Copolymer, composition, coated device, coated medical device, and method for producing coated medical device

Abstract

To provide a copolymer capable of imparting, in addition to sufficient hydrophilicity and lubricity on the surface of a device, a property of suppressing protein adhesion.SOLUTION: The present invention provides a copolymer comprising the following monomer components (A), (B), and (C): (A) a compound having a zwitterion; (B) a compound represented by a specific chemical structural formula, and (C) an acrylamide derivative.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to copolymers, compositions, coated devices, coated medical devices, and methods for making coated medical devices. [Background technology]

[0002] For various devices used daily, not only are materials appropriately selected depending on their application, but surface modification is also sometimes required. For example, medical devices are made of soft materials such as silicone rubber and hydrogels, or hard materials such as metals and glass, depending on the application.

[0003] When a medical device is inserted into a living body or attached to a living surface, it is important to improve the biocompatibility of the device in order to suppress inflammatory reactions and side effects. Therefore, if the surface of the medical device is modified to impart excellent properties such as hydrophilicity, slipperiness, or antifouling properties to the surface of the medical device, it can be expected to improve the user's experience (reduced discomfort) and alleviate symptoms.

[0004] A known method for modifying the surface of a medical device is to autoclave sterilize the medical device in a solution of pH 6 to 9 containing a copolymer of a compound having an amide group, such as N,N-dimethylacrylamide or vinylpyrrolidone, to form a coating on the surface, thereby improving the usability of the medical device (Patent Documents 1 to 4). [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Patent No. 5154231 [Patent Document 2] Japanese Patent Application Laid-Open No. 2012-8854 [Patent Document 3] Japanese Patent Application Laid-Open No. 2010-508563 [Patent Document 4] Japanese Patent Application Publication No. 2017-176821 Summary of the Invention [Problem to be solved by the invention]

[0006] However, the inventions disclosed in Patent Documents 1 to 4 involve complicated surface treatment procedures, and none of them can impart sufficient hydrophilicity, slipperiness, etc. to the surface of a medical device, nor can they impart protein adhesion inhibitory properties. Furthermore, coating methods that utilize interactions through hydrophobic groups have the problem of a large difference in refractive index between the copolymer coating layer and the lens surface, causing cloudiness.

[0007] Therefore, an object of the present invention is to provide a copolymer that can impart sufficient hydrophilicity and lubricity to the surface of a device, as well as protein adhesion inhibitory properties. [Means for solving the problem]

[0008] In order to achieve the above object, the present invention provides a copolymer containing, as monomer components, a compound (A) having a zwitterion, a compound (B) represented by the following general formula (I), and an acrylamide derivative (C):

[0009] [ka]

[0010] [In the general formula (I), m is an average value and represents an integer of 1 to 200; R 1 represents a hydrogen atom or a methyl group, X represents an oxygen atom, NA or NA2 (where N represents a nitrogen atom, A represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms), and Y represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.] [Effects of the Invention]

[0011] According to the present invention, it is possible to provide a copolymer that can impart excellent hydrophilicity, slipperiness, and biocompatibility based on the inhibition of protein adhesion to the surface of a medical device without requiring complicated operations. DETAILED DESCRIPTION OF THE INVENTION

[0012] The copolymer of the present invention is required to contain, as monomer components, a compound (A) having a zwitterion, a compound (B) represented by the following general formula (I), and an acrylamide derivative (C).

[0013] [ka]

[0014] [In the general formula (I), m is an average value and represents an integer of 1 to 200; R 1 represents a hydrogen atom or a methyl group, X represents an oxygen atom, NA or NA2 (where N represents a nitrogen atom, A represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms), and Y represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.] The copolymer of the present invention may be crosslinked or non-crosslinked. In the case of a non-crosslinked copolymer, it may be linear or branched, but from the viewpoint of ease of production, a linear copolymer is preferred. The copolymer of the present invention may be any of a random copolymer, an alternating copolymer, a block copolymer, and a graft copolymer, but from the viewpoint of ease of production, a random copolymer is preferred.

[0015] The "monomer components" used as raw materials for the copolymer of the present invention refer to low-molecular-weight compounds that can be polymerized and / or crosslinked using a photopolymerization initiator and / or a thermal polymerization initiator. Furthermore, the term "a copolymer containing the above-mentioned (A), (B), and (C) as monomer components" means that the copolymer contains structures derived from the above-mentioned monomer components (A), (B), and (C).

[0016] Monomer component (A), i.e., a "compound having a zwitterion," refers to a compound having both a positive charge and a negative charge in one molecule, such as sulfobetaine, carboxybetaine, phosphobetaine (phosphorylcholine), dimethylamine oxide, dimethylsulfonylpropionate, heparin, or chondroitin sulfate. Compounds partially corresponding to these compounds include, for example, 2-[[2-(methacryloyloxy)ethyl]dimethylammonio]acetic acid, 3-[[2-(methacryloyloxy)ethyl]dimethylammonio]propanoic acid (hereinafter referred to as "CBMA"), 3-[(3-acrylamidopropyl)dimethylammonio]propanoic acid (CBAA), 3-[[2-(methacryloyloxy)ethyl]dimethylammonio]propane-1-sulfonic acid (SBMA), 4-[[2-(methacryloyloxy)ethyl]dimethylammonio]butane-1-sulfonic acid, 3- Examples include [[2-(acryloyloxy)ethyl]dimethylammonio]propane-1-sulfonic acid (SPDA), 2-methacryloyloxyethyl phosphorylcholine (MPC), bis[2-(methacryloyloxy)ethyl](methyl)ammonio]propane-1-sulfonic acid, 3-[(3-methacrylamidopropyl)dimethylammonio]propane-1-sulfonic acid, 4-[(3-methacrylamidopropyl)dimethylammonio]butane-1-sulfonic acid, and 3-[(3-acrylamidopropyl)dimethylammonio]propane-1-sulfonic acid.

[0017] The alkyl group having 1 to 5 carbon atoms or the alkyl group having 1 to 4 carbon atoms that may be contained in the monomer component (B), i.e., the compound represented by the general formula (I), may be linear or branched. When the resulting coated device is an ophthalmic lens made of a hydrogel, m in the general formula (I) is preferably 2 to 30, more preferably 9 to 30, and even more preferably 20 to 30, from the viewpoint of exhibiting high durability and hydrophilicity.

[0018] Examples of the monomer component (B), i.e., the "compound represented by general formula (I)" above, include methoxypolyethylene glycol monomethacrylate (hereinafter referred to as "mPEG methacrylate"), methoxypolyethylene glycol acrylate (mPEG acrylate), ethylene glycol monomethacrylate, ethylene glycol acrylate, polyethylene glycol monomethacrylate (PEG methacrylate), and polyethylene glycol acrylate (PEG acrylate).

[0019] Examples of the monomer component (C), i.e., the "acrylamide derivative", include acrylamide, N-isopropylacrylamide, N,N-dimethylacrylamide (hereinafter referred to as "DMAA"), N,N-diethylacrylamide, N-methyl-N-ethylacrylamide, and N,N-di(hydroxyethyl)acrylamide, and from the viewpoint of polymerization stability, DMAA is preferred.

[0020] The proportions of the monomer components (A), (B), and (C) in the copolymer of the present invention greatly affect the temperature responsiveness of the copolymer, so that the proportion of compound (A) is preferably 1 to 40 mol %, the proportion of compound (B) is preferably 1 to 35 mol %, and the proportion of compound (C) is preferably 25 to 98 mol %. From the viewpoint of further improving durability, the proportion of compound (A) is preferably 1 to 35 mol %.

[0021] The copolymer of the present invention can be produced by polymerizing and / or crosslinking the monomers containing the monomer components (A), (B) and (C) using a photopolymerization initiator and / or a thermal polymerization initiator.

[0022] Examples of the thermal polymerization initiator include peroxides and azo compounds. The thermal polymerization initiator may be selected from those having optimal decomposition characteristics at the desired reaction temperature, but generally, azo compounds or peroxides with a 10-hour half-life temperature of 40 to 120°C are preferred.

[0023] More specifically, for example, 2,2'-azobis(isobutyronitrile) (AIBN), 2,2'-azobis(2-methylbutyronitrile), 2,2'-azobis(2,4-dimethylvaleronitrile), 1,1'-azobis(cyclohexane-1-carbonitrile), 2,2'-azobis[2-(2-imidazolin-2-yl)propane], 2,2'-azobis(2-methylpropionamidine) dihydrochloride (hereinafter referred to as "V-50"), 2,2'-azobis[N-(2- carboxyethyl)-2-methylpropionamidine], 2,2'-azobis[2-methyl-N-(2-hydroxyethyl)propionamide], 2,2'-azobis(N-butyl-2-methylpropionamide), 2,2'-azobis(2-methylpropionate)dimethyl, 4,4'-azobis(4-cyanovaleric acid), tert-butyl hydroperoxide, cumene hydroperoxide, di-tert-butyl peroxide, or benzoyl peroxide.

[0024] Examples of the photopolymerization initiator include aromatic α-hydroxyketones, alkoxyoxybenzoins, acetophenones, carbonyl compounds such as acylphosphine oxides or bisacylphosphine oxides, tertiary amines plus diketones, peroxides, azo compounds, sulfur compounds, halogen compounds, and metal salts.

[0025] More specifically, examples include 1-hydroxycyclohexyl phenyl ketone, 2-hydroxy-2-methyl-1-phenyl-propan-1-one, bis(2,6-dimethoxybenzoyl)-2,4,4-trimethylpentylphosphine oxide (DMBAPO), bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide (Irgacure (registered trademark) 819), 2,4,6-trimethylbenzyldiphenylphosphine oxide, and 2,4,6-trimethylbenzoyldiphenylphosphine oxide, and combinations of benzoin methyl ether or camphorquinone with ethyl 4-(N,N-dimethylamino)benzoate.

[0026] These polymerization initiators may be used alone or in combination, but in order to obtain a copolymer with a desired molecular weight while appropriately promoting the polymerization and crosslinking of the monomer components, the proportion of the polymerization initiator in the polymerization mixture is preferably 5% by mass or less.

[0027] Here, the term "polymerization mixture" refers to a mixture obtained by dissolving each monomer component for obtaining a copolymer, a polymerization initiator, and a chain transfer agent that may be added as needed in a solvent.

[0028] Examples of the solvent for obtaining the polymerization mixture include water, alcohol-based solvents such as methanol, ethanol, propanol, 2-propanol, butanol, 2-butanol, tert-butanol, tert-amyl alcohol, 3,7-dimethyl-3-octanol, ethylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, and polyethylene glycol; aromatic hydrocarbon-based solvents such as benzene, toluene, and xylene; aliphatic hydrocarbon-based solvents such as hexane, heptane, octane, decane, petroleum ether, kerosene, ligroin, and paraffin; alicyclic hydrocarbon-based solvents such as cyclopentane, cyclohexane, and ethylcyclohexane; ketone-based solvents such as acetone, methyl ethyl ketone, and methyl isobutyl ketone; ester-based solvents such as ethyl acetate, butyl acetate, amyl acetate, ethyl lactate, methyl benzoate, and ethylene glycol diacetate; and ether-based solvents such as diethyl ether, tert-butyl methyl ether, tetrahydrofuran, dioxane, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, triethylene glycol dimethyl ether, tetraethylene glycol dimethyl ether, and polyethylene glycol dimethyl ether. These solvents may be used alone or in combination. However, from the viewpoint of being less likely to inhibit radical polymerization, water, methanol, tert-butanol, tert-amyl alcohol, 3,7-dimethyl-3-octanol, tetrahydrofuran, or a mixed solvent thereof is preferred, and water is more preferred.

[0029] The total proportion of the monomer components in the polymerization mixture is preferably 1 to 80% by mass, more preferably 3 to 30% by mass, in order to obtain a copolymer with a desired molecular weight while appropriately suppressing runaway due to the heat of polymerization.

[0030] The reaction temperature when polymerizing and / or crosslinking the monomers in the polymerization mixture may be selected depending on the decomposition temperature of the polymerization initiator, the boiling points of the solvent and monomers, the reaction time, etc., but in order to obtain the desired copolymer in good yield, it is preferably 20 to 180° C., more preferably 50 to 150° C., and even more preferably 60 to 120° C. Furthermore, the reaction time may be selected depending on the type and concentration of the polymerization initiator and monomers used, the reaction temperature, etc., but in order to obtain the desired copolymer in good yield, it is preferably 1 to 48 hours, more preferably 2 to 24 hours, and even more preferably 3 to 12 hours.

[0031] The composition of the present invention is required to contain the copolymer of the present invention and a solvent, and can be used to obtain the coated device of the present invention by coating at least a part of the surface of the device with the copolymer of the present invention.

[0032] Examples of the solvent contained in the composition of the present invention include the same solvents as those used to obtain the above-mentioned "polymerization mixture."

[0033] The surface of a device can be coated with the copolymer of the present invention by physically contacting the composition of the present invention with the surface of the device. That is, the method for producing a coated medical device of the present invention requires a coating step in which the composition of the present invention is brought into contact with the surface of a medical device to obtain a coated medical device.

[0034] For example, when the medical device is an ophthalmic lens, the surface of the ophthalmic lens can be coated with the copolymer of the present invention by sealing the composition of the present invention and the ophthalmic lens in a container, bringing them into contact with each other, and then heat-treating them (coating step).

[0035] Examples of the heat treatment method include a high-pressure steam method, irradiation with electromagnetic waves such as visible light, infrared rays, or microwaves, an electric heating method, an electromagnetic induction heating method, a dry heat method, and a flame method. From the viewpoint of improving hydrophilicity and slipperiness and shortening the production process, the high-pressure steam method using an autoclave is preferred.

[0036] The heating temperature in the heat treatment is preferably 20 to 200°C, more preferably 80 to 180°C, even more preferably 100 to 170°C, and particularly preferably 110 to 150°C, in order to obtain a coated medical device surface that exhibits good hydrophilicity and slipperiness while maintaining the strength of the medical device itself.

[0037] The heating time in the heat treatment is preferably 5 to 600 minutes, more preferably 10 to 400 minutes, and even more preferably 15 to 300 minutes, in order to obtain a coated medical device surface that exhibits good hydrophilicity and slipperiness while maintaining the strength of the medical device itself.

[0038] The initial pH of the composition of the present invention is preferably 2.0 to 10.0, more preferably 2.5 to 9.0, and even more preferably 4.5 to 8.5, since the composition does not become turbid and a medical device having good transparency and surface hydrophilicity and slipperiness can be obtained. A buffer may be added to the composition of the present invention to facilitate fine adjustment of the pH.

[0039] Examples of buffering agents include borates such as boric acid or sodium borate, citrates such as citric acid or potassium citrate, bicarbonates such as sodium bicarbonate, phosphates such as NaHPO, NaHPO, or KHPO, TRIS (tris(hydroxymethyl)aminomethane), 2-bis(2-hydroxyethyl)amino-2-(hydroxymethyl)-1,3-propanediol, bis-aminopolyol, triethanolamine, ACES (N-(2-acetamido)-2-aminoethanesulfonic acid), BES (N,N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid), H Examples of the buffer include EPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), MES (2-(N-morpholino)ethanesulfonic acid), MOPS (3-[N-morpholino]-propanesulfonic acid), PIPES (piperazine-N,N'-bis(2-ethanesulfonic acid), TES (N-[tris(hydroxymethyl)methyl]-2-aminoethanesulfonic acid), and salts thereof. In order to achieve a desired pH, the proportion of the buffer in the composition of the present invention is preferably 0.001 to 2.000 mass%, more preferably 0.010 to 1.000 mass%, and even more preferably 0.050 to 0.300 mass%.

[0040] The coated medical device obtained by the above coating process may be further subjected to other treatments, such as a treatment of repeating the same coating process as above, a treatment of contacting the surface of the coated medical device with a solvent or buffer solution not containing the copolymer of the present invention and then similarly heating the device, irradiation, an LbL (Layer by Layer) treatment in which copolymers having opposite charges are alternately coated one layer at a time, a crosslinking treatment with metal ions, or a chemical crosslinking treatment.

[0041] The coated device of the present invention requires that at least a portion of the surface of the device is coated with the copolymer of the present invention.

[0042] Examples of the device include medical devices such as ophthalmic lenses, skin covering materials, wound covering materials, skin protective materials, cutaneous drug carriers, infusion tubes, gas transport tubes, drainage tubes, blood circuits, covering tubes, catheters, stents, sheath biosensor chips, heart-lung machines, endoscope covering materials, measuring instrument probes or measuring instrument nozzles, etc. Among these, application to ophthalmic lenses and stents, which have a high demand for the effects of the present invention, is preferred.

[0043] The material of the medical device may be any of water-containing materials such as silicone hydrogel or hydrogel, low-water-containing soft materials or low-water-containing hard materials with a water content of 10% by mass or less, or non-water-containing materials such as acrylic resins such as polymethyl methacrylate, silicone materials with siloxane bonds, metals such as aluminum, glass, etc. Among these, hydrogels are preferred because of their excellent ability to inhibit protein adhesion.

[0044] When the medical device is a contact lens, the low water content soft material or low water content hard material is preferably a material containing silicon atoms, which exhibits high oxygen permeability that allows sufficient oxygen to be supplied to the cornea.

[0045] The low water content hard material is preferably a low water content hard material that falls into the contact lens category defined by the US Food and Drug Administration (FDA).

[0046] Such low-water-absorbent hard materials are preferably polymers having silicon atoms such as siloxane bonds in the main chain and / or side chain, and more preferably homopolymers using highly oxygen-permeable tris(trimethylsiloxy)silylpropyl methacrylate, polydimethylsiloxane having double bonds at both ends, or silicone-containing acrylate or silicone-containing methacrylate, or copolymers of these with other monomers.

[0047] Specifically, the low water content hard material is preferably selected from the group consisting of neofocon, pasifocon, telefocon, silafocon, paflufocon, petrafocon, and fluorofocon. Among them, neofocon, pasifocon, telefocon, and silafocon are more preferred because they exhibit good lipid adhesion inhibition and antifouling properties, neofocon, pasifocon, and telefocon are even more preferred, and neofocon is particularly preferred.

[0048] When the medical device is other than a contact lens, the low water-absorbent hard material is preferably polyethylene, polypropylene, polysulfone, polyetherimide, polystyrene, polymethyl methacrylate, polyamide, polyester, epoxy resin, polyurethane, or polyvinyl chloride. Among these, polysulfone, polystyrene, polymethyl methacrylate, polyurethane, or polyamide is more preferred, and polymethyl methacrylate is even more preferred, as they exhibit good lipid adhesion inhibition and antifouling properties.

[0049] Examples of low-water-content soft materials include the material disclosed in WO 2013 / 024799, which has a water content of 10% by mass or less, an elastic modulus of 100 to 2,000 kPa, and a tensile elongation of 50 to 3,000%, and elastofilcon. [Example]

[0050] The present invention will be specifically explained below with reference to examples, but the present invention is not limited to these. First, analytical methods and evaluation methods used in the examples will be described.

[0051] <Composition of phosphate buffer solution> The phosphate buffer solution used had the following composition: KCl: 0.2 g / L, KH2PO4: 0.2 g / L, NaCl: 8.0 g / L, Na2HPO4: 1.2 g / L, EDTA: 0.5 g / L. <Hydrophilicity> (liquid film retention time) A device was immersed in the solution (composition) in a container and heated in an autoclave at 121°C for 30 minutes (hereinafter referred to as "heat processing"), and then allowed to cool to room temperature (20-23°C). The coated device (or devices) was then lifted from the solution in the container and held in the air with its length aligned with gravity. The time from when the device began to be held in the air until part of the liquid film covering the device surface broke was visually observed, and the average of N=3 values ​​was evaluated according to the following criteria. The maximum measurement value was 120 seconds. "Part of the liquid film breaks" refers to a state in which the liquid film on the device surface can no longer maintain its shape, and part of the device surface is no longer covered by the liquid film. A: The liquid film on the surface is maintained for more than 60 seconds. B: The liquid film on the surface disappears in 50 to 60 seconds. C: The liquid film on the surface disappears in 20 to 50 seconds. D: The liquid film on the surface disappears in 5 to 20 seconds. E: The liquid film on the surface disappears instantly (less than 5 seconds).

[0052] <Hydrophilicity after immersion in fresh phosphate buffer solution for 24 hours> (Liquid film retention time after 24 hours) To eliminate the influence of insufficiently adsorbed copolymer on the device surface, the coated device or devices after heat processing were left to stand in 4 mL of fresh phosphate buffer solution (hereinafter "PBS") in a glass vial at room temperature for 24 hours. The coated medical device or medical device was then removed from the PBS in the glass vial and used as a sample (hereinafter "Sample S"), which was evaluated in the same manner as for "hydrophilicity" above.

[0053] <Slippery> The above sample S was prepared separately, and a sensory evaluation was carried out when it was rubbed five times with a finger (N=1), and the evaluation was made according to the following criteria. A: Excellent slipperiness (fingers glide smoothly over the surface of Sample S with no resistance whatsoever). B: Fairly excellent slipperiness (somewhere between A and C). C: Moderately slippery (a finger slides across the surface of Sample S with almost no resistance). D: Almost no slipperiness (somewhere between C and E). E: No slipperiness (fingers do not slide easily on the surface of Sample S, and a large resistance is felt).

[0054] <Evaluation of mucin adhesion amount> For contact lens test samples, test specimens measuring 5 mm wide (at the smallest point) and 14 mm long were cut from the device and coated device using a die. A 0.1% by mass mucin aqueous solution was prepared using Mucin, Bovine Submaxillary Gland (Millipore; Catalog No. 499643) as the mucin, and the test specimens were immersed in the solution at 37°C for 104 hours. These specimens were designated Sample M and Coated Sample M. Blank samples were also immersed under the same conditions using PBS instead of the mucin aqueous solution. These specimens were designated Sample P and Coated Sample P. After immersion, the samples were washed twice with PBS and then immersed in 1 mL of blocking buffer (ThermoFisher Scientific 37570) and incubated at room temperature for 1 hour. After incubation, the samples were washed twice with PBS and then immersed in 1 mL of WGA (Vector Laboratories Biotinylated Wheat Germ Agglutinin) diluted 500-fold with PBS, followed by further incubation at room temperature for 1 hour. After the second incubation, the samples were washed twice with PBS and then immersed in 500 μL of HRP-streptavidin (Sigma-Aldrich) diluted 500-fold with PBS and incubated at room temperature for 1 hour. After the third incubation, the samples were washed twice with PBS and then 250 μL of TMB (3,3',5,5'-Tetramethylbendine (TMB) substrate) solution (Thermo Scientific) was added and incubated at room temperature for 30 minutes. The samples were then removed, 125 μL of 4 M sulfuric acid was added, and the absorbance at 450 nm was measured using a microplate reader (Molecular Devices Japan, SpectraMax M5). The amount of mucin attached (%) was calculated as shown in Equation 1. These procedures were repeated four times, and the average value was used as the amount of mucin attached. Mucin adhesion amount (%) = (As - Asb) × 100 / (Ac - Acb) (Equation 1) As: absorbance of sample M or coated sample M Asb: absorbance of sample P or coated sample P Ac: absorbance of sample M Acb: absorbance of sample P <Droplet contact angle> The contact angle was measured using a contact angle measuring device (sessile drop method) Dropmaster DM500 (Kyowa Interface Science Co., Ltd.). Specifically, after wiping off the moisture from the surface of the coated device (or device), the device was placed on a hemispherical polypropylene plate with a diameter of 14 mm to prepare a sample. The sample was set in the contact angle measuring device, and phosphate buffer solution was dropped onto it to measure the droplet contact angle. The amount of the dropped phosphate buffer solution was 1 μL. The droplet contact angle was determined as the average of the contact angles measured 1 second and 30 seconds after dropping (N=3).

[0055] <Droplet contact angle (droplet contact angle X) after immersion in fresh phosphate buffer solution (PBS) for 24 hours> The above sample was prepared separately and evaluated in the same manner as in the "droplet contact angle" above.

[0056] (Synthesis Example 1) The monomer components and solvents listed in Table 1 were placed in a four-neck flask, and ultrasonic degassing and nitrogen substitution were performed five times each to remove dissolved oxygen. 0.0027 g of a polymerization initiator (V-50) was then added at 65° C., and the mixture was stirred for 4 hours at 70° C. After stirring, the four-neck flask was air-cooled to obtain an aqueous solution of copolymer 1.

[0057] (Synthesis Examples 2 to 8) Aqueous solutions of copolymers 2 to 8 were obtained in the same manner as in Synthesis Example 1, except that the monomer components and solvents were as shown in Table 1.

[0058] [Table 1]

[0059] [Example 1] The "device" used was a commercially available hydrogel lens "Medalist 1day Plus" (registered trademark) (hilafilconB manufactured by Bausch & Lomb) whose main component is 2-hydroxyethyl methacrylate. Copolymer 1 was added to PBS to a concentration of 0.3% by mass to obtain Composition 1. 3 mL of Composition 1 was then transferred to a glass vial, and the device was immersed in the composition and heated in an autoclave at 121°C for 30 minutes to obtain a coated device. The results of evaluating the obtained coated device using the above method are shown in Table 2.

[0060] [Examples 2 to 4] Coated devices were obtained in the same manner as in Example 1, except that copolymers 2 to 4 were used instead of copolymer 1 and compositions 2 to 4 were used instead of composition 1. The results of evaluating the obtained coated devices by the above-mentioned methods are shown in Table 2.

[0061] [Comparative Example 1] A device was obtained in the same manner as in Example 1, except that a phosphate buffer solution was used instead of Composition 1. The obtained device was evaluated by the above-mentioned method, and the results are shown in Table 2.

[0062] [Comparative Examples 2 to 5] Coated devices were obtained in the same manner as in Example 1, except that copolymers 5 to 8 were used instead of copolymer 1 and compositions 5 to 8 were used instead of composition 1. The results of evaluating the obtained coated devices by the above-mentioned methods are shown in Table 2.

[0063] [Table 2]

[0064] Compared with Comparative Example 1, Examples 1 to 4 and Comparative Examples 2 to 5 exhibited improved hydrophilicity (liquid film retention time) and decreased droplet contact angles immediately after sterilization, confirming that copolymer coating imparted hydrophilicity to the surface of the hydrogel lens. In particular, the droplet contact angles immediately after sterilization for Examples 1 to 4 were lower than those for Comparative Examples 1 to 5, which used compositions not containing a zwitterion-containing compound, i.e., monomer component (A), imparting good hydrophilicity to the device surface. Furthermore, Examples 1 to 3 and Comparative Examples 3 to 5 indicated that copolymers with longer repeating units in the copolymer side chains derived from monomer component (B) exhibited good hydrophilicity and slipperiness even after 24 hours of immersion in PBS, suggesting that the coating on the device surface was highly durable.

Claims

1. A copolymer comprising the following (A), (B), and (C) as monomer components: (A) Compounds having zwitterions (B) A compound represented by the following general formula (I): 【Chemical 1】 [In general formula (I), m is an average value and represents an integer of 1 to 200; R １ represents a hydrogen atom or a methyl group, and X represents an oxygen atom, NA or NA ２ (wherein N represents a nitrogen atom, A represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, and Y represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.) (C) Acrylamide derivative

2. 2. The copolymer according to claim 1, wherein m in the compound represented by general formula (I) represents an integer of 2 to 30.

3. 2. The copolymer according to claim 1, wherein m in the compound represented by general formula (I) represents an integer of 9 to 30.

4. 2. The copolymer according to claim 1, wherein m in the compound represented by general formula (I) represents an integer of 20 to 30.

5. 3. The copolymer according to claim 1, wherein the content of the compound having a zwitterion is 1 to 30% by mass.

6. A composition comprising the copolymer according to claim 1 or 2 and a solvent.

7. A coated device, the surface of which is coated with the copolymer according to claim 1 or 2.

8. 8. The coated medical device of claim 7, wherein the coated device is selected from the group consisting of ophthalmic lenses, skin coverings, wound coverings, skin protective materials, dermal drug carriers, infusion tubes, gas transport tubes, drainage tubes, blood circuits, coating tubes, catheters, stents, sheath biosensor chips, heart-lung machines, endoscopic coverings, measuring instrument probes, and measuring instrument nozzles.

9. The coated medical device of claim 8 , wherein the ophthalmic lens is a contact lens.

10. The coated medical device of claim 9 , wherein the contact lens is a hydrogel contact lens.

11. A method for producing a coated medical device, comprising a coating step of contacting the composition according to claim 6 with the surface of a medical device to obtain a coated medical device.

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