UV-curable coatings for medical devices

Abstract

The present invention relates to hydrophobic and hydrophilic coating compositions for medical devices or implants. The hydrophilic coating composition comprises a polymer soluble in water or a water-alcohol solution, the polymer being made from (a) at least one monomer that is a photoradical generator and (b) at least one monomer that contains (i) an ethylenic monomer having at least one acidic group and (ii) one or more acrylates or acrylamides, wherein the molar ratio of the photoradical generator to the ethylenic monomer having at least one acidic group and the one or more acrylates or acrylamides is 20:1 to 500:1. The hydrophilic coating composition can provide the entire coating or can be used as the topcoat of a two-coat system along with a hydrophobic basecoat. The hydrophobic coating composition comprises a polymer made from a monomer having (a) 1 to 12 mol % of at least one photoactive monomer that is a hydrogen atom abstracting agent, and (b) 99 to 88 mol % of one or more of acrylamide, methacrylamide, acrylate, methacrylate, and N-vinylpyrrolidone, the polymer having a glass transition temperature (Tg) of less than 40° C. The hydrophobic polymer forms a base coat for the hydrophilic polymer described above or a hydrophilic polymer coating that does not contain a photoradical-generating component.

Description

[Technical field]

[0001] The present invention relates to ultraviolet curable coatings for medical devices and implants. [Background technology]

[0002] The present invention relates to the field of non-thrombogenic and lubricious coatings for medical devices, particularly devices intended for temporary or permanent implantation within the body and blood contact applications.

[0003] Among the many advances in medical practice in recent years are medical devices that complement the surgeon's skills. Examples of these are vascular catheters and guidewires, which are used to treat remote areas of the circulatory system that were previously only treatable by surgery. Others are stents, devices that reinforce arterial walls and prevent blockages after angioplasty. Others are intraocular lenses that restore vision to elderly people suffering from cataracts. Still other devices are heart valves, artificial pacemakers, orthopedic implants, and the list goes on and on.

[0004] Nearly all of these devices are constructed from plastics and metals that are not intended to penetrate the human body, and sometimes not for extended periods of time, and that have surfaces that are generally hydrophilic, slippery and bear little resemblance to the biocompatible surfaces of human organs.

[0005] Equally important for devices that must be inserted and moved through body tissue is their lubricity: many metals and plastics have poor lubricity relative to body tissue, causing mechanical wear and discomfort as the device passes over the tissue.

[0006] The surfaces of devices designed and manufactured from such materials can be made more biocompatible, hydrophilic, and slippery with appropriately designed coatings. Thus, the way is open to constructing medical devices from traditional plastics and metals that have the specific physical properties required and then applying appropriate coatings to impart the desired properties to their surfaces.

[0007] Polymers with low wet friction coefficients have been shown to be water-soluble polymers that are crosslinked or otherwise immobilized and swell but do not dissolve when exposed to water. Polysaccharides have been shown to be useful for creating hydrophilic, lubricious coatings on substrates. Such coatings are described in U.S. Patent Nos. 4,801,000, 4,801,475, 5,023,114, 5,037,677, and 6,673,453, the disclosures of which are incorporated herein by reference. Polysaccharide-based lubricious coatings exhibit excellent biocompatibility and lubricity, but are relatively poorly resistant to ionizing radiation.

[0008] It is desirable for some applications to have a lubricious coating made of synthetic polymers due to the advantages of longer shelf life and stability against radiation sterilization.Hydrophilic synthetic polymers such as poly(acrylic acid) and its copolymers have often been proposed to create lubricious hydrophilic coatings due to their ability to generate a hydration layer on the surface.

[0009] There have been many attempts to immobilize poly(acrylic acid) on surfaces and use it as a coating for medical devices. The methods in U.S. Patents 4,642,267 and 4,990,357 involve the physical mixing of poly(acrylic acid) copolymers with polyurethane dispersions. This method suffers from the drawback that the interpolymer network that physically attaches the hydrophilic polymer to the substrate surface is often disrupted by prolonged turbulent flow or immersion, allowing the hydrophilic species to be washed away, thereby rendering the article insufficiently lubricated.

[0010] Other methods that have been devised for utilizing poly(acrylic acid) as a hydrophilic coating on surfaces include radiation grafting of carboxylic acid monomers and polymers thereof as described in U.S. Pat. Nos. 2,999,056, 5,531,715, 5,789,018, and 6,221,061, and EP 0669837, as well as U.S. Pat. Nos. 5,091,205, 5,509,899, and 5,510,970. and methods of fixing polyacrylic acid using a primer layer containing isocyanate, aziridine, amine and hydroxyl functional groups as described in US Pat. Nos. 5,702,754, 6,048,620, 6,558,798, 6,709,706, 6,087,416, 6,534,559, and EP 0379156, EP 0480809, EP 0728487 and EP 0963761, the disclosures of all of which are incorporated herein by reference.

[0011] The above poly(acrylic acid) coatings exhibit relatively poor lubricity and / or durability due to insufficient coating thickness of the hydrophilic polymer and / or insufficient bonding strength to the surface. It is difficult to achieve high density surface coverage, whether by photoinitiated polymerization grafting or surface chemical attachment of the polymer. Although multiple repeated coating processes can increase the thickness of the photoinitiated polymerization coating, they result in a significant decrease in productivity and an increase in manufacturing costs.

[0012] The use of crosslinking agents can significantly increase the thickness of hydrophilic coatings. Prior art includes methods of crosslinking polyacrylic coatings by photoirradiation and by reaction of multifunctional reactive compounds such as melamine and aziridine, as described in US Pat. Nos. 5,531,715, 6,558,798, and EP 533821. However, crosslinked hydrophilic coatings in the art often face a trade-off between lubricity and abrasion resistance, both of which are essential properties for hydrophilic coatings. Highly crosslinked coatings have poor lubricity due to low hydration capacity and low mobility of polymer segments in aqueous media. Also, coatings with low crosslinking density have high swelling ratios and generally poor abrasion resistance and poor mechanical strength.

[0013] US Patent Application Publication No. 2011 / 0200828 teaches a two-layer coating comprising a base coat that adheres firmly to a substrate and a top coat that is chemically grafted to the base coat. The top coat has a mixture of a water-soluble polymer containing carboxylic acid groups and a water-soluble chromium (III) compound. The coating forms a very durable and lubricious layer when wet. However, the carboxylate anions that make up the coating perform poorly in thrombogenicity tests such as the partial thromboplastin time (PTT) test. The disclosures of the above cited documents are incorporated herein by reference.

[0014] Contact between blood and a foreign body having a plastic or metal surface triggers a complex series of thrombogenic reactions at the blood-surface interface. Thromboembolism is a major complication associated with the clinical use of prosthetic devices, such as catheters, guidewires, mechanical heart valves, ventricular assist devices, implantable artificial hearts, and vascular grafts. In particular, thromboembolism is a significant complication associated with angiographic procedures, especially catheter and guidewire manipulations in close proximity to the brachiocephalic artery.

[0015] Surface modification is commonly performed to make materials more hemocompatible while minimizing the loss of mechanical properties. Two approaches are commonly used for surface modification. Suppression of nonspecific protein adsorption using coatings of polyethylene oxide (PEO) (a neutral, hydrophilic, and highly flexible polymer) and other hydrophilic polymers has been explored for surface passivation. Nonspecific protein adsorption occurs usually within seconds after a foreign body comes into contact with blood and can initiate blood clotting and complement pathways.

[0016] The second approach has been to use coatings that actively support the anticoagulant activity of the surface. Certain plasma proteins (such as antithrombin (AT), which can inhibit thrombin and factor Xa (FXa)) or heparin (a glycosaminoglycan that catalyzes the reaction of plasma AT) have been used for this purpose. Frech et al., in "A Simple Noninvasive Technique to Test Nonthrombogenic Surfaces," The American Journal of Roentgenology, vol. 113 (1971), p. 765-768, disclose coating guidewires with benzalkonium-heparin complexes. Ovitt et al., in "Guidewire Thrombogenicity and Its Reduction," Radiology, vol. 111 (1974), p. 43-46, report Teflon-coated guidewires treated with benzalkonium heparin. US Patent No. 4,349,467 (William) teaches applying heparin to a solid polymer resin substrate by immersing the substrate in a solution of an ammonium salt and contacting the substrate with a heparin salt solution.

[0017] Also, many attempts have been made to invent hydrophilic polymers for the applications of electrophoresis, hair treatment, paper treatment, etc. As revealed by Albarghouthi et al. in "Poly-N-hydroxyethylacrylamide (polyDuramide): A novel, hydrophilic, self-coating polymer matrix for DNA sequencing by capillary electrophoresis", Electrophoresis, vol. 23 (2002), p. 1429-1440, nonionic monomers such as N-hydroxyethylacrylamide have excellent hydrophilicity.

[0018] The following documents, namely WO10041527A, W010041530A, W011125713A, JP2011046619A, JP2011046652A, JP2010126482A, and JP2010090049A teach copolymers composed of 5-30 mol% carboxylic acid monomers and 70-95 mol% alcohol-containing acrylic monomers for use in hair treatment formulations. These patent applications do not disclose the lubricity, utility of the copolymers as biocompatible coatings, and their resistance to ionizing radiation. JP2006176934A teaches copolymers from methacrylamide, hydroxyethylacrylamide, and ionic vinyl monomers for use as additives to increase the strength of paper. The latter reference does not disclose the utility of the copolymers as lubricious biocompatible coatings, nor does it disclose resistance to ionizing radiation.

[0019] There is a need for improved lubricious biocompatible coatings that are resistant to ionizing radiation.

[0020] Typically, in medical devices or implants, a base coat is present between the substrate and the lubricious coating. The base coat can improve the stability of the lubricious coating. There is a need in the art for an improved base coat that bonds more quickly with a lubricious top coat. A base coat that bonds to a hydrophilic top coat via ultraviolet (UV) curing would fill this need. The prior art documents relevant to the invention of this application are as follows (including documents cited during the international phase after the international filing date and documents cited when the application entered the national phase in other countries). (Prior art document) (Patent Documents) (Patent Document 1) U.S. Patent No. 11,441,092 (Patent Document 2) U.S. Patent No. 7,384,984 (Patent Document 3) U.S. Patent No. 11,634,656 (Patent Document 4) U.S. Patent No. 10,525,170 (Patent Document 5) U.S. Patent No. 7,550,444 (Patent Document 6) U.S. Patent Application Publication No. 2008 / 0206096 (Patent Document 7) Chinese Patent Application Publication No. 108603136 (Patent Document 8) China Patent Application Publication No. 1889982 (Patent Document 9) Taiwan Patent No. 1287564 (Patent Document 10) Chinese Patent Application Publication No. 109966560 (Patent Document 11) Chinese Patent Application Publication No. 107206119 (Patent Document 12) China Patent Application Publication No. 1950116 (Patent Document 13) International Publication No. 2000 / 078884 (Patent Document 14) European Patent Application Publication No. 0790839 (Patent Document 15) International Publication No. 9614885 (Patent Document 16) U.S. Patent Application Publication No. 2018 / 0244927 (Patent Document 17) International Publication No. 2018 / 237224 (Patent Document 18) U.S. Patent No. 2,999,056 (Patent Document 19) U.S. Patent No. 4,349,467 (Patent Document 20) U.S. Patent No. 4,642,267 (Patent Document 21) U.S. Patent No. 4,801,475 (Patent Document 22) U.S. Patent No. 4,990,357 (Patent Document 23) U.S. Patent No. 5,023,114 (Patent Document 24) U.S. Patent No. 5,037,677 (Patent Document 25) U.S. Patent No. 5,091,205 (Patent Document 26) U.S. Patent No. 5,509,899 (Patent Document 27) U.S. Patent No. 5,531,715 (Patent Document 28) U.S. Patent No. 5,702,754 (Patent Document 29) U.S. Patent No. 5,789,018 (Patent Document 30) U.S. Patent No. 6,048,620 (Patent Document 31) U.S. Patent No. 6,087,416 (Patent Document 32) U.S. Patent No. 6,221,061 (Patent Document 33) U.S. Patent No. 6,534,559 (Patent Document 34) U.S. Patent No. 6,558,798 (Patent Document 35) U.S. Patent No. 6,673,453 (Patent Document 36) U.S. Patent No. 6,709,706 (Patent Document 37) U.S. Patent No. 5,443,455 (Patent Document 38) U.S. Patent No. 5,002,582 (Patent Document 39) U.S. Patent No. 5,217,492 (Patent Document 40) U.S. Patent No. 5,749,837 (Patent Document 41) U.S. Patent No. 6,278,018 (Patent Document 42) U.S. Patent No. 9,375,517 (Patent Document 43) U.S. Patent No. 9,737,639 (Patent Document 44) U.S. Patent No. 8,541,498 (Patent Document 45) U.S. Patent No. 8,318,263 (Patent Document 46) U.S. Patent No. 8,163,327 (Patent Document 47) U.S. Patent Application Publication No. 2011 / 0200828 (Patent Document 48) U.S. Patent Application Publication No. 2013 / 0323291 (Patent Document 49) U.S. Patent Application Publication No. 2007 / 0032882 (Patent Document 50) U.S. Patent Application Publication No. 2011 / 0134387 (Patent Document 51) U.S. Patent Application Publication No. 2007 / 0286959 (Patent Document 52) ​​U.S. Patent Application Publication No. 2007 / 0141365 (Patent Document 53) U.S. Patent Application Publication No. 2017 / 0281831 (Patent Document 54) U.S. Patent Application Publication No. 2012 / 0178872 (Patent Document 55) U.S. Patent Application Publication No. 2011 / 0063567 (Patent Document 56) U.S. Patent Application Publication No. 2002 / 0037984 (Patent Document 57) U.S. Patent Application Publication No. 2014 / 0193474 (Patent Document 58) U.S. Patent Application Publication No. 2008 / 0213334 (Patent Document 59) U.S. Patent Application Publication No. 2010 / 0247599 (Patent Document 60) U.S. Patent Application Publication No. 2014 / 0004170 (Patent Document 61) European Patent Application Publication No. 0220919 (Patent Document 62) European Patent Application Publication No. 0379156 (Patent Document 63) European Patent Application Publication No. 0480809 (Patent Document 64) European Patent Application Publication No. 0669837 (Patent Document 65) European Patent Application Publication No. 0728487 (Patent Document 66) European Patent Application Publication No. 0963761 (Patent Document 67) Japanese Patent Publication No. 2006-176934 (Patent Document 68) Japanese Patent Publication No. 2010-090049 (Patent Document 69) Japanese Patent Publication No. 2010-126482 (Patent Document 70) Japanese Patent Publication No. 2011-046619 (Patent Document 71) Japanese Patent Publication No. 2011-046652 (Patent Document 72) International Publication No. 2010 / 041527 (Patent Document 73) International Publication No. 2010 / 041530 (Patent Document 74) International Publication No. 2011 / 125713 (Patent Document 75) U.S. Patent Application Publication No. 2002 / 0041899 (Patent Document 76) Japanese Patent Publication No. 2004-520088 (Patent Document 77) International Publication No. 2014 / 036498 (Patent Document 78) U.S. Patent Application Publication No. 2012 / 0059111 (Patent Document 79) U.S. Patent Application Publication No. 2013 / 0197433 (Non-licensed document) (Unauthorized Document 1) Frech et al., "A Simple Noninvasive Technique to Test Nonthrombogenic Surfaces," The American Journal of Roentgenology, vol. 113 (1971), p. 765-768 (Non-patent document 2) Ovitt et al., "Guidewire Thrombogenicity and Its Reduction", Radiology, vol. 111 (1974), p. 43-46 (Unauthorized Document 3) Albarghouthi et al., "Poly-N-hydroxyethylacrylamide (polyDuramide ): A novel, hydrophilic, self-coating polymer matrix for DNA sequencing by capillary electrophoresis", Electrophoresis, vol. 23 (2002), p. 1429-1440 Summary of the Invention

[0021] The present invention relates to coating compositions for medical devices or implants. These novel compositions include a hydrophobic basecoat polymer and a hydrophilic topcoat polymer.

[0022] In some embodiments, the present invention provides (a) 1 to 12 mol % of at least one photoactive monomer that is a hydrogen atom abstracting agent; (b) 99 to 88 mol % of one or more of acrylamide, methacrylamide, acrylate, methacrylate, and N-vinylpyrrolidone; The present invention relates to a coating composition having a hydrophobic polymer for use as a photoreactive basecoat for a medical device or implant, the coating composition having a polymer made from a monomer having the formula:

[0023] In certain embodiments, the base coat further comprises a polyfunctional aziridine: (a) 95 to 99.8 wt % of a hydrophobic polymer described herein; and (b) 0.2 to 5 wt % of a polyfunctional aziridine, based on the total weight of the base coat.

[0024] The present invention also relates to a medical device or implant having a photoreactive base coat with the coating composition described herein. In a preferred composition, the base coat is hydrophobic. In some embodiments, the device or implant includes a hydrophilic top coat, where the base coat is present on a substrate and the top coat is present on the base coat. The hydrophilic top coat composition may or may not include a photoreactive group.

[0025] In another embodiment, the present invention is directed to a coating solution having the hydrophobic basecoat coating composition described herein and a solvent.

[0026] In another embodiment, the coating solution has a polymer soluble in water or a water-alcohol solution, the polymer being made from monomers having (a) at least one monomer that is a photoradical generator, and (b) at least one monomer having one or both of (i) an ethylenic monomer having at least one acidic group, and (ii) one or more of an acrylate or an acrylamide; wherein the molar ratio of the (i) ethylenic monomer having at least one acidic group and (ii) one or more of an acrylate or an acrylamide to the photoradical generator is from 20:1 to 500:1.

[0027] The present invention also relates to a coated substrate having a substrate and a lubricious coating made with the coating composition described herein.

[0028] Additional embodiments relate to coating the compositions described herein in an aqueous solution.

[0029] In yet another embodiment, the present invention relates to a method of coating a substrate, in some embodiments, both a base coat and a top coat are applied to the substrate, where both the base coat and the top coat are cured with UV light, either (a) the base coat is applied and cured before the top coat is applied, or (b) the base coat is applied and dried, the top coat is applied, and then both the base coat and the top coat are cured with UV light.

[0030] Yet other embodiments include medical devices or implants in which the lubricious coating includes a pharmaceutical or antimicrobial agent incorporated into the coating composition. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0031] The requirements for coatings intended for use on medical devices are first defined and described, and then the specification describes how the present invention meets those requirements.

[0032] The coating of the present invention is suitable for use on medical devices. The coating of the present invention has the following properties: (1) The coating must be capable of forming a good, continuous, adherent film on the surface of the material being coated upon drying. This means that the minimum film-forming temperature of the coating solution must be lower than the drying temperature expected during device manufacture. (2) The formed polymeric film must have sufficient flexibility and adhesion to accommodate the bending and twisting of the coated device without fracture under expected conditions of use. (3) The film must not weaken or lose integrity when the coated device is immersed in an aqueous medium, such as human blood, for extended periods of time. (4) The coating must present a surface that is non-cytotoxic and hemocompatible: when in contact with human blood, the coating must not initiate blood coagulation or complement pathways. (5) The coating must be tightly and securely bonded to the substrate so that particles, fragments, or leachable components do not contaminate aqueous media such as human blood. (6) The coating must withstand acceptable forms of sterilization without loss of integrity, durability, or biocompatibility.

[0033] A coating meeting the above requirements is produced as follows.

[0034] The present disclosure may be more readily understood by reference to the following description taken in conjunction with the accompanying figures and examples, all of which constitute a part of this disclosure. It will be understood that the present disclosure is not limited to the specific products, methods, conditions or parameters described and / or shown herein, and that the terms used herein are for illustrative purposes of describing certain embodiments and are not intended to limit the disclosure of any claims. Similarly, unless otherwise specified, any description of a possible mechanism or mechanism of action or reason for improvement is intended to be illustrative only, and the invention herein should not be constrained by the correctness or incorrectness of the mechanism or mechanism of action or reason for improvement so suggested. It is recognized that throughout this specification, the description refers to both the method of operating the apparatus and system, and the apparatus and system that provides said method. That is, when the present disclosure describes and / or claims a coating composition, a medical device, a coating solution or a method, it is understood that these descriptions and / or claims also describe and / or claim an apparatus, device, or system for achieving these methods.

[0035] In some embodiments, the present invention provides (a) 1 to 12 mol % of at least one photoactive monomer that is a hydrogen atom abstracting agent; (b) 99 to 88 mol % of one or more of acrylamide, methacrylamide, acrylate, methacrylate, and N-vinylpyrrolidone; The present invention relates to a coating composition having a hydrophobic polymer for use as a photoreactive base coat for a medical device or implant, the coating composition having a polymer made from a monomer having the formula:

[0036] Preferred hydrophobic polymers have a glass transition temperature of less than 40°C, 20°C, 15°C or 10°C.

[0037] In a preferred embodiment of the hydrophobic polymer, the photoactive monomer that is a hydrogen atom abstracting agent is a benzophenone compound. In a particular embodiment, the photoactive monomer that is a hydrogen atom abstracting agent comprises one or more of 4-methacryloxy 2-hydroxybenzophenone, 4-acryloxybenzophenone, 4-methacryloxybenzophenone, acrylamidobenzophenone, methacrylamidebenzophenone, 2-hydroxy-4-acryloxyethoxybenzophenone, and 2-hydroxy-4-methacryloxyethoxybenzophenone.

[0038] 4-Methacryloxy-2-hydroxybenzophenone (MHB) can be copolymerized with (meth)acrylate monomers to produce a hydrophobic photoactive polymer. This polymer acts as a tie layer to bond the substrate and hydrophilic topcoat layer upon UV curing. Topcoats cured in the presence of this photoactive basecoat bond well even when the topcoat does not contain a photoactive component. [ka]

[0039] The monomer that copolymerizes with the photoactive monomer may be one or more of an acrylate, methacrylate, or other monomer known to copolymerize well therewith. In certain embodiments, the polymer has a methacrylate of the following structure: [ka] R is an optionally substituted C1-C 20 R is an alkyl. In some embodiments, R may be methyl, ethyl, or butyl. Preferably, the copolymer will include ethylhexyl, isodecyl, dodecyl, or other monomers that contribute to a low glass temperature copolymer. The copolymer will also include a monomer that has some hydrophilic properties to provide good interaction between the topcoat solution and the polymer. For example, hydroxyethyl methacrylate and N-vinylpyrrolidone monomers.

[0040] In certain embodiments, the monomers that contribute a low glass temperature to the hydrophobic polymer are C4-C 20 Acrylates having an alkyl group, for example, butyl acrylate.

[0041] In yet another aspect, the invention relates to a coating solution having 2-15 wt% of a hydrophobic polymer coating composition described herein. In other embodiments, the solution has 3-13 wt% or 4-12 wt% or 5-10 wt% of a coating composition described herein. In a preferred embodiment, the solution has an organic solvent. Preferred solvents include one or more of toluene, ethanol, acetone, isopropanol, ethyl acetate, dimethylformamide, tetrahydrofuran, butanol, N-methyl-2-pyrrolidone, n-butyl acetate, 1,2-propanediol monomethyl ether acetate, isobutyl acetate, isopropyl acetate, methyl acetate, 3-methyl-1-butanol, methyl ethyl ketone, 2-methyl-1-propanol, 1-pentanol, 2-propanol, propyl acetate, dichloromethane, dimethyl sulfoxide, methyl butyl ketone, and xylene.

[0042] In certain embodiments, the base coat further comprises a polyfunctional aziridine. In some embodiments, the coating composition comprises (a) 95-99.8 wt. % of a hydrophobic polymer; and (b) 0.2-5 wt. % of a polyfunctional aziridine. In other embodiments, the coating composition comprises (a) 98-99.5 wt. % of a hydrophobic polymer; and (b) 0.5-2 wt. % of a polyfunctional aziridine.

[0043] In some embodiments, the present invention relates to a hydrophilic polymeric coating composition for a medical device or medical implant having a polymer that is soluble in water or a water-alcohol solution, said polymer comprising: (a) at least one monomer that is a photoradical generator, and (b) (i) an ethylenic monomer having at least one acid group, and (ii) at least one monomer having one or both of an acrylate or an acrylamide; wherein the molar ratio of one or both of (i) an ethylenic monomer having at least one acidic group and (ii) one or more of an acrylate or an acrylamide to the photoradical generating group is from 20:1 to 500:1.

[0044] The polymer may be packaged in water or a water-alcohol mixture. The alcohol is typically a C1-C6 alcohol. Preferred alcohols include methanol, ethanol and isopropanol. The ratio of water to alcohol can be from 100:0 to 50:50.

[0045] Some preferred photoradical generators for hydrophobic polymers are benzophenone compounds.In some embodiments, the photoradical generator comprises one or more of 4-methacryloxy 2-hydroxybenzophenone, 4-acryloxy benzophenone, 4-methacryloxy benzophenone, acrylamide benzophenone, methacrylamide benzophenone, 2-hydroxy-4-acryloxyethoxybenzophenone, 2,4-dihydroxy-4'-vinyl benzophenone, and 2-hydroxy-4-methacryloxyethoxybenzophenone.One of the preferred photoradical generators comprises 4-methacryloxy 2-hydroxybenzophenone.

[0046] 4-Methacryloxy 2-hydroxybenzophenone (MHB) can be copolymerized with acrylic acid and polar acrylates such as N-(2-hydroxyethyl)acrylamide to produce hydrophilic, photoactive polymers. Upon UV curing, this polymer acts as a lubricious topcoat. It can also be used in addition to other hydrophilic (non-photoactive) polymers to form lubricious coatings after UV curing. [ka]

[0047] A variety of ethylenic monomers can be used to form hydrophilic polymers. In some embodiments, the monomers have at least one acidic group, including acrylic acid, methacrylic acid, 2-ethylacrylic acid, 2-propylacrylic acid, acryloxypropionic acid, isocrotonic acid, maleic anhydride, maleic acid and half esters, half amides and half thioesters of maleic acid, fumaric acid, and itaconic acid, and mixtures thereof. In some embodiments, the ethylenic monomers have N-(2-hydroxyethyl)acrylamide and acrylic acid. In certain embodiments, the molar ratio of N-(2-hydroxyethyl)acrylamide to acrylic acid is 2:1 to 5:1.

[0048] Preferred acrylates and acrylamides include acrylamide, N-(2-hydroxyethyl)acrylamide, 2-hydroxyethyl methacrylate, 2-hydroxypropyl acrylate, 2-hydroxypropyl methacrylate, and N-(2-hydroxyethyl)methacrylamide, N-acryloylamido-ethoxyethanol, N-(hydroxymethyl)acrylamide, N-[tris(hydroxymethyl)methyl]acrylamide, 4-hydroxybutyl acrylate, hydroxypropyl acrylate, methyl 3-hydroxy-2-methylenebutyrate, hydroxypropyl methacrylate, 2-allyloxyethanol, 3-allyloxy-1,2-propanediol, 1,4-butanediol vinyl ether, di(ethylene glycol) vinyl ether, ethylene glycol vinyl ether, N,N-1,2-dihydroxyethylene-bis-acrylamide, N,N-1,2-dihydroxyethylene-bis-methylacrylamide, N-hydroxymethyl methacrylamide, N-tri(hydroxymethyl)-methyl-methacrylamide, or any mixture thereof.

[0049] In some embodiments, the molar ratio of (i) the ethylenic monomer having at least one acidic group and (ii) one or more of the acrylates or acrylamides to the photoradical generator having at least one photopolymerizable group is from 40:1 to 200:1.

[0050] In certain embodiments, the hydrophilic polymer has a weight average molecular weight (Mw) of 20,000 to 800,000 or 20,000 to 400,000 or 50,000, and 400,000.

[0051] Some hydrophilic polymer coating compositions further comprise a second polymer that is soluble in water or a water-alcohol solution. In some embodiments, the second polymer comprises (i) an ethylenic monomer having at least one acidic group, and (ii) one or more of an acrylate or an acrylamide. In the second polymer, the ethylenic monomer of the second polymer comprises at least one acidic group and comprises at least one of acrylic acid, methacrylic acid, 2-ethylacrylic acid, 2-propylacrylic acid, acryloxypropionic acid, isocrotonic acid, maleic anhydride, maleic acid and half ester, half amide, half thioester of maleic acid, fumaric acid, itaconic acid, and any combination thereof. Further, in the second polymer, the acrylate or acrylamide may be selected from acrylamide, N-(2-hydroxyethyl)acrylamide, 2-hydroxyethyl methacrylate, 2-hydroxypropyl acrylate, 2-hydroxypropyl methacrylate, and N-(2-hydroxyethyl)methacrylamide, N-acryloylamide-ethoxyethanol, N-(hydroxymethyl)acrylamide, N-[tris(hydroxymethyl)methyl]acrylamide, 4-hydroxybutyl acrylate, hydroxypropyl acrylate, methyl 3- Hydroxy-2-methylene butyrate, hydroxypropyl methacrylate, 2-allyloxyethanol, 3-allyloxy-1,2-propanediol, 1,4-butanediol vinyl ether, di(ethylene glycol) vinyl ether, ethylene glycol vinyl ether, N,N-1,2-dihydroxyethylene-bis-acrylamide, N,N-1,2-dihydroxyethylene-bis-methylacrylamide, N-hydroxymethyl methacrylamide, N-tri(hydroxymethyl)-methyl-methacrylamide and any mixtures thereof.

[0052] In some embodiments, the second polymer has a weight average molecular weight (Mw) of 50,000 to 800,000.

[0053] The present invention also relates to a coated substrate having a substrate and a lubricious coating made with the coating composition described herein. A preferred embodiment further has a basecoat in contact with both the substrate and the lubricious coating composition. A preferred basecoat is hydrophobic.

[0054] The present invention also relates to a medical device or implant having a photoreactive base coat comprising the coating composition described herein. In some embodiments, the base coat is between the substrate and the hydrophilic top coat. Some preferred top coats comprise one or more of polyacrylate, polyvinylpyrrolidone, hyaluronic acid, and polyacrylamide. In other embodiments, the top coat comprises an N-(2-hydroxyethyl)acrylamide and acrylic acid copolymer. Some embodiments have multiple covalent crosslinks between the base coat and the hydrophilic top coat.

[0055] The coatings can be used on any medical device or implant suitable for the application of the coating, hi some embodiments, the substrate is plastic or metal.

[0056] Preferred coated substrates have a lubricity of less than 25 gf of friction and a durability of less than 50 gf of friction as measured by a pinch test.

[0057] The present invention also relates to medical devices and medical implants having the coated substrates described herein. In some embodiments, the medical device or medical implant is sterilized by at least one of gamma radiation, E-beam, and ethylene oxide.

[0058] In additional embodiments, the coatings described herein include a pharmaceutical or antimicrobial agent formulated in the coating composition.

[0059] Preferred medical devices include catheters and guidewires.

[0060] In some aspects, the present invention relates to a method for coating an article. Some methods include coating a substrate with a base coat having a coating composition as described herein. The base coat may be cured by exposing the base coat to UV light. In some embodiments, the base coat may be coated with a hydrophilic top coat.

[0061] In yet another embodiment, a coating method includes coating a substrate with a basecoat having a coating composition described herein, coating the basecoat with a hydrophilic topcoat, and UV curing the basecoat and topcoat. The hydrophilic topcoat may be photoactive (i.e., contains groups that absorb UV radiation and react when exposed to UV radiation), but photoactive groups need not be present in the topcoat.

[0062] The present invention relates to at least the following aspects.

[0063] Embodiment 1A. A coating composition having a hydrophobic polymer for use as a photoreactive basecoat for a medical device or implant, the coating composition having a polymer made from monomers having: (a) 1-12 mol % of at least one photoactive monomer that is a hydrogen atom abstracting agent; and (b) 99-88 mol % of one or more of acrylamide, methacrylamide, acrylate, methacrylate, and N-vinylpyrrolidone, the polymer having a glass transition temperature (Tg) of less than 40° C.

[0064] Embodiment 1B. A coating composition having a hydrophobic polymer for use as a photoreactive basecoat for a medical device or implant, the coating composition having a polymer made from monomers having: (a) 1-5 mol % of at least one photoactive monomer that is a hydrogen atom abstracting agent; and (b) 99-95 mol % of one or more of acrylamide, methacrylamide, acrylate, methacrylate, and N-vinylpyrrolidone, the polymer having a glass transition temperature (Tg) of less than 40° C.

[0065] Embodiment 2. The coating composition of Embodiments 1A-1B, further comprising a polyfunctional aziridine.

[0066] Aspect 3. The coating composition of aspect 2, comprising: (a) 95-99.8 wt. % of said hydrophobic polymer; and (b) 0.2-5 wt. % of a polyfunctional aziridine.

[0067] Aspect 4. The coating composition of any one of Aspects 1A-3, comprising the following structure: [ka] (R is an optionally substituted C1-C 20 (It is alkyl) The coating composition according to claim 1,

[0068] Embodiment 5. The coating composition of embodiment 4, wherein R is one or more of methyl, ethylhexyl, isodecyl, and dodecyl.

[0069] Embodiment 6. The coating composition of embodiment 4, wherein the hydrophobic polymer comprises hydroxyethyl methacrylate and N-vinylpyrrolidone.

[0070] Embodiment 7. The coating composition of any one of embodiments 1A-6, wherein the hydrophobic polymer is a C4-C 20A coating composition having an acrylate having an alkyl group.

[0071] Aspect 8. The coating composition of any one of Aspects 1A-7, wherein the hydrogen atom abstracting agent photoactive monomer has a benzophenone moiety.

[0072] Embodiment 9. The coating composition of embodiment 8, wherein the hydrogen atom abstracting photoactive monomer comprises one or more of 4-methacryloxy-2-hydroxybenzophenone, 4-acryloxybenzophenone, 4-methacryloxybenzophenone, acrylamidobenzophenone, methacrylamidebenzophenone, 2-hydroxy-4-acryloxyethoxybenzophenone, and 2-hydroxy-4-methacryloxyethoxybenzophenone.

[0073] Embodiment 10. The coating composition of any one of Embodiments 1A-9, wherein the coating composition has a Tg of less than 20° C.

[0074] Embodiment 11. A medical device or implant having a photoreactive basecoat having the coating composition of any one of Embodiments 1A-10.

[0075] Aspect 12. The medical device of aspect 11, wherein the base coat is between the substrate and the hydrophilic top coat.

[0076] Example 13. The medical device of Example 12, wherein the topcoat comprises one or more of polyacrylate, polyvinylpyrrolidone, hyaluronic acid, and polyacrylamide.

[0077] Aspect 14. The medical device of Aspect 12, wherein the topcoat comprises an N-(2-hydroxyethyl)acrylamide and acrylic acid copolymer.

[0078] Aspect 15. The medical device of aspect 11, wherein the medical device is a catheter or a guidewire.

[0079] Example 16. The medical device of Example 12, comprising a plurality of covalent crosslinks between the base coat and the hydrophilic top coat.

[0080] Embodiment 17. A coating solution having 2-15 wt % of the coating composition of any one of Embodiments 1-10 in a solvent.

[0081] Example 18. The coating solution of Example 17, wherein the solvent is an organic solvent.

[0082] Aspect 19. The coating solution of aspect 18, wherein the solvent comprises one or more of toluene, ethanol, acetone, isopropanol, ethyl acetate, dimethylformamide, tetrahydrofuran, butanol, N-methyl-2-pyrrolidone, n-butyl acetate, 1,2-propanediol monomethyl ether acetate, isobutyl acetate, isopropyl acetate, methyl acetate, 3-methyl-1-butanol, methyl ethyl ketone, 2-methyl-1-propanol, 1-pentanol, 2-propanol, propyl acetate, dichloromethane, dimethyl sulfoxide, methyl butyl ketone, and xylene.

[0083] Embodiment 20. A method of forming a coated article comprising coating a substrate with a basecoat having the coating composition of any one of Embodiments 1A-10.

[0084] Example 21. The method of Example 20, further comprising curing the base coat by exposing the base coat to UV light.

[0085] Example 22. The method of Example 21, further comprising the step of coating the base coat with a hydrophilic top coat.

[0086] Example 23. The method of example 20, further comprising the steps of (a) coating the base coat with a hydrophilic top coat, and (b) curing the base coat and top coat with UV light.

[0087] Aspect 24. A coating composition for a medical device or medical implant having a polymer soluble in water or a water-alcohol solution, the polymer being made from (a) at least one monomer that is a photoradical generator having one or more of 4-methacryloxy2-hydroxybenzophenone, 4-acryloxybenzophenone, 4-methacryloxybenzophenone, acrylamidobenzophenone, methacrylamidebenzophenone, 2-hydroxy-4-acryloxyethoxybenzophenone, 2,4-dihydroxy-4'-vinylbenzophenone, and 2-hydroxy-4-methacryloxyethoxybenzophenone, and (b) a monomer having (i) an ethylenic monomer having at least one acidic group and (ii) at least one monomer having one or both of an acrylate or an acrylamide, the ethylenic monomer having at least one acidic group being selected from the group consisting of acrylic acid, methacrylic acid, 2-ethylacrylic acid, 2-propylacrylic acid, acryloxypropionic acid, isocrotonic acid, maleic anhydride, maleic acid, methacrylic ... and mixtures thereof, wherein the acrylate or acrylamide is selected from the group consisting of acrylamide, N-(2-hydroxyethyl)acrylamide, 2-hydroxyethyl methacrylate, 2-hydroxypropyl acrylate, 2-hydroxypropyl methacrylate, and N-(2-hydroxyethyl)methacrylamide, N-acryloylamido-ethoxyethanol, N-(hydroxymethyl)acrylamide, N-[tris(hydroxymethyl)methyl]acrylamide, 4-hydroxybutyl acrylate, hydroxypropyl acrylate, methyl 3-hydroxy-2-methylenebutyrate, hydroxypropyl methacrylate, 2-allyloxyethanol, 3-allyloxy-1,2-propanediol, 1,4-butanediol vinyl ether, di(ethylene glycol) vinyl ether, ethylene glycol vinyl ether, N,N-1,2-dihydroxyethylene-bis-acrylamide ...A coating composition having 2-dihydroxyethylene-bis-methylacrylamide, N-hydroxymethylmethacrylamide, N-tri(hydroxymethyl)-methyl-methacrylamide or any mixture thereof, wherein the molar ratio of one or both of (i) an ethylenic monomer having at least one acidic group, and (ii) one or more of an acrylate or an acrylamide to a photoradical generating group is 20:1 to 500:1.

[0088] Aspect 25. The coating composition of aspect 24, wherein the photoradical generating group comprises 4-methacryloxy-2-hydroxybenzophenone.

[0089] Example 26. The coating composition of Example 24, wherein the ethylenic monomers comprise N-(2-hydroxyethyl)acrylamide and acrylic acid.

[0090] Aspect 27. The coating composition of aspect 26, wherein the molar ratio of the N-(2-hydroxyethyl)acrylamide and the acrylic acid is from 2:1 to 5:1.

[0091] Embodiment 28. The coating composition of embodiment 24, wherein the molar ratio of one or both of (i) the ethylenic monomer having at least one acidic group and (ii) the one or more of acrylates or acrylamides to the photoradical generator having at least one photopolymerizable group is 40:1 to 200:1.

[0092] Embodiment 29. The coating composition of embodiment 24, wherein the polymer has a weight average molecular weight (Mw) of 20,000 to 800,000.

[0093] Embodiment 30. The coating composition of embodiment 24, further comprising a second polymer that is soluble in water or a water-alcohol solution.

[0094] Example 31. The coating composition of example 30, comprising one or both of: (i) an ethylenic monomer having at least one acidic group; and (ii) one or more of an acrylate or an acrylamide.

[0095] Example 32. The coating composition of example 31, wherein the ethylenic monomer of the second polymer has at least one acidic group, and the ethylenic monomer of the second polymer having at least one acidic group is one or more of acrylic acid, methacrylic acid, 2-ethylacrylic acid, 2-propylacrylic acid, acryloxypropionic acid, isocrotonic acid, maleic anhydride, maleic acid and half esters, half amides and half thioesters of maleic acid, fumaric acid, itaconic acid, and any combination thereof.

[0096] Embodiment 33. The coating composition of embodiment 31, wherein the acrylate or acrylamide of the second polymer is selected from the group consisting of acrylamide, N-(2-hydroxyethyl)acrylamide, 2-hydroxyethyl methacrylate, 2-hydroxypropyl acrylate, 2-hydroxypropyl methacrylate, and N-(2-hydroxyethyl)methacrylamide, N-acryloylamido-ethoxyethanol, N-(hydroxymethyl)acrylamide, N-[tris(hydroxymethyl)methyl]acrylamide, 4-hydroxybutyl acrylate, hydroxypropyl acrylate, methyl 1. A coating composition having 3-hydroxy-2-methylenebutyrate, hydroxypropyl methacrylate, 2-allyloxyethanol, 3-allyloxy-1,2-propanediol, 1,4-butanediol vinyl ether, di(ethylene glycol) vinyl ether, ethylene glycol vinyl ether, N,N-1,2-dihydroxyethylene-bis-acrylamide, N,N-1,2-dihydroxyethylene-bis-methylacrylamide, N-hydroxymethyl methacrylamide, N-tri(hydroxymethyl)-methyl-methacrylamide and any mixture thereof.

[0097] Embodiment 34. The coating composition of embodiment 31, wherein the second polymer has a weight average molecular weight (Mw) of 50,000 to 800,000.

[0098] Embodiment 35 The coating composition of embodiment 24, further comprising water or a water / alcohol mixture.

[0099] Embodiment 36. A coated substrate having a substrate and a lubricious coating made with the coating composition of any one of embodiments 24-35.

[0100] Embodiment 37. The coated substrate of embodiment 36, further comprising a basecoat in contact with both the substrate and the lubricious coating composition.

[0101] Example 38. The coated substrate of Example 37, wherein the base coat is hydrophobic.

[0102] Embodiment 39. The coated substrate of embodiment 36, wherein the substrate is plastic.

[0103] Embodiment 40. The coated substrate of embodiment 36, wherein the substrate is a metal.

[0104] Embodiment 41. The coated substrate of any one of embodiments 36 to 40, wherein the coated substrate has a lubricity of friction less than 25 gf and a durability of friction less than 50 gf as measured by a pinch test.

[0105] Embodiment 42. A medical device or medical implant having the coated substrate of any one of embodiments 36-41.

[0106] Embodiment 43. The medical device or medical implant of embodiment 42, wherein said medical device or medical implant is sterilized by at least one of gamma radiation, E-beam, and ethylene oxide.

[0107] Embodiment 44 The medical device or medical implant of embodiment 42 or 43, wherein the lubricious coating comprises a pharmaceutical or antimicrobial agent incorporated into the coating composition.

[0108] Working Example The invention is illustrated by the following non-limiting examples.

[0109] The following abbreviations are used in this document: MHB-4-methacryloxy-2-hydroxybenzophenone was the monomer that imparted photoactivity to the copolymer. It was purchased from Polysciences and Bimax. Purity was confirmed by nuclear magnetic resonance NMR performed on a Bruker 400 MHz NMR from USscience. BA-Butyl Acrylate MMA - Methyl Methacrylate HEMA-Hydroxyethyl Methacrylate NVP-N-vinylpyrrolidone EHMA-Ethylhexyl Methacrylate iDMA-Isodecyl Methacrylate DDMA - Dodecyl Methacrylate AA-acrylic acid HEAA-N-(2-hydroxyethyl)acrylamide PVP-Polyvinylpyrrolidone HAP - Hydrophilic Acrylic Copolymer, a copolymer of AA and HEAA

[0110] The coatings were applied to the various substrates in the form of rods and tubes. The rods were stainless steel or PMMA and had a diameter of 0.125 inches. The Pebax™ 35D and 55D plastic tubes had an outer diameter of 0.079 inches and a wall thickness of 0.005 inches. The tubes were placed over the stainless steel rods to ensure stability prior to coating. The coating process consisted of wiping the rods with isopropyl alcohol, dip coating in the basecoat solution at 0.2 in / sec, drying at 60°C for 10 minutes, dip coating in the topcoat solution at 0.2 in / sec, and drying at 60°C for 10 minutes. After all coatings were completed, the rods were exposed to UV radiation.

[0111] UV curing was performed with a Uvitron IntelliRay model UV0832 UV Cure unit equipped with a UVA 600 watt metal halide lamp. Irradiance was measured using an EIT Uvicure Plus II radiometer purchased from INPRO Technologies. This single channel UVA radiometer measures radiation from 320 to 390 nanometers (nm).

[0112] To achieve uniform radiation around the circumference of the rod, two different methods were used. In the first method, a hexagonal coupler was attached to the rod, providing a fixed geometry for rotating the coated rod while curing. The sample was then rotated six times, allowing all faces to be exposed. The rotation pattern was 0°, 120°, 240°, 60°, 180°, and 300°. In the second method, the rod was rotated continuously by a motor at 20 rpm while UV curing.

[0113] Typical irradiation times in the examples are 2-30 minutes, and typical doses are 100-200 mW / cm2 (for 320-390 nm from a UVA metal halide lamp). Note that not all 320-390 nm irradiation is useful for photocrosslinking, only wavelengths that are actually absorbed by the photoactive groups can lead to reaction. It is also understood that lower irradiances than those used in these examples can be accommodated by increasing the irradiation time.

[0114] The friction of the coatings was tested with a Chatillon CS225 Force Measurement Machine. It was equipped with a heated water bath and pinch pads that pressed together with a constant force. The water bath was filled with PBS solution and heated to 37°C. The pinch pads were submerged in the water and pressed together with a force of 470 grams (g). Friction is measured as grams of force required to push or pull the sample through the pads. Lubricity and durability are determined by averaging the grams of force as the sample is pulled through the pads. Lubricity is the average of 1-3 cycles and durability is the force over 30 cycles.

[0115] Photoactive basecoats were prepared by copolymerizing 4-methacryloxy 2-hydroxybenzophenone with low glass temperature (meth)acrylate monomers. The photoactive basecoat polymers synthesized are summarized in Table 1. [Table 1]

[0116] Poly(methyl methacrylate) (PMMA) rods were coated with a basecoat polymer BP-5 and a polyvinylpyrrolidone (PVP) topcoat (Aldrich 1,300,000 molecular weight by light scattering). The coated rods had a power output of 186 milliwatts per square centimeter (mW / cm). 2) for each of six rotations. After the pinch test, the rods were rinsed with cold tap water for 10 seconds, immersed in a 0.5% aqueous Congo red solution, and rinsed again for 10 seconds. The presence of bound PVP, shown as a deep red color, indicates that grafting has occurred between the photoactive basecoat and the PVP topcoat.

[0117] PVP topcoats with four different UV cured basecoat polymers were tested on PMMA substrate rods. The UV cure was at 166 mW / cm 2 The exposure was performed for 20 minutes for each of 6 rotations with a dose of 100 μg / s. The samples showed significant lubricity, but only lasted for 10–20 cycles. The results are summarized in Table 2. [Table 2] A hydrophilic acrylic polymer and a blend of this hydrophilic acrylic polymer and PVP were evaluated as topcoats (with added surfactant). The hydrophilic acrylic polymer (HAP) is a copolymer of acrylic acid and 2-hydroxyethylacrylamide. UV curing was performed at a dose of 180 mW / cm. 2 The results are shown in Table 3. All three rods of each sample showed good lubricity and durability over the 30 cycles. [Table 3]

[0118] The results summarized in the above examples show that good lubricity and durability can be achieved with a photoactivated basecoat, even without photoactivity in the topcoat. A drawback of the UV curing process used in these examples is that the UV cure must be stopped mid-cure and the sample rotated manually 5 times. To solve this, a motor was installed to continuously rotate the sample at 20 rpm during cure. This is expected to result in a more uniform UV cure around the circumference of the rod or tube. Not only was this method more convenient, but it also provided better lubricity and durability with a shorter cure time, as shown below.

[0119] Table 4 shows a comparison of several compositions using different monomer compositions and different amounts of photoactive monomer. The results show that a variety of low glass temperature monomers can be used to provide lubricious, durable coatings. In these examples, the topcoat does not contain a photoactive component. [Table 4] Footnotes to Table 4: The base coat is applied over a tube of Pebax™ 55D. After the basecoat dried, a surfactant-containing poly(HEAA-co-AA) topcoat was added and allowed to dry before UV curing.

[0120] Inclusion of a trifunctional aziridine such as trimethylolpropane tris(2-methyl-1-aziridinepropionate) (crosslinker CX-100) in the basecoat can result in coated rods with better durability. Multifunctional aziridines are known crosslinkers in the thermal cure process. The results in Table 5 show the improved durability. [Table 5] Footnotes to Table 5: The base coat is coated onto a Pebax™ 55D tube. After the basecoat was dried, the poly(HEAA-co-AA) topcoat was added and allowed to dry. 6 (+heat) indicates that the sample was UV cured and then heated at 60° C. for 30 minutes. 6 * indicates that the sample was immersed in a PBS aqueous solution at 50°C for 18 hours before the pinch test.

[0121] The previous examples demonstrate that the combination of the photoactive basecoat of the present invention with a hydrophilic topcoat without photoactivity provides good lubricity and durability. The following examples show that even better performance is obtained when photoactivity is incorporated into the topcoat.

[0122] Poly(HEAA-co-AA) in Table 6. The polymer was made by reacting 29.79 g of N-(2-hydroxyethyl)acrylamide (HEAA) and 6.21 g of acrylic acid (AA) in 263 mL of water. The polymerization initiators were ammonium persulfate and sodium hydroxymethanesulfinate hydrate. 0.015 mL of 1% FeSO4 solution was added to catalyze the reaction. The polymerization was carried out at 40° C. under N2. The polymer was purified by dialysis or precipitation with acetone (similar to Example 1 of US2013 / 0323291 A1).

[0123] Poly(HEAA-co-AA-co-MHB) 1-4 in Table 6. Photoactive polymers were made by reacting 15.29 g of HEAA, 3.19 g of AA, 1.00 g, 0.50 g, or 0.25 g of MHB in 40 mL of IPA and 30 mL of water. 0.59 mL of a 50 mg / mL solution of azobisisobutyronitrile (AiBN) in THF was added to the monomer solution. The solution was sparged for 30 min to remove oxygen and then heated to 60 °C for 24 h. After the reaction was complete, the polymer was precipitated with 150 mL of ethyl acetate. The solvent was decanted off and the polymer was dried in an oven at 60 °C, and the remaining solvent was removed under vacuum. The polymer was dissolved in a 50:50 mixture of IPA and water.

[0124] Poly(HEAA-co-AA-co-MHB) 5-7 in Table 6. Photoactive polymers were made by reacting 15.29 g of HEAA, 3.19 g of AA, 1.00 g, 0.50 g, or 0.25 g of MHB in 40 mL of ethanol and 30 mL of water. 0.245 mL of a 20 mg / mL solution of (AiBN) in THF was added to the monomer solution. The solution was sparged for 30 min to remove oxygen and then heated to 60 °C for 24 h. After the reaction was complete, the polymer was precipitated with 150 mL of ethyl acetate. The solvent was decanted off, the polymer was dried in an oven at 60 °C, and the remaining solvent was removed under vacuum. The polymer was dissolved in a 50:50 mixture of ethanol and water.

[0125] The molecular weights of these hydrophilic photoactive polymers were determined by SEC using a Waters 1515 isocratic high-performance liquid chromatography HPLC pump, a Waters 2489 UV / visible detector set at 276 and 290 nm, a Waters 2414 refractive index detector, and three columns: two Waters Ultrahydrogel 2000 and one Waters Ultrahydrogel 250. Molecular weights were calculated relative to poly(acrylic acid) standards using Empower3 software. [Table 6]

[0126] The coatings were applied to Pebax™ 55D plastic tubing by dip coating. The Pebax™ tubing had an outer diameter of 0.079 inches and a wall thickness of 0.005 inches. The tube was placed on a stainless steel rod to ensure stability. The tube was first dipped into the basecoat, extracted at 0.2 inches per second, rotated in a UV chamber for 5 minutes, and set to the desired intensity. The tube was then dipped into the topcoat, extracted at 0.2 inches per second, rotated in a UV chamber for 5 minutes, and set to the desired intensity.

[0127] UV curing was performed with a Uvitron IntelliRay model UV0832 UV Cure unit equipped with a UVA 600 watt metal halide lamp. Irradiance was measured using an EIT Uvicure Plus II radiometer purchased from INPRO Technologies. This single channel UVA radiometer measures radiation from 320 to 390 nm.

[0128] The friction of the coatings was pinch tested on a Tinius Olsen 5ST Electromechanical Testing Machine equipped with a 10N load cell and data collected with Horizon software. The Tinius Olsen is equipped with a heated water bath and pinch pads that are pressed together with a constant force. The water bath is filled with PBS solution and heated to 37°C. The pinch pads are submerged in the water and pressed together with a force of 450g. Friction is measured in grams of force required to push or pull the sample through the pads. Lubricity and durability are determined by the average value of grams of force as the sample is pulled through the pads. Lubricity is the average value over 2-4 cycles and durability is the average value over 28-30 cycles.

[0129] Basecoat solutions were made using the two previously mentioned photoactive basecoat polymers. The basecoat polymers can be diluted with a variety of solvents including isopropanol (IPA) and ethanol. Basecoat A: A 10 wt% solution of copolymers of 2-ethylhexyl methacrylate (EHMA), N-vinylpyrrolidone (NVP), (hydroxyethyl) methacrylate (HEMA) and MHB in propylene glycol methyl ether acetate, PMA with added polyaziridine crosslinker. Basecoat B: A 10 wt% solution of copolymers of butyl acrylate (BA), methyl methacrylate (MMA), NVP, HEMA and MHB in PMA with added polyaziridine crosslinker.

[0130] A Pebax™ 55D tube was coated with basecoat A and after 5 minutes of UV curing, it was coated in water with a topcoat containing the photoactive polymer listed in Table 6 along with 2% poly(HEAA-co-AA) and a surfactant. Table 7 shows the results of the rub tests for different topcoats cured at different UV light intensities. [Table 7]

[0131] Table 8 shows the results of the rub tests of the different topcoats with basecoat B. The photoactive topcoats were poly(HEAA-co-AA-co-MHB), poly(HEAA-co-AA), and surfactants in water as described in Table 1. [Table 8]

[0132] The examples in Table 9 show that the photoactive basecoats work well when applied directly to a substrate; that is, a hydrophobic basecoat is not necessary for good lubricity and durability with the photoactive hydrophilic topcoat. The photoactive topcoat was applied in two coats and cured for 5 minutes after each application. As above, the topcoat solution had one of the photoactive topcoats in Table 6, poly(HEAA-co-AA), and a surfactant in water. [Table 9]

[0133] In this specification, unless otherwise specified, words will be used that have their ordinary meaning as understood by those of ordinary skill in the relevant art, however, to avoid any doubt, the meaning of certain terms will be specifically defined or clarified.

[0134] In this disclosure, the singular forms "a," "an," and "the" include plural references and a reference to a particular value includes at least that particular value unless the context clearly dictates otherwise. Thus, for example, a reference to "a material" is a reference to at least one of such materials and equivalents thereof known to those of ordinary skill in the art.

[0135] It is understood that the terms used herein are for the purpose of describing particular aspects only and are not intended to be limiting. As used herein and in the claims, the term "comprising" can include the embodiments "consisting of" and "consisting essentially of". Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. In this specification and the claims that follow, reference will be made to a number of terms defined herein.

[0136] When values ​​are expressed as approximations by use of the descriptor "about", it will be understood that the particular value forms another embodiment. In general, the use of the term "about" indicates an approximation that may vary depending on the desired properties sought to be obtained by the disclosed subject matter and should be interpreted in the particular context in which it is used based on its function. A person skilled in the art would be able to interpret it routinely. In some cases, the number of significant figures used for a particular value may be one non-limiting way to determine the scope of the term "about". In other cases, the scale used in a series of values ​​may be used to determine the intended range that can be used with the term "about" for each value.

[0137] In this case, all ranges are inclusive and combinable, that is, the values ​​stated within a range include every value within that range, including the endpoints.

[0138] When lists are presented, unless otherwise stated, it is to be understood that each individual element of the list and every combination of that list is to be interpreted as a separate embodiment. For example, a list of embodiments presented as "A, B, or C" is to be interpreted as including the embodiments "A," "B," "C," "A and B," "A and C," "B and C," or "A, B, and C."

[0139] For clarity, it should be understood that certain features of the invention described herein in the context of separate embodiments may also be provided in combination in a single embodiment. That is, unless expressly incompatible or expressly excluded, each embodiment is considered combinable with other possible embodiment(s), and such combinations are considered to be separate embodiments. Conversely, various features of the invention that are described for brevity in the context of a single embodiment may also be provided separately or in any subcombination. Furthermore, while an embodiment may be described as part of a series of steps or as part of a more general structure, each said step or portion may also be considered to be an independent embodiment in itself.

[0140] As used herein, the terms "article" and "substrate" may refer to a layer, layers, or block of material having at least one surface that is modified by the coating compositions described herein, and are not limited to any shape or size.

[0141] The glass transition temperature (Tg) is determined using the Fox equation and literature values ​​for homopolymers. The Fox equation is: TIFF0007621347000014.tif16153, where T g,mix and T g,i are the glass transition temperatures in Kelvin of the blend / copolymer and components, respectively, and ω i is the mass fraction of component i. Low T g Monomers that form homopolymers have low T g' is needed to produce copolymers with a Tg of -54°C. Examples include butyl acrylate (Tg = -54°C), 2-ethylhexyl methacrylate (-10), isodecyl methacrylate (-30), and dodecyl methacrylate (-65). The homopolymer Tg of some of the other monomers used are 100°C for MMA, 20°C for BMA, 120°C for NVP, 105°C for HEMA, 143°C for MHB, and 105°C for acrylic acid.

[0142] For two components A and B, the Fox equation reduces to: TIFF0007621347000015.tif18151

[0143] As used herein, the term "hydrophobic" refers to a polymer that is not soluble in an aqueous solution. A crosslinked hydrophobic polymer does not swell significantly (less than 50%) in water.

[0144] The term "hydrophilic" refers to a polymer that is soluble in water or a water-alcohol solution. A crosslinked hydrophilic polymer will swell significantly (>100%) in an aqueous solution. A "hydrophilic" substrate surface is one made of a polymer where the uncured or uncrosslinked polymer is soluble in water or in a water-alcohol solution that is greater than 50% water.

[0145] Unless otherwise stated, all molecular weights are weight average molecular weight (Mw).

Claims

1. (a) 1-12 mol % of at least one photoactive monomer that is a hydrogen atom abstracting agent; (b) 99 to 88 mol % of one or more of acrylamide, methacrylamide, acrylate, methacrylate, and N-vinylpyrrolidone; 1. A coating composition having a hydrophobic polymer for use as a photoreactive base coat for a medical device or implant, the ... polymer made from a monomer having The polymer has a glass transition temperature (Tg) of less than 40° C. Coating composition.

2. 10. The coating composition of claim 1 further comprising a polyfunctional aziridine.

3. 3. The coating composition of claim 2, (a) 95 to 99.8 wt % of the hydrophobic polymer; (b) 0.2 to 5 wt % of a polyfunctional aziridine; The coating composition comprising:

4. 4. A coating composition according to any one of claims 1 to 3, comprising the following structure: 【Chemistry 5】 (R is an optionally substituted C １ -C ２０ is alkyl) The coating composition according to claim 1,

5. 5. The coating composition of claim 4, wherein R is one or more of methyl, ethylhexyl, isodecyl, or dodecyl.

6. The coating composition of claim 4, wherein the hydrophobic polymer comprises hydroxyethyl methacrylate and N-vinylpyrrolidone.

7. In the coating composition according to any one of claims 1 to 6, the hydrophobic polymer is ４ -C ２０ A coating composition having an acrylate having an alkyl group.

8. 8. The coating composition according to claim 1, wherein the photoactive monomer that is a hydrogen atom abstracting agent has a benzophenone moiety.

9. 9. The coating composition of claim 8, wherein the photoactive monomer that is a hydrogen atom abstracting agent comprises one or more of 4-methacryloxy 2-hydroxybenzophenone, 4-acryloxybenzophenone, 4-methacryloxybenzophenone, acrylamide benzophenone, methacrylamide benzophenone, 2-hydroxy-4-acryloxyethoxybenzophenone, and 2-hydroxy-4-methacryloxyethoxybenzophenone.

10. 10. The coating composition according to any one of claims 1 to 9, having a Tg of less than 20°C.

11. A medical device or implant having a photoreactive base coat comprising the coating composition of any one of claims 1 to 10.

12. 12. The medical device of claim 11, wherein the base coat is between a substrate and a hydrophilic top coat.

13. 13. The medical device of claim 12, wherein the topcoat comprises one or more of polyacrylate, polyvinylpyrrolidone, hyaluronic acid, and polyacrylamide.

14. The medical device of claim 12, wherein the topcoat comprises an N-(2-hydroxyethyl)acrylamide and acrylic acid copolymer.

15. 12. The medical device of claim 11, wherein the medical device is a catheter or a guidewire.

16. 13. The medical device of claim 12, comprising a plurality of covalent crosslinks between said base coat and said hydrophilic top coat.

17. A coating solution having 2 to 15 wt % of the coating composition of any one of claims 1 to 10 in a solvent.

18. 20. The coating solution of claim 17, wherein the solvent is an organic solvent.

19. 20. The coating solution of claim 18, wherein the solvent comprises one or more of toluene, ethanol, acetone, isopropanol, ethyl acetate, dimethylformamide, tetrahydrofuran, butanol, N-methyl-2-pyrrolidone, n-butyl acetate, 1,2-propanediol monomethyl ether acetate, isobutyl acetate, isopropyl acetate, methyl acetate, 3-methyl-1-butanol, methyl ethyl ketone, 2-methyl-1-propanol, 1-pentanol, 2-propanol, propyl acetate, dichloromethane, dimethylsulfoxide, methyl butyl ketone, and xylene.

20. A method of forming a coated article comprising the step of coating a substrate with a basecoat comprising the coating composition of any one of claims 1-10.

21. 21. The method of claim 20, further comprising curing the base coat by exposing the base coat to UV light.

22. 22. The method of claim 21, further comprising coating the base coat with a hydrophilic top coat.

23. 21. The method of claim 20, further comprising the steps of: (a) coating the basecoat with a hydrophilic topcoat; and (b) curing the basecoat and topcoat with UV light.

24. The medical device of claim 12, wherein the hydrophilic top coat comprises a coating composition having a polymer soluble in water or a water-alcohol solution, the polymer being: (a) at least one monomer that is a photoradical generator having one or more of 4-methacryloxy 2-hydroxybenzophenone, 4-acryloxybenzophenone, 4-methacryloxybenzophenone, acrylamide benzophenone, methacrylamide benzophenone, 2-hydroxy-4-acryloxyethoxybenzophenone, 2,4-dihydroxy-4′-vinyl benzophenone, and 2-hydroxy-4-methacryloxyethoxybenzophenone; and (b) made from monomers having (i) an ethylenic monomer having at least one acidic group and (ii) at least one monomer having one or both of an acrylate or an acrylamide; The ethylenic monomers having at least one acidic group include acrylic acid, methacrylic acid, 2-ethylacrylic acid, 2-propylacrylic acid, acryloxypropionic acid, isocrotonic acid, maleic anhydride, maleic acid and half esters, half amides and half thioesters of maleic acid, fumaric acid and itaconic acid, and mixtures thereof; The acrylate or acrylamide comprises acrylamide, N-(2-hydroxyethyl)acrylamide, 2-hydroxyethyl methacrylate, 2-hydroxypropyl acrylate, 2-hydroxypropyl methacrylate, and N-(2-hydroxyethyl)methacrylamide, N-acryloylamide-ethoxyethanol, N-(hydroxymethyl)acrylamide, N-[tris(hydroxymethyl)methyl]acrylamide, 4-hydroxybutyl acrylate, hydroxypropyl acrylate, methyl 3-hydroxy-2-methylenebutyrate, hydroxypropyl methacrylate, 2-allyloxyethanol, 3-allyloxy-1,2-propanediol, 1,4-butanediol vinyl ether, di(ethylene glycol)vinyl ether, ethylene glycol vinyl ether, N,N-1,2-dihydroxyethylene-bis-acrylamide, N,N-1,2-dihydroxyethylene-bis-methylacrylamide, N-hydroxymethyl methacrylamide, N-tri(hydroxymethyl)-methyl-methacrylamide, or any mixture thereof; the molar ratio of one or both of (i) the ethylenic monomer having at least one acidic group, and (ii) the one or more of the acrylates or acrylamides to the photoradical generating group is from 20:1 to 500:1; Medical equipment.

25. 25. The medical device according to claim 24, wherein the photoradical generating group comprises 4-methacryloxy-2-hydroxybenzophenone.

26. 25. The medical device of claim 24, wherein the ethylenic monomers comprise N-(2-hydroxyethyl)acrylamide and acrylic acid.

27. 27. The medical device of claim 26, wherein the molar ratio of N-(2-hydroxyethyl)acrylamide and acrylic acid is from 2:1 to 5:

1.

28. 25. The medical device of claim 24, wherein the molar ratio of one or both of (i) an ethylenic monomer having at least one acidic group and (ii) one or more of an acrylate or an acrylamide to a photoradical generator having at least one photopolymerizable group is 40:1 to 200:

1.

29. 25. The medical device of claim 24, wherein the polymer has a weight average molecular weight (Mw) of 20,000 to 800,000.

30. 25. The medical device of claim 24, further comprising a second polymer that is soluble in water or a water-alcohol solution.

31. 31. The medical device of claim 30, wherein the second polymer comprises one or both of: (i) an ethylenic monomer having at least one acidic group; and (ii) one or more of an acrylate or an acrylamide.

32. 32. The medical device of claim 31, wherein the ethylenic monomer of the second polymer has at least one acidic group, and the ethylenic monomer of the second polymer having at least one acidic group comprises one or more of acrylic acid, methacrylic acid, 2-ethylacrylic acid, 2-propylacrylic acid, acryloxypropionic acid, isocrotonic acid, maleic anhydride, maleic acid and half esters, half amides and half thioesters of maleic acid, fumaric acid, itaconic acid, and any combination thereof.

33. In the medical device of claim 31, the acrylate or acrylamide of the second polymer is selected from the group consisting of acrylamide, N-(2-hydroxyethyl)acrylamide, 2-hydroxyethyl methacrylate, 2-hydroxypropyl acrylate, 2-hydroxypropyl methacrylate, and N-(2-hydroxyethyl)methacrylamide, N-acryloylamide-ethoxyethanol, N-(hydroxymethyl)acrylamide, N-[tris(hydroxymethyl)methyl]acrylamide, 4-hydroxybutyl acrylate, hydroxypropyl acrylate, methyl the medical device comprising N,N-1,2-dihydroxyethylene-bis-acrylamide, N,N-1,2-dihydroxyethylene-bis-methylacrylamide, N-hydroxymethylmethacrylamide, N-tri(hydroxymethyl)-methyl-methacrylamide, and any mixture thereof.

34. 32. The medical device of claim 31, wherein the second polymer has a weight average molecular weight (Mw) of 50,000 to 800,000.

35. 25. The medical device of claim 24, further comprising water or a water / alcohol mixture.

36. A substrate; A photoreactive base coat made with the coating composition according to any one of claims 1 to 10, and Hydrophilic top coat The coated substrate having the following structure:

37. 37. The coated substrate of claim 36, wherein the hydrophilic topcoat is prepared using a coating composition having a polymer soluble in water or a water-alcohol solution, the polymer comprising: (a) at least one monomer that is a photoradical generator having one or more of 4-methacryloxy 2-hydroxybenzophenone, 4-acryloxybenzophenone, 4-methacryloxybenzophenone, acrylamide benzophenone, methacrylamide benzophenone, 2-hydroxy-4-acryloxyethoxybenzophenone, 2,4-dihydroxy-4′-vinyl benzophenone, and 2-hydroxy-4-methacryloxyethoxybenzophenone; and (b) a monomer having (i) at least one ethylenic monomer having an acidic group and (ii) at least one monomer having one or both of an acrylate or an acrylamide; It is made from The ethylenic monomers having at least one acidic group include acrylic acid, methacrylic acid, 2-ethylacrylic acid, 2-propylacrylic acid, acryloxypropionic acid, isocrotonic acid, maleic anhydride, maleic acid and half esters, half amides and half thioesters of maleic acid, fumaric acid and itaconic acid, and mixtures thereof; The acrylate or acrylamide comprises acrylamide, N-(2-hydroxyethyl)acrylamide, 2-hydroxyethyl methacrylate, 2-hydroxypropyl acrylate, 2-hydroxypropyl methacrylate, and N-(2-hydroxyethyl)methacrylamide, N-acryloylamide-ethoxyethanol, N-(hydroxymethyl)acrylamide, N-[tris(hydroxymethyl)methyl]acrylamide, 4-hydroxybutyl acrylate, hydroxypropyl acrylate, methyl 3-hydroxy-2-methylenebutyrate, hydroxypropyl methacrylate, 2-allyloxyethanol, 3-allyloxy-1,2-propanediol, 1,4-butanediol vinyl ether, di(ethylene glycol)vinyl ether, ethylene glycol vinyl ether, N,N-1,2-dihydroxyethylene-bis-acrylamide, N,N-1,2-dihydroxyethylene-bis-methylacrylamide, N-hydroxymethyl methacrylamide, N-tri(hydroxymethyl)-methyl-methacrylamide, or any mixture thereof; the molar ratio of one or both of (i) the ethylenic monomer having at least one acidic group, and (ii) the one or more of the acrylates or acrylamides to the photoradical generating group is from 20:1 to 500:1; Coated substrate.

38. 37. The coated substrate of claim 36, wherein the substrate is plastic.

39. 37. The coated substrate of claim 36, wherein the substrate is a metal.

40. 40. The coated substrate of any one of claims 36 to 39, wherein the coated substrate has a lubricity of less than 25 gf of friction and a durability of less than 50 gf of friction as measured by a pinch test.

41. 36. The medical device or medical implant of any one of claims 11-16 and 24-35, wherein said medical device or medical implant is sterilized by at least one of gamma radiation, E-beam, and ethylene oxide.

42. 42. The medical device or medical implant of any one of claims 24 to 35 or claim 41, wherein the lubricious coating comprises a pharmaceutical or antimicrobial agent formulated in the coating composition.

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