JP2022109720A - Polymer material, coating liquid, coating film, additive and medical tool - Google Patents

Abstract

To provide a polymer material that has a high effect of inhibiting adsorption of protein and the like and also has high shear resistance, and provide a coating liquid, a coating film, an additive and a medical tool.SOLUTION: The present invention discloses a polymer material for use in a coating liquid, a coating film, an additive and a medical tool, the polymer material including: at least one selected from a unit based on a hydrophilic polyoxyalkylene chain-bearing monomer (A1) and a residue of a hydrophilic polyoxyalkylene chain-bearing polymerization initiator (A2); and a unit based on a specific cyclic monomer (B). The total content of the unit based on the monomer (A1) and the residue of the polymerization initiator (A2) is 8 mass% or more.SELECTED DRAWING: None

Description

TECHNICAL FIELD The present invention relates to polymeric materials, coating liquids, coating films, additives and medical devices.

When blood, protein, etc. adhere to a medical device that comes into contact with the living body, its performance is significantly reduced, and there is a possibility of causing a serious injury to the patient. Therefore, attempts have been made to form a coating film made of a polymer having a polyoxyethylene chain on the surface of a medical device to suppress the adsorption of blood and proteins (for example, Patent Document 1).

JP 2016-112396 A

However, in the ecological environment, medical devices are exposed to the shearing environment of blood and body fluids. It is difficult to obtain sufficient shear resistance with conventional coating films such as those disclosed in Patent Document 1. As a method for improving shear resistance, for example, it is conceivable to introduce a cross-linking component into the polymer and harden it to increase the rigidity of the coating film. However, when the mobility of the polymer is reduced by cross-linking, the effect of inhibiting adsorption of proteins and the like is remarkably reduced.

An object of the present invention is to provide a polymer material, a coating liquid, a coating film, an additive, and a medical device that have a high effect of suppressing adsorption of proteins and the like and are also excellent in shear resistance.

The present invention has the following aspects.
[1] at least one selected from units based on a monomer (A1) having a hydrophilic polyoxyalkylene chain and residues of a polymerization initiator (A2) having a hydrophilic polyoxyalkylene chain;
Based on at least one cyclic monomer (B) selected from monomers represented by the following formula (1) and monomers represented by the following formula (2), each of which has a homopolymer glass transition temperature of 80° C. or higher including units and
A polymer material, wherein the total content of units based on the monomer (A1) and residues of the polymerization initiator (A2) is 8% by mass or more.

(In the above formula, R ¹ is a hydrogen atom, a fluorine atom, a phenyl group, an alkyl group having 1 to 4 carbon atoms, a perfluoroalkyl group having 1 to 6 carbon atoms, an epoxy group, an isocyanate group, a hydroxy group, an amino group. , or a carboxy group, R ² to R ⁴ are each independently a hydrogen atom, a fluorine atom, a phenyl group, an alkyl group having 1 to 4 carbon atoms, a perfluoroalkyl group having 1 to 6 carbon atoms, an epoxy group, an isocyanate group , a hydroxy group, an amino group, or a carboxy group.)
[2] The total content of units based on the monomer (A1) and residues of the polymerization initiator (A2) is 8 to 35% by mass, and the content of units based on the cyclic monomer (B) is 10. The polymer material according to [1], which is ∼35% by mass.
[3] The polymer material according to [1] or [2], which contains a residue of the polymerization initiator (A2), and the polymerization initiator (A2) is a polymerization initiator having a polyoxyethylene chain.
[4] The polymerization initiator having a polyoxyethylene chain is an ester of 4,4′-azobis(4-cyanovaleric acid) and polyoxyethylenediol, polyoxyethylene-bis(2-bromoisobutyrate), Alternatively, the polymeric material according to [3], which is methoxypolyoxyethylene-2-bromoisobutyrate.
[5] The unit according to any one of [1] to [4], wherein the unit based on the cyclic monomer (B) includes a unit based on the monomer represented by the formula (1), wherein R ¹ is a phenyl group. polymer material.
[6] Any one of [1] to [5], wherein the unit based on the cyclic monomer (B) includes a unit based on the monomer represented by the formula (2) in which all of R ² to R ⁴ are hydrogen atoms. The polymeric material according to 1.
[7] A coating liquid containing the polymer material according to any one of [1] to [6].
[8] The coating liquid according to [7], which is a coating agent for medical devices.
[9] The coating liquid according to [7], which is a coating agent for water treatment.
[10] A coating film formed by drying with the coating liquid according to any one of [7] to [9].
[11] The coating film according to [10], wherein the change in elastic modulus defined below from the film surface in water is 2.0 or more.
Change in elastic modulus: A coating solution is applied to a silicon wafer cut into 2 cm squares, dried in an oven at 40° C. for 30 minutes to form a coating film with a thickness of 1 μm, and left to stand in a phosphate buffer solution for 1 hour. do. Using an atomic force microscope (AFM Cypher S), the elastic modulus of the coating film is measured in force curve mode with a probe having a spring constant of 2 N/m and a tip curvature radius R of 7 nm. X is the average elastic modulus at a distance of 0 to 0.2 μm in the film thickness direction from the film surface, and Y is the average elastic modulus at a distance of 0.2 μm to 0.4 μm in the film thickness direction from the film surface. Define Y/X as the modulus change.
[12] An additive comprising the polymeric material according to any one of [1] to [6].
[13] A medical device provided with the coating film of [10] or [11], or to which the additive of [12] is added.
[14] The medical device according to [13], which is a catheter, stent, endoscope, heart-lung machine, dialysis membrane, or artificial blood vessel.

An object of the present invention is to provide a polymer material, a coating liquid, a coating film, an additive, and a medical device, which have a high effect of inhibiting adsorption of proteins and the like and have excellent shear resistance.

Definitions of the following terms used herein are as follows.
A "monomer" refers to a compound having a polymerizable unsaturated bond. Examples of polymerizable unsaturated bonds include double bonds and triple bonds between carbon atoms.
A "unit based on a monomer" refers to an atomic group directly formed from one molecule of a monomer by polymerization and an atomic group obtained by chemically converting a part of the atomic group in the polymer.
"(Meth)acrylate" is a generic term for acrylate and methacrylate.
"~" indicating a numerical range includes the numerical values described before and after it as a lower limit and an upper limit.

[Polymer material]
The polymeric material of the present invention comprises at least one selected from units based on a monomer (A1) having a hydrophilic polyoxyalkylene chain and residues of a polymerization initiator (A2) having a hydrophilic polyoxyalkylene chain, All of them are polymers containing units based on a specific cyclic monomer (B) whose homopolymer has a glass transition point of 80° C. or higher. In addition to units based on the monomer (A1), residues of the polymerization initiator (A2), and units based on the cyclic monomer (B), the polymeric material of the present invention includes units based on the hydrophobic monomer (C), and hydrophilic At least one of the units based on the polar monomer (D) may be included.

The polymeric material of the present invention may contain either one of the units based on the monomer (A1) and the residue of the polymerization initiator (A2), or may contain both. The polymeric material of the present invention preferably contains a residue of the polymerization initiator (A2).

The hydrophilic polyoxyalkylene chains possessed by the monomer (A1) and the polymerization initiator (A2) are polyoxyalkylene chains mainly composed of oxyethylene groups.
The polyoxyalkylene chain may have an oxyalkylene group other than an oxyethylene group, and the oxyalkylene group other than the oxyethylene group is preferably an oxyalkylene group having 3 to 6 carbon atoms, and an oxyalkylene group having 3 carbon atoms. groups are more preferred. Oxyalkylene groups other than oxyethylene groups include 1,2-oxypropylene group, 1,2-oxybutylene group, 2,3-oxybutylene group and 1,4-oxybutylene group. When the hydrophilic polyoxyalkylene chain has an oxyalkylene group other than an oxyethylene group, the arrangement of the oxyethylene group and the other oxyalkylene group may be random, block or alternate.

A hydrophilic polyoxyalkylene chain is a polyoxyalkylene chain in which the ratio of the number of oxyethylene groups to the total number of oxyalkylene groups is 30% or more. The percentage of oxyethylene groups in the hydrophilic polyoxyalkylene chain is preferably 30% or more, more preferably 50% or more, still more preferably 70% or more, and particularly 90% or more, relative to the total number of oxyalkylene groups. preferable.

The monomer (A1) and the polymerization initiator (A2) are preferably diols or monool derivatives having a hydrophilic polyoxyalkylene chain. Further, a monomer or initiator having an active hydrogen-containing group capable of ring-opening addition polymerization of alkylene oxide may be subjected to ring-opening addition polymerization of alkylene oxide such as ethylene oxide to obtain a monomer (A1) or a polymerization initiator (A2). can. The active hydrogen-containing group with which the alkylene oxide can undergo ring-opening addition polymerization is a group having a hydrogen atom bonded to an oxygen atom, a nitrogen atom, or the like (hydroxyl group, carboxyl group, amino group, etc.).
Diols having a polyoxyethylene chain include diols obtained by ring-opening addition polymerization of ethylene oxide to a compound having two active hydrogens such as ethylene glycol and propylene glycol. Examples of monools having a polyoxyethylene chain include diols obtained by ring-opening addition polymerization of ethylene oxide to compounds having one active hydrogen such as alkanols and monocarboxylic acids. As the diol, polyoxyethylene diol (also called polyethylene glycol) having a structure obtained by ring-opening addition polymerization of ethylene oxide to ethylene glycol is preferable. Monool has a structure obtained by ring-opening addition polymerization of ethylene oxide to alkanol such as methanol and ethanol. Alkoxypolyoxyethylene monools (also called alkoxypolyethylene glycols) are preferred. A monomer (A1) or a polymerization initiator (A2) can be obtained by reacting these diols or monools with a monomer having a hydroxyl group-reactive group (for example, a carboxyl group) or an initiator.

Examples of the monomer (A1) include (meth)acrylates having hydrophilic polyoxyalkylene chains, vinyl ethers, styrene derivatives, and (di)ester fumarates. Specifically, for example, methoxypolyethylene glycol (meth)acrylate, ethoxypolyethylene glycol (meth)acrylate, and polyethylene glycol (meth)acrylate can be exemplified. From the viewpoint of protein adsorption suppression effect, the monomer (A1) is preferably a (meth)acrylate having a polyoxyalkylene chain, more preferably a methoxypolyethyleneglycol (meth)acrylate or an ethoxypolyethyleneglycol (meth)acrylate. When the monomer (A1) is used in the polymer material of the present invention, the number of monomers (A1) used may be one, or two or more.

Examples of the polymerization initiator (A2) include the following polymerization initiators (A21) to (A23). The polymerization initiator (A2) is preferably a polymerization initiator having a polyoxyethylene chain, more preferably a polymerization initiator (A21), a polymerization initiator (A22) and a polymerization initiator (A23), and a polymerization initiator (A21 ) is particularly preferred.
Polymerization initiator (A21): ester of 4,4′-azobis (4-cyanovaleric acid) and polyoxyethylenediol Polymerization initiator (A22): polyoxyethylene-bis(2-bromoisobutyrate)
Polymerization initiator (A23): methoxypolyoxyethylene-2-bromoisobutyrate

The polymerization initiator (A21) is a polymer having a structure represented by the formula (a21) below.

a in the formula (a21) is an integer of 5-300. b is an integer from 1 to 20;

From the viewpoint that proteins and the like are less likely to be adsorbed, a is preferably an integer of 10 to 200, particularly preferably an integer of 20 to 100.
b is preferably an integer of 2 to 20, particularly preferably an integer of 5 to 15, from the viewpoint of facilitating polymerization.
As the polymerization initiator (A21), Wako Pure Chemical Industries, Ltd.'s VPE series (VPE-0201, VPE-0401, VPE-0601) can be exemplified.

The cyclic monomer (B) includes a monomer represented by the following formula (1) (hereinafter also referred to as "monomer (B1)") and a monomer represented by the following formula (2) (hereinafter referred to as "monomer (B2) " is also described.) is a monomer selected from the group consisting of. Both the homopolymer of the monomer (B1) and the homopolymer of the monomer (B2) have a glass transition point of 80° C. or higher.

However, in the above formula, R ¹ is a hydrogen atom, a fluorine atom, a phenyl group, an alkyl group having 1 to 4 carbon atoms, a perfluoroalkyl group having 1 to 6 carbon atoms, an epoxy group, a cycloalkyl group, an isocyanate group, a hydroxy group. , an amino group, or a carboxy group. R ² to R ⁴ each independently represent a hydrogen atom, a fluorine atom, a phenyl group, an alkyl group having 1 to 4 carbon atoms, a fluoroalkyl group having 1 to 6 carbon atoms, an epoxy group, an isocyanate group, a hydroxy group, an amino group, or a carboxy group.

From the viewpoint of shear durability, R ¹ is preferably a phenyl group, an alkyl group having 1 to 4 carbon atoms, a perfluoroalkyl group having 1 to 6 carbon atoms, an epoxy group, or a cycloalkyl group. 4 alkyl groups, C 1-6 perfluoroalkyl groups and cycloalkyl groups are more preferred, and a phenyl group is particularly preferred.

From the viewpoint of availability, R ² to R ⁴ are each independently preferably a hydrogen atom, a methyl group, an ethyl group, a hydroxy group, an amino group, or a perfluoroalkyl group, more preferably a hydrogen atom or a hydroxy group, and a hydrogen atom. Atoms are particularly preferred.

The cyclic monomer (B) may contain only one of the monomer (B1) and the monomer (B2), or may contain both the monomer (B1) and the monomer (B2). The cyclic monomer (B) preferably contains at least one of a monomer (B1) in which R ¹ is a phenyl group and a monomer (B2) in which all of R ² to R ⁴ are hydrogen atoms.

The homopolymer of the cyclic monomer (B) has a glass transition point of 80° C. or higher, more preferably 90° C. or higher. When the glass transition point is at least the lower limit of the range, shear resistance is excellent.
The cyclic monomer (B) used in the polymeric material of the present invention may be one kind or two or more kinds.

Hydrophobic monomer (C) is a monomer selected from the group consisting of fluorine-containing monomers, silicone monomers, and (meth)acrylates having an alkyl group or a cycloalkyl group. Including units based on the hydrophobic monomer (C) in the polymeric material of the present invention enhances water resistance and shear resistance. The number of hydrophobic monomers (C) used in the polymeric material of the present invention may be one, or two or more.

The fluorine-containing monomer is a monomer having a fluorine atom, and is preferably a monomer represented by the following formula (3) (hereinafter also referred to as "monomer (C1)").

However, in the above formula, ^R5 is a hydrogen atom, a chlorine atom or a methyl group. c is an integer from 0 to 3; ^R6 and ^R7 are each independently a hydrogen atom, a fluorine atom or a trifluoromethyl group. R ^f1 is a perfluoroalkyl group having 1 to 20 carbon atoms.

In formula (3), R ⁵ is preferably a hydrogen atom or a methyl group from the viewpoint of ease of polymerization.
c is preferably an integer of 1 to 3, particularly preferably 1 or 2, from the viewpoint of excellent flexibility of the polymeric material.
As R ⁶ and R ⁷ , a fluorine atom is preferable from the viewpoint of excellent water resistance.
The perfluoroalkyl group of R ^f1 may be linear or branched. R ^f1 is preferably a perfluoroalkyl group having 1 to 10 carbon atoms, particularly preferably a perfluoroalkyl group having 1 to 6 carbon atoms, from the viewpoint of easy availability of raw materials.

Specific examples of the monomer (C1) include the following compounds.
_CH2 =C( _CH3 )COO( _CH2 ) _{2 (} CF2) _{5CF3 (} hereinafter also referred to as "C6FMA"),
_CH2 =CHCOO( _CH2 ) _{2 (} CF2) _{5CF3 (} hereinafter also referred to as "C6FA"),
_CH2 =C( _CH3 ) _{COOCH2CF3 ,
CH2} = _{CHCOOCH2CF3 ,
CH2 =} ^CR5COO _{( CH2} ) _{eCF2CF2CF3 ,
CH2} = ^CR5COO ( _CH2 ) _{eCF2CF ( CF3} ) ₂ ,
_CH2 = ^CR5COOCH ( _CF3 ) ₂ ,
_CH2 = ^CR5COOC ( _CF3 ) ₃ and the like.

As the monomer (C1), C6FMA and C6FA are preferable from the viewpoint of availability.
One type or two or more types of fluorine-containing monomers may be used in the polymer material of the present invention.

The silicone monomer is a monomer having a hydrolyzable silyl group, preferably a monomer represented by the following formula (4) (hereinafter also referred to as "monomer (C2)").

However, ⁱⁿ said formula, R8 is a hydrogen atom, a chlorine atom, or a methyl group. d is an integer from 0 to 3; R ⁹ and R ¹⁰ are each independently an alkyl group having 1 to 22 carbon atoms. R ¹¹ is an alkyl group having 1 to 22 carbon atoms. e is an integer from 1 to 200;

In formula (4), R ⁸ is preferably a hydrogen atom or a methyl group from the viewpoint of ease of polymerization.
d is preferably an integer of 1 to 3, particularly preferably 1 or 2, from the viewpoint of excellent flexibility of the polymeric material.
The alkyl groups of R ⁹ to R ¹¹ may be linear or branched. From the standpoint of availability, R ⁹ and R ¹⁰ are preferably alkyl groups having 1 to 3 carbon atoms, and particularly preferably methyl groups. R ¹¹ is preferably an alkyl group having 1 to 3 carbon atoms, particularly preferably an alkyl group having 1 to 2 carbon atoms, from the standpoint of availability.

As the monomer (C2), from the standpoint of availability, in formula (4), R ⁸ to R ¹⁰ are methyl groups, d is 2, e is 1 to 200, and R ¹¹ has a number of carbon atoms. Compounds with 1 to 2 alkyl groups are preferred.
One type or two or more types of silicone monomers may be used in the polymer material of the present invention.

As the (meth)acrylate having an alkyl group or a cycloalkyl group, a monomer represented by the following formula (5) (hereinafter also referred to as "monomer (C3)") is preferable.
CH ₂ =CR ¹² -COO-R ¹³ (5)
However, in said formula, ^R12 is a hydrogen atom, a chlorine atom, or a methyl group. R ¹³ is an alkyl group having 1 to 22 carbon atoms or a cycloalkyl group having 3 to 30 carbon atoms.

In formula (5), R ¹² is preferably a hydrogen atom or a methyl group from the viewpoint of ease of polymerization.
The alkyl group of R ¹³ may be linear or branched. From the viewpoint of hydrophobicity, R ¹³ is preferably an alkyl group having 1 to 22 carbon atoms, a cycloalkyl group having 3 to 30 carbon atoms, an alkyl group having 4 to 22 carbon atoms, or a cycloalkyl group having 5 to 10 carbon atoms. is particularly preferred.

Examples of the monomer (C3) include butyl (meth)acrylate, 2-ethylhexyl (meth)acrylate, dodecyl (meth)acrylate, stearyl (meth)acrylate), behenyl (meth)acrylate, and isobornyl (meth)acrylate. .
One type or two or more types of (meth)acrylates having an alkyl group or a cycloalkyl group may be used in the polymer material of the present invention.

A hydrophilic polar monomer (D) is a monomer having a hydrophilic functional group. When the polymer material of the present invention contains units based on the hydrophilic polar monomer (D), shear resistance and the effect of inhibiting adsorption of proteins and the like are enhanced. The hydrophilic polar monomer (D) used in the polymer material of the present invention may be one type or two or more types. A hydroxy group can be exemplified as the hydrophilic functional group.

Examples of hydrophilic polar monomers (D) include (meth)acrylates having a hydroxy group. Specifically, for example, 2-hydroxyethyl (meth) acrylate, 1-hydroxypropyl (meth) acrylate, 2-hydroxypropyl (meth) acrylate, 3-hydroxypropyl (meth) acrylate, 1-hydroxybutyl (meth) Acrylates can be exemplified. Among them, 2-hydroxyethyl methacrylate (HEMA) and 2-hydroxypropyl methacrylate (HPMA) are preferable from the standpoint of availability. The hydrophilic polar monomer (D) used in the polymer material of the present invention may be one type or two or more types.

The polymeric material of the present invention may contain units based on monomers other than monomer (A1), cyclic monomer (B), hydrophobic monomer (C) and hydrophilic polar monomer (D). Other monomers are not particularly limited, and examples thereof include ethylene, propylene, various butenes, various pentenes, various hexenes, various heptenes, various octenes, diisobutylene, and triisobutylene. The other monomer used in the polymer material of the present invention may be one kind or two or more kinds.

The total content of units based on the monomer (A1) and residues of the polymerization initiator (A2) in the polymer material of the present invention is 8% by mass or more with respect to the total mass of the polymer material of the present invention. 8 to 35% by mass is preferable, 8 to 30% by mass is more preferable, 8 to 25% by mass is more preferable, and 10 to 20% by mass is particularly preferable. When the total content is at least the lower limit of the range, the effect of suppressing adsorption of proteins and the like is high. When the total content is equal to or less than the upper limit value of the range, shear resistance is excellent.

The content of units based on the cyclic monomer (B) in the polymeric material of the present invention is preferably 10 to 35% by mass, more preferably 15 to 35% by mass, relative to the total mass of the polymeric material of the present invention. , more preferably 15 to 25% by mass, particularly preferably 15 to 25% by mass. When the content of the unit is at least the lower limit of the range, the shear resistance is excellent. When the content of the unit is equal to or less than the upper limit of the range, the effect of inhibiting adsorption of proteins and the like is high.

When the polymeric material of the present invention contains units based on the hydrophobic monomer (C), the content of units based on the hydrophobic monomer (C) in the polymeric material of the present invention is the total amount of the polymeric material of the present invention. It is preferably 0.1 to 20% by mass, more preferably 1 to 20% by mass, even more preferably 3 to 20% by mass, and particularly preferably 3 to 15% by mass. When the content of the unit is at least the lower limit of the range, the shear resistance is excellent. When the content of the unit is equal to or less than the upper limit of the range, the effect of inhibiting adsorption of proteins and the like is high.

When the polymeric material of the present invention contains units based on the hydrophilic polar monomer (D), the content of units based on the hydrophilic polar monomer (D) in the polymeric material of the present invention is is preferably 20 to 80% by mass, more preferably 30 to 70% by mass, even more preferably 35 to 65% by mass, and particularly preferably 40 to 60% by mass, based on the total mass of When the content of the unit is at least the lower limit of the range, the effect of inhibiting adsorption of proteins and the like is high. If the content of the unit is equal to or less than the upper limit of the range, the shear resistance is excellent.

The total content of units based on the monomer (A1), residues of the polymerization initiator (A2), and units based on the hydrophilic polar monomer (D) in the polymeric material of the present invention is It is preferably 50% by mass or more, more preferably 55% by mass or more, still more preferably 60% by mass or more, and particularly preferably 65% by mass or more, relative to the total mass. When the total content is above the lower limit, the effect of suppressing adsorption of proteins and the like is high.

The content of units based on other monomers in the polymeric material of the present invention is preferably 20% by mass or less, more preferably 15% by mass or less, and 12% by mass relative to the total mass of the polymeric material of the present invention. The following are more preferable, and 10% by mass or less is particularly preferable.

The number average molecular weight (Mn) of the polymeric material is preferably 5,000 to 500,000, particularly preferably 10,000 to 300,000. When Mn is at least the lower limit of the above range, the durability is excellent. If Mn is below the said upper limit, it will be excellent in workability.
The mass average molecular weight (Mw) of the polymeric material is preferably 5,000 to 500,000, particularly preferably 10,000 to 300,000. If Mw is more than the said lower limit, it will be excellent in durability. When Mw is at most the upper limit of the range, the workability is excellent.

The molecular weight distribution (Mw/Mn) of the polymeric material is preferably 1.0 to 3.0, particularly preferably 1.0 to 2.5. If Mw/Mn is within the above range, it is excellent in water resistance and hardly adsorbs proteins and the like.
The Mn and Mw of the polymer material are measured in terms of polystyrene by gel permeation chromatography (GPC) using tetrahydrofuran (THF) as an eluent.

The form of use of the polymeric material of the present invention is not particularly limited. For example, it may be dissolved in a solvent and used as a coating liquid, or it may be used as an additive added to a molding material.
The method for producing the polymeric material of the present invention is not particularly limited, and for example, it can be produced by polymerizing each monomer in a polymerization solvent.

The polymerization solvent is not particularly limited, and may be ketones (acetone, etc.), alcohols (methanol, etc.), esters (ethyl acetate, etc.), ethers (diisopropyl ether, etc.), glycol ethers (ethylene glycol ethyl ether, etc.). , aliphatic hydrocarbons (hexane, etc.), aromatic hydrocarbons (toluene, etc.), halogenated hydrocarbons (meta-xylene hexafluoride, etc.), dimethylformamide, N-methyl-2-pyrrolidone, butyroacetone, dimethyl sulfoxide (DMSO) can be exemplified.
The total concentration of all monomers in the reaction solution in the polymerization reaction for obtaining the polymeric material is preferably 5-60% by mass, particularly preferably 10-40% by mass.

A polymerization initiator is preferably used in the polymerization reaction for obtaining the polymeric material. As the polymerization initiator, the polymerization initiator (A2) is preferred. When the polymerization initiator (A2) is not used, it is preferable to use a polymerization initiator other than the polymerization initiator (A2). Other polymerization initiators include, for example, peroxides (benzyl peroxide, lauryl peroxide, succinyl peroxide, tert-butyl perpivalate, etc.), azo compounds (2,2′-azoisobutyronitrile, dimethyl -2,2'-azo (2-methylpropionate), etc.). Initiator A2 may be used in combination with another polymerization initiator.

When other polymerization initiators are used, the amount of the other polymerization initiators used is preferably 0.1 to 1.5 parts by mass, preferably 0.2 to 1.0 parts by mass, with respect to 100 parts by mass of the total amount of the monomers. Parts by mass are more preferred.

A chain transfer agent may be used in the polymerization reaction to control the degree of polymerization (molecular weight) of the polymeric material. The use of a chain transfer agent also has the effect of increasing the total concentration of monomers in the polymerization solvent. Examples of chain transfer agents include n-dodecylmercaptan, stearylmercaptan, and aminoethanethiol.
The amount of the chain transfer agent used is preferably 0 to 2 parts by mass, more preferably 0.1 to 1.5 parts by mass, per 100 parts by mass of the total amount of the monomers.

The reaction temperature in the polymerization reaction is preferably in the range from room temperature to the boiling point of the reaction solution. From the viewpoint of efficient use of the polymerization initiator, the temperature is preferably equal to or higher than the half-life temperature of the polymerization initiator, more preferably 30 to 90°C, and even more preferably 40 to 80°C.

[Coating liquid, coating film]
The coating liquid of the present invention is a coating liquid containing the polymeric material of the present invention. A coating film is formed by applying the coating liquid of the present invention to the surface of an object to be processed and drying it. The application of the coating liquid of the present invention is not particularly limited, but it is particularly useful as a coating agent for medical devices and a water treatment coating agent for filters used in sludge treatment.

The solvent used for the coating liquid is not particularly limited, and ethanol, methanol, acetone, chloroform, tetrahydrofuran, toluene, xylene, trifluoroethanol, hexafluoroisopropanol, methoxypropanol, and dimethylformamide can be exemplified.

The concentration of the polymeric material in the coating liquid is preferably 0.01 to 30% by mass, more preferably 0.1 to 10% by mass. If the concentration of the polymer material is within the above range, it can be applied uniformly, and a uniform coating film can be easily formed.

The coating liquid of the present invention may contain components other than the polymeric material and solvent of the present invention, if necessary. Other components include, for example, leveling agents.

The thickness of the coating film is preferably 0.01-100 μm, more preferably 0.1-10 μm. If the thickness of the coating film is at least the lower limit of the above range, sufficient film strength can be obtained. If the thickness of the coating film is equal to or less than the upper limit value of the range, the utilization efficiency of the material is high.

The change in elastic modulus of the coating film from the film surface in water is preferably 2.0 or more, more preferably 3.0 or more, and even more preferably 5.0 or more. When the change in elastic modulus is at least the lower limit, the shear resistance is excellent, and the effect of suppressing protein adsorption is high.

The elastic modulus change is measured by the following method.
A silicon wafer cut into 2 cm squares is coated with the coating liquid, dried in an oven at 40° C. for 30 minutes to form a coating film having a thickness of 1 μm, and left standing in a phosphate buffer solution for 1 hour. Using an atomic force microscope (AFM Cypher S), the elastic modulus of the coating film is measured in force curve mode using a probe having a spring constant of 2 N/m and a tip curvature radius R of 7 nm. As the probe, for example, AC240TS-C3 (spring constant: 2 N/m, tip curvature radius R: 7 nm, manufactured by Olympus) can be used. X is the average elastic modulus at a distance of 0 to 0.2 μm in the film thickness direction from the film surface, and Y is the average elastic modulus at a distance of 0.2 μm to 0.4 μm in the film thickness direction from the film surface. Define Y/X as the modulus change.

[Medical equipment]
The medical device of the present invention is a medical device provided with the coating film of the present invention or to which an additive comprising the polymeric material of the present invention is added. Examples include a medical device having the coating film of the present invention formed on its surface, and a medical device molded using a molding material to which an additive comprising the polymeric material of the present invention is added.

Examples of medical devices include vials, syringes, ampoules, cartridges, bottles, pouches, pumps, sprayers, stoppers, plungers, caps, lids, needles, stents, catheters, implants, contact lenses, and endoscopes. , heart-lung machine, artificial blood vessel, microplate, and dialysis membrane. Among others, the present invention is useful for catheters, stents, endoscopes, heart-lung machines, dialysis membranes and artificial blood vessels.

The material forming the medical device is not particularly limited, and examples thereof include resin materials such as polystyrene, polypropylene, polycarbonate resin, fluorine-containing polymer, polyurethane resin, and silicone resin, and glass.

As described above, in the present invention, at least one of units based on the monomer (A1) and the residue of the polymerization initiator (A2) in a specific ratio, and a polymer containing units based on the cyclic monomer (B) Use materials. Since the monomer (A1) and the polymerization initiator (A2) have hydrophilic polyoxyalkylene chains, adsorption of proteins and the like is suppressed. Moreover, since it has a unit based on the cyclic monomer (B), it has excellent shear resistance, and the coating film does not easily peel off even in an ecological environment.

EXAMPLES The present invention will be specifically described below with reference to Examples, but the present invention is not limited by the following description. Examples 1-18 are working examples, and examples 19-22 are comparative examples.

[Glass transition point (Tg)]
The glass transition point of the homopolymer was measured by DSC (manufactured by TA Instruments) by raising and lowering the temperature from -30°C to 200°C at a rate of 10°C/min. The glass transition point was defined as the temperature at which the rubber state changed to the glass state in the second cycle when the temperature was lowered.

[material]
The abbreviations of the raw materials used in this example are shown below.
(Polymerization initiator (A2))
VPE-0201: trade name (polymer initiator, polymer having a structure represented by formula (a21), a = 45 to 46, b = 6 to 14, manufactured by Wako Pure Chemical Industries, Ltd.).
(Monomer (A1))
AME-400: trade name (methoxy polyethylene glycol acrylate, manufactured by NOF Corporation).

(Cyclic monomer (B))
St: styrene (Tg of homopolymer: 80°C).
PhMI: phenylmaleimide (Tg of homopolymer: 300°C or higher).

(Hydrophobic monomer (C))
X-22-174AX: trade name (modified silicone, manufactured by Shin-Etsu Silicone Co., Ltd.).
C6FMA: _CH2 =C( _CH3 )COO _{( CH2} ) _{2 (} CF2) _5CF3 .
DodecylMA: dodecyl methacrylate.
IBOMA: isobornyl methacrylate.
2-EHA: 2-ethylhexyl acrylate.

(Hydrophilic polar monomer (D))
HEMA: 2-hydroxyethyl methacrylate.
HPMA: 2-hydroxypropyl methacrylate.

[Examples 1 to 22]
A reaction solution obtained by dissolving each component having the composition shown in Tables 1 and 2 in 1-methoxy-2-propanol as a solvent so that the solid content concentration is 30% by mass was charged into a pressure-resistant glass bottle, sealed, and heated to 80°C. for 24 hours, and the resulting polymer was dried under reduced pressure to obtain a polymeric material.
In Examples 8, 9, 11 and 22, 1 part by mass of azobisisobutyronitrile was used as a polymerization initiator with respect to 100 parts by mass of the monomer.

[Non-adsorptive]
(1) Preparation of coloring solution and protein solution The coloring solution consists of 50 mL of peroxidase coloring solution (3,3',5,5'-tetramethylbenzidine (TMBZ), manufactured by KPL) and 50 mL of TMB Peroxidase Substrate (manufactured by KPL). I used a mixture of
As the protein solution, a protein (POD-goat anti-mouse IgG, Biorad) diluted 16,000-fold with a phosphate buffer solution (D-PBS, Sigma) was used.
(2) Protein adsorption 2 mL of the protein solution was dispensed into 3 wells of a 24-well microplate with a coating film formed on the surface of each well (2 mL was used for each well) and allowed to stand at room temperature for 1 hour. As a blank, 2 μL of protein solution was dispensed into 3 wells in a 96-well microplate (2 μL was used per well).
(3) Well washing Next, 4 mL of a phosphate buffer solution (D-PBS, manufactured by Sigma) containing 0.05% by mass of a surfactant (Tween 20, manufactured by Wako Pure Chemical Industries, Ltd.) was applied to each well of a 24-well microplate. Wells were washed 4 times (4 mL used per well). Blanks were similarly washed.
(4) Dispensing Coloring Solution Next, 2 mL of the coloring solution was dispensed into the washed 24-well microplate (2 mL was used for each well), and color development reaction was carried out for 7 minutes. The color reaction was stopped by adding 1 mL of 2N sulfuric acid (using 1 mL per well). Blanks were prepared by dispensing 100 μL of the coloring solution into a 96-well microplate (using 100 μL per well), performing the coloring reaction for 7 minutes, and adding 50 μL of 2N sulfuric acid (using 50 μL per well). ) stopped the color reaction.
(5) Preparation for Absorbance Measurement Next, 150 μL of liquid was taken from each well of the 24-well microplate and transferred to a 96-well microplate.
(6) Absorbance measurement and protein adsorption rate Absorbance was measured at 450 nm using MTP-810Lab (manufactured by Corona Denki Co., Ltd.). Here, the average value of blank absorbance (N ₌ 3) was defined as A0. The absorbance of the liquid transferred from the 24-well microplate to the 96 _- well microplate was defined as A1. The adsorption rate Q1 was obtained from the following formula, and the average value was taken as the protein adsorption rate.
Q1 = A ₁ / {A ₀ × (100/dispensed amount of blank protein solution)} × 100
= A ₁ / {A ₀ × (100/2 μL)} × 100 [%]

[Shear resistance]
A coating solution was prepared by dissolving the polymer material of each example in methoxypropanol to a concentration of 10% by mass. A coating liquid was applied to the surface of the _SiO2 substrate and dried to form a coating film with a thickness of 1 μm. A 10 mm×20 mm square cut-out base material with a film was placed in a PVC tube with an inner diameter of 12 mm. An aqueous sodium dodecylsulfate solution adjusted to 2 mM was circulated in the PVC tube at a flow rate of 3 L/min using a liquid feed pump (MASTERFLEX easy-LOAD model 77601-10), and after 72 hours, the film-coated substrate was taken out. The film-coated substrate was dried in an oven at 40° C. for 12 hours, and the film thickness was measured with a Filmetrics thin film measurement device F20 to measure the film thickness reduction rate relative to the initial film thickness.

[Coatability]
A 2.5 cm square SiO ₂ substrate was ultrasonically cleaned with an isopropyl alcohol (IPA) solution for 3 minutes to obtain a coated substrate. 0.1 mL of hexamethylenedisilazane (HMDS) was dropped onto the washed coated substrate and spin-coated at 2000 rpm for 30 seconds. The HMDS-coated substrate was heat treated at 120° C. for 30 minutes. 0.1 ppm by mass of rhodamine b was dissolved in a coating liquid prepared by dissolving the polymer material of each example in methoxypropanol to a concentration of 0.5% by mass. The coated substrate was immersed in the coating liquid at an arbitrary speed and pulled up at 1 mm/sec. The surface of the coated substrate was confirmed, and the coatability was evaluated according to the following evaluation criteria.
(Evaluation criteria)
○: Coloring was observed on the entire surface of the coated substrate.
Δ: Coloring was observed in part of the coated substrate, but no coloring was observed as a whole.
x: Coloring was not observed on the entire surface of the coated substrate.

Tables 1 and 2 show the composition of the polymeric material of each example and the evaluation results.

As shown in Tables 1 and 2, in Examples 1 to 18 containing at least one of the units based on the monomer (A1) and the residue of the polymerization initiator (A2) and the units based on the cyclic monomer (B) in a specific ratio , protein adsorption was suppressed, and shear resistance was also obtained. Shear resistance was not obtained in Examples 19 and 21, which did not contain units based on the cyclic monomer (B). In Example 20, which has few units based on the monomer (A1) and residues of the polymerization initiator (A2), and Example 22, which does not contain units based on the monomer (A1) and residues of the polymerization initiator (A2), protein adsorption was not sufficiently suppressed.

Claims (14)

At least one selected from units based on a monomer (A1) having a hydrophilic polyoxyalkylene chain and residues of a polymerization initiator (A2) having a hydrophilic polyoxyalkylene chain,
Based on at least one cyclic monomer (B) selected from monomers represented by the following formula (1) and monomers represented by the following formula (2), each of which has a homopolymer glass transition temperature of 80° C. or higher including units and
A polymer material, wherein the total content of units based on the monomer (A1) and residues of the polymerization initiator (A2) is 8% by mass or more.

(In the above formula, R ¹ is a hydrogen atom, a fluorine atom, a phenyl group, an alkyl group having 1 to 4 carbon atoms, a perfluoroalkyl group having 1 to 6 carbon atoms, an epoxy group, an isocyanate group, a hydroxy group, an amino group. , or a carboxy group, R ² to R ⁴ are each independently a hydrogen atom, a fluorine atom, a phenyl group, an alkyl group having 1 to 4 carbon atoms, a fluoroalkyl group having 1 to 6 carbon atoms, an epoxy group, an isocyanate group , a hydroxy group, an amino group, or a carboxy group.) The total content of the units based on the monomer (A1) and the residue of the polymerization initiator (A2) is 8 to 35 mass%, and the content of the units based on the cyclic monomer (B) is 10 to 35 mass%. %. 3. The polymeric material according to claim 1, which contains a residue of the polymerization initiator (A2), wherein the polymerization initiator (A2) is a polymerization initiator having a polyoxyethylene chain. The polymerization initiator having a polyoxyethylene chain is an ester of 4,4′-azobis(4-cyanovaleric acid) and polyoxyethylenediol, polyoxyethylene-bis(2-bromoisobutyrate), or methoxy 4. The polymeric material according to claim 3, which is polyoxyethylene-2-bromoisobutyrate. 5. The polymeric material according to any one of claims 1 to 4, wherein the unit based on the cyclic monomer (B) includes a unit based on the monomer represented by the formula (1), wherein R ¹ is a phenyl group. . 6. The unit according to any one of claims 1 to 5, wherein the unit based on the cyclic monomer (B) includes a unit based on the monomer represented by the formula (2) in which all of R ² to R ⁴ are hydrogen atoms. polymer material. A coating liquid comprising the polymeric material according to any one of claims 1 to 6. The coating liquid according to claim 7, which is a coating agent for medical devices. The coating liquid according to claim 7, which is a coating agent for water treatment. A coating film formed by drying with the coating liquid according to any one of claims 7 to 9. 11. The coating membrane of claim 10, wherein the modulus change defined below from the membrane surface in water is 2.0 or greater.
Change in elastic modulus: A coating solution is applied to a silicon wafer cut into 2 cm squares, dried in an oven at 40° C. for 30 minutes to form a coating film with a thickness of 1 μm, and left to stand in a phosphate buffer solution for 1 hour. do. Using an atomic force microscope (AFM Cypher S), the elastic modulus of the coating film is measured in force curve mode using a probe having a spring constant of 2 N/m and a tip curvature radius R of 7 nm. X is the average elastic modulus at a distance of 0 to 0.2 μm in the film thickness direction from the film surface, and Y is the average elastic modulus at a distance of 0.2 μm to 0.4 μm in the film thickness direction from the film surface. Define Y/X as the modulus change. An additive comprising the polymeric material according to any one of claims 1 to 6. A medical device comprising the coating film according to claim 10 or 11 or to which the additive according to claim 12 is added. 14. The medical device of claim 13, which is a catheter, stent, endoscope, heart-lung machine, or vascular graft.