing compound present in the polymeric lens body, or in the hydrogel contact lens. Oxidation can occur after the phosphine-containing compound has been combined with the hydrophilic monomer in the polymerizable composition. Oxidation can occur before the polymerizable composition is inserted into a section of the contact lens mold. Oxidation can occur after the polymerizable composition has been inserted into a section of the contact lens mold. Oxidation can occur before the polymerizable composition is cured to form a polymeric lens body. Oxidation can occur during curing of the polymerizable composition to form a polymeric lens body.
[00019] It is to be understood that both the preceding general description and the following detailed description are illustrative and explanatory and are intended to provide a further explanation of the present invention as claimed.
[00020] The attached figures, which are incorporated in and constitute a part of this application, are exemplary illustrations of the present invention and, together with the description, serve to explain the principles of the present invention. Brief description of the design
[00021] FIG. 1 is a series of illustrations of hydrogel contact lenses.
[00022] FIG. 2 is a series of drawings illustrating axial edge elevation (AEL) measurement for different hydrogel contact lenses.
[00023] FIG. 3 is a series of photographs showing the hydrogel contact lenses having acceptable shape conservation and having unacceptable levels of shape deformation. Detailed Description
[00024] As described in this document, it has now been found that hydrogel contact lenses can be formed from polymerizable compositions comprising (a) at least one hydrophilic monomer, and (b) at least one phosphine-containing compound, where the phosphine-containing compound is present in an unoxidized form when it is combined with the at least one hydrophilic monomer in the polymerizable composition.
[00025] The present hydrogel contact lenses comprise, or consist of, hydrated lens bodies comprising a polymeric component and a liquid component. The polymer component comprises units of at least one hydrophilic monomer. The hydrophilic monomer is understood to be a non-silicone polymerizable ingredient having only one polymerizable functional group present in its molecular structure. It can, therefore, be understood that the polymeric component is the reaction product of a polymerizable composition comprising one or more hydrophilic monomers, and can optionally include units of any additional polymerizable ingredients present in the polymerizable composition. The ingredients of the polymerizable composition may optionally and additionally comprise additional monomers or macromers or prepolymers or polymers, or combinations thereof. The additional monomers or macromers or prepolymers or polymers, or combinations thereof, can be silicon-containing compounds or they can be non-silicon compounds. As used herein, a non-silicon compound is understood to be a compound that does not have a silicon atom in its molecular structure. The phosphine-containing compound, which is present in an unoxidized form when combined with the hydrophilic monomer, as well as the optional additional ingredients of the polymerizable composition can be polymerizable ingredients or non-polymerizable ingredients. As used herein, a polymerizable ingredient is understood to be a compound that has a polymerizable double bond as part of its molecular structure. Thus, a non-polymerizable ingredient does not have a polymerizable double bond as part of its molecular structure. When present in the polymerizable composition, the at least one crosslinking agent, the at least one hydrophilic monomer, and the at least one hydrophobic monomer of the polymerizable composition are understood to be non-silicon polymerizable ingredients. As used herein, the at least one crosslinking agent may be understood to comprise a single crosslinking agent or comprise a crosslinking agent component composed of two or more crosslinking agents. Similarly, the at least one optional hydrophilic monomer may be understood to comprise a single hydrophilic monomer, or comprise a hydrophilic monomer component composed of two or more hydrophilic monomers. The at least one optional hydrophobic monomer may be understood to comprise a single hydrophobic monomer, or comprise a hydrophobic monomer component composed of two or more hydrophobic monomers. The at least one optional siloxane monomer may be understood to comprise a single siloxane monomer, or comprise a siloxane monomer component composed of two or more siloxane monomers. Additionally, the polymerizable composition may optionally include at least one initiator, or at least one organic diluent, or at least one surfactant, or at least one oxygen scavenger, or at least one coloring agent, or at least one absorber. of UV, or at least one chain transfer agent or any combination thereof. The at least one initiator, the at least one organic diluent, the at least one surfactant, the at least one oxygen scavenger, the at least one coloring agent, the at least one UV absorber, or the at least one agent Optional chain transfer agents are understood to be non-silicon ingredients, and may be non-polymerizable ingredients or polymerizable ingredients (ie, ingredients having a polymerizable functional group as part of their molecular structure).
[00026] The combination of polymer component and liquid component is present as a hydrated lens body, which is suitable for placement over a person's eye. The hydrated lens body has a generally convex anterior surface and a generally concave posterior surface, and has an equilibrium water content (EWC) greater than 10% weight by weight (w/w). Thus, the present contact lenses can be understood to be soft contact lenses, which, as used in this document, refers to contact lenses which, when fully hydrated, can be folded over without breaking.
[00027] As understood in the industry, a daily disposable contact lens is an unused contact lens that is removed from its sterile, sealed packaging (primary packaging), produced by a contact lens manufacturer, placed over the eye of a person, and is removed and discarded after the person wears the lens at the end of the day. Typically, the lens wear duration for disposable contact lenses daily is eight to fourteen hours, and they are then discarded after use. Daily disposable lenses are not cleaned or exposed to cleaning solutions prior to placement in the eye, as they are sterile prior to opening the package. A daily disposable hydrogel silicone contact lens is a disposable hydrogel silicone contact lens that is replaced daily. In contrast, non-daily disposable contact lenses are disposable contact lenses that are replaced less frequently than daily (eg, weekly, biweekly, or monthly). Non-daily disposable contact lenses are removed from the eye and cleaned with a cleaning solution on a regular basis, or are worn continuously without removing the eye. The present contact lenses can be either daily disposable contact lenses or non-daily disposable contact lenses. The present disclosure relates to polymerizable compositions comprising at least one phosphine-containing compound, which is present in an unoxidized form when combined with the hydrophilic monomer in the polymerizable composition, to polymeric lens bodies which are the products of reaction of these polymerizable compositions, to hydrogel contact lenses comprising these polymeric lens bodies in hydrated form, to packages comprising these hydrogel contact lenses and to a packaging solution in a sealed package, and to methods of manufacturing these lenses of hydrogel contact.
[00028] In one example, the present disclosure is directed to a polymerizable composition comprising at least one hydrophilic monomer and at least one phosphine-containing compound, where the phosphine-containing compound is present in an unoxidized form at the time it is combined with the at least one hydrophilic monomer in the polymerizable composition.
[00029] As discussed above, the phosphine-containing compound is present in an unoxidized form at the time it is combined with the at least one hydrophilic monomer in the polymerizable composition. In other words, the phosphine-containing compound is not a phosphine oxide-containing compound since it does not have an oxygen atom attached to the phosphorus atom of the phosphine group at the time it is added to the polymerizable composition. However, during the manufacturing process, the phosphine-containing compound can be oxidized to become a phosphine oxide-containing compound, such as, for example, by reaction with the oxygen present in the polymerizable composition, or by reaction with the oxygen present in a contact lens mold during the filling process, or by reacting with oxygen present in an atmosphere of a curing oven during a curing process, or by reacting with oxygen present in a wash solution following demolding and lens removal, or combinations thereof. The oxygen that reacts with the phosphine-containing compound during the manufacturing process may be present as dissolved oxygen gas, or as oxygen gas present in a mixture of gases, such as air, or as an oxidant, such as pe. - hydrogen oxide, or as a kind of reactive oxygen, such as singlet oxygen, or combinations thereof.
[00030] The phosphine-containing compound can be an organophosphorous compound. The phosphine-containing compound can be an organophosphorous compound having a tertiary phosphine present in its molecular structure, i.e., an organophorous compound where the phosphorus atom is attached to three alkyl groups or three aryl groups or polymerizable groups or any combination of three groups selected from alkyl groups, aryl groups and polymerizable groups. In one example, the phosphine-containing compound may have the structure represented by formula (1);
where X1, X2, and X3 are the same or different and are an alkyl group or an aryl group or a polymerizable group. The alkyl group and the aryl group can be unsubstituted or substituted. The alkyl group can be a C1 to C10 alkyl, or a C1 to C5 alkyl, or a C1 to C3 alkyl. The alkyl group can be a straight chain or a branched chain. The aryl group can be any functional group or substituent derived from a simple aromatic ring. The aryl group can comprise a single aromatic ring or a fused ring structure. The aryl group can be non-heterocyclic or heterocyclic. In one example, the aryl group can be phenyl, benzyl, tolyl, naphthalenyl, pyridyl, or quinolinyl. As shown by the structure, in this example the phosphine oxides are not included by the tertiary phosphine of structure (1).
[00031] In another example, the tertiary phosphine is trimethyl phosphine, triethyl phosphine, triisopropyl phosphine, tributyl phosphine, triisobutyl phosphine, tripentyl phosphine, triisopentyl phosphine, diethyl methyl phosphine, dimethyl phenyl phosphine, a dimethyl ethyl phosphine, diethyl propyl phosphine, triphenyl phosphine, tritolyl phosphine, tribenzyl phosphine, diethyl phenyl phosphine, and dipropyl phenyl phosphine.
[00032] Triphenyl phosphine (TPP) has the following general structure of formula (2):

Methods for preparing tertiary phosphine compounds of formula (1) are known, such as the methods illustrated in U.S. Patent Nos. 3,079,311, and 4,150,058, both of which are incorporated in their entirety herein by reference.
[00034] The phosphine-containing compound of the present disclosure, which is present in an unoxidized form when combined with the hydrophilic monomer, may, in some examples, be a polymerizable phosphine-containing compound. In other words, the structure of the phosphine-containing compound can include a polymerizable group, such as, for example, a vinyl group or an acrylate or methacrylate group. In one example, the phosphine-containing compound comprises a vinyl polymerizable group that is not part of an acrylate or methacrylate polymerizable group. The polymerizable phosphine-containing compound may be a phosphine-containing compound comprising at least one vinyl substituted aryl group. In one example, one, two or three of X1, X2, and X3 are an aryl group substituted with vinyl group, where the phosphine-containing compound can comprise at least one aryl group substituted with vinyl group. In a further example, the vinyl group can be vinyl, allyl, or other ethylenically unsaturated carbon chain group. In a particular example, the phosphine-containing compound may be diphenyl(4-vinylphenyl)phosphine (pTPP). Diphenyl(4-vinylphenyl)phosphine can be represented by formula (3):

[00035] The styrenic structure diphenyl(4-vinylphenyl)phosphine (pTPP) undergoes polymerization with the cure of the lens formulation.
[00036] In some examples, the phosphine-containing compound, which is present in an unoxidized form when combined with the hydrophilic monomer, may be present in the polymerizable composition in an amount of about 0.01 to 5 parts of the unit , such as from 0.02 to 2 parts of the unit, or from 0.05 to 1 part of the unit. In an example where the phosphine-containing compound is a tertiary phosphine (such as TPP or pTPP), a relatively small amount of the tertiary phosphine, for example, can be used in the polymerizable lens formulation. The phosphine-containing compound can be used, for example, in the polymerizable composition in amounts of from about 0.1 to about 1 part of the unit, or from about 0.2 to about 0.8 part of the unit, or from about 0.25 to about 0.75 part of the unit, or from about 0.3 to about 0.6 part of the unit, or other amounts.
[00037] It is known to use compounds containing phosphine oxide as polymerization initiators in polymerizable compositions to form contact lenses. According to the present disclosure, when the phosphine-containing composition is oxidized to a phosphine oxide-containing compound during the manufacturing process, such as, for example, by expelling oxygen, the amount of the phosphine oxide-containing compound in the polymerizable composition, at the beginning of the polymerization process, may be below an amount of the phosphine oxide initiator required to effectively polymerize the polymerizable composition and form a polymeric lens body having acceptable properties for use as a contact lens. In other words, if all of the phosphine-containing compound present in the polymerizable composition were to be converted to the phosphine oxide-containing compound before the start of polymerization of the polymerizable composition, and the phosphine oxide-containing compound were the only initiator present in the polymerizable composition , the phosphine oxide-containing compound would not be present at a high enough level to properly polymerize the polymerizable composition and form a polymeric lens body having acceptable properties such as shape conservation, modulus, dimensional stability over time, etc.
[00038] The present disclosure is directed to a polymerizable composition comprising at least one hydrophilic monomer and at least one phosphine-containing compound, which is present in an unoxidized form when combined with the hydrophilic monomer, where the at least one compound containing phosphine is present in the polymerizable composition in an amount effective to expel at least some of the oxygen present in the polymerizable composition during the manufacturing process. The amount of the phosphine-containing compound can be effective to scavenge oxygen from the polymerizable composition when the polymerizable composition is initially prepared, or it can be an effective amount to scavenge oxygen from the polymerizable composition and void space as the polymerizable composition waits to be inserted into the mold sections, or it may be an effective amount to expel oxygen from the polymerizable composition, the mold section and the atmosphere during the process of filling and closing the mold sections, or the amount may be effective to expel oxygen from the polymerizable composition, mold sections and atmosphere during the curing process, or combinations thereof. In other words, oxidation of the phosphine-containing compound to a phosphine oxide-containing compound can occur after the phosphine-containing compound has been combined with the hydrophilic monomer in the polymerizable composition, or before the polymerizable composition is inserted into a section of the contact lens mold, or after the polymerizable composition has been inserted into a section of the contact lens mold, or before the polymerizable composition is cured to form a polymeric lens body, or during curing of the polymerizable composition to form a body. of polymeric lens, or any combination thereof.
[00039] In one example, the amount of the phosphine-containing compound, which is present in an unoxidized form when combined with the hydrophilic monomer, which is present in the polymerizable composition, may be an amount that is effective to allow the composition is inserted into molds in the presence of an oxygen-containing atmosphere, and produces ophthalmically acceptable contact lenses when cured. Ophthalmically acceptable contact lenses can be contact lenses having adequate conservation of their molded shape, or contact lenses having similar properties to lenses made by inserting the polymerizable composition under an inert atmosphere, or contact lenses having both adequate shape conservation and properties of lenses similar to contact lenses made by an insertion process under an inert atmosphere. For example, the oxygen-containing atmosphere may be air at ambient pressure, or an atmosphere containing more than about 1% oxygen gas by volume, an atmosphere containing less than about 20% nitrogen gas by volume. The inert atmosphere can comprise a low oxygen atmosphere, such as an atmosphere containing less than 80% nitrogen gas by volume, or a low pressure atmosphere, such as a vacuum. Similar lenses can be lenses formed from a substantially identical polymerizable composition.
[00040] In another example, the amount of the phosphine-containing compound, which is present in an unoxidized form when combined with the hydrophilic monomer, which is present in the polymerizable composition, may be an amount that is effective to allow the composition to be reacted in the presence of an oxygen-containing atmosphere, and still produce ophthalmically acceptable contact lenses, such as contact lenses having adequate conservation of their molded shape, or having similar properties to lenses cured under an inert atmosphere, or having both adequate shape conservation and properties of similar lenses. For example, the oxygen-containing atmosphere can be air at ambient pressure, or an atmosphere containing more than about 1% oxygen gas by volume, or an atmosphere containing less than about 20% nitrogen gas by volume. The inert atmosphere can comprise a low oxygen atmosphere, such as an atmosphere containing less than 80% nitrogen gas by volume, or a low pressure atmosphere, such as a vacuum. Similar lenses can be lenses formed from a substantially identical polymerizable composition.
[00041] In yet another example, the amount of the phosphine-containing compound, which is present in an unoxidized form when combined with the hydrophilic monomer, which is present in the polymerizable composition, may be an effective amount to allow the composition is either inserted into molds or reacted in the presence of an oxygen-containing atmosphere, without the need for an inert atmosphere, and still produces ophthalmically acceptable contact lenses, such as contact lenses having adequate conservation of their molded shape, or having similar properties to lenses inserted and cured under an inert atmosphere, or having both adequate shape conservation and similar lens properties. For example, the oxygen-containing atmosphere can be air at ambient pressure, or an atmosphere containing more than about 1% oxygen gas by volume, or an atmosphere containing less than about 20% nitrogen gas by volume. The inert atmosphere can comprise a low oxygen atmosphere, such as an atmosphere containing less than 80% nitrogen gas by volume, or a low pressure atmosphere, such as a vacuum. Similar lenses can be lenses formed from a substantially identical polymerizable composition.
[00042] The present disclosure is also directed to a polymerizable composition comprising at least one hydrophilic monomer and at least one phosphine-containing compound, which is present in an unoxidized form when combined with the hydrophilic monomer, where the polymerizable composition contains an amount of the phosphine-containing compound effective to produce a polymeric lens body having a reduced amount of axial edge elevation (AEL), as compared to a second hydrogel contact lens body formed from a second, substantially identical, polymerizable composition to the polymerizable composition, except without the phosphine-containing compound and using a manufacturing process substantially identical to the hydrogel contact lens manufacturing process.
[00043] Figure 1 is a series of illustrations of hydrogel contact lenses having no axial edge elevation (10A lens and 10B lens) and contact lenses having some degree of edge elevation, ranging from minimum ( 10C lens) until progressively very low (10D lens, 10E lens and 10F lens, respectively). The illustrations in FIG. 1 include dashed lines illustrating the rear optical zone curve of each lens. Thus, 11A is the posterior optical zone curve of the lens 10A, 11B is the posterior optical zone curve of the lens 10B, 11C is the posterior optical zone curve of the lens 10C, 11D is the posterior optical zone curve of the lens lens 10D, 11E is the optical rear zone curve of lens 10E, and 11F is the optical rear zone curve of lens 10F. The optical posterior zone radius (BOZR) is illustrated by radius 12, which is the radius of the optical posterior zone curve of lens 10B (and which is the same curve, and BOZR, for all lenses 10A-10F).
[00044] Figure 2 is an illustration of the hydrogel contact lenses of FIG. 1 having some degree of edge lift. Vertical lines 13C, 13D, 13E, and 13F illustrate the axial edge elevation (AEL) of the respective lenses 10C, 10D, 10E, and 10F, as measured from the rear optical zone curve 11C, 11D, 11E, and 11F. AEL can be measured over sectional lenses or using other means known in the art. Some lens designs may intentionally include a small amount of edge lift. An acceptable level of AEL can be less than about 40 micrometers, or less than about 30 micrometers. Lenses having an unsatisfactory shape conservation often "swell up" at the edge, showing AEL values greater than about 50 micrometers, such as, for example, greater than about 75 micrometers or greater than about about 100 micrometers.
[00045] In another example, the polymerizable composition contains an amount of the phosphine-containing compound, which is present in an unoxidized form when combined with the hydrophilic monomer, which is an effective amount to reduce the deformation of the lens of hydrogel contact. For example, the amount of phosphine-containing compound can be effective to reduce deformation of the hydrogel contact lens as compared to a second hydrogel contact lens body formed from a second polymerizable composition substantially identical to the polymerizable composition. , except without the phosphine-containing compound, and using a manufacturing process substantially identical to the hydrogel contact lens manufacturing process. The deformation can be shape deformation, or it can be optical deformation.
[00046] In a specific example, contact lenses formed from a polymerizable composition comprising a phosphine-containing compound, which is present in an unoxidized form when combined with the hydrophilic monomer, have acceptable levels of shape conservation, without damage to the final properties of the lens. The presence of the phosphine-containing compound in the polymerizable composition, and in the resulting polymerized lens bodies, is effective in stabilizing the shape of the hydrogel contact lenses, while still providing a hydrogel contact lens having ophthalmic physical properties. - te acceptable, such as, for example, an equilibrium water content greater than 30%, or an oxygen permeability greater than 55 barrers, or a voltage modulus of 0.2 MPa to 0.85 MPa, or their combinations. Such contact lenses retain their molded shapes after being autoclaved and fully hydrated.
[00047] Figure 3 is a series of photographs of hydrogel contact lenses formed from polymerizable compositions having the same components, except with (3A and 3C) and without (3B and 3D) a phosphine-containing compound . Lenses 3A and 3B were manufactured using the same process, including polymerization in an air atmosphere. The 3C and 3D lenses were manufactured using the same process, including polymerization in an inert atmosphere. Lenses formed from compositions comprising the phosphine-containing compound had acceptable shapes (3A and 3C), while lenses formed from compositions without the phosphine-containing compound had crooked shapes (3B and 3D).
[00048] According to the lenses and lens manufacturing methods disclosed in this document, the polymerizable composition can be reacted in an atmosphere comprising air. The polymerizable composition can be reacted in an atmosphere consisting essentially of air. The polymerizable composition can be reacted in an atmosphere comprising air. The polymerizable composition can also be reacted in an atmosphere comprising an inert gas in a concentration greater than that found in air. The polymerizable composition can also be reacted in an atmosphere comprising a low concentration of an inert gas, such as an atmosphere containing less than 80% nitrogen gas by volume. Alternatively, the polymerizable composition can be reacted under an atmosphere containing a high concentration of an inert gas, such as a nitrogen atmosphere, including an atmosphere comprising greater than 80% nitrogen gas by volume.
[00049] Similarly, the polymerizable composition can be stored in an atmosphere comprising air. The polymerizable composition can be stored in an atmosphere consisting essentially of air. The polymerizable composition can be stored in an atmosphere consisting of air. The polymerizable composition can also be stored in an atmosphere comprising an inert gas at a higher concentration than is found in air. The polymerizable composition can also be stored in an atmosphere comprising a low concentration of an inert gas, such as an atmosphere containing less than 80% nitrogen gas by volume. Alternatively, the polymerizable composition can be stored under an atmosphere containing a high concentration of an inert gas, such as a nitrogen atmosphere, including an atmosphere comprising greater than 80% nitrogen gas by volume.
[00050] Additionally, in some examples, the polymerizable composition can be inserted into the mold sections in an atmosphere comprising air. The polymerizable composition can be inserted into the mold sections in an atmosphere consisting essentially of air. The polymerizable composition can be inserted into the mold sections in an atmosphere consisting of air. The polymerizable composition can also be placed in an atmosphere comprising an inert gas in a concentration greater than that found in air. The polymerizable composition can also be placed in an atmosphere comprising a low concentration of an inert gas, such as an atmosphere containing less than 80% nitrogen gas by volume. Alternatively, the polymerizable composition can be placed under an atmosphere containing a high concentration of an inert gas, such as a nitrogen atmosphere, including an atmosphere comprising greater than 80% nitrogen gas by volume.
[00051] In another example, the polymerizable composition may contain an amount of the phosphine-containing compound, which is present in an unoxidized form when combined with the hydrophilic monomer, which is an effective amount to reduce contact lens discoloration for at least 1 year when stored at room temperature, or for an equivalent period of time under accelerated test conditions. In some formulations, the presence of low concentrations of phosphine-containing compounds has been found to be effective in eliminating or reducing the yellowness of hydrogel contact lenses when stored for long periods of time. The amount of phosphine-containing compound can be effective to reduce contact lens discoloration compared to a second hydrogel contact lens body formed from a second polymerizable composition substantially identical to the polymerizable composition, except without the a phosphine-containing compound and using a manufacturing process substantially identical to the hydrogel contact lens manufacturing process.
[00052] The reduction in discoloration may comprise a reduction in the level of yellowing of the lenses. The level of yellowness can be detected using a color analyzer. For example, the color analyzer can be based on a multi-coordinate color system, such as the CIE L*a*b* system. The three coordinates of the CIE system L*a*b* represent the luminosity of the color (L* = 0 produces black and L* = 100 indicates diffuse white; specular white may be greater), its position between red /magenta and green (a*, negative values indicate green, while positive values indicate magenta) and its position between yellow and blue (b*, negative values indicate blue and positive values indicate yellow). When using such a system, the reduction in the yellowness level of the lenses may comprise a reduction in the L* value, or a reduction in a positive b* value, or an increase in a negative b* value.
[00053] As stated above, the phosphine-containing compound, which is present in an unoxidized form when combined with the hydrophilic monomer, is part of, or is within, the unitary construction of the lens body. In one example, when the phosphine-containing compound is a polymerizable phosphine-containing compound, the phosphine-containing compound is present as a unit of the copolymer comprising the polymerized lens body. In such an example, the phosphine-containing compound may be chemically, physically, or both chemically and physically immobilized on the lens body.
[00054] The phosphine-containing compound, which is present in an unoxidized form when combined with the hydrophilic monomer, may be present throughout the entire polymerized lens body. Various concentration gradients of the phosphine-containing compound can be present throughout the lens body such that the concentration of the phosphine-containing compound is uniform throughout the lens body, that is, non-uniform throughout the lens body. The concentration of the phosphine-containing compound can be substantially uniform throughout the lens body and this can be achieved by adding the phosphine-containing compound to the polymerizable composition and distributing the phosphine-containing compound evenly throughout the composition, prior to formation of the lens, for example, before inserting the polymerizable composition into a mold. As an option, the phosphine-containing compound can be added to the composition at least in part or completely before polymerization begins with the active components that form the lens composition. As an option, a higher concentration of the phosphine-containing compound may be present on (a) surface(s) of the lens body where exposure to oxygen may occur.
[00055] With the present invention, the phosphine-containing compound, which is present in an unoxidized form when combined with the hydrophilic monomer, is not present due to a post-treatment on the already formed lens body, such as by a surface coating. Although, as an option, a coating of a phosphine-containing compound may be present, in addition to the phosphine-containing component, in the polymerizable composition. As stated, the phosphine-containing compound is part of the polymerizable composition used to form the lens body, it is part of the polymerized lens body after polymerization, and remains part of the lens body, at least until the polymerizable composition, the color. lens powder, or both are exposed to conditions that oxidize the phosphine-containing compound to become a phosphine oxide-containing compound. Similarly, the phosphine-containing compound remains part of the polymerized lens body at least until the polymerizable lens body is contacted by a liquid, for example, as part of a demolding process, a lens removal process, a process to oxidize the remaining phosphine-containing component, a washing or extraction process, contact with a conditioning solution, a sterilization process, etc., which comprise part of the process of transforming the polymeric lens body into a finished hydrogel contact lens .
[00056] While it is optional to include an additional layer on the lens surface of the lens body which may include a phosphine-containing compound, it is to be understood that this is not necessary and indeed with the present invention per se. having a phosphine-containing compound incorporated as part of the overall lens composition and part of the overall lens, there is no need to have a separate coating or layer of the phosphine-containing compound for any purpose.
[00057] As discussed above, the phosphine-containing compound, which is present in an unoxidized form when combined with the hydrophilic monomer, is part of the polymerizable composition, which is reacted to polymerize and form the lens body. In addition to at least one phosphine-containing compound, the polymerizable composition comprises at least one hydrophilic monomer. The polymerizable composition can be reacted to form a polymeric lens body. The lens body polymer can be a homopolymer, or a copolymer comprising units of the hydrophilic monomer, including a cross-linked copolymer or a branched-chain copolymer or a linear copolymer, or a network of interpenetrating polymers of two polymers or copolymers , each of which is cross-linked to itself, or a network of pseudo-interpenetrating polymers of two polymers or copolymer, only one of which is cross-linked to itself. When the phosphine-containing component comprises a polymerizable phosphine-containing component, the polymeric lens body copolymer includes polymerized units of the phosphine-containing component in addition to polymerized units of the hydrophilic monomer. Optionally, the polymerizable composition can further comprise at least one siloxane monomer, at least one crosslinking agent, at least one initiator, at least one coloring agent; at least one UV blocking agent, and combinations and subgroups thereof. As used herein, the hydrophilic monomer of the polymerizable composition is understood to be a non-silicon hydrophilic monomer and, as such, is different from a siloxane monomer. The hydrophilicity or hydrophobicity of a monomer (including both silicon-containing and non-silicon-containing monomers) can be determined using conventional techniques, such as, for example, based on the aqueous solubility of the monomer. For purposes of the present disclosure, a hydrophilic monomer is a monomer that is visibly soluble in an aqueous solution at room temperature (eg, about 20-25 degrees C). For example, a hydrophilic monomer can be understood to be any monomer for which 50 grams or more of the monomer is visibly and fully soluble in 1 liter of water, at 20 degrees C (ie, the monomer is soluble at a level of at least 5% w/w in water), as determined using a standard shake flask method, as known to those of ordinary skill in the art. A hydrophobic monomer, as used herein, is a monomer that is visibly insoluble in an aqueous solution, at room temperature, such that separate, visually identifiable phases are present in the aqueous solution, or such that the aqueous solution appears turbid and separate into two distinct phases over time after standing at room temperature. For example, a hydrophobic monomer can be understood to be any monomer for which 50 grams of the monomer are not visibly and fully soluble in 1 liter of water, at 20 degrees C (ie the monomer is soluble at a level of minus than 5% w/w in water).
[00058] Examples of hydrophilic monomers that can be included in the present polymerizable compositions may include, for example, N,N-dimethylacrylamide (DMA), or 2-hydroxyethyl acrylate, or 2-hydroxyethyl methacrylate (HEMA) , or 2-hydroxypropyl methacrylate, or 2-hydroxybutyl methacrylate (HOB), or 2-hydroxybutyl acrylate, or 4-hydroxybutyl acrylate, or glycerol methacrylate, or 2-hydroxyethyl methacrylamide, or polyethylene glycol monomethacrylate, or methacrylic acid, or acrylic acid, or any combination thereof.
[00059] In one example, the hydrophilic monomer or the hydrophilic monomer component may comprise or consist of a vinyl-containing monomer. Examples of hydrophilic vinyl-containing monomers which may be provided in polymerizable compositions include, without limitation, N-vinyl formamide, or N-vinyl acetamide, or N-vinyl-N-ethyl acetamide, or N-vinyl isopropylamide, or N-vinyl-N-methyl acetamide (VMA), or N-vinyl pyrrolidone (NVP), or N-vinyl caprolactam, or N-vinyl-N-ethyl formamide , or N-vinyl formamide, or N-2-hydroxyethyl vinyl carbamate, or N-carboxy-β-alanine N-vinyl ester, 1,4-butanediol vinyl ether (BVE), or ethylene glycol ether vinyl (EGVE), or diethylene glycol vinyl ether (DEGVE), or any combination thereof.
[00060] In another example, the hydrophilic monomer or the hydrophilic monomer component of the polymerizable composition may comprise or consist of a hydrophilic amide monomer. The hydrophilic amide monomer may be a hydrophilic amide monomer having an N-vinyl group, such as, for example, N-vinyl formamide, or N-vinyl acetamide, or N-vinyl-N-ethyl acetamide, or N-vinyl isopropylamide, or N-vinyl-N-methyl acetamide (VMA), or N-vinyl pyrrolidone (NVP), or N-vinyl caprolactam, or any combination thereof. In one example, the hydrophilic monomer or hydrophilic monomer component comprises N-vinyl-N-methyl acetamide (VMA). For example, the hydrophilic monomer or monomer component can comprise or consist of VMA. In a particular example, the hydrophilic monomer could be VMA.
[00061] In another example, the hydrophilic vinyl-containing monomer or monomer component may comprise or consist of a vinyl ether-containing monomer. Examples of vinyl ether containing monomers include, without limitation, 1,4-butanediol vinyl ether (BVE), or ethylene glycol vinyl ether (EGVE), or diethylene glycol vinyl ether (DEGVE), or any combination thereof. In one example, the hydrophilic monomer component comprises or consists of BVE. In another example, the hydrophilic monomer component comprises or consists of EGVE. In yet another example, the hydrophilic vinyl component comprises or consists of DEGVE.
[00062] In yet another example, the hydrophilic vinyl-containing monomer component may comprise or consist of a combination of a first hydrophilic monomer or monomer component, and a second hydrophilic monomer or hydrophilic monomer component. In one example, the first hydrophilic monomer has a different polymerizable functional group than the second hydrophilic monomer. In another example, each monomer of the first hydrophilic monomer has a different polymerizable functional group than the second hydrophilic monomer. In another example, the first hydrophilic monomer has a different polymerizable functional group than each monomer of the second hydrophilic monomer component. In yet another example, each monomer of the first hydrophilic monomer component has a different polymerizable functional group than each monomer of the second hydrophilic monomer component.
[00063] For example, when the first hydrophilic monomer or monomer component comprises or consists of one or more amide containing monomers, the second hydrophilic monomer monomer or component may comprise or consist of one or more monomers without amide ( that is, one or more monomers, each of which does not have an amide functional group as part of their molecular structures). As another example, when the first hydrophilic monomer or monomer component comprises or consists of one or more vinyl-containing monomers, the second hydrophilic monomer monomer or component may comprise one or more non-vinyl monomers (i.e., one or more monomers, each one of which does not have a polymerizable vinyl functional group as part of their molecular structures). In another example, when the first hydrophilic monomer or monomer component comprises or consists of one or more amide monomers each having an N-vinyl group, the second hydrophilic monomer or monomer component may comprise or consist of one or more monomers without amide. When the first hydrophilic monomer or monomer component comprises or consists of one or more non-acrylate monomers (i.e., one or more monomers, each of which does not have an acrylate or methacrylate polymerizable functional group as part of its moiety structures). -lecular), the second hydrophilic monomer or monomer component may comprise or consist of one or more acrylate-containing monomers, or one or more methacrylate-containing monomers, or any combination thereof. When the first hydrophilic monomer or monomer component comprises or consists of one or more monomers not containing vinyl ether (ie, one or more monomers, each of which does not have a polymerizable vinyl ether functional group such as part of their molecular structures), the second monomer or hydrophilic monomer component may comprise or consist of one or more vinyl ether containing monomers. In a particular example, the first hydrophilic monomer or monomer component may comprise or consist of one or more amide containing monomers, each having an N-vinyl group, and the second hydrophilic monomer monomer or component may comprise or consist of one or more vinyl ether-containing monomers.
[00064] In one example, when the first hydrophilic monomer or monomer component comprises or consists of a hydrophilic amide containing monomer having an N-vinyl group, the second hydrophilic monomer or monomer component may comprise or consist of a monomer containing vinyl ether. In a particular example, the first hydrophilic monomer may comprise VMA, and the second hydrophilic monomer monomer or component may comprise BVE or EGVE or DEGVE or any combination thereof. The first hydrophilic monomer can comprise VMA and the second hydrophilic monomer can comprise BVE. The first hydrophilic monomer can comprise VMA and the second hydrophilic monomer can comprise EGVE. The first hydrophilic monomer can comprise VMA and the second hydrophilic monomer can comprise DEGVE. The first hydrophilic monomer can comprise VMA, and the second hydrophilic monomer component can comprise EGVE and DEGVE.
[00065] Similarly, the first hydrophilic monomer may be VMA, and the second hydrophilic monomer monomer or component may comprise BVE or EGVE or DEGVE or any combination thereof. The first hydrophilic monomer can be VMA and the second hydrophilic monomer can be BVE. The first hydrophilic monomer can be VMA and the second hydrophilic monomer can be EGVE. The first hydrophilic monomer can comprise VMA and the second hydrophilic monomer can be DEGVE. The first hydrophilic monomer can be VMA, and the second hydrophilic monomer component can be a combination of EGVE and DEGVE.
[00066] In another example, the silicon-free hydrophilic vinyl-containing monomer can have any molecular weight, such as a molecular weight less than 400 daltons, or less than 300 daltons, or less than 250 daltons, or less than 200 daltons, or less than 150 daltons, or from about 75 to about 200 daltons.
[00067] When a hydrophilic monomer or hydrophilic monomer component is present in the polymerizable composition, the hydrophilic monomer or monomer component may be present in the polymerizable composition in an amount of 30 to 60 parts of the polymerizable composition unit. The hydrophilic monomer or monomer component can be present in the polymerizable composition from 40 to 55 parts of the unit, or from 45 to 50 parts of the unit by weight. When the hydrophilic monomer component of the polymerizable composition comprises a first hydrophilic monomer or monomer component and a second hydrophilic monomer monomer or component, the second hydrophilic monomer or monomer component may be present in the polymerizable composition in an amount of 0. 1 to 20 parts of the polymerizable composition unit. For example, of the total amount of 30 to 60 parts of the hydrophilic monomer unit or monomer component present in the polymerizable composition, 29.9 to 40 parts of the unit may comprise the first hydrophilic monomer or monomer component, and 0.1 to 20 parts of the unit may comprise the second hydrophilic monomer or monomer component. In another example, the second hydrophilic monomer or monomer component may be present in the polymerizable composition from 1 to 15 parts of the unit, or from 2 to 10 parts of the unit, or from 3 to 7 parts of the unit.
[00068] As used herein, a vinyl-containing monomer is a monomer having a single polymerizable carbon-carbon double bond (ie, a polymerizable vinyl functional group) present in its molecular structure, where, under free radical polymerization, the bond The carbon-carbon double bond in the vinyl polymerizable functional group is less reactive than the carbon-carbon double bond present in an acrylate or methacrylate polymerizable functional group. In other words, although a carbon-carbon double bond is present in both acrylate groups and methacrylate groups, as understood herein, monomers that comprise a single polymerizable acrylate or methacrylate group are not considered to be vinyl-containing monomers. Examples of polymerizable groups having carbon-carbon double bonds that are less reactive than the carbon-carbon double bonds of the polymerizable groups of acrylate or methacrylate include the polymerizable groups of vinyl amide, vinyl ether, vinyl ester, and ester. allyl. Thus, as used herein, examples of vinyl-containing monomers include monomers having a single polymerizable vinyl amide group, a single vinyl ether, a single vinyl ester, or a single allylic ester.
[00069] In any or each of the preceding examples, as discussed above, the amount of the hydrophilic monomer or monomer component (e.g., the one or more hydrophilic monomers present in the polymerizable composition) may be from 30 to 60 parts of the polymerizable composition unit. In certain examples, the monomer or component mixture of hydrophilic monomers may constitute from 40 to 55 parts of the polymerizable composition unit, or from 45 to 50 parts of the composition unit. When VMA is present in the polymerizable composition, it can be present in an amount of 30 parts of the unit to 60 parts of the unit. In certain examples, VMA is present in the polymerizable composition in an amount of from about 40 parts of the unit to about 55 parts of the unit, or from 45 to 50 parts of the unit. If the hydrophilic monomers, N,N-dimethylacrylamide (DMA), 2-hydroxyethyl methacrylate (HEMA), or 2-hydroxylbutyl methacrylate (HOB), are present in the polymerizable composition as an optional second hydrophilic monomer or monomer blend, they they can be present in amounts from about 3 to about 10 parts of the unit.
[00070] As used herein, a molecular weight is understood to refer to the number average molecular weight. The numerical average molecular weight is the common arithmetic average or the average of the molecular weights of the individual molecules present in a monomer sample. Since the individual molecules in a monomer sample may vary slightly from one another in molar mass, some level of polydispersity may be present in the sample. As used herein, when the siloxane monomer, or any other monomer, macromer, prepolymer, or polymer, of the polymerizable composition is polydispersed, the term "molecular weight" refers to the number average molecular weight of the monomer or ingredient . As an example, a siloxane monomer sample may have a number average molecular weight of about 15,000 daltons, however, if the sample is polydispersed, the actual molecular weights of the individual monomers present in the sample can range from 12,000 daltons to 18,000 daltons to 18,000 daltons daltons.
[00071] The number average molecular weight can be the absolute number average molecular weight, as determined by end-group analysis through proton nuclear magnetic resonance (NMR), as understood by those of ordinary skill in the art. Molecular weights can also be determined using gel permeation chromatography, as understood by those of ordinary skill in the art, or can be provided by suppliers of the chemical.
[00072] As used in this document, the parts of the unit are understood to mean the parts of the unit by weight. For example, to prepare a formulation described as comprising z parts of a phosphine-containing compound unit and y parts of a hydrophilic monomer unit, the composition can be prepared by combining z grams of the phosphine-containing compound with y grams of the hydrophilic monomer to obtain a total of y+z grams of polymerizable composition, or combining z ounces of the phosphine-containing compound with y ounces of the hydrophilic monomer to obtain a total of y+z ounces of polymerizable composition, and so on. When the composition further comprises additional optional ingredients, such as, for example, x parts of a cross-linking agent unit, x grams of the cross-linking agent are combined with z grams of the phosphine-containing compound and y grams of the hydrophilic monomer to obtain a total of x+ y+z grams of the polymerizable composition, and so on. When the composition comprises an additional optional ingredient comprising an ingredient component composed of two ingredients, such as, for example, a hydrophobic monomer component consisting of a first hydrophobic monomer and a second hydrophobic monomer, in addition to the z-part compound unit containing phosphine, of the y parts of the hydrophilic monomer unit and the x parts of the crosslinker unit, w parts of the unit of the first hydrophobic monomer and v parts of the unit of the second hydrophobic monomer are combined to obtain a total amount of v+w+x +y+z parts of the polymerizable composition unit. It is understood that the unit parts of the at least one hydrophobic monomer present in such polymerizable is the sum of the unit parts of the first hydrophobic monomer and the unit parts of the second hydrophobic monomer, e.g., v+w parts of the unit in this example. Typically, a formula for a polymerizable composition will comprise ingredients in amounts totaling from about 90 to about 110 parts of the unit by weight. When the amounts of the components of the polymerizable composition are referred to herein as being in unit parts, it is to be understood that the unit parts of these components are based on a formula providing a total composition weight ranging from about 90 to 110 parts of the unity. In one example, parts unit by weight can be based on a formula providing a total weight of the composition ranging from about 95 to 105 parts unit by weight, or from about 98 to 102 parts unit by weight.
[00073] In one example, the present disclosure is directed to hydrogel contact lenses essentially free of silicon-containing ingredients, i.e., contact lenses formed from a hydrogel containing less than 0.1% (w/w) of an ingredient containing silicon. In another example, the present disclosure is directed to silicone hydrogel contact lenses. As used herein, "silicone hydrogel" or "silicone hydrogel material" refers to a particular hydrogel that includes a silicone component (SiO). For example, a silicone hydrogel is typically prepared by combining a silicon-containing material with conventional hydrophilic hydrogel precursors. A silicone hydrogel contact lens is a contact lens, including a vision-correcting contact lens, which comprises of a silicone hydrogel material. A siloxane monomer is a monomer that contains at least one siloxane bond [-Si-O-Si-]. In a siloxane monomer, each silicon atom may optionally have one or more organic radical substituents (R 1 , R 2 ) or substituted organic radical substituents which may be the same or different, e.g., -SiR 1 R 2 O-. Similarly, a non-silicon ingredient is an ingredient containing less than 0.1% (w/w) silicon.
[00074] In some examples of the present invention, the polymerizable composition may additionally comprise at least one siloxane monomer. In such an example, the polymeric lens body will include polymerized units of at least one siloxane monomer, and the hydrogel contact lens will comprise a silicone hydrogel contact lens. As used herein, a reactive ingredient, which can be reacted to form a part of a polymer unit, is referred to as a monomer, regardless of its size. The at least one optional siloxane monomer can comprise a single siloxane monomer, or can comprise a siloxane monomer component composed of two or more siloxane monomers. The at least one siloxane monomer can be a hydrophilic siloxane monomer, or a hydrophobic siloxane monomer, or it can have both hydrophilic regions and hydrophobic regions, depending on the amount and position of any hydrophilic components, such as the units of ethylene glycol, polyethylene glycol and the like, present in the molecular structure of siloxane monomers.
[00075] For example, the siloxane monomer may contain hydrophilic components within the main chain of the siloxane molecule, may contain hydrophilic components within one or more side chains of the siloxane molecule, or any combination thereof. For example, the siloxane monomer can have at least one ethylene glycol unit adjacent to a polymerizable functional group on the backbone of the siloxane molecule. As used herein, adjacent is understood to mean either immediately adjacent or separated only by 10 or fewer carbon atoms. The at least one ethylene glycol unit adjacent to a polymerizable functional group in the backbone of the siloxane molecule may be separated from the polymerizable functional group by 1-5 carbon chain length units (i.e., where the ethylene glycol unit is bonded to the first carbon in the 1-5 carbon chain length units, and the polymerizable functional group is bonded to the last carbon in the 1-5 carbon chain length unit, in other words, the ethylene glycol unit and the polymerizable group are not immediately adjacent but are separated by 1-5 carbon atoms). The siloxane monomer can have at least one ethylene glycol unit adjacent to the polymerizable functional groups present on both ends of the backbone of the siloxane molecule. The siloxane monomer can have at least one ethylene glycol unit present in at least one side chain of the siloxane molecule. The at least one ethylene glycol moiety present in at least one side chain of the siloxane molecule can be part of a side chain attached to a silicon atom of the backbone of the siloxane molecule. The siloxane molecule can have either at least one ethylene glycol unit adjacent to the polymerizable functional groups present on both ends of the backbone of the siloxane molecule, or at least one ethylene glycol unit present on at least one side chain of the siloxane molecule. siloxane molecule.
[00076] In an example of the present disclosure, when present in the polymerizable com-position, the at least one optional siloxane monomer may be a multifunctional siloxane monomer. If the siloxane monomer has two functional groups, such as two methacrylate groups, it is a bifunctional monomer. If the siloxane monomer has three functional groups, it is a trifunctional monomer.
[00077] The optional siloxane monomer may be a siloxane monomer having a polymerizable functional group present on one end of the main chain of the monomer. The siloxane monomer can be a siloxane monomer having a polymerizable functional group on both ends of the monomer backbone. The siloxane monomer can be a siloxane monomer having a polymerizable functional group present on at least one side chain of the monomer. The siloxane monomer can be a siloxane monomer having a polymerizable functional group present on only one side chain of the monomer.
[00078] The optional siloxane monomer of the polymerizable composition can be an acrylate-containing siloxane monomer, in other words, a siloxane monomer having at least one polymerizable functional group of acrylate as part of its molecular structure. In one example, the acrylate-containing siloxane monomer may be a methacrylate-containing siloxane monomer, that is, a siloxane monomer having at least one polymerizable methacrylate functional group as part of its molecular structure.
[00079] The optional siloxane monomer may be a siloxane monomer having a number average molecular weight of at least 3000 daltons. In another example, the siloxane monomer can be a siloxane monomer having a molecular weight of at least 4,000 daltons, or at least 7,000 daltons, or at least 9,000 daltons, or at least 11,000 daltons.
[00080] The optional siloxane monomer can be a siloxane monomer having a molecular weight less than 20,000 daltons. In another example, the siloxane monomer may be a siloxane monomer having a molecular weight of less than 15,000 daltons, or less than 11,000 daltons, or less than 9,000 daltons, or less than 7,000 daltons, or less than than 5,000 daltons.
[00081] The optional siloxane monomer can be a siloxane monomer having a molecular weight of 3,000 daltons to 20,000 daltons. In another example, the siloxane monomer may be a siloxane monomer having a molecular weight from 5,000 daltons to 20,000 daltons, or from 5,000 daltons to 10,000 daltons, or from 7,000 daltons to 15,000 daltons.
[00082] In one example, the optional siloxane monomer has more than one functional group and has a number average molecular weight of at least 3,000 daltons.
[00083] Optional siloxane monomer may include poly(organosiloxane) monomers or macromers or prepolymers, such as, for example, 3-[tris(trimethylsiloxy)silyl]propyl allyl carbamate, or carbamate of 3-[tris(trimethylsiloxy)silyl]propyl vinyl, or trimethylsilylethyl vinyl carbonate, or trimethylsilylmethyl vinyl carbonate, or 3-[tris(trimethylsilyloxy)silyl]propyl methacrylate (TRIS), or 3 -methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilane (SiGMA), or methyldi(trimethylsiloxy)silylpropylglyceroethyl methacrylate (SiGEMA), or monomethacryloxypropyl terminated polydimethylsiloxane (MCS-M11), MCR-M07, or polydimethyl mono-n-butyl terminated mono-methacryloxypropyl terminated siloxane (mPDMS), or any combinations thereof. In an example of a polymerizable composition of the present disclosure, the optional siloxane monomer can comprise a first siloxane monomer and a second siloxane monomer, where the second siloxane monomer differs from the first siloxane present in the polymerizable composition based on weight molecular structure, molecular structure, or both molecular weight and structure. For example, the optional second siloxane monomer or at least one third siloxane monomer can be a formula (1) siloxane monomer having a different molecular weight than the first siloxane monomer of the polymerizable composition. In another example, the optional second siloxane monomer or at least one third siloxane may comprise at least one of the siloxanes disclosed in the following patents: US2007/0066706, US2008/0048350, US3808178, US4120570, US4136250, US4153641, US470533, US5070215, US5998498 , US5760100, US6367929, and EP080539, the entire contents of which are hereby incorporated by reference.
[00084] In another example of the present contact lenses, the optional siloxane monomer may be a double-ended methacrylate end capped polydimethylsiloxane having a number average molecular weight of at least 4,000 daltons. It will be understood that such siloxane monomers are bifunctional.
[00085] In an example of the present contact lenses, the optional siloxane monomer may have a number average molecular weight of at least 4,000 daltons, or at least 7,000 daltons, or at least 9,000 daltons, or at least 11,000 daltons. The number average molecular weight of siloxane monomer can be less than 20,000 daltons. Thus, in some contexts, siloxane monomer may be considered a macrometer, but it will be referred to as a monomer in this document as it forms a part of a polymer unit formed with the other reactive components of the polymerizable composition.
[00086] Examples of siloxane monomers may include the monofunctional siloxane monomers having at least one urethane bond, such as the examples of the monofunctional siloxane monomers represented by the formula
where n of formula (4) is 0-30, or is 10-15. In a particular example, the siloxane monomer may be the formula (4) monomer, where n of formula (4) is 12-13 and having a molecular weight of about 1500 daltons. Examples of such monofunctional siloxane monomers are described in US 6,867,245, which is hereby incorporated by reference.
[00087] Examples of siloxane monomers may include bifunctional siloxane monomers having at least two urethane bonds, such as the examples of bifunctional siloxane monomers represented by formula (5:
where n of formula (5) is an integer from about 100-150, m of formula (5) is an integer from about 5 to about 10, and h is an integer from about 2 to 8. further example of such bifunctional siloxane monomer, and methods of preparing compounds of formula (5) are described in U.S. Pat. US No. 6,867,245, which is hereby incorporated by reference. In a particular example, the siloxane monomer may be a bifunctional siloxane monomer having two urethane bonds and having a molecular weight greater than 10,000 daltons, such as, for example, a molecular weight of greater than about 15,000 daltons.
[00088] The siloxane monomer can be a mono-functional siloxane monomer represented by the formula (6):
where m of formula (6) represents an integer from 3 to 10, n of formula (6) represents an integer from 1 to 10, R1 of formula (6) is an alkyl group having 1 to 4 carbon atoms, and each R2 of formula (6) is independently a hydrogen atom or a methyl group. In other words, on a single molecule of the siloxane monomer represented by formula 1, the first R2 of formula (6), which is attached to the CH2 group adjacent to the siloxane group, can be a hydrogen atom or a methyl group, and the second R2 of the formula (6), which is bonded to the C of the methacrylate end group, may also be a hydrogen atom or a methyl group, regardless of whether the first R2 of the formula (6) is a hydrogen atom or a methyl group. In a particular example of the siloxane monomer of formula (6), m of formula (6) is 4, n of formula (6) is 1, R1 of formula (6) is a butyl group, and each R2 of formula (6) is independently a hydrogen atom or a methyl group. The molecular weight of the formula (6) siloxane monomer can be less than 2000 daltons. In some examples, the molecular weight of the formula (6) siloxane monomer is less than 1,000 daltons. Often, the molecular weight of the first siloxane monomer is 400 to 700 daltons. Further details of the siloxane monomer of formula (6) can be understood from US20090299022, the entire contents of which are hereby incorporated by reference. As can be appreciated from formula (6), the first siloxane monomer has a single methacrylic functional end group.
[00089] The siloxane monomer can be a bifunctional siloxane monomer.
where R1 of formula (7) is selected from hydrogen atom or a methyl group; R2 of formula (7) is selected from hydrogen atom or a hydrocarbon group having 1 to 4 carbon atoms; m of formula (7) represents an integer from 0 to 10; n of formula (7) represents an integer from 4 to 100; a and b represent integers of 1 or more; a+b is equal to 20-500; b/(a+b) is equal to 0.01-0.22; and the configuration of the siloxane units includes a random configuration. In some examples where the second siloxane monomer is a monomer represented by formula (7), m of formula (7) is 0, n of formula (7) is an integer from 5 to 15, a is an integer of 65 to 90, b is an integer from 1 to 10, R1 of formula (7) is a methyl group, and R2 of formula (7) is a hydrogen atom or a hydrocarbon group having 1 to 4 carbon atoms . An example of such a second siloxane monomer as represented by formula (7) is abbreviated Si2 in the examples. In certain examples, the number average molecular weight for this second siloxane monomer represented by formula (7) is from about 9,000 daltons to about 10,000 daltons. In other examples, the second siloxane monomer represented by formula (7) is from about 5,000 daltons to about 10,000 daltons. It can be appreciated that the second siloxane represented by formula (7) is a bifunctional siloxane having two terminal methacrylic groups. Additional details of this second siloxane monomer can be found in US20090234089, the entire contents of which are incorporated herein by reference.
[00090] The siloxane monomer can be a bifunctional siloxane monomer represented by the formula (8):
where R3 is selected from a hydrogen atom or a methyl group, m of formula (8) represents an integer from 0 to 15, and n of formula (8) represents an integer from 1 to 500. In one example, the siloxane monomer is represented by formula (8), and R3 is a methyl group, m of formula (8) is 0, and n of formula (8) is an integer from 40 to 60.
[00091] In another example, the siloxane monomer may be a bifunctional siloxane monomer represented by formula (9), and is abbreviated Si3 in the examples (available from Gelest, Inc., Morrisville, PA as product code DMS- R18):

[00092] In certain examples, the siloxane of formula (9) has a number average molecular weight of about 4,000 to about 4,500 daltons.
[00093] In certain examples, the polymerizable composition may also comprise a second siloxane monomer. The second siloxane monomer can have more than one functional group, or it can have a number average molecular weight of at least 3,000 daltons, or it can have both more than one functional group and a number average molecular weight of at least 3,000 daltons. 3,000 Daltons less. If the second siloxane monomer has two functional groups, such as two methacrylate groups, it is a bifunctional monomer. If the second siloxane monomer has three functional groups, it is a trifunctional monomer.
[00094] When the polymerizable composition comprises a first siloxane and a second siloxane, the first siloxane monomer and the second siloxane monomer may be present in amounts such as the ratio of the first siloxane monomer to the second siloxane monomer. siloxane is at least 1:1 based on parts of the unit, ie at least 2:1 based on parts of the unit. For example, the first siloxane monomer and the second siloxane monomer can be present in the polymerizable composition in a ratio of from about 2:1 to about 10:1 based on parts of the unit. In another example, the first siloxane monomer and the second siloxane monomer may be present in the polymerizable composition in a ratio of from about 3:1 to about 6:1, based on parts of the unit. In one example, the first siloxane monomer and the second siloxane monomer may be present in the polymerizable composition in a ratio of about 4:1 based on parts of the unit.
[00095] When the polymerizable composition comprises at least one siloxane monomer, the total amount of siloxane monomers present in the polymerizable composition (e.g., the sum of the unit parts of the optional first siloxane monomer, of the second monomer of optional siloxane, and any other optional siloxane monomers present in the polymerizable composition) can be from about 10 to about 60 parts of the unit, or from about 25 to about 50 parts of the unit, or of about 35 to about 40 parts of the unit.
[00096] In a particular example, when the siloxane monomer component comprises a combination of at least two siloxane monomers, each having a different molecular weight, the molecular weight of the first siloxane monomer may be less than than 2,000 daltons. In some examples, the molecular weight of the first siloxane monomer may be less than 1,000 daltons. Often, the molecular weight of the first siloxane monomer is 400 to 700 daltons.
[00097] When the at least one siloxane monomer is present in the polymerizable composition, as discussed above, the at least one siloxane monomer may comprise a first siloxane monomer and a second siloxane monomer. In one example, the first siloxane monomer may consist of a formula (5) siloxane monomer and the second siloxane monomer may consist of a formula (4) siloxane monomer. In another example, the first siloxane monomer may consist of a formula (4) siloxane monomer, and the second siloxane monomer may consist of a formula (5) siloxane monomer. In another example, the first siloxane monomer may consist of a formula (6) siloxane monomer, and the second siloxane may consist of a formula (7) siloxane monomer. In another example, the first siloxane monomer may consist of a formula (7) siloxane monomer, and the second siloxane monomer may consist of a formula (6) siloxane monomer. In another example, the first siloxane monomer may consist of a formula (4) siloxane monomer, and the second siloxane monomer may consist of a formula (7) siloxane monomer. In yet another example, the first siloxane monomer may consist of a formula (7) siloxane monomer, and the second siloxane monomer may consist of a formula (4) siloxane monomer. In any or all of the examples described herein, the siloxane monomer component can comprise a third siloxane monomer. For example, the third siloxane monomer can consist of a siloxane monomer of formula (8).
[00098] Optionally, the polymerizable compositions of the present disclosure may optionally comprise at least one non-silicon hydrophobic monomer. It is understood that the hydrophobic monomer is a non-silicone polymerizable ingredient having only one polymerizable functional group present in its molecular structure. The at least one hydrophobic monomer of the polymerizable composition can be a hydrophobic monomer, or it can comprise a hydrophobic monomer component composed of at least two hydrophobic monomers. Examples of hydrophobic monomers that can be used in the polymerizable compositions disclosed herein include, without limitation, acrylate-containing hydrophobic monomers, or methacrylate-containing hydrophobic monomers, or any combination thereof. Examples of hydrophobic monomers include, without limitation, methyl acrylate, or ethyl acrylate, or propyl acrylate, or isopropyl acrylate, or cyclohexyl acrylate, or 2-ethylhexyl acrylate, or me - methyl methacrylate (MMA), or ethyl methacrylate, or propyl methacrylate, or butyl acrylate, or vinyl acetate, or vinyl propionate, or vinyl butyrate, or vinyl valerate, or styrene, or chloroprene, or vinyl chloride, or vinylidene chloride, or acrylonitrile, or 1-butene, or butadiene, or methacrylonitrile, or vinyltoluene, or vinyl ethyl ether, or perfluorohexylthiocarbonylaminoethyl methacrylate, or isobornyl methacrylate, or trifluorethyl methacrylate, or hexafluoroisopropyl methacrylate, or hexafluorobutyl methacrylate, or ethylene glycol methyl ether methacrylate (EGMA), or any combination thereof . In a particular example, the hydrophobic monomer or monomer component may comprise or consist of MMA, or EGMA, or both.
[00099] When present in the polymerizable composition, the hydrophobic monomer or monomer component may be present in an amount of from about 5 to about 25 parts of the unit, or from about 10 to about 20 parts of the unit.
[000100] In one example, the hydrophobic monomer component may comprise at least two hydrophobic monomers, each having different polymerizable functional groups. In another example, the hydrophobic monomer component can comprise at least two hydrophobic monomers, each having the same polymerizable functional group. The hydrophobic monomer component can comprise or consist of two hydrophobic monomers both having the same polymerizable functional group. In one example, the hydrophobic monomer component can comprise or consist of two methacrylate-containing hydrophobic monomers. The hydrophobic monomer component can comprise or consist of MMA and EGMA. In one example, the at least two hydrophobic monomers of the hydrophobic monomer component may comprise or consist of MMA and EGMA, and the ratio of the MMA unit parts to the EGMA unit parts present in the polymerizable composition may be about 6:1 to about 1:1. The ratio of the MMA and EGMA unit parts present in the polymerizable composition can be about 2:1 based on the MMA unit parts to the EGMA unit parts.
[000101] According to the present disclosure, it is understood that a crosslinking agent is a monomer having more than one polymerizable functional group as part of its molecular structure, such as two or three or four polymerizable functional groups, i.e. , a multifunctional monomer, such as a bifunctional or trifunctional or tetrafunctional monomer. Non-silicon crosslinking agents that can be used in the polymerizable compositions disclosed herein include, for example, without limitation, allyl (meth)acrylate, or lower alkylene glycol di(meth)acrylate, or di(meth)acrylate of poly(lower alkylene) glycol, or lower alkylene di(meth)acrylate, or divinyl ether, or divinyl sulfone, or di- and trivinylbenzene, or trimethylolpropane tri(meth)acrylate, or tetra pentaerythritol (meth)acrylate, or bisphenol A di(meth)acrylate, or methylenebis(meth)acrylamide, or triallyl phthalate and diallyl phthalate, or any combination thereof. Crosslinking agents as disclosed in Examples 1-37 include, for example, ethylene glycol dimethacrylate (EGDMA), or triethylene glycol dimethacrylate (TEGDMA), or triethylene glycol divinyl ether (TEGDVE), or any combination of them. In one example, the crosslinking agent may have a molecular weight less than 1500 daltons, or less than 1000 daltons, or less than 500 daltons, or less than 200 daltons.
[000102] In one example, the crosslinking agent or crosslinking agent component may comprise or consist of a vinyl-containing crosslinking agent. As used herein, a vinyl-containing crosslinking agent is a monomer having at least two polymerizable carbon-carbon double bonds (ie, at least two polymerizable vinyl functional groups) present in its molecular structure, where each of the at least two polymerizable carbon-carbon double bonds present in the polymerizable vinyl functional groups of the vinyl-containing crosslinking agent is less reactive than a carbon-on-carbon double bond present in a polymerizable functional group of acrylate or methacrylate. While carbon-carbon double bonds are present in the polymerizable functional groups of acrylate and methacrylate, as understood herein, crosslinking agents comprising one or more polymerizable groups of acrylate or methacrylate (e.g., a crosslinking agent containing acrylate or a methacrylate-containing cross-linking agent) are not considered to be vinyl-containing cross-linking agents. Polymerizable functional groups having carbon-carbon double bonds that are less reactive than the carbon-carbon double bonds of the polymerizable groups of acrylate or methacrylate include, for example, the polymerizable functional groups of vinyl amide, vinyl ester, vinyl ether, and allyl ester . Thus, as used herein, vinyl-containing crosslinking agents include, for example, crosslinking agents having at least two polymerizable functional groups selected from a vinyl amide, a vinyl ether, a vinyl ester, an allylic ester, and any combination of them. As used herein, a mixed vinyl-containing crosslinking agent is a crosslinking agent having at least one polymerizable carbon-carbon double bond (i.e., at least one polymerizable vinyl functional group) present in its structure, which is less reactive. than the carbon-carbon double bond present in a polymerizable functional group of acrylate or methacrylate, and at least one polymerizable functional group present in its structure having a carbon-carbon double bond that is at least as reactive as the carbon-carbon double bond in the polymerizable functional group of acrylate or methacrylate.
[000103] When present in the polymerizable composition, the vinyl-containing crosslinking agent or crosslinking agent component may be present in an amount of from about 0.01 part unit to about 2.0 part unit, or from about 0.01 part of the unit to about 0.80 part of the unit, or from about 0.01 part of the unit to about 0.30 part of the unit, or from about 0.05 part of the unit to about 0.20 part of the unit, or in an amount of about 0.1 part of the unit.
[000104] In one example, the cross-linking agent or cross-linking agent component may comprise or consist of a non-vinyl-containing cross-linking agent, i.e., a cross-linking agent that is not a vinyl-containing cross-linking agent. For example, the cross-linking agent or non-vinyl-containing cross-linking agent component may comprise or consist of an acrylate-containing cross-linking agent (i.e., a cross-linking agent having at least two polymerizable acrylate functional groups), or a methacrylate-containing crosslinker (i.e., at least two polymerizable functional groups of methacrylate), or at least one acrylate-containing crosslinker and at least one methacrylate-containing crosslinker.
[000105] When present in the polymerizable composition, the crosslinking agent or non-vinyl crosslinking agent component may be present in an amount of from about 0.01 part of the unit to about 5 parts of the unit, or about from 0.1 part of the unit to about 4 parts of the unit, or from about 0.3 part of the unit to about 3.0 parts of the unit, or from about 0.2 part of the unit to about 2, 0 part of the unit.
[000106] The crosslinking agent component may comprise or consist of a combination of two or more crosslinking agents, each of which has a different polymerizable functional group. For example, the crosslinking agent component can comprise a vinyl-containing crosslinking agent, and an acrylate-containing crosslinking agent. The crosslinking agent component can comprise a vinyl-containing crosslinking agent and a methacrylate-containing crosslinking group. The crosslinking agent component can comprise or consist of a crosslinking agent containing vinyl ether, and a crosslinking agent containing methacrylate.
[000107] When the polymerizable composition comprises at least one crosslinking agent, the total amount of crosslinking agents (i.e., the total unit parts of all crosslinking agents present in the polymerizable composition) may be an amount of about 0. 01 part of the unit to about 5 parts of the unit, or from about 0.1 part of the unit to about 4 parts of the unit, or from about 0.3 part of the unit to about 3.0 parts of the unit unit, or from about 0.2 part unit to about 2.0 part unit, or from about 0.6 to about 1.5 part unit.
[000108] In one example, when the present polymerizable composition comprises at least one vinyl-containing crosslinker, the total amount of vinyl-containing crosslinkers present in the polymerizable composition may be an amount of about 0.01 part of the a unit of about 2.0 parts of the unit, or from about 0.01 part of the unit to about 0.80 part of the unit, or from about 0.01 part of the unit to about 0.30 part of the unit, or from about 0.05 part of the unit to about 0.20 part of the unit, or in an amount of about 0.1 part of the unit.
[000109] When the polymerizable composition comprises a first siloxane monomer and at least one crosslinking agent, the first siloxane monomer (e.g., a first siloxane monomer present as the only siloxane monomer of the polymerizable composition , or a first siloxane monomer present as part of a siloxane monomer component comprised of two or more siloxane monomers) and the at least one crosslinking agent (i.e., a single crosslinking agent or a crosslinking agent component composed of two or more crosslinking agents) may be present in the polymerizable composition in a ratio of at least 10:1, based on the total unit parts by weight of the first siloxane monomer to the total unit parts by weight of the at least one agent crosslinker (i.e., the sum of the unit parts of all vinyl-containing crosslinkers present in the polymerizable composition). For example, the ratio can be at least 25:1 or at least 50:1 or at least 100:1 based on parts of the unit by weight.
[000110] In an example, the at least one cross-linking agent may comprise at least one vinyl-containing cross-linker and at least one methacrylate-containing cross-linking agent. In another example, the at least one cross-linking agent can consist of only one or more vinyl-containing cross-linking agents. In another example, the at least one cross-linking agent may comprise or consist of at least one vinyl ether-containing cross-linking agent. In yet another example, the at least one crosslinking agent can consist of only one or more vinyl-containing crosslinking agents. In a particular example, the at least one cross-linking agent may comprise or consist of at least one vinyl ether-containing cross-linking agent.
[000111] When the at least one crosslinking agent comprises or consists of at least one vinyl-containing crosslinking agent (i.e. a single vinyl-containing crosslinking agent or a vinyl-containing crosslinking agent component composed of two or more vinyl-containing crosslinking agents ), the first siloxane monomer and the at least one vinyl-containing crosslinker may be present in the polymerizable composition in a ratio of at least about 50:1, based on a ratio of a total number of parts of the unit. siloxane monomer for a total number of unit parts of the at least one vinyl-containing cross-linking agent (i.e., the sum of the unit parts of all vinyl-containing cross-linking agents present in the polymerizable composition). For example, the ratio can be from about 50:1 to about 500:1, or from about 100:1 to about 400:1, or from about 200:1 to about 300:1, based on in the unit parts by weight.
[000112] When the polymerizable composition comprises a first siloxane monomer and at least one additional siloxane monomer (i.e. a second siloxane, and optionally a third siloxane monomer, a fourth siloxane monomer, etc.) in combination with at least one crosslinking agent, the siloxane monomers and the at least one vinyl-containing monomer can be present in the polymerizable composition in a ratio of at least about 100:1, based on a ratio of a total number of unit parts of each siloxane monomer present in the polymerizable composition (ie, the sum of the unit parts of the first siloxane and the second siloxane monomer and, if present, the third siloxane monomer, etc.) to one total number of unit parts of the at least one vinyl-containing crosslinker (i.e., the sum of the unit parts of all vinyl-containing crosslinkers present in the polymerizable composition). For example, the ratio can be from about 50:1 to about 500:1, or from about 100:1 to about 400:1, or from about 200:1 to about 300:1, based on in the unit parts by weight.
[000113] In an example, a total amount of siloxane monomers present in the polymerizable composition (that is, the total unit parts of the first siloxane monomer and, if present, of a second siloxane monomer, and at least one a third siloxane monomer) can be an amount of about 30 to 45 parts of the unit, or about 36 to 40 parts of the unit.
[000114] The polymerizable composition may optionally include one or more organic diluents, one or more polymerization inhibitors (i.e. ultraviolet (UV) inhibitors or thermal inhibitors, or both), or one or more UV absorbing agents, or one or more coloring agents, or one or more oxygen scavengers, or one or more chain transfer agents, or any combination thereof. These optional ingredients can be polymerizable or non-polymerizable ingredients. In one example, the polymerizable compositions may be without diluents in that they do not contain any organic diluents to achieve miscibility between the siloxanes and other lens-forming ingredients such as hydrophilic monomers, hydrophobic monomer, and the optional crosslinking agents. Furthermore, many of the present polymerizable compositions are essentially free of water (e.g., contain no more than 3.0% or 2.0% water by weight).
[000115] The polymerizable compositions disclosed herein may optionally comprise one or more organic diluents, that is, the polymerizable composition may comprise an organic diluent, or may comprise an organic diluent component comprising two or more organic diluents. Organic diluents which may optionally be included in the present polymerizable compositions include alcohols, including lower alcohols, such as, for example, without limitation, pentanol, or hexanol, or octanol, or de-canol, or any combination from them. When included, the organic diluent or organic diluent component may be provided in the polymerizable composition in an amount of from about 1 to about 70 parts of the unit, or from about 2 parts of the unit to about 50 parts of the unit, or from about 5 parts of the unit to about 30 parts of the unit.
[000116] The present polymerizable compositions may optionally comprise one or more polymerization initiators, i.e., the polymerizable composition may comprise an initiator, or may comprise an initiator component comprising two or more polymerization initiators. Polymerization initiators that can be included in the present polymerizable compositions include, for example, azo compounds, or organic peroxides, or both. Initiators that may be present in the polymerizable composition include, for example, without limitation, benzoin ethyl ether, or benzyl dimethyl ketal, or alpha, alpha-diethoxyacetophenone, or 2,4,6-trimethylbenzoyl diphenyl phosphine oxide, or benzoin peroxide, or t-butyl peroxide, or azobisisobutyronitrile, or azobisdimethylvaleronitoryl, or any combination thereof. UV photoinitiators may include, for example, phosphine oxides such as diphenyl(2,4,6-trimethyl benzoyl)phosphine oxide, or benzoin methyl ether, or 1-hydroxycyclohexylphenyl ketone, or Darocur (available from BASF, Florham Park, NJ, USA), or Irgacur (also available from BASF), or any combination of them. In many of the Examples 1-37 disclosed herein, the polymerization initiator is thermal initiator 2,2'-azobis-2-methyl propanenitrile (VAZO-64 from EI DuPont de Nemours & Co., Wil-mington, DE, USA ). Other commonly used thermoinitiators can include 2,2'-azobis(2,4-dimethylpentanenitrile) (VAZO-52) and 1,1'-azo bis(cyanocyclohexane) (VAZO-88). The polymerization initiator or initiator component can be present in the polymerizable composition in an amount of from about 0.01 part of the unit to about 2.0 parts of the unit, or in an amount of about 0.1 part of the unit to about 1.0 part of the unit, or from about 0.2 part of the unit to about 0.6 part of the unit by weight.
[000117] Optionally, the present polymerizable compositions may comprise one or more UV absorbing agents, i.e. the polymerizable composition may comprise a UV absorbing agent, or may comprise a UV absorbing agent component comprising two or more agents UV absorbers. UV absorbing agents that can be included in the present polymerizable compositions include, for example, the benzophenones, or the benzotriazoles, or any combination thereof. In many of the Examples 1-37 disclosed herein, the UV absorbing agent is 2-(4-benzoyl-3-hydroxyphenoxy)ethyl acrylate (UV-416) or 2-(3-(2H-benzotriazole) methacrylate -2-yl)-4-hydroxy-phenyl)ethyl (NORBLOC® 7966 from Noramco, Athens, GA, USA). The UV absorbing agent or UV absorbing agent component can be present in the polymerizable composition in an amount of from about 0.01 part unit to about 5.0 part unit, or in an amount of about 0.01 part unit. 0.1 part unit to about 3.0 parts unit, or from about 0.2 part unit to about 2.0 parts unit by weight.
[000118] The polymerizable compositions of the present disclosure may also optionally include at least one coloring agent (i.e., a coloring agent or a coloring agent component comprising two or more coloring agents), although both colored and colored lens products are contemplated. transparent. In one example, the coloring agent may be a reactive dye or pigment effective to impart color to the resulting lens product. The coloring agent or coloring agent component of the polymerizable composition can comprise a polymerizable coloring agent, or it can comprise a non-polymerizable coloring agent, or any combination thereof. The polymerizable coloring agent can be a coloring agent whose molecular structure comprises a polymerizable functional group, or it can be a coloring agent whose molecular structure includes both a monomer part and a dye part, i.e., the coloring agent can be a dye-monomer compound. The molecular structure of the coloring agent may comprise a beta sulfone functional group, or it may comprise a triazine functional group. Coloring agents may include, for example, VAT Blue 6 (7,16-Dichloro-6,15-dihydroanthrazine-5,9,14,18-tetrone), or 1-Amino-4-[3-( beta-sulfatoethylsulfonyl)anilium]-2-anthraquinonesulfonic (Reactive Blue CI 19, RB-19), or a dye-monomer compound of Reactive Blue 19 and hydroxyethyl methacrylate (RB-19 HEMA), or to 1.4 -bis[4-[(2-methacryl-oxyethyl)phenylamino]anthraquinone (Reactive Blue 246, RB-246, available from Arran Chemical Company, Athlone, Ireland), or the 1,4-bis[(2- hydroxyethyl)amino]-9,10-anthracenedione bis(2-propenoic) (RB-247), or Reactive Blue 4, RB-4, or a dye-monomer compound of Reactive Blue 4 and hydroxyethyl methacrylate (RB- 4 HEMA or "Blue HEMA"), or any combination thereof. In one example, the coloring agent or coloring agent component may comprise a polymerizable coloring agent. The polymerizable coloring agent component may comprise, for example, RB-246, or RB-274, or RB-4 HEMA, or RB-19 HEMA, or any combination thereof. Examples of dye-monomer compounds include RB-4 HEMA and RB-19 HEMA. Additional examples of dye-monomer compounds are described in US5944853 and US7216975, both of which are incorporated in their entirety by reference herein. Illustrative coloring agents are disclosed, for example, in U.S. Patent Application Publication No. 2008/0048350, the entire disclosure of which is incorporated by reference. In many of the Examples 1-37 disclosed herein, the coloring agent is a reactive blue dye, such as those described in US4997897, the disclosure of which is incorporated in its entirety herein by reference. Other coloring agents suitable for use in accordance with the present invention are phthalocyanine pigments, such as phthalocyanine blue, or phthalocyanine green, or chromic-alumina-cobalt oxide, or chromium oxides, or the various iron oxides for the colors red, yellow, brown and black, or any combination of them. Opacifying agents, such as titanium dioxide, can also be incorporated. For certain applications, a combination of coloring agents having different colors can be employed as the coloring agent component. If employed, the coloring agent or coloring agent component may be present in the polymerizable composition in an amount ranging from about 0.001 part unit to about 15.0 part unit, or about 0.005 part unit to about 10 .0 part of unit, or about 0.01 part of unit to about 8.0 part of unit.
[000119] Chain transfer is a polymerization reaction in which the activity of a growing polymer chain is transferred to another molecule, reducing the average molecular weight of the final polymer. The polymerizable compositions of the present disclosure may optionally comprise at least one chain transfer agent, that is, they may comprise a chain transfer agent, or they may comprise a chain transfer agent component comprising at least two chain transfer agents. Examples of chain transfer agents which may be included as the chain transfer agent or the chain transfer component of the present polymerizable compositions include, for example, the thiol compounds, or the halocarbon compounds, or the C3-C5 hydrocarbons, or any combination thereof. In many of the Examples 1-37 disclosed in this document, the chain transfer agent is allyloxy ethanol. When present in the polymerizable composition, the chain transfer agent or chain transfer agent component may be present in an amount of from about 0.01 part per unit to about 1.5 part per unit, e.g. about 0.1 part of the unit to about 0.5 part of the unit.
[000120] Several methods of measuring contact angles, including the trapped bubble method, are known to those of ordinary skill in the art. The contact angle can be a static or dynamic contact angle.
[000121] The silicone hydrogel contact lenses of the present invention may have contact angles that dynamically advance per trapped bubble of less than 120 degrees, such as, for example, less than 90 degrees when fully hydrated, less than that 80 degrees when fully hydrated, less than 70 degrees when fully hydrated, or less than 65 degrees when fully hydrated, or less than 60 degrees when fully hydrated, or less than 50 degrees when fully hydrated.
[000122] The silicone hydrogel contact lenses of the present invention may have trapped bubble static contact angles of less than 70 degrees when fully hydrated, or less than 60 degrees when fully hydrated, or less than 55 degrees when fully hydrated, or less than 50 degrees when fully hydrated, or less than 45 degrees when fully hydrated.
[000123] According to the present disclosure, silicone hydrogel contact lenses can have, when fully hydrated, equilibrium water contents (EWC)s of about 30 to about 70%. For example, contact lenses can have an EWC of from about 45% to about 65%, or from about 50% to about 63%, or from about 50% to about 67%, or from about 55% to about 65% by weight when fully hydrated. Methods of determining EWC are known to those of ordinary skill in the art, and may be based on the weight loss of a lens during a drying process.
[000124] The present contact lenses may have an oxygen permeability (or Dk) of at least 55 barrers (Dk > 55 barrers), or an oxygen permeability of at least 60 barrers (Dk > 60 barrers), or a permeability to oxygen of at least 65 barrers (Dk > 65 barrers). The lenses can have an oxygen permeability of from about 55 barrers to about 135 barrers, or from about 60 barrers to about 120 barrers, or from about 65 barrers to about 90 barrers, or about from 50 barrers to about 75 barrers. Several methods of determining oxygen permeability are known to those of ordinary skill in the art.
[000125] The present contact lenses may have an oxygen permeability of at least 55 barrers (Dk > 55 barrers), or an EWC of about 30% to about 70%, or a dynamic advancing contact angle per bubble trapped less than 90 degrees, or a static contact angle per trapped bubble less than 70 degrees, or any combination thereof. In one example, contact lenses may have an oxygen permeability of at least 60 barrers (Dk > 60 barrers), or an EWC of about 35% to about 65%, or a dynamically advancing contact angle per bubble trapped less than 70 degrees, or a static contact angle per trapped bubble less than 55 degrees, or any combination thereof. In another example, the present contact lenses may have an oxygen permeability of at least 65 barrers, or an EWC of about 45% to about 65%, or a contact angle that advances dynamically by trapped bubble smaller than the than 70 degrees, or a static contact angle per trapped bubble of less than 55 degrees, or any combination thereof.
[000126] In one example, the present contact lenses may have, when fully hydrated, an oxygen permeability of at least 55 barrers (Dk > 55 barrers), and a tension modulus of from about 0.2 MPa to about 0.9 MPa, and a dynamic advancing contact angle per trapped bubble less than 70 degrees, and a static contact angle per trapped bubble less than 55 degrees.
[000127] The silicone hydrogel contact lenses of the present disclosure can have, when fully hydrated, an average tension modulus of about 0.20 MPa to about 0.90 MPa. For example, the average modulus can be from about 0.30 MPa to about 0.80 MPa, or from about 0.40 MPa to about 0.75 MPa, or from about 0.50 MPa to about 0.70 MPa.
[000128] As used herein, the modulus of a contact lens or lens body is understood to refer to the tension modulus, also known as Young's modulus. It is a measure of the stiffness of an elastic material. The modulus of voltage can be measured using a method according to ANSI standard Z80.20. In one example, the modulus voltage can be measured using an Instron Model 3342 or Model 3343 mechanical test system.
[000129] The silicone hydrogel contact lenses of the present disclosure can have, when fully hydrated, an average percentage energy loss of about 25% to about 40%. For example, the average percentage of energy loss can be from about 27% to about 40%, or it can be from about 30% to about 37%.
[000130] As used in this document, percent energy loss is a measure of energy lost as heat when energy charge and discharge cycles are applied to viscoelastic materials. The percentage of energy loss can be determined using several methods known to those of ordinary skill in the art. For example, the force involved in extending a sample to 100% strain, and then returning it to 0% at a constant rate can be determined and used to calculate the percentage energy loss for the material.
[000131] The present contact lenses, when fully hydrated, may have an ionoflux less than about 8.0 x 10-3 mm2/min, or less than about 7.0 x 10-3 mm2/ min, or less than about 5.0 x 10-3 mm2/min. The various methods of determining ionoflux are conventional and are known to those of ordinary skill in the art.
[000132] In one example, the present contact lenses may have a wet extractable component. The wet extractable component is determined based on the weight lost during methanol extraction of contact lenses, which have been fully hydrated and sterilized prior to drying and extraction testing. The wet extractable component may comprise unreacted or partially reacted polymerizable ingredients of the polymerizable composition. The wet extractable component consists of organic solvent extractable materials that remain in the lens body after the lens body has been fully processed to form a sterile contact lens, for lenses formed from polymerizable compositions comprising non-polymerizing ingredients. available. For lenses extracted during manufacture in an extraction liquid comprising a volatile organic solvent or an extraction liquid free of an organic solvent, in most cases, substantially all of the non-polymerizable ingredients will have been removed from the lens body and Thus, the wet extractable component can consist essentially of extractable components formed from reactive polymerizable ingredients of the polymerizable composition, i.e., unreacted polymerizable components and partially reacted polymerizable ingredients. In lenses made from a thinner-free polymerizable composition, the wet extractable component may be present in the contact lens in an amount of from about 1% w/w to about 15% w/w, or from about 2% w/w about 10% w/w, or from about 3% w/w about 8% w/w, based on the dry weight of the lens body prior to the extraction test. In lenses made from a polymerizable composition comprising a diluent, the wet extractable component may consist of a part of the diluent, as well as unreacted and partially reacted polymerizable ingredients, and may be present in the contact lens in an amount of about 1 % w/w about 20% w/w, or from about 2% w/w about 15% w/w of the lens, or from about 3% w/w about 10% w/w, based on the dry weight of the lens body before the extraction test.
[000133] In one example, the present contact lenses have a dry extractable component. The dry extractable component is determined based on the weight lost during methanol extraction of polymeric lens bodies which have not been washed, extracted (as part of a manufacturing process), hydrated or sterilized prior to drying and extraction testing . The dry extractable component may comprise unreacted or partially reacted polymerizable ingredients of the polymerizable composition. When optional non-polymerizable ingredients, such as diluents and the like, are present in the polymerizable composition, the dry extractable component can additionally comprise the non-polymerizable ingredients.
[000134] In lenses made from a thinner-free polymerizable composition, the dry extractable component of the lens consists mainly of dry extractable components, contributed by polymerizable ingredients of the polymerizable composition (i.e., unreacted or partial polymerizable ingredients. reacted), and may also include dry extractable materials contributed by optional non-polymerizable components, present in the polymerizable composition in small amounts (e.g., less than 3% w/w), such as, for example, coloring agents, oxygen scavengers, and the like. In lenses made of a polymerizable composition free from a diluent, the dry extractable component may be present in the polymeric lens body in an amount of from about 1% w/w to about 30% w/w of the lens body, or about 2% w/w about 25% w/w, or from about 3% w/w about 20% w/w, or from about 4% w/w about 15% w/w, or from 2% w/p less than 10% w/w based on dry weight of lens body prior to extraction test.
[000135] In lenses made from a polymerizable composition comprising a large amount (eg, greater than 3% w/w) of an optional non-polymerizable ingredient, such as a thinner, the dry extractable component consists of materials extractables contributed by reactive ingredients, as well as extractable components contributed by non-polymerizable ingredients of the polymerizable composition. The total amount of dry extractable components, contributed by reactive ingredients and non-polymerizable ingredients present in the contact lens, may consist of an amount of about 1% w/w about 75% w/w, or about 2 % w/w about 50% w/w of the lens, or from about 3% w/w to about 40% w/w, or from about 4% w/w to about 20% w/w, or from about 5% to about 10%, based on the dry weight of the polymeric lens body prior to the extraction test. The total amount of dry extractable components contributed by polymerizable ingredients (i.e. unreacted or partially reacted polymerizable ingredients) can be an amount of about 1% w/w to about 30% w/w of the lens body , or from about 2% w/w to about 25% w/w, or from about 3% w/w to about 20% w/w, or from about 4% w/pa about 15% w/ p, or 2% w/p to less than 10% w/w, based on the dry weight of the lens body prior to the extraction test.
[000136] It is also to be understood that the reference to the contact lens formed from the compositions described herein is a lens body with an anterior surface and a posterior surface, the posterior surface being configured to be placed in contact with the cornea of an eye of a contact lens wearer. The lens body of the present invention may be entirely transparent. Alternatively, when the contact lens is a cosmetic lens configured to alter the appearance of an iris of a contact lens wearer, the lens body may comprise a transparent optical zone.
[000137] This invention is useful for contact lenses that, when worn, may be in contact with the epithelial tissue or other tissues of the eye. This invention is useful for all known types of contact lenses, including both soft and hard lens materials. In an example of the contact lens of the present invention, the contact lens is a lens with at least one optical zone configured to provide vision correction, improve visual acuity, or both to provide vision correction and improve visual acuity . For example, the optical zone can be configured to provide a spherical correction, a toric correction, or a third-order or higher correction. The optical zone can be configured to improve visual acuity at near-seeing distances, at far-seeing distances, or at both near- and far-seeing distances. Other features and examples of the contact lenses of the present invention are illustrated in the following sections.
[000138] The present hydrogel contact lenses are contact lenses that correct vision or improve vision. The lenses can be spherical lenses or aspherical lenses. The lenses can be monofocal lenses or multifocal lenses, including bifocal lenses. In certain examples, the present lenses are rotationally stabilized lenses, such as the rotationally stabilized toric contact lens. A rotatably stabilized contact lens can be a contact lens that comprises a lens body that includes a ballast. For example, the lens body may have a prism ballast, a perilastr, and/or one or more finely tuned upper and lower regions.
[000139] The present lenses also comprise lens bodies that include a peripheral edge region. The peripheral edge region may include a rounded portion. For example, the peripheral edge region can comprise a rounded trailing edge surface, a rounded leading edge surface, or a combination of these. The peripheral edge can be completely rounded from the anterior surface to the posterior surface. Therefore, it can be understood that the lens body of the present lenses may comprise a rounded peripheral edge.
[000140] The contact lenses of the present disclosure, as they are configured to be placed or disposed over a cornea of an animal or human eye, are ophthalmically acceptable contact lenses. As used herein, an ophthalmically acceptable contact lens is understood to be a contact lens having at least one of several different properties as described below. An ophthalmically acceptable contact lens can be formed from, and packaged in, ophthalmically acceptable ingredients such that the lens is not cytotoxic and does not release irritating and/or toxic ingredients during use. An ophthalmically acceptable contact lens may have a level of transparency in the optical zone of the lens (ie, the part of the lens that provides vision correction) sufficient for its intended use in contact with the cornea of an eye, by example, a transmittance of at least 80%, or at least 90%, or at least 95% visible light. An ophthalmically acceptable contact lens may have sufficient mechanical properties to facilitate handling and care of the lens for a duration of time based on its intended lifetime. For example, its modulus, tensile strength, and elongation may be sufficient to support insertion, wear, removal and, optionally, cleaning during the intended life of the lens. The level of these properties that are appropriate will vary depending on the intended lifespan and use of the lens (eg, single daily use disposable, multiple monthly use, etc.). An ophthalmically acceptable contact lens may have an effective or suitable ionoflux to substantially inhibit or substantially prevent corneal staining after continuous wear of the lens over a cornea for 8 or more hours. An ophthalmically acceptable contact lens may have a level of oxygen permeability sufficient to allow oxygen to reach the cornea of a lens-wearing eye in an amount sufficient for long-lasting corneal health. An ophthalmically acceptable contact lens can be a lens that does not cause substantial or undue swelling in an eye using the lens, for example, no more than 5% or 10% corneal swelling after being worn over a cornea of a eye during a night sleep. An ophthalmically acceptable contact lens can be a lens that allows the lens to move over the cornea of an eye that uses the lens enough to facilitate the flow of tears between the lens and the eye, in other words, don't cause the lens adhere to the eye with sufficient force to prevent normal lens movement, and have a low enough level of movement over the eye to allow vision correction. An ophthalmically acceptable contact lens can be a lens that allows the lens to be worn over the eye without undue or significant discomfort and/or irritation and/or pain. An ophthalmically acceptable contact lens can be a lens that inhibits or substantially prevents the deposit of lipids and/or proteins sufficient to cause the lens wearer to remove the lens because of such deposits. An ophthalmically acceptable contact lens may have at least one of a water content, or a surface wettability, or a module or a design, or any combination thereof, that is effective to facilitate the ophthalmically compatible use of the contact lens by a contact lens wearer for at least one day. Ophthalmically compatible use is understood to refer to the use of a lens by a lens wearer with little or no discomfort, and with little or no occurrence of corneal staining. Determining whether a contact lens is ophthalmically acceptable can be obtained using conventional clinical methods, such as those performed by a professional treating the eye, and as understood by persons of ordinary skill in the art.
[000141] In an example of the present disclosure, the contact lens may have ophthalmic and acceptably wettable lens surfaces. For example, the contact lens can have ophthalmic lens surfaces and acceptably wettable when the polymerizable composition used to form the polymeric lens body is free of an internal wetting agent, or when the polymerizable composition used to form the lens. polymeric lens body is free of an organic diluent, or when the polymeric lens body is extracted into water or an aqueous solution free of a volatile organic solvent, or when the polymeric lens body is free of a treatment. surface by plasma, or any combination thereof.
[000142] A commonly used approach in the art to increase the wettability of contact lens surfaces is to apply treatments to lens surfaces or modify lens surfaces. In accordance with the present disclosure, silicone hydrogel contact lenses can have ophthalmic and acceptably wet lens surfaces without the presence of a surface treatment or surface modification. Surface treatments include, for example, plasma and corona treatments, which increase the hydrophilicity of the lens surface. While it is possible to apply one or more plasma surface treatments to the present lens bodies, it is not necessary to do so to obtain a silicone hydrogel contact lens having the lens surfaces ophthalmic and acceptably wet when fully hydrated. In other words, in one example, the silicone hydrogel contact lenses of the present disclosure may be exempt from a surface treatment by plasma or corona effect.
[000143] Surface modifications include binding wetting agents to the lens surface, such as, for example, binding a wetting agent, such as a hydrophilic polymer, to at least one lens surface per alloy. chemical -tion or other form of chemical interaction. In some cases, the wetting agent can be bonded to the lens surface, as well as to at least a portion of the lens polymer matrix, i.e., to at least a portion of the lens mass, by chemical bonding or other form of chemical interaction. The surfaces of the ophthalmic and acceptably wettable lenses of the present disclosure can be ophthalmically and acceptably wettable without the presence of a wetting agent (e.g., a polymeric material or a non-polymeric material) bonded at least to the surface of the lens. -you. While it is possible to attach one or more wetting agents to the present lenses, it is not necessary to do so to obtain a silicone hydrogel contact lens having the lens surfaces ophthalmic and acceptably wet when fully hydrated. Thus, in one example, the lenses of the present disclosure may comprise wetting agents, such as, for example, hydrophilic polymers and including polyvinyl pyrrolidone, bonded to a surface of the lens. Alternatively, in another example, the silicone hydrogel contact lenses of the present disclosure may be free of a wetting agent attached to the lens surface.
[000144] Another method of increasing lens wettability is to physically capture a wetting agent within the lens body or contact lens, such as by introducing the wetting agent into the lens body when the lens body is swollen, and then return the lens body to a less swollen state, thereby capturing a portion of a wetting agent within the lens body. The wetting agent can be permanently trapped within the lens body, or it can be released from the lens over time, such as during use. The ophthalmic and acceptably wet lens surfaces of the present disclosure may be ophthalmically and acceptably wet without the presence of a wetting agent (e.g., a polymeric material or a non-polymeric material) physically trapped in the body of lens after polymeric lens body formation. While it is possible to physically capture one or more wetting agents in the present lenses, it is not necessary to do so to obtain a hydrogel silicone contact lens having the lens surfaces ophthalmic and acceptably wet when fully hydrated. Thus, in one example, the lenses of the present disclosure may comprise wetting agents, such as, for example, hydrophilic polymers and including polyvinyl pyrrolidone, trapped within the lens. Alternatively, the hydrogel contact lenses of the present disclosure, for example the silicone hydrogel contact lenses of the present disclosure, can be free of a wetting agent physically trapped within the lens. As used herein, physically captured refers to immobilizing a wetting agent, or other ingredient, in the polymeric matrix of the lens, with little or no chemical bonding or chemical interaction being present between the wetting agent and/or the other ingredient and the matrix polymeric. This is in contrast to ingredients that are chemically bonded to the polymeric matrix, such as by ionic bonds, covalent bonds, Van der Waals forces, and the like.
[000145] Another approach commonly used in the art to increase the wettability of hydrogel contact lenses, for example, silicone hydrogel contact lenses, includes adding one or more wetting agents to the polymerizable composition. In one example, the wetting agent can be a polymeric wetting agent. However, the contact lenses of the present disclosure can have ophthalmic lens surfaces and be acceptably wettable when the polymerizable composition used to form the polymeric lens body is free of a wetting agent. While it is possible to include one or more wetting agents in the present polymerizable compositions to increase the wettability of the hydrogel contact lenses of the present disclosure, it is not necessary to do so to obtain a hydrogel contact lens having ophthalmic and ophthalmic lens surfaces. acceptably wettable. In other words, in one example, the hydrogel contact lenses of the present disclosure can be formed from wetting agent-free polymerizable compositions. Alternatively, in another example, the polymerizable compositions of the present invention may additionally comprise a wetting agent.
[000146] In an example, the wetting agent may be an internal wetting agent. The internal wetting agent can be bonded within at least a portion of the polymer matrix of the lens. For example, the internal wetting agent can be bonded within at least a portion of the lens polymer matrix by chemical bonding or other form of chemical interaction. In some cases, the wetting agent can be attached to the lens surface as well. The internal wetting agent can comprise a polymeric material or a non-polymeric material. While it is possible to bind one or more internal wetting agents within the polymer matrix of the present lenses, it is not necessary to do so to obtain a hydrogel contact lens having the lens surfaces ophthalmic and acceptably wet when fully hydrated. Thus, in one example, the lenses of the present disclosure can comprise internal wetting agents bonded to at least a portion of the polymer matrix of the lens. Alternatively, in another example, the hydrogel contact lenses of the present disclosure may be free of an internal wetting agent bonded to at least a portion of the polymer matrix of the lens.
[000147] In another example, the wetting agent may be an internal polymeric wetting agent. The polymeric inner wetting agent may be present in the polymeric lens body as part of an interpenetrating polymer network (IPN) or a semi-IPN. A network of interpenetrating polymers is made up of at least two polymers, each of which is cross-linked to itself, but neither of which is cross-linked to the other. Similarly, a semi-IPN is formed from at least two polymers, at least one of which is cross-linked to itself but not to the other polymer, and the other is not cross-linked to itself or the other polymer. In one example of the present disclosure, the contact lens can have ophthalmic and acceptably wet lens surfaces when the polymeric lens body is free of an internal polymeric wetting agent present in the lens body such as an IPN or a semi-IPN. Alternatively, the contact lens can comprise an internal polymeric wetting agent present in the lens body such as an IPN or a semi-IPN.
[000148] In yet another example, the wetting agent may be a binding compound present in the polymerizable composition used to form the lens body, or a binding agent physically captured within the polymeric lens body after the lens body. lens have been formed. When the wetting agent is a binding compound, after polymerization of the lens body or capture of the binding agent in the polymeric lens body, the binding compound may subsequently bind a second wetting agent to the lens body when the body lens is contacted by the wetting agent. Bonding can occur as part of the manufacturing process, for example as a washing process, or it can occur when the lens body is contacted by a conditioning solution. The bond can take the form of an ionic bond, or a covalent bond, or a form of a Van der Waals attraction. The bonding agent may comprise a boronic acid moiety or group such that a polymerized boronic acid moiety or group is present in the polymeric lens body, or such that a boronic acid moiety or group is physically captured in the polymeric lens body. For example, when the binding agent comprises a form of boronic acid, the second wetting agent may comprise a form of poly(vinyl alcohol), which becomes bound to the form of boronic acid. Optionally, the silicone hydrogel contact lenses of the present disclosure can be understood to be free of bonding agents. In one example, silicone hydrogel contact lenses may be free of boronic acid moieties or groups, including polymerized boronic acid moieties or groups, namely, specifically, silicone contact lenses hydrogels can be formed from a polymerizable composition free of a form of boronic acid, such as, for example, a polymerizable form of boronic acid, including vinyl phenyl boronic acid (VPB), can be formed from a polymer free of units derived from a polymerizable form of boronic acid, such as vinyl phenyl boronic acid (VPB), and the polymeric lens body and silicone hydrogel contact lenses may be free from a form of boronic acid, including the polymeric form. or non-polymeric boronic acid, physically trapped in them. Alternatively, the polymerizable composition, or the polymeric lens body, or the hydrogel contact lens, or any combination thereof, can comprise at least one binding agent.
[000149] In addition to the inclusion of wetting agents in the polymerizable composition and the modification of lens surfaces, washing polymeric lens bodies in volatile organic solvents or aqueous solutions of volatile organic solvent has been used to increase the wettability of the lenses. lens surfaces, particularly the surfaces of silicone hydrogel contact lenses. While it is possible to wash the present polymeric lens bodies in a volatile organic solvent or an aqueous solution of a volatile organic solvent, in accordance with the present disclosure, it is not necessary to do so to obtain a hydrogel contact lens having surfaces of ophthalmic lenses and acceptably wet when fully hydrated. In other words, in one example, the hydrogel contact lenses of the present invention were not exposed to a volatile organic solvent, including a solution of a volatile organic solvent, as part of a manufacturing process. In one example, the hydrogel contact lenses of the present invention can be formed from a polymerizable composition free of a wetting agent, or the polymeric lens body and/or hydrated contact lens can be free of an agent. wetting, or free from surface treatment, or free from a surface modification, or has not been exposed to a volatile organic solvent during the manufacturing process, or any combination thereof. In contrast, for example, hydrogel contact lenses can be washed in a washing liquid free from a volatile organic solvent, such as, for example, water or an aqueous solution free from a volatile organic solvent, including liquids. free from a volatile lower alcohol.
[000150] The use of volatile organic solvents to extract the lens bodies significantly contributes to production costs, due to factors such as the cost of organic solvents, the cost of removing the solvents, the need to employ production equipment explosion-proof, the need to remove solvents from the lenses before packaging, and the like. However, it can be challenging to develop polymerizable compositions capable of consistently producing contact lenses with ophthalmic lens surfaces and acceptably wet when extracted in an aqueous liquid free of volatile organic solvents. For example, it is common to find non-wetting regions present on the surfaces of contact lenses that have been extracted in an aqueous liquid free of volatile organic solvents.
[000151] As discussed above, in an example of the present disclosure, contact lenses are contact lenses that had not been exposed to a volatile organic solvent, such as a lower alcohol, during their manufacture. In other words, the washing, extraction and moisturizing liquid used for such lenses, as well as all liquids used during wet demolding, or wet lens removal, or washing, or any other stage of manufacturing, are all free of volatile organic solvents. In one example, the polymerizable composition used to form these lenses which are not contacted by a volatile organic solvent may comprise a hydrophilic vinyl-ether-containing monomer or component, such as, for example, a hydrophilic vinyl ether-containing monomer. The hydrophilic vinyl-containing monomer or monomer component can include, for example, VMA. Vinyl ether-containing monomers can include, for example, BVE, or EGVE, or DEGVE, or any combination thereof. In a particular example, the vinyl ether-containing monomer may be a vinyl ether-containing monomer that is more hydrophilic than BVE, such as, for example, DEGVE. In another example, the hydrophilic monomer component of the polymerizable composition may be a mixture of a first hydrophilic monomer, which is a vinyl-containing monomer, but which is not a vinyl ether-containing monomer, and a second hydrophilic monomer. , which is a monomer containing vinyl ether. Such mixtures include, for example, mixtures of VMA and one or more vinyl ethers, such as, for example, BVE, or DEGVE, or EGVE, or any combination thereof.
[000152] When present, the hydrophilic monomer or monomer component containing vinyl ether may be present in the polymerizable composition in an amount of from about 1 to about 15 parts of the unit, or from about 3 to about 10 parts of the unit. When present as a mixture with a vinyl-containing hydrophilic monomer that is not a vinyl ether, the part of the vinyl-containing hydrophilic monomer or monomer component that is not a vinyl ether and the hydrophilic monomer-containing monomer or component Vinyl ether may be present in the polymerizable composition in a ratio of at least 3:1, or from about 3:1 to about 15:1, or from about 4:1, based on the ratio of the parts of the unit. by weight of the vinyl ether-containing hydrophilic monomer or monomer component that is not a vinyl ether to the unit parts by weight of the vinyl ether-containing hydrophilic monomer or monomer component.
[000153] Another approach to producing contact lenses having ophthalmic and acceptably wettable lens surfaces in accordance with the present disclosure, particularly lenses extracted in a liquid free of a volatile organic solvent and including lenses that are not contacted by a volatile organic solvent during manufacture, it may be to limit the amount of a crosslinking agent or vinyl-containing crosslinking agent component included in the polymerizable composition. For example, a crosslinking agent or vinyl-containing crosslinking agent component can be present in the polymerizable composition in an amount of from about 0.01 to about 0.80 part of the unit, or from 0.01 to about 0.01 to about 0.30 part of the unit, or from about 0.05 to about 0.20 part of the unit, or in an amount of about 0.1 part of the unit. In one example, a crosslinking agent or vinyl-containing crosslinking agent component may be present in the polymerizable composition in an effective amount to produce a contact lens having improved wettability compared to a contact lens produced from the same polymerizable composition, however having an amount of the crosslinking agent or vinyl-containing crosslinking agent component greater than about 2.0 parts of the unit, or greater than 1.0 part of the unit, or greater than about 0.8 part of unit, or greater than about 0.5 part of unit, or greater than about 0.3 part of unit.
[000154] While limiting the amount of crosslinking agent or vinyl-containing crosslinking agent component can improve wettability, in one example, the inclusion of a crosslinking agent or vinyl-containing crosslinking agent component in the polymerizable composition can improve dimensional stability. -onal of the resulting contact lens, formed from the polymerizable composition. Thus, in some polymerizable compositions, a crosslinking agent or vinyl-containing crosslinking agent component may be present in the polymerizable in an effective amount to produce a contact lens having improved dimensional stability compared to a contact lens produced by from the same polymerizable composition, but without the crosslinking agent or vinyl-containing crosslinking agent component.
[000155] Yet another approach to producing contact lenses having ophthalmic and acceptably wettable lens surfaces in accordance with the present disclosure, particularly lenses washed in a liquid free of a volatile organic solvent, may be to include an amount of an agent crosslinker or vinyl-containing crosslinker component in the polymerizable composition, based on the ratio of the unit parts by weight of the monomer or hydrophilic vinyl-containing monomer component present in the composition to the unit parts by weight of the crosslinker or of the vinyl-containing crosslinking agent component present in the composition. For example, the total unit parts of the vinyl-containing hydrophilic monomer or monomer component and the total unit parts of the vinyl-containing crosslinker or crosslinker component may be present in the polymerizable composition in a ratio greater than about from about 125:1, or from about 150:1 to about 625:1, or from about 200:1 to about 600:1, or from about 250:1 to about 500:1, or from about from 450:1 to about 500:1, based on the ratio of the unit parts by weight of all hydrophilic vinyl-containing monomers present in the polymerizable composition to the total unit parts by weight of all vinyl-containing crosslinkers present in the polymerizable composition.
[000156] In one example, the contact lenses of the present disclosure are ophthalmically compatible silicone hydrogel contact lenses. Many different criteria can be evaluated to determine whether a contact lens is ophthalmically compatible or not, as will be discussed later. In one example, ophthalmically acceptable contact lenses have ophthalmic and acceptably wet surfaces when fully hydrated. A silicone-cone hydrogel contact lens having an ophthalmic and acceptably wettable surface can be understood to refer to a silicone hydrogel contact lens that does not adversely affect the tear film of a lens wearer's eye to a degree that results in the lens wearer experiencing or reporting discomfort associated with placing or wearing a silicone hydrogel contact lens over one eye.
[000157] An example of the disclosed polymerizable composition may be miscible when initially prepared, and may remain miscible for a period of time suitable for the commercial manufacture of contact lenses, such as, for example, for about 2 weeks , or about 1 week, or about 5 days. Typically, when polymerized and processed into contact lenses, miscible polymerizable compositions result in contact lenses having ophthalmically acceptable transparencies.
[000158] Commonly employed approaches to increase the miscibility of hydrophilic monomers and less hydrophilic or relatively hydrophobic monomers, including siloxane monomers, include adding organic diluents to the polymerizable composition to act as compatibilizing agents between the more hydrophilic monomers and the less hydrophilic monomers. For example, using only siloxane monomers having low molecular weights (eg, molecular weights below 2500 daltons) can also increase miscibility. In an example where the polymerizable composition comprises a first siloxane and a second siloxane monomer, the use of a first siloxane of formula (6), as described above, makes it possible to include both an optional second high molecular weight siloxane and a high level of the at least one hydrophilic monomer in the polymerizable compositions of the present disclosure. And while it is possible to include one or more organic diluents in the present polymerizable compositions disclosed herein, it may not be necessary to do so to obtain a miscible polymerizable composition in accordance with the present disclosure. In other words, in one example, the hydrogel contact lenses of the present disclosure are formed from polymerizable compositions that are free of an organic diluent.
[000159] The present hydrogel contact lenses may be provided in a sealed package. For example, the present hydrogel contact lenses may be provided in sealed cartons or other similar containers suitable for delivery to lens wearers. Lenses can be stored in an aqueous solution, such as saline, inside the package. Some suitable solutions include phosphate-buffered saline and borate-buffered solutions. The solutions can include a disinfecting agent, if desired, or can be free of a disinfecting agent or preservative. Solutions can also include a surfactant, such as a poloxamer and the like, if desired.
[000160] The lenses in sealed packages are preferably sterile. For example, lenses can be sterilized prior to sealing the package or can be sterilized in the sealed package. Sterile lenses can be lenses that have been exposed to sterilizing amounts of radiation. For example, the lenses can be autoclaved lenses, gamma radiated lenses, lenses exposed to ultraviolet radiation, and the like.
[000161] With respect to the contact lens package, the package may further comprise a base element with a cavity configured to hold the contact lens body and the packaging solution, and a seal joined to the base element, configured to keep the contact lens and conditioning solution in a sterile condition for a period of time equivalent to the life of the contact lens.
[000162] Certain specific examples of silicone hydrogel contact lenses will now be described in accordance with the present teachings.
[000163] As an example (example A), a silicone hydrogel contact lens comprises a polymeric lens body which is the reaction product of a polymerizable composition comprising at least one hydrophilic monomer, at least one phosphine-containing compound, and at least one siloxane monomer. In one example, the at least one monomer comprises a first siloxane monomer represented by formula (6), where m of formula (6) represents an integer from 3 to 10, n of formula (6) represents an integer from 1 to 10, R1 is an alkyl group having 1 to 4 carbon atoms, and each R2 of formula (6) is independently a hydrogen atom or a methyl group.
[000164] As a second example (example B), a silicone hydrogel contact lens comprises a polymeric lens body which is the reaction product of a polymerizable composition, as described in example A, and where the polymerizable additionally comprises a second siloxane monomer. In one example, the first siloxane monomer and the second siloxane monomer may be present in a ratio of at least 2:1, based on the unit parts by weight of the first siloxane monomer to the unit parts by weight of the second siloxane monomer, present in the polymerizable composition.
[000165] As a third example (example C), a silicone hydrogel contact lens comprises a polymeric lens body which is the reaction product of a polymerizable composition as described in example A or B, and where the composition polymerizable further comprises a hydrophobic monomer or monomer component. For example, the hydrophilic monomer can comprise or consist of methyl methacrylate (MMA), or EGMA, or any combination thereof.
[000166] As a fourth example (example D), a silicone hydrogel contact lens comprises a polymeric lens body which is the reaction product of a polymerizable composition as described in example A or B or C, and where the The polymerizable composition further comprises a crosslinking agent or vinyl-containing crosslinking agent component. In one example, the crosslinking agent or crosslinking agent component may comprise or consist of a crosslinking agent or crosslinking agent component containing vinyl ether, specifically the crosslinking agent or crosslinking agent component may comprise or consist of ether divinyl triethylene glycol (TEGVE).
[000167] As a fifth example (example E), a silicone hydrogel contact lens comprises a polymeric lens body which is the reaction product of a polymerizable composition as described in example A or B or C or D, and where the polymerizable composition further comprises a thermal initiator or thermal initiator component.
[000168] As a sixth example (example F), a silicon-cone hydrogel contact lens comprises a polymeric lens body which is the reaction product of a polymerizable composition as described in example A or B or C or D or And, and where the at least one hydrophilic monomer comprises a hydrophilic monomer component comprising a first hydrophilic monomer and a second hydrophilic monomer. In one example, the first hydrophilic monomer can comprise an amide-containing hydrophilic monomer, and the second hydrophilic monomer can comprise a vinyl ether-containing monomer.
[000169] As a seventh example (example G), a silicone hydrogel contact lens comprises a polymeric lens body which is the reaction product of a polymerizable composition as described in example A or B or C or D or E or F, and where the polymerizable composition further comprises a UV absorbing agent or UV absorbing agent component.
[000170] As an eighth example (example H), a silicone hydrogel contact lens comprises a polymeric lens body which is the reaction product of a polymerizable composition as described in example A or B or C or D or E or F or G, and where the polymerizable composition further comprises a coloring agent or coloring agent component.
[000171] As a ninth example (example I), a silicon-cone hydrogel contact lens comprises a polymeric lens body which is the reaction product of a polymerizable composition as described in example A or B or C or D or E or F or G or H, and where the polymerizable composition comprises a siloxane monomer represented by formula (5), where R1 of formula (5) is selected from a hydrogen atom or a methyl group; R2 of formula (5) is selected from hydrogen or a hydrocarbon group having 1 to 4 carbon atoms; m of formula (5) represents an integer from 0 to 10; n of formula (5) represents an integer from 4 to 100; a and b represent integers of 1 or more; a+b is equal to 20-500; b/(a+b) is equal to 0.01-0.22; and the configuration of the siloxane units includes a random configuration. As an example, the siloxane monomer can be represented by formula (5), where m of formula (5) is 0, n of formula (5) is an integer from 5 to 10, a is an integer from 65 to 90, b is an integer from 1 to 10, R1 of formula (5) is a methyl group, and R2 of formula (5) is a hydrogen atom or a hydrocarbon group having 1 to 4 carbon atoms.
[000172] As a tenth example (Example J), a silicone hydrogel contact lens comprises a polymeric lens body which is the reaction product of a polymerizable composition as described in example A or B or C or D or E or F or G or H or I, and where the polymerizable composition further comprises a crosslinking agent or methacrylate-containing crosslinking agent component, specifically the crosslinking agent or agent component may comprise or consist of ethylene glycol dimethacrylate (EGDMA). In this example, where the polymerizable composition also comprises a vinyl ether-containing crosslinking agent as part of the crosslinking agent component, specifically the crosslinking agent component may comprise or consist of triethylene glycol divinyl ether (TGDVE) in combination with a meta-containing crosslinking agent. acrylate, which may specifically comprise or consist of ethylene glycol dimethacrylate (EGDMA). In this example, it can be appreciated that the polymerizable composition comprises two crosslinking agents, each having different reactivity ratios, i.e., the polymerizable composition comprises a crosslinking agent component comprising or consisting of a vinyl-containing crosslinking agent and a methacrylate-containing crosslinking agent means the methacrylate-containing crosslinking agent having polymerizable functional groups that are more reactive and thus react at a faster rate than the polymerizable vinyl functional groups present in the vinyl-containing crosslinking agent.
[000173] As an eleventh example (example K), a silicone hydrogel contact lens comprises a polymeric lens body which is the reaction product of a polymerizable composition as described in example A or B or C or D or E or F or G or H or I or J, and where the polymerizable composition further comprises a chain transfer agent or chain transfer agent component, which may specifically comprise or consist of allyloxy ethanol (AE) .
[000174] As a twelfth example (example L), a silicone hydrogel contact lens comprises a polymeric lens body which is the reaction product of a polymerizable composition as described in example A or B or C or D or E or F or G or H or I or J or K, and where the at least one hydrophilic monomer comprises a hydrophilic monomer or monomer component containing vinyl ether, for example, the hydrophilic monomer or monomer component vinyl ether containing may comprise or consist of 1,4-butanediol vinyl ether (BVE), or ethylene glycol vinyl ether (EGVE), or diethylene glycol vinyl ether (DEGVE), or any combination thereof.
[000175] As a thirteenth example (example M), a silicone hydrogel contact lens comprises a polymeric lens body which is the reaction product of a polymerizable composition as described in example A or B or C or D or E or F or G or H or I or J or K or L, where the contact lens has ophthalmic lens surfaces and is acceptably wet when the polymerizable composition used to form the lens is free of a wetting agent internal, or when the polymerizable composition used to form the polymeric lens body is free of an organic diluent, or when the polymeric lens body is extracted into a liquid free of a volatile organic solvent, or when the lens is exempt from a plasma surface treatment, or any combination thereof.
[000176] In any or each of the foregoing examples A-M, as well as in any or all of the other examples disclosed in this document, the amount of the first siloxane monomer may be from 20 to 45 parts of the polymerizable composition unit. The amount of the first siloxane monomer can be from 25 to 40 parts of the polymerizable composition unit. The amount of the first siloxane monomer can be from 27 to 35 parts of the polymerizable composition unit.
[000177] In any or each of the foregoing AM examples, as well as in any or all of the other examples disclosed in this document, the amount of the optional second siloxane monomer may be from 1 to 20 parts of the polymerizable composition unit . The amount of the second siloxane monomer can be from 2 to 15 parts of the polymerizable composition unit. The amount of the second siloxane monomer can be from 5 to 13 parts of the polymerizable composition unit. In another example, the ratio of the unit parts of the first siloxane monomer to the second siloxane can be at least 1:1, or at least 2:1.
[000178] In any or each of the foregoing AM examples, as well as in any or all of the other examples disclosed in this document, the amount of the hydrophilic monomer or monomer component present in the polymerizable composition may be 1 to 60 parts of the polymerizable composition unit. The hydrophilic monomer component can make up from 4 to 60 parts of the polymerizable composition unit. When the hydrophilic monomer comprises or consists of the VMA, it may be present in an amount from 30 parts of the unit to 60 parts of the unit. The VMA can be present in the polymerizable composition in an amount from about 40 parts of the unit to about 50 parts of the unit. When the hydrophilic monomers, N,N-dimethylacrylamide (DMA), 2-hydroxyethyl methacrylate (HEMA), or 2-hydroxylbutyl methacrylate (HOB), or any combination thereof, are present in the polymerizable composition as the hydrophilic monomer in the hydrophilic monomer component, each or all may be present in amounts of from about 3 to about 10 parts of the unit.
[000179] In any or each of the foregoing AM examples, as well as in any or all of the other examples disclosed in this document, the amount of the hydrophobic monomer or monomer component present in the polymerizable composition may be from 1 to 30 parts of the polymerizable composition unit. For example, the total amount of monomer or hydrophobic monomer component can be from about 5 to about 20 parts of the polymerizable composition unit. In polymerizable compositions in which the hydrophobic MMA monomer is present as the hydrophobic monomer or as part of the hydrophobic monomer component, the MMA may be present in an amount of from about 5 to about 20 parts of the unit, or from about 8 to about 15 parts of the unit.
[000180] In any or each of the foregoing AM examples, as well as in any or all of the other examples disclosed in this document, the amount of the crosslinking agent or crosslinking agent component present in the polymerizable composition may be 0. 01 to 4 parts of the polymerizable composition unit. TEGDVE may be present in amounts from 0.01 to 1.0 part of the unit. EGDMA can be present in amounts of 0.01 to 1.0 part of the unit. TEGDMA may be present in amounts from 0.1 to 2.0 parts of the unit. Each of these non-silicon crosslinking agents can be present alone or in any combination in the polymerizable composition.
[000181] In any or each of the preceding AM examples, as well as in any or all other examples disclosed in this document, when the polymerizable composition contains EGMA, BVE, DEGVE, EGVE, or any combination of these, they are each present in amounts from 1 part of the unit to 20 parts of the unit of the polymerizable composition. EGMA can be present in an amount from about 2 parts of the unit to about 15 parts of the unit. BVE can be present in an amount from 1 part of the unit to about 15 parts of the unit. BVE can be present in an amount from about 3 parts of the unit to about 7 parts of the unit. DEGVE can be present in an amount from 1 part of the unit to about 15 parts of the unit. DEGVE can be present in an amount from about 7 parts of the unit to about 10 parts of the unit. EGVE can be present in an amount of 1 part unit to about 15 parts unit, or in an amount of about 3 parts unit to about 7 parts unit.
[000182] In any or each of the foregoing AM examples, as well as in any or all of the other examples disclosed in this document, the other optional components, such as the initiators or the initiator component, the coloring agents or the coloring agent components, UV absorbing agents or UV absorbing agent components, or chain transfer agents or chain transfer agent components, may each be present in amounts of about 0.01 part of the unit to about 3 parts of the unit. An initiator or initiator component may be present in the polymerizable in an amount of 0.1 part unit to 1.0 part unit. When a thermal initiator or thermal initiator component is present, such as Vazo-64, it can be present in an amount of from about 0.3 to about 0.5 part of the unit. The coloring agents or coloring agent components may be present in amounts from 0.01 part unit to 1 part unit. When reactive dyes are used as coloring agents or as part of a coloring agent component, such as Reactive Blue 246 or Reactive Blue 247, they may each be present in amounts of about 0.01 part of the unit. The UV absorbing agents or UV absorbing agent components can be present in amounts from 0.1 part of the unit to 2.0 parts of the unit. For example, the UV UV1 absorbing agent described in Examples 1-37 below may be present in an amount of from about 0.8 to about 1.0 part of the unit, such as 0.9 part of the unit; or the UV UV2 absorbing agent described in Examples 137 below may be present in an amount from 0.5 part unit to 2.5 parts unit, such as from about 0.9 part unit to about 2.1 parts of the unit. Oxygen scavengers or oxygen scavenger components can be present in amounts from 0.1 part of a unit to 1.0 part of a unit. As an example, when triphenyl phosphine (TPP) or diphenyl(P-vinylphenyl)phosphine (pTPP) or any combination thereof is used as the phosphine-containing compound in the polymerizable composition, each or the combination may be present in an amount of 0.3 part of the unit to 0.7 part of the unit, such as about 0.5 part of the unit. Chain transfer reagents or chain transfer reagent components may be present in the polymerizable composition in an amount of 0.1 part unit to 2.0 part unit, and in many of Examples 1-37 below are present in an amount of 0.2 part of the unit to 1.6 part of the unit. For example, the allyloxy ethanol (EA) chain transfer reagent can be present in an amount of from about 0.3 to about 1.4 part of the unit.
[000183] In any or each of the foregoing AM examples, as well as in any or all of the other examples disclosed in this document, the silicone hydrogel contact lenses may be free of a wetting agent that is present in the polymerizable composition , or on the polymeric lens body, or on the silicone hydrogel contact lens. Similarly, the silicone hydrogel contact lens may have lens surfaces that are free from surface treatment or surface modification. However, in another example, the silicone hydrogel contact lens can include at least one wetting agent (ie, a single wetting agent or two or more wetting agents present as a wetting agent component) in the composition. polymerizable, polymeric lens body, or silicone hydrogel contact lens. The silicone hydrogel contact lens may have treated or modified lens surfaces. In addition, or alternatively, any or each of the preceding AM examples, as well as any or all other examples of silicone hydrogel contact lenses disclosed herein, the contact lenses may be understood to be free of an agent. binding agent, such as, for example, a form of boronic acid.
[000184] In another example, new polymerizable compositions are provided, including any and all polymerizable compositions described in this document in reference to silicone hydrogel contact lenses and methods. The polymerizable compositions can be free of diluents as they do not contain an organic solvent, such as alcohols and the like, which can help reduce phase separation of the polymerizable composition. However, such diluent-free polymerizable compositions may further contain one or more chain transfer agents, such as allyloxy ethanol. However, if desired, the polymerizable composition can include a diluent or a diluent component, which may be present in an amount of from 1 to 20 parts of the unit.
[000185] As described herein, the present hydrogel contact lenses, which comprise polymeric lens bodies comprising units derived from at least one hydrophilic monomer, including silicone hydrogel contact lenses which comprise derived units the at least one hydrophilic monomer and at least one siloxane monomer; when fully hydrated, they have an average equilibrium water content (EWC) of about 30% w/w about 70% w/w, or an average oxygen permeability of at least 55 barrers, or a contact angle a dynamic advancing per mean trapped bubble less than 70 degrees, or an average trapped bubble static contact angle less than 55 degrees, or any combination thereof, based on the averages of the values determined for at least 20 individual lenses of the batch. Thus, the present disclosure also relates to a lot of hydrogel contact lenses.
[000186] As used in this document, a lot of hydrogel contact lenses refers to a group of two or more hydrogel contact lenses, and often, a lot refers to at least 10, or at least 100 , or at least 1,000 hydrogel contact lenses. In accordance with the present disclosure, a batch of hydrogel contact lenses comprises a plurality of any of the hydrogel contact lenses described herein, including the silicone hydrogel contact lenses described herein.
[000187] In one example, the batch hydrogel contact lenses may have an average axial edge elevation (AEL) variance based on averaging the AEL measurements of a representative number of lenses in the batch at different points of time. For a lot of lenses, an average AEL variance of less than plus or minus one hundred percent (± 100%), or less than plus or minus fifty percent (± 50%), or of less than twenty percent (± 20%) for a period of time from two weeks to seven years, at room temperature or, when stored under accelerated life test conditions, for a period of time and temperature equivalent to storage. from two weeks to seven years at room temperature. In one example, the accelerated life test conditions that are especially useful in determining the mean AEL variance are for 4 weeks at 70 degrees C, although other time and temperature periods may be used. The mean AEL variance is determined by averaging the AEL values for each of the representative lenses using the representative lenses' actual AEL measurements before (EELInitial) and after (EELFinal) storage at room temperature or under living conditions expedited useful. The mean AEL variability is determined using the following equation (A): ((AELFinal - AELInitial) / AELInitial) x 100(A).
[000188] On average, batch hydrogel contact lens AELs vary by less than twenty percent in any direction from a target value, or less than ten percent in any direction from a target value , or less than five percent in either direction of a target value. As an example, if a contact lens has a target AEL of 20 µm ± 50%, the present lot of hydrogel contact lenses will have an average AEL of 10 µm to 30 µm over the course of the life study. A representative number of tested lenses from the batch may be 20 or more individual lenses.
[000189] In accelerated life studies, lens properties, such as the AEL value or color, can be determined for contact lenses that have been stored for a period of time at an elevated temperature, as above 40 degrees C, such as 50 degrees C, or 55 degrees C, or 65 degrees C, or 70 degrees C, or 80 degrees C, or 95 degrees C, and the like. Or, lens properties can be determined for contact lenses that have been stored for a period of time at room temperature (eg, about 20-25 degrees C).
[000190] For accelerated shelf life studies, the following formula can be used to determine the number of months of storage at a particular temperature that is equivalent to storage for the desired length of time at room temperature: Desired shelf life = [ N x 2y] + n(B) where N = number of months of storage under accelerated conditions 2y = acceleration factor y = 2.0 for every 10°C above ambient temperature (25°C), for storage at , or above, 45°C y = 1.0 for every 10°C above room temperature (25°C), for storage at 35°C to 45°C n = age of lenses (in months) in start of study
[000191] Based on this equation, the following storage times were calculated: 6 months storage at 35 degrees C is equivalent to 1 year aging at 25 degrees C, 3 months storage at 45 degrees C is equivalent to 1 year aging at 25 degrees C, 3 months storage at 55 degrees C is equivalent to 2 years aging at 25 degrees C, and 3 months storage at 65 degrees C is equivalent to 4 years aging at 25 degrees C.
[000192] In one example, the batch comprises a batch of hydrogel contact lenses comprising a plurality of the hydrogel contact lenses according to the present disclosure, wherein the batch of hydrogel contact lenses has at least two selected mean values from an average oxygen permeability of at least 55 barrers, an average stress modulus of about 0.2 MPa to about 0.9 MPa when fully hydrated, and an average EWC of about 30% w/pa about 70% w/w; based on the averages of the values determined for at least 20 individual lenses in the batch.
[000193] In one example, when initially tested shortly after fabrication and then tested again at a later time point, a batch of lenses may exhibit a change in their average physical dimensions. Since batches of lenses in accordance with the present disclosure are dimensionally stable, they can exhibit an acceptable level of change in their average physical dimensions. As used in this document, dimensional stability variance is understood to refer to a variance in a value of a physical dimension between a physical dimension value determined when the batch of lenses is initially tested soon after their manufacture, and the physical dimension value determined when the batch of lenses is retested at a later time point. The later time point can be, for example, from at least 2 weeks after the start time point, up to 7 years after the start time point. Batch silicone-cone hydrogel contact lenses have an average dimensional stability variance of less than plus or minus three percent (± 3.0%), based on the average of the lens diameter measurements of a representative number of batch lenses, such as, for example, 20 batch lenses. For a lot of lenses, a variance of the mean dimensional stability of less than plus or minus three percent (± 3.0%) is considered to be a dimensionally stable lot, where the variance of the mean dimensional stability is the variance in a value of a physical dimension when measured at an initial time point within one day of a lot manufacturing date of the lenses, and at a second time point, where the second time point is from two weeks to seven years after the initial time point when the batch is stored at room temperature, or, when the batch is stored at a higher temperature (ie, under accelerated life test conditions), the second time point of time is a representative time point of batch storage from two weeks to seven years at room temperature. In one example, the accelerated life test conditions, which are especially useful in determining the mean dimensional stability variance, are for 4 weeks at 70 degrees C, although other time periods and other temperatures may be used. The mean dimensional stability variance is determined by averaging the individual dimensional stability variances for each of the representative lenses using the actual diameters of the representative lenses measured initially (Original Diameter) and the actual diameters of the representative lenses measured after (Final Diameter ) storage at room temperature or under accelerated shelf life conditions. The representative lenses measured initially and the representative lenses measured after storage can be the same or different lenses. As used in this document, the mean dimensional stability variance is represented as a percentage (%). The individual dimensional stability variances are determined using the following equation (C): ((Final Diameter - Original Diameter) / Original Diameter) x 100 (C).
[000194] On average, Yote's silicone hydrogel contact lens diameters vary by less than three percent in any direction from a target value (± 3.0%). As an example, if a contact lens has a target diameter (string diameter) of 14.20 mm, the present yote of hydrogel contact lenses will have an average diameter (batch population mean) of 13.77 mm at 14.63 mm. In one example, the dimensional stability variance is less than plus or minus two percent (± 2.0%). As an example, if a contact lens has a target diameter (string diameter) of 14.20 mm, the present batch of hydrogel contact lenses will have an average diameter (average population in the batch) of 13.92 mm to 14.48 mm. Preferably, the average batch diameter of hydrogel contact lenses does not vary by more than about 0.20 mm from the target diameter, which is commonly 13.00 mm to 15.00 mm.
[000195] In accelerated life studies, the mean dimensional stability variance can be determined for contact lenses that have been stored for a period of time at an elevated temperature, such as above 40 degrees C, including , for example, 50 degrees C, or 55 degrees C, or 65 degrees C, or 70 degrees C, or 80 degrees C, or 95 degrees C, and the like. Or the average dimensional stability can be determined for contact lenses that have been stored for a period of time at room temperature (eg, about 20-25 degrees C).
[000196] Another example of the present disclosure provides methods of manufacturing hydrogel contact lenses. In accordance with the present teachings, the method comprises providing a polymerizable composition.
[000197] The method may also comprise a step of polymerizing the polymerizable composition to form a polymeric lens body. The step of polymerizing the polymerizable composition can be conducted in a contact lens molding unit. The polymerizable composition can be molded by casting between molds formed from a thermoplastic polymer. The thermoplastic polymer used to form the molding surfaces of the mold can comprise a polar polymer, or it can comprise a non-polar polymer. Alternatively, the polymerizable composition can be formed into a lens by various methods known to those of ordinary skill in the art, such as rotation casting, injection molding, forming a polymerized rod which is subsequently polymerized. turned to form a lens body, etc.
[000198] The polymerization of the polymerizable composition can be initiated thermally or using light, such as using ultraviolet (UV) light. In some examples, polymerization can be conducted in an atmosphere comprising air, or in an inert atmosphere.
[000199] The method may also comprise contacting the polymeric lens body with a washing liquid to remove extractable material, such as unreacted monomers, uncrosslinked materials that are not otherwise physically immobilized in the body of the lens. polymeric lens, thinners, and the like. The wash liquid can be a liquid free of a volatile organic solvent, or it can comprise a volatile organic solvent (e.g., it can be a volatile organic solvent or a solution of a volatile organic solvent).
[000200] Contact can be effective to remove at least a portion of the phosphine-containing or phosphine oxide-containing components from the polymeric lens body. As discussed above, the washing liquid can be water or an aqueous solution free of a volatile organic solvent, or it can be an organic solvent or a solution of an organic solvent. Alternatively, in some examples, the method does not comprise a step of contacting the polymeric lens body with a wash liquid or any liquid, i.e. where the polymeric lens body is not contacted with any liquid before being placed in a blister pack with the packaging solution and sealed The method may be a method not comprising a washing step which involves the use of a washing liquid comprising a volatile organic solvent, i.e. where the polymeric lens body is contacted by a washing liquid, but is not contacted with a washing liquid comprising a volatile organic solvent, and is not contacted by a volatile organic solvent before being placed in a blister-type package with the conditioning solution and sealed.
[000201] In methods that include a step of contacting the lens body with a wash liquid, the step of contacting the polymeric lens body with a wash liquid can be understood to be an extraction step, because extractable materials are removed from the polymeric lens body. In some methods, the contacting step comprises contacting the polymeric lens body with a washing liquid comprising a volatile organic solvent, such as a liquid containing a primary alcohol, such as methanol, ethanol, n-propyl alcohol. , It's similar. The use of a wash liquid containing one or more volatile organic solvents can be useful in removing hydrophobic materials from the polymeric lens body and, thus, can increase the wettability of lens surfaces. Such methods can be understood to be alcohol-based extraction steps. In other methods, the contacting step comprises contacting the polymeric lens body with an aqueous washing liquid that is free of a volatile organic solvent. Such methods can be understood to be aqueous extraction steps. Examples of aqueous washing liquid that can be used in such methods include water, such as deionized water, saline solutions, buffered solutions, or aqueous solutions containing surfactants or other non-volatile ingredients that can improve the removal of hydrophobic components from polymeric contact lens bodies, or can reduce deformation of polymeric contact lens bodies, compared to the use of deionized water alone. In one example, when washed using a washing liquid free of volatile organic solvents, the surfaces of the lens bodies of the present disclosure have ophthalmic and acceptably wettable surfaces.
[000202] In some examples, the polymeric lens body may be exposed to an oxidize step to oxidize the phosphine-containing compound present in the polymeric lens body. The oxidize step can be effective to oxidize most of the phosphine-containing compound present in the polymeric lens body, or to oxidize most of the phosphine-containing compound present on the surface of the lens body. The step of oxidizing may comprise exposing the polymeric lens body to hydrogen peroxide, such as, for example, hydrogen peroxide gas or an aqueous hydrogen peroxide solution or a lower alcohol-free hydrogel peroxide solution. For some phosphine-containing compounds, such as, for example, TPP, the oxidized form (phosphine oxide) has greater aqueous solubility than the unoxidized form. For formulations containing these forms of phosphine-containing compounds, it may be useful to expose the polymeric lens bodies to an oxidizing agent, prior to exposing the lens bodies to a washing step, to increase the amount of phosphine-containing compound extracted from the lens bodies (by extracting the compound containing phosphine in its oxide form).
[000203] After washing, contact lenses can be placed in packaging, such as plastic sheets, with a conditioning solution, such as a buffered saline solution, which may or may not contain surfactants, anti-inflammatory agents, agents antimicrobials, contact lens wetting agents, and the like, and are sealed and sterilized. The conditioning solution used to condition the silicone hydrogel contact lenses of the present disclosure can comprise a wetting agent to increase the wettability of the lens surfaces. However, it will be understood that the lens surfaces of the silicone hydrogel contact lenses of the present disclosure have ophthalmic and acceptably wettable surfaces prior to contacting with a conditioning solution comprising a wetting agent, and the use of a wetting agent in the The conditioning solution is only to increase the wettability of the already ophthalmic and acceptably wet surfaces, and thus it is not necessary to provide the contact lens with an ophthalmic and acceptably wet surface.
[000204] After washing, contact lenses can be placed in packaging, such as plastic sheets, with a conditioning solution, such as a buffered saline solution, which may or may not contain surfactants, anti-inflammatory agents, agents antimicrobials, contact lens wetting agents, and the like, and can be sealed and sterilized.
[000205] According to the present disclosure, the polymeric lens body can be packaged together with a contact lens packaging solution in a contact lens package, such as a blister pack or a small glass vial. After packaging, the packaging can be sealed and the polymeric lens body and contact lens packaging solution can be sterilized, for example, by sterilizing the sealed package in an autoclave, to produce a silicone hydrogel contact lens product .
[000206] The present method may further comprise repeating the steps to produce a plurality of hydrogel contact lenses. The present method may further comprise manufacturing a batch of hydrogel contact lenses. Examples
[000207] Examples 1-37 below illustrate certain aspects and advantages of the present invention, which is to be understood not to be limited thereto.
[000208] The following chemical substances are referred to in Examples 1-37, and may be referred to by their abbreviations. Si1: 2-methyl-, 2-[3-(9-butyl-1,1,3,3,5,5,7,7,9,9-decamethylpentasiloxan-1-yl)propoxy]ethyl ester 2 -propenoic (CAS number 1052075-57-6). (Si1 was obtained from Shin-Etsu Chemical Co., Ltd. (Japan) as product number X-22-1622). Si2: α,w-Bis (methacryloxypropyl)-poly(dimethyl siloxane)-poly(w-methoxy-poly(ethylenegylcol)propylmethylsiloxane) (the synthesis of this compound can be carried out as described in US20090234089) 513: Poly(dimethyl siloxane), methacryloxypropyl terminated (CAS number 58130-03-3; DMS-R18 available from Gelest, Morrisville, PA) 514: SiGMA: 3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilane (available from Gelest, Morrisville, PA 515: TRIS: 3-[Tris(trimethylsilyloxy)silyl]propyl methacrylate 516: MCS-M11: A monomethacryloxypropyl terminated polydimethylsiloxane (Gelest, Morrisville, PA, USA). VMA: N-vinyl-N-methylacetamide (CAS number 003195786) DMA: N,N-dimethylacrylamide (CAS number 2680-03-7) HEMA: 2-hydroxyethyl methacrylate (CAS number 868-77-9) HOB: methacrylate 2-hydroxylbutyl (CAS number 29008-35-3) EGMA: Ethylene glycol methyl ether methacrylate (CAS number 6976-93-8) MMA: Methyl methacrylate (CAS number 80-62-6) EGDMA: Ethylene glycol dimethacrylate ( CAS number 97-90-5) TEGDMA: triethylene glycol dimethacrylate (CAS number 109-16-0) BVE: 1,4-butanediol vinyl ether (CAS number 17832-28-9) DEGVE: diethylene glycol vinyl ether (CAS number 929-37-3) EGVE: ethylene glycol vinyl ether (CAS number 764-48-7) TEGDVE: triethylene glycol divinyl ether (CAS number 765-12-8) AE: 2-Allyloxy ethanol (CAS number 111-45-5 ) V-64: 2,2'-Azobis-2-methyl propanenitrile (CAS number 78-67-1) UV1: 2-(4-benzoyl-3-hydroxyphenoxy)ethyl acrylate (CAS number 16432-81-8) UV2: 2-(3-(2H-benzotriazol-2-yl)-4-hydroxy-phenyl) ethyl methacrylate (CAS number 96478-09-0) RBT1: 1,4-Bis[4-( 2-methacryloxyethyl)phenylamino]anthroquinone (CAS number 121888-69-5) RBT2: 1,4-bis[(2-hydroxyethyl)amino]-9,10-anthracenedione bis(2-propenoic) ester (No. CAS Reg. 109561071) TPP: Triphenyl phosphine (CAS number 603-35-0) pTPP: TPP polymerizable: diphenyl(P-vinylphenyl)phosphine (CAS number 40538-112) Hydrogel Contact Lenses Fabrication and Test Procedure
[000209] The chemical compounds presented in Examples 1-37 were, for each example, weighed in amounts corresponding to the parts of the unit described, and combined to form a mixture. The mixture was filtered through a 0.2-5.0 micron syringe filter into a vial. The mixtures were stored for up to about 2 weeks. Blends are understood to be polymerizable silicone hydrogel contact lens precursor compositions, or as used herein, polymerizable compositions. In Examples 1-37, the listed amounts of ingredients are given as parts of the polymerizable composition unit by weight.
[000210] A volume of the polymerizable composition was cast by casting the composition into contact with a lens-defining surface of a female mold element. In all of Examples 1-37 below, the casting surface of the female molding element was formed from a non-polar resin, specifically polypropylene. A male mold element was contacted with the female mold element to form a contact lens mold unit comprising a contact lens-shaped cavity containing the polymerizable composition. In Examples 1-37 below, the molding surface of the male mold element was formed from a non-polar resin, specifically polypropylene.
[000211] The contact lens molding units were placed in an oven filled with nitrogen to allow the precursor compositions to thermally cure. For all Examples 1-37, the contact lens mold units were exposed to temperatures of at least about 55°C for about 2 hours. Examples of cure profiles that can be used to cure the silicone hydrogel contact lenses described in this document include exposing contact lens molding units to temperatures of 55°C for 40 minutes, 80°C for 40 minutes, and 100°C for 40 minutes. Other contact lenses can be prepared with the same cure profile, but instead of the first temperature being 55°C, it can be 65°C.
[000212] After polymerizing the polymerizable compositions, the contact lens mold units were demolded to separate the male and female mold elements. The polymeric lens body remained adhered to the male mold or the female mold. A dry demolding process can be used, where the mold unit is not contacted with a liquid medium, or a wet demolding process can be used, where the mold unit is contacted with a liquid medium, such as by example, water or an aqueous solution. A mechanical dry demoulding process may involve applying mechanical force to a portion of one or both mold elements to separate the mold elements. In all of Examples 1-37 below, a dry demoulding process was used.
[000213] The polymeric lens body was then removed from the male mold or the female mold to produce a removed polymeric lens body. In an example of a method of removing the lens, the polymeric lens body can be removed from the male mold element using a dry removal process, such as by manual peeling of the lens from the male mold element or by pressing the mold element. male mold and pointing a gas towards the male mold element and the polymeric lens body, and removing the polymeric lens body with a vacuum device from the male mold element, which is discarded. In other methods, the polymeric lens body can be removed using a wet removal process, by contacting the dry polymeric lens body with a liquid release medium, such as water or an aqueous solution. For example, a male mold element with an attached polymeric lens body can be immersed in a receptacle containing a liquid until the polymeric lens body separates from the male mold element. Or, a volume of liquid release medium can be added to the female mold to soak the polymeric lens body in the liquid and separate the lens body from the female mold element. In Examples 1-37 below, a dry stripping process was used. After separation, the lens body can be removed from the mold element manually using tweezers or using a vacuum device and placed in a tray.
[000214] The removed lens product was then washed to remove extractable materials from the polymeric lens body, and hydrated. Extractable materials included polymerizable components, such as, for example, monomers, crosslinking agents, or any optional polymerizable ingredients, such as dyes or UV blockers, or combinations thereof, present in the polymerizable composition that remain present in the polymeric lens body in an unreacted form, in a partially reacted form, or in an uncrosslinked form, or any combination thereof, after polymerization of the lens body and prior to extraction of the lens body. Extractable materials may also have included any non-polymerizable ingredients present in the polymerizable composition, for example, any coloring agents, or UV blocking agents, or optional non-polymerizable thinners, or chain transfer agents, or any combination thereof, that remain. present in the polymeric lens body after polymerization of the polymeric lens body, but before extraction of the polymeric lens body.
[000215] In another method, such as a method that involves removing the lens by compressing the male mold element and pointing the gas flow toward the male mold element, the removed polymerized contact lens bodies may be placed in vehicle cavities or lens trays, where the removed polymeric lens bodies can then be contacted with one or more volumes of an extraction liquid, such as an aqueous extraction liquid free of a volatile organic solvent, for example, deionized water or an aqueous solution of a surfactant, such as Tween 80, or an extracting liquid based on an organic solvent, such as ethanol, or an aqueous solution of a volatile organic solvent, such as ethanol. .
[000216] In other methods, such as those involving wet lens removal by contacting the mold and lens with a liquid release medium, the removed polymerized contact lens bodies can be washed to remove the components extractables from lens bodies using a washing liquid that is free of a volatile organic solvent, such as a lower alcohol, e.g. methanol, ethanol, or any combination thereof. For example, removed polymerized contact lens bodies can be washed to remove extractable components from the lens bodies by contacting the lens bodies with an aqueous washing liquid free of a volatile organic solvent, such as, for example , deionized water, or a surfactant solution, or a saline solution, or a buffer solution, or any combination thereof. Washing can take place in the final contact lens package, or it can take place in a wash tray or wash tank.
[000217] In Examples 1-37 below, after the dry demolding and dry lens removal steps, the removed lens bodies were placed in tray cavities, and the removed polymeric lens bodies were extracted and hydrated by contacting the polymeric lens bodies with one or more volumes of extraction fluid. The extraction and hydration liquid used in the extraction and hydration process consisted of a) a combination of a volatile organic solvent-based extraction liquid and a volatile organic solvent-free hydration liquid, or (b) an extraction liquid and volatile organic solvent-free hydration, ie, extraction and hydration liquid entirely based on water. Specifically, in Examples 1-5 below, the extraction and hydration process comprised at least two steps of extraction into separate portions of ethanol, followed by at least one step of extraction into one portion of a 50:50 solution. w/w ethanol: Tween 80 water, followed by at least three extraction and hydration steps in separate portions of a solution of Tween 80 in deionized water, where each extraction or extraction and hydration step lasted about 5 minutes to 3 hours. In Examples 6-25 below, the extraction and hydration process used comprised at least three steps of extraction and hydration in separate portions of a solution of Tween 80 in deionized water, where the temperature of the solution of Tween 80 The portions ranged from room temperature to about 90 degrees C, and where each extraction and hydration step lasted from about 15 minutes to about 3 hours.
[000218] The washed, extracted and hydrated lenses were then placed individually in blister packs of contact lenses with a conditioning solution of phosphate-buffered saline solution. The blister packs were sealed and sterilized by autoclave.
[000219] After sterilization, lens properties such as contact angle, including dynamic and static contact angle, oxygen permeability, ionoflux, modulus, elongation, tensile strength, water content, and the like were determined as described in this document.
[000220] For present contact lenses, contact angles, including dynamic and static contact angles, can be determined using routine methods known to those of ordinary skill in the art. For example, the advancing contact angle and the receding contact angle of the contact lenses provided in this document can be measured using a conventional drop shaping method, such as the still drop method or the trapped bubble method.
[000221] In Examples 1-37 below, the advancing and receding contact angle of silicone hydrogel contact lenses was determined using a Kruss DSA 100 instrument (Kruss GmbH, Hamburg), and as described in DA Brandreth: "Dynamic contact angles and contact angle hysteresis", Journal of Colloid and Interface Science, vol. 62, 1977, p. 205-212 and R. Knapikowski, M. Kudra: Kontaktwinkelmessungen nach dem Wilhelmy-Prinzip-Ein statistischer Ansatz zur Fehierbeurteilung", Chem. Technik, vol. 45, 1993, pp. 179-185, and US Pat. No. 6,436. 481, all of which are incorporated by reference in this document.
[000222] As an example, the advancing contact angle and the receding contact angle were determined using a trapped bubble method, using phosphate buffered saline (PBS; pH = 7.2). The lens was flattened onto a quartz surface and rehydrated with PBS for at least 10 minutes prior to testing. An air bubble was placed on a lens surface using an automated syringe system. The size of the air bubble was increased and decreased to obtain the receding angle (the plateau obtained when increasing the bubble size) and the advancing angle (the plateau obtained when decreasing the bubble size).
[000223] The modulus, elongation, and tensile strength values of the present lenses can be determined using routine methods known to those of ordinary skill in the art, such as, for example, a test method according to ANSI Z80.20. The modulus, elongation, and tensile strength values described in this document were determined using an Instron Model 3342 or 3343 mechanical test system (Instron Corporation, Norwo-od, MA, USA) and Bluehill Materials Test Software, using a custom built rectangular contact lens cutting die to prepare the rectangular sample strip. Modulus, elongation and tensile strength were determined within a chamber having a relative humidity of at least 70%. The lens to be tested was soaked in phosphate buffered solution (PBS) for at least 10 minutes before testing. While keeping the concave of the lens upright, a central strip of the lens was cut using the cutting matrix. Strip thickness was determined using a calibrated gauge (Rehder electronic thickness gauge, Rehder Development Company, Castro Valley, CA, USA). Using the tweezers, the strip was loaded into the jaws of the calibrated Instron apparatus, with the strip fitting over at least 75% of the jaw surface of each jaw. A test method designed to determine the maximum load (N), tensile strength (MPa), strain at maximum load (% elongation) and mean and standard deviation of the modulus of stress (MPa) was run, and the results were recorded.
[000224] The percent energy loss of the present silicone hydrogel contact lenses can be determined using routine methods known to those of ordinary skill in the art. For Examples 1-37 below, the percent energy loss was determined using an Instron Model 3343 mechanical test system (Instron Corporation, Norwood, MA, USA) with a 10 N force transducer (Instron model no. 2519-101) and Bluehill Materials Testing Software including a TestProfiler module. Energy loss was determined within a chamber having a relative humidity of at least 70%. Before testing, each lens was soaked in phosphate-buffered solution (PBS) for at least 10 minutes. Using the tweezers, the lens was loaded into the jaws of the calibrated Instron apparatus, with the lens loaded vertically between the jaws as symmetrically as possible so that the lens fit over at least 75% of the jaw surface of each jaw. A test designed to determine the energy required to extend the lens to 100% strain and then return it to 0% strain at a rate of 50 mm/minute was then run over the lens. The test was conducted only once on a single lens. Once the test was completed, the energy loss was calculated using the following equation: Lost Energy (%) = (Energy up to 100% deformation - Energy to return to 0% deformation) / Energy up to 100% deformation x 100%.
[000225] The ionoflux of the present lenses can be determined using routine methods known to those of ordinary skill in the art. For the lenses of Examples 1-37 below, ionoflux was measured using a technique substantially similar to the "Ionoflux Technique" described in U.S. Patent 5,849,811, which is incorporated by reference herein. Prior to measurement, a hydrated lens was equilibrated in deionized water for at least 10 minutes. The lens to be measured was placed in a device that retains the lens, between the male and female portions. The male and female portions included flexible sealing rings that were positioned between the lens and the respective male or female portion. After positioning the lens on the lens retaining device, the lens retaining device was then placed in a screw cap. The cap was screwed onto a glass tube to define a donor chamber. The donor chamber was filled with 16 ml of 0.1 molar NaCl solution. A receiving chamber was filled with 80 ml of deionized water. The conductivity meter leads were immersed in the deionized water of the receiving chamber and a stir bar was added to the receiving chamber. The recipient chamber was placed in a water bath and the temperature was maintained at around 35°C. Finally, the donor chamber was immersed in the recipient chamber in such a way that the NaCl solution inside the donor chamber was leveled with the water inside the receiving chamber. Once the temperature inside the receiving chamber was equilibrated to 35 degrees C, conductivity measurements were taken every 2 minutes for at least 10 minutes. The conductivity versus time data was substantially linear, and was used to calculate the ionoflux value for the tested lens.
[000226] The oxygen permeability (Dk) of the present lenses can be determined using routine methods known to those of ordinary skill in the art. For example, the Dk value can be determined using an instrument commercially available under the model designation MOCON® Ox-Tran System (Mocon Inc., Minneapolis, MN, USA), for example using the Mocon Method as described in US Patent No. 5,817,924, which is incorporated by reference herein. The Dk values of the lenses of Examples 1-37 below were determined using the method described by Chhabra et al. (2007), A single-lens polarographic measurement of oxygen permeability (Dk) for hypertransmissible soft contact lenses. Biomaterials 28: 4331-4342, which is incorporated by reference herein.
[000227] The equilibrium water content (EWC) of the present lenses can be determined using routine methods known to those of ordinary skill in the art. For the lenses of Examples 1-37 below, a hydrated silicone hydrogel contact lens was removed from an aqueous liquid, dried to remove excess surface water, and weighed. The weighed lens was then dried in an oven at 80 degrees C, under a vacuum, and the dried lens was then weighed. The difference in weight was determined by subtracting the dry lens weight from the hydrated lens weight. The water content (%) is (difference in hydrated weight/weight) x 100.
[000228] The percentage of wet extractable component or dry extractable component in a lens can be determined by extracting the lenses in an organic solvent in which the polymeric lens body is not soluble, according to methods known to those of common ability in technique. For the lenses of Examples 1-37 below, a methanol extraction was used using a Sohxlet extraction process. For the determination of the wet extractable component, a sample (eg, at least 5 lenses per lot) of fully hydrated and sterilized contact lenses was prepared by removing excess conditioning solution from each lens and drying them overnight in a vacuum oven at 80°C. For the determination of the dry extractable component, a sample of polymeric lens bodies that had not been washed, extracted, hydrated or sterilized was prepared by drying the lens bodies overnight in a vacuum oven at 80°C. When dried and cooled, each lens was weighed to determine its initial dry weight (W1). Each lens was then placed in a pierced, stackable Telfon thimble, and the thimbles were stacked to form an extraction column, with an empty thimble placed on top of the column. The extraction column was placed in a small Sohxlet extractor coupled with a condenser and a round bottom flask containing 70-80 ml of methanol. Water was circulated through the condenser and the methanol was heated until it gently boiled. The lenses were extracted for at least 4 hours from the moment condensed methanol first appeared. The extracted lenses were again dried overnight at 80°C in a vacuum oven. When dried and cooled, each lens was weighed to obtain the dry weight of the extracted lens (W2), and the following calculation was made for each lens to determine the percentage of wet extractable component: [(W1-W2)/W1] x 100 EXAMPLES 1-28
[000229] Table 1 lists the ingredients of polymerizable compositions 1-14. Table 2 lists the ingredients of polymerizable compositions 15-28. Polymerizable compositions 1-28 were prepared as described in Hydrogel Contact Lenses Fabrication and Testing Procedure given above, and were used to prepare and test hydrogel contact lenses as described in Lenses Fabrication Hydrogel Contact and Test Procedure. All lenses prepared in Examples 1-28 were manually dry demolded and removed. With the exception of polymerizable composition 1, all polymerizable compositions include a phosphine-containing component (TPP or pTPP).
[000230] Table 3 shows the lens properties for lenses formed using polymerizable compositions 1-14 when initially fabricated. Table 4 shows lens properties for lenses formed using polymerizable compositions 15-28 when initially manufactured. Hydrogel contact lenses formed from polymerizable compositions 2-28 had acceptable lens properties when initially manufactured, as shown in Tables 3 and 4.
[000231] Hydrogel contact lenses formed from polymerizable compositions 2-28 also had both shape conservation and acceptable color value when initially manufactured and after storage for at least 1 month at room temperature, and at least 2 weeks at elevated temperatures. For example, the lenses of formulations 2, 3, and 4 had acceptable shape retention after being stored for at least 20 days at 95 degrees C. The lenses of formulations 5, 6, 7, 8, 11, 12, 14, 15 , 16, 18, 19, 20, 24, and 25 had acceptable shape retention after storage for at least 14 days at 80 degrees C. Formulation 9 lenses had acceptable shape retention after storage for at least 6 days at 95°C. degrees C. The lenses of formulations 10 and 13 had acceptable shape retention after storage for at least 7 days at 80 degrees C. The lenses of formulations 17, 21, 22, and 23 had acceptable shape retention after storage for at least 4.4 weeks at 80 degrees C. Table 1



EXAMPLES 29-37
[000232] Table 5 lists the ingredients of the polymerizable compositions 29-37. Polymerizable compositions 29-37 were prepared as described in Fabrication of Hydrogel Contact Lenses and Test Procedure given above, and were used to prepare and test hydrogel contact lenses as described in Fabrication of Hydrogel Contact Lenses and Test Procedure. All of these lenses were demolded using a dry demolding process, removed using a dry lens removal process, and extracted using a liquid free of a volatile organic solvent. With the exception of polymerizable compositions 29, 32 and 35, all polymerizable compositions include a phosphine-containing component (TPP or pTPP).
[000233] Table 6 shows the lens properties for lenses formed using the polymerizable compositions 29-37 when initially manufactured. Hydrogel contact lenses formed from polymerizable compositions 30, 31, 33, 34, 36, and 37 (lenses formed from a polymerizable composition with a phosphine-containing component) had acceptable lens properties when initially manufactured. As can be seen from Table 6, the lens properties of lenses formed from the formulations containing the phosphine-containing component were similar to the lens properties of lenses formed from the same formulations, except without the components containing the phosphine. -bearing phosphine when prepared using the same manufacturing process. The lenses of formulations 30, 31, 33, 34, 36 and 37 also had both an acceptable shape conservation and color value when initially manufactured and for at least 1 month when stored at room temperature. Lenses formed from formulations without the phosphine-containing component, however, did not have the shape conservation or acceptable AEL when initially manufactured.
[000234] Formulations 30 and 31 were also used to prepare the lenses using a preparation process as described in Hydrogel Contact Lenses Fabrication and Testing Procedure, demolded using a dry demolding process, removed using a removal process of dry lens, and extracted using a liquid free of a volatile organic solvent, except that the lenses were cured under an atmosphere of air. Air-cured lenses had lens properties similar to air-cured lenses prepared from the same formulation, except without the phosphine-containing component (formulation 29). However, the lenses of formulations 30 and 31 had an acceptable shape retention (including an acceptable AEL) and an acceptable color value when air-cured, while the lenses of formulation 29 did not have an acceptable shape retention or an acceptable AEL. when cured with air. Table 5

[000235] Although the disclosure contained herein refers to certain illustrative embodiments, it is to be understood that these embodiments are presented by way of example and not by way of limitation. The purpose of the foregoing detailed description, while discussing illustrative embodiments, is to be interpreted to cover all modifications, alternatives, and equivalents of the embodiments as may fall within the spirit and scope of the invention, as defined by the Additional Disclosure .
[000236] Several publications and patents have been cited above. Each of the cited publications and patents is hereby incorporated by reference in their entirety.

权利要求:
Claims (15)
[0001]
1. Method for manufacturing a hydrogel contact lens, CHARACTERIZED in that it comprises: providing a polymerizable composition comprising: (a) at least one hydrophilic monomer, and (b) at least one phosphine-containing compound, wherein the hair at least one phosphine-containing compound is present in an unoxidized form when it is combined with the at least one hydrophilic monomer in the polymerizable composition; and reacting the polymerizable composition to form a polymeric lens body.
[0002]
2. Method according to claim 1, CHARACTERIZED by the fact that the phosphine-containing compound has a structure represented by the formula (1):
[0003]
3. Method according to claim 1 or 2, CHARACTERIZED by the fact that the phosphine-containing compound is a polymerizable phosphine-containing compound.
[0004]
4. Method according to any one of claims 1 to 3, CHARACTERIZED by the fact that the phosphine-containing compound comprises triphenylphosphine or diphenyl(4-vinylphenyl)phosphine, or both.
[0005]
5. Method according to any one of claims 1 to 4, CHARACTERIZED by the fact that the phosphine compound is present in the polymerizable composition in an amount of 0.01 to 5 unit parts.
[0006]
6. Method according to any one of claims 1 to 5, CHARACTERIZED by the fact that: the polymerizable composition contains an amount of the phosphine-containing compound effective to expel at least a part of the oxygen present in the polymerizable composition during manufacturing; the polymerizable composition contains an amount of the phosphine-containing compound effective to produce a polymeric lens body having a reduced amount of axial edge lift (AEL) as compared to a second hydrogel contact lens body formed from a second polymerizable composition substantially identical to the polymerizable composition, except without the phosphine-containing compound, and using a manufacturing process substantially identical to the process for manufacturing the hydrogel contact lens; the polymerizable composition contains an amount of the phosphine-containing compound effective to reduce deformation of the hydrogel contact lens, compared to a second hydrogel contact lens body formed from a second polymerizable composition substantially identical to the polymeric composition. zable, except without the phosphine-containing compound, and using a manufacturing process substantially identical to the process for manufacturing the hydrogel contact lens; and/or the polymerizable composition contains an amount of the phosphine-containing compound effective to reduce contact lens discoloration for at least 1 year when stored at room temperature, compared to a second contact lens formed from a substantially polymerizable second composition. identical to the first polymerizable composition, except without the phosphine-containing compound, and using a manufacturing process substantially identical to the process for manufacturing the hydrogel contact lens.
[0007]
7. Method according to any one of claims 1 to 6, CHARACTERIZED by the fact that the reaction of the polymerizable composition is conducted in an atmosphere comprising air.
[0008]
8. Method according to any one of claims 1 to 7, CHARACTERIZED by the fact that the reaction of the polymerizable composition is conducted in an atmosphere comprising an inert gas in a concentration greater than that found in air.
[0009]
9. Method according to any one of claims 1 to 8, CHARACTERIZED by the fact that the polymerizable composition further comprises at least one siloxane monomer.
[0010]
10. The method according to any one of claims 1 to 9, CHARACTERIZED by the fact that the reaction comprises casting molding the polymerizable composition in a contact lens mold assembly to form a polymeric lens body.
[0011]
11. Method according to any one of claims 1 to 10, CHARACTERIZED in that it further comprises contacting the polymeric lens body with a washing liquid to remove extractable material from the polymeric lens body, which contact optionally removes a portion of the at least one phosphine compound of the polymeric lens body; and/or further comprises oxidizing at least a portion of the phosphine-containing compound present in the polymeric lens body or hydrogel contact lens.
[0012]
12. Hydrogel Contact Lens CHARACTERIZED in that it comprises: a polymeric lens body that is the reaction product of a polymerizable composition, the polymerizable composition comprising: (a) at least one hydrophilic monomer, and (b) at least one phosphine-containing compound, wherein the at least one phosphine-containing compound is present in an unoxidized form at the time it is combined with the at least one hydrophilic monomer in the polymerizable composition.
[0013]
13. Batch of hydrogel contact lenses CHARACTERIZED by the fact that it comprises a plurality of hydrogel contact lenses prepared in accordance with the method as defined in any one of claims 1 to 11.
[0014]
14. Batch of hydrogel contact lenses, according to claim 13, CHARACTERIZED by the fact that the batch of hydrogel contact lenses has an average axial edge elevation (AEL) variance of less than plus or minus 50% du -for a period of time from two weeks to seven years, when stored at room temperature or when stored under accelerated shelf-life conditions for a period of time and temperature equivalent to the storage of two weeks to seven years at room temperature, as determined on the basis of at least 20 individual lenses in the lot, the percentage of AEP variance being determined for each of the individual lenses by the following equation (A): ((AELFinal - AELInitial) / AELInitial) x 100 (A).
[0015]
15. Hydrogel contact lens packaging CHARACTERIZED by the fact that it comprises: a polymeric lens body that is the reaction product of a polymerizable composition, the polymerizable composition comprising: (a) at least one hydrophilic monomer, and (b) at least one phosphine-containing compound, wherein the at least one phosphine-containing compound is present in an unoxidized form at the time it is combined with the at least one hydrophilic monomer in the polymerizable composition; a conditioning solution comprising a lens moisturizing agent; and a contact lens package base element having a cavity configured to hold the contact lens body and the packaging solution, and a seal joined to the base element configured to hold the contact lens and the packaging solution in a sterile condition for a duration of time equivalent to a contact lens life at room temperature.

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法律状态:
2018-12-18| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|

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2020-01-28| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|

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2020-10-20| B06A| Patent application procedure suspended [chapter 6.1 patent gazette]|

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2021-05-04| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|

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2021-06-08| B350| Update of information on the portal [chapter 15.35 patent gazette]|

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2021-06-22| 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 23/02/2012, OBSERVADAS AS CONDICOES LEGAIS. |

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2021-08-24| B25G| Requested change of headquarter approved|Owner name: COOPERVISION INTERNATIONAL HOLDING COMPANY, LP (BB) |

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2021-09-14| B25A| Requested transfer of rights approved|Owner name: COOPERVISION INTERNATIONAL LIMITED (GB) |

优先权:

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申请号 | 申请日 | 专利标题

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US201161447152P| true| 2011-02-28|2011-02-28|

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US61/447,152|2011-02-28|

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PCT/US2012/026211|WO2012118671A1|2011-02-28|2012-02-23|Phosphine-containing hydrogel contact lenses|

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