Coatings for medical devices

Abstract

Coatings for medical devices are described. Some coatings include block copolymers comprising polyacrylate and polyester polymers. Some coatings are cured using UV light. Methods of preparing the coatings, methods of coating medical devices, and methods of using the coated devices are also described.

Description

COATINGS FOR MEDICAL DEVICESCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 675,991 , filed July 26, 2024, the entirety of which is incorporated herein.FIELD

[0002] Described herein are coatings for medical devices.BACKGROUND

[0003] Lubricous coatings are desirable for intravascular devices such as catheters. The coatings function by reducing friction forces between the catheter and the blood vessel wall. The result is better maneuverability for the physicians, less damage to the blood vessel wall, and greater comfort for the patients. However, the issue of coating separation from intravascular medical devices persists as a significant concern for manufacturers for lubricous coatings. In 2019, the Food and Drug Administration (FDA) issued a guidance document addressing labeling considerations for devices containing lubricious coatings and advising that the labels should inform health care providers on the possibility of coating separation from the device under various circumstances and the consequences resulting from the separation. Therefore, there is a need in the field for improved lubricious coatings for medical devices.SUMMARY

[0004] This disclosure relates to the preparation and use of durable, lubricious coatings for medical devices. In some embodiments, the coatings are UV-cured. In some embodiments, the coatings can be for use with lumens, for example catheters and microcatheters, to be used inside vasculature (e.g., the urinary tract). The durable lubricious coatings enable the long-term use of catheters inside the urinary tract without any separation of the coating from the catheter.

[0005] Coatings described herein can comprise multiple coating layers, for example two coating layers, for example a base coat and a top coat. The base coat functions as a “tie” layer between the polymer of the catheter, typically a silicone or latex, and the top coat. The base coat is designed to adhere to the catheter. The top coat is designed to adhere to the base coat, covalently or non-covalently, and enhance the lubricious nature and durability of the catheter. In some embodiments, the top coat is designed to be UV-curable.

[0006] Provided herein is a copolymer, wherein the copolymer is a reaction product of:A) a first monomer, comprising a compound having a formulawhereinR1is H or C1-6 alkyl;R2is OR3or N(R4)R5;R3is C1-6 alkyl;R4is H or C1-6 alkyl; andR5is Ci_6alkyl;B) a second monomer, comprising a compound having a formulawhereinR6is a bond or C1-30 alkylenyl;R7is a bond, C1-30 alkylenyl, or C3-10 cycloalkylenyl; andR8is a bond or C1-30 alkylenyl; m is an integer ranging from 1 to 20; n is an integer ranging from 1 to 50; p is an integer ranging from 1 to 20; andC) a third monomer, comprising a compound having a formulawhereinR9is H or C1-6 alkyl;R10is OR11or N(R12)R13;R11is (C1-20 alkylene)OH, (C1-20 alkylene)NH2, (C1-20 alkylene)SH, (Ce-is arylene)OH, (Ce-ie arylene) NH2, or (Ce-16 arylene)SH;R12is H or C1-6 alkyl; andR13is (C1-20 alkylene)OH, (C1-20 alkylene)NH2, (C1-20 alkylene)SH, (Ce-16 arylene)OH, (Ce-16 arylene) NH2, or (Ce-16 arylene)SH.

[0007] Further embodiments include a method of preparing a coated catheter comprising forming a base coat by dissolving two or more monomers and an initiator in a solvent; polymerizing the monomers to form a copolymer; adding a reactive group to the copolymer to form a derivatized copolymer; forming a top coat by dissolving two or more monomers and an initiator in a solvent; applying the base coat to the catheter; and applying the top coat to the catheter. In embodiments, the solvent can be at least one of benzene, toluene, xylene, dimethylformamide, dimethyl sulfoxide, dioxane, 2-methyltetrahydrofuran, anisole, benzonitrile, chlorinated aromatic solvents, diisopropyl ether, diglyme, butanol, and combinations thereof.

[0008] Further embodiments comprise a method of preparing a coated catheter comprise initiating polymerization by at least one of a reduction-oxidation, radiation, or heat. In embodiments the initiator comprises azobisisobutyronitrile (AIBN) or a water soluble AIBN derivative (2,2'-azobis(2-methylpropionamidine) dihydrochloride), or 4,4'-azobis(4- cyanopentanoic acid), N,N,N',N'-tetramethylethylenediamine, ammonium persulfate, benzoyl peroxides, and combinations thereof including azobisisobutyronitriles. In embodiments the initiator is present at about 0.25% to about 2% w / w of the mass of the monomers in solution. In embodiments the radiation initiation is applied with infrared, ultraviolet or visible light.

[0009] In embodiments comprising a method of preparing a coated catheter, a reactive group is added to the copolymer to form a derivatized copolymer.

[0010] Further embodiments include a catheter comprising a coating formulation comprising: a base coat comprising a copolymer (e.g., of tetrahydrofurfuryl acrylate) and a monomer comprising a functional group amenable to further derivatization, wherein the copolymer is further modified to contain a plurality of reactive moieties; and a top coat which is a described herein.

[0011] In some, embodiments the catheter is a urinary catheter.DETAILED DESCRIPTION

[0012] Device Coatings

[0013] Embodiments disclosed herein comprise coatings. In some embodiments, these coatings can be for medical devices such as, but not limited to, medical lumens, catheters, and microcatheters.

[0014] In one embodiment, the coatings can be for urinary catheters. These catheters aretypically formed of silicones, latexes, poly(vinyl chloride), and copolymers thereof and derivatives thereof. The coating can comprise two layers; a top coat and a base coat, which can adhere to the polymeric substrate of the catheter and provide binding sites for a top coat.

[0015] A block copolymer currently used as a top coat comprises a poly(glycidyl methacrylate) block and a poly(N,N-dimethylacrylamide) block, and it is applied via heat-curing. By contrast, embodiments disclosed herein can be applied via UV-curing, which is more advantageous for having a smaller footprint for coating machine and shorter batch turnover time. In some embodiments, the topcoat block copolymer described herein comprises a UV-curable block and a polar block. The UV-curable block is able to crosslink and renders the coating durability. The polar block renders the coating lubricity. Further, the dipole-dipole moments and dipole-ionic interactions allow for strong non-covalent interactions. Therefore, the polarity of the polar block contributes to durability as well.Base Coat

[0016] In some embodiments, the base coat polymer comprises a copolymer of tetrahydrofurfuryl acrylate and at least one other monomer with functional groups capable of further chemical reaction such as hydroxyl, amine, and carboxylic acid groups. Suitable monomers containing hydroxyl groups comprise hydroxyethyl methacrylate, hydroxyethyl acrylate, hydroxypropyl acrylate, hydroxypropyl methacrylate, hydroxybutyl acrylate, hydroxybutyl methacrylate, combinations thereof, and derivatives thereof. Suitable monomers containing amine groups comprise N-(3-aminopropyl) methacrylamide, 2-aminoethyl methacrylate, 2-aminoethyl methacrylamide, combinations thereof, and derivatives thereof. Suitable monomers containing carboxylic acids comprise acrylic acid, methacrylic acid, beta-carboxyethyl acrylate, combinations thereof, and derivatives thereof.

[0017] In embodiments, to prepare the base coat copolymer, the two or more monomers and an initiator are dissolved in a solvent. In general, any solvent that dissolves the two or more monomers and the initiator can be used. Suitable solvents comprise benzene, toluene, xylene, dimethylformamide, dimethyl sulfoxide, dioxane, 2-methyltetrahydrofuran, anisole, benzonitrile, chlorinated aromatic solvents, diisopropyl ether, diglyme, butanol, and combinations thereof. In some embodiments, the solvent may have a low boiling point.

[0018] In embodiments, polymerization initiators can be used to start the polymerization of the monomers in the solution. The polymerization can be initiated by reduction-oxidation, radiation, heat, or any other method known in the art. Radiation polymerization of the monomer solution canbe achieved with ultraviolet light or visible light with suitable initiators or ionizing radiation (e.g. electron beam or gamma ray) without initiators. Polymerization can be achieved by application of heat, either by conventionally heating the solution using a heat source such as a heating well, or by application of infrared light to the monomer solution. In some embodiments, the basecoat block copolymer is a UV-curable polymer that may or may not covalently bind to the top coat.

[0019] In one embodiment, the polymerization initiator comprises azobisisobutyronitrile (AIBN) or a water soluble AIBN derivative (2,2'-azobis(2-methylpropionamidine) dihydrochloride), or 4,4'- azobis(4-cyanopentanoic acid). In other embodiments, the initiator may comprise N,N,N',N'- tetramethylethylenediamine, ammonium persulfate, benzoyl peroxides, and combinations thereof, including azobisisobutyronitriles. In embodiments, concentrations of the initiator can range from about 0.25% to about 2% w / w of the mass of the monomers in solution. For example, the initiator concentration can be 0.25%, 0.5%, 1 %, 1.5%, 2%, or the like.

[0020] Disclosed base coat polymerization reactions can be performed at elevated temperatures, preferably in the range from about 65°C to about 85°C. After the polymerization is completed, the copolymer is recovered by precipitation in a non-solvent and dried under vacuum. In embodiments, the resulting copolymer has a molecular weight between about 15,000 and about 350,000 g / mole. In some embodiments, the molecular weight is between about 25,000 and about 100,000 g / mole, when analyzed by gel permeation chromatography with polystyrene standards.

[0021] In some embodiments, following polymerization, reactive groups, preferably acrylates and / or methacrylates, may be added to the copolymer via the hydroxyl, amine, and / or carboxylic acid groups of the second or more monomer. In some embodiments, the derivatization compound can be a heterobifunctional compound. One moiety reacts with the hydroxyl, amine, and / or carboxylic acid groups of the copolymer. The other moiety is an acrylate or methacrylate group.

[0022] In some embodiments, derivatization compounds can comprise 2-isocyanatoethyl acrylate, 2-isocyanatoethyl methacrylate, acrylic acid N-hydroxysuccinimide ester, methacrylic acid N-hydroxysuccinimide ester, hetero-bifunctional polyethylene glycol) with acrylate and isocyanate groups, combinations thereof, and derivatives thereof. In some embodiments, the base coat comprises acrylate functionalized poly(tetrahydrofurfuryl acrylate)-co-poly(3- hydrox propyl acrylate) or equivalent. In some embodiments, the base coat comprises a thiol- functionalized compound or polymer (e.g., tris[2-(3-mercaptopropionyloxy)ethyl]isocyanurate). In some embodiments, when the base coat contains thiol moieties, a top coat is capable of reacting with the base coat via a thiol-ene reaction, in some embodiments, a portion of the top coat may act as a derivatization compound, thus covalently binding to the base coat.

[0023] To prepare the derivatized copolymer, the copolymer, derivatization compound, and any catalyst are dissolved in a solvent. In general, any solvent that dissolves the two or more monomers and the initiator can be used. Solvents comprise dimethyl formamide, dimethyl sulfoxide, toluene, acetone, acetonitrile, N,N-dimethylacetamide, N-methyl-2-pyrrolidone, and combinations thereof. In some embodiments, the solvent may have a low boiling point.

[0024] In some embodiments, when reacting a derivatization with a nucleophilic group of the base coat copolymer, the molar equivalent of the derivatization agent ranges from about 5% to about 80% of the available nucleophilic groups. In some embodiments, the molar equivalent of the derivatization agent ranges from about 10% to about 50% of the available nucleophilic groups, for example 10%, 20%, 30%, 40%, or 50%. In some embodiments, this level of derivatization corresponds to a range of about 4 to about 50 reactive groups per molecule. Additionally, in embodiments the addition of a Lewis base as a catalyst can be used. Lewis bases can comprise, for example, triethylamine and pyridine, typically in a concentration of about 1 % to about 10% of the moles of the derivatization compound added. The reaction proceeds at ambient or elevated temperature, such as 30 °C, 40 °C, or 45 °C. After the derivatization is complete, the completed, decorated copolymer is recovered by precipitation in a non-solvent and dried under vacuum.Top Coat

[0025] In some embodiments, the top coat comprises vinylic monomers which may include, but not limited to, acrylates, methacrylates, acrylamides, methacrylamides, vinyl ethers, vinyl amines, vinyl esters, mono-epoxydienes, and the like. In some embodiments, the top coat comprises a polyester. In some embodiments, the top coat comprises a polyester polyperoxide.

[0026] Monomers containing amines comprise 3-aminopropyl methacrylamide, 2-aminoethyl methacrylate, N-(3-methylpyridine)acrylamide, 2- A / ,A / -dimethylamino)ethyl methacrylate, 2-(N,N- dimethylamino)ethyl acrylate, 2-(tert-butylamino)ethyl methacrylate, methacryloyl-L-lysine, A / -(2- (4-aminophenyl)ethyl)acrylamide, A / -(4-aminobenzyl)acrylamide, and / V-(2-(4- imidazolyl)ethyl)acrylamide, derivatives thereof, and combinations thereof. Monomers including carboxylic acids comprise acrylic acid, methacrylic acid, derivatives thereof, and combinations thereof. Monomers containing hydroxyl groups comprise 2-hydroxyethyl acrylate, 2-hydroxyethyl methacrylate, 2-hydroxypropyl acrylate, 4-hydroxybutyl acrylate, derivatives thereof, and combinations thereof. Examples of additional vinylic monomers include and are not limited to vinyl ethers (e.g., ethyl vinyl ether, isobutyl vinyl ether), vinyl amines (e.g., vinyl amine, A / -vinyl- / V- methylacetamide, / V-vinylpyrrolidone, / V-vinylformamide, / V-vinylisobutyramide), and vinyl esters (e.g., vinyl acetate, vinyl chloroacetate, vinyl benzoate).

[0027] Provided herein is a copolymer, wherein the copolymer is a reaction product of:A) a first monomer, comprising a compound having a formula:whereinR1is H or C1-6 alkyl;R2is OR3or N(R4)R5;R3is C1-6 alkyl;R4is H or C1-6 alkyl; andR5is Ci_6alkyl;B) a second monomer, comprising a compound having a formula:whereinR6is a bond or C1-30 alkylenyl;R7is a bond, C1-30 alkylenyl, or C3-10 cycloalkylenyl; andR8is a bond or C1-30 alkylenyl; m is an integer ranging from 1 to 20; n is an integer ranging from 1 to 50; p is an integer ranging from 1 to 20; andC) a third monomer, comprising a compound having a formula:whereinR9is H or C1-6 alkyl;R10is OR11or N(R12)R13;R11is (C1-20 alkylene)OH, (C1-20 alkylene)NH2, (C1-20 alkylene)SH, (Ce-16 arylene)OH, (Ce-16 arylene) NH2, or (Ce-16 arylene)SH;R12is H or C1-6 alkyl; andR13is (C1-20 alkylene)OH, (C1-20 alkylene)NH2, (C1-20 alkylene)SH, (Ce-16 arylene)OH, (Ce-16 arylene) NH2, or (Ce-16 arylene)SH.

[0028] In some embodiments, R6and R8are part of diacids each independently selected from ethanedioic acid, propanedioic acid; butanedioic acid, pentanedioic acid, hexanedioic acid, heptanedioic acid, octanedioic acid, 1 ,4-cyclohexanedicarboxylic acid, nonanedioic acid, decanedioic acid, undecanedioic acid, dodecanedioic acid, tridecanedioic acid, hexadecanedioic acid, heneicosanedioic acid, docosanedioic acid, and triacontanedioic acid. In some embodiments, R6and R8are part of diacids each independently selected from oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, and sebacic acid. In some embodiments, R6and R8are C4-alkylene.

[0029] In some embodiments, R7is propylene or ethylene. In some embodiments, R1is H or methyl. In some embodiment, R9is hydrogen or methyl.

[0030] In some embodiments, provided is a block copolymer having a formulawherein R1, R2, R6, R7, R8, R9, R10, m, n, and p are as defined above, and a, b, c, are each independently selected from 0.001 to 10000, or 1 to 5000. In some embodiments, a is an integer ranging from 1 to 5000; b is an integer ranging from 1 to 2500; and c is an integer ranging from 1 to 5000.

[0031] In some embodiments, the ratio a:c is 60:1 to 10:1 , the ratio b:c is 0.01:1 to 1 :1.

[0032] In some embodiments, provided is a copolymer, wherein the copolymer is a reaction product of:A) a first monomer, comprising a compound having a formulawhereinR1is H or Ci 6 alkyl;R2is OR3or N(R4)R5;R3is C1-6 alkyl;R4is H or C1-6 alkyl; andR5is Ci-6alkyl; andB) a second monomer, comprising a compound having a formulawhereinR6is a bond or C1-30 alkylenyl;R7is a bond, C1-30 alkylenyl, or C3-10 cycloalkylenyl;R8is a bond or C1-30 alkylenyl; m is an integer ranging from 1 to 20; n is an integer ranging from 1 to 50; and p is an integer ranging from 1 to 20.

[0033] In some embodiments, provided is a block copolymer having a formulawherein R1, R2, R6, R7, R8, m, n, and p are as defined above, and a and b are each independently selected from 0.001 to 10000, or 1 to 5000.

[0034] In some embodiments, provided is a copolymer, wherein the copolymer is a reaction product of:A) a first monomer, comprising a compound having a formula:whereinR6is a bond or C1-30 alkylenyl;R7is a bond, C1-30 alkylenyl, or C3-10 cycloalkylenyl; andR8is a bond or C1-30 alkylenyl; m is an integer ranging from 1 to 20; n is an integer ranging from 1 to 50; p is an integer ranging from 1 to 20;B) a second monomer, comprising a compound having a formula:whereinR9is H or C1-6 alkyl;R10is OR11or N(R12)R13;R11is (C1-20 alkylene)OH, (C1-20 alkylene)NH2, (C1-20 alkylene)SH, (Ce-16 arylene)OH, (Ce-16 arylene) NH2, or (Ce-16 arylene)SH;R12is H or C1-6 alkyl; andR13is (Ci_2o alkylene)OH, (Ci_2o alkylene)NH2, (Ci_20alkylene)SH, (C6-16 arylene)OH, (C6-16 arylene) NH2, or (Ce-16 arylene)SH.

[0035] In some embodiments, provided is a block copolymer having a formula:wherein R6, R7, R8, R9, R10, m, n, and p are as defined above, and b and c are each independently selected from 0.001 to 10000, or 1 to 5000.

[0036] In some embodiments, the ratio b:c is 0.01 :1 to 1:1.

[0037] Also provided is a block copolymer which is a reaction product of: a first block including at least one polymerizable monomer comprising a vinyl moiety; a second block including a polyester which is a reaction product of at least one diacid and a polyalkylene glycol; and a third block including at least one polymerizable monomer comprising a vinyl moiety, wherein at least one monomer in the third block further comprises a Ci-i2alkyl substituted with -OH, -SH, -NH2, pyrrolidone, or -COOH, a C1-12 alkenyl, or an aryl substituted with -OH, -SH, -NH2, pyrrolidone, or -COOH; wherein the block copolymer is further reacted with at least one polymerizable monomer comprising a vinyl moiety.

[0038] In some embodiments, the polymerizable monomer comprising a vinyl moiety is selected from an acrylate, an acrylamide, or a monomer having a formula:whereinR20is selected from -OR25, -OC(=O)R25, -N(R26)(R27), and -N(R26)(C(=O)R27);R25is selected from hydrogen, C1-12 alkyl substituted with -OH, -SH, -NH2, pyrrolidone, or -COOH,C1-12 alkenyl, and aryl substituted with -OH, -SH, -NH2, pyrrolidone, or -COOH; andR26and R27are independently selected from H and C1-6 alkyl, or R26and R27together with the nitrogen atom to which they are attached form a 5-7 membered heterocycle.

[0039] In some embodiments, the first block in the block copolymer includes at least one monomer having a formula:whereinR23is selected from H and CH3;R24is selected fromR25is selected from hydrogen, C1-12 alkyl substituted with -OH, -SH, -NH2, pyrrolidone, or -COOH,C1-12 alkenyl, and aryl substituted with -OH, -SH, -NH2, pyrrolidone, or -COOH; andR26and R27are independently selected from H and C1-6 alkyl, or R26and R27together with the nitrogen atom to which they are attached form a 5-7 membered heterocycle.

[0040] In some embodiments, the second block in the block copolymer includes a polyester having a formula:wherein each q is independently an integer ranging from 1 to 20; and r is an integer ranging from 1 to 50.

[0041] In some embodiments, the third block in the block copolymer includes at least one monomer having a formula:whereinR21is selected fromR22is selected fromR25is selected from hydrogen, C1-12 alkyl substituted with -OH, -SH, -NH2, pyrrolidone, or -COOH,C1-12 alkenyl, and aryl substituted with -OH, -SH, -NH2, pyrrolidone, or -COOH; andR26and R27are independently selected from H and C1-6 alkyl, or R26and R27together with the nitrogen atom to which they are attached form a 5-7 membered heterocycle.

[0042] In some embodiments, the block copolymer has a formula:R25is selected from hydrogen, C1-12 alkyl substituted with -OH, -SH, -NH2, pyrrolidone, or -COOH,C1-12 alkenyl, and aryl substituted with -OH, -SH, -NH2, pyrrolidone, or -COOH;R26and R27are independently selected from H and C1-5 alkyl, or R26and R27together with the nitrogen atom to which they are attached form a 5-7 membered heterocycle;R28is a C1-20 alkylene; a is an integer ranging from 1 to 5000; b is an integer ranging from 1 to 2500; c is an integer ranging from 1 to 5000; each q is independently an integer ranging from 1 to 20; and r is an integer ranging from 1 to 50.

[0043] In some embodiments, the block copolymer has a formula:

[0044] In some embodiments, the block copolymer has a formula:

[0045] In some embodiments, the block copolymer has a formula:

[0046] In some embodiments, the block copolymer has a formula:whereinR22Ais selected from -OR25, -OC(=O)R25, -N(R26)(R27), -N(R26)(C(=O)R27); and R24Ais selected from -OR25, -OC(=O)R25, -N(R26)(R27), -N(R26)(C(=O)R27).

[0047] In some embodiments of the block copolymer, the ratio of a:c in the block copolymer ranges from about 60:1 to about 10:1. In some embodiments of the block copolymer, the ratio of a:c in the block copolymer ranges from about 40:1 to about 10:1. In some embodiments of the block copolymer, the ratio of a:c in the block copolymer ranges from about 20:1 to about 10:1. In some embodiments of the block copolymer, the ratio of a:c in the block copolymer is about 20:1 .

[0048] In some embodiments of the block copolymer, the ratio of b:c in the block copolymer ranges from about 0.01 :1 to about 1:1. In some embodiments of the block copolymer, the ratio of b:c in the block copolymer ranges from about 0.04:1 to about 1 :1. In some embodiments of the block copolymer, the ratio of b:c in the block copolymer ranges from about 0.06:1 to about 1 :1. In some embodiments of the block copolymer, the ratio of b:c in the block copolymer ranges from about 0.08:1 to about 1 :1. In some embodiments of the block copolymer, the ratio of b:c in the block copolymer is about 0.08:1. In some embodiments of the block copolymer, the ratio of b:c in the block copolymer is about 0.08:1.

[0049] In some embodiments of the block copolymer, the ratio of the at least one acid to polyalkylene glycol ranges from about 1 :1 to about 2:1. In some embodiments of the block copolymer, the ratio of the at least one acid to polyalkylene glycol is about 2:1 .

[0050] In some embodiments of the block copolymer, the first block includes at least one monomer selected from glycidyl acrylate, glycidyl methacrylate, acrylic acid, methacrylate, methyl methacrylate, ethyl acrylate, ethyl methacrylate, 2-ethylhexyl acrylate, 2-hydroxyethyl acrylate, hydroxyethyl methacrylate, hydroxybutyl acrylate, hydroxybutyl methacrylate, 2-aminoethylmethacrylate, sulfopropyl acrylate, sulfopropyl methacrylate, methacrylamide, 3-aminopropyl methacrylamide, N,N-dimethylacrylamide, aminoethyl methacrylamide, N-(3-methylpyridine )acrylamide, N-(2-(4-aminophenyl)ethyl)acrylamide, N-(4-aminobenzyl)acrylamide, and N-(2-(4- imidazolyl)ethyl)acrylamide, and any combination thereof.

[0051] In some embodiments of the block copolymer, the at least one diacid in the second block is selected from ethanedioic acid, propanedioic acid; butanedioic acid, pentanedioic acid, hexanedioic acid, heptanedioic acid, octanedioic acid, 1 ,4-cyclohexanedicarboxylic acid, nonanedioic acid, decanedioic acid, undecanedioic acid, dodecanedioic acid, tridecanedioic acid, hexadecanedioic acid, heneicosanedioic acid, docosanedioic acid, and triacontanedioic acid. In some embodiments of the block copolymer, the at least one diacid in the second block is selected from oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, and sebacic acid.

[0052] In some embodiments of the block copolymer, the at least one polyalkylene glycol in the second block is selected from polyethylene glycol, polypropylene glycol and polybutylene glycol, and any combination thereof.

[0053] In some embodiments of the block copolymer, the third block includes at least one monomer selected from glycidyl acrylate, glycidyl methacrylate, acrylic acid, methacrylate, methyl methacrylate, ethyl acrylate, ethyl methacrylate, 2-ethylhexyl acrylate, 2-hydroxyethyl acrylate, hydroxyethyl methacrylate, hydroxybutyl acrylate, hydroxybutyl methacrylate, 2-aminoethyl methacrylate, sulfopropyl acrylate, sulfopropyl methacrylate, methacrylamide, 3-aminopropyl methacrylamide, N,N-dimethylacrylamide, aminoethyl methacrylamide, N-(3- methylpyridine)acrylamide, N-(2-(4-aminophenyl)ethyl)acrylamide, N-(4- aminobenzyl)acrylamide, and N-(2-(4-imidazolyl)ethyl)acrylamide, and any combination thereof.

[0054] In some embodiments, the block copolymer herein is a block copolymer comprising a reaction product of a first polymer and hydroxyethyl acrylate, wherein the first polymer comprises a reaction product of a polyperoxide-monomer initiator and A / ,A / -dimethylacrylamide, wherein the polyperoxide-monomer initiator comprises a reaction product of a polyperoxide and a monomer, wherein the monomer comprises one or more of glycidyl methacrylate, (3,4- epoxycyclohexyl)methyl acrylate, glycidyl acrylate, 2-isocyanatoethyl acrylate, 2-isocyanatoethyl methacrylate, 1 ,3-butadiene monoepoxide, 1 ,2,-epoxy-4-vinylcyclohexane, or allyl glycidyl ether.

[0055] Thus, in some embodiments, the block copolymer herein is a block copolymer comprising a reaction product of a first polymer and hydroxyethyl acrylate, wherein the first polymercomprises a reaction product of a polyperoxide-monomer initiator and A / , / V-dimethylacrylamide, wherein the polyperoxide-monomer initiator comprises a reaction product of a polyperoxide and a monomer, wherein the monomer comprises one or more of (3,4-epoxycyclohexyl)methyl acrylate, glycidyl acrylate, 2-isocyanatoethyl acrylate, 2-isocyanatoethyl methacrylate, 1 ,3- butadiene monoepoxide, 1 ,2,-epoxy-4-vinylcyclohexane, or allyl glycidyl ether.

[0056] Thus, in some embodiments, the block copolymer herein is a block copolymer comprising a reaction product of a first polymer and hydroxyethyl acrylate, wherein the first polymer comprises a reaction product of a polyperoxide-monomer initiator and A / , / V-dimethylacrylamide, wherein the polyperoxide-monomer initiator comprises a reaction product of a polyperoxide and a monomer, wherein the monomer comprises glycidyl methacrylate.

[0057] Thus, in some embodiments, the block copolymer herein is a block copolymer comprising a reaction product of a first polymer and hydroxyethyl acrylate, wherein the first polymer comprises a reaction product of a polyperoxide-monomer initiator and A / , / V-dimethylacrylamide, wherein the polyperoxide-monomer initiator comprises a reaction product of a polyperoxide and a monomer, wherein the monomer comprises (3,4-epoxycyclohexyl)methyl acrylate.

[0058] Thus, in some embodiments, the block copolymer herein is a block copolymer comprising a reaction product of a first polymer and hydroxyethyl acrylate, wherein the first polymer comprises a reaction product of a polyperoxide-monomer initiator and A / , / V-dimethylacrylamide, wherein the polyperoxide-monomer initiator comprises a reaction product of a polyperoxide and a monomer, wherein the monomer comprises glycidyl acrylate.

[0059] Thus, in some embodiments, the block copolymer herein is a block copolymer comprising a reaction product of a first polymer and hydroxyethyl acrylate, wherein the first polymer comprises a reaction product of a polyperoxide-monomer initiator and A / , / V-dimethylacrylamide, wherein the polyperoxide-monomer initiator comprises a reaction product of a polyperoxide and a monomer, wherein the monomer comprises 2-isocyanatoethyl acrylate.

[0060] Thus, in some embodiments, the block copolymer herein is a block copolymer comprising a reaction product of a first polymer and hydroxyethyl acrylate, wherein the first polymer comprises a reaction product of a polyperoxide-monomer initiator and A / , / V-dimethylacrylamide, wherein the polyperoxide-monomer initiator comprises a reaction product of a polyperoxide and a monomer, wherein the monomer comprises 2-isocyanatoethyl methacrylate.

[0061] Thus, in some embodiments, the block copolymer herein is a block copolymer comprising a reaction product of a first polymer and hydroxyethyl acrylate, wherein the first polymercomprises a reaction product of a polyperoxide-monomer initiator and A / , / V-dimethylacrylamide, wherein the polyperoxide-monomer initiator comprises a reaction product of a polyperoxide and a monomer, wherein the monomer comprises 1,3-butadiene monoepoxide.

[0062] Thus, in some embodiments, the block copolymer herein is a block copolymer comprising a reaction product of a first polymer and hydroxyethyl acrylate, wherein the first polymer comprises a reaction product of a polyperoxide-monomer initiator and A / , / V-dimethylacrylamide, wherein the polyperoxide-monomer initiator comprises a reaction product of a polyperoxide and a monomer, wherein the monomer comprises 1,2,-epoxy-4-vinylcyclohexane.

[0063] Thus, in some embodiments, the block copolymer herein is a block copolymer comprising a reaction product of a first polymer and hydroxyethyl acrylate, wherein the first polymer comprises a reaction product of a polyperoxide-monomer initiator and A / , / V-dimethylacrylamide, wherein the polyperoxide-monomer initiator comprises a reaction product of a polyperoxide and a monomer, wherein the monomer comprises allyl glycidyl ether.

[0064] Thus, in some embodiments, the block copolymer herein is a block copolymer comprising a reaction product of a first polymer and A / ,A / -dimethylacrylamide, wherein the first polymer comprises a reaction product of a polyperoxide-monomer and hydroxyethyl acrylate.

[0065] In some embodiments, wherein the block copolymer is a reaction product of a first polymer and A / , / V-dimethylacrylamide, wherein the first polymer comprises a reaction product of a polyperoxide-monomer and hydroxyethyl acrylate, the block copolymer thus obtained is optionally further derivatized with one or more monomers comprising glycidyl methacrylate, (3,4- epoxycyclohexyl)methyl acrylate, glycidyl acrylate, 2-isocyanatoethyl acrylate, 2-isocyanatoethyl methacrylate, 1 ,3-butadiene monoepoxide, 1 ,2,-epoxy-4-vinylcyclohexane, allyl glycidyl ether, acrylic acid, methacrylate, methyl methacrylate, ethyl acrylate, ethyl methacrylate, 2-ethylhexyl acrylate, 2-hydroxyethyl acrylate, 2-hydroxyethyl methacrylate, hydroxybutyl acrylate, hydroxybutyl methacrylate, 2-aminoethyl methacrylate, sulfopropyl acrylate, sulfopropyl methacrylate, methacrylamide, 3-aminopropyl methacrylamide, N,N-dimethylacrylamide, aminoethyl methacrylamide, N-(3-methylpyridine)acrylamide, N-(2-(4- aminophenyl)ethyl)acrylamide, N-(4-aminobenzyl)acrylamide, N-(2-(4- imidazolyl)ethyl)acrylamide, or a combination thereof.

[0066] In some embodiments, wherein the block copolymer is a reaction product of a first polymer and hydroxyethyl acrylate, wherein the first polymer comprises a reaction product of a polyperoxide-monomer and A / ,A / -dimethylacrylamide, the block copolymer thus obtained isoptionally further derivatized with one or more monomers comprising glycidyl methacrylate, (3,4- epoxycyclohexyl)methyl acrylate, glycidyl acrylate, 2-isocyanatoethyl acrylate, 2-isocyanatoethyl methacrylate, 1 ,3-butadiene monoepoxide, 1 ,2,-epoxy-4-vinylcyclohexane, allyl glycidyl ether, acrylic acid, methacrylate, methyl methacrylate, ethyl acrylate, ethyl methacrylate, 2-ethylhexyl acrylate, 2-hydroxyethyl acrylate, 2-hydroxyethyl methacrylate, hydroxybutyl acrylate, hydroxybutyl methacrylate, 2-aminoethyl methacrylate, sulfopropyl acrylate, sulfopropyl methacrylate, methacrylamide, 3-aminopropyl methacrylamide, N,N-dimethylacrylamide, aminoethyl methacrylamide, N-(3-methylpyridine)acrylamide, N-(2-(4- aminophenyl)ethyl)acrylamide, N-(4-aminobenzyl)acrylamide, N-(2-(4- imidazolyl)ethyl)acrylamide, or a combination thereof.

[0067] In some embodiments of the block copolymers herein, the block copolymer is curable by ultraviolet (UV) light.

[0068] Provided herein is a block copolymer, comprising a reaction product of J5and J6, wherein:J5is a polymerizable monomer comprising a vinyl moiety and a functional group selected from an OH, NH2, SH, vinylene, and a second vinyl moiety;J6comprises a reaction product of J3and J7;J3is a polymerizable monomer comprising a vinyl moiety;J7comprises a reaction product of J4and hydrogen peroxide;J4comprises a reaction product of J1and J2;q is an integer ranging from 1 to 20;R28is a C1-20 alkylene;r is an integer ranging from 1 to 50.

[0069] Provided herein is a block copolymer, comprising a reaction product of J3and J7, wherein:J3is a polymerizable monomer comprising a vinyl moiety;J7comprises a reaction product of J4and hydrogen peroxide;J4comprises a reaction product of J1and J2;q is an integer ranging from 1 to 20;R28is a C1-20 alkylene;r is an integer ranging from 1 to 50.

[0070] In some embodiments of the block copolymer, the polymerizable monomer comprising a vinyl moiety is an acrylate or an acrylamide.

[0071] Provided is a compound selected from:R25is selected from hydrogen, C1-12 alkyl substituted with -OH, -SH, -NH2, pyrrolidone, or -COOH, C1-12 alkenyl, and aryl substituted with -OH, -SH, -NH2, pyrrolidone, or -COOH;R28is a C1-20 alkylene; c is an integer ranging from 1 to 5000; each m is independently an integer ranging from 1 to 20; each q is independently an integer ranging from 1 to 20; and r is an integer ranging from 1 to 50.General methods for preparation of polymers

[0072] In some embodiments, to prepare a polymer, two or more monomers and an initiator are dissolved in a solvent In general, any solvent that dissolves the two or more monomers and the initiator can be used. Solvents can comprise methanol / water, ethanol / water, isopropanol / water, dioxane / water, tetrahydrofuran / water, dimethylformamide / water, dimethyl sulfoxide and / or water, and combinations thereof. With carboxylic acid and hydroxyl containing monomers, a wider range of solvents can be utilized, including toluene, xylene, dimethyl sulfoxide, dioxane, tetrahydrofuran, methanol, ethanol, and dimethyl formamide.

[0073] Polymerization initiators can be used to start the polymerization of the monomers in the solution. The polymerization can be initiated by reduction-oxidation, radiation, heat, or any other method known in the art. Radiation polymerization of the monomer solution can be achieved with ultraviolet light or visible light with suitable initiators or ionizing radiation (e.g. electron beam or gamma ray) without initiators. Polymerization can be achieved by application of heat, either by conventionally heating the solution using a heat source such as a heating well, or by application of infrared light to the monomer solution.

[0074] In one embodiment, the polymerization initiator is azobisisobutyronitrile (A TRN) ora water soluble AIBN derivatives (2,2'-azobis(2- methylpropionamidine) dihydrochloride), or4,4'-azobis(4- cyanopentanoic acid). Other initiators can comprise N,N,N',N'-tetramethylethylenediamine, ammonium persulfate, benzoyl peroxides, and combinations thereof, including azobisisobutyronitriles. Concentrations of the initiator can range from about 0.25% to about 2% w / w of the mass of the monomers in solution.

[0075] The polymerization reaction can be performed at elevated temperatures, such as in the range from about 65°C to about 85°C. For example, in embodiments the polymerization reaction is performed at 65°C, 70°C, 75°C, 80°C, or 85°C. After the polymerization is completed, the polymer is recovered by precipitation in a non-solvent and dried under vacuum. The molecularweight of the copolymer can range from about 500 g / mole to about 100,000 g / mole, or from about 1 ,000-40,000 g / mole, about 500-1 ,000 g / mole, about 1 ,000-2,000 g / mole, about 2,000-3,000 g / mole, about 3,000-4,000 g / mole, about 4,000-5,000 g / mole, about 5,000-6,000 g / mole, about 6,000-8,000 g / mole, about 8,000-10,000 g / mole, about 10,000-15,000 g / mole, about 15,000- 20,000 g / mole, about 10,000-15,000 g / mole, about 15,000-20,000 g / mole, about 20,000-25,000 g / mole, about 25,000-30,000 g / mole, about 30,000-35,000 g / mole, about 35,000-40,000 g / mole, about 40,000-50,000 g / mole, about 50,000-60,000 g / mole, about 60,000-70,000 g / mole, about 70,000-80,000 g / mole, about 80,000-90,000 g / mole, about 90,000-100,000 g / mole, or any molecular weight in a range bounded by any of these values.

[0076] In embodiments, the base coat copolymer can have a characteristic viscosity when dissolved in solvent. Base coat copolymer dissolved in propylene glycol monomethyl ether acetate at 15% w / w can have viscosity ranging from about 2 cP (centipoise) to about 15 cP. In some embodiments, viscosity range can be from about 6 cP to about 13 cP.

[0077] In disclosed embodiments, following the selection of the base coat, reactive groups, such as acrylates and / or methacrylates, are added to the polymer via any convenient reactive moiety, such as hydroxyls, amines, or carboxylic acids, with a derivatization compound. In general, the derivatization compound can be a hetero-bifunctional compound. One moiety reacts with the hydroxyl, amine, and / or carboxylic acid groups of the copolymer. The other moiety is an acrylate or methacrylate group. Derivatization compounds can comprise acryloyl chloride, methacryloyl chloride, 2-isocyanatoethyl acrylate, 2-isocyanatoethyl methacrylate, acrylic acid N- hydroxysuccinimide ester, methacrylic acid N-hydroxysuccinimide ester, hetero-bifunctional polyethylene glycol) with acrylate and isocyanate groups, combinations thereof, and derivatives thereof.

[0078] In embodiments, to prepare the derivatized polymer, the polymer, derivatization compound, and any catalyst are dissolved in a solvent. In general, any solvent that dissolves the top coat polymer, derivatization agent, and the initiator can be used. Solvents can comprise aromatic and chlorinated solvents, including benzene, toluene, xylene, dichloromethane, chloroform, and combinations thereof.

[0079] When reacting a derivatization agent with a reactive moiety of the top coat polymer, the target derivatization can correspond to less than 2 groups per molecule. Additionally, the addition of a Lewis base as a catalyst can be used. Lewis bases can comprise triethylamine and pyridine, typically in a concentration of about 1 % to about 10%, or about 2% to about 9%, or about 4% to about 7%, of the moles of the derivatization compound added. The reaction proceeds at roomtemperature. After the derivatization is complete, the activated polymer is recovered by precipitation in a nonsolvent and dried under vacuum.

[0080] In an embodiment, by way of non-limiting example, synthesis of the top coat polymer begins with preparation of a diacid chloride J1of formulaThe diacid may be selected from ethanedioic acid, propanedioic acid; butanedioic acid, pentanedioic acid, hexanedioic acid, heptanedioic acid, octanedioic acid, 1 ,4-cyclohexanedicarboxylic acid, nonanedioic acid, decanedioic acid, undecanedioic acid, dodecanedioic acid, tridecanedioic acid, hexadecanedioic acid, heneicosanedioic acid, docosanedioic acid, or triacontanedioic acid.Diacid chloride J1is reacted with a compound J2of formulato provide apolyester comprising J4-1 of formula O O . The polyester forms the second block and is converted to a polyperoxide comprising J7-1 of formula O O m0 0 in the presence of hydrogen peroxide.Polymerization with a monomer of the third block provides a polymer comprising J6-1 of formulaFurther polymerization introduces the first block to provide a polymer comprising J8-1 of formula

[0081] Top coat polymers can have a characteristic viscosity when dissolved in solvent. Top coat polymer dissolved in methanol at 25% w / w can have viscosity ranging from about 2 cP to about15 cP. In some embodiments, viscosity range can be from about 6 cP to about 13 cP, or 8 cP to 11 cP, or the like.

[0082] Base Coat Solutions

[0083] After the base coat polymer is synthesized it is incorporated into a base coat solution. The base coating solution can comprise the solvent, base coat copolymer, initiator and optionally a surfactant. In general, any solvent or mixtures of solvents may be utilized, provided that the components can be dissolved into the solvent or solvent mixtures. Suitable solvents comprise water, alcohols, glycol ethers, aromatics, polar aprotic solvents, methanol, ethanol, isopropyl alcohol, 2-ethoxy ethanol, propylene glycol monomethyl ether acetate, benzene, toluene, xylene, dimethyl formamide, dimethyl sulfoxide, and combinations thereof. The base coat copolymer is dissolved into the selected solvent at a concentration ranging from about 0.2% w / w to about 35% w / w. In some embodiments, the concentration range is about 0.7% to about 1.2% w / w.

[0084] In one embodiment, initiators comprise Norrish Type I initiators, Norrish Type II initiators, and combinations thereof. The initiator concentration in the solvent ranges from about 0.1 % to about 6%, or about 0.5%. Examples of suitable Norrish Type I or free-radical photo-initiators are benzoin derivatives, methylolbenzoin and 4-benzoyl-1 ,3-dioxolane derivatives, benzilketals, a,a- dialkoxyacetophenones, a-hydroxy alkylphenones, a-aminoalkylphenones, acylphosphine oxides, bisacylphosphine oxides, acylphosphine sulphides, halogenated acetophenone derivatives, and the like. Commercial examples of suitable Norrish Type I photoinitiators are Irgacure 2959 (2-hydroxy-4'-(2-hydroxyethoxy)-2-methyl propiophenone), Irgacure 651 (benzildimethyl ketal or 2,2-dimethoxy-1,2-diphenylethanone) (Ciba-Geigy), Irgacure 184 (1- hydroxy-cyclohexyl-phenyl ketone as the active component (Ciba-Geigy), Darocur 1173 (2- hydroxy-2-methyl-1-phenylpropan-1-one as the active component) (Ciba-Geigy), Irgacure 907 (2- methyl-1-[4-(methylthio)phenyl]-2-morpholino propan-1-one) (Ciba-Geigy), Irgacure 369 (2- benzyl-2-dimethylamino-1-(4-morpholinophenyl)-butan-1-one as the active component) (Ciba- Geigy), Esacure KIP 150 (poly{2-hydroxy-2-methyl-1-[4-(lmethylvinyl)phenyl]propan-1-one}) (Fratelli Lamberti), Esacure KIP 100 F (blend of poly {2-hydroxy-2-methyl-1-[4-(1- methylvinyl)phenyl]propan-1-one} and 2-hydroxy-2-methyl-1-phenyl-propan-1-one) (Fratelli Lamberti), Esacure KTO 46 (blend of poly {2-hydroxy-2-methyl-1-[ 4-(1- methylvinyl)phenyl]propan-1-one}, 2,4,6-trimethylbenzoyldiphenyl-phosphine oxide, and methylbenzophenone derivatives) (Fratelli Lamberti), acylphosphine oxides such as Lucirin TPO (2,4,6-trimethylbenzoyl di phenyl phosphine oxide) (BASF), Irgacure 819 (bis(2,4,6- trimethylbenzoyl)-phenylphosphine-oxide) (Ciba-Geigy), Irgacure 1700 (25:75% blend of bis(2,6-dimethoxybenzoyl)2,4,4-trimethyl-pentyl phosphine oxide and 2-hydroxy-2-methyl-1-phenyl- propan-l-one) (Ciba-Geigy), and the like. Also, mixtures of type I photo-initiators can be used.

[0085] Norrish Type II photo-initiators that can be used in disclosed medical coating formulations can comprise aromatic ketones such as benzophenone, xanthone, derivatives of benzophenone (e.g. chlorobenzophenone), blends of benzophenone and benzophenone derivatives ( e.g. Photocure 81 , a 50 / 50 blend of 4-methyl-benzophenone and benzophenone), Michler's Ketone, Ethyl Michler's Ketone, thioxanthone and other xanthone derivatives like Quantacure ITX (isopropyl thioxanthone), benzil, anthraquinones (e.g. 2-ethyl anthraquinone), coumarin, or chemical derivatives or combinations of these photo initiators.

[0086] In embodiments, the base coat coating solution may also contain a surfactant. In general, any surfactant may be used. Disclosed surfactants suitable for use comprise sodium lauryl sulfate, Tween 20, Span 80, Triton X-100, Pluronic F68, Pluronic L-81 , combinations thereof, and derivatives thereof. In some embodiments, the optional surfactant is dissolved into the selected solvent at a concentration ranging from about 0.08% w / w to about 15% w / w.

[0087] Top Coat Solutions

[0088] Next, the top coat solution is prepared. In embodiments, the top coating solution is comprised of the solvent, top coat polymer, initiator and optionally a surfactant. In general, any solvent or mixtures of solvents may be utilized, provided that the components can be dissolved into the solvent or solvent mixtures. In embodiments, suitable solvents comprise water, alcohols, glycol ethers, aromatics, polar aprotic solvents, and combinations thereof. Preferred solvents comprise methanol, ethanol, isopropyl alcohol, 2-ethoxy ethanol, propylene glycol monomethyl ether acetate, benzene, toluene, xylene, dimethyl formamide, dimethyl sulfoxide, acetonitrile, and combinations thereof. In some embodiments, the top coat polymer is dissolved into the selected solvent at a concentration ranging from 5% w / w to 75% w / w or more, depending on the desired viscosity of the top coat solution. In some embodiments, the concentration of top coat copolymer is 29% w / w.

[0089] Initiators can comprise Norrish Type I initiators, Norrish Type II initiators, and combinations thereof. In some embodiments, the initiator concentration in the solvent ranges from about 0.1 % w / w to about 6% w / w. In some embodiments, the initiator concentration in the solvent is about 0.3% w / w. Examples of suitable Norrish Type I or free-radical photo-initiators are benzoin derivatives, methylolbenzoin and 4-benzoyl-1 ,3-dioxolane derivatives, benzilketals, a,a- dialkoxyacetophenones, a-hydroxy alkylphenones, a-aminoalkylphenones, acylphosphineoxides, bisacylphosphine oxides, acylphosphine sulphides, halogenated acetophenone derivatives, and the like.

[0090] Other suitable Norrish Type I photoinitiators are Irgacure 2959 (2-hydroxy-4'-(2- hydroxyethoxy)-2-methyl propiophenone), Irgacure 651 (benzildimethyl ketal or 2,2-dimethoxy- 1 ,2-diphenylethanone) (Ciba-Geigy), Irgacure 184 (1-hydroxycyclohexyl-phenyl ketone as the active component) (Ciba-Geigy), Darocur 1173 (2-hydroxy-2-methyl-1-phenylpropan-1-one as the active component) (Ciba-Geigy), Irgacure 907 (2-methyl-1-[4-(methylthio)phenyl]-2- morpholino propan-1-one) (CibaGeigy), Irgacure 369 (2-benzyl-2-dimethylamino-1-(4- morpholinophenyl)-butan-1-one as the active component) (Ciba-Geigy), Esacure KIP 150 (poly {2-hydroxy-2-methyl-1-[4-(1-methylvinyl)phenyl]propan-1-one}) (Fratelli Lamberti), Esacure KIP 100 F (blend of poly{2-hydroxy-2-methyl-1-[4-(1-methylvinyl)phenyl]propan-1-one} and 2- hydroxy-2-methyl-1-phenyl-propan-1-one) (Fratelli Lamberti), Esacure KTO 46 (blend of poly {2- hydroxy-2-methyl-1-[4-(1-methylvinyl)phenyl]propan-1-one}, 2,4,6-trimethylbenzoyldiphenyl- phosphine oxide, and methylbenzophenone derivatives) (Fratelli Lamberti), acylphosphine oxides such as Lucirin TPO (2,4,6-trimethylbenzoyl di phenyl phosphine oxide) (BASF), Irgacure 819 (bis(2,4,6-trimethylbenzoyl)-phenylphosphine-oxide) (Ciba-Geigy), Irgacure 1700 (25:75% blend of bis(2,6-dimethoxybenzoyl)-2,4,4-trimethyl-pentyl phosphine oxide, and 2-hydroxy-2-methyl-1- phenyl-propan-1-one) (Ciba-Geigy), and the like. Also, mixtures of type I photo-initiators can be used.

[0091] Norrish Type II photo-initiators that can be used comprise aromatic ketones such as benzophenone, xanthone, derivatives of benzophenone (e.g. chlorobenzophenone), blends of benzophenone and benzophenone derivatives (e.g. Photocure 81, a 50 / 50 blend of 4-methyl- benzophenone and benzophenone), Michler's Ketone, Ethyl Michler's Ketone, thioxanthone and other xanthone derivatives like Quantacure ITX (isopropyl thioxanthone), benzil, anthraquinones (e.g. 2-ethyl anthraquinone), coumarin, or chemical derivatives or combinations of these photoinitiators.

[0092] In embodiments, the top coat coating solution may also contain a surfactant. In general, any surfactant may be used. Suitable surfactants can comprise sodium lauryl sulfate, Tween 20, Span 80, Triton X-100, Pluronic F68, Pluronic L-81 , combinations thereof, and derivatives thereof. In some embodiments, the optional surfactant is dissolved into the selected solvent at a concentration ranging from about 0.08 % w / w to about 5% w / w.

[0093] Coating Medical Devices

[0094] In some embodiments, an article or a device is coated with the polymeric compositions described herein. In some embodiments, the article or the device has a surface. In some embodiments, the surface of the article or the device is coated with a base coat described herein. In some embodiments, the article or the device coated with the base coat is coated with a top coat described herein.Base Coat Application

[0095] To prepare an article for coating, the surface of the article is first treated with plasma. Then the surface is primed with the basecoat. The basecoat solution can consist of UV initiators, basecoat copolymer or compound, and surfactant that are dissolved in any suitable solvent. The solvent is preferably a low-boiling point one. The article is then dipped in the basecoat, drawn from the basecoat at a given speed, and cured under a suitable UV source.

[0096] In some embodiments, the catheter is first cleaned by a solvent wipe to remove any gross contamination from its surface. In general, any solvent can be used if it does not dissolve or degrade the catheter shaft. Such solvents can comprise glycol ethers, methyl ethyl ketone, chlorinated solvents, tetra hydrofuran, hexane, ethyl acetate and acetone. Following solvent cleaning, the catheter shaft can be plasma treated to further clean its surface. Plasmas derived from various gases can be used, but preferred gases are argon and oxygen. In some embodiments, both argon and oxygen plasmas may be utilized. With the catheter suitability cleaned, it is ready to be coated.

[0097] Sequential application and UV curing of the base coat followed by top coat to a selected urinary catheter can be done with a Harland PCX coating machine or equivalent. In embodiments, the coating machine is charged with base coat and top coat solutions. Next, the urinary catheter is placed in the coating machine above the coating solutions. The coating machine first dips the catheter into a tube filled with base coat. The catheter is then extracted at a constant rate of about 0.1 to about 10.0 cm / sec, such as about 5.0 cm / sec. After extraction, the catheter is exposed to ultraviolet radiation with a wavelength ranging from about 10 nm to about 400 nm. Combinations of wavelengths in this range will also provide a suitably cured base coat. Preferred wavelengths comprise about 254 nm and about 365 nm. The base coat cure time ranges from about 0.1 min to about 6 min such as about 0.5 min. After the base coat is cured, the coating machine dips the catheter into the top coat solution.Top Coat Application

[0098] After priming with the base coat, the surface is ready to be coated with the top coatsolution. The top coat solution can be made of UV initiators, top coat copolymer, and surfactants that are dissolved in a suitable solvent. A preferred solvent should have a low boiling point. The article is then dipped in the top coat solution, drawn from the top coat solution at a given speed, and cured under a UV source.

[0099] The catheter is typically drawn from the top coat solution at a constant rate of about 0.1 cm / sec to about 10.0 cm / sec, or at 0.6 cm / sec. Finally, the top coat is exposed to ultraviolet radiation ranging from about 10 nm to about 400 nm, or combinations of wavelengths in this range. Preferred wavelengths to suitably cure the top coat comprise about 254 nm and about 365 nm. The top coat cure time ranges from about 0.1 minutes to about 6 minutes, in some embodiments, about 5.5 minutes. The coating process is complete after the top coat cure time has elapsed.

[0100] In embodiments, following the coating process, the catheter may be washed in a solvent bath to remove unbound coating components such as initiator and surfactant. Any solvent may be used that does not degrade the coating or catheter. Suitable solvents can comprise ethanol, methanol, acetone, acetonitrile, propylene glycol methyl ether acetate, and combinations thereof. Catheters are washed by soaking in selected solvent for time ranging from 1 minute to 15 minutes. In embodiments, a preferred time is 5 minutes.

[0101] Accordingly, provided herein is a device wherein the copolymer described herein forms a top coat that is coated onto the device. In some embodiments, the top coat is covalently bound to a basecoat on the device. In some embodiments, the top coat is not covalently bound to a basecoat on the device.

[0102] In some embodiments, the device is a catheter, a stent, an ocular insert, or a surgical mesh.

[0103] Also provided herein is a method for treating a cardiovascular condition in a subject, the method comprising inserting the coated device described herein into the subject.

[0104] Provided is a method for preparing a coated device comprising applying a base coat to the device, applying a top coat comprising the copolymer described herein to the base-coated device, and curing the top coat with UV light.

[0105] In some embodiments, the base coat is UV-cured. In some embodiments, the base coat is not UV-cured (for example, may be therm o-cu red).

[0106] These and other embodiments are described in more detail below.Example 1Synthesis of polyester

[0107] To a 1000 ml_ reaction vessel with a removable top fitted with an overhead stirrer and an addition funnel was added sebacoyl chloride (181.2g, 757.7 mmol) under dry argon. The flask was placed in an oil bath (50°C) and allowed to warm up for 20 min. To the addition funnel was added triethylene glycol (56 g, 372.9 mmol). To the sebacoyl chloride was added triethylene glycol dropwise. After the addition was completed, the reaction was stirred for 3 hours at 50°C. To work up, hydrochloric gas was removed on a membrane pump and captured by aqueous sodium hydroxide solution. The polyester was obtained as a light yellow oily solid (204.7 g).Example 2Synthesis of polyperoxide ester

[0108] To a 500 mL jacketed reaction vessel with a removable top fitted with an addition funnel and an overhead stirrer were added H2O (214.1 g), NaOH (8.87 g, 187 mol), H2O2 (31 %, 10.6 mL, 93.5 mmol), and dioctylphosphate (0.658 g) sequentially. After all the sodium hydroxide was dissolved, the reaction vessel was attached to a -8 °C recirculating water bath and allowed to cool for 20 min. Oligoester acid chloride (62.4 g) was mixed in methyl ethyl ketone (12.5 g). This solution was added to the addition funnel and later added to the reaction dropwise. After 20 min of reaction, white solids in powder form began precipitating to the bottom of the vessel. To recover the product, the reaction was filtered on a medium porosity plastic-fritted funnel. The solid product was transferred to a beaker and washed with cold methanol followed by distilled water. The wash was performed four times total. The product was dried for 24 hours under reduced pressure to yield a white “wet” solid (109.4 g).Example 3Polymerization of glycidyl methacrylate with polyperoxide

[0109] To a 3-neck round bottom flask fitted with an addition funnel and a stir bar were added glycidyl methacrylate (35.5 mL) and benzene (120 mL). In a separate flask, suspend polyperoxide (1.98 g) in benzene (17 mL) into a thick white suspension. Add this suspension to the addition funnel. Sparge with argon both the glycidyl methacrylate solution and the polymer initiator solution for 2 hours. Place the round bottom flask into a 65°C oil bath and allow the content to warm up for 40 min. Add the content of the addition funnel into the monomer solution. 1.6 hours into polymerization, the product was collected by precipitation in methyl terf-butyl ether. Dissolve thesolid in dichloromethane and precipitate in methyl tert-butyl ether again. Collect the solid and dry under reduced pressure. Product is a white solid (12.6 g) and is used as an intermediate, to be used for further modification, such as in Example 4, and subsequently in Example 5.

[0110] Other intermediates are prepared according to the procedure described in this example by replacing the glycidyl methacrylate monomer with one or more monomers comprising (3,4- epoxycyclohexyl)methyl acrylate, glycidyl acrylate, 2-isocyanatoethyl acrylate, 2-isocyanatoethyl methacrylate, 1 ,3-butadiene monoepoxide, 1 ,2,-epoxy-4-vinylcyclohexane, allyl glycidyl ether, acrylic acid, methacrylate, methyl methacrylate, ethyl acrylate, ethyl methacrylate, 2-ethylhexyl acrylate, 2-hydroxyethyl acrylate, 2-hydroxyethyl methacrylate, hydroxybutyl acrylate, hydroxybutyl methacrylate, 2-aminoethyl methacrylate, sulfopropyl acrylate, sulfopropyl methacrylate, methacrylamide, 3-aminopropyl methacrylamide, N,N-dimethylacrylamide, aminoethyl methacrylamide, N-(3-methylpyridine)acrylamide, N-(2-(4- aminophenyl)ethyl)acrylamide, N-(4-aminobenzyl)acrylamide, N-(2-(4- imidazolyl)ethyl)acrylamide, or a combination thereof.Example 4Polymerization of N,N-dimethylacrylamide

[0111] To a 1000 mL jacketed reaction flask with a removable top fitted with an overhead stirrer were added A / ,A / -dimethylacrylamide (65.5 mL) and DMSO (500 mL). Dissolve polyperoxide- glycidyl methacrylate (or other monomer in place of glycidyl methacrylate) initiator (7g) in DMSO (68 mL). Sparge both the initiator solution and the / V, / V-dimethylacrylamide / DMSO solution for 2 hours. Place the 3-neck round bottom flask in 80°C oil bath and allow the content to warm up for 40 min. Add the initiator solution into the reaction with a funnel. Allow the reaction to proceed for 2 hours. The reaction mixture was converted to a clear gel an hour after the initiator was added.Example 5 Modification of the diblock copolymer

[0112] Added to the polymer prepared in Example 4 (50g) in dichloromethane (142.52 mL) were hydroxyethyl acrylate (4.97g), p-toluenesulfonic acid (61.4 mg), and monomethyl ether of hydroquinone (MEHQ) (24.8 mg). The polymer was collected by precipitation and dried under reduced pressure.Example 6Preparation of a coating solution

[0113] 144 g of the polymer prepared in Example 5 was dissolved in 900 ml_ of tetrahydrofuran with shaking, then 0.7 g of benzophenone and 0.7 g of 1 -hydroxycyclohexyl phenyl ketone were added. The components were thoroughly mixed and dissolved.Example 7 Coating of an article

[0114] A 17 cm length microcatheter with an external surface comprised of Grilamid was prepared for coating by first inserting a tightly fitting nitinol mandrel into the hollow inner lumen, then wiping the outer surface with acetone. To clean the surface of the microcatheter, the surface is first treated with oxygen plasma. The surface activation was confirmed by contact angle. An automated Harland PCX coating machine was used for coating and prepared by charging the machine with the solutions prepared in Example 6. The microcatheter prepared above was inserted into the machine for coating. The machine program dipped the microcatheter into coating solution and then extracted it at a rate of 0.1-1 cm / s. The microcatheter was then cured by UV radiation inside the Harland coating machine.Example 8Measurement of Lubricity

[0115] To determine the lubricity of the coating, microcatheter samples prepared in Example 7 were tested on an Instron 5943 fitted with a 5N static load cell. The top of the sample was fixed to the load cell by mechanical clamping. It was submerged in 37oC water bath while being pulled through a hydraulic clamp. Once the length of the pulling reached 10 cm, the hydraulic clamp opened, and the load cell with the sample was repositioned to the starting position, and the cycle was repeated 19 more times. The maximum dynamic friction force and average dynamic friction force at the 60 mm displacement mark were recorded. A maximum dynamic friction force below 40 gf is desirable.Example 9Polymerization of monomer with polyperoxide

[0116] To a 3-neck round bottom flask fitted with an addition funnel and a stir bar are added monomer [one or more chosen from monomers listed above in the second paragraph of example 3] (35.5 mL) and benzene (120 mL). In a separate flask, suspend polyperoxide (1.98 g) in benzene (17 mL) into a thick white suspension. Add this suspension to the addition funnel. Sparge withargon both the monomer solution and the polymer initiator solution for 2 hours. Place the round bottom flask into a 65°C oil bath and allow the content to warm up for 40 min. Add the content of the addition funnel into the monomer solution. 1.6 hours into polymerization, the product was collected by precipitation in methyl tert-butyl ether. Dissolve the solid in dichloromethane and precipitate in methyl tert-butyl ether again. Collect the solid and dry under reduced pressure. Product is a white solid and is used as an intermediate, to be used for further modification, such as in Example 10, and subsequently in Example 11.Example 10Polymerization of N,N-dimethylacrylamide

[0117] To a 1000 mL jacketed reaction flask with a removable top fitted with an overhead stirrer were added A / , / V-dimethylacrylamide (65.5 mL) and DMSO (500 mL). Dissolve polyperoxidemonomer initiator (7g, from Example 9) in DMSO (68 mL). Sparge both the initiator solution and the / V,A / -dimethylacrylamide / DMSO solution for 2 hours. Place the 3-neck round bottom flask in 80°C oil bath and allow the content to warm up for 40 min. Add the initiator solution into the reaction with a funnel. Allow the reaction to proceed for 2 hours. The reaction mixture was converted to a clear gel an hour after the initiator was added.Example 11 Modification of the diblock copolymer

[0118] Added to the polymer prepared in Example 10 (50g) in dichloromethane (142.52 mL) were hydroxyethyl acrylate (4.97g), p-toluenesulfonic acid (61.4 mg), and monomethyl ether of hydroquinone (MEHQ) (24.8 mg). The polymer was collected by precipitation and dried under reduced pressure.

[0119] Unless otherwise indicated, all numbers expressing quantities of ingredients, properties such as molecular weight, reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the present invention. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values set forth in the specific examplesare reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements.

[0120] The terms “a,” “an,” “the” and similar referents used in the context of describing the invention (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. Recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., “such as”) provided herein is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention otherwise claimed. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the invention.

[0121] Groupings of alternative elements or embodiments of the invention disclosed herein are not to be construed as limitations. Each group member may be referred to and claimed individually or in any combination with other members of the group or other elements found herein. It is anticipated that one or more members of a group may be included in, or deleted from, a group for reasons of convenience and / or patentability. When any such inclusion or deletion occurs, the specification is deemed to contain the group as modified thus fulfilling the written description of all Markush groups used in the appended claims.

[0122] Furthermore, numerous references have been made to patents and printed publications throughout this specification. Each of the above-cited references and printed publications are individually incorporated herein by reference in their entirety.

[0123] In closing, it is to be understood that the embodiments of the invention disclosed herein are illustrative of the principles of the present invention. Other modifications that may be employed are within the scope of the invention. Thus, by way of example, but not of limitation, alternative configurations of the present invention may be utilized in accordance with the teachings herein. Accordingly, the present invention is not limited to that precisely as shown and described.

Claims

1. CLAIMSWe claim:

1. A block copolymer comprising is a reaction product of: a first block comprising at least one polymerizable monomer comprising a vinyl moiety; a second block comprising a polyester which is a reaction product of at least one diacid and a polyalkylene glycol; and a third block comprising at least one polymerizable monomer comprising a vinyl moiety, wherein at least one monomer in the third block further comprises a C1-12 alkyl substituted with - OH, -SH, -NH2, pyrrolidone, or -COOH, or a C1.12 alkenyl, or an aryl substituted with -OH, -SH, - NH2, pyrrolidone, or -COOH; wherein the block copolymer is optionally further reacted with at least one polymerizable monomer comprising a vinyl moiety.

2. The block copolymer of claim 1 , wherein the first block comprises at least one monomer having a formula:whereinR23is H or C1-6 alkyl;R24comprises -R25comprises hydrogen (H), C1-12 alkyl substituted with -OH, -SH, -NH2, pyrrolidone, or -COOH, C1-12 alkenyl, or aryl substituted with -OH, -SH, -NH2, pyrrolidone, or -COOH; andR26and R27are independently selected from H and C1-6 alkyl, or R26and R27together with the nitrogen atom to which they are attached form a 5-7 membered heterocycle.

3. The block copolymer of claim 1 , wherein the second block comprises at least one monomer having a formula:whereinR6is a bond or C1-30 alkylenyl;R7is a bond, C1-30 alkylenyl, or C3-10 cycloalkylenyl; andR8is a bond or C1-30 alkylenyl; m is an integer ranging from 1 to 20; n is an integer ranging from 1 to 50; p is an integer ranging from 1 to 20.

4. The block copolymer of claim 1 , wherein the third block comprises at least one monomer having a formula:R25comprises from H, C1.12 alkyl substituted with -OH, -SH, -NH2, pyrrolidone, or -COOH, C1-12 alkenyl, or aryl substituted with -OH, -SH, -NH2, pyrrolidone, or -COOH; andR26and R27are independently selected from H and C1-6 alkyl, or R26and R27together with the nitrogen atom to which they are attached form a 5-7 membered heterocycle.

5. The block copolymer of claim 1 , having a formula:whereinR21and R23are independently selected from H and CH3;R25comprises H, C1-12 alkyl substituted with -OH, -SH, -NH2, pyrrolidone, or -COOH, C1-12 alkenyl, or aryl substituted with -OH, -SH, -NH2, pyrrolidone, or -COOH;R26and R27are independently selected from H and C1.6 alkyl, or R26and R27together with the nitrogen atom to which they are attached form a 5-7 membered heterocycle;R28is a C1-20 alkylene; a is an integer ranging from 1 to 5000; b is an integer ranging from 1 to 2500; c is an integer ranging from 1 to 5000; each q is independently an integer ranging from 1 to 20; and r is an integer ranging from 1 to 50.

6. The block copolymer of claim 1 , wherein when the block copolymer is further reacted with at least one polymerizable monomer comprising a vinyl moiety, the polymerizable monomer comprising a vinyl moiety is selected from an acrylate, an acrylamide, a methacrylate, a methacrylamide, or a monomer having a formula:whereinR25comprises H, C1-12 alkyl substituted with -OH, -SH, -NH2, pyrrolidone, or -COOH, C1-12 alkenyl, or aryl substituted with -OH, -SH, -NH2, pyrrolidone, or -COOH; andR26and R27are independently selected from H and C1-6 alkyl, or R26and R27together with the nitrogen atom to which they are attached form a 5-7 membered heterocycle.

7. The block copolymer of claim 5, wherein the ratio of a:c in the block copolymer ranges from about 60: 1 to about 10:1.

8. The block copolymer of claim 5, wherein the ratio of b:c in the block copolymer ranges from about 0.01 :1 to about 1 :1.

9. The block copolymer of claim 1 , the ratio of the at least one diacid to polyalkylene glycol ranges from about 1:1 to about 2:1.

10. The block copolymer of claim 1 , wherein the first block comprises at least one of glycidyl acrylate, glycidyl methacrylate, acrylic acid, methacrylate, methyl methacrylate, ethyl acrylate, ethyl methacrylate, 2-ethylhexyl acrylate, 2-hydroxyethyl acrylate, 2-hydroxyethyl methacrylate, hydroxybutyl acrylate, hydroxybutyl methacrylate, 2-aminoethyl methacrylate, sulfopropyl acrylate, sulfopropyl methacrylate, methacrylamide, 3-aminopropyl methacrylamide, N,N- dimethylacrylamide, aminoethyl methacrylamide, N-(3-methylpyridine)acrylamide, N-(2-(4- aminophenyl)ethyl)acrylamide, N-(4-aminobenzyl)acrylamide, N-(2-(4- imidazolyl)ethyl)acrylamide, or any combination thereof.

11. The block copolymer of claim 1 , wherein the at least one diacid in the second block comprises ethanedioic acid, propanedioic acid; butanedioic acid, pentanedioic acid, hexanedioic acid, heptanedioic acid, octanedioic acid, 1 ,4-cyclohexanedicarboxylic acid, nonanedioic acid, decanedioic acid, undecanedioic acid, dodecanedioic acid, tridecanedioic acid, hexadecanedioic acid, heneicosanedioic acid, docosanedioic acid, triacontanedioic acid, or a combination thereof.

12. The block copolymer of claim 1, wherein the at least one polyalkylene glycol in the second block comprises polyethylene glycol, polypropylene glycol and polybutylene glycol, or any combination thereof.

13. The block copolymer of claim 1, wherein the third block comprises at least one of glycidyl acrylate, glycidyl methacrylate, acrylic acid, methacrylate, methyl methacrylate, ethyl acrylate, ethyl methacrylate, 2-ethylhexyl acrylate, 2-hydroxyethyl acrylate, 2-hydroxyethyl methacrylate, hydroxybutyl acrylate, hydroxybutyl methacrylate, 2-aminoethyl methacrylate, sulfopropyl acrylate, sulfopropyl methacrylate, methacrylamide, 3-aminopropyl methacrylamide, N,N- dimethylacrylamide, aminoethyl methacrylamide, N-(3-methylpyridine)acrylamide, N-(2-(4- aminophenyl)ethyl)acrylamide, N-(4-aminobenzyl)acrylamide, N-(2-(4- imidazolyl)ethyl)acrylamide, or any combination thereof.

14. The block copolymer of claim 1, having a formula:whereinR21and R23are independently selected from H and CH3;R25comprises H, C1-12 alkyl substituted with -OH, -SH, -NH2, pyrrolidone, or -COOH, C1-12 alkenyl, or aryl substituted with -OH, -SH, -NH2, pyrrolidone, or -COOH;R26and R27are independently selected from H and Ci.6alkyl, or R26and R27together with the nitrogen atom to which they are attached form a 5-7 membered heterocycle;R28is a C1-20 alkylene; a is an integer ranging from 1 to 5000; b is an integer ranging from 1 to 2500; c is an integer ranging from 1 to 5000; each q is independently an integer ranging from 1 to 20; and r is an integer ranging from 1 to 50.

15. The block copolymer of claim 1 , wherein the block copolymer is curable by ultraviolet (UV) light.

16. A medical device, comprising: a surface, wherein the surface of the device is coated with a base coat; wherein the device coated with the base coat is coated with a top coat; and wherein the top coat comprises the block copolymer of any one of claims 1-15.

17. The medical device of claim 16, wherein the base coat is a polymer comprising tetra hydrofurfuryl acrylate, 3-hydroxypropylacrylate, tris[2-(3- mercaptopropionyloxy)ethyl]isocyanurate or a combination thereof.

18. The medical device of one of claims 16-17, wherein the device is a catheter, a stent, an ocular insert, or a surgical mesh.

19. Use of the medical device of any one of claims 16-18 for treating a cardiovascular condition in a subject in need thereof, comprising inserting the coated device into the subject.

20. A method for preparing a coated medical device, the method comprising applying a base coat to a device; applying a top coat comprising the block copolymer of one of claims 1-15 to the basecoated device; and curing the top coat with UV light.

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