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    • 专利摘要:
    coating for a lubricating medical device with low particulate content, medical device and method of production thereof. embodiments of the invention relate to lubricating medical device coatings. in one embodiment, the invention includes a coating for a medical device that includes a first layer comprising polyvinylpyrrolidone derivatized with a photoreactive group; and a first crosslinking agent comprising at least two photoreactive groups; a second layer disposed on the first layer comprising polyvinylpyrrolidone derivatized with a photoreactive group; a second crosslinking agent comprising at least two photoreactive groups; and a polymer comprising polyacrylamide, the polymer derivatized with at least one photoreactive group. other modalities are included in this document.
    公开号:BR112014017675B1
    申请号:R112014017675-2
    申请日:2013-01-18
    公开日:2021-06-22
    发明作者:David E. Babcock
    申请人:Surmodics, Inc；
    IPC主号:
    专利说明:

    FIELD OF THE INVENTION
    [001] The present invention relates to coatings for medical devices. More specifically, the present invention relates to lubricated medical device coatings with low particulate generation, and medical devices and methods related thereto. BACKGROUND OF THE INVENTION
    [002] Medical devices include, among others, those that are chronically implanted, devices that are transiently implanted, and those that are not implanted at all. Many types of medical device can be improved by reducing friction between the device and the environment surrounding the medical device, particularly during insertion of a device. A classic example of this is in the context of catheters that are inserted, at least transiently, into an individual's body. Reducing friction can lead to improved patient comfort, ease of procedures for the care provider, reduced chances of infection, as well as reduced tissue disruption, among other benefits. One approach to reducing friction between a medical device and the environment surrounding the medical device is to apply a lubricated coating to the medical device. SUMMARY OF THE INVENTION
    [003] Embodiments of the invention include lubricated medical device coatings. In one embodiment, the invention includes a coating for a medical device that includes a first layer that includes polyvinylpyrrolidone derivatized with a photoreactive group and a first crosslinking agent that comprises at least two photoreactive groups. The coating may also include a second layer disposed on the first layer comprising polyvinylpyrrolidone derivatized with a photoreactive group, a second crosslinking agent comprising at least two photoreactive groups, and a polymer comprising polyacrylamide, the polymer being derivatized with at least one photoreactive group.
    [004] In one embodiment, the invention includes a medical device having a substrate, a first layer disposed on the substrate, the first layer comprising polyvinylpyrrolidone derivatized with a photoreactive group and a first crosslinking agent comprising at least two photoreactive groups. The medical device may also include a second layer disposed in the first layer comprising polyvinylpyrrolidone derivatized with a photoreactive group, a second crosslinking agent comprising at least two photoreactive groups, and a polymer comprising polyacrylamide, the polymer being der. - vatized with at least one photoreactive group.
    [005] In one embodiment, the invention includes a method for making a medical device comprising applying a first coating solution to a substrate to form a first layer, the first coating solution comprising polyvinylpyrrolidone derivatized with a photoreactive group. first, a first cross-linking agent comprising at least two photoreactive groups, and a first solvent. The method may also include applying a second coating solution to the first layer to form a second layer, the second coating solution comprising polyvinylpyrrolidone derivatized with a photoreactive group, a second crosslinking agent comprising at least two groups. photoreactive, a polymer comprising polyacrylamide, wherein the polymer is derivatized with at least one photoreactive group, and a second solvent.
    [006] The above summary of the present invention is not intended to describe each embodiment discussed in the present invention. That is the purpose of the figures and the detailed description that follows. BRIEF DESCRIPTION OF THE FIGURES
    [007] The invention can be understood more fully in connection with the following drawings, in which:
    [008] Figure 1 is a schematic view of a coating in accordance with an embodiment herein.
    [009] Figure 2 is a schematic view of a device in accordance with an embodiment in this document.
    [0010] Figure 3 is a graph showing the average frictional force measured in a vertical compression test over numerous test cycles.
    [0011] Figure 4 is a graph showing the average frictional force measured in a vertical compression test over numerous test cycles.
    [0012] Figure 5 is a graph showing the average frictional force measured in a vertical compression test over numerous test cycles.
    [0013] Figure 6 is a graph showing the average frictional force measured in a vertical compression test over numerous test cycles.
    [0014] Figure 7 is a graph showing particulates measured for various coatings.
    [0015] Figure 8 is a graph showing the average frictional force measured in a vertical compression test over numerous test cycles.
    [0016] Figure 9 is a graph showing the friction force measured in a vertical compression test versus immersion speed used for immersion of the coating.
    [0017] Figure 10 is a graph showing measured particulates versus immersion velocity used for coating immersion.
    [0018] Figure 11 is a graph that shows the average friction force measured in a vertical compression test over numerous test cycles.
    [0019] Figure 12 is a graph showing the average frictional force measured in a vertical compression test over numerous test cycles.
    [0020] Figure 13 is a graph showing the average frictional force measured in a vertical compression test over numerous test cycles.
    [0021] Although the invention is susceptible to varied modifications and alternative forms, the specifications of the same have been shown by way of example and drawings, and will be described in detail. It should be understood, however, that the invention is not limited to the particular embodiments described. Rather, the intention is to cover modifications, equivalents and alternatives that fall within the scope of the invention. DETAILED DESCRIPTION OF THE INVENTION
    [0022] As described above, one approach to reducing friction between a medical device and the environment surrounding the medical device is to apply a lubricated coating to the medical device. However, many lubricated coatings are relatively ineffective in reducing friction between the device and the environment surrounding the device (such as an intravascular space, for example). In addition, many lubricated coatings do not have sufficient durability to lead to a rapid increase in friction during the course of use. Finally, many lubricated coatings, upon exposure to an aqueous environment (such as inside a patient) release particulate matter that may be unwanted.
    [0023] The embodiments herein include coatings that are highly lubricated and relatively durable. In addition, embodiments herein include lubricated coatings that exhibit relatively low or reduced particulate matter release. Referring now to Figure 1, a schematic cross-sectional view is shown of a coating on a substrate in accordance with an embodiment herein. The coating may include a first layer 102 and a second layer 104. The second layer 104 may be disposed on the first layer 102. The first layer 102 may be disposed on a substrate 106. Exemplary substrate materials are described in more details below. In some embodiments, first layer 102 is directly disposed on substrate 106. In other embodiments, other components may be disposed between first layer 102 and substrate 106. The thickness of first layer 102 and second layer 104 together may be from about 100 nm to about 3000 nm when dry. In some embodiments, the thickness can be from about 1800 nm to about 2200 nm when dry. In some embodiments, the thickness can be around 2000 nm. In some embodiments, the thickness can be around 1000 nm. However, it will be appreciated that, in some embodiments, the thickness can be from about 200 nm to about 400 nm. In some embodiments, the thickness can be about 300 nm.
    [0024] In some embodiments, the first layer may include polyvinylpyrrolidone derivatized with a photoreactive group (or Photo-PVP) and a first crosslinking agent comprising at least two photoreactive groups. Methods for preparing Photo-PVP are described in U.S. Patent No. 5,414,075, incorporated herein by reference. Exemplary crosslinking agents comprising at least two photoreactive groups are described in more detail below. Within the first layer, the components can be mixed homogeneously in some modalities.
    [0025] In some embodiments, the ratio of derivatized polyvinylpyrrolidone with a photoreactive group in the first layer to the first crosslinking agent comprising at least two photoreactive groups is from about 2:1 to about 30:1 (w/ for). In some embodiments, the ratio of derivatized polyvinylpyrrolidone with a photoreactive group in the first layer to the first crosslinking agent comprising at least two photoreactive groups is from about 8:1 to about 20:1 (p /for). In some embodiments, the ratio of derivatized polyvinylpyrrolidone with a photoreactive group in the first layer to the first crosslinking agent comprising at least two photoreactive groups is from about 8:1 to about 16:1 (w/w). In some embodiments, the ratio of derivatized polyvinylpyrrolidone with a photoreactive group in the first layer to the first crosslinking agent comprising at least two photoreactive groups is about 13:1 (w/w). first layer are derivatized with photoreactive groups.
    [0026] In some embodiments, the first layer may also include non-derivatized polyvinylpyrrolidone (PVP). PVP can be of varying molecular weights. In some embodiments, the ratio of derivatized polyvinylpyrrolidone with a photoreactive group in the first layer to underivatized polyvinylpyrrolidone in the first layer for the first crosslinking agent comprising at least two photoreactive groups is from about 13:0.1:1 to 13: 8:1 (w/w/w). In some embodiments, the ratio of derivatized polyvinylpyrrolidone with a photoreactive group in the first layer to underivatized polyvinylpyrrolidone in the first layer for the first crosslinking agent comprising at least two photoreactive groups is about 13:5:1 (w/w /for). In some embodiments, the ratio of underivatized polyvinylpyrrolidone in the first layer to the first crosslinking agent comprising at least two photoreactive groups is from about 0.1:1 to 8:1 (w/w).
    [0027] In some embodiments, the second layer may include polyvinylpyrrolidone derivatized with a photoreactive group, a second crosslinking agent comprising at least two photoreactive groups, and a polymer comprising polyacrylamide, the polymer being derivatized with at least a photoreactive group. The second cross-linking agent can be the same or different from the first cross-linking agent. In some embodiments, the polyacrylamide-comprising polymer can also include methylpropane acrylamino-2-sulfonate (AMPS) groups and polyethylene glycol segments. In a specific embodiment, the polymer comprising polyacrylamide may be N-Acetylated poly[acrylamide-co-sodium-2-acrylamino-2-sulfonate methylpropane-co-N-(3-(4-benzoyl benzamido)propyl) methacrylamide]-co-methoxy poly(ethylene glycol) monomethacrylate. Polyacrylamide-comprising polymers, in accordance with the embodiments herein, are described in U.S. Patent Nos. 4,979,959; 5,263,992; and 5,512,329, the contents of which are incorporated herein by reference in their entirety. In some embodiments, all components of the second layer are derivatized with photoreactive groups. Within the second layer, the components can be mixed homogeneously in some modalities.
    [0028] In some embodiments, PVP (non-derivatized PVP) can be added to the top coat.
    [0029] In some embodiments, the ratio of derivatized polyvinylpyrrolidone with a photoreactive group in the second layer to the polymer comprising polyacrylamide in the second layer is between approximately 10:1 and 1:10 (w/w). In some embodiments, the ratio of derivatized polyvinylpyrrolidone with a photoactive group in the second layer to the polyacrylamide-comprising polymer in the second layer is between approximately 3:1 and 1:3 (w/w). In some embodiments, the ratio of derivatized polyvinylpyrrolidone with a photoreactive group in the second layer to the polyacrylamide-comprising polymer in the second layer is between approximately 2:1 and 1:2 (w/w).
    [0030] The coating may exhibit lubricity. It will be appreciated that lubricity can be seen as relative low friction. In some embodiments, the coating can be lubricated after exposure to water. The coating can exhibit lubricity of between 0 and 50 grams of strength when wetted as measured by a vertical compression test such as the one described below. The coating can exhibit lubricity of between 0 and 40 grams of strength when wetted as measured by a vertical compression test such as the one described below. In still other embodiments the coating may exhibit lubricity of between 0 and 30 grams of strength when wetted as measured by a vertical compression test such as that described below. In some embodiments the coating may exhibit lubricity of less than about 20 grams of strength when wetted. In some embodiments the coating may exhibit lubricity of less than about 15 grams of strength when wetted.
    [0031] In varied embodiments, coating lubricity can be a durable property. For example, lubricity can be retained for an extended period of time. For example, in some embodiments, lubricity can be maintained by a plurality of friction test cycles. In some embodiments, the coating can exhibit a lubricity of between 0 and 30 grams of strength when wetted for at least 10 consecutive test cycles. In some embodiments, such as those in which at least 15 friction test cycles are performed, the measured lubricity will increase no more than 30% between the average of 1 to 5 cycles and the average of 10 to 15 cycles of the test .
    [0032] The coating may exhibit a relatively low amount of particulate release when exposed to an aqueous environment. For example, the coating will generate fewer than 70,000 particles larger than 10 microns in size in an aqueous environment. In some embodiments, the coating will generate less than 50,000 particles larger than 10 microns in size in an aqueous environment. In some embodiments, the coating will generate less than 30,000 particles larger than 10 microns in size in an aqueous environment. In some embodiments, the coating will generate less than 25,000 particles larger than 10 microns in size in an aqueous environment. In some embodiments, the coating will generate less than 20,000 particles larger than 10 microns in size in an aqueous environment. In some embodiments, the coating will generate less than 15,000 particles larger than 10 microns in size in an aqueous environment. In some embodiments, the coating will generate less than 10,000 particles larger than 10 microns in size in an aqueous environment. In some embodiments, the coating will generate less than 8,000 particles larger than 10 microns in size in an aqueous environment. In some embodiments, the coating will generate fewer than 6,000 particles larger than 10 microns in size in an aqueous environment. It will be appreciated that, in accordance with varied embodiments herein, both lubricity properties and low particulate release are present. PHOTOREACTIVE GROUPS
    [0033] As used herein, the terms "latent photoreactive group" and "photoreactive group" are used interchangeably and refer to a chemical fraction that is sufficiently stable to remain in an inactive state (ie, ground state ) under normal storage conditions, but which can undergo a transformation from an inactive state to an activated state when subjected to an appropriate energy source. Unless otherwise noted, references to photoreactive groups in this document should also include the reaction products of the photoreactive groups. Photoreactive groups respond to specific external stimuli to undergo the generation of active species with resulting covalent bond to an adjacent chemical structure. For example, in one embodiment, a photoreactive group can be activated and can abstract a hydrogen atom from an alkyl group. A covalent bond can then form between the compound with the photoreactive group and the compound with the CH bond. Suitable photoreactive groups are described in U.S. Patent No. 5,002,582, the disclosure of which is incorporated herein by reference.
    [0034] Photoreactive groups can be chosen to be responsive to varying portions of actinic radiation. Typically, groups that can be photoactivated using either ultraviolet rays or visible radiation are chosen. Suitable photoreactive groups include, for example, azides, diazos, diazirines, ketones, and quinones. Photoreactive groups generate active species such as free radicals which include, for example, nitrenes, carbenes, and ketone agitation states in the absorption of electromagnetic energy.
    [0035] In some embodiments, the photoreactive group is an aryl ketone, such as acetophenone, benzophenone, anthrone, and anthrone-like heterocycles (i.e., heterocyclic analogs of anthrone such as those that have N, O, or S in the position. tion-10), or their substituted derivatives (eg, substituted ring). Examples of aryl ketones include heterocyclic derivatizes of anthrone, which include acridone, xanthone, and thioxanthone, and their substituted ring derivatizes. Other suitable photoreactive groups include quinone such as, for example, anthraquinone.
    [0036] The functional groups of such aryl ketones can undergo multiple activation/inactivation/reactivation cycles. For example, benzophenone is capable of photochemical excitation with the initial formation of an excited singlet state that undergoes intersystem crossing to the triplet state. The excited triplet state can insert into carbon-hydrogen bonds by abstracting a hydrogen atom (from a polymeric coating layer, for example), which thus creates a radical pair. The subsequent collapse of the radical pair leads to the formation of a new carbon-hydrogen bond. If a reactive bond (eg carbon/hydrogen) is not available for the bond, the ultraviolet light induced excitation of the benzophenone group is reversible and the molecule returns to the ground state energy level upon removal of the energy source. . Photoreactive aryl ketones, such as benzophenone and acetophenone, can undergo multiple reactivations in water and therefore can provide increased coating efficiency.
    Azides constitute another class of photoreactive groups and include aryl azides (C6R5N3) such as phenyl azide and 4-fluoro-3-nitrophenyl azide; acyl azides (—CO—N3), such as benzoyl azide and p-methylbenzoyl azide; azido formates (-O-CO-N3), such as ethyl azidoformate and phenyl azidoformate; sulfonyl azides (—SO2—N3), such as benzene sulfonyl azide; and phosphoryl azides (RO)2PON3 such as diphenyl phosphoryl azide and diethyl phosphoryl azide.
    Diazo compounds constitute another class of photoreactive groups and include diazoalkanes (—CHN2), such as diazomethane and diphenyl diazomethane; diazoketones (—CO—CHN2) such as diazoacetophenone and 1-trifluoromethyl-1-diazo-2-pentanone; diazoacetates (-O-CO-CHN2), such as t-butyl diazoacetate and phenyl diazoacetate; and beta-keto-alpha-diazoacetates (—CO—CN2—CO—O—) such as t-butyl alpha diazoacetoacetate.
    [0039] Other photoreactive groups include the diazirines (—CHN2), such as 3-trifluoromethyl-3-phenyldiazirine; and ketenes (-CH=C=O), such as ketene and diphenylketene.
    [0040] In particular embodiments, the photoreactive groups are aryl ketones, such as benzophenone. RETICULATION AGENTS
    [0041] Crosslinking agents used in accordance with the embodiments herein may include those with at least two photoreactive groups. Exemplary crosslinking agents are described in U.S. Patent Application Publication No. 2011/0245367, the contents of which are incorporated herein by reference in its entirety.
    In some embodiments, the first and/or second cross-linking agent may have a molecular weight of less than about 1500 kDa. In some embodiments, the crosslinking agent can have a molecular weight of less than about 1,200, 1,100, 1,000, 900, 800, 700, 600, 500, or 400.
    [0043] In some embodiments, at least one of the first and second crosslinking agents that comprise a binding agent that has the formula Foto1-LG-Foto2, wherein Foto1 and Foto2, independently represent at least one photoreactive group , and LG represents a linking group comprising at least one silicon or phosphorus atom, wherein there is a covalent bond between at least one photoreactive group and the linking group, wherein the covalent bond between at least one photoreactive group and the linking group is interrupted by at least one heteroatom.
    [0044] In some embodiments, at least one of the first and second crosslinking agents that comprise a linking agent that has a formula selected from:

    [0045] wherein R1, R2, R8 and R9 are any substitution; R3, R4, R6 and R7 are alkyl, aryl, or a combination thereof; R5 is any replacement; and each x independently is O, N, Se, S, or alkyl, or a combination thereof;

    [0046] wherein R1 and R5 are any substitution; R2 and R4 can be any substitution except OH; R3 can be alkyl, aryl, or a combination thereof; and X independently are O, N, Se, S, alkylene, or a combination thereof;

    [0047] wherein R1, R2, R4 and R5 are any substitution; R3 is any replacement; R6 and R7 are alkyl, aryl, or a combination thereof; and each X independently can be O, N, Se, S, alkylene or a combination thereof; and

    [0048] in a particular embodiment, the cross-linking agent may be bis(4-benzoylphenyl) phosphate.
    [0049] In some embodiments, the photoactivatable crosslinking agent may be ionic, and may have good solubility in an aqueous composition, such as the first and/or second coating composition. Thus, in some embodiments, at least one ionic photoactivatable crosslinking agent is used to form the coating. In some cases, an ionic photoactivatable crosslinking agent can crosslink the polymers within the second coating layer which can also improve the durability of the coating.
    [0050] Any suitable ionic photoactivatable crosslinking agent can be used. In some embodiments, the ionic photoactivatable crosslinking agent is a compound of the formula I: X1--Y--X2 wherein Y is a radical containing at least one acidic group, basic group, or a salt of an acidic group or group basic. X1 and X2 are each independently a radical that contains a latent photoreactive group. Photoreactive groups can be the same as those described in this document. Spacers can also be part of X1 or X2 along with the latent photoreactive group. In some embodiments, the latent photoreactive group includes an aryl ketone or a quinone.
    [0051] The radical Y in formula I provides the desired water solubility for the ionic photoactivatable crosslinking agent. Solubility in water (at room temperature and ideal pH) is at least about 0.05 mg/ml. In some embodiments, the solubility is about 0.1 to about 10 mg/ml or about 1 to about 5 mg/ml.
    [0052] In some embodiments of formula I, Y is a radical containing at least one acidic group or salt thereof. Such a photoactivatable crosslinking agent can be anionic depending on the pH of the coating composition. Suitable acidic groups include, for example, sulfonic acids, carboxylic acids, phosphoric acids, and the like. Suitable salts of such groups include, for example, sulfonate, carboxylate and phosphate salts. In some embodiments, the ionic crosslinking agent includes a sulfonic acid or sulfonate group. Suitable counterions include alkali, alkaline ferrous metals, ammonium, protonated amines and the like.
    [0053] For example, a compound of formula I may have a radical Y that contains a sulfonate or sulfonic acid group; X1 and X2 can contain photoreactive groups such as aryl ketones. Such compounds include 4,5-bis(4-benzoylphenylmethyleneoxy)benzene-1,3-disulfonic acid or salt; 2,5-bis(4-benzoylphenylmethyleneoxy)benzene-1,4-disulfonic acid or salt; 2,5-bis(4-benzoylmethyleneoxy)benzene-1 or 2,5-bis(4-benzoylmethyleneoxy)benzene-1sulfonic acid salt; N,N-bis[2-(4-benzoylbenzyloxy)ethyl]-2-aminoethanesulfonic acid or salt, and the like. See U.S. Patent No. 6,278,018. The counterion of the salt can be, for example, ammonium or an alkali metal such as sodium, potassium, or lithium.
    [0054] In other embodiments of formula I, Y may be a radical containing a basic group or a salt thereof. Such Y radicals can include, for example, an ammonium, phosphonium or sulfonium group. The group can be neutral or positively charged, depending on the pH of the coating composition. In some embodiments, the Y radical includes an ammonium group. Suitable counterions include, for example, carboxylates, halides, sulfate, and phosphate. For example, the compounds of formula I can have a radical Y that contains an ammonium group; X1 and X2 can contain photoreactive groups that include aryl ketones. Such photoactivatable crosslinking agents include ethylenebis(4-benzoylbenzyldimethylammonium) salt; hexamethylenebis(4-benzoylbenzyldimethylammonium salt); 1,4-bis(4-benzoylbenzyl)-1,4-dimethylpiperazidinium salt), bis(4-benzoylbenzyl) hexamethylenetetraminedium salt, bis[2-(4-benzoylbenzyldimethylammonio)ethyl]-4-benzoylbenzylmethylammonium salt; 4,4-bis(4-benzoylbenzyl)morpholinium salt; ethylenebis[(2-(4-benzoylbenzyldimethylammonium)ethyl)-4-benzoylbenzylmethylammonium salt] salt; and 1,1,4,4-tetrakis(4-benzoylbenzyl) piperzinedinium salt. See U.S. Patent No. 5,714,360. The counterion is typically a carboxylate or halide ion. In one modality, the halide is bromide.
    [0055] In other embodiments, the ionic photoactivatable crosslinking agent may be a compound having the formula:
    where X1 includes a first photoreactive group; X2 includes a second photoreactive group; Y includes a core molecule; Z includes at least one loaded group; D1 includes a degradable first binder; and D2 includes a second degradable binder. Additional exemplary degradable ionic photoactivatable crosslinking agents are described in US Patent Application Publication No. 2011/0144373 (Swan et al., "Water Soluble Degradable Crosslinker"), the disclosure of which is incorporated herein by reference.
    [0056] In some respects a non-ionic photoactivatable crosslinking agent can be used. In one embodiment, the nonionic photoactivatable crosslinking agent has the formula XR1R2R3R4, where X is a chemical backbone, and R1, R2, R3, and R4 are radicals that include a latent photoreactive group. Exemplary nonionic crosslinking agents are described, for example, in Patent Nos. U.S. 5,414,075 and 5,637,460 (Swan et al., "Restrained Multifunctional Reagent for Surface Modification"). Chemically, the first and second photoreactive groups, and their respective spacers, can be the same or different.
    [0057] In other embodiments, the non-ionic photoactivatable crosslinking agent can be represented by the formula: PG2-LE2-X-LE1-PG1 wherein PG1 and PG2 independently include one or more photoreactive groups, for example an aryl ketone photoreactive group, which includes, but is not limited to, aryl ketones such as acetophenone, benzophenone, anthraquinone, anthrone, anthrone-like heterocycles, substituted derivatives thereof, or a combination thereof; LE1 and LE2 are independently linkers, which include, for example, segments that include urea, carbamate, or a combination thereof; and X represents a core molecule, which can be either polymeric or non-polymeric, which includes, but is not limited to, a hydrocarbon, which includes a hydrocarbon that is linear, branched, cyclic, or a combination thereof; aromatic, non-aromatic, or a combination thereof; monocyclic, polycyclic, carbocyclic, heterocyclic, or a combination thereof; benzene or a derivative thereof; or a combination of these. Other non-ionic crosslinking agents are described, for example, in U.S. Patent Application. 13/316,030 filed December 9, 2011 (Publication No. US 2012/0149934) (Kurdyumov, “Photocrosslinker”), the disclosure of which is herein by reference.
    [0058] Additional embodiments of nonionic photoactivatable crosslinking agents may include, for example, those described in Provisional Patent Application No. US 61/494,724 filed June 8, 2011 (now Patent Application No. 13/490,994) (Swan et al., "Photo-Vinyl Primers/Crosslinkers"), the disclosure of which is incorporated herein by reference. Exemplary crosslinking agents may include nonionic photoactivatable crosslinking agents having the general formula R1 - X - R2 where R1 is a radical comprising a vinyl group, X is a radical comprising from about one to about of twenty carbon atoms, and R2 is a radical comprising a photoreactive group.
    Some suitable crosslinking agents are those formed by a mixture of the chemical backbone molecule (such as pentaerythritol) and an excess of a photoreactive group derivatized (such as 4-bromomethylbenzophenone). An exemplary product is tetrakis(4-benzoylbenzyl ether) of pentaerythritol (tetrakis(4-benzoylphenylmethoxymethyl)methane). See Patent Nos. US 5,414,075 and 5,637,460.
    [0060] A single photoactivatable crosslinking agent or any combination of photoactivatable crosslinking agents can be used in forming the coating. In some embodiments, at least one nonionic crosslinking agent, such as tetrakis(4-benzoylbenzyl ether) pentaerythritol, can be used with at least one ionic crosslinking agent. For example, at least one nonionic photoactivatable crosslinking agent can be used with at least one cationic photoactivatable crosslinking agent, such as an ethylenebis(4-benzoylbenzyldimethylammonium) salt or at least one such anionic photoactivatable crosslinking agent as 4,5-bis(4-benzoyl-phenylmethyleneoxy)benzene-1,3-disulfonic acid or salt. In another example, at least one nonionic crosslinking agent can be used with at least one cationic crosslinking agent and at least one anionic crosslinking agent. In yet another example, at least one cationic crosslinking agent can be used with at least one anionic crosslinking agent but without a nonionic crosslinking agent.
    [0061] An exemplary crosslinking agent is 4,5-bis[(4-benzoylbenzyl)oxy]-1,3-benzenedisulfonate disodium (DBDS). This reagent can be prepared by combining 4,5-dihydroxylbenzyl-1,3-disulfonate (CHBDS) with 4-bromomethylbenzophenone (BMBP) in THF and sodium hydroxide, then refluxing and cooling the mixture followed by purification and recrystallization (also per described in US Patent Application No. 5,714,360, incorporated herein by reference).
    [0062] A further exemplary crosslinking agent is ethylenebis(4-benzoylbenzyldimethylammonium) dibromide. The agent can be prepared as described in U.S. Patent Application No. 5,714,360, the contents of which are hereby incorporated by reference.
    [0063] Additional cross-linking agents may include the cross-linking agents described in Patent Application Publication No. US 2010/0274012 and Patent No. US 7,772,393, the contents of which are hereby incorporated by reference. .
    [0064] In some embodiments, crosslinking agents may include boron-containing linkers including, but not limited to, the boron-containing linkers disclosed in US 61/666,516 entitled "Boron-Containing Linking Agents ” by Kurdyumov et al., the content of which is incorporated herein by reference. By way of example, binding agents can include borate, borazine, or boronate groups and coatings and devices that incorporate binding agents, along with related methods. In one embodiment, the binding agent includes a compound that has the structure (I):

    [0065] wherein R1 is a radical comprising a photoreactive group; R2 is selected from OH and a radical comprising a photoreactive group, an alkyl group and an aryl group; and R3 is selected from OH and a radical comprising a photoreactive group. In some embodiments the bonds B-R1, B-R2 and B-R3 can be independently chosen to be interrupted by a heteroatom, such as O, N, S, or mixtures thereof.
    Additional agents for use with embodiments herein may include stilbene-based reactive compounds including, but not limited to, those disclosed in US 61/736,436 entitled "Stilbene-Based Reactive Compounds, Polymeric Matrices Formed Therefrom, and Articles Visualizable by Fluorescence” by Kurdyumov et al., the content of which is incorporated herein by reference.
    [0067] Additional photoreactive agents, crosslinking agents, hydrophilic coatings, and associated reagents are disclosed in US 2011/0059874; US 2011/0046255; and US 2010/0198168, the contents of which are incorporated herein by reference. METHODS FOR FORMING THE COATING
    [0068] In some embodiments, a first coating solution is formed by combining compounds with a solvent. For example, the compounds can include comprising polyvinylpyrrolidone derivatized with a photoreactive group and a first crosslinking agent comprising at least two photoreactive groups. In some embodiments, the first coating solution can also include underivatized polyvinylpyrrolidone. The solvent for the first coating solution can include assorted components. In some embodiments, the solvent for the first coating solution can be 100% IPA. In some embodiments, the solvent for the first coating solution can include water and isopropyl alcohol (IPA). The ratio of IPA to water can be between about 95% IPA - 5% water to about 10% IPA - 90% water. For example, in some embodiments, the IPA:water ratio can be about 95:5, 90:10, 85:15, 80:20, 75:25, 70:30, 65:35, 60:40, 55 :45, 50:50, 45:55, 40:60, 35:65, 30:70, 25:75, 20:80, 15:85, 10:90, or it can be within a range with extremes that include two of those ratios such that the total relative portions of IPA and water equal 100. In some embodiments, the solvent may include about 75% isopropyl alcohol and about 25% water.
    [0069] In some embodiments of the present disclosure, other exemplary polar solvents (for example acetone, alcohols and DMSO) may be substituted for those described above.
    [0070] In some embodiments, a second coating solution is formed by combining compounds with a solvent. For example, the compounds can include polyvinylpyrrolidone derivatized with a photoreactive group, a second crosslinking agent that comprises at least two photoreactive groups, and a polymer that comprises polyacrylamide, wherein the polymer is derivatized with at least one photoreactive group. The solvent for the second coating solution can include assorted components. In some embodiments, the solvent for the second coating solution can include water and isopropyl alcohol (IPA). The ratio of IPA to water can be from about 0% IPA to 100 water to about 60 IPA to 40 water. For example, in some embodiments, the IPA:water ratio can be about 0:100, 5:95, 10:90, 15:85, 20:80, 25:75, 30:70, 35:65, 40: 60, 45:55, 50:50, 55:45, 60:40, or it can be within a range with extremes that include two of any of these ratios so that the total relative portions of IPA and water equal 100. In some embodiments, the solvent can include about 15% isopropyl alcohol and about 85% water.
    [0071] The viscosity of solutions may vary. In some embodiments, the viscosity of the second solution is less than about 100 centipoise (cP). In some embodiments, the viscosity of the second solution is equal to or less than about 90, 80, 70, 60, 50, 40, 30, 20, or 10 cP.
    [0072] The first coating solution can be applied to a substrate. Prior to applying the coating solution to the substrate, many different pretreatment steps can be taken. In some embodiments, the substrate surface can be cleaned. For example, the surface can be rubbed or immersed in an alcohol such as isopropyl alcohol. In some embodiments, the substrate can be placed in a detergent solution such as a VALTRON solution and sonicated. In some embodiments, a composite can be disposed on the surface of the substrate to act as an anchor layer. In some embodiments the substrate surface can be sterilized.
    [0073] Many different techniques can be used to apply the solution to the substrate. By way of example, exemplary techniques may include drip coating, blade coating, dip coating, spray coating, and the like. In varied modalities, the solution is applied by dip coating. Dip coating speed may vary. For example, the substrate can be immersed in the first coating solution and then withdrawn at speeds between 0.01 and 10 cm/sec. In some embodiments, the substrate can be immersed in the first coating solution and then withdrawn at rates between 0.1 and 4 cm/sec. In some embodiments, the substrate can be immersed in the first coating solution and then withdrawn at speeds between 0.1 and 0.5 cm/sec. In some embodiments, the substrate can be withdrawn at speeds between 0.2 and 0.4 cm/sec. In some embodiments, the substrate can be removed at speeds of about 0.3 cm/sec.
    [0074] After the first coating solution is applied to the substrate, then actinic radiation, such as UV radiation, can be applied to activated photoreactive groups within the components of the first coating solution that form the first layer. Actinic radiation can be provided by any suitable light source that promotes activation of photoreactive groups. Preferred light sources (such as those available from Dymax Corp.) provide UV irradiation in the range of 190 nm to 360 nm. An exemplary UV light source is a Dymax 2000-EC series UV diffused lamp with a 400 Watt metal halide bulb. A suitable radiation dose is in the range of from about 0.5 mW/cm2 to about 2.0 mW/cm2. Optionally, the first coating solution can be dried, either before or during the application of actinic radiation.
    [0075] The second coating solution can be applied on top of the first coating layer. Many different techniques can be used to apply the solution to the substrate. In one particular embodiment, the solution is applied by dip coating. Dip coating speed may vary. For example, the substrate can be immersed in the second coating solution and then withdrawn at speeds between 0.01 and 10 cm/sec. In some embodiments, the substrate can be immersed in the second coating solution and then withdrawn at speeds between 0.1 and 4 cm/sec. In some embodiments, the substrate can be immersed in the second coating solution and then withdrawn at speeds between 0.1 and 0.5 cm/sec. In some embodiments, the substrate can be withdrawn at speeds between 0.2 and 0.4 cm/sec. In some embodiments, the substrate can be removed at speeds of about 0.3 cm/sec.
    [0076] After the second coating solution is applied, then actinic radiation, such as UV radiation with a desired wavelength, can be applied to activated photoreactive groups within the components of the second coating solution. Optionally, the second coating solution can be dried, either before or during the application of actinic radiation. SUBSTRATES
    [0077] The substrates can be partially or entirely fabricated from a metal, ceramic, glass, the like, or a combination of these. Substrates can include polymers such as polyurethanes and polyurethane copolymers, polyethylene, polyolefins, styrene-butadiene copolymers, polyisoprene, isobutylene-isoprene copolymers (butyl rubber), which includes halogenated butyl rubber, butadiene-styrene copolymers. acrylonitrile, silicone polymers, fluorosilicone polymers, polycarbonates, polyamides, polyesters, polyvinyl chloride, polyether-polyester copolymers, polyether-polyamide copolymers, and the like. The substrate can be made from a single material or a combination of materials.
    [0078] Substrate polymers can also include those formed from synthetic polymers, which include oligomers, homopolymers, and copolymers resulting from addition or condensation polymerizations. Examples of suitable addition polymers include, but are not limited to, acrylics such as those polymerized from methyl acrylate, methyl methacrylate, hydroxyethyl methacrylate, hydroxyethyl acrylate, acrylic acid, methacrylic acid, acrylate of glyceryl, glyceryl methacrylate, methacrylamide, and acrylamide; vinyls such as ethylene, propylene, vinyl chloride, vinyl acetate, vinyl pyrrolidone, vinylidene difluoride and styrene. Examples of condensation polymers include, but are not limited to, nylons such as polycaprolactam, polylauryl lactam, polyhexamethylene adipamide, and polyhexamethylene dodecanediamide as well as polyurethanes, polycarbonates, polyamides, polysulfones, poly(ethylene terephthalate), polydimethylsiloxanes, and polyetherketone .
    [0079] In some embodiments, the substrate includes a polymer selected from the group consisting of polyamide, polyimide, block polyether starch (PEBAX), polyether ether ketone (PEEK), high density polyethylene (HDPE), polyethylene, polyurethane, and polyethylene vinyl acetate.
    [0080] Metals that can be used in medical articles include platinum, gold or tungsten, as well as other metals such as rhenium, palladium, rhodium, ruthenium, titanium, nickel, and alloys of these metals such as stainless steel alloys, titanium /nickel, nitinol, cobalt chromium alloys, non-ferrous alloys, and platinum/iridium alloys. An exemplary alloy is MP35. Medical Devices
    [0081] The methods and materials of the invention can be used to coat virtually any medical device for which it is desired to provide a lubricating and hydrophilic coating on a surface thereof. In particular, sheaths are particularly useful for medical articles that can be inserted into the body and moved within the body.
    [0082] Exemplary medical devices include vascular grafts and implants, surgical devices; synthetic prostheses; vascular prostheses that include stents, stent grafts, and endovascular stent combinations; small diameter grafts, abdominal aortic aneurysm grafts; wound dressings and wound treatment device; hemostatic barriers; hernia and mesh plugs; patches, including uterine hemorrhage patches, atrial septic defect patches (ASD), patent oval window patches (PFO), ventricular septal defect patches (VSD), and other generic cardiac patches; ASD, PFO and VSD closures; percutaneous closure devices, mitral valve repair devices; left atrial appendage filters; valve annuloplasty devices, catheters; central venous access catheters, vascular access catheters, abscess drainage catheters, drug infusion catheters, parenteral feeding catheters, intravenous catheters (eg, treated with antithrombotic agents), effusion therapy catheters, catheters stent graft and blood pressure; interventional cardiology devices that include cables and guide wires (eg, stimulation, electricity delivery, defibrillation); anastomosis devices and anastomotic closures; aneurysm exclusion devices; biosensors such as glucose sensors; cardiac sensors (and other sensors for analytical purposes); birth control devices; breast implants; infection control devices; membranes; fabric scaffolding; fabric-related materials; shunts that include cerebral spinal fluid shunts (CSF), glaucoma drainage shunts; dental devices and dental implants; hearing devices such as ear drainage tubes, tympanotomy ventilation tubes; ophthalmic devices; sleeves and sleeve portions of devices including drain tube sleeves, implanted drug infusion tube sleeves, catheter sleeve; suture sleeve; neurological and spinal devices; nerve regeneration conduits; neurological catheters; neuroplasters; orthopedic devices such as orthopedic joint implants, bone reinforcement/repair devices, cartilage repair devices; urological devices and urethral devices such as urological implants, bladder devices, renal devices and hemodialysis devices, colostomy bag attachment devices; biliary drainage products.
    [0083] Referring now to Figure 2, a schematic view of an exemplary device is shown according to a specific embodiment. Device 200 can be, for example, a catheter, such as a balloon angioplasty catheter. Balloon catheter constructions are well known in the art and are described in various documents, for example, US Patents 4,195,637, 5,041,089, 5,087,246, 5,318,587, 5,382,234, 5,571,089, 5,776 101, 5,807,331, 5,882,336, 6,394,995, 6,517,515, 6,623,504, 6,896,842 and 7,163,523. Additional examples of exemplary devices are described in more detail below. Device 200 includes a catheter shaft 202 and a dispenser end 205. Device 200 also includes an inflatable balloon 204 disposed around catheter shaft 202. In Figure 2, balloon 204 is shown in an inflated configuration. Catheter shaft 202 may include a channel for transporting air through catheter shaft 202 and into or from balloon 204 so that balloon 204 can selectively transition from a deflated to an inflated configuration. and vice versa. The catheter shaft and/or balloon may have a coating, such as those described herein, disposed thereon.
    [0084] The present invention can be better understood with reference to the following examples. These examples are intended to be representative of specific embodiments of the invention and are not intended to limit the scope of the invention. EXAMPLES
    [0085] The following reagents, coating solutions and substrates were used for the examples in this document: PA-BBA-AMPS-PEG
    [0086] Poly[acrylamide93.6%-co-sodium-2-acrylamido-2-methylpropanesulfonate4.9%-co-N-(3-(4-benzoylbenzamido)propyl)methacrylamide0.9%]-co-methoxy poly( ethylene glycol)1000 monomethacrylate 0.6% N-acetylated (percentages are molar percentages) was obtained (PA-BBA-AMPS-PEG). Such a reagent can be prepared as described in U.S. Patents 4,979,959; 5,263,992; and 5,512,329. PA-AMPS-BBA-MA
    [0087] Poly[acrylamide-co-sodium-2-acrylamido-2-methylpropanesulfonate-co-N-(3-(4-benzoylbenzamido)propyl)methacrylamide] was prepared according to the procedure described in documents in US 4,973,493 , US 5,002,582 and US 5,263,992. Photo-PVP
    [0088] Polyvinylpyrrolidone having an average molecular weight of approximately 1,450 kDa with benzophenone photoreactive groups was prepared according to the methods described in U.S. Patent 5,512,329. BPP
    The sodium bis(4-benzoylphenyl) phosphate crosslinking agent was prepared according to the methods described in U.S. Patent Application Publication 2012/0046384. PVP-K90
    [0090] Underivatized PVP (eg unmodified PVP) having an average molecular weight of 1200 kDa was obtained from BASF. DBDS
    [0091] 4,5-bis[(4-benzoylbenzyl)oxy]-1,3-benzenedisulfonate disodium (DBDS) was obtained. This reagent can be prepared by combining 4,5-Dihydroxybenzyl-1,3-disulfonate (CHBDS) with 4-bromomethylbenzophenone (BMBP) in THF and sodium hydroxide, refluxing and cooling, then the mixture followed by purification and recrystallization (also as described in US Patent No. 5,714,360).
    [0092] TetraPhos: tetra-benzophenonates bisphosphonate in Patent Application Publication No. US 2012/0046384.

    [0093] TriPhos: tri-benzophenone phosphate prepared according to the methods described in Patent Application Publication No. US 2012/0046384.

    [0094] DSE: dibenzophenone tetraisopropyldisiloxane Patent Application Publication No. US 2012/0046384.
    Coating Solution A
    [0095] A coating solution was prepared by mixing Photo-PVP at 13 g/l; PVP-K90 at 5 g/l; and sodium bis(4-benzoylphenyl) phosphate at 1 g/l in a solvent of 75% isopropyl alcohol and 25% water. Coating Solution B
    [0096] A coating solution was prepared by mixing Photo-PVP at 10.5 g/l; PA-BBA-AMPS-PEG at 10.5 g/l; sodium bis(4-benzoylphenyl) phosphate in 0.1 g/l in a solvent of 15% isopropyl alcohol and 85% water. Coating Solution C
    [0097] A third coating solution was prepared by mixing Photo-PVP in 13 g/l and sodium bis(4-benzoylphenyl) phosphate in 1 g/l in a solvent of 75% isopropyl alcohol and 25% water. Coating Solution D
    [0098] A coating solution was prepared by mixing Photo-PVP at 10.5 g/l; PA-AMPS-BBA-MA at 10.5 g/l; sodium bis(4-benzoylphenyl) phosphate at 0.1 g/l in a solvent of 15% isopropyl alcohol and 85% water. Coating Solution E (w/PVP-K90)
    [0099] A coating solution was prepared by mixing Photo-PVP at 13 g/l; PVP-K90 at 5 g/l; and DBDS at 1 g/l in a solvent of 75% isopropyl alcohol and 25% water. Coating Solution F
    [00100] A coating solution was prepared by mixing Photo-PVP at 10.5 g/l; PA-BBA-AMPS-PEG at 10.5 g/l; DBDS at 0.1 g/l in a solvent of 15% isopropyl alcohol and 85% water. Coating Solution G
    [00101] A coating solution was prepared by mixing Photo-PVP at 16.36 g/l; and TetraPhos at 0.91 g/l in a solvent of 68% isopropyl alcohol and 32% acetone. Coating Solution H
    [00102] A coating solution was prepared by mixing Photo-PVP at 18 g/l; and TriPhos at 1 g/l in a solvent of 75% isopropyl alcohol and 25% acetone. Coating Solution I
    [00103] A coating solution was prepared by mixing Photo-PVP at 18 g/l; and DSE at 1 g/l in a solvent of 75% isopropyl alcohol and 25% water. Coating Solution J
    [00104] A coating solution was prepared by mixing Photo-PVP at 10 g/l; PA-BBA-AMPs-PEG at 10.5 g/l; and DSE at 0.1 g/l in a solvent of 25% isopropyl alcohol and 75% water. Coating Solution K
    [00105] A coating solution was prepared by mixing Photo-PVP at 18 g/l; and BPP at 1 g/l in a solvent of 75% isopropyl alcohol and 25% water. Test Substrates
    [00106] Test substrates included Pebax rods (72D; 63D; and 35D - 40% BASO4) obtained from Medicine Lake Extrusion, Plymouth, MN; NYLON-12 rods obtained from Medicine Lake Extrusion, Plymouth, MN; PEEK stems obtained from Zeus, Orangeburg, SC; and high density polyethylene (HDPE) rods available from Universal Plastics, Denver, CO, USA. Durability and Friction Test (Lubricity)
    [00107] The coated substrates of the examples were evaluated for lubricity/durability by friction measurements using a Vertical Compression method as described in International Application No. WO 03/055611 with the following modifications. The coated substrate samples were inserted into the end of a rod retainer, which was placed between the two jaws of a compression tester and immersed in a cylinder of water or saline. The grips of the compression tester were closed as the sample was pulled in a vertical direction for 10 cm at a travel rate of 1 cm/second and opened when the coated sample was returned to the original position. Unless otherwise specified herein, a force of 750 g was applied as the coated substrates were pulled upward through the compression jaws. The tensile force exerted on the substrate was then measured (grams). The tensile force (g) is equal to the coefficient of friction (COF) multiplied by the compression force (g). The apparatus used for the vertical compression test method is described in U.S. Patent 7,348,055, the contents of which are incorporated herein by reference. Particulate Test
    [00108] The test of particulates generated in aqueous solution for the examples in this document was carried out according to the following procedure. As a derivative of the procedures described in ASTM F2394, the substrates were passed through a tortuous path in an aqueous solution described as follows.
    [00109] The distal portion of a “6 French” guiding catheter (Vista Brite Tip, Cordis) was cut and discarded so that the catheter was 30 cm long. The guide catheter was inserted into ASTM model F2394-07. A hemostatic valve connector (Qosina) was attached to the guide catheter. The model was cleaned by washing with 120 ml of Isoton (Becton, Dickinson, and Company) using a 60 ml syringe and discarding the wash. A baseline wash with 60 ml of Isoton was analyzed by light obscuration to determine background level of particulates. 60 cm (1 mm diameter) 20 cm coated rods were hydrated in Isoton for > 1 minute. The nails were inserted into the guide catheter and advanced until the distal portion of the nail left the model. A 30 ml wash with Isoton was performed and collected in a glass beaker. The rod was removed and an additional 30 ml wash with Isoton was performed in the same glass beaker. The collected isoton was immediately analyzed by light obscuration for particulates > 10 and > 25 microns. The model was cleaned with 120 ml of Isoton and the next coated rod was tested. Example 1: Formation of Lubricant Coating on 72D Pebax Rods
    [00110] Coating solution A was applied to the substrate (72D Pebax rods) using a dip coating method. Specifically, the substrate was immersed in the basecoat coating solution with a residence time of 5 seconds. The substrate was then extracted from the solution at a speed of 0.3 cm/s. The first layer was then air dried for at least 10 minutes. The first layer was then UV cured. Specifically, the coated substrate was spun in front of a Dymax 2000-EC series UV diffused lamp with a 400 Watt metal halide bulb for 3 minutes, approximately 20 cm from the light source.
    [00111] Then, coating solution B was applied to the first layer, also by dip coating at the same speed to form the second layer. The second coat was then air dried and UV cured using the same conditions as for the first coat.
    [00112] The friction of the coating was then tested in accordance with the test procedure outlined above. The results are shown in Figure 3. Example 2: Effect of Variation of Polyacrylamide Containing Polymer on Second Layer
    [00113] Coating solution A was applied to the substrate (72D Pebax rods) using a dip coating method. Specifically, the substrate was immersed in the basecoat coating solution with a residence time of 5 seconds. The substrate was then extracted from the solution at a speed of 0.3 cm/s. The first layer was then air dried for at least 10 minutes. The first layer was then UV cured. Specifically, the coated substrate was spun in front of a Dymax 2000-EC series UV diffused lamp with a 400 Watt metal halide bulb for 3 minutes, approximately 20 cm from the light source.
    [00114] Then, coating solution B (n=4) or solution D (n=4) were applied to the first layer, also by dip coating at the same speed to form the second layer or top coating. Then the second layer was air dried and UV cured using the same conditions as for the first layer.
    [00115] Then, the friction of the coating was tested according to the test procedure outlined above. The results are shown in Figure 4.
    [00116] The particulate generation test was also performed. For an average of 3 stalks, it was observed that the PA-AMPS-BBA-MA group generated 4,447(+/- 567) particulates greater than 10 microns in size and the PA-BBA-AMPS-PEG group generated 4,140(+ /-725) particulates greater than 10 microns in size. Example 3: Effect of Substrate Variation on Lubricity and Durability
    [00117] The coatings were deposited on each of the Pebax rods (72D; 63D; and 35D - 40% BASO4), NYLON-12 rods, PEEK rods and HDPE rods.
    [00118] Specifically, coating solution A was applied to each substrate using a dip coating method. Specifically, the substrate was immersed in the basecoat coating solution with a residence time of 5 seconds. Then, the substrate was extracted from the solution at a speed of 0.3 cm/s. Then the first layer was air dried for at least 10 minutes. Then the first layer was UV cured. Specifically, the coated substrate was rotated in front of a Dymax 2000-EC series UV diffused lamp with a 400 Watt metal halide bulb for 3 minutes, approximately 20 cm from the light source.
    [00119] Then, coating solution B was applied to the first layer, also by dip coating at the same speed to form the second layer. Then the second layer was air dried and UV cured using the same conditions as for the first layer.
    [00120] The friction of the coating on each substrate was then tested in accordance with the test procedure outlined above. The results are shown in Figure 5. Example 4: Effect of Two-Layer Combinations on Lubricity and Durability
    [00121] For a first set of rods (72D Pebax - n=7), coating solution A was applied to the substrate (72D Pebax rods) using a dip coating method. Specifically, the substrate was immersed in the basecoat coating solution with a residence time of 5 seconds. Then, the substrate was extracted from the solution at a speed of 0.3 cm/s. Then the first layer was air dried for at least 10 minutes. Then the first layer was UV cured. Specifically, the coated substrate was spun in front of a Dymax 2000-EC series UV diffused lamp with a 400 Watt metal halide bulb for 3 minutes, approximately 20 cm from the light source. Then, another layer of coating solution A was applied to the first layer, also by dip coating at the same speed to form the second layer. Then the second layer was air dried and UV cured using the same conditions as for the first layer.
    [00122] For a second set of rods (72D Pebax - n=4), coating solution B was applied to the substrate (72D Pebax rods) using a dip coating method. Specifically, the substrate was immersed in the basecoat coating solution with a residence time of 5 seconds. Then, the substrate was extracted from the solution at a speed of 0.3 cm/s. Then the first layer was air dried for at least 10 minutes. Then the first layer was UV cured. Specifically, the coated substrate was spun in front of a Dymax 2000-EC series UV diffused lamp with a 400 Watt metal halide bulb for 3 minutes, approximately 20 cm from the light source. Then another layer of coating solution B was applied to the first layer, also by dip coating at the same speed to form the second layer. Then the second layer was air dried and UV cured using the same conditions as for the first layer.
    [00123] For a third set of rods (72D Pebax - n=9), coating solution A was applied to the substrate (72D Pebax rods) using a dip coating method. Specifically, the substrate was immersed in the basecoat coating solution with a residence time of 5 seconds. Then, the substrate was extracted from the solution at a speed of 0.3 cm/s. Then the first layer was air dried for at least 10 minutes. Then the first layer was UV cured. Specifically, the coated substrate was spun in front of a Dymax 2000-EC series UV diffused lamp with a 400 Watt metal halide bulb for 3 minutes, approximately 20 cm from the light source. Then, a layer of coating solution B was applied to the first layer, also by dip coating at the same speed to form the second layer. Then the second layer was air dried and UV cured using the same conditions as for the first layer.
    [00124] The friction of the coating was then tested according to the test procedure outlined above. The results are shown in Figure 6. In addition, observations were made regarding the swelling behavior of the coatings. It was observed that the first set of nails (including two “base” layers) exhibited the least amount of swelling. It was observed that the second set of nails (including two “top” layers) exhibited the greatest swelling. It was observed that the third set of stems (including a base layer and a top layer) exhibited an intermediate amount of swelling. Table 1 includes a summary of the coating thickness measurements and the calculated swelling ratio for each blade. Table 1. Summary of coating thickness measurements and calculated swelling ratio for each slide.
    Example 5: Effects of Layered Crosslinking Agents
    [00125] For a first set ("In BC - base coat and TC - top coat") of rods, coating solution A was applied to the substrate (72D Pebax rods) using a dip coating method . Specifically, the substrate was immersed in the basecoat coating solution with a residence time of 5 seconds. Then, the substrate was extracted from the solution at a speed of 0.3 cm/s. Then the first layer was air dried for at least 10 minutes. Then the first layer was UV cured. Specifically, the coated substrate was spun in front of a Dymax 2000-EC series UV diffused lamp with a 400 Watt metal halide bulb for 3 minutes, approximately 20 cm from the light source. Then, a layer of coating solution B was applied to the first layer, also by dip coating at the same speed to form the second layer. Then the second layer was air dried and UV cured using the same conditions as for the first layer.
    [00126] For a second set ("On TC Only") of rods, a coating solution similar to A, except sodium-free bis(4-benzoylphenyl) phosphate, was applied to the substrate (72D Pebax rods) using of a dip coating method. Specifically, the substrate was immersed in the basecoat coating solution with a residence time of 5 seconds. Then, the substrate was extracted from the solution at a speed of 0.3 cm/s. Then the first layer was air dried for at least 10 minutes. Then the first layer was UV cured. Specifically, the coated substrate was spun in front of a Dymax 2000-EC series UV diffused lamp with a 400 Watt metal halide bulb for 3 minutes, approximately 20 cm from the light source. Then, a layer of coating solution B was applied to the first layer, also by dip coating at the same speed to form the second layer. Then the second layer was air dried and UV cured using the same conditions as for the first layer.
    [00127] For a third set (“On BC Only”) of rods coating solution A was applied to the substrate (72D Pebax rods) using a dip coating method. Specifically, the substrate was immersed in the basecoat coating solution with a residence time of 5 seconds. Then, the substrate was extracted from the solution at a speed of 0.3 cm/s. Then the first layer was air dried for at least 10 minutes. Then the first layer was UV cured. Specifically, the coated substrate was spun in front of a Dymax 2000-EC series UV diffused lamp with a 400 Watt metal halide bulb for 3 minutes, approximately 20 cm from the light source. Then a layer of a coating solution similar to B, except that no sodium bis(4-benzoylphenyl) phosphate, was applied to the first layer, also by dip coating at the same speed to form the second layer. Then the second layer was air dried and UV cured using the same conditions as for the first layer.
    [00128] The particulate generation of the coating was then tested according to the test procedure outlined above. The results are shown in Figure 7. Example 6: Effects of Varying Amounts of Components on the Second Layer
    [00129] Coating solution A was applied to the substrate (72D Pebax rods) using a dip coating method. Specifically, the substrate was immersed in the basecoat coating solution with a residence time of 5 seconds. Then, the substrate was extracted from the solution at a speed of 0.3 cm/s. Then the first layer was air dried for at least 10 minutes. Then the first layer was UV cured. Specifically, the coated substrate was spun in front of a Dymax 2000-EC series UV diffused lamp with a 400 Watt metal halide bulb for 3 minutes, approximately 20 cm from the light source.
    [00130] Then, a layer of a coating solution was applied to the first layer, also by dip coating at the same speed to form the second layer. The different solutions used for the second coating layer were similar to coating solution B, but the Photo-PVP:PA-BBA-AMPS-PEG ratios varied. For the control, the ratio was 1:1 as in coating solution B. The other ratios were 1:2 and 2:1. In another coating solution, photo-PVP was completely eliminated. In yet another coating solution, PA-BBA-AMPS-PEG (PBAP) was completely eliminated. In all cases, the second layer was air dried and then UV cured using the same conditions as for the first layer.
    [00131] The friction of the coating was then tested according to the test procedure outlined above. The results are shown in Figure 8. Example 7: Effects of Varying Viscosity and Immersion Speed
    [00132] Coating solution C was applied to a plurality of substrates (72D Pebax rods) using a dip coating method. Specifically, the substrate was immersed in the basecoat coating solution with a residence time of 5 seconds. Then, the substrate was extracted from the solution at a speed of 1.0 cm/s. Then the first layer was UV cured without the first drying. Specifically, the coated substrate was rotated in front of a Dymax 2000-EC series UV diffused lamp with a 400 Watt metal halide bulb for 30 seconds, approximately 20 cm from the light source.
    [00133] Coating solution B variations were prepared. One variation had sufficient solids concentration to result in a coating solution with a viscosity of 20 cP. Another variation had a solids concentration sufficient to result in a coating solution with a viscosity of 13.8 cP. Yet another variation had a sufficient solids concentration to result in a coating solution with a viscosity of 8.91 cP. Then, the substrate was immersed in the coating coating solutions with a residence time of 5 seconds and variable extraction speeds including 0.3; 0.5; 0.8; 1; 1.5 and 2 cm/s. The second layer was not allowed to dry, but UV cured immediately. Specifically, the coated substrate was rotated in front of a Dymax 2000-EC series UV diffused lamp with a 400 Watt metal halide bulb for 30 seconds, approximately 20 cm from the light source.
    [00134] The friction of the coating was then tested in accordance with the test procedure outlined above. The results are shown in Figure 9.
    [00135] The particulates for the coatings were then tested according to the test procedure outlined above. The results are shown in Figure 10. Example 8: Lubricant Coating Formation on 72D Pebax Rods
    [00136] Coating solution E was applied to the substrate (72D Pebax rods) using a dip coating method. Specifically, the substrate was immersed in the basecoat coating solution with a residence time of 5 seconds. Then, the substrate was extracted from the solution at a speed of 0.3 cm/s. Then the first layer was air dried for at least 10 minutes. Then the first layer was UV cured. Specifically, the coated substrate was spun in front of a Dymax 2000-EC series UV diffused lamp with a 400 Watt metal halide bulb for 3 minutes, approximately 20 cm from the light source.
    [00137] Then, coating solution F was applied to the first layer, also by dip coating at the same speed to form the second layer. Then the second layer was air dried and UV cured using the same conditions as for the first layer.
    [00138] The friction of the coating was then tested in accordance with the test procedure outlined above. The results are shown in Figure 11. Example 9: Effects of Different Crosslinking Agents on Base and/or Top Coatings a) Each of coating solutions G, H, I or K was applied to four separate rods of substrate material (72D Pebax rods) using a dip coating method and curing step as per Example 1 (with the exception that the K coating was dip coated at a rate of 1.5 cm/sec). This coating served as the base coating for these four examples. b) Coating solution B was applied to the first layer of coated samples of G and H described in a) above using the same dip coating method and curing step as in Example 1. This coating served as the top coating . c) Coating solution J was applied to the first layer of samples I described in a) above using the same dip coating method and curing step as in Example 1. This coating served as the top coat. d) Coating solution B was applied to the first layer of samples K described in a) above using the same dip coating method and curing step as in Example 1. This coating served as the top coat.
    [00139] The friction (Figures 12 and 13) and the particulate test (Table 2) were then carried out according to the test procedures described above. Table 2

    [00140] It should be noted that, as used in this specification and the appended claims, the singular forms "a", "an" and "the" include the plural references unless the content clearly dictates the contrary. Accordingly, for example, reference to a composition containing "a compound" includes a mixture of two or more compounds. It should also be noted that the term “or” is generally used in the sense that it includes “and/or” unless the content clearly states otherwise.
    [00141] It should also be noted that, as used in this specification and the accompanying claims, the term "configured" describes a system, apparatus or other structure that is built or configured to perform a particular task or adopt a particular configuration. The term "configured" may be used interchangeably with other similar expressions such as arranged and configured, constructed and disposed, constructed, manufactured and disposed, and the like.
    [00142] All publications and patent applications in this descriptive report are indicative of the common level of skill in the art to which this invention belongs. All publications and patent applications are incorporated herein by reference in the same way as if each individual publication or patent application were specifically and individually indicated by reference. Nothing in this document should be construed as an admission that the inventors are not entitled to advance any publication and/or patent, including any publication and/or patent cited herein.
    [00143] The invention has been described with reference to various specific and preferred techniques and embodiments. However, it should be understood that many variations and modifications can be made while remaining within the spirit and scope of the invention.
    权利要求:
    Claims (18)
    [0001]
    1. Coating for a medical device CHARACTERIZED in that it comprises: a first layer comprising polyvinylpyrrolidone derivatized with a photoreactive group; and a first crosslinking agent comprising at least two photoreactive groups; a second layer disposed on the first layer comprising polyvinylpyrrolidone derivatized with a photoreactive group; a second crosslinking agent comprising at least two photoreactive groups; and a polymer comprising poly[acrylamide-co-sodium-2-acrylamido-2-methylpropanesulfonate-co-N-(3-(4-benzoylbenzamido)propyl)methacrylamide]-co-methoxy poly(ethylene glycol)N-monomethacrylate acetylated.
    [0002]
    2. Coating according to claim 1, CHARACTERIZED by the fact that the first cross-linking agent is different from the second cross-linking agent.
    [0003]
    3. Coating according to claim 1 or 2, CHARACTERIZED by the fact that the ratio of polyvinylpyrrolidone derivatized with a photoreactive group in the second layer to the polymer in the second layer is between approximately 3:1 and 1:3 (weight /Weight).
    [0004]
    4. Coating according to any one of claims 1 to 3, CHARACTERIZED by the fact that the ratio of polyvinylpyrrolidone derivatized with a photoreactive group in the first layer to the first crosslinking agent comprising at least two photoreactive groups is approximately 8: 1 to approximately 16:1 (weight/weight).
    [0005]
    5. Coating according to any one of claims 1 to 4, CHARACTERIZED by the fact that at least one of the first and second crosslinking agents comprises a binding agent having the formula Photo1-LG-Photo2, in that Photo1 and Photo2 independently represent at least one photoreactive group and LG represents a linking group comprising at least one silicon atom or at least one phosphorus atom, there being a covalent bond between at least one photoreactive group and the linking group , wherein the covalent bond between at least one photoreactive group and the linking group is interrupted by at least one heteroatom.
    [0006]
    6. Coating, according to any one of claims 1 to 5, CHARACTERIZED by the fact that at least one of the first and second crosslinking agents comprises a binding agent that has a formula selected from:
    [0007]
    7. Coating according to any one of claims 1 to 6, CHARACTERIZED by the fact that at least one of the first and second crosslinking agents comprises 4,5-bis[(4-benzoylbenzyl)oxy]-1,3 - disodium benzenedisulfonate (DBDS).
    [0008]
    8. Coating, according to any one of claims 1 to 7, CHARACTERIZED by the fact that at least one of the first and second crosslinking agents comprises sodium bis(4-benzoylphenyl) phosphate (BPP):
    [0009]
    9. Coating, according to any one of claims 1 to 8, CHARACTERIZED by the fact that at least one of the first and second crosslinking agents comprises ethylenebis(4-benzoylbenzyldimethylammonium) dibromide.
    [0010]
    10. Coating according to any one of claims 1 to 9, CHARACTERIZED by the fact that the first layer additionally comprises non-derivatized polyvinylpyrrolidone.
    [0011]
    11. Coating according to any one of claims 1 to 10, CHARACTERIZED by the fact that the ratio of derivatized polyvinylpyrrolidone with a photoreactive group in the first layer to non-derivatized polyvinylpyrrolidone in the first layer for the first crosslinking agent comprising at least two photoreactive groups is approximately 13:0.1:1 to 13:8:1.
    [0012]
    12. Coating, according to any one of claims 1 to 11, CHARACTERIZED by the fact that the coating exhibits a lubricity when wet between 0 and 30 grams of force and the coating releases particulates of less than 20,000 particles larger than 10 microns.
    [0013]
    13. Coating according to any one of claims 1 to 12, CHARACTERIZED by the fact that the photoreactive group comprises an aryl ketone.
    [0014]
    14. Coating according to any one of claims 1 to 13, CHARACTERIZED by the fact that the photoreactive group is benzophenone.
    [0015]
    15. Medical device CHARACTERIZED by the fact that it comprises: a substrate; a first layer disposed on the substrate, the first layer comprising polyvinylpyrrolidone derivatized with a photoreactive group; and a first crosslinking agent comprising at least two photoreactive groups; a second layer disposed on the first layer comprising polyvinylpyrrolidone derivatized with a photoreactive group; a second crosslinking agent comprising at least two photoreactive groups; and a polymer comprising poly[acrylamide-co-sodium-2-acrylamido-2-methylpropanesulfonate-co-N-(3-(4-benzoylbenzamido)propyl)methacrylamide]-co-methoxy poly(ethylene glycol)N-monomethacrylate acetylated.
    [0016]
    16. Medical device according to claim 15, CHARACTERIZED by the fact that the substrate comprises a polymer selected from the group consisting of polyamide, polyimide, polyether block amide (PEBAX), polyether ether ketone (PEEK), polyethylene of high density (HDPE), polyethylene, polyurethane and polyethylene vinyl acetate.
    [0017]
    17. Medical device according to claim 15 or 16, CHARACTERIZED by the fact that the medical device comprises a catheter.
    [0018]
    18. A method of producing a medical device CHARACTERIZED in that it comprises: applying a first coating solution on a substrate to form a first layer, the first coating solution comprising polyvinylpyrrolidone derivatized with a photoreactive group; a first cross-linking agent comprising at least two photoreactive groups; and a first solvent; and applying a second coating solution over the first layer to form a second layer, the second coating solution comprising polyvinylpyrrolidone derivatized with a photoreactive group; a second crosslinking agent comprising at least two photoreactive groups; a polymer comprising poly[acrylamide-co-sodium-2-acrylamido-2-methylpropanesulfonate-co-N-(3-(4-benzoylbenzamido)propyl)methacrylamide]-comethoxy poly(ethylene glycol) N-acetylated monomethacrylate .
    类似技术:
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    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    CH616337A5|1977-10-21|1980-03-31|Schneider Medintag Ag|
    US4973493A|1982-09-29|1990-11-27|Bio-Metric Systems, Inc.|Method of improving the biocompatibility of solid surfaces|
    US5512329A|1982-09-29|1996-04-30|Bsi Corporation|Substrate surface preparation|
    US5002582A|1982-09-29|1991-03-26|Bio-Metric Systems, Inc.|Preparation of polymeric surfaces via covalently attaching polymers|
    US4979959A|1986-10-17|1990-12-25|Bio-Metric Systems, Inc.|Biocompatible coating for solid surfaces|
    US5263992A|1986-10-17|1993-11-23|Bio-Metric Systems, Inc.|Biocompatible device with covalently bonded biocompatible agent|
    US5001009A|1987-09-02|1991-03-19|Sterilization Technical Services, Inc.|Lubricious hydrophilic composite coated on substrates|
    US5041089A|1987-12-11|1991-08-20|Devices For Vascular Intervention, Inc.|Vascular dilation catheter construction|
    US5087246A|1988-12-29|1992-02-11|C. R. Bard, Inc.|Dilation catheter with fluted balloon|
    US4990357A|1989-05-04|1991-02-05|Becton, Dickinson And Company|Elastomeric segmented hydrophilic polyetherurethane based lubricious coatings|
    US5318587A|1989-08-25|1994-06-07|C. R. Bard, Inc.|Pleated balloon dilatation catheter and method of use|
    US5039485A|1990-09-26|1991-08-13|Union Carbide Industrial Gases Technology Corporation|Sterilization method|
    ES2071279T3|1990-10-04|1995-06-16|Schneider Europ Ag|EXPANSION BALL CATHETER.|
    US5414075A|1992-11-06|1995-05-09|Bsi Corporation|Restrained multifunctional reagent for surface modification|
    US5382234A|1993-04-08|1995-01-17|Scimed Life Systems, Inc.|Over-the-wire balloon catheter|
    US5344402A|1993-06-30|1994-09-06|Cardiovascular Dynamics, Inc.|Low profile perfusion catheter|
    US6896842B1|1993-10-01|2005-05-24|Boston Scientific Corporation|Medical device balloons containing thermoplastic elastomers|
    WO1995028983A1|1994-04-20|1995-11-02|Solar Ronald J|Active perfusion dilatation catheter|
    US5670558A|1994-07-07|1997-09-23|Terumo Kabushiki Kaisha|Medical instruments that exhibit surface lubricity when wetted|
    US5849846A|1994-07-25|1998-12-15|Advanced Cardiovascular Systems, Inc.|Balloons for medical catheters|
    US5554120A|1994-07-25|1996-09-10|Advanced Cardiovascular Systems, Inc.|Polymer blends for use in making medical devices including catheters and balloons for dilatation catheters|
    US5667493A|1994-12-30|1997-09-16|Janacek; Jaroslav|Dilation catheter|
    US5662960A|1995-02-01|1997-09-02|Schneider Inc.|Process for producing slippery, tenaciously adhering hydrogel coatings containing a polyurethane-urea polymer hydrogel commingled with a poly polymer hydrogel|
    US5731087A|1995-06-07|1998-03-24|Union Carbide Chemicals & Plastics Technology Corporation|Lubricious coatings containing polymers with vinyl and carboxylic acid moieties|
    US5714360A|1995-11-03|1998-02-03|Bsi Corporation|Photoactivatable water soluble cross-linking agents containing an onium group|
    JP3336600B2|1996-04-18|2002-10-21|ニプロ株式会社|Medical guidewire and method of manufacturing the same|
    SE9602529D0|1996-06-26|1996-06-26|Astra Ab|Medical device|
    JP3362186B2|1996-08-09|2003-01-07|ニプロ株式会社|Medical device and manufacturing method thereof|
    US5858653A|1997-09-30|1999-01-12|Surmodics, Inc.|Reagent and method for attaching target molecules to a surface|
    JP4183024B2|1997-10-20|2008-11-19|日本シャーウッド株式会社|Medical device having lubricious coating and method for producing the same|
    US6221425B1|1998-01-30|2001-04-24|Advanced Cardiovascular Systems, Inc.|Lubricious hydrophilic coating for an intracorporeal medical device|
    US6517515B1|1998-03-04|2003-02-11|Scimed Life Systems, Inc.|Catheter having variable size guide wire lumen|
    US6007833A|1998-03-19|1999-12-28|Surmodics, Inc.|Crosslinkable macromers bearing initiator groups|
    US6394995B1|1998-05-15|2002-05-28|X Technologies Inc.|Enhanced balloon dilatation system|
    US6176849B1|1999-05-21|2001-01-23|Scimed Life Systems, Inc.|Hydrophilic lubricity coating for medical devices comprising a hydrophobic top coat|
    JP4143883B2|1999-07-06|2008-09-03|日本シャーウッド株式会社|Medical device and manufacturing method thereof|
    US6278018B1|1999-12-14|2001-08-21|Surmodics, Inc.|Surface coating agents|
    AT323517T|2000-08-15|2006-05-15|Surmodics Inc|MATRIX FOR THE ADMINISTRATION OF MEDICINAL PRODUCTS|
    US6623504B2|2000-12-08|2003-09-23|Scimed Life Systems, Inc.|Balloon catheter with radiopaque distal tip|
    US7348055B2|2001-12-21|2008-03-25|Surmodics, Inc.|Reagent and method for providing coatings on surfaces|
    BR0309340A|2002-04-19|2005-03-08|Novartis Ag|Materials, their preparation and use|
    US7192484B2|2002-09-27|2007-03-20|Surmodics, Inc.|Advanced coating apparatus and method|
    EP1596898B1|2003-02-26|2009-04-08|Boston Scientific Limited|Balloon catheter|
    CN1813059A|2003-05-02|2006-08-02|西格玛-奥尔德利希公司|Solid phase cell lysis and capture platform|
    CA2560507C|2004-03-26|2011-08-16|Surmodics, Inc.|Composition and method for preparing biocompatible surfaces|
    WO2006063181A1|2004-12-06|2006-06-15|Surmodics, Inc.|Multifunctional medical articles|
    AT453692T|2005-06-02|2010-01-15|Surmodics Inc|HYDROPHILIC POLYMER COATINGS FOR MEDICAL TECHNICAL DEVICES|
    US7772393B2|2005-06-13|2010-08-10|Innovative Surface Technologies, Inc.|Photochemical crosslinkers for polymer coatings and substrate tie-layer|
    WO2008042748A2|2006-09-29|2008-04-10|Surmodics, Inc.|Polyelectrolyte media for bioactive agent delivery|
    EP2125061A2|2007-02-28|2009-12-02|DSM IP Assets B.V.|Hydrophilic coating|
    WO2008104572A2|2007-02-28|2008-09-04|Dsm Ip Assets B.V.|Hydrophilic coating|
    CA2711490A1|2008-01-14|2009-07-23|Surmodics, Inc.|Devices and methods for elution of nucleic acid delivery complexes|
    DK2252661T3|2008-03-12|2017-01-16|Dsm Ip Assets Bv|HYDROPHIL COATING|
    WO2009126830A2|2008-04-09|2009-10-15|Surmodics, Inc.|Delivery of nucleic acid complexes from materials including negatively charged groups|
    WO2010129328A2|2009-04-28|2010-11-11|Surmodics, Inc.|Devices and methods for delivery of bioactive agents|
    US20110144373A1|2009-12-10|2011-06-16|Surmodics, Inc.|Water-soluble degradable photo-crosslinker|
    RU2594729C2|2010-03-30|2016-08-20|Сурмодикс, Инк.|Degradable photo cross-linking agent|
    CA2803361C|2010-06-30|2020-07-21|Surmodics, Inc.|Lipid coating for medical devices delivering bioactive agent|
    US10315987B2|2010-12-13|2019-06-11|Surmodics, Inc.|Photo-crosslinker|
    JP5690631B2|2011-03-30|2015-03-25|日本コヴィディエン株式会社|Lubricating medical device and method for manufacturing the same|
    US9861727B2|2011-05-20|2018-01-09|Surmodics, Inc.|Delivery of hydrophobic active agent particles|
    WO2012170706A2|2011-06-08|2012-12-13|Surmodics, Inc.|Photo-vinyl linking agents|
    CN104185661B|2012-01-18|2016-08-17|苏尔莫迪克斯公司|The lubricity medical treatment device coating of low microgranule|
    US9308355B2|2012-06-01|2016-04-12|Surmodies, Inc.|Apparatus and methods for coating medical devices|
    US9631190B2|2012-06-29|2017-04-25|Surmodics, Inc.|Cell attachment coatings and methods using phosphorous-containing photoreagent|
    EP2692365A1|2012-08-03|2014-02-05|MaRVis Medical GmbH|Implantable or insertable MRI-detectable medical device having a coating comprising paramagnetic ions and a process for preparing it|
    US9629945B2|2012-12-12|2017-04-25|Surmodics, Inc.|Stilbene-based reactive compounds, polymeric matrices formed therefrom, and articles visualizable by fluorescence|
    US9340876B2|2012-12-12|2016-05-17|Applied Materials, Inc.|Mask for deposition process|
    CA2896107C|2013-01-04|2021-11-23|Surmodics, Inc.|Low particulate lubricious coating with vinyl pyrrolidone and acidic polymer-containing layers|
    JP6335179B2|2013-09-02|2018-05-30|テルモ株式会社|Medical device and manufacturing method thereof|
    EP3071249B1|2013-11-20|2018-08-29|DSM IP Assets B.V.|Reducing the deterioraton of wetted hydrophilic coatings comprising water subjected to sterilization by radiation|
    US10124088B2|2014-09-29|2018-11-13|Surmodics, Inc.|Lubricious medical device elements|
    US11174447B2|2015-12-29|2021-11-16|Surmodics, Inc.|Lubricious coatings with surface salt groups|
    US10342898B2|2015-12-29|2019-07-09|Surmodics, Inc.|Lubricious coatings with surface salt groups|WO2007037241A1|2005-09-28|2007-04-05|Japan Science And Technology Agency|Shear measuring method and its device|
    WO2010129328A2|2009-04-28|2010-11-11|Surmodics, Inc.|Devices and methods for delivery of bioactive agents|
    US9861727B2|2011-05-20|2018-01-09|Surmodics, Inc.|Delivery of hydrophobic active agent particles|
    US10213529B2|2011-05-20|2019-02-26|Surmodics, Inc.|Delivery of coated hydrophobic active agent particles|
    CN104185661B|2012-01-18|2016-08-17|苏尔莫迪克斯公司|The lubricity medical treatment device coating of low microgranule|
    JP6438406B2|2012-11-05|2018-12-12|サーモディクス，インコーポレイテッド|Compositions and methods for delivering hydrophobic bioactive agents|
    US11246963B2|2012-11-05|2022-02-15|Surmodics, Inc.|Compositions and methods for delivery of hydrophobic active agents|
    WO2015031265A1|2013-08-25|2015-03-05|Surmodics, Inc.|Conductive polymeric coatings, medical devices, coating solutions and methods|
    US10124088B2|2014-09-29|2018-11-13|Surmodics, Inc.|Lubricious medical device elements|
    CN107949403A|2015-04-16|2018-04-20|好利司泰公司|Hydrophilic coating and forming method thereof|
    CN105251095B|2015-10-22|2018-05-15|江苏康诺医疗器械有限公司|PVC ultra-smooth urinary catheters and preparation method thereof|
    US10342898B2|2015-12-29|2019-07-09|Surmodics, Inc.|Lubricious coatings with surface salt groups|
    US11174447B2|2015-12-29|2021-11-16|Surmodics, Inc.|Lubricious coatings with surface salt groups|
    EP3436096A1|2016-03-31|2019-02-06|Surmodics, Inc.|Lubricious coating for medical device|
    US10898446B2|2016-12-20|2021-01-26|Surmodics, Inc.|Delivery of hydrophobic active agents from hydrophilic polyether block amide copolymer surfaces|
    WO2020004385A1|2018-06-27|2020-01-02|テルモ株式会社|Hydrophilic copolymer and medical instrument|
    法律状态:
    2018-03-27| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|
    2019-08-20| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|
    2021-01-05| B06A| Notification to applicant to reply to the report for non-patentability or inadequacy of the application [chapter 6.1 patent gazette]|
    2021-05-04| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|
    2021-06-22| B16A| Patent or certificate of addition of invention granted|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 18/01/2013, OBSERVADAS AS CONDICOES LEGAIS. |
    优先权:
    申请号 | 申请日 | 专利标题
    US201261587944P| true| 2012-01-18|2012-01-18|
    US201261587929P| true| 2012-01-18|2012-01-18|
    US61/587,944|2012-01-18|
    US61/587,929|2012-01-18|
    PCT/US2013/022202|WO2013109930A1|2012-01-18|2013-01-18|Lubricious medical device coating with low particulates|
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