Melt forming materials and formed articles

Abstract

To provide a copolymer for inhibiting protein adhesion which prevents adhesion of protein and is suitable for manufacturing an article to be in contact with protein, a method for producing a copolymer, and a resin modifier, a molding material, a copolymer-containing composition, a coating film and an article each of which uses the copolymer.SOLUTION: A copolymer for inhibiting protein adhesion has a polymer chain containing a constitutional unit (a) represented by the following formula (1) and a polymer chain containing a constitutional unit (b) represented by the following formula (2), in one molecule of the copolymer.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a copolymer for inhibiting protein adhesion, a method for producing the copolymer, and a resin modifier, molding material, copolymer-containing composition, coating film and article each using the copolymer. This application claims priority based on Japanese Patent Application No. 2018-180898 filed in Japan on September 26, 2018, and Japanese Patent Application No. 2019-047265 filed in Japan on March 14, 2019, the contents of which are incorporated herein by reference. [Background technology]

[0002] In recent years, in the fields of medical instruments, biochemical analysis, and protein separation and purification, various polymer materials (polystyrene, polypropylene, polyethylene, polyurethane, polyvinyl chloride, nylon), glass, and metals such as stainless steel are used for various parts and containers such as various reaction vessels, centrifuge tubes, tubes, syringes, pipettes, filters, and separation columns. However, proteins tend to adhere to all of these materials, which can lead to reduced detection sensitivity, reduced reproducibility, and poor purification. In addition, catheters, cannulas, stents, plasma separation membranes, artificial organs such as heart-lung machines, etc. come into contact with circulating blood and metabolic substances in the body, and therefore require biocompatibility to suppress the adhesion of proteins and the formation of blood clots and other conditions caused by the adhesion of plasma proteins.

[0003] Patent Document 1 describes that polymethoxyethyl acrylate (PMEA) has biocompatibility, such as antithrombogenicity and low protein adhesion ability. Patent Document 2 describes a method for obtaining a film to which platelets do not easily adhere by heat-treating a coating of a blend solution of polymethyl methacrylate (PMMA) and PMEA, and exposing it to ultrapure water. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] JP 2004-161954 A [Patent Document 2] JP 2013-121430 A Summary of the Invention [Problem to be solved by the invention]

[0005] However, the glass transition temperature of PMEA described in Patent Document 1 is very low, about -50° C. For this reason, it is difficult to use it as a molding material, and when used as a paint, it is difficult to obtain a coating film with sufficient hardness, making it less practical. Furthermore, the method described in Patent Document 2 has the drawbacks of complicated manufacturing steps and long processing times.

[0006] The present invention provides a protein adhesion-inhibiting copolymer to which proteins are unlikely to adhere and which is suitable for producing articles that come into contact with proteins, a method for producing the copolymer, and a resin modifier, molding material, copolymer-containing composition, coating film, and article each using the copolymer. [Means for solving the problem]

[0007] The present invention has the following aspects. [1] A copolymer for inhibiting protein adhesion, comprising a structural unit (a) represented by the following formula (1) and a structural unit (b) represented by the following formula (2):

[0008] [ka]

[0009] (In the formula, R 1 represents a hydrogen atom or a methyl group, and R 2 OR 33 , halogen atom, COR 34 , COOR 35 , C.N., C.O.N. 36 R 37 or R 38 and R 33 ~R 37each independently represents a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alicyclic group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted non-aromatic heterocyclic group, a substituted or unsubstituted aralkyl group, a substituted or unsubstituted alkaryl group, or a substituted or unsubstituted organosilyl group; R 38 represents a substituted or unsubstituted aryl group, or a substituted or unsubstituted heteroaryl group.

[0010] [ka]

[0011] (In the formula, R 3 represents a hydrogen atom or a methyl group, and R 4 represents an alkylene group having 1 to 4 carbon atoms, R 5 represents a hydrocarbon group having 1 to 6 carbon atoms. [2] The protein adhesion inhibiting copolymer according to [1], wherein the structural unit (a) is a structural unit derived from a (meth)acrylic acid ester. [3] The protein adhesion inhibitor copolymer according to [1] or [2], which has a structural unit (d) derived from a macromonomer containing the structural unit (a). [4] The copolymer for inhibiting protein adhesion according to [3], wherein the macromonomer is represented by the following formula (4):

[0012] [ka]

[0013] (In the formula, R 6 each independently represents a hydrogen atom, an unsubstituted or substituted alkyl group, an unsubstituted or substituted alicyclic group, an unsubstituted or substituted aryl group, an unsubstituted or substituted heteroaryl group, or an unsubstituted or substituted non-aromatic heterocyclic group; 6 may be the same or different, R 7represents a hydrogen atom or a methyl group, and multiple R 7 may be the same or different, Z is a terminal group, and n1 is a natural number from 2 to 10,000. [5] The structural unit (b) is selected from the group consisting of methoxymethyl acrylate, methoxyethyl acrylate, methoxypropyl acrylate, methoxybutyl acrylate, ethoxymethyl acrylate, ethoxyethyl acrylate, ethoxypropyl acrylate, ethoxybutyl acrylate, propoxymethyl acrylate, propoxyethyl acrylate, propoxypropyl acrylate, propoxybutyl acrylate, butoxymethyl acrylate, butoxyethyl acrylate, butoxypropyl acrylate, butoxybutyl acrylate, methoxymethyl methacrylate, and methoxyethyl methacrylate. The copolymer for inhibiting protein adhesion according to any one of [1] to [4], which is derived from a monomer selected from the group consisting of methacrylate, methoxypropyl methacrylate, methoxybutyl methacrylate, ethoxymethyl methacrylate, ethoxyethyl methacrylate, ethoxypropyl methacrylate, ethoxybutyl methacrylate, propoxymethyl methacrylate, propoxyethyl methacrylate, propoxypropyl methacrylate, propoxybutyl methacrylate, butoxymethyl methacrylate, butoxyethyl methacrylate, butoxypropyl methacrylate, and butoxybutyl methacrylate. [6] A copolymer for inhibiting protein adhesion according to any one of [1] to [5], having a weight-average molecular weight (Mw) of 75,000 or more. [7] The copolymer for inhibiting protein adhesion according to any one of [1] to [6], wherein the total mass of the structural units (b) is greater than the total mass of the structural units (a) among all the structural units. [8] A resin modifier comprising the protein adhesion inhibiting copolymer according to any one of [1] to [7] above. [9] A molding material comprising the protein adhesion inhibiting copolymer according to any one of [1] to [7] above.

[10] The molding material according to [9], further comprising a thermoplastic resin and containing 1 mass % or more of the protein adhesion inhibiting copolymer.

[11] The molding material according to

[10] , wherein the thermoplastic resin is a (meth)acrylic resin or an olefin resin.

[12] An article that comes into contact with protein, the article being molded from any one of the molding materials [9] to

[11] .

[13] The molded article according to

[12] , wherein the molded article is any one selected from the group consisting of medical instruments, biochemical instruments, and cell therapy devices which come into contact with plasma proteins, or any one selected from the group consisting of cell culture dishes, cell culture cells, cell culture microplates, cell culture bags, cell culture plates, cell culture tubes, cell culture flasks, biopharmaceutical petri dishes, biopharmaceutical cells, biopharmaceutical microplates, biopharmaceutical plates, biopharmaceutical tubes, biopharmaceutical bags, biopharmaceutical containers, biopharmaceutical syringes, biopharmaceutical flasks, antibody pharmaceutical petri dishes, antibody pharmaceutical cells, antibody pharmaceutical microplates, antibody pharmaceutical plates, antibody pharmaceutical tubes, antibody pharmaceutical bags, antibody pharmaceutical containers, antibody pharmaceutical syringes, and antibody pharmaceutical flasks, blood bags, blood product vials, and blood product bags which come into contact with proteins other than plasma proteins.

[14] A copolymer-containing composition comprising the copolymer for inhibiting protein adhesion according to any one of [1] to [7] above and a solvent.

[15] A coating film formed using the copolymer-containing composition according to

[14] .

[16] An article that comes into contact with proteins, having a coating film of

[15] on the surface that comes into contact with proteins.

[17] The article having a coating film according to

[16] , wherein the article having the coating film is any one selected from the group consisting of medical instruments, biochemical instruments, and cell therapy devices, each having the coating film on a surface that comes into contact with plasma proteins, or any one selected from the group consisting of a petri dish for cell culture, a cell culture cell, a microplate for cell culture, a bag for cell culture, a plate for cell culture, a tube for cell culture, a flask for cell culture, a petri dish for a biopharmaceutical, a cell for a biopharmaceutical, a microplate for a biopharmaceutical, a plate for a biopharmaceutical, a tube for a biopharmaceutical, a bag for a biopharmaceutical, a container for a biopharmaceutical, a syringe for a biopharmaceutical, a flask for a biopharmaceutical, a petri dish for an antibody pharmaceutical, a cell for an antibody pharmaceutical, a microplate for an antibody pharmaceutical, a plate for an antibody pharmaceutical, a tube for an antibody pharmaceutical, a bag for an antibody pharmaceutical, a container for an antibody pharmaceutical, a syringe for an antibody pharmaceutical, a flask for an antibody pharmaceutical, a blood bag, a vial for a blood product, and a bag for a blood product, each having the coating film on a surface that comes into contact with a protein other than plasma proteins.

[18] A method for producing a copolymer, comprising suspension polymerizing a monomer mixture containing a macromonomer (d') which contains a structural unit (a) represented by the following formula (1) and has a radical polymerizable group, and a monomer (b') represented by the following formula (2'):

[0014] [ka]

[0015] (In the formula, R 1 represents a hydrogen atom or a methyl group, and R 2 OR 33 , halogen atom, COR 34 , COOR 35 , C.N., C.O.N. 36 R 37 or R 38 and R 33 ~R 37each independently represents a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alicyclic group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted non-aromatic heterocyclic group, a substituted or unsubstituted aralkyl group (arylalkyl group), a substituted or unsubstituted alkaryl group (alkylaryl group), or a substituted or unsubstituted organosilyl group; R 38 represents a substituted or unsubstituted aryl group, or a substituted or unsubstituted heteroaryl group.

[0016] [ka]

[0017] (In the formula, R 3 represents a hydrogen atom or a methyl group, and R 4 represents an alkylene group having 1 to 4 carbon atoms, R 5 represents a hydrocarbon group having 1 to 6 carbon atoms.

[19] The monomer (b') is selected from the group consisting of methoxymethyl acrylate, methoxyethyl acrylate, methoxypropyl acrylate, methoxybutyl acrylate, ethoxymethyl acrylate, ethoxyethyl acrylate, ethoxypropyl acrylate, ethoxybutyl acrylate, propoxymethyl acrylate, propoxyethyl acrylate, propoxypropyl acrylate, propoxybutyl acrylate, butoxymethyl acrylate, butoxyethyl acrylate, butoxypropyl acrylate, butoxybutyl acrylate, methoxymethyl methacrylate, methoxy The method for producing a copolymer according to

[18] , wherein the copolymer is one or more selected from the group consisting of ethyl methacrylate, methoxypropyl methacrylate, methoxybutyl methacrylate, ethoxymethyl methacrylate, ethoxyethyl methacrylate, ethoxypropyl methacrylate, ethoxybutyl methacrylate, propoxymethyl methacrylate, propoxyethyl methacrylate, propoxypropyl methacrylate, propoxybutyl methacrylate, butoxymethyl methacrylate, butoxyethyl methacrylate, butoxypropyl methacrylate, and butoxybutyl methacrylate.

[20] The method for producing a copolymer according to

[18] or

[19] , wherein the total mass of the monomers (b') present in the monomer mixture is greater than the total mass of the structural units (a).

[21] A method for producing a copolymer according to any one of

[18] to

[20] , comprising synthesizing the macromonomer (d') by a suspension polymerization method.

[0018] The present invention may have the following combinations: [1] A copolymer having a structural unit (a) represented by the following formula (1) and a structural unit (b) represented by the following formula (2):

[0019] [ka]

[0020] (In the formula, R 1 represents a hydrogen atom or a methyl group, and R 2OR 33 , halogen atom, COR 34 , COOR 35 , C.N., C.O.N. 36 R 37 or R 38 and R 33 ~R 37 each independently represents a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alicyclic group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted non-aromatic heterocyclic group, a substituted or unsubstituted aralkyl group (arylalkyl group), a substituted or unsubstituted alkaryl group (alkylaryl group), or a substituted or unsubstituted organosilyl group; R 38 represents a substituted or unsubstituted aryl group, or a substituted or unsubstituted heteroaryl group.

[0021] [ka]

[0022] (In the formula, R 3 represents a hydrogen atom or a methyl group, and R 4 represents an alkylene group having 1 to 4 carbon atoms, R 5 represents a hydrocarbon group having 1 to 6 carbon atoms. [2] R 4 is a copolymer of methylene, ethylene, propylene, or butylene groups,[1]. [3] R 5 represents a methyl group, ethyl group, propyl group, butyl group, pentyl group, or hexyl group, a copolymer of [1] or [2]. [4] The copolymer according to any one of [1] to [3], wherein the structural unit (a) is a structural unit derived from a (meth)acrylic acid ester. [5] A copolymer according to any one of [1] to [4], which has a structural unit (d) derived from a macromonomer containing the structural unit (a). [6] The copolymer according to [5], wherein the macromonomer is represented by the following formula (4):

[0023] [ka]

[0024] (In the formula, R 6 each independently represents a hydrogen atom, an unsubstituted or substituted alkyl group, an unsubstituted or substituted alicyclic group, an unsubstituted or substituted aryl group, an unsubstituted or substituted heteroaryl group, or an unsubstituted or substituted non-aromatic heterocyclic group; 6 may be the same or different, R 7 represents a hydrogen atom or a methyl group, and multiple R 7 may be the same or different, Z is a terminal group, and n1 is a natural number from 2 to 10,000. [7] The copolymer according to [6], wherein the substituent is an alkyl group having 1 to 5 carbon atoms, an aryl group having 6 to 20 carbon atoms, or a halogen atom. [8] R 6 each independently represents a hydrogen atom or a methyl group, 6 may be the same or different, R 7 represents a hydrogen atom or a methyl group, and multiple R 7 may be the same or different, a copolymer of [6] or [7]. [9] The copolymer of any of [6] to [8], wherein the number average molecular weight (Mn) of the macromonomer is preferably 200 to 100,000, more preferably 500 to 100,000, further preferably 1,000 to 50,000, and particularly preferably 2,000 to 50,000.

[10] The copolymer of any of [6] to [9], wherein the molecular weight distribution of the macromonomer is preferably from 1.5 to 3.0, and more preferably from 2.0 to 2.5.

[11] The structural unit (b) is selected from the group consisting of methoxymethyl acrylate, methoxyethyl acrylate, methoxypropyl acrylate, methoxybutyl acrylate, ethoxymethyl acrylate, ethoxyethyl acrylate, ethoxypropyl acrylate, ethoxybutyl acrylate, propoxymethyl acrylate, propoxyethyl acrylate, propoxypropyl acrylate, propoxybutyl acrylate, butoxymethyl acrylate, butoxyethyl acrylate, butoxypropyl acrylate, butoxybutyl acrylate, methoxymethyl methacrylate, and methoxyethyl The copolymer of any of [1] to

[10] is derived from a monomer selected from the group consisting of methacrylate, methoxypropyl methacrylate, methoxybutyl methacrylate, ethoxymethyl methacrylate, ethoxyethyl methacrylate, ethoxypropyl methacrylate, ethoxybutyl methacrylate, propoxymethyl methacrylate, propoxyethyl methacrylate, propoxypropyl methacrylate, propoxybutyl methacrylate, butoxymethyl methacrylate, butoxyethyl methacrylate, butoxypropyl methacrylate, and butoxybutyl methacrylate.

[12] A copolymer of any of [1] to

[11] , having a weight average molecular weight (Mw) of 75,000 or more.

[13] The copolymer of any of [1] to

[12] , wherein the total mass of the structural units (b) is greater than the total mass of the structural units (a) in all structural units.

[14] A copolymer according to any one of [1] to

[13] , wherein the weight average molecular weight (Mw) is preferably from 75,000 to 1,000,000, and more preferably from 80,000 to 500,000.

[15] The proportion of the structural unit (b) is preferably more than 50 mass% but not more than 95 mass%, more preferably more than 50 mass% but not more than 80 mass%, and even more preferably more than 50 mass% but not more than 75 mass%, based on the total mass of all structural units.

[16] A copolymer according to any one of [1] to

[15] , wherein the proportion of the structural unit (a) is preferably from 30 to 70 mass %, and more preferably from 40 to 60 mass %, based on the total mass of all structural units.

[17] A resin modifier comprising a copolymer according to any one of [1] to

[16] above.

[18] A molding material comprising the copolymer of any one of [1] to

[16] above.

[19] The molding material according to

[18] , further comprising a thermoplastic resin and containing the copolymer at 1 mass % or more.

[20] The molding material according to

[19] , wherein the thermoplastic resin is a (meth)acrylic resin or an olefin resin.

[21] The molding material according to

[19] , wherein the thermoplastic resin is polymethyl methacrylate or an olefin resin.

[22] An article that comes into contact with protein, the article being molded from any one of the molding materials

[18] to

[21] .

[23] The molded article according to

[22] , wherein the molded article is any one selected from the group consisting of medical instruments, biochemical instruments, and cell therapy devices which come into contact with plasma proteins, or any one selected from the group consisting of cell culture dishes, cell culture cells, cell culture microplates, cell culture bags, cell culture plates, cell culture tubes, cell culture flasks, biopharmaceutical petri dishes, biopharmaceutical cells, biopharmaceutical microplates, biopharmaceutical plates, biopharmaceutical tubes, biopharmaceutical bags, biopharmaceutical containers, biopharmaceutical syringes, biopharmaceutical flasks, antibody pharmaceutical petri dishes, antibody pharmaceutical cells, antibody pharmaceutical microplates, antibody pharmaceutical plates, antibody pharmaceutical tubes, antibody pharmaceutical bags, antibody pharmaceutical containers, antibody pharmaceutical syringes, and antibody pharmaceutical flasks, blood bags, blood product vials, and blood product bags which come into contact with proteins other than plasma proteins.

[24] A copolymer-containing composition comprising the copolymer according to any one of [1] to

[16] above and a solvent.

[25] The copolymer-containing composition according to

[24] , wherein the content of the copolymer in the copolymer-containing composition is preferably 1 to 85 mass%, more preferably 5 to 80 mass%, further preferably 10 to 75 mass%, and particularly preferably 15 to 70 mass%.

[26] The copolymer-containing composition according to

[24] or

[25] , wherein the content of the solvent in the copolymer-containing composition is preferably 15 to 99 mass%, more preferably 20 to 95 mass%, and particularly preferably 25 to 90 mass%.

[27] A coating film formed using a copolymer-containing composition according to any one of

[24] to

[26] .

[28] An article that comes into contact with proteins, having a coating film according to

[27] on the surface that comes into contact with proteins.

[29] The article having a coating film according to

[28] , wherein the article having the coating film is any one selected from the group consisting of medical instruments, biochemical instruments, and cell therapy devices, each having the coating film on a surface that comes into contact with plasma proteins, or any one selected from the group consisting of a petri dish for cell culture, a cell culture cell, a microplate for cell culture, a bag for cell culture, a plate for cell culture, a tube for cell culture, a flask for cell culture, a petri dish for a biopharmaceutical, a cell for a biopharmaceutical, a microplate for a biopharmaceutical, a plate for a biopharmaceutical, a tube for a biopharmaceutical, a bag for a biopharmaceutical, a container for a biopharmaceutical, a syringe for a biopharmaceutical, a flask for a biopharmaceutical, a petri dish for an antibody pharmaceutical, a cell for an antibody pharmaceutical, a microplate for an antibody pharmaceutical, a plate for an antibody pharmaceutical, a tube for an antibody pharmaceutical, a bag for an antibody pharmaceutical, a container for an antibody pharmaceutical, a syringe for an antibody pharmaceutical, a flask for an antibody pharmaceutical, a blood bag, a vial for a blood product, and a bag for a blood product, each having the coating film on a surface that comes into contact with a protein other than plasma proteins.

[30] A method for producing a copolymer, comprising suspension polymerizing a monomer mixture containing a macromonomer (d') which contains a structural unit (a) represented by the following formula (1) and has a radical polymerizable group, and a monomer (b') represented by the following formula (2'):

[0025] [ka]

[0026] (In the formula, R 1 represents a hydrogen atom or a methyl group, and R 2 OR 33 , halogen atom, COR34 , COOR 35 , C.N., C.O.N. 36 R 37 or R 38 and R 33 ~R 37 each independently represents a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alicyclic group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted non-aromatic heterocyclic group, a substituted or unsubstituted aralkyl group, a substituted or unsubstituted alkaryl group, or a substituted or unsubstituted organosilyl group; R 38 represents a substituted or unsubstituted aryl group, or a substituted or unsubstituted heteroaryl group.

[0027] [ka]

[0028] (In the formula, R 3 represents a hydrogen atom or a methyl group, and R 4 represents an alkylene group having 1 to 4 carbon atoms, R 5 represents a hydrocarbon group having 1 to 6 carbon atoms.

[31] The monomer (b') is selected from the group consisting of methoxymethyl acrylate, methoxyethyl acrylate, methoxypropyl acrylate, methoxybutyl acrylate, ethoxymethyl acrylate, ethoxyethyl acrylate, ethoxypropyl acrylate, ethoxybutyl acrylate, propoxymethyl acrylate, propoxyethyl acrylate, propoxypropyl acrylate, propoxybutyl acrylate, butoxymethyl acrylate, butoxyethyl acrylate, butoxypropyl acrylate, butoxybutyl acrylate, methoxymethyl methacrylate, methoxy The method for producing a copolymer according to

[30] , wherein the copolymer is one or more selected from the group consisting of ethyl methacrylate, methoxypropyl methacrylate, methoxybutyl methacrylate, ethoxymethyl methacrylate, ethoxyethyl methacrylate, ethoxypropyl methacrylate, ethoxybutyl methacrylate, propoxymethyl methacrylate, propoxyethyl methacrylate, propoxypropyl methacrylate, propoxybutyl methacrylate, butoxymethyl methacrylate, butoxyethyl methacrylate, butoxypropyl methacrylate, and butoxybutyl methacrylate.

[32] The method for producing the copolymer according to

[30] or

[31] , wherein the total mass of the monomers (b') present in the monomer mixture is greater than the total mass of the structural units (a).

[33] A method for producing a copolymer according to any one of

[30] to

[32] , comprising synthesizing the macromonomer (d') by a suspension polymerization method.

[34] A method for producing a copolymer of any one of

[30] to

[32] for producing a copolymer of any one of [1] to

[16] .

[35] A copolymer of any of [1] to

[16] for inhibiting protein adhesion. Effect of the Invention

[0029] The copolymer of the present invention has a protein adhesion inhibiting effect and is suitable for producing articles that come into contact with proteins. According to the method for producing a copolymer of the present invention, it is possible to obtain a copolymer which is excellent in moldability and has a protein adhesion inhibiting effect. The resin modifier of the present invention can improve the protein adhesion inhibiting effect of the resin composition. According to the molding material of the present invention, a molded article having a protein adhesion inhibiting effect can be produced. The article of the present invention has a protein adhesion inhibiting effect. According to the copolymer-containing composition of the present invention, a coating film having a protein adhesion inhibiting effect can be formed. The coating film of the present invention has the effect of inhibiting protein adhesion. [Brief description of the drawings]

[0030] [Figure 1] 1 is a graph showing the results of a protein adhesion test for Comparative Examples and Examples. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0031] The following definitions of terms apply throughout the specification and claims. "(Meth)acrylic monomer" means a monomer having a (meth)acryloyl group. The term "(meth)acryloyl group" is a general term for acryloyl groups and methacryloyl groups. "(Meth)acrylate" is a general term for acrylate and methacrylate. "(Meth)acrylic acid" is a general term for acrylic acid and methacrylic acid. The symbol "~" indicating a range of numerical values ​​means that the numerical values ​​before and after it are included as the lower limit and upper limit. By "substituted or unsubstituted" is meant that the hydrocarbon group is "unsubstituted or has a substituent."

[0032] Hereinafter, embodiments of the present invention will be described. The following embodiments are merely examples for explaining the present invention, and are not intended to limit the present invention to these embodiments. The present invention can be implemented in various forms without departing from the spirit of the present invention.

[0033] <Protein adhesion inhibitor copolymer> The protein adhesion inhibiting copolymer of this embodiment (hereinafter simply referred to as "copolymer") has a constitutional unit (a) represented by the following formula (1) and a constitutional unit (b) represented by the following formula (2).

[0034] [ka]

[0035] In formula (1), R 1 represents a hydrogen atom or a methyl group, and R 2 OR 33 , halogen atom, COR 34 , COOR 35 , C.N., C.O.N. 36 R 37 or R 38 and R 33 ~R 37 each independently represents a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alicyclic group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted non-aromatic heterocyclic group, a substituted or unsubstituted aralkyl group, a substituted or unsubstituted alkaryl group, or a substituted or unsubstituted organosilyl group; R 38 represents a substituted or unsubstituted aryl group, or a substituted or unsubstituted heteroaryl group. In formula (2), R 3 represents a hydrogen atom or a methyl group, and R 4 represents an alkylene group having 1 to 4 carbon atoms, R 5 represents a hydrocarbon group having 1 to 6 carbon atoms.

[0036] The copolymer may be a random copolymer, but from the viewpoint of inhibiting protein adhesion, it preferably has a block copolymer or graft copolymer structure having a polymer chain (3A) of structural unit (a) represented by the following formula (3A) and a polymer chain (3B) of structural unit (b) represented by the following formula (3B).

[0037] [ka]

[0038] R in formula (3A) 1 , R 2 is R in formula (1). 1 , R 2 and n is a natural number of 1 to 1,000,000. From the viewpoint of suppressing protein adhesion, n is preferably 2 to 1,000, more preferably 5 to 1,000, even more preferably 10 to 500, and particularly preferably 20 to 500. R in formula (3B) 3 ~R 5 is R in Eq. (2). 3 ~R 5 and m is a natural number of 1 to 1,000,000. From the viewpoint of suppressing protein adhesion, m is preferably 2 to 100,000, and more preferably 5 to 50,000. Furthermore, when m is equal to or more than the lower limit, the protein adhesion suppression effect is superior, and when m is equal to or less than the upper limit, the moldability is superior. When two or more polymer chains (3A) are present in one molecule of the copolymer, the degrees of polymerization (n) of the respective polymer chains (3A) may be the same as or different from each other. When two or more polymer chains (3B) are present in one molecule of the copolymer, the degrees of polymerization (m) of the respective polymer chains (3B) may be the same as or different from each other.

[0039] <Constituent unit (a)> The structural unit (a) has a structure represented by the above formula (1). The structural unit (a) is preferably a structural unit derived from a (meth)acrylic acid ester. R 1 is preferably a hydrogen atom or a methyl group, and R 2 As COOR 35 is preferred.

[0040] R 33 ~R 37Examples of the unsubstituted alkyl group include branched or linear alkyl groups having 1 to 22 carbon atoms. Specific examples of branched or linear alkyl groups having 1 to 22 carbon atoms include methyl, ethyl, n-propyl, i-propyl, n-butyl, t-butyl, i-butyl, pentyl (amyl), i-pentyl, hexyl, heptyl, 2-ethylhexyl, octyl, i-octyl, nonyl, i-nonyl, decyl, i-decyl, undecyl, dodecyl (lauryl), tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl (stearyl), i-octadecyl, nonadecyl, icosyl, and docosyl groups.

[0041] R 33 ~R 37 The unsubstituted alicyclic group may be a monocyclic or polycyclic group, and examples thereof include alicyclic groups having a carbon number of 3 to 20. As the alicyclic group, a saturated alicyclic group is preferable, and specific examples thereof include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, a bicyclo[2.2.1]heptyl group, a cyclooctyl group, and an adamantyl group.

[0042] R 33 ~R 37 Examples of the unsubstituted aryl group include an aryl group having a carbon number of 6 to 18. Specific examples of the aryl group having a carbon number of 6 to 18 include a phenyl group and a naphthyl group. R 33 ~R 37 Examples of the unsubstituted heteroaryl group include heteroaryl groups having 4 to 18 carbon atoms. Specific examples of the heteroaryl group having 4 to 18 carbon atoms include a pyridyl group and a carbazolyl group. R 33 ~R 37Examples of the unsubstituted non-aromatic heterocyclic group include heterocyclic groups having 4 to 18 carbon atoms. Specific examples of the heterocyclic group having 4 to 18 carbon atoms include oxygen atom-containing heterocyclic groups such as a tetrahydrofuryl group and a tetrahydropyranyl group, and nitrogen atom-containing heterocyclic groups such as a γ-butyrolactone group, an ε-caprolactone group, a pyrrolidinyl group, a pyrrolidone group, and a morpholino group. R 33 ~R 37 Examples of the unsubstituted aralkyl group include a benzyl group and a phenylethyl group.

[0043] R 33 ~R 37 Examples of the unsubstituted organosilyl group include -SiR 17 R 18 R 19 (where R 17 ~R 19 each independently represents a substituted or unsubstituted alkyl group, a substituted or unsubstituted alicyclic group, or a substituted or unsubstituted aryl group. R 17 ~R 19 Examples of the substituted or unsubstituted alkyl group in include the same as those described above, such as a methyl group, an ethyl group, an n-propyl group, an n-butyl group, an n-amyl group, an n-hexyl group, an n-octyl group, an n-dodecyl group, a stearyl group, a lauryl group, an isopropyl group, an isobutyl group, an s-butyl group, a 2-methylisopropyl group, a benzyl group, and the like. R 17 ~R 19 The substituted or unsubstituted alicyclic group in may be the same as those described above, for example, a cyclohexyl group. R 17 ~R 19 The substituted or unsubstituted aryl group in the formula (I) includes the same as those mentioned above, such as a phenyl group, p-methylphenyl group, etc. R 17 ~R 19 may be the same or different.

[0044] R33 ~R 37 The substituent of is, for example, an alkyl group (where R 33 ~R 37 is an alkyl group having a substituent), an aryl group, -COOR 11 , cyano group, -OR 12 , -NR 13 R 14 , -CONR 15 R 16 , a halogen atom, an allyl group, an epoxy group, a siloxy group, and a group exhibiting hydrophilicity or ionicity. Here, R 11 ~R 16 each independently represents a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alicyclic group, or a substituted or unsubstituted aryl group.

[0045] The alkyl group and aryl group in the above-mentioned substituents include the same as the unsubstituted alkyl group and unsubstituted aryl group described above, respectively. -COOR in the above substituents 11 R 11 is preferably a hydrogen atom or an unsubstituted alkyl group. 11 is preferably a carboxy group or an alkoxycarbonyl group. Examples of the alkoxycarbonyl group include a methoxycarbonyl group. -OR in the above substituents 12 R 12 is preferably a hydrogen atom or an unsubstituted alkyl group. 12 is preferably a hydroxy group or an alkoxy group. Examples of the alkoxy group include alkoxy groups having 1 to 12 carbon atoms, and a specific example is a methoxy group.

[0046] -NR in the above substituents 13 R 14 Examples of the amino group include an amino group, a monomethylamino group, and a dimethylamino group. -CONR in the above substituents 15 R16 Examples of the alkyl group include a carbamoyl group (-CONH2), an N-methylcarbamoyl group (-CONHCH3), and an N,N-dimethylcarbamoyl group (dimethylamide group: -CON(CH3)2).

[0047] Examples of the halogen atom in the above substituent include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom. Examples of the hydrophilic or ionic group in the above-mentioned substituent include an alkali salt of a carboxy group or an alkali salt of a sulfo group, a poly(alkylene oxide) group such as a polyethylene oxide group or a polypropylene oxide group, and a cationic substituent such as a quaternary ammonium base.

[0048] Examples of the structural unit (a) represented by the above formula (1) include structural units derived from the following polymerizable monomer (a'). Examples of the polymerizable monomer (a') include methyl (meth)acrylate, ethyl (meth)acrylate, n-propyl (meth)acrylate, isopropyl (meth)acrylate, n-butyl (meth)acrylate, isobutyl (meth)acrylate, t-butyl (meth)acrylate, isoamyl (meth)acrylate, hexyl (meth)acrylate, 2-ethylhexyl (meth)acrylate, octyl (meth)acrylate, isooctyl (meth)acrylate, nonyl (meth)acrylate, isononyl (meth)acrylate, decyl (meth)acrylate, isodecyl (meth)acrylate, lauryl (meth)acrylate, hexa (meth)acrylate, and the like. Hydrocarbon group-containing (meth)acrylic acid esters such as decyl, stearyl (meth)acrylate, isostearyl (meth)acrylate, phenyl (meth)acrylate, benzyl (meth)acrylate, cyclohexyl (meth)acrylate, tetrahydrofurfuryl (meth)acrylate, isobornyl (meth)acrylate, 3,5,5-trimethylcyclohexyl (meth)acrylate, dicyclopentanyl (meth)acrylate, dicyclopentenyl (meth)acrylate, dicyclopentenyloxyethyl (meth)acrylate, terpene acrylate and derivatives thereof, hydrogenated rosin acrylate and derivatives thereof, and docosyl (meth)acrylate; hydroxyl group-containing (meth)acrylic acid esters such as 2-hydroxyethyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate, 2-hydroxybutyl (meth)acrylate, 3-hydroxybutyl (meth)acrylate, 4-hydroxybutyl (meth)acrylate, and glycerol (meth)acrylate; (Meth)acrylic acid, 2-(meth)acryloyloxyethyl hexahydrophthalic acid, 2-(meth)acryloyloxypropyl hexahydrophthalic acid, 2-(meth)acryloyloxyethyl phthalic acid, 2-(meth)acryloyloxypropyl phthalic acid, 2-(meth)acryloyloxyethyl maleic acid, 2-(meth)acryloyloxypropyl maleic acid, 2-(meth)acryloyloxyethyl succinic acid, 2-(meth)acryloyloxyethyl Carboxyl group-containing vinyl monomers such as aryloxypropylsuccinic acid, crotonic acid, fumaric acid, maleic acid, itaconic acid, citraconic acid, monomethyl maleate, monoethyl maleate, monooctyl maleate, monomethyl itaconate, monoethyl itaconate, monobutyl itaconate, monooctyl itaconate, monomethyl fumarate, monoethyl fumarate, monobutyl fumarate, monooctyl fumarate, and monoethyl citraconic acid; Vinyl monomers containing an acid anhydride group, such as maleic anhydride and itaconic anhydride; Unsaturated dicarboxylic acid diester monomers such as dimethyl malate, dibutyl malate, dimethyl fumarate, dibutyl fumarate, dibutyl itaconate, and diperfluorocyclohexyl fumarate; Epoxy group-containing vinyl monomers such as glycidyl (meth)acrylate, α-ethyl glycidyl acrylate, and 3,4-epoxybutyl (meth)acrylate; Amino group-containing (meth)acrylic acid ester vinyl monomers such as dimethylaminoethyl (meth)acrylate and diethylaminoethyl (meth)acrylate; Vinyl monomers containing an amide group, such as (meth)acrylamide, dimethyl(meth)acrylamide, diethyl(meth)acrylamide, Nt-butyl(meth)acrylamide, N-methylol(meth)acrylamide, N-isopropylacrylamide, hydroxyethylacrylamide, N-methoxymethyl(meth)acrylamide, N-butoxymethyl(meth)acrylamide, diacetone acrylamide, maleic acid amide, and maleimide; Vinyl monomers such as styrene, α-methylstyrene, vinyltoluene, (meth)acrylonitrile, vinyl chloride, vinyl acetate, and vinyl propionate; Divinylbenzene, ethylene glycol di(meth)acrylate, 1,3-butylene glycol di(meth)acrylate, 1,4-butanediol di(meth)acrylate, 1,6-hexanediol di(meth)acrylate, diethylene glycol di(meth)acrylate, triethylene glycol di(meth)acrylate, tetraethylene glycol di(meth)acrylate, polyethylene glycol di(meth)acrylate, tripropylene glycol di(meth)acrylate, neopentyl glycol polyfunctional vinyl monomers such as diol di(meth)acrylate, 1,9-nonanediol di(meth)acrylate, 1,10-decanediol di(meth)acrylate, trimethylolpropane tri(meth)acrylate, pentaerythritol tetra(meth)acrylate, dipentaerythritol hexa(meth)acrylate, allyl (meth)acrylate, triallyl cyanurate, diallyl maleate, polypropylene glycol diallyl ether, and N,N'-methylenebis(meth)acrylamide; Heterocyclic monomers such as (meth)acryloylmorpholine, vinylpyrrolidone, vinylpyridine, and vinylcarbazole; Polyethylene glycol (meth)acrylate, polypropylene glycol (meth)acrylate, methoxyethyl (meth)acrylate, ethoxyethyl (meth)acrylate, n-butoxyethyl (meth)acrylate, isobutoxyethyl (meth)acrylate, t-butoxyethyl (meth)acrylate, ethoxyethoxyethyl (meth)acrylate, phenoxyethyl (meth)acrylate, nonylphenoxyethyl (meth)acrylate, 3-methoxybutyl (meth)acrylate, acetoxyethyl (meth)acrylate, "Placcel FM" (caprolactone addition monomer, product name, manufactured by Daicel Chemical Industries, Ltd.), "Blenmer PME-100" (methoxypolyethylene glycol methacrylate (ethylene glycol chains of 2), product name, manufactured by NOF Corporation), "Blenmer PME-200" (methoxypolyethylene glycol methacrylate, product name, manufactured by NOF Corporation) glycol ester monomers such as "Blenmer PME-400" (methoxypolyethylene glycol methacrylate (ethylene glycol chains are 9), product name, manufactured by NOF Corp.), "Blenmer 50POEP-800B" (octoxypolyethylene glycol-polypropylene glycol-methacrylate (ethylene glycol chains are 8 and propylene glycol chains are 6), product name, manufactured by NOF Corp.), "Blenmer 20ANEP-600" (nonylphenoxy (ethylene glycol-polypropylene glycol) monoacrylate, product name, manufactured by NOF Corp.), "Blenmer AME-100" (manufactured by NOF Corp., product name), "Blenmer AME-200" (manufactured by NOF Corp., product name), and "Blenmer 50AOEP-800B" (manufactured by NOF Corp., product name); Monomers containing a silane coupling agent, such as 3-(meth)acryloxypropyltrimethoxysilane, 3-(meth)acryloxypropylmethyldiethoxysilane, 3-(meth)acryloxypropyltriethoxysilane, 3-acryloxypropyltrimethoxysilane, vinyltrimethoxysilane, and vinyltriethoxysilane; Trimethylsilyl (meth)acrylate, triethylsilyl (meth)acrylate, tri-n-propylsilyl (meth)acrylate, tri-n-butylsilyl (meth)acrylate, tri-n-amylsilyl (meth)acrylate, tri-n-hexylsilyl (meth)acrylate, tri-n-octylsilyl (meth)acrylate, tri-n-dodecylsilyl (meth)acrylate, triphenylsilyl (meth)acrylate, tri-p-methylphenylsilyl (meth)acrylate, tribenzylsilyl (meth)acrylate, triisopropyl Pyrsilyl (meth)acrylate, triisobutylsilyl (meth)acrylate, tri-s-butylsilyl (meth)acrylate, tri-2-methylisopropylsilyl (meth)acrylate, tri-t-butylsilyl (meth)acrylate, ethyldimethylsilyl (meth)acrylate, n-butyldimethylsilyl (meth)acrylate, diisopropyl-n-butylsilyl (meth)acrylate, n-octyldi-n-butylsilyl (meth)acrylate, diisopropylstearylsilyl (meth)acrylate, dicyclohexylphenylsilyl (meth)acrylate, t-butyldiphenylsilyl (meth)acrylate, lauryldiphenylsilyl (meth)acrylate, triisopropylsilylmethyl maleate, triisopropylsilylamyl maleate, tri-n-butylsilyl-n-butyl maleate, t-butyldiphenylsilylmethyl maleate, t-butyldiphenylsilyl-n-butyl maleate, triisopropylsilylmethyl fumarate, triisopropylsilylamyl fumarate, tri-n-butylsilyl-n-butyl fumarate, t-butyldiphenylsilylmethyl fumarate t-Butyldiphenylsilyl-n-butyl fumarate, Silaplane FM-0711 (manufactured by JNC Corporation, trade name), Silaplane FM-0721 (manufactured by JNC Corporation, trade name), Silaplane FM-0725 (manufactured by JNC Corporation, trade name), Silaplane TM-0701 (manufactured by JNC Corporation, trade name), Silaplane TM-0701T (manufactured by JNC Corporation, trade name), X-22-174ASX (manufactured by Shin-Etsu Chemical Co., Ltd., trade name), X-22-174BX (manufactured by Shin-Etsu Chemical Co., Ltd., trade name), KF-2012 (manufactured by Shin-Etsu Chemical Co., Ltd., trade name),Organosilyl group-containing monomers other than silane coupling agent-containing monomers, such as X-22-2426 (trade name, manufactured by Shin-Etsu Chemical Co., Ltd.) and X-22-2404 (trade name, manufactured by Shin-Etsu Chemical Co., Ltd.); halogenated olefins such as vinyl chloride, vinylidene chloride, vinyl fluoride, vinylidene fluoride, and chlorotrifluoroethylene; 2-isocyanatoethyl (meth)acrylate, 2,2,2-trifluoroethyl (meth)acrylate, 2,2,3,3,3-pentafluorophenyl (meth)acrylate, 2-(perfluorobutyl)ethyl (meth)acrylate, 3-(perfluorobutyl)-2-hydroxypropyl (meth)acrylate, 2-(perfluorohexyl)ethyl (meth)acrylate, 3-perfluorohexyl-2-hydroxypropyl (meth)acrylate, 3-(perfluoro-3-methylbutyl)-2-hydroxypropyl (meth)acrylate, 2,2,3,3-tetrafluoroethylene Fluorine-containing monomers (excluding halogenated olefins), such as tetrafluoropropyl (meth)acrylate, 1H,1H,5H-octafluoropentyl (meth)acrylate, 1H,1H,5H-octafluoropentyl (meth)methacrylate, 1H,1H,2H,2H-tridecafluorooctyl (meth)acrylate, 1H-1-(trifluoromethyl)trifluoroethyl (meth)acrylate, 1H,1H,3H-hexafluorobutyl (meth)acrylate, and 1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl (meth)acrylate; Monomers having an acetal structure, such as 1-butoxyethyl (meth)acrylate, 1-(2-ethylhexyloxy)ethyl (meth)acrylate, 1-(cyclohexyloxy)ethyl methacrylate, and 2-tetrahydropyranyl (meth)acrylate; Examples thereof include 4-methacryloyloxybenzophenone and 2-isocyanatoethyl (meth)acrylate.

[0049] These polymerizable monomers (a') may be used alone or in combination of two or more. As the polymerizable monomer (a'), from the viewpoint of copolymerizability, a (meth)acrylic acid ester is preferred, a hydrocarbon group-containing (meth)acrylic acid ester is more preferred, and methyl (meth)acrylate is particularly preferred.

[0050] <Macromonomer (d')> The copolymer of the present embodiment may have a structural unit (d') derived from a macromonomer containing the structural unit (a). The repeating unit constituting the macromonomer (d') may be only the structural unit (a). The macromonomer means one having a polymerizable functional group. The macromonomer (d') preferably has a structural unit (a) and a radically polymerizable group. When the macromonomer (d') has a radically polymerizable group, the copolymer of this embodiment can be produced by copolymerizing the macromonomer (d') and the monomer (b') by radical polymerization.

[0051] The radical polymerizable group contained in the macromonomer (d') is preferably a group having an ethylenically unsaturated bond. Examples of the group having an ethylenically unsaturated bond include CH2=C(COOR 6 )-CH2-, a (meth)acryloyl group, a 2-(hydroxymethyl)acryloyl group, a vinyl group, and the like. Here, R 6 represents a hydrogen atom, an unsubstituted or substituted alkyl group, an unsubstituted or substituted alicyclic group, an unsubstituted or substituted aryl group, an unsubstituted or substituted heteroaryl group, or an unsubstituted or substituted non-aromatic heterocyclic group. R 6 Specific examples of the unsubstituted alkyl group, the unsubstituted alicyclic group, the unsubstituted aryl group, the unsubstituted heteroaryl group, the unsubstituted non-aromatic heterocyclic group, and the substituents of each group as R 2 COOR as 35 R 35 The same can be mentioned.

[0052] R 6As the alkyl group, an unsubstituted or substituted alkyl group, or an unsubstituted or substituted alicyclic group is preferable, and an unsubstituted alkyl group, or an unsubstituted or substituted alicyclic group is more preferable. Among the above, in terms of ease of availability, a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-butyl group, a t-butyl group, a pentyl group, a hexyl group, a heptyl group, an octyl group, a cyclopropyl group, a cyclobutyl group, an isobornyl group, and an adamantyl group are preferred, and a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-butyl group, a t-butyl group, a cyclopropyl group, a cyclobutyl group, an isobornyl group, and an adamantyl group are more preferred.

[0053] The macromonomer (d') preferably has two or more constitutional units derived from a monomer having a radically polymerizable group. The macromonomer (d') preferably has two or more structural units (a). The macromonomer (d') preferably has one or more polymer chains represented by the above formula (3A). The macromonomer (d') more preferably has a structure represented by the following formula (4).

[0054] [ka]

[0055] In formula (4), R 6 each independently represents a hydrogen atom, an unsubstituted or substituted alkyl group, an unsubstituted or substituted alicyclic group, an unsubstituted or substituted aryl group, an unsubstituted or substituted heteroaryl group, or an unsubstituted or substituted non-aromatic heterocyclic group; 6 may be the same or different, R 7 represents a hydrogen atom or a methyl group, and multiple R 7 may be the same or different, Z is a terminal group, and n1 is a natural number from 2 to 10,000. Examples of Z include a hydrogen atom, a group derived from a radical polymerization initiator, a radical polymerizable group, and the like, similar to the terminal group of a polymer obtained by known radical polymerization. n1 is 2-10,000, and from the viewpoint of moldability, it is preferably 2-1,000, more preferably 5-1,000, even more preferably 10-500, and particularly preferably 20-500. Z is an end group of the macromonomer (d'). Examples of Z include a hydrogen atom, a group derived from a radical polymerization initiator, a radical polymerizable group, and the like, similar to the end groups of polymers obtained by known radical polymerization.

[0056] R in Equation (4) 6 is a group having an ethylenically unsaturated bond, CH2=C(COOR 6 )-CH2-R 6 is the same as: R in the copolymer 6 From the viewpoint of maintaining hydrophobicity, is preferably an alkyl group, an alicyclic group, an aryl group, a heteroaryl group, or a non-aromatic heterocyclic group, more preferably an alkyl group or an alicyclic group, and particularly preferably an alkyl group.

[0057] The number average molecular weight (Mn) of the macromonomer (d') is preferably from 200 to 100,000, more preferably from 500 to 100,000, more preferably from 1000 to 50,000, and even more preferably from 2,000 to 50,000. When the number average molecular weight of the macromonomer (d') is not less than the above lower limit, the coating performance is better, and when it is not more than the above upper limit, the moldability is better. The number average molecular weight of the macromonomer (d') is measured by gel permeation chromatography (GPC) using polystyrene as a standard resin.

[0058] The proportion of the structural unit (a) relative to the total (100 mass%) of all structural units constituting the macromonomer (d') is preferably 40 mass% or more, more preferably 50 mass% or more, and particularly preferably 100 mass% from the viewpoint of coating film performance. <Constituent unit (b)> The structural unit (b) has a structure represented by the above formula (2). The structural unit (b) is a structural unit derived from a monomer (b') represented by the following formula (2'). 3 , R 4 , and R 5 is R in the above formula (2). 3 , R 4 , and R 5 are the same as

[0059] [ka]

[0060] Examples of the monomer (b') include the following. Methoxymethyl acrylate, methoxyethyl acrylate, methoxypropyl acrylate, methoxybutyl acrylate, ethoxymethyl acrylate, ethoxyethyl acrylate, ethoxypropyl acrylate, ethoxybutyl acrylate, propoxymethyl acrylate, propoxyethyl acrylate, propoxypropyl acrylate, propoxybutyl acrylate, butoxymethyl acrylate, butoxyethyl acrylate, butoxypropyl acrylate, butoxybutyl acrylate, methoxymethyl methacrylate, methoxyethyl methacrylate, methoxypropyl methacrylate, methoxybutyl methacrylate, ethoxymethyl methacrylate, ethoxyethyl Examples of such methacrylates include methoxypolyethylene glycol methacrylate, ethoxypropyl methacrylate, ethoxybutyl methacrylate, propoxymethyl methacrylate, propoxyethyl methacrylate, propoxypropyl methacrylate, propoxybutyl methacrylate, butoxymethyl methacrylate, butoxyethyl methacrylate, butoxypropyl methacrylate, butoxybutyl methacrylate, "Blemmer PME-100" (methoxypolyethylene glycol methacrylate (having 2 ethylene glycol chains) manufactured by NOF Corporation, trade name), and "Blemmer PME-200" (methoxypolyethylene glycol methacrylate (having 4 ethylene glycol chains) manufactured by NOF Corporation, trade name).

[0061] Among these, from the viewpoint of suppressing protein adhesion, methoxyalkyl (meth)acrylates such as methoxymethyl acrylate, methoxyethyl acrylate, methoxypropyl acrylate, methoxybutyl acrylate, methoxymethyl methacrylate, methoxyethyl methacrylate, methoxypropyl methacrylate, and methoxybutyl methacrylate are preferred, with methoxyethyl acrylate and methoxyethyl methacrylate being particularly preferred.

[0062] The reason why the structural unit (b) has the ability to inhibit protein adhesion is believed to be as follows. It is known that the water that hydrates the polymer surface includes free water that interacts weakly with the polymer, intermediate water that interacts intermediately with the polymer, and unfrozen water that interacts strongly with the polymer. It is believed that the presence of intermediate water on the polymer surface makes it difficult for proteins to adhere to the polymer surface, and as a result, protein adhesion inhibition ability is imparted. In order to have intermediate water present on the polymer surface, it is believed to be effective to include a structural unit derived from the monomer (b') represented by the above formula (2'), and among these, structural units based on methoxyethyl acrylate and methoxyethyl methacrylate are particularly effective.

[0063] <Constituent unit (c)> The copolymer of the present embodiment preferably contains a structural unit (c) having a structure represented by the following formula (5).

[0064] [ka]

[0065] In formula (5), R 8 represents a hydrogen atom or a methyl group, and R 9 is a hydrogen atom, halogen atom, OH, OR 35 , C.N., N.R. 20 R 21 or R 22 and R 20 , R 21 , OR 35 each independently represents a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alicyclic group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted non-aromatic heterocyclic group, a substituted or unsubstituted aralkyl group, a substituted or unsubstituted alkaryl group, or a substituted or unsubstituted organosilyl group; R 22 represents a substituted or unsubstituted aryl group, or a substituted or unsubstituted heteroaryl group.

[0066] An example of the structural unit (c) is a structural unit derived from the polymerizable monomer (c') shown below. Methyl (meth)acrylate, ethyl (meth)acrylate, n-propyl (meth)acrylate, isopropyl (meth)acrylate, n-butyl (meth)acrylate, isobutyl (meth)acrylate, t-butyl (meth)acrylate, isoamyl (meth)acrylate, hexyl (meth)acrylate, 2-ethylhexyl (meth)acrylate, octyl (meth)acrylate, isooctyl (meth)acrylate, nonyl (meth)acrylate, isononyl (meth)acrylate, decyl (meth)acrylate, isodecyl (meth)acrylate, lauryl (meth)acrylate, hexadecyl (meth)acrylate, (meth) Hydrocarbon group-containing (meth)acrylic acid esters such as stearyl acrylate, isostearyl (meth)acrylate, phenyl (meth)acrylate, benzyl (meth)acrylate, cyclohexyl (meth)acrylate, tetrahydrofurfuryl (meth)acrylate, isobornyl (meth)acrylate, 3,5,5-trimethylcyclohexyl (meth)acrylate, dicyclopentanyl (meth)acrylate, dicyclopentenyl (meth)acrylate, dicyclopentenyloxyethyl (meth)acrylate, terpene acrylate and derivatives thereof, hydrogenated rosin acrylate and derivatives thereof, and docosyl (meth)acrylate; hydroxyl group-containing (meth)acrylic acid esters such as 2-hydroxyethyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate, 2-hydroxybutyl (meth)acrylate, 3-hydroxybutyl (meth)acrylate, 4-hydroxybutyl (meth)acrylate, and glycerol (meth)acrylate; 2-(meth)acryloyloxyethyl hexahydrophthalic acid, 2-(meth)acryloyloxypropyl hexahydrophthalic acid, 2-(meth)acryloyloxyethyl phthalic acid, 2-(meth)acryloyloxypropyl phthalic acid, 2-(meth)acryloyloxyethyl maleic acid, 2-(meth)acryloyloxypropyl maleic acid, 2-(meth)acryloyloxyethyl succinic acid, 2-(meth)acryloyloxypropyl Carboxyl group-containing vinyl monomers such as succinic acid, (meth)acrylic acid, crotonic acid, fumaric acid, maleic acid, itaconic acid, citraconic acid, monomethyl maleate, monoethyl maleate, monooctyl maleate, monomethyl itaconate, monoethyl itaconate, monobutyl itaconate, monooctyl itaconate, monomethyl fumarate, monoethyl fumarate, monobutyl fumarate, monooctyl fumarate, and monoethyl citraconic acid; Vinyl monomers containing an acid anhydride group, such as maleic anhydride and itaconic anhydride; Unsaturated dicarboxylic acid diester monomers such as dimethyl malate, dibutyl malate, dimethyl fumarate, dibutyl fumarate, dibutyl itaconate, and diperfluorocyclohexyl fumarate; Epoxy group-containing vinyl monomers such as glycidyl (meth)acrylate, α-ethyl glycidyl acrylate, and 3,4-epoxybutyl (meth)acrylate; Amino group-containing (meth)acrylic acid ester vinyl monomers such as dimethylaminoethyl (meth)acrylate and diethylaminoethyl (meth)acrylate; Vinyl monomers containing an amide group, such as (meth)acrylamide, N-methyl(meth)acrylamide, N,N'-dimethyl(meth)acrylamide, N-isopropylacrylamide, N-(hydroxymethyl)acrylamide, diethyl(meth)acrylamide, hydroxyethylacrylamide, N-butoxymethyl(meth)acrylamide, diacetone acrylamide, maleic acid amide, and maleimide; Ethylene glycol di(meth)acrylate, 1,3-butylene glycol di(meth)acrylate, 1,4-butanediol di(meth)acrylate, 1,6-hexanediol di(meth)acrylate, diethylene glycol di(meth)acrylate, triethylene glycol di(meth)acrylate, tetraethylene glycol di(meth)acrylate, polyethylene glycol di(meth)acrylate, tripropylene glycol di(meth)acrylate, neopentyl glycol di(meth)acrylate t) polyfunctional vinyl monomers such as acrylate, 1,9-nonanediol di(meth)acrylate, 1,10-decanediol di(meth)acrylate, trimethylolpropane tri(meth)acrylate, pentaerythritol tetra(meth)acrylate, dipentaerythritol hexa(meth)acrylate, allyl (meth)acrylate, triallyl cyanurate, diallyl maleate, polypropylene glycol diallyl ether, and N,N'-methylenebis(meth)acrylamide; Heterocyclic monomers such as (meth)acryloylmorpholine, vinylpyrrolidone, vinylpyridine, and vinylcarbazole; Polyethylene glycol (meth)acrylate, polypropylene glycol (meth)acrylate, phenoxyethyl (meth)acrylate, nonylphenoxyethyl (meth)acrylate, acetoxyethyl (meth)acrylate, "Placcel FM" (caprolactone addition monomer, product name, manufactured by Daicel Chemical Industries, Ltd.), Monomers containing a silane coupling agent, such as 3-(meth)acryloxypropyltrimethoxysilane, 3-(meth)acryloxypropylmethyldiethoxysilane, 3-(meth)acryloxypropyltriethoxysilane, 3-acryloxypropyltrimethoxysilane, vinyltrimethoxysilane, and vinyltriethoxysilane; Trimethylsilyl (meth)acrylate, triethylsilyl (meth)acrylate, tri-n-propylsilyl (meth)acrylate, tri-n-butylsilyl (meth)acrylate, tri-n-amylsilyl (meth)acrylate, tri-n-hexylsilyl (meth)acrylate, tri-n-octylsilyl (meth)acrylate, tri-n-dodecylsilyl (meth)acrylate, triphenylsilyl (meth)acrylate, tri-p-methylphenylsilyl (meth)acrylate, tribenzylsilyl (meth)acrylate, triisopropylsilyl (meth)acrylate, triisobutylsilyl (meth)acrylate, tri-s-butylsilyl (meth)acrylate, tri-2-methylisopropylsilyl (meth)acrylate, tri-t-butylsilyl (meth)acrylate, p) acrylate, ethyl dimethylsilyl (meth)acrylate, n-butyl dimethylsilyl (meth)acrylate, diisopropyl-n-butylsilyl (meth)acrylate, n-octyl di-n-butylsilyl (meth)acrylate, diisopropyl stearyl silyl (meth)acrylate, dicyclohexyl phenyl silyl (meth)acrylate, t-butyl diphenyl silyl (meth)acrylate, lauryl diphenyl silyl (meth)acrylate, triisopropyl silyl methyl maleate, triisopropyl silyl amyl maleate, tri-n-butyl silyl-n-butyl maleate, t-butyl diphenyl silyl methyl maleate, t-butyl diphenyl silyl-n-butyl maleate, and other organosilyl group-containing monomers other than silane coupling agent-containing monomers; 2-isocyanatoethyl (meth)acrylate, 2,2,2-trifluoroethyl (meth)acrylate, 2,2,3,3,3-pentafluorophenyl (meth)acrylate, 2-(perfluorobutyl)ethyl (meth)acrylate, 3-(perfluorobutyl)-2-hydroxypropyl (meth)acrylate, 2-(perfluorohexyl)ethyl (meth)acrylate, 3-perfluorohexyl-2-hydroxypropyl (meth)acrylate, 3-(perfluoro-3-methylbutyl)-2-hydroxypropyl (meth)acrylate, 2,2,3,3-tetrafluoroethylene Fluorine-containing monomers (excluding halogenated olefins), such as tetrafluoropropyl (meth)acrylate, 1H,1H,5H-octafluoropentyl (meth)acrylate, 1H,1H,5H-octafluoropentyl (meth)methacrylate, 1H,1H,2H,2H-tridecafluorooctyl (meth)acrylate, 1H-1-(trifluoromethyl)trifluoroethyl (meth)acrylate, 1H,1H,3H-hexafluorobutyl (meth)acrylate, and 1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl (meth)acrylate; Monomers having an acetal structure, such as 1-butoxyethyl (meth)acrylate, 1-(2-ethylhexyloxy)ethyl (meth)acrylate, 1-(cyclohexyloxy)ethyl methacrylate, and 2-tetrahydropyranyl (meth)acrylate; Examples thereof include 4-methacryloyloxybenzophenone and 2-isocyanatoethyl (meth)acrylate. Among these, from the viewpoint of ease of handling, preferred are hydrocarbon group-containing (meth)acrylic acid esters such as methyl (meth)acrylate, ethyl (meth)acrylate, n-propyl (meth)acrylate, isopropyl (meth)acrylate, n-butyl (meth)acrylate, isobutyl (meth)acrylate, t-butyl (meth)acrylate, hexyl (meth)acrylate, 2-ethylhexyl (meth)acrylate, octyl (meth)acrylate, isooctyl (meth)acrylate, nonyl (meth)acrylate, isononyl (meth)acrylate, decyl (meth)acrylate, isodecyl (meth)acrylate, lauryl (meth)acrylate, hexadecyl (meth)acrylate, stearyl (meth)acrylate, isostearyl (meth)acrylate, phenyl (meth)acrylate, benzyl (meth)acrylate, cyclohexyl (meth)acrylate, tetrahydrofurfuryl (meth)acrylate, isobornyl (meth)acrylate, and terpene acrylates and derivatives thereof; hydroxyl group-containing (meth)acrylic acid esters such as 2-hydroxyethyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate, 2-hydroxybutyl (meth)acrylate, 3-hydroxybutyl (meth)acrylate, and 4-hydroxybutyl (meth)acrylate; Carboxyl group-containing vinyl monomers such as (meth)acrylic acid; Epoxy group-containing vinyl monomers such as glycidyl (meth)acrylate and glycidyl α-ethylacrylate; Amino group-containing (meth)acrylic acid ester vinyl monomers such as dimethylaminoethyl (meth)acrylate and diethylaminoethyl (meth)acrylate; Vinyl monomers containing an amide group, such as (meth)acrylamide, N-methyl(meth)acrylamide, N,N'-dimethyl(meth)acrylamide, N-isopropylacrylamide, and N-(hydroxymethyl)acrylamide; polyfunctional vinyl monomers such as ethylene glycol di(meth)acrylate, 1,3-butylene glycol di(meth)acrylate, 1,4-butanediol di(meth)acrylate, 1,6-hexanediol di(meth)acrylate, diethylene glycol di(meth)acrylate, triethylene glycol di(meth)acrylate, tetraethylene glycol di(meth)acrylate, pentaerythritol tetra(meth)acrylate, allyl (meth)acrylate, and N,N'-methylenebis(meth)acrylamide; Heterocyclic monomers such as (meth)acryloylmorpholine, vinylpyrrolidone, vinylpyridine, and vinylcarbazole; Monomers containing a silane coupling agent, such as 3-(meth)acryloxypropyltrimethoxysilane, 3-(meth)acryloxypropylmethyldiethoxysilane, 3-(meth)acryloxypropyltriethoxysilane, and 3-acryloxypropyltrimethoxysilane; Organosilyl group-containing monomers other than silane coupling agent-containing monomers, such as trimethylsilyl (meth)acrylate, triethylsilyl (meth)acrylate, tri-n-propylsilyl (meth)acrylate, and tri-n-butylsilyl (meth)acrylate; Fluorine-containing monomers such as 2,2,2-trifluoroethyl (meth)acrylate and 2,2,3,3-tetrafluoropropyl (meth)acrylate (excluding halogenated olefins); Monomers having an acetal structure such as 1-butoxyethyl (meth)acrylate and 1-(2-ethylhexyloxy)ethyl (meth)acrylate are preferred.

[0067] It is preferable that the total mass of the structural units (b) in all the structural units is greater than the total mass of the structural units (a). Relative to the total mass of the structural units (a) and (b) present in the copolymer, the structural unit (b) is preferably more than 50% by mass and not more than 95% by mass, more preferably more than 50% by mass and not more than 80% by mass, and even more preferably more than 50% by mass and not more than 75% by mass. When the proportion of the structural unit (b) is not less than the above lower limit, the protein adhesion inhibitory effect is excellent, and when it is not more than the upper limit, the moldability is excellent.

[0068] When the copolymer contains the structural unit (c), the total mass of the structural unit (c) is preferably from 0.5 to 33 mass%, more preferably from 0.5 to 25 mass%, and even more preferably from 0.5 to 20 mass%, based on the total mass of all structural units. When the content of the structural unit (c) is at least the lower limit of the above range, excellent film-forming properties are achieved, and when it is no more than the upper limit, excellent moldability is achieved.

[0069] The weight average molecular weight of the copolymer is preferably at least 75,000, more preferably from 75,000 to 1,000,000, and even more preferably from 80,000 to 500,000. When the weight average molecular weight is at least the lower limit of the above range, excellent film-forming properties are achieved, and when it is at most the upper limit, excellent moldability is achieved. The weight average molecular weight of the copolymer is measured by gel permeation chromatography (GPC) using polystyrene as a standard resin.

[0070] <Method of producing copolymer> The method for producing the copolymer of this embodiment includes bulk polymerization, suspension polymerization, and solution polymerization of the monomer mixture (I-1) containing the macromonomer (d') and the monomer (b'). A preferred method is to perform suspension polymerization of a raw material composition (I) containing 0.001 to 5 parts by mass of a non-metallic chain transfer agent based on 100 parts by mass of the monomer mixture (I-1). The raw material composition (I) preferably contains a dispersant. By suspension polymerization, a copolymer with excellent moldability and easy processing can be obtained. By solution polymerization, a copolymer with a narrow molecular weight distribution can be obtained. For example, a bead-like copolymer may be recovered from the suspension obtained by suspension polymerization and used to produce a molded product, or the bead-like copolymer may be molded into pellets and used to produce a molded product. For example, a polymer solution obtained by solution polymerization may be dropped into a poor solvent to be reprecipitated, or a solvent may be removed by a method such as degassing extrusion to recover a powdered copolymer and used to produce a molded product, or the powdered copolymer may be molded into pellets and used to produce a molded product.

[0071] Preferred methods for producing the copolymer by suspension polymerization include, for example, the following methods (A), (B) and (C). In the method (A), the macromonomer (d') is dissolved in the monomer (b') to prepare a monomer mixture (I-1), and then a radical polymerization initiator and, if necessary, a nonmetallic chain transfer agent are added to the monomer mixture (I-1) to prepare a raw material composition (I).Then, the raw material composition (I) is dispersed in an aqueous solution to which a dispersant is added if necessary to prepare a syrup dispersion of the raw material composition (I), and the obtained syrup dispersion of the raw material composition (I) is subjected to suspension polymerization. In method (B), a syrup dispersion of a monomer mixture (I-1) is prepared by adding a monomer (b') to an aqueous suspension in which a macromonomer (d') and a dispersant added as necessary are dispersed in water. A radical polymerization initiator and a non-metallic chain transfer agent as necessary are added to the syrup dispersion of the monomer mixture (I-1) to prepare a syrup dispersion of a raw material composition (I). Then, the syrup dispersion of the raw material composition (I) is subjected to suspension polymerization. In method (C), macromonomer (d') is dissolved in monomer (b') to prepare monomer mixture (I-1), and then a radical polymerization initiator and, if necessary, a nonmetallic chain transfer agent are added to the monomer mixture (I-1) to prepare raw material composition (I). Then, raw material composition (I) is dispersed in water to prepare a syrup dispersion of raw material composition (I). This is a method in which a dispersant is added immediately before polymerization, and then the syrup dispersion of raw material composition (I) is suspension polymerized. The term "aqueous suspension" as used herein means a state in which monomers and syrup are dispersed in water.

[0072] In the above method (A), a syrup is prepared in which the macromonomer particles are completely dissolved in the monomer (b'), and particles having a uniform composition are easily obtained. Therefore, the copolymer obtained by method (A) has excellent mechanical strength when molded. Method (B) can shorten the manufacturing process because it is possible to omit the step of recovering the macromonomer (d'). That is, in method (B), a suspension obtained by synthesizing the macromonomer (d') by a suspension polymerization method is used as the aqueous suspension, and the monomer (b') can be added to this suspension for copolymerization, so that the step of recovering the macromonomer (d') can be omitted. A known method can be used to synthesize the macromonomer (d') by suspension polymerization. In contrast, in method (A), the macromonomer (d') synthesized by suspension polymerization is recovered as particles and used. Method (C) can stabilize the state of monomer dispersion in the system, and therefore makes it easier to obtain particles having a uniform composition than method (A).

[0073] In any of the above methods (A), (B) and (C), it is preferable to heat the mixture when dissolving the macromonomer (d') in the monomer (b'). The heating temperature when dissolving the macromonomer (d') in the monomer (b') is preferably 30 to 90°C. When the heating temperature is 30°C or higher, the solubility of the macromonomer (d') in the monomer (b') tends to be good, and when the heating temperature is 90°C or lower, the volatilization of the monomer mixture (I-1) tends to be suppressed. The lower limit of the heating temperature is more preferably 35°C or higher. Also, the upper limit of the heating temperature is more preferably 75°C or lower. That is, when dissolving the macromonomer (d') in the monomer (b'), the monomer mixture (I-1) is preferably heated to 30 to 90°C, more preferably 35 to 75°C.

[0074] When a radical polymerization initiator is used in polymerizing the monomer mixture (I-1) containing the macromonomer (d'), the radical polymerization initiator is preferably added after dissolving the macromonomer (d') in the monomer (b'). That is, it is preferable to dissolve the macromonomer (d') in the monomer (b') to prepare the monomer mixture (I-1), and then add the radical polymerization initiator to the monomer mixture (I-1).

[0075] The temperature of the monomer mixture (I-1) when the radical polymerization initiator is added is preferably 0°C or higher and not higher than the temperature obtained by subtracting 15°C from the 10-hour half-life temperature of the radical polymerization initiator used. When the temperature when the radical polymerization initiator is added is 0°C or higher, the solubility of the radical polymerization initiator in the monomer (b') tends to be good. In addition, when the temperature when the radical polymerization initiator is added is not higher than the temperature obtained by subtracting 15°C from the 10-hour half-life temperature of the radical polymerization initiator, the polymerization tends to be stable.

[0076] Examples of the radical polymerization initiator include organic peroxides and azo compounds. Specific examples of organic peroxides include 2,4-dichlorobenzoyl peroxide, t-butyl peroxypivalate, o-methylbenzoyl peroxide, bis-3,5,5-trimethylhexanoyl peroxide, octanoyl peroxide, t-butylperoxy-2-ethylhexanoate, cyclohexanone peroxide, benzoyl peroxide, methyl ethyl ketone peroxide, dicumyl peroxide, lauroyl peroxide, diisopropylbenzene hydroperoxide, t-butyl hydroperoxide, and di-t-butyl peroxide. Specific examples of azo compounds include 2,2'-azobisisobutyronitrile, 2,2'-azobis(2-methylbutyronitrile), 2,2'-azobis(2,4-dimethylvaleronitrile) and 2,2'-azobis(2,4-dimethyl-4-methoxyvaleronitrile).

[0077] Among the above radical polymerization initiators, benzoyl peroxide, 2,2'-azobisisobutyronitrile, 2,2'-azobis(2-methylbutyronitrile), 2,2'-azobis(2,4-dimethylvaleronitrile) and 2,2'-azobis(2,4-dimethyl-4-methoxyvaleronitrile) are preferred in terms of availability. The radical polymerization initiators can be used alone or in combination of two or more kinds. The amount of the radical polymerization initiator added is preferably 0.0001 to 10 parts by mass, more preferably 0.0005 to 5 parts by mass, per 100 parts by mass of the total amount of the macromonomer (d') and the monomer (b'), from the viewpoint of controlling heat generated by polymerization.

[0078] In the above-mentioned method (A) or method (B), the polymerization temperature when the raw material composition (I) is subjected to suspension polymerization is not particularly limited, and generally, it is preferably 50 to 120°C, and more preferably 70 to 100°C. The polymerization time is preferably from 1 to 6 hours, more preferably from 1.5 to 4 hours. The stirring conditions are preferably 100 to 800 rpm, and more preferably 150 to 600 rpm.

[0079] Examples of dispersants used in suspension polymerization include alkali metal salts of poly(meth)acrylic acid, copolymers of alkali metal salts of (meth)acrylic acid and (meth)acrylic acid esters, copolymers of alkali metal salts of (meth)acrylic acid sulfoalkyl and (meth)acrylic acid esters, alkali metal salts of polystyrene sulfonic acid, copolymers of alkali metal salts of styrene sulfonic acid and (meth)acrylic acid esters, alkali metal salts of (meth)acrylic acid, alkali metal salts of (meth)acrylic acid sulfoalkyl, alkali metal salts of styrene sulfonic acid and (meth)acrylic acid, Examples of the copolymer include a copolymer of an alkali metal salt of (meth)acrylic acid, an alkali metal salt of a sulfoalkyl (meth)acrylate, and a (meth)acrylic acid ester, a copolymer of an alkali metal salt of (meth)acrylic acid, an alkali metal salt of styrenesulfonic acid, and a (meth)acrylic acid ester, and a copolymer of an alkali metal salt of a sulfoalkyl (meth)acrylate, an alkali metal salt of styrenesulfonic acid, and a (meth)acrylic acid ester; a polyvinyl alcohol having a saponification degree of 70 to 100%; methylcellulose; starch; and hydroxyapatite. These may be used alone or in combination of two or more. Among these, a copolymer of an alkali metal salt of a sulfoalkyl (meth)acrylate and a (meth)acrylic acid ester, which has good dispersion stability during suspension polymerization, is preferred.

[0080] The content of the dispersant in the aqueous suspension is preferably 0.005 to 5% by mass, more preferably 0.01 to 1% by mass, based on the total mass of the aqueous suspension. If the content of the dispersant in the aqueous suspension is 0.005% by mass or more, the dispersion stability of the suspension polymerization liquid is good, and the washability, dewaterability, drying property and flowability of the obtained polymer tend to be good. In addition, if the content of the dispersant is 5% by mass or less, foaming during polymerization tends to be small, and polymerization stability tends to be good.

[0081] For the purpose of improving the dispersion stability of the aqueous suspension, electrolytes such as sodium carbonate, sodium sulfate, manganese sulfate, etc. may be added to the aqueous suspension. In this case, the ratio of these additives is preferably 0.01 to 0.5 mass% based on the total mass of the aqueous suspension in the case of the method (A). In addition, the preferred ratio of the electrolyte in the aqueous suspension is 0.01 to 10 mass% in the case of the method (B).

[0082] It is preferable to obtain a copolymer by polymerizing a raw material composition (I) containing the monomer mixture (I-1) and a nonmetallic chain transfer agent described below.

[0083] <Non-metallic chain transfer agents> The nonmetallic chain transfer agent is added to the monomer mixture (I-1) when a polymer is obtained, and is preferably added particularly when a polymer is obtained by suspension polymerization. By using a nonmetallic chain transfer agent as a chain transfer agent during the production of a polymer, the amount of unreacted macromonomer contained in the polymer can be reduced.

[0084] Examples of non-metallic chain transfer agents include sulfur-containing chain transfer agents such as t-dodecyl mercaptan and n-octyl mercaptan, α-methylstyrene dimer, carbon tetrachloride, and terpenoids. From the viewpoints of availability and high chain transfer ability, sulfur-containing chain transfer agents are preferred. The content of the nonmetallic chain transfer agent is preferably 0.01 to 0.5 parts by mass based on 100 parts by mass of the monomer mixture (I-1). When the content of the non-metallic chain transfer agent is at least the lower limit of the above range, the effect of adding the agent is sufficiently obtained, whereas when the content is at most the upper limit, the mechanical strength after curing is excellent. The content of the nonmetallic chain transfer agent is more preferably from 0.03 to 0.3 parts by mass, and particularly preferably from 0.05 to 0.2 parts by mass.

[0085] The copolymer of the present embodiment has a protein adhesion inhibiting function, and in the following protein adhesion test (1), the copolymer was found to have a protein adhesion inhibiting function of 1 cm at a fibrinogen concentration of 34 ppm (by mass). 2The amount of fibrinogen adsorption per unit time can be 45 ng (nanograms) or less, preferably 30 ng or less, and more preferably 20 ng or less. The copolymer of the present invention has a molecular weight of 1 cm at an albumin concentration of 2000 ppm (mass basis). 2 The amount of albumin adsorption per unit time can be 320 ng (nanograms) or less, and the amount of albumin adsorption per unit time is preferably 300 ng or less. [Protein adhesion test (1)] The copolymer to be tested is dissolved in a solvent, methyl cellosolve, to prepare a copolymer solution with a copolymer concentration of 0.1 to 0.5% by mass. The copolymer solution is applied to the sensor chip of a quartz crystal microbalance method device so that the amount of copolymer applied per unit area is 20.7 ng / mm 2 ~62ng / mm 2 Then, the copolymer is spin-coated so as to obtain a copolymer having a thickness of 100 nm and dried at 80° C. for 15 minutes to immobilize the copolymer on the sensor chip. In order to obtain reproducibility, the sensor chip surface is preliminarily cleaned by, for example, irradiating it with excimer light at a wavelength of 172 nm, or by dropping a piranha solution onto the sensor chip surface, leaving it for 5 to 10 minutes, and then cleaning it with pure water. Fibrinogen (derived from human plasma) is dissolved in phosphate buffer (water 99.0435% by weight, sodium chloride 0.9% by weight, disodium hydrogen phosphate 0.0421% by weight, potassium dihydrogen phosphate 0.0144% by weight, pH 7.1 to 7.3) to a specified concentration to prepare a test solution. The fibrinogen concentration of the test solution is 1000 (unit: ppm by mass). The surface of the sensor chip is immersed in the phosphate buffer solution for 12 hours or more to stabilize it, and then the sensor is set again in the specified amount of phosphate buffer solution on the quartz crystal microbalance device and measurement of the oscillation frequency is started. After the oscillation frequency is stabilized for about 30 minutes to 1 hour, the test liquid is dropped every 15 minutes. The amount of each drop is 0.5 to 1.0 μL. The amount of fibrinogen adsorbed to the sensor is calculated from the measurement data of the oscillation frequency. Analysis software can be used to analyze the measurement data. From a graph showing the correlation between the fibrinogen concentration in the system into which the test liquid was dropped and the amount of adsorption to the sensor, it was found that the sensor area (4.8 mm2) at a fibrinogen concentration of 34 ppm (by mass) was 1.2 ppm. 2 ) and calculate the amount of fibrinogen adsorbed per unit area. The same experiment can be carried out for albumin (derived from bovine serum albumin, BSA). In this case, the albumin concentration of the test solution is set to two levels: 10,000 and 30,000 (unit: ppm by mass). From the graph showing the correlation between albumin concentration and the amount of adsorption to the sensor, the sensor area (4.8 mm2) at an albumin concentration of 2000 ppm (by mass) was 2 ) and calculate the amount of albumin adsorbed per unit area.

[0086] <Application> As shown in the examples described later, the copolymer of the present embodiment has excellent moldability, and the molded article has a protein adhesion inhibitory effect, and is therefore suitable for the manufacture of articles that come into contact with proteins, particularly plasma proteins. The copolymer of the present embodiment is suitable as a resin modifier. By adding the resin modifier made of the copolymer to a resin composition, the protein adhesion suppression effect of the resin composition can be improved. The copolymer of the present embodiment is suitable as a molding material. When a molding material containing the copolymer is molded, an article (molded body) having a protein adhesion inhibitory effect can be obtained.

[0087] <Molding material> The molding material may contain other polymers in addition to the copolymer, if necessary. It may further contain other components, if necessary. Examples of other polymers include (meth)acrylic resins such as PMMA, polyolefins, polystyrene, polyamides, polyurethanes, unsaturated polyesters, saturated polyesters such as polyethylene terephthalate and polybutylene terephthalate, polycarbonates, polyvinyl chloride, silicone resins, epoxy resins, polyether ether ketones, and polyvinylidene fluoride. As other polymers, thermoplastic resins are preferred, and among them, (meth)acrylic resins and olefin resins are preferred. Examples of other components include release agents, antioxidants, heat stabilizers, impact resistance modifiers, flexibility imparting agents, weather resistance modifiers, colorants, inorganic pigments, organic pigments, carbon black, ferrite, conductivity imparting agents, ultraviolet absorbers, infrared absorbers, lubricants, inorganic fillers, reinforcing agents, plasticizers, antiplasticizers, neutralizing agents, crosslinking agents, flame retardants, preservatives, insect repellents, fragrances, radical scavengers, sound absorbing materials, and core-shell rubber. Examples of a method for mixing the copolymer, other polymers, and other components to be blended as necessary include a physical mixing method using a Henschel mixer, a blender, etc., and a melt kneading method using a mixer such as a Brabender, a kneader, or an extruder. There are no particular limitations on the shape of the molding material, but when it is envisaged that the molding material will be used to melt-mold a molded body, it is preferable to melt-knead the copolymer, other polymers, and other components to be blended as necessary in advance and process them into pellets or beads. The content of the copolymer relative to the total mass of the molding material is preferably 1% by mass or more, more preferably 5% by mass or more, and even more preferably 10% by mass or more. It may be 100% by mass. When it is equal to or more than the lower limit, the protein adhesion suppression ability is excellent. The amount of the other polymer is preferably 0 to 95 mass %, more preferably 20 to 80 mass %, based on the total mass of the molding material.

[0088] The molding material containing the copolymer of this embodiment has a protein adhesion inhibiting function, and in the following protein adhesion test (2), 2The albumin adsorption amount per unit time can be achieved to be 1.5 μg (micrograms) or less, preferably 1.25 μg or less, and more preferably 1.10 μg or less. [Protein adhesion test (2): μBCA method] The molding material to be tested is immersed in a 1 mg / mL albumin solution dissolved in phosphate buffered saline (PBS) for 2 hours at 37°C. After immersion for 2 hours, the molding material is washed with PBS, then immersed in 6 mL of sodium dodecyl sulfate aqueous solution and ultrasonically cleaned for 5 minutes. 150 μL of the ultrasonically cleaned solution is placed in a 96-well plate, and 150 μL of protein quantification reagent from a commercially available BCA kit is placed in the same area as the ultrasonically cleaned solution, and the plate is kept at 37°C for 2 hours. After holding for 2 hours, the absorbance at 562 nm is measured using a plate reader, and the amount of albumin adsorption is calculated by applying it to a calibration curve obtained from an albumin solution of known concentration.

[0089] <Molded articles> The shape of the article (molded body) may be, for example, a sheet shape or a three-dimensional shape. The method for producing an article (molded body) by molding the molding material is preferably a melt molding method, such as injection molding, compression molding, blow molding, extrusion molding, rotational molding, casting, and solvent casting. Of these, injection molding and extrusion molding are preferred.

[0090] The article (molded article) is preferably an article that comes into contact with proteins, and is preferably used as an inner layer in a multi-layer film that comes into contact with plasma proteins, antibody drugs, and biopharmaceuticals. Examples of articles that come into contact with plasma proteins include medical instruments such as contact lenses, cannulas, catheters, syringes, intravenous drip routes, intravenous drip bags, infusion bags, blood bags, stents, and endoscopes; biochemical instruments such as pipette tips, petri dishes, cells, microplates, storage bags, plates, reagent storage containers, tubes, and flasks; and cell therapy equipment such as mixers, bioreactors, and jar fermenters. Examples of articles that come into contact with proteins other than plasma proteins include petri dishes for cell culture, cells for cell culture, microplates for cell culture, bags for cell culture, plates for cell culture, tubes for cell culture, flasks for cell culture, petri dishes for biopharmaceuticals, cells for biopharmaceuticals, microplates for biopharmaceuticals, plates for biopharmaceuticals, tubes for biopharmaceuticals, bags for biopharmaceuticals, containers for biopharmaceuticals, syringes for biopharmaceuticals, flasks for biopharmaceuticals, petri dishes for antibody pharmaceuticals, cells for antibody pharmaceuticals, microplates for antibody pharmaceuticals, plates for antibody pharmaceuticals, tubes for antibody pharmaceuticals, bags for antibody pharmaceuticals, containers for antibody pharmaceuticals, syringes for antibody pharmaceuticals, flasks for antibody pharmaceuticals, blood bags (whole blood, plasma, platelets, red blood cells), vials for blood products, bags for blood products, etc.

[0091] <Coating film> The copolymer of the present embodiment can be used by dissolving it in a solvent. As shown in the examples below, a coating film formed using a copolymer-containing composition containing the copolymer and a solvent contains the copolymer and has a protein adhesion suppression effect. The copolymer contained in the copolymer-containing composition may be one type or two or more types. It is preferable to form a coating film using the copolymer-containing composition on at least the surface of an article that comes into contact with a protein, which is in contact with the protein. In particular, it is preferable to form a coating film using the copolymer-containing composition on at least the surface of an article that comes into contact with a plasma protein, which is in contact with the plasma protein.

[0092] The solvent in the copolymer-containing composition is not particularly limited as long as it can dissolve the copolymer of the present embodiment. For example, monohydric alcohols such as methyl alcohol, ethyl alcohol, isopropyl alcohol, etc.; polyhydric alcohols such as ethylene glycol, 1,2-propylene glycol, etc.; ketones such as acetone, methyl ethyl ketone, acetylacetone, butyl acetate, etc.; ethers such as methyl ethyl ether, dioxane, etc.; glycol ethers such as ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, propylene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol mono n-propyl ether, ethylene glycol dimethyl ether, diethylene glycol monomethyl ether, diethylene glycol dimethyl ether, dipropylene glycol monopropyl ether, etc.; glycol acetates such as ethylene glycol monoacetate, ethylene glycol diacetate, ethylene glycol monomethyl ether acetate, etc.; aliphatic hydrocarbons such as n-pentane, n-hexane, etc.; aromatic hydrocarbons such as toluene, xylene, solvent naphtha, etc.; etc. These may be used alone or in combination of two or more.

[0093] The content of the solvent in the copolymer-containing composition is preferably 15 to 99% by mass, more preferably 20 to 95% by mass, and particularly preferably 25 to 90% by mass. When the content of the solvent is equal to or more than the lower limit, the coating property is excellent. The copolymer-containing composition may further contain other components in addition to the copolymer. The content of the copolymer in the copolymer-containing composition is preferably 1 to 85 mass%, more preferably 5 to 80 mass%, further preferably 10 to 75 mass%, and particularly preferably 15 to 70 mass%. When the content of the copolymer is equal to or more than the lower limit, the coating film has an excellent effect of suppressing protein adhesion. The content of the copolymer relative to the total solid content of the copolymer-containing composition is preferably 10% by mass or more, more preferably 30% by mass or more, and may be 100% by mass.

[0094] The method for forming a coating film using the copolymer-containing composition is not particularly limited, but for example, a coating film can be formed on a substrate by a coating method such as dipping, spraying, or spin coating. The material of the substrate is not particularly limited, but examples thereof include polystyrene, polypropylene, polyethylene, polyurethane, PVC, nylon, silicone resin, glass, and metals such as stainless steel that can be coated on the surface.

[0095] Examples of articles having the coating film on a surface that comes into contact with plasma proteins include medical instruments such as scalpels, tweezers, contact lenses, cannulas, catheters, syringes, injection needles, intravenous routes, intravenous needles, intravenous bags, blood bags, gauze, stents, and endoscopes; biochemical instruments such as pipette tips, petri dishes, cells, microplates, storage bags, plates, reagent storage containers, and tubes; and cell therapy devices such as mixers, bioreactors, and jar fermenters. Examples of articles having the coating film on a surface that comes into contact with proteins other than plasma proteins include petri dishes for cell culture, cells for cell culture, microplates for cell culture, bags for cell culture, plates for cell culture, tubes for cell culture, flasks for cell culture, petri dishes for biopharmaceuticals, cells for biopharmaceuticals, microplates for biopharmaceuticals, plates for biopharmaceuticals, tubes for biopharmaceuticals, bags for biopharmaceuticals, containers for biopharmaceuticals, syringes for biopharmaceuticals, flasks for biopharmaceuticals, petri dishes for antibody pharmaceuticals, cells for antibody pharmaceuticals, microplates for antibody pharmaceuticals, plates for antibody pharmaceuticals, tubes for antibody pharmaceuticals, bags for antibody pharmaceuticals, containers for antibody pharmaceuticals, syringes for antibody pharmaceuticals, flasks for antibody pharmaceuticals, blood bags (whole blood, plasma, platelets, red blood cells), vials for blood products, bags for blood products, etc. EXAMPLES

[0096] The present invention will be described in more detail below with reference to examples and comparative examples, but the present invention is not limited to these examples. In the examples, "parts" refers to parts by mass.

[0097] <Measurement and evaluation methods> (Weight average molecular weight (Mw), number average molecular weight (Mn)) Measurements were performed using gel permeation chromatography (GPC) (Tosoh Corporation, HLC-8220). The columns used were TSKgel α-M (Tosoh Corporation, 7.8 mm x 30 cm) and TSKguard column α (Tosoh Corporation, 6.0 mm x 4 cm). A calibration curve was created using F288 / F1 / 28 / F80 / F40 / F20 / F2 / A1000 (Tosoh Corporation, standard polystyrene) and styrene monomer.

[0098] (Moldability evaluation) The copolymer or polymer of each example was molded using a press molding machine manufactured by Shoji Iron Works Co., Ltd. The molding conditions were 200° C., 18 MPa, and holding for 5 minutes to prepare a test plate with a thickness of 2 mm. The appearance and releasability of the test pieces obtained by press molding were observed, and the moldability was evaluated according to the following criteria. ◎: No molding defects, good demoldability. ◯: No molding defects, poor releasability. △: Molding is possible, but molding defects occur. ×: Difficult to mold.

[0099] (Indentation Elasticity) The indentation elastic modulus of the test plates prepared in the above moldability evaluation was measured using a microhardness tester (HM-2000, manufactured by Fisher Instruments) under the following measurement conditions: Vickers indenter, load 7 mN / 100 s, creep 60 s, R = 0.4 mN / 100 s.

[0100] (Protein adhesion test 1) Bovine serum albumin (BSA, Wako Pure Chemical Industries, Ltd.) was used as the protein to analyze the amount of adsorption. The BSA concentration and the sensor area (4.8 mm 2 The correlation between the amount of adsorption per unit area was calculated. The measurement was performed using a quartz crystal microbalance (QCM) device (AFFNIX Q8, manufactured by ULVAC, Inc.). The sensor chip was washed using an electrodeless excimer 172 nm irradiation device (model number: MDIRH-M-1-330, manufactured by MDCOM Co., Ltd.) The sensor chip surface was set to be within the treatment range, and treatment was performed 20 times at 5 mm / sec in automatic transport mode to wash and hydrophilize the sensor chip surface. The measurement data was analyzed using analysis software (AQUA, manufactured by ULVAC, Inc.).

[0101] (Protein adhesion test 2) Measurement and analysis were performed in the same manner as in Protein Adhesion Test 1, except that the protein for which the adsorption amount was analyzed was fibrinogen (derived from human plasma, Wako Pure Chemical Industries, Ltd.). (Protein adhesion test 3) The amount of BSA adsorbed to the molding material was evaluated by the above-mentioned Protein Adhesion Test (2) (μBCA method). (Protein adhesion test 4) Measurement and evaluation were performed in the same manner as in Protein Adhesion Test 3, except that the adsorbed protein was fibrinogen (derived from human plasma, Wako Pure Chemical Industries, Ltd.). (Protein adhesion test 5) Measurement and evaluation were performed in the same manner as in Protein Adhesion Test 3, except that the adsorbed protein was γ-globulin (derived from human plasma, Wako Pure Chemical Industries, Ltd.).

[0102] (Production Example 1) In a polymerization apparatus equipped with a stirrer, a cooling tube, and a thermometer, 900 parts of deionized water, 60 parts of 2-sulfoethyl sodium methacrylate, 10 parts of potassium methacrylate, and 12 parts of methyl methacrylate (MMA) were put and stirred, and the temperature was raised to 50°C while replacing the inside of the polymerization apparatus with nitrogen. 0.08 parts of 2,2'-azobis(2-methylpropionamidine) dihydrochloride were added thereto as a polymerization initiator, and the temperature was further raised to 60°C. After the temperature was raised, MMA was continuously dropped at a rate of 0.24 parts / min for 75 minutes using a dropping pump. The reaction solution was kept at 60°C for 6 hours, and then cooled to room temperature to obtain a dispersant 1 having a solid content of 10% by mass as a transparent aqueous solution.

[0103] Next, 145 parts of deionized water, 0.1 parts of sodium sulfate, and 0.25 parts of dispersant 1 (solid content 10% by mass) were added to a polymerization apparatus equipped with a stirrer, a cooling tube, and a thermometer, and stirred to obtain a uniform aqueous solution. Next, 100 parts of MMA, 0.0010 parts of bis[(difluoroboryl)diphenylglyoximate]cobalt(II) as a chain transfer agent, and 0.1 parts of "Perocta O" (registered trademark) (1,1,3,3-tetramethylbutylperoxy 2-ethylhexanoate, manufactured by NOF Corporation) as a polymerization initiator were added to obtain an aqueous suspension.

[0104] Next, the inside of the polymerization apparatus was replaced with nitrogen, the temperature was raised to 80°C and the reaction was carried out for 4 hours, and in order to further increase the polymerization rate, the temperature was raised to 90°C and maintained for 2 hours. Thereafter, the reaction liquid was cooled to 40°C to obtain an aqueous suspension containing a macromonomer. This aqueous suspension was filtered, and the filtrate was washed with deionized water, dehydrated, and dried at 40°C for 16 hours to obtain a macromonomer (MM1). The number average molecular weight of this macromonomer (MM1) was 15,000, and the molecular weight distribution (Mw / Mn) was 2.4.

[0105] (Production Example 2) The same procedure as in Production Example 1 was repeated except that 100 parts of MMA, 0.0009 parts of bis[(difluoroboryl)diphenylglyoximate]cobalt(II) as a chain transfer agent, and 0.12 parts of "Perocta O" (registered trademark) (1,1,3,3-tetramethylbutylperoxy 2-ethylhexanoate, manufactured by NOF Corporation) as a polymerization initiator were added. The number average molecular weight of the obtained macromonomer (MM2) was 21,000, and the molecular weight distribution (Mw / Mn) was 2.1.

[0106] (Production Example 3) The same procedure as in Production Example 1 was repeated except that 95 parts of MMA, 5 parts of MA, 0.0016 parts of bis[(difluoroboryl)diphenylglyoximate]cobalt(II) as a chain transfer agent, and 0.12 parts of "Perocta O" (registered trademark) (1,1,3,3-tetramethylbutylperoxy 2-ethylhexanoate, manufactured by NOF Corporation) as a polymerization initiator were added. The number average molecular weight of the obtained macromonomer (MM3) was 15,000, and the molecular weight distribution (Mw / Mn) was 2.3.

[0107] The following Example 1 is an embodiment, and Examples 2 to 4 are comparative examples. In Table 1, St represents styrene, MMA represents methyl methacrylate, MEA represents methoxyethyl acrylate, and n-OM represents n-octyl mercaptan.

[0108] [Example 1] An aqueous dispersion medium for suspension was prepared by mixing 145 parts of deionized water, 0.3 parts of sodium sulfate, and 0.26 parts of Dispersant 1 produced in Production Example 1. In a flask equipped with a condenser, 40 parts of the macromonomer (MM1) produced in Production Example 1, 60 parts of methoxyethyl acrylate (Osaka Organic Chemical Co., Ltd.), and 0.2 parts of n-octyl mercaptan (Kanto Chemical Co., Ltd., product name) as a nonmetallic chain transfer agent were charged, and the mixture was heated to 55°C with stirring to obtain a composition in a syrup state. After cooling the composition to 40°C or lower, 0.325 parts of AMBN (Fujifilm Wako Pure Chemical Industries, Ltd., 2,2'-azobis(2-methylbutyronitrile), product name) was dissolved in the composition to obtain a raw material composition.

[0109] Next, the above-mentioned aqueous dispersion medium for suspension was added to the raw material composition, and the atmosphere inside the separable flask was replaced with nitrogen by nitrogen bubbling while increasing the stirring speed to obtain a syrup dispersion.

[0110] The temperature of the syrup dispersion was increased to 75° C., and the external temperature of the separable flask was maintained at that temperature. After the peak of the heat generated by polymerization appeared, when the temperature of the syrup dispersion reached 75° C., the temperature of the syrup dispersion was increased to 85° C. and maintained for 30 minutes to complete the polymerization, thereby obtaining a suspension.

[0111] After cooling the suspension to below 40°C, the suspension was filtered through a filter cloth, and the filtrate was washed with deionized water and dried at 70°C for 12 hours to obtain a copolymer. The molecular weights (Mn, Mw) and physical properties (formability, indentation modulus) of the obtained copolymer are shown in Table 1 (the same applies below). Table 1 also shows the mass ratio of structural unit (a) to structural unit (b) and the amount of non-metallic chain transfer agent added per 100 parts by mass of the total of structural unit (a) and structural unit (b) (hereinafter the same).

[0112] The copolymer obtained was dissolved in methylcellulose and subjected to a protein adhesion test. The results are shown in Table 1 (the same applies below).

[0113] [Example 2] Into a flask equipped with a cooling tube, 100 parts of methoxyethyl acrylate (Osaka Organic Co., Ltd.) and 250 parts of methyl cellosolve (Kanto Chemical Co., Ltd., special grade reagent) were charged as a solvent, and the inside was replaced with nitrogen by nitrogen bubbling. Next, the monomer composition in the flask was heated to keep the internal temperature at 70°C, and 0.8 parts of 2,2'-azobisisobutyronitrile (AIBN) (Wako Pure Chemical Co., Ltd., special grade reagent) was added as a radical polymerization initiator to the monomer composition, and the mixture was held for 4 hours, then heated to 80°C and held for 1 hour to complete the polymerization. After this, the polymerization reaction product was cooled to room temperature and reprecipitated with a large amount of diisopropyl ether (Junsei Chemical Co., Ltd.). The polymer precipitated by reprecipitation was collected and vacuum-dried overnight at 50°C and 50mmHg (6.67kPa) or less to obtain a copolymer. The resulting copolymer was a viscous polymer with high fluidity and could not be molded. The resulting copolymer was dissolved in methylcellulose and subjected to a protein adhesion test.

[0114] [Example 3] A polystyrene powder (standard polystyrene, F-4, Tosoh Corporation) with a number average molecular weight of 50,000 and a weight average molecular weight of 50,500 was dissolved in xylene (Wako Pure Chemical Industries, Ltd.) and spin-coated onto a substrate, then dried to form a coating film. A protein adhesion test was performed on the resulting coating film. The moldability was also evaluated using the above method.

[0115] [Example 4] Polymethyl methacrylate (VHK000, manufactured by Mitsubishi Chemical Corporation) with a number average molecular weight of 54,900 and a weight average molecular weight of 108,000 was dissolved in xylene (manufactured by Wako Pure Chemical Industries, Ltd.) and spin-coated onto a substrate, then dried to form a coating film. A protein adhesion test was conducted on the resulting coating film. The moldability was also evaluated by the above-mentioned method.

[0116] [Table 1]

[0117] Figure 1 is a graph showing the results of the protein adhesion test in Table 1. In Figure 1, the horizontal axis represents the BSA concentration, and the vertical axis represents the amount of BSA adsorbed by the copolymer. As shown in the results of Table 1 and FIG. 1, the copolymer of Example 1 has a superior protein adhesion inhibitory effect to the polymers of Examples 2-4. Moreover, the molded article of the copolymer of Example 1 has a lower indentation modulus of elasticity than the molded articles of the polymers of Examples 3 and 4, and is excellent in moldability.

[0118] The following Examples 5, 6, 9 to 23, 24, and 26 to 30 are working examples, and Examples 7, 8, 25, and 32 are comparative examples. [Example 5] A molding material was prepared by kneading 70 parts of polymethyl methacrylate (VHK000) and 30 parts of the copolymer obtained in Example 1 in a Labo Plastomill at 250°C and 30 rpm for 5 minutes. The obtained molding material was molded in a press molding machine manufactured by Shoji Iron Works Co., Ltd. The molding conditions were 200°C and 18 MPa, and the molded body was held for 5 minutes to produce a molded body with a thickness of 2 mm. The obtained molded body was subjected to a protein adhesion test by the protein adhesion test (2) (μBCA method) described above. The test results are shown in Table 3 (same below). [Example 6] The same procedure as in Example 5 was repeated, except that the amount of the copolymer obtained in Example 1 was changed to 100 parts. [Example 7] The same procedure as in Example 5 was repeated, except that the amount of VHK000 used was changed to 100 parts. [Example 8] The same procedure as in Example 5 was repeated, except that the amount of olefin resin MC638 (trade name, manufactured by Mitsubishi Chemical Corporation) used was changed to 100 parts. [Example 9] Into a flask equipped with a cooling tube, 51 parts of methoxyethyl acrylate (manufactured by Osaka Organic Co., Ltd.), 9 parts of 2-hydroxyethyl methacrylate (manufactured by Mitsubishi Chemical Corporation, Acryester (registered trademark) HO), 40 parts of the macromonomer (MM2) produced in Production Example 2, and 150 parts of N,N-dimethylacetamide (manufactured by Wako Pure Chemical Industries, Ltd., special grade reagent) as a solvent were charged, and the inside was replaced with nitrogen by nitrogen bubbling. Next, the monomer composition in the flask was heated to keep the internal temperature at 55°C, and 0.1 parts of 2,2'-azobis(2,4'-dimethylvaleronitrile) (manufactured by Wako Pure Chemical Industries, Ltd., trade name: V-65) was added as a radical polymerization initiator to the monomer composition, and then the mixture was held for 4 hours. Next, the temperature was raised to 80°C, 0.15 parts of V-65 was added, and the mixture was held for 60 minutes to complete the polymerization. The polymerization reaction product was then cooled to room temperature and reprecipitated with a large amount of pure water. The polymer precipitated by reprecipitation was collected and vacuum dried overnight at 50°C and 50 mmHg (6.67 kPa) or less to obtain a copolymer. The number average molecular weight was 66,000 and the weight average molecular weight was 217,000. The same procedure as in Example 5 was repeated except that the amount of the obtained copolymer was changed to 100 parts by weight. [Example 10] An aqueous dispersion medium for suspension was prepared by mixing 144 parts of deionized water and 0.3 parts of sodium sulfate. In a flask equipped with a condenser, 40 parts of the macromonomer (MM3) produced in Production Example 3, 58 parts of methoxyethyl acrylate (Osaka Organic Co., Ltd.), 2 parts of 2-hydroxyethyl methacrylate (Mitsubishi Chemical Co., Ltd., Acryester (registered trademark) HO), and 0.2 parts of n-octyl mercaptan (Kanto Chemical Co., Ltd., product name) as a nonmetallic chain transfer agent were charged, and the mixture was heated to 55°C while stirring to obtain a composition in a syrup state. After cooling the composition to 40°C or lower, 0.325 parts of AMBN (Fujifilm Wako Pure Chemical Co., Ltd., 2,2'-azobis(2-methylbutyronitrile), product name) was dissolved in the composition to obtain a raw material composition.

[0119] Next, the above-mentioned aqueous dispersion medium for suspension was added to the raw material composition, and the atmosphere inside the separable flask was replaced with nitrogen by nitrogen bubbling while increasing the stirring speed to obtain a syrup dispersion.

[0120] An aqueous dispersion medium prepared by mixing 0.26 parts of Dispersant 1 prepared in Preparation Example 1 and 1 part of deionized water was charged into a flask, and then the temperature was raised to 75° C. and the external temperature of the separable flask was maintained. After the peak of the heat generated by polymerization appeared, when the syrup dispersion reached 75° C., the temperature of the syrup dispersion was raised to 85° C. and maintained for 30 minutes to complete the polymerization, thereby obtaining a suspension.

[0121] After cooling the suspension to 40° C. or less, the suspension was filtered through a filter cloth, and the filtrate was washed with deionized water and dried at 70° C. for 12 hours to obtain a copolymer. The number average molecular weight was 37,500 and the weight average molecular weight was 224,000. The same procedure as in Example 5 was repeated, except that the amount of the obtained copolymer was changed to 100 parts by weight. [Example 11] The same procedure was carried out as in Example 1, except that the macromonomer (MM3) produced in Production Example 3 was used. The number average molecular weight was 42,700, and the weight average molecular weight was 295,000. The same procedure was carried out as in Example 5, except that the amount of the obtained copolymer used was changed to 100 parts by weight. The copolymers of Example 1 and Examples 9 to 11 are summarized in Table 2. [Example 12 to Example 18] The same procedure as in Example 5 was repeated except that the copolymer and thermoplastic resin were changed to the ratios shown in Table 4. [Example 19 to Example 25] The same procedure as in Example 5 was repeated, except that the protein was changed to fibrinogen (FB) and the copolymer and thermoplastic resin were changed to the ratios shown in Table 5. [Example 26 to Example 32] The same procedure as in Example 5 was repeated except that the protein was changed to gamma globulin (IgG) and the copolymer and thermoplastic resin were changed to the ratios shown in Table 6.

[0122] [Table 2]

[0123] [Table 3]

[0124] [Table 4]

[0125] [Table 5]

[0126] [Table 6]

[0127] As shown in the results of Tables 3 to 6, the molding materials of Examples 5, 6, 9 to 24, and 26 to 31, which contain the copolymer of the present invention, have a superior protein adhesion inhibitory effect to the molding materials of Examples 7, 8, 25, and 32, which do not contain the copolymer of the present invention. [Industrial Applicability]

[0128] The copolymer of the present invention can impart a protein adhesion inhibitory effect to a molded article. The copolymer of the present invention can impart a protein adhesion inhibitory effect to a coating film. The copolymers of the present invention are suitable for the manufacture of articles that come into contact with proteins. For example, the present invention is suitable for the manufacture of medical instruments such as scalpels, tweezers, contact lenses, cannulas, catheters, syringes, injection needles, intravenous routes, intravenous needles, intravenous bags, blood bags, gauze, stents, and endoscopes; and articles that come into contact with plasma proteins, such as pipette tips, petri dishes, cells, microplates, storage bags, plates, reagent storage containers, and tubes.

Claims

1. A melt molding material comprising a protein adhesion inhibiting copolymer, A melt molding material comprising a copolymer for inhibiting protein adhesion, the copolymer having, in one molecule thereof, a polymer chain (3A) containing a structural unit (a) represented by the following formula (3A) and a polymer chain (3B) containing a structural unit (b) represented by the following formula (3B), the copolymer having a weight average molecular weight of 75,000 or more and 1,000,000 or less as measured by gel filtration chromatography, and the structural unit (b) accounting for more than 50 mass% and 95 mass% or less of the total mass of the structural units (a) and (b) present in the copolymer. 【Chemistry 1】 (In formula (3A), R １ represents a hydrogen atom or a methyl group, R ２ Is OR ３３ , halogen atom, COR ３４ , COOR ３５ , C.N., C.O.R. ３６ R ３７ Or R ３８ and R ３３ ~R ３７ each independently represents a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alicyclic group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted non-aromatic heterocyclic group, a substituted or unsubstituted aralkyl group, a substituted or unsubstituted alkaryl group, or a substituted or unsubstituted organosilyl group; R ３８ represents a substituted or unsubstituted aryl group, or a substituted or unsubstituted heteroaryl group; and n is a natural number from 1 to 1,000,000. (In formula (3B), R ３ represents a hydrogen atom or a methyl group, R ４ represents an alkylene group having 1 to 4 carbon atoms; R ５ represents a hydrocarbon group having 1 to 6 carbon atoms. m is a natural number from 1 to 1,000,000.

2. The melt molding material according to claim 1 , wherein the structural unit (a) is a structural unit derived from a (meth)acrylic acid ester.

3. The melt molding material according to claim 1 or 2, which has a structural unit (d) derived from a macromonomer represented by the following formula (4) containing the structural unit (a): 【Chemistry 2】 (In the formula, R ６ each independently represents a hydrogen atom, an unsubstituted or substituted alkyl group, an unsubstituted or substituted alicyclic group, an unsubstituted or substituted aryl group, an unsubstituted or substituted heteroaryl group, or an unsubstituted or substituted non-aromatic heterocyclic group; ６ may be the same or different, R ７ represents a hydrogen atom or a methyl group, and a plurality of R ７ may be the same or different, Z is a terminal group, n １ is a natural number between 2 and 10,000.)

4. The structural unit (b) is selected from the group consisting of methoxymethyl acrylate, methoxyethyl acrylate, methoxypropyl acrylate, methoxybutyl acrylate, ethoxymethyl acrylate, ethoxyethyl acrylate, ethoxypropyl acrylate, ethoxybutyl acrylate, propoxymethyl acrylate, propoxyethyl acrylate, propoxypropyl acrylate, propoxybutyl acrylate, butoxymethyl acrylate, butoxyethyl acrylate, butoxypropyl acrylate, butoxybutyl acrylate, methoxymethyl methacrylate, and methoxyethyl methacrylate. The melt molding material according to any one of claims 1 to 3, which is derived from a monomer selected from the group consisting of methoxypropyl methacrylate, methoxybutyl methacrylate, ethoxymethyl methacrylate, ethoxyethyl methacrylate, ethoxypropyl methacrylate, ethoxybutyl methacrylate, propoxymethyl methacrylate, propoxyethyl methacrylate, propoxypropyl methacrylate, propoxybutyl methacrylate, butoxymethyl methacrylate, butoxyethyl methacrylate, butoxypropyl methacrylate, and butoxybutyl methacrylate.

5. The melt molding material according to any one of claims 1 to 4, wherein the total mass of the structural units (b) in all structural units is greater than the total mass of the structural units (a).

6. The melt molding material according to any one of claims 1 to 5, further comprising a thermoplastic resin and containing 1% by mass or more of the protein adhesion inhibiting copolymer.

7. The melt molding material according to claim 6, wherein the thermoplastic resin is a (meth)acrylic resin or an olefin resin.

8. An article molded from the melt molding material according to any one of claims 1 to 7, The molded article is any one selected from the group consisting of medical instruments, biochemical instruments, and cell therapy devices, which come into contact with plasma proteins, or any one selected from the group consisting of a petri dish for cell culture, a cell culture cell, a microplate for cell culture, a bag for cell culture, a cell culture plate, a tube for cell culture, a flask for cell culture, a petri dish for a biopharmaceutical, a cell for a biopharmaceutical, a microplate for a biopharmaceutical, a plate for a biopharmaceutical, a tube for a biopharmaceutical, a bag for a biopharmaceutical, a container for a biopharmaceutical, a syringe for a biopharmaceutical, a flask for a biopharmaceutical, a petri dish for an antibody pharmaceutical, a cell for an antibody pharmaceutical, a microplate for an antibody pharmaceutical, a plate for an antibody pharmaceutical, a tube for an antibody pharmaceutical, a bag for an antibody pharmaceutical, a container for an antibody pharmaceutical, a syringe for an antibody pharmaceutical, and a flask for an antibody pharmaceutical, a blood bag, a vial for a blood product, and a bag for a blood product, which come into contact with proteins other than plasma proteins.

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