Method for producing copolymer and material containing said copolymer

Abstract

To provide a method for producing a copolymer that can make the surface of a substrate resistant to deposition of protein and lipid, and a material containing the copolymer.SOLUTION: A method for producing a copolymer includes step 1 and step 2. Two or more monomers used in the step 2 include a hydrophilic monomer and a hydrophobic monomer. The hydrophilic monomer includes an amide group, and the hydrophobic monomer includes a vinyl carboxylate. In the step 1, the substrate is bound to an initiator. In the step 2, following the step 1, two or more monomers are brought into contact with each other, and light or heat is added thereto, for graft polymerization.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a method for producing a copolymer that can impart an effect of inhibiting the adhesion of proteins and lipids to the surface of a substrate, and to a material containing the copolymer. [Background technology]

[0002] In various fields, including textiles and medicine, the adhesion of proteins and lipids to the surface of substrates is a problem. For example, in the textile field, such as clothing, staining caused by the adhesion of substances to the surface of textile structures and yellowing caused by the oxidation of the adhered substances are issues, and there is a strong demand for improvement. On the other hand, in the medical field, when biological components such as blood and body fluids come into contact with the surface of substrates used in medical devices, the device is recognized as a foreign body, leading to the adhesion of platelets and proteins, a decrease in device performance, and even biological reactions, which can cause serious problems.

[0003] Various studies have been conducted to address this problem by applying a copolymer that inhibits the adhesion of proteins and lipids to the surface of the substrate. For example, Patent Documents 1 and 2 report a method in which a vinylpyrrolidone / vinyl acetate copolymer that inhibits the adhesion of proteins and platelets is crosslinked and immobilized on the surface of a substrate made of a hollow fiber membrane by irradiating the copolymer in water with radiation. Meanwhile, Patent Document 3 reports a method in which a functional group is introduced into a vinylpyrrolidone / vinyl propanoate copolymer and chemically immobilized to the substrate. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Patent No. 4888559 [Patent Document 2] Patent No. 5857407 [Patent Document 3] International Publication No. 2018 / 061916 Summary of the Invention [Problem to be solved by the invention]

[0005] However, the methods described in Patent Documents 1 and 2 have the problem that, depending on the type of substrate, radiation exposure can cause deterioration, resulting in a loss of sufficient strength as a device, or discoloration. Also, the method described in Patent Document 3 has the problem that the amount of functional groups that can be introduced is limited, and that an excessive amount of functional groups can induce the adhesion of proteins and the like.

[0006] An object of the present invention is to provide a material having an inhibitory effect on the adhesion of proteins and lipids to the surface of a substrate, by a copolymer production method different from the above-mentioned methods. [Means for solving the problem]

[0007] The present inventors have conducted extensive research to solve the above problems and have found the following production method and material that significantly suppresses the adhesion of proteins and lipids. (1) A method for producing a copolymer comprising steps 1 and 2, The two or more types of monomers used in step 2 include a hydrophilic monomer and a hydrophobic monomer, The hydrophilic monomer comprises an amide group, and the hydrophobic monomer comprises a vinyl carboxylic acid ester.

[0008] Step 1: Combining the substrate and initiator.

[0009] Step 2: After step 1, a step of contacting two or more types of monomers and applying light or heat to cause graft polymerization. (2) The method for producing a copolymer according to (1), wherein the initiator contains at least one functional group selected from the group consisting of a carboxy group, an amino group, and a hydroxyl group. (3) The method for producing a copolymer according to (1) or (2), wherein the hydrophilic monomer includes vinylpyrrolidone. (4) The method according to any one of (1) to (3), wherein the hydrophobic monomer comprises at least one selected from the group consisting of vinyl acetate, vinyl propanoate, vinyl butyrate, vinyl pentanoate, vinyl pivalate, and vinyl hexanoate. (5) A material comprising a substrate, an initiator moiety, and a copolymer, the substrate and the initiator moiety are bonded together; the initiator moiety and the copolymer are bonded together; The copolymer comprises a hydrophilic monomer unit and a hydrophobic monomer unit, the hydrophilic monomer unit contains an amide group, The hydrophobic monomer unit includes a carboxylic acid vinyl ester unit. material. (6) The material according to (5), wherein the substrate and the initiator moiety are bonded via an ester bond or an amide bond. (7) The material according to (5) or (6), wherein the hydrophilic monomer unit includes a vinylpyrrolidone unit. (8) The material according to any one of (5) to (7), wherein the hydrophobic monomer unit includes at least one selected from the group consisting of a vinyl acetate unit, a vinyl propanoate unit, a vinyl butyrate unit, a vinyl pentanoate unit, a vinyl pivalate unit, and a vinyl hexanoate unit. [Effects of the Invention]

[0010] The copolymer produced by the method of the present invention and the material of the present invention have an excellent effect of inhibiting the adhesion of proteins and lipids. DETAILED DESCRIPTION OF THE INVENTION

[0011] The present invention will be described in detail below.

[0012] The production method of the present invention is a method for producing a copolymer, comprising steps 1 and 2, wherein the two or more types of monomers used in step 2 include a hydrophilic monomer and a hydrophobic monomer, the hydrophilic monomer includes an amide group, and the hydrophobic monomer includes a vinyl carboxylic acid ester.

[0013] Step 1: Combining the substrate and initiator.

[0014] Step 2: After the above step 1, a step of contacting two or more types of monomers and applying light or heat to cause graft polymerization.

[0015] The material of the present invention is also a material comprising a substrate, an initiator moiety, and a copolymer, wherein the substrate and the initiator moiety are bonded together, the initiator moiety and the copolymer are bonded together, the copolymer comprises a hydrophilic monomer unit and a hydrophobic monomer unit, the hydrophilic monomer unit comprises an amide group, and the hydrophobic monomer unit comprises a carboxylic acid vinyl ester unit.

[0016] Such a material of the present invention can be suitably produced by the above-mentioned production method of the present invention, but the production method of the material of the present invention is not limited to this, and it is also possible to produce the material by other methods that do not include step 1 or step 2.

[0017] First, the meanings of terms used in the production method and material of the present invention will be described below.

[0018] The term "copolymer" refers to a polymer compound obtained by copolymerizing two or more types of monomers.

[0019] The term "hydrophilic monomer" is defined as a monomer whose homopolymer is readily soluble in water. Here, "easily soluble in water" means that the solubility in 100 g of pure water at 20°C is greater than 1 g, preferably greater than 10 g.

[0020] The term "hydrophilic monomer unit" refers to a repeating unit derived from a hydrophilic monomer in a polymer.

[0021] A "hydrophobic monomer" is defined as a repeating unit that is poorly soluble or insoluble in water when polymerized by itself. Here, "poorly soluble or insoluble in water" means that the solubility in 100 g of pure water at 20°C is 1 g or less.

[0022] The term "hydrophobic monomer unit" refers to a repeating unit derived from a hydrophobic monomer in a polymer.

[0023] The "substrate" refers to the material that is present before the initiator and copolymer are applied. In the case of a material that does not have an initiator or copolymer, the "substrate" refers to the material itself.

[0024] The term "initiator" refers to a compound that decomposes upon stimulation with light, heat, or radiation to generate radicals or ions (cations, anions).

[0025] The term "initiator moiety" refers to a residual moiety resulting from decomposition of the initiator. In particular, in the material of the present invention obtained using the production method of the present invention, the term refers to a residual moiety of the initiator that has been decomposed through bonding to the substrate or polymerization with the copolymer via Step 1 or Step 2.

[0026] The manufacturing method of the present invention and the material of the present invention will be described in detail below.

[0027] The substrate in the present invention is not particularly limited, but is preferably a substrate made of metal or a substrate made of a hydrophobic polymer in order to provide the material with sufficient strength.

[0028] When the substrate is made of a hydrophobic polymer, examples of the hydrophobic polymer constituting the substrate include polyester polymers, expanded porous polytetrafluoroethylene, polyurethane, polyether urethane, polyamide, vinyl chloride polymers, polycarbonate, polystyrene, polyethylene, polypropylene, polymethylpentene, and polymethyl methacrylate. Among these, from the viewpoint of high versatility, the substrate is more preferably a polyester polymer, i.e., a polymer having a repeating unit containing an ester bond in the main chain. Examples include polyethylene terephthalate (hereinafter referred to as "PET"), polytrimethylene terephthalate, polybutylene terephthalate, polyethylene naphthalate, and polybutylene naphthalate. Among these, PET is more preferred due to its high versatility.

[0029] A hydrophobic polymer refers to a polymer whose solubility in 100 g of pure water at 20° C. is 0.1 g or less when the number average molecular weight of the polymer is 1,000 or more and 50,000 or less.

[0030] For example, when the hydrophobic polymer has a functional group such as a urethane group, it is possible to condense an initiator having a hydroxyl group or the like and immobilize it on the surface of the substrate.

[0031] Even if the hydrophobic polymer does not have a functional group, it is possible to immobilize the initiator on the surface of the substrate by introducing a functional group by treating the surface of the substrate with plasma, corona, or the like.

[0032] Furthermore, in the case of a substrate made of a polyester polymer, although not particularly limited, the ester bonds on the surface of the substrate can be hydrolyzed by acid or alkali treatment, and the carboxyl groups generated on the surface of the substrate can be subjected to a condensation reaction with the functional groups in the initiator, thereby immobilizing the substrate.

[0033] When the substrate is made of metal or glass, the surface of the substrate can be treated with plasma, corona, or the like to introduce functional groups into the substrate, thereby immobilizing the initiator on the surface of the substrate.

[0034] Hydroxyl groups can also be introduced onto the surface of a substrate by immersing metal or glass in a mixed solution of concentrated sulfuric acid and hydrogen peroxide (hereinafter also referred to as "piranha solution"). In this method, the ratio of concentrated sulfuric acid to hydrogen peroxide is preferably in the range of 80 / 20 to 60 / 40 vol%. The temperature of the mixed solution during immersion is preferably 30°C or higher to facilitate the formation of functional groups, and is preferably 80°C or lower to prevent damage such as deformation of the substrate. The immersion time is preferably 10 minutes to 12 hours, and more preferably 1 hour to 6 hours.

[0035] As mentioned above, the term "initiator" refers to a compound that decomposes upon stimulation with light, heat, or radiation to generate radicals or ions (cations, anions). In the present invention, an initiator that generates any of radicals, cations, or anions may be used, but a radical polymerization initiator is preferably used because it is less likely to cause decomposition of the monomer.

[0036] The initiator preferably contains at least one functional group selected from the group consisting of a carboxyl group, an amino group, and a hydroxyl group, since it easily bonds to the substrate. Examples of initiators containing a carboxyl group include 4,4'-azobis(4-cyanovaleric acid), 2,2'-azobis[N-(2-carboxyethyl)-2-methylpropionamidine], and 2-benzoylbenzoic acid benzophenone-2-carboxylic acid. Examples of initiators containing an amino group include 2,2'-azobis(2-methylpropionamidine) and 2,2'-azobis[2-(2-imidazolin-2-yl)propane]. Examples of initiators containing a hydroxyl group include 2,2'-azobis[2-methyl-N-(2-hydroxyethyl)propionamide] and 4,4'-dihydroxybenzophenone. The functional group may form a salt; for example, the amino group may form a salt with a chloride ion. The initiator may also form a hydrate. Furthermore, the initiator may have only one functional group or a plurality of functional groups in one molecule.

[0037] The method for producing the copolymer of the present invention includes step 1 of bonding a base material and an initiator. In step 1, for example, functional groups of a base material having a carboxyl group-containing initiator and a hydroxyl group introduced therein, a base material having an amino group-containing initiator and a carboxyl group introduced therein, or a base material having a hydroxyl group-containing initiator and a carboxyl group introduced therein, can be condensed to bond the base material and the initiator.

[0038] Therefore, in the material of the present invention produced by this method, the substrate and the initiator moiety are preferably bonded via an ester bond or an amide bond. An ester bond can be formed by a condensation reaction between a carboxy group and a hydroxyl group. An amide group can be formed by a condensation reaction between an amino group and a carboxy group. When the condensation reaction is carried out in a solution, the concentration of the initiator is preferably in the range of 0.1 to 10 wt%, more preferably in the range of 0.5 to 5 wt%.

[0039] In step 1, when the initiator and the substrate are bonded by a condensation reaction between the functional groups of the substrate and the initiator, it is preferable to use a condensing agent from the viewpoint of proceeding with the reaction. The type of the condensing agent is not particularly limited, but examples thereof include N,N'-dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, 1-ether-3-(3-dimethylaminopropyl)carbodiimide, 1-ether-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, 1,3-bis(2,2-dimethyl-1,3-dioxolan-4-ylmethyl)carbodiimide, N-{3-(dimethylamino)propyl-}-N'-ethylcarbodiimide, N-{3-(dimethylamino)propyl}-N'-ethylcarbodiimide, and N-{3-(dimethylamino)propyl}-N'-ethylcarbodiimide. Examples of suitable carbodiimide compounds include propyl-N'-ethylcarbodiimide methiodide, N-tert-butyl-N'-ethylcarbodiimide, N-cyclohexyl-N'-(2-morphoethyl)carbodiimide, meso-p-toluenesulfonate, N,N'-di-tert-butylcarbodiimide, and N,N'-di-p-tricarbodiimide, and triazine compounds such as 4(-4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride n-hydrate. The concentration of the condensing agent is preferably in the range of 0.01 to 5 wt %, more preferably in the range of 0.1 to 1 wt %, based on the total weight of the solution.

[0040] The condensing agent may be used together with a dehydration condensation promoter. The dehydration condensation promoter to be used is not particularly limited, but examples thereof include pyridine, 4-dimethylaminopyridine, triethylamine, isopropylamine, 1-hydroxybenzotriazole, and N-hydroxysuccinimide.

[0041] The reaction solvent used in the condensation reaction of step 1 is preferably a solvent that dissolves the initiator and the condensing agent but does not dissolve the substrate. Depending on the type of substrate, for example, an ether solvent such as dioxane or tetrahydrofuran, an amide solvent such as N,N-dimethylformamide, a sulfoxide solvent such as dimethyl sulfoxide, an aromatic hydrocarbon solvent such as benzene or toluene, an alcohol solvent such as methanol, ethanol, isopropyl alcohol, amyl alcohol or hexanol, or water may be used, but an alcohol solvent or water is preferred because of its low toxicity.

[0042] The liquid temperature during the condensation reaction in step 1 is preferably 20°C or higher, more preferably 30°C or higher, from the viewpoint of proceeding with the reaction. The liquid temperature is preferably 60°C or lower, more preferably 50°C or lower, from the viewpoint of preventing decomposition of the initiator. The reaction time is preferably in the range of 0.5 to 12 hours, more preferably 1 to 8 hours.

[0043] The method for producing a copolymer of the present invention includes, after step 1, step 2 of bringing two or more types of monomers into contact with each other and applying light or heat to carry out graft polymerization. Here, "graft polymerization" refers to a reaction in which a polymer is polymerized by chain-linking monomers starting from an initiator site generated by decomposition of an initiator bonded to a substrate.

[0044] In the method for producing a copolymer of the present invention, the two or more monomers include a hydrophilic monomer and a hydrophobic monomer. By including the hydrophilic monomer, the hydrophilicity of the produced copolymer is improved, and adhesion of lipids and proteins is suppressed. Furthermore, by including the hydrophobic monomer, the hydrophilicity of the produced copolymer is not too strong, and there is little risk of denaturing the structure of biological components such as proteins.

[0045] In the present invention, the hydrophilic monomer used in step 2 contains an amide group. Therefore, in the material of the present invention, the copolymer in the material of the present invention also contains a hydrophilic monomer unit and a hydrophobic monomer unit, and the hydrophilic monomer unit contains an amide group. Here, the amide group is hydrophilic and has the effect of inhibiting lipid adhesion. On the other hand, because the hydrophilicity is not too strong, there is little risk of adsorption of biological components having ionic groups, such as proteins.

[0046] Examples of hydrophilic monomers containing an amide group used in step 2 include vinylpyrrolidone, vinylcaprolactam, N-vinylacetamide, N-vinylpropylamide, N-methylacrylamide, and N-butylacrylamide. From the viewpoint of ease of copolymerization with the hydrophobic monomer described below, it is preferable that the hydrophilic monomer contains vinylpyrrolidone. For the same reason, the material of the present invention produced by the production method of the present invention contains a hydrophilic monomer unit in the polymer, and the hydrophilic monomer unit contains an amide group. Examples of the hydrophilic monomer unit containing an amide group include a vinylpyrrolidone unit, a vinylcaprolactam unit, an N-vinylacetamide unit, an N-vinylpropylamide unit, an N-methylacrylamide unit, and an N-butylacrylamide unit. It is preferable that the hydrophilic monomer unit contains a vinylpyrrolidone unit.

[0047] On the other hand, in the present invention, the hydrophobic monomer used in step 2 includes a vinyl carboxylate ester. Here, the vinyl carboxylate ester is a monomer having a structure in which a carboxylic acid and a vinyl alcohol are condensed via an ester bond. From the viewpoint of preventing the monomer from being too hydrophobic, the vinyl carboxylate ester contained in the hydrophobic monomer preferably includes at least one selected from the group consisting of vinyl acetate, vinyl propanoate, vinyl butyrate, vinyl pentanoate, vinyl pivalate, and vinyl hexanoate. For the same reason, the material of the present invention produced by the production method of the present invention contains a hydrophobic monomer unit in the copolymer, and the hydrophobic monomer unit includes a vinyl carboxylate ester unit. The vinyl carboxylate ester unit preferably includes at least one selected from the group consisting of a vinyl acetate unit, a vinyl propanoate unit, a vinyl butyrate unit, a vinyl pentanoate unit, a vinyl pivalate unit, and a vinyl hexanoate unit. Among these, from the viewpoint of easily achieving a balance between the hydrophobicity and hydrophilicity of the entire copolymer, the vinyl carboxylate ester used in the production method of the present invention more preferably includes at least one selected from the group consisting of vinyl propanoate, vinyl butyrate, vinyl pentanoate, and vinyl pivalate. That is, the vinyl carboxylate unit in the material of the present invention more preferably contains at least one selected from the group consisting of a vinyl propanoate unit, a vinyl butyrate unit, a vinyl pentanoate unit, and a vinyl pivalate unit.

[0048] When graft polymerization is carried out in step 2, the ratio of the hydrophilic monomer to the hydrophobic monomer is preferably in the range of 90 / 10 to 30 / 70 mol % in order to impart appropriate hydrophilicity to the resulting copolymer, and the ratio of the total monomers to the polymerization solvent is preferably in the range of 10 / 90 to 70 / 30 wt %.

[0049] When graft polymerization is carried out by applying heat in step 2, the liquid temperature during the reaction is preferably in the range of 40 to 90° C., more preferably in the range of 50 to 80° C., from the viewpoint of efficiently decomposing the initiator and initiating polymerization. The reaction time is preferably in the range of 0.5 to 12 hours, more preferably in the range of 1 to 8 hours.

[0050] When graft polymerization is carried out by applying light in step 2, it is preferable to use light with a wavelength in the ultraviolet region of 250 to 400 nm. Examples of light sources that can be used include mercury lamps, high-pressure mercury lamps, xenon lamps, and carbon arc lamps. The irradiation time is generally preferably in the range of 10 seconds to 60 minutes, and more preferably in the range of 0.5 to 30 minutes.

[0051] In the present invention, the graft polymerization may be carried out by applying light or heat, but when a substrate that may be deteriorated by light is used, the graft polymerization method by applying heat is preferred.

[0052] The polymerization solvent used in the graft polymerization reaction is not particularly limited as long as it is a solvent that is compatible with the monomers. For example, an ether solvent such as dioxane or tetrahydrofuran, an amide solvent such as N,N-dimethylformamide, a sulfoxide solvent such as dimethyl sulfoxide, an aromatic hydrocarbon solvent such as benzene or toluene, an alcohol solvent such as methanol, ethanol, isopropyl alcohol, amyl alcohol or hexanol, or water may be used. However, it is preferable to use an ether solvent or an alcohol solvent because they have good compatibility with both the hydrophilic monomer and the hydrophobic monomer.

[0053] The protein adhesion to the polymer obtained by the production method of the present invention or the material of the present invention can be evaluated by the method described below using albumin, a type of protein. In this evaluation, the protein adhesion amount was 10.0 μg / cm 2 Less than 6.0 μg / cm is preferred 2 The lower limit of the amount of adhesion is 0 μg / cm 2 is.

[0054] In the present invention, the adhesiveness of lipids can be evaluated by the method described below using methyl palmitate, which is a type of lipid.

[0055] Whether or not the copolymer has been grafted onto the surface of the substrate can be confirmed by a decrease in the static contact angle of water. The contact angle is measured by the sessile drop method described below, and is preferably in the range of 5 to 70 degrees, more preferably 10 to 50 degrees, from the viewpoint of imparting appropriate hydrophilicity to the surface. Whether or not the copolymer has been grafted onto the surface of the substrate can also be confirmed by surface chemical analysis such as X-ray photoelectron spectroscopy or time-of-flight secondary ion mass spectrometry.

[0056] As described above, the material of the present invention is a material comprising a substrate, an initiator moiety, and a copolymer, wherein the substrate and the initiator moiety are bonded, the initiator moiety and the copolymer are bonded, the copolymer comprises a hydrophilic monomer unit and a hydrophobic monomer unit, the hydrophilic monomer unit comprises an amide group, and the hydrophobic monomer unit comprises a vinyl carboxylate unit. As described above, the method for producing the material of the present invention is not particularly limited, but the material can be suitably obtained by the method for producing a polymer of the present invention.

[0057] Here, the material of the present invention comprises a substrate, an initiator moiety, and a copolymer, and the copolymer comprises a hydrophilic monomer unit and a hydrophobic monomer unit, and such a copolymer in the material can be obtained by step 2 in the production method of the present invention. Furthermore, an embodiment in which the initiator moiety and the copolymer are bonded in the material of the present invention can also be obtained by step 2 in the production method of the present invention.

[0058] The material of the present invention includes a substrate, an initiator moiety, and a copolymer, and the substrate and the initiator moiety are bonded together. The material in which the substrate and the initiator moiety are bonded together can be obtained by step 1 in the production method of the present invention. [Example]

[0059] The present invention will be described below with reference to examples, but the present invention is not limited to these examples.

[0060] <Evaluation method> (1) Protein adhesion measurement A 0.1 wt% albumin phosphate buffer solution was prepared, and the target sample was soaked for 4 hours. The sample was collected and washed with phosphate buffer, after which 1 mL of BCA reagent was added and immediately shaken at 60°C for 1 hour using a micromixer. The colored BCA reagent was transferred to a cuvette using a pipette, and the absorbance at 562 nm was measured. The same measurement was performed on the calibration curve sample (Albumin standard (Wako Pure Chemical Industries, Ltd.) diluted with saline to adjust the concentration to 31.25-2000 μg / mL). The amount of protein attached to the target sample was calculated from the absorbance of the calibration curve sample.

[0061] (2) Lipid adhesion test A 0.2 wt% aqueous solution of methyl palmitate was prepared, and the target sample was immersed in it for 4 hours. The sample was then recovered, washed with pure water, and then immersed in another batch of pure water and left to stand at 0°C for 12 hours.

[0062] Thereafter, when white crystals derived from methyl palmitate were clearly precipitated, the sample was evaluated as "X", when only a portion of the sample was precipitated, the sample was evaluated as "Δ", and in all other cases, the sample was evaluated as "O".

[0063] (3) Measurement of static contact angle of water Using an automatic contact angle meter, DropMaster DM500 (Kyowa Interface Science Co., Ltd.), 1000 μL of water was deposited on the sample surface, and the contact angle of pure water 1 second after the water droplet was measured using image analysis with a curve fitting method to determine the angle θ between the polymer-water droplet interface and the water droplet-air interface at the edge of the droplet. Three measurements were taken on the same sample in air at 25°C, and the average value of the angle θ was calculated as the static contact angle of water on the polymer.

[0064] Example 1 A PET film (1 cm long x 1 cm wide, hereafter referred to as "PET film") was used as the substrate. The surface of the PET film was subjected to UV / ozone treatment to form carboxyl groups. The PET film was immersed in 10 g of an aqueous solution containing 5 wt% 2,2'-azobis[2-methyl-N-(2-hydroxyethyl)propionamide] and 0.5 wt% N,N'-diisopropylcarbodiimide and reacted at 50°C for 2 hours to bond an initiator to the PET film surface. The initiator-bonded PET film was then immersed in a mixed solution of 1.0 g of vinylpyrrolidone monomer, 1.0 g of vinyl propanoate monomer, and 3.0 g of ethanol and reacted at 65°C for 5 hours to carry out graft polymerization. After washing with distilled water, a PET film graft-polymerized with vinylpyrrolidone / vinyl propanoate copolymer was obtained.

[0065] The protein adhesion amount of the above PET film is 5.2 μg / cm 2 The result of the lipid adhesion test was "Good." Furthermore, the static contact angle of water was 40 degrees.

[0066] Example 2 SUS304 plates (1 cm long x 0.5 cm wide, hereafter referred to as "SUS plates") were used as substrates. First, the SUS plates were ultrasonically cleaned with distilled water and vacuum dried. Subsequently, they were immersed in a piranha solution (sulfuric acid / hydrogen peroxide solution = 7 / 3 vol) at 40°C for 1 hour and then washed with distilled water. Next, they were immersed in 10 g of an aqueous solution containing 5 wt% 4,4'-azobis(4-cyanovaleric acid) and 0.5 wt% N,N'-diisopropylcarbodiimide and reacted at 40°C for 6 hours to bond the initiator to the SUS plate surface. The SUS plate with the immobilized initiator was then immersed in a mixed solution of 1.0 g of vinylpyrrolidone monomer, 1.0 g of vinyl propanoate monomer, and 3.0 g of ethanol and reacted at 65°C for 5 hours to carry out graft polymerization. After washing with distilled water, a SUS plate graft-polymerized with vinylpyrrolidone / vinyl propanoate copolymer was obtained.

[0067] The amount of protein attached to the above SUS plate was 5.0 μg / cm 2The result of the lipid adhesion test was "Good." Furthermore, the static contact angle of water was 45 degrees.

[0068] (Comparative Example 1) The PET film in Example 1 was evaluated as it was, without immobilizing an initiator or graft polymerization. The amount of protein attached to the SUS plate was 12.8 μg / cm 2 The result of the lipid adhesion test was "X." Furthermore, the static contact angle of water was 75 degrees.

[0069] (Comparative Example 2) The SUS plate in Example 2 was evaluated as it was without immobilizing an initiator or graft polymerization. The amount of protein attached to the SUS plate was 13.7 μg / cm 2 The result of the lipid adhesion test was "X." Furthermore, the static contact angle of water was 92 degrees. [Industrial Applicability]

[0070] According to the present invention, a material that inhibits adhesion of lipids and proteins can be obtained.

Claims

1. A method for producing a copolymer, comprising steps 1 and 2, The two or more types of monomers used in step 2 include a hydrophilic monomer and a hydrophobic monomer, The initiator used in step 1 contains at least one functional group selected from the group consisting of a carboxy group, an amino group, and a hydroxyl group, the hydrophilic monomer comprises vinylpyrrolidone; The hydrophilic monomer comprises an amide group, and the hydrophobic monomer comprises a vinyl carboxylic acid ester. Step 1: Combining the substrate and initiator. Step 2: After step 1, a step of contacting two or more types of monomers and applying light or heat to cause graft polymerization.

2. 2. The method according to claim 1, wherein the hydrophobic monomer comprises at least one selected from the group consisting of vinyl acetate, vinyl propanoate, vinyl butyrate, vinyl pentanoate, vinyl pivalate, and vinyl hexanoate.

3. The method according to claim 1 or 2, wherein adhesion of proteins and lipids is suppressed.