Hydrophilic treatment agent and hydrophilic article

Abstract

To provide a hydrophilization treatment agent that can form a biocompatible film having a low elution into an aqueous medium and a high initial water wettability.SOLUTION: Provided is a hydrophilization treatment agent that contains a block copolymer having a hydrophobic segment containing a constitutional unit (A) based on at least one alkyl group-containing methacrylate selected from the group consisting of methyl methacrylate, tert-butyl methacrylate, and isobornyl methacrylate, and a hydrophilic segment containing a constitutional unit (B) based on a phosphorylcholine group-containing methacrylate described in formula (1). (In the above formula (1), R1 represents a hydrogen atom or a methyl group).SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a hydrophilic treatment agent containing a water-insoluble block copolymer that forms a biocompatible coating film with high initial water wettability, and to a hydrophilized article having a hydrophilic coating film formed from the hydrophilic treatment agent. [Background technology]

[0002] Polymers containing structural units based on 2-methacryloyloxyethyl phosphorylcholine (hereinafter sometimes abbreviated as MPC), which has the same polar group as the phospholipids that constitute cell membranes, have been widely used as surface treatment agents for medical devices due to their excellent biocompatibility, typified by hemocompatibility. Specifically, they are used as surface treatment agents for various medical devices, such as artificial hearts, artificial lungs, artificial blood vessels, and contact lenses (Non-Patent Document 1). Many of the phosphorylcholine group-containing polymers used as such surface treatment agents are used to modify the substrate surface to a biocompatible surface by physically adsorbing the polymer to the substrate surface. To prevent the coating layer from leaching, the copolymer composition and molecular weight of the phosphorylcholine group-containing polymer are designed within a range that exhibits biocompatibility (Patent Document 1). [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Application Publication No. 3-39309 [Non-patent literature]

[0004] [Non-Patent Document 1] Kazuhiko Ishihara, "Medical Forest: Prospects for Tomorrow (2): New Medical Material "MPC Polymer"", MMJ the Mainichi Medical Journal, 2010, Vol. 6, No. 2, pp. 68-70 Summary of the Invention [Problem to be solved by the invention]

[0005] The water-insoluble phosphorylcholine group-containing random polymer described in Patent Document 1 has high biocompatibility, but is designed to have a high content of hydrophobic monomers and a high molecular weight to reduce elution in aqueous media. Furthermore, the polymer is a random copolymer. Therefore, coatings formed from the polymer have low initial water wettability, and have not been used in fields where initial water wettability is required.

[0006] An object of the present invention is to provide a hydrophilization treatment agent that is capable of forming a biocompatible coating that has low elution into aqueous media and high initial water wettability. [Means for solving the problem]

[0007] As a result of intensive research in light of the above-mentioned problems, the present inventors have discovered that a hydrophilization treatment agent containing a block copolymer having a structural unit based on at least one alkyl group-containing methacrylate selected from the group consisting of methyl methacrylate, tert-butyl methacrylate, and isobornyl methacrylate, and a structural unit based on a phosphorylcholine group-containing (meth)acrylate, can solve the above-mentioned problems, and have completed the present invention.

[0008] That is, the present invention relates to the following [1] and [2]. [1] A hydrophilization treatment agent containing a block copolymer having a hydrophobic segment containing a structural unit (A) based on at least one alkyl group-containing methacrylate selected from the group consisting of methyl methacrylate, tert-butyl methacrylate, and isobornyl methacrylate, and a hydrophilic segment containing a structural unit (B) based on a phosphorylcholine group-containing (meth)acrylate represented by formula (1):

[0009] [ka]

[0010] (In the above formula (1), R 1indicates a hydrogen atom or a methyl group.)

[0011] [2] A hydrophilized article having a hydrophilized coating formed from the hydrophilization treatment agent according to [1] on a substrate. [Effects of the Invention]

[0012] The hydrophilization treatment agent of the present invention has low elution into aqueous media and can provide a biocompatible coating with high initial water wettability. DETAILED DESCRIPTION OF THE INVENTION

[0013] The present invention will now be described in further detail.

[0014] [Block copolymer (P)] The hydrophilic treatment agent of the present invention contains a block copolymer (P) having a hydrophobic segment composed of a structural unit (A) based on at least one alkyl group-containing methacrylate selected from the group consisting of methyl methacrylate, tert-butyl methacrylate, and isobornyl methacrylate, and a hydrophilic segment composed of a structural unit (B) based on a phosphorylcholine group-containing (meth)acrylate.

[0015] The presence of the structural unit (A) based on an alkyl group-containing methacrylate in the block copolymer (P) makes it possible to make the block copolymer water-insoluble. Furthermore, the solubility in aqueous media, etc., can be finely adjusted by adjusting the content, molecular weight, and type of alkyl group of the structural unit (A). By including the structural unit (A), the block copolymer (P) can reduce its solubility in aqueous media even when the ratio of hydrophobic monomers is reduced. Furthermore, because the block copolymer (P) is a block copolymer having the hydrophobic and hydrophilic segments described below, the initial water wettability of a coating formed from the block copolymer (P) can be improved.

[0016] [Hydrophobic segment containing structural unit (A) based on alkyl group-containing methacrylate] The block copolymer (P) contains a hydrophobic segment containing a structural unit (A) based on an alkyl group-containing methacrylate in its copolymer structure. The alkyl group contained in the structural unit (A) based on the alkyl group-containing methacrylate can adsorb the block copolymer (P) to the surface of a substrate through hydrophobic interaction with the substrate surface. Therefore, by introducing the structural unit (A) based on the alkyl group-containing methacrylate into the copolymer (P), the copolymer (P) can be adsorbed to the surface of the substrate through hydrophobic interaction, thereby enabling surface treatment of the substrate. The structural unit (A) based on the alkyl group-containing methacrylate is represented by the following formula (2), and more specifically, is obtained by polymerizing a monomer represented by the following formula (2'):

[0017] [ka]

[0018] [ka]

[0019] In the above formula (2) and formula (2'), R 2 represents a methyl group, a tert-butyl group, or an isobornyl group.

[0020] Representative monomers constituting the alkyl group-containing methacrylate-based structural unit (A) in the block copolymer (P) include methyl methacrylate, tert-butyl methacrylate, and isobornyl methacrylate, preferably methyl methacrylate and isobornyl methacrylate, and combinations thereof. By using block copolymers (P) based on these monomers in hydrophilic treatment agents, it is possible to obtain biocompatible coatings that exhibit low elution in aqueous media and high initial water wettability. Furthermore, the hydrophobic segment containing the alkyl group-containing methacrylate-based structural unit (A) may contain other monomers as long as the effects of the present invention are not significantly impaired.

[0021] The content of the structural unit (A) based on the alkyl group-containing methacrylate in the hydrophobic segment is 60 to 100 mass %, preferably 70 to 100 mass %, more preferably 80 to 100 mass %, and most preferably 100 mass %, relative to the total mass of the hydrophobic segment, from the viewpoint of improving the hydrophilicity of the substrate surface and suppressing adsorption of biological components.

[0022] The content of the structural unit (A) based on an alkyl group-containing methacrylate in the block copolymer (P) is preferably 5 to 90 mass %, more preferably 30 to 60 mass %, and even more preferably 40 to 50 mass %, based on the total mass of the block copolymer (P), from the viewpoint of reducing solubility in water and improving adhesion to the surface of a substrate. By increasing the content of the structural unit (A), the block copolymer (P) can be made water-insoluble, and by decreasing the content of the structural unit (A), it is easier to impart biocompatibility to the block copolymer (P).

[0023] The weight-average molecular weight of the hydrophobic segment is preferably 5,000 or more, more preferably 10,000 or more, from the viewpoint of reducing solubility in water and increasing the amount adsorbed to the substrate. The upper limit of the weight-average molecular weight of the hydrophobic segment is not particularly limited, but can be set to 200,000 or less, preferably 20,000 or less. When the block copolymer (P) has multiple hydrophobic segments, the weight-average molecular weight of the hydrophobic segment is the total value of the weight-average molecular weights of all the hydrophobic segments.

[0024] [Hydrophilic Segment Containing Structural Unit (B) Based on Phosphorylcholine Group-Containing (Meth)acrylate] The block copolymer (P) contains a hydrophilic segment containing a structural unit (B) based on a phosphorylcholine group-containing (meth)acrylate in its copolymer structure. The structural unit (B) based on a phosphorylcholine group-containing (meth)acrylate improves the hydrophilicity of the substrate surface and can suppress adsorption of biological components. The structural unit (B) based on a phosphorylcholine group-containing (meth)acrylate is represented by the following formula (3), and more specifically, is obtained by polymerization of a monomer represented by formula (3').

[0025] [ka]

[0026] [ka]

[0027] In the above formula (3) and formula (3'), R 1 represents a hydrogen atom or a methyl group.

[0028] A typical monomer of the constituent unit (B) based on a phosphorylcholine group-containing (meth)acrylate in the block copolymer (P) is 2-methacryloyloxyethyl phosphorylcholine. The hydrophilic segment containing the constituent unit (B) based on a phosphorylcholine group-containing (meth)acrylate may contain a monomer other than those mentioned above, as long as it exhibits the desired hydrophilicity.

[0029] The content of the structural unit (B) based on a phosphorylcholine group-containing (meth)acrylate in the hydrophilic segment is 60 to 100% by mass, preferably 70 to 100% by mass, more preferably 80 to 100% by mass, and most preferably 100% by mass, relative to the total mass of the hydrophilic segment, from the viewpoint of improving the hydrophilicity of the substrate surface and suppressing adsorption of biological components.

[0030] The content of the structural unit (B) based on a phosphorylcholine group-containing (meth)acrylate in the block copolymer (P) is preferably 10 to 95% by mass, more preferably 40 to 70% by mass, and even more preferably 50 to 60% by mass, relative to the total mass of the block copolymer (P), from the viewpoints of improving the hydrophilicity of the substrate surface and suppressing adsorption of biological components.

[0031] Furthermore, the content of the structural unit (B) based on a phosphorylcholine group-containing (meth)acrylate in the block copolymer (P) is preferably 10 to 95 mol %, more preferably 15 to 60 mol %, and even more preferably 20 to 40 mol %, relative to the total number of moles of the monomers constituting the block copolymer (P), from the viewpoints of improving the hydrophilicity of the substrate surface and suppressing adsorption of biological components.

[0032] The weight-average molecular weight of the hydrophilic segment is 5,000 or more, preferably 10,000 or more, from the viewpoint of improving the hydrophilicity of the substrate surface and suppressing adsorption of biological components. The upper limit of the weight-average molecular weight of the hydrophilic segment is not particularly limited, but can be 500,000 or less, preferably 20,000 or less. When the block copolymer (P) has multiple hydrophilic segments, the weight-average molecular weight of the hydrophilic segment is the sum of the weight-average molecular weights of all the hydrophilic segments.

[0033] The block copolymer (P) may contain structural units other than the hydrophobic segment containing the structural unit (A) based on an alkyl group-containing methacrylate and the hydrophilic segment containing the structural unit (B) based on a phosphorylcholine group-containing (meth)acrylate, within the range that does not significantly impair the effects of the present invention.

[0034] The weight-average molecular weight of the block copolymer (P) is preferably in the range of 10,000 to 1,000,000, more preferably 10,000 to 700,000, and even more preferably 30,000 to 70,000. Increasing the weight-average molecular weight makes it easier to purify the polymer, and keeping the weight-average molecular weight within a moderate range prevents excessive viscosity during production and makes handling easier. Furthermore, since the block copolymer (P) has low elution in aqueous media even when the weight-average molecular weight is low, the weight-average molecular weight can be adjusted over a wide range, allowing for more flexible design of the composition of the hydrophilic treatment agent.

[0035] [Method for producing block copolymer] The method for producing each block used in the present invention is not particularly limited and can be any known method, for example, controlled radical polymerization, such as atom transfer radical polymerization (ATRP), iodine transfer radical polymerization, nitroxy-mediated polymerization (NMP), reversible addition-fragmentation chain transfer (RAFT) polymerization, and reversible chain transfer catalyzed polymerization (RTCP).

[0036] In the case of a block copolymer consisting of two types of blocks, for example, a block copolymer can be obtained by combining a step of polymerizing a first block and a step of polymerizing a second block. Specifically, the block copolymer can be obtained by polymerizing the first block and then polymerizing the second block using the first block polymer as a macroinitiator. When polymerizing the second block, the first polymer may be isolated and purified before use. Alternatively, the block copolymer can be obtained by adding a second monomer to the polymerization solution of the first polymer during or upon completion of the polymerization of the first polymer without isolating and purifying the first polymer.

[0037] [Hydrophilic Treatment Agent] The hydrophilic treatment agent of the present invention contains a block copolymer (P) and may contain a suitable solvent in which the block copolymer (P) can be dissolved, such as ethanol, methanol, propanol, isopropanol, or a mixture of these.

[0038] The surface treatment agent of the present invention contains a block copolymer (P). The content of the block copolymer (P) in the surface treatment agent of the present invention is preferably in the range of 0.01 to 20% by mass, based on the total mass of the surface treatment agent. If the concentration of the block copolymer (P) is 0.01% by mass or more, the block copolymer can be easily immobilized sufficiently on the surface of the substrate. If the concentration is 20% by mass or less, a coating of the block copolymer (hydrophilic coating) of uniform thickness can be easily formed on the surface of the substrate.

[0039] The surface treatment agent of the present invention may contain, in addition to the block copolymer (P), preservatives (e.g., sodium benzoate, sodium salicylate, potassium sorbate, benzalkonium chloride, etc.), surfactants (e.g., polysorbate 80, sorbitan monooleate, squalane, sodium lauryl sulfate, etc.), hydrophilic copolymers other than the block copolymer (P) (e.g., polyethylene glycol, polyvinyl alcohol, etc.), wetting agents (e.g., concentrated glycerin, methylcellulose, hyaluronic acid, 2-methacryloyloxyethyl phosphorylcholine homopolymer, 2-methacryloyloxyethyl phosphorylcholine-n-butyl methacrylate copolymer, liquid paraffin, etc.), amino acids, etc., to the extent that they do not adversely affect the initial water wettability or the ability to inhibit adsorption of biological components. The composition may contain various compounds such as steroids (e.g., indomethacin, dexamethasone, etc.), anticoagulants (e.g., heparin, sodium citrate, ethylenediaminetetraacetic acid, acetylsalicylic acid, urokinase, warfarin, etc.), anticancer drugs (e.g., taxol, leustatin, adriamycin, bleomycin, imatinib, etc.), antibiotics (e.g., kanamycin, streptomycin, polymyxin B, etc.), absorption enhancers (e.g., sodium caprate, etc.), stabilizers (e.g., calcium citrate, natural vitamin E, human serum albumin, dextran, etc.), radiation absorbers (e.g., metals such as barium, silver, tin, platinum, gold, zirconium, etc., and compounds containing these metals such as sulfates, carbonates, and nitrates), and various other compounds.

[0040] The method for treating the surface of a substrate with the surface treatment agent of the present invention is not particularly limited, and for example, spin coating, spray coating, cast coating, dip coating, roll coating, flow coating, etc. can be used.

[0041] The material of the substrate used in the present invention is not particularly limited, but examples include various plastic materials such as polyethylene terephthalate (PET), polystyrene, polyethylene, polypropylene, cyclic polyolefin, polyester, polyurethane, polymethylpentene, polycarbonate, polyvinyl chloride, acrylic resin, methacrylic resin, AS resin, ABS resin, nylon, silicone, cellulose, cellulose acetate, polysulfone, and fluororesin.

[0042] In addition to plastic materials, metal materials include various stainless steels such as SUS304, SUS316, SUS316L, SUS420J2, and SUS630, gold, platinum, silver, copper, nickel, cobalt, iron, aluminum, tin, titanium, and various alloys such as nickel-titanium alloy, nickel-cobalt alloy, cobalt-chromium alloy, and zinc-tungsten alloy.

[0043] The shape of the substrate is not particularly limited, but specific examples include a membrane (film), plate, particle, porous, gel, test tube, vial, tube, and flask shape.

[0044] A hydrophilized article having a hydrophilized coating formed by the hydrophilization treatment agent of the present invention can be used in applications requiring initial water wettability and high biocompatibility, such as culture vessels with fine wells and microchannel devices. [Example]

[0045] The present invention will be described in more detail below with reference to Examples. In the Synthesis Examples, the weight average molecular weight was measured according to the method shown below.

[0046] 1. Copolymer synthesis <Weight average molecular weight of block copolymer (P)> Column: TSKgel SuperAW4000, 5000, 6000 in series (Tosoh Corporation); Mobile phase: Trifluoroethanol containing 10 mM sodium trifluoroacetate; Standard substance: Polymethyl methacrylate (PMMA) (Agilent Technologies); Detection: Differential refractometer; Weight average molecular weight (M w Calculation of: molecular weight analyzer program (GPC program for SC-8020), flow rate: 0.3 mL / min, column temperature: 40°C, sample solution injection amount: 100 μL, measurement time: 60 min

[0047] <Weight-average molecular weight of copolymer of Comparative Example 5> Column: PLgel 5 μm MIXED-C × 2 in series (Agilent Technologies), Mobile phase: Chloroform / methanol (6 / 4 (volume ratio)) mixed solvent containing 0.5 mass% lithium bromide, Standard substance: Polymethyl methacrylate (PMMA) (Agilent Technologies), Detection: Differential refractometer, Weight average molecular weight (M w Calculation of: molecular weight analyzer program (GPC program for SC-8020), flow rate: 1.0 mL / min, column temperature: 40°C, sample solution injection volume: 100 μL, measurement time: 30 min

[0048] [Synthesis Example of Copolymer of Example 1] (Process 1) 10.00 g (0.10 mol) of methyl methacrylate (MMA) and 0.0922 g (0.33 mmol) of 2-cyano-2-propyl benzodithioate (CPDB) were dissolved in 18.22 g of toluene and placed in a 300 mL four-necked eggplant flask equipped with a thermometer and condenser. Nitrogen was then bubbled through the solution for 30 minutes. The reaction was then initiated by adding 5.0171 g (0.10 mmol) of a 0.34 wt% toluene solution of azoisobutyronitrile (AIBN) at 60 °C. After confirming 50% conversion of MMA, the reaction solution was cooled on ice while air was bubbled through, terminating the polymerization. The resulting polymer with MMA blocks was then purified by precipitation into methanol.

[0049] (Process 2) 1.00 g of the polymer obtained in step 1 was dissolved in 29.52 g of a mixed solvent of ethoxyethanol (EtOEtOH) / N,N-dimethylformamide (DMF) (EtOEtOH / DMF = 6:4 (weight ratio)) and 6.88 g (0.023 mol) of 2-methacryloyloxyethyl-2-triethylammonioethylphosphate (MPC). The solution was placed in a 300 mL four-necked eggplant flask equipped with a thermometer and condenser and nitrogen was bubbled through for 30 minutes. Then, 2.0068 g (0.041 mmol) of a 0.34 wt% solution of AIBN in TFEtOH was added at 60 °C and the reaction was allowed to proceed for 24 hours. The reaction solution was then cooled on ice while air was bubbled through to terminate the polymerization. The resulting mixture was then purified by precipitation into acetone to obtain block copolymer P1 containing MMA and MPC.

[0050] [Synthesis Examples of Copolymers in Examples 2 to 6] Block copolymers P2 to P6 were synthesized in the same manner as in Synthesis Example 1, except that the charged compositions of MMA and MPC were changed as shown in Tables 1 to 3.

[0051] [Synthesis Examples of Copolymers in Examples 7 to 9] Block copolymers P7 to P9 were synthesized in the same manner as in Example 1, except that the MMA in Example 1 was changed to tert-butyl methacrylate (tBMA) and isobornyl methacrylate (IbMA), and the feed compositions were changed as shown in Tables 1 to 3.

[0052] [Synthesis example of copolymer of Comparative Example 1] 1.27 g (0.013 mol) of MMA, 8.73 g (0.030 mol) of MPC, and 0.0221 g (0.10 mmol) of CPDB were dissolved in 18.30 g of ethanol and placed in a 50 mL three-necked eggplant flask equipped with a thermometer and condenser. Nitrogen was then bubbled through the mixture for 30 minutes. 5.0082 g (0.050 mmol) of a 0.16 wt% toluene solution of azoisobutyronitrile (AIBN) was then added at 60 °C. The reaction was allowed to proceed for 24 hours. The reaction solution was then cooled on ice while air was bubbled through the solution, completing the polymerization. The copolymer P10, consisting of MMA and MPC, was then obtained by precipitation in acetone.

[0053] [Synthesis examples of copolymers of Comparative Examples 2 to 4] Copolymers P11 to P13 were synthesized in the same manner as in Comparative Example 1, except that the MMA in Comparative Example 2 was changed to IbMA or tBMA, or only MPC was used, and the feed compositions were changed as shown in Tables 4 and 5.

[0054] [Synthesis example of copolymer of Comparative Example 5] 23.50 g (0.080 mol) of MPC and 26.50 g (0.186 mol) of n-butyl methacrylate (nBMA) (MPC / nBMA = 3 / 7 (molar ratio)) were dissolved in 75.00 g of ethanol, and the solution was placed in a 200 mL four-neck flask equipped with a thermometer, stirrer, and reflux condenser, and nitrogen was bubbled through for 30 minutes. Then, 0.41 g of azobisisobutyronitrile was added at 55°C and the mixture was allowed to react for 24 hours. 1 The quantitative reaction of each monomer was confirmed by the disappearance of the double bond peaks of each monomer in H NMR. After the reaction, the copolymer was purified by precipitation with acetone to obtain copolymer P14.

[0055] [Synthesis examples of copolymers of Comparative Examples 7 to 9] Copolymers P15 to P17 were synthesized in the same manner as in Synthesis Example 1, except that the MMA in Synthesis Example 1 was changed to BMA and the feed composition was changed as shown in Table 6.

[0056] 2. Evaluation of copolymers <Evaluation of initial water wettability after applying a surface treatment agent> (substrate plate) A polystyrene substrate measuring 10 mm in length, 150 mm in width, and 2 mm in thickness was prepared, immersed in ethanol, ultrasonically cleaned for 30 minutes, and dried to prepare a substrate plate.

[0057] Example 1 An ethanol solution with a copolymer concentration of 0.5% by mass was prepared using the block copolymer P1 obtained in Synthesis Example 1. The substrate plate was immersed in the ethanol solution for 30 seconds, gently shaken to remove excess solution, and then dried in a dryer at 50°C. After drying, the contact angle after 3 seconds was measured using the sessile drop method (the smaller the contact angle, the higher the initial water wettability) using a dynamic contact angle meter (Kyowa Interface Science Co., Ltd., product name: Dropmaster500), and this was recorded as the contact angle before cleaning. After measurement, the plate was immersed in water and allowed to stand in a 37°C incubator for 12 hours, then removed and dried again in a 50°C dryer. After drying, the contact angle after 3 seconds was measured using the sessile drop method, and this was recorded as the contact angle after cleaning. The average value of five measurements for each contact angle was used for evaluation. A smaller contact angle indicates higher water wettability.

[0058] Examples 2 to 9 The experiment was carried out in the same manner as in Example 1, except that copolymers P2 to P9 were used instead of copolymer P1.

[0059] (Comparative Examples 1 to 5) An experiment was carried out in the same manner as in Example 1, except that copolymers P10 to P14 were used instead of copolymer P1.

[0060] (Comparative Example 6) An experiment was carried out in the same manner as in Example 1, except that water was used instead of copolymer P1.

[0061] (Comparative Examples 7 to 9) An experiment was carried out in the same manner as in Example 1, except that copolymers P15 to P17 were used instead of copolymer P1.

[0062] <Evaluation of the ability of surface treatment agents to suppress protein adsorption> The copolymer P1 obtained in Example 1 was dissolved in ethanol to a concentration of 0.5% by mass to prepare a surface treatment agent solution 1.

[0063] Surface treatment agent solution 1 was added at 200 μL / well, aspirated, and dried in a 50°C oven for 3 hours. Dulbecco's Phosphate Buffered Saline (-) (hereinafter referred to as PBS) was added at 200 μL / well, and the plate was left to stand in a 37°C incubator for 12 hours, after which it was aspirated. PBS was then added at 200 μL / well and removed three times. HRP-labeled IgG (BioRad) diluted 12,000-fold with PBS was added at 100 μL / well and the plate was left to stand at room temperature for 1 hour. The HRP-labeled IgG solution was removed from the wells, and PBS containing 0.05% Tween 20 was added at 200 μL / well. This washing process was repeated four times. After washing, 100 μL / well of HRP coloring solution (KPL) was added and allowed to react at room temperature for 10 minutes. After 10 minutes, 50 μL / well of 2N sulfuric acid was added to stop the reaction. Protein adsorbed in the wells was detected by measuring the absorbance at 450 nm using a microplate reader (Molecular Devices). The average absorbance value obtained from five measurements was used. Lower absorbance indicates greater suppression of protein adsorption.

[0064] The protein adsorption inhibitory effect was evaluated based on the relative protein adsorption rate calculated using the following formula from the absorbance of Example 1 and the absorbance of Comparative Example 6. That is, the protein adsorption rate to the plate of Example 1 was evaluated as a relative adsorption rate when the protein adsorption rate to the plate of Comparative Example 6 was set to 100%. (Absorbance of Example 1) / (Absorbance of Comparative Example 6)×100 (%)

[0065] Examples 2 to 9 The experiment was carried out in the same manner as in Example 1, except that copolymers P2 to P9 were used instead of copolymer P1.

[0066] (Comparative Examples 1 to 5, 7 to 9) An experiment was carried out in the same manner as in Example 1, except that copolymers P10 to P14 were used instead of copolymer P1.

[0067] (Comparative Example 6) The immunoassay reaction was carried out in the same manner as in Example 1, except that PBS not dissolving the copolymer was used instead of the surface treatment agent solution, and the absorbance was measured in the same manner as in Example 1. The results are shown in the table. The protein adsorption rate of Comparative Example 6 is set to 100%.

[0068] (Comparative Examples 7 to 9) An experiment was carried out in the same manner as in Example 1, except that copolymers P15 to P17 were used instead of copolymer P1.

[0069] The results are shown in Tables 1 to 6.

[0070] [Table 1]

[0071] [Table 2]

[0072] [Table 3]

[0073] [Table 4]

[0074] [Table 5]

[0075] [Table 6]

[0076] As is clear from Tables 1 to 3, by forming the copolymer coatings of Examples 1 to 9 on the substrate surface, the contact angle was smaller than that of Comparative Example 6 (untreated substrate plate), confirming that the initial water wettability was improved. Furthermore, even after immersion washing in water, the contact angle remained the same as before immersion washing, confirming that the copolymer coatings remained without being eluted by immersion washing in water.

[0077] On the other hand, as is clear from Tables 4 and 5, Comparative Examples 1 to 5 showed values ​​similar to those of Comparative Example 6 (untreated substrate plate) after immersion cleaning, confirming that the copolymer coating was dissolved by immersion cleaning in water and water wettability was not maintained. Furthermore, in Comparative Example 5, the copolymer used for evaluation had a large molecular weight and was water-insoluble, so no change in contact angle was observed before and after immersion cleaning, but all contact angles were around 115°, resulting in lower initial water wettability compared to the Examples.

[0078] Furthermore, as is clear from Table 6, in Comparative Examples 7 to 9, the initial water wettability was low and the glass transition temperature of the hydrophobic segment was low, so the hydrophobic segment was prone to segregation on the substrate surface during drying, and water wettability tended not to be maintained.

[0079] These results confirm that the surface treatment agent for medical devices of the present invention is capable of forming a biocompatible coating that has low elution in water and high initial water wettability.

[0080] Furthermore, as is clear from Tables 1 to 3, it was confirmed that by forming a coating of the copolymers of Examples 1 to 9 on the surface of a substrate, a substrate surface was formed that suppressed the adsorption of protein (horseradish peroxidase-labeled IgG) even after immersion washing with PBS.

[0081] Furthermore, as is clear from Tables 4 and 5, in Comparative Examples 1 to 4, since the polymer was water-soluble, the copolymer was washed away in the immersion washing step using PBS, resulting in the adsorption of proteins.

[0082] From the above results, it was confirmed that the surface treatment agent of the present invention can impart biocompatibility (ability to prevent protein adsorption) to the surface of a substrate by forming an adsorption layer of the copolymer on the surface of the substrate. [Industrial Applicability]

[0083] Provided is a surface treatment agent that forms a biocompatible coating film that exhibits low elution in water and high initial water wettability.

Claims

1. A hydrophilic treatment agent comprising a block copolymer having a hydrophobic segment containing a structural unit (A) based on at least one alkyl group-containing methacrylate selected from the group consisting of tert-butyl methacrylate and isobornyl methacrylate, and a hydrophilic segment containing a structural unit (B) based on a phosphorylcholine group-containing (meth)acrylate according to formula (1): 【Chemistry 1】 (In the above formula (1), R １ indicates a hydrogen atom or a methyl group.)

2. A hydrophilized article having a hydrophilized coating formed from the hydrophilization treatment agent according to claim 1 on a substrate.

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