JP2001106749A - Copolymer, method for producing the same, material for medical use and material for ophthalmology - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a copolymer excellent in biocompatibility, especially having thermoformability and/or a tensile strength after the forming to a certain extent and, if necessary, having hydrophilicity, water absorbency or the like, and further to provide a method for producing the copolymer, a material for medical use and a material for ophthalmology. SOLUTION: This copolymer has constituent units of formula (1) to (4) [R1, R2 and R3 are each divalent organic group; R4 IS H or CH3; R5, R6 and R7 are each H, a 1-6C hydrocarbon or a hydroxyhydrocarbon; m is 0 or 1; n is 2-4; X is a divalent organic group; Y is a 1-6C alkyleneoxy group; and Z is H or a group of the formula (R8 is a 1-10C alkyl group or a 1-10C hydroxyalkyl group)], and further has the constituent unit of formula (3) wherein the R3 is a difunctional group containing a polysiloxanyl group. The method for producing the copolymer, the material for the medical use and the material for the ophthalmology are also provided.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a copolymer having biocompatibility and at least one of hydrophilic, water-absorbing, thermoplastic and elastic properties and useful for medical materials and ophthalmic materials. And a method for producing the same, and a medical material and an ophthalmic material containing the copolymer as an active ingredient.

[0002]

2. Description of the Related Art There are many types of phospholipids in living organisms, and these phospholipids play an important role in maintaining the life of living organisms. For example, a phospholipid having a phosphorylcholine-like group or the like is a constituent of a cytoplasm such as a cell membrane, and is closely related to various metabolic processes in a living body. Phospholipids also play an important role in the energy source of brain tissue, transportation and absorption of fat, coagulation of blood, taste of food, and the like. Various attempts have been made to substitute such phospholipids and to utilize the biocompatibility of phospholipids. For example, attempts have been made to use a polymer or the like having a phospholipid-like functional group as a medical material for artificial organs or to apply it to sensors such as biosensors.
(JP-A-3-039309, JP-A-4-2836)
No. 53). Further, a block copolymer obtained by polymerizing a polymerizable monomer having a phosphorylcholine group in a side chain by using an azo-based polymerization initiator having a polysiloxane group has been proposed, and the block copolymer is used for medical purposes. It is known to use as a material (Japanese Patent Application Laid-Open No. 9-296019). However, the conventionally proposed copolymer containing a phosphorylcholine-like group is particularly inferior in thermoplasticity useful for heat moldability and elasticity that affects tensile strength after molding, so that the range of the molding process is limited. And its low tensile strength limits its use.

[0003]

SUMMARY OF THE INVENTION An object of the present invention is to provide a phosphorylcholine-like group having excellent biocompatibility, and particularly to have heat moldability and / or a certain degree of tensile strength after molding, and An object of the present invention is to provide a copolymer, such as a block copolymer, having hydrophilicity or water absorption and a method for producing the same. Another object of the present invention is to provide a medical material which is excellent in biocompatibility, has heat moldability and / or has a certain tensile strength after molding, and is provided with hydrophilicity, water absorption, transparency and the like as necessary. Material and ophthalmic material.

[0004]

Means for Solving the Problems The present inventors have conducted intensive studies in order to solve the above-mentioned problems, and as a result, have shown an expression indicating biocompatibility.
In addition to the phosphorylcholine analog represented by formula (4),
The copolymer having the constitutional units of (3) to (3) has not only biocompatibility but also, in particular, heat moldability and / or a certain degree of tensile strength after molding, and further has hydrophilicity, water absorption, and transparency. The present invention was found to be useful for medical materials and ophthalmic materials, and completed the present invention. Also,
The present inventors have found that the above-mentioned copolymer can be easily prepared by polymerizing a polymerizable monomer having a phosphorylcholine-like group with a polysiloxane-polyamide copolymer having an azo group in a molecule as an initiator. It was found that the present invention was obtained, and the present invention was completed.

That is, according to the present invention, formulas (1) to (4)
Having a structural unit represented by ^ThreeIs polysiloxani
A structural unit represented by the formula (3), which is a bifunctional group containing
Is provided.

Embedded image (In the formulas (1) to (3), R ¹ , R ² and R ³ each independently represent a divalent organic group. In the formula (4), R ⁴ represents a hydrogen atom or a methyl group, R ⁵ , R ⁶ and R ⁷ are the same or different and represent a hydrogen atom, a hydrocarbon group having 1 to 6 carbon atoms or a hydroxy hydrocarbon group, m represents 0 or 1 and n represents
Represents an integer of 2 to 4. X represents a divalent organic group; Y represents an alkyleneoxy group having 1 to 6 carbon atoms;
Represents a hydrogen atom or a group represented by the following formula (here, R ⁸
Represents an alkyl group having 1 to 10 carbon atoms or a hydroxyalkyl group having 1 to 10 carbon atoms))).

Embedded image Further, according to the present invention, a repeating unit (A) having a structural unit represented by Formulas (1) to (3), and a repeating unit (B) represented by Formula (4), And the proportion of (B) is 5 to 99.9: 0.1 to 95 by weight, and the repeating unit
(A) The ratio of the structural unit represented by the formula (1) is 0.01 to
The block copolymer according to claim 1, which is 50% by weight. Further according to the invention, R ³
Are polymerizable monomers represented by formulas (5) to (7), including a polymerizable monomer represented by formula (7), which is a polysiloxanyl group-containing bifunctional group; -After obtaining the polyamide copolymer, the obtained copolymer

Embedded image (In the formulas (5) to (7), A ¹ and A ² each independently represent a hydroxyl group or a chlorine atom, and R ^{1 to} R ^{3 each} represent a divalent organic group.) Phosphorylcholine represented by the formula (8) There is provided a method for producing the block copolymer, which comprises polymerizing a similar group-containing monomer.

Embedded image (In the formula, R ⁴ represents a hydrogen atom or a methyl group, and R ⁵ , R ⁶ and R ⁷ are the same or different groups, and represent a hydrogen atom, a hydrocarbon group having 1 to 6 carbon atoms or a hydroxy hydrocarbon group. M is 0 or 1, and n is an integer of 2 to 4.
X represents a divalent organic group, Y represents an alkyleneoxy group having 1 to 6 carbon atoms, Z represents a hydrogen atom or a group represented by the following formula (where R ⁸ represents 1 to 10 carbon atoms). Represents an alkyl group or a hydroxyalkyl group having 1 to 10 carbon atoms))).

Embedded image Further, according to the present invention, there is provided a medical or ophthalmic material comprising the above-mentioned copolymer or block copolymer as an active ingredient.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION The copolymer of the present invention has the above formula (1)
To (4), and as a structural unit represented by the formula (3), at least a structural unit represented by the formula (3) in which R ³ is a polysiloxanyl group-containing bifunctional group. Is a copolymer. The type of the copolymer may be any of a random copolymer, a block copolymer, and a graft copolymer. Although the molecular weight of the copolymer of the present invention is not particularly limited, the weight average molecular weight is 1,000 to 500.
0000 is preferable, and in particular, 10,000 to 500,000.
Is preferred.

In the formula (1), R ¹ is a divalent organic group such as a methylene group, an ethylene group, a propylene group, a butylene group, a pentamethylene group, a hexamethylene group, a decamethylene group, a dodecamethylene group, etc. A linear alkylene group; a branched alkylene group such as a 2-methylpropylene group; an oxygen-containing organic group such as a polyoxymethylene group and a polyoxyethylene group; a p-phenylene group, an m-phenylene group;
o-phenylene group, 4,4'-diphenylene ether group, 3,4'-diphenylene ether group, 4,4'-biphenylene group, 3,4'-biphenylene group, 4,4'-
Phenylenedimethylene group, 4,4′-propylenediphenylene group, 3,4′-propylenediphenylene group, 4,
Arylene groups such as 4'-methylenediphenylene group and 3,4'-methylenediphenylene group; and the following structural units. However, the alkylene group and the arylene group may be substituted with a nitrogen atom and / or an oxygen atom.

[0008]

Embedded image

The structural unit represented by the formula (1) includes R ¹
May include only the same one type of structural unit, or may include two or more types of structural units having different R ¹ . The content ratio of the structural unit represented by the formula (1) is not particularly limited, but is preferably 0.01 to 25% by weight based on the total of the structural units represented by the formulas (1) to (4). 0.0
If the amount is less than 1% by weight, the copolymer of the present invention may not be obtained. If the amount is more than 25% by weight, a polyamide chain is not sufficiently contained in the obtained copolymer, so that elasticity and thermoplasticity may not be obtained. Is not preferred because there is a possibility that desirable properties such as above may not be obtained.

In the formula (2), R ² is a divalent organic group such as a methylene group, an ethylene group, a propylene group, a butylene group, a pentamethylene group, a hexamethylene group, a decamethylene group, a dodecamethylene group, etc. A linear alkylene group; a branched alkylene group such as a 2-methylpropylene group; an oxygen-containing organic group such as a polyoxymethylene group and a polyoxyethylene group; a p-phenylene group, an m-phenylene group;
o-phenylene group, 4,4'-diphenylene ether group, 3,4'-diphenylene ether group, 4,4'-biphenylene group, 3,4'-biphenylene group, 4,4'-
Phenylenedimethylene group, 4,4′-propylenediphenylene group, 3,4′-propylenediphenylene group, 4,
And an arylene group such as a 4'-methylenediphenylene group and a 3,4'-methylenediphenylene group. However,
The alkylene group and the arylene group may be substituted with a nitrogen atom and / or an oxygen atom. The structural unit represented by the formula (2) may be a case in which only one type of structural unit in which R ² is the same is included, or may include two or more types of structural units in which R ² is different. The content ratio of the structural unit represented by the formula (2) is preferably 1 to 50% by weight based on the total of the structural units represented by the formulas (1) to (4). If the amount is less than 1% by weight, polyamide copolymers are not sufficiently contained in the obtained copolymer, so that preferable properties such as elasticity and thermoplasticity may not be obtained.
It is not preferable because the structural unit represented by the formula (4) may not be introduced into the obtained copolymer.

In the formula (3), R ³ is a divalent organic group, for example, a methylene group, an ethylene group, a propylene group, a butylene group, a pentamethylene group, a hexamethylene group, a decamethylene group, a dodecamethylene group and the like. A branched alkylene group such as a 2-methylpropylene group; an oxygen-containing organic group such as a polyoxymethylene group and a polyoxyethylene group; a p-phenylene group, an m-phenylene group;
o-phenylene group, 4,4'-diphenylene ether group, 3,4'-diphenylene ether group, 4,4'-biphenylene group, 3,4'-biphenylene group, 4,4'-
Phenylenedimethylene group, 4,4′-propylenediphenylene group, 3,4′-propylenediphenylene group, 4,
Arylene groups such as 4′-methylenediphenylene group and 3,4′-methylenediphenylene group; and polysiloxanyl group-containing bifunctional groups.

As the polyfunctional siloxanyl group-containing bifunctional group as R ³ , for example, a group represented by the formula (3a) is preferably exemplified. In particular, from the viewpoint of availability of raw materials, the formula (3a)
A group in which both R ⁹ and R ¹⁰ are a methyl group and both R ¹¹ and R ¹² are a propylene group is preferred.

[0013]

Embedded image (Wherein R ⁹ and R ¹⁰ are the same or different groups,
An alkyl group or a phenyl group having 1 to 6 carbon atoms, R ¹¹
And R ¹² are the same or different groups and represent a divalent organic group having 1 to 30 carbon atoms such as an alkylene group. y is 10
Shows an integer of ~ 200. )

The structural unit represented by the formula (3) includes R ³
Is a polysiloxanyl group-containing bifunctional group, even when only the same or different structural units are included, R ³ is a polysiloxanyl group-containing bifunctional group, and a polyfunctional group other than the polysiloxanyl group-containing bifunctional group. It may contain two or more different structural units including a group. The content ratio of the structural unit represented by the formula (3) is preferably 1 to 90% by weight based on the total of the structural units represented by the formulas (1) to (4). At this time, the content ratio of the structural unit represented by the formula (3) in which R ³ is a polysiloxanyl group-containing bifunctional group is represented by the formula (1)
It is preferably from 5 to 85% by weight based on the total of the structural units represented by (4). If the amount is less than 1% by weight, the resulting copolymer does not contain a sufficient amount of polyamide chains, resulting in elasticity,
There is a possibility that desirable properties such as thermoplasticity may not be obtained.
If it exceeds 0% by weight, the resulting copolymer has the formula
It is not preferable because the structural unit represented by (4) is not introduced and desirable properties such as biocompatibility, hydrophilicity, and water absorbency exhibited by the phosphorylcholine-like group may not be obtained.

In the formula (4), R ⁴ represents a hydrogen atom or a methyl group. R ^{5 to} R ⁷ are the same or different groups, and each represents a hydrogen atom; a methyl group, an ethyl group, a propyl group,
A hydrocarbon group having 1 to 6 carbon atoms such as a butyl group, a pentyl group, and a hexyl group; or a hydroxymethyl group, a 2-hydroxyethyl group, a 3-hydroxypropyl group, a 4-hydroxybutyl group, a 5-hydroxypentyl group, -Represents a hydroxy hydrocarbon group having 1 to 6 carbon atoms such as a hydroxyhexyl group. X represents a divalent organic group such as an oxygen atom, a methyleneoxy group, an ethyleneoxy group, a propyleneoxy group, a benzyl group, a benzyloxy group, a benzoyloxy group, a phenoxy group, a carbonyl group, a carbonyloxy group, and an oxycarbonyl group. Show. Y is a carbon number of 1 to 1 such as a methyleneoxy group, an ethyleneoxy group, a propyleneoxy group, a butyleneoxy group, a pentyleneoxy group, and a hexyleneoxy group.
6 represents an alkyleneoxy group, m represents 0 or 1, and n represents an integer of 2 to 4. Z represents a hydrogen atom or a group represented by the following formula, wherein R ⁸ represents an alkyl group having 1 to 10 carbon atoms or a hydroxyalkyl group having 1 to 10 carbon atoms.

Embedded image

The structural unit represented by the formula (4) includes R ²
May include only the same one type of structural unit, or may include two or more types of structural units having different R ² . The content ratio of the structural unit represented by the formula (4) is calculated by the formula
0.1 to the total of the structural units shown in (1) to (4)
~ 95% by weight is preferred. If the amount is less than 0.1% by weight, preferable properties such as biocompatibility, hydrophilicity, and water absorbability exhibited by the phosphorylcholine-like group may not be obtained. If the amount exceeds 95% by weight, the polysiloxane-polyamide component may not be obtained. It is not preferable because desirable properties such as thermoplasticity and elasticity may not be obtained.

The copolymer of the present invention only needs to have the structural units represented by the above formulas (1) to (4), and the arrangement thereof is not particularly limited. Further, other structural units may be included within a range not to impair the object of the present invention. In the copolymer of the present invention, the sequence of the structural units represented by the formulas (1) to (4) is preferably a repeating unit (A) having a structural unit represented by the formulas (1) to (3). And a repeating unit (B) having a structural unit represented by Formula (4). In the block copolymer, the ratio between the repeating unit (A) and the repeating unit (B) is 5 to 5 by weight.
99.9: 0.1 to 95 is preferred. When the proportion of the repeating unit (B) is less than 0.1% by weight, the obtained block copolymer does not exhibit favorable properties such as biocompatibility, hydrophilicity, and water absorbability, while the amount exceeds 95% by weight. In
It is not preferable because the heat formability and elasticity decrease.

In the repeating unit (A) of the block copolymer, the proportion of the structural unit represented by the formula (1) is preferably 0.01 to 50% by weight, more preferably 0.1 to 50% by weight, based on the repeating unit (A).
25% by weight is particularly preferred. If the amount is less than 0.01% by weight, a desired copolymer may not be obtained.
If the amount exceeds 50% by weight, the resulting copolymer hardly contains polyamide repeating units, which is not preferable. Formula (2) and Formula in the repeating unit (A)
Although the ratio of the structural unit represented by (3) is not particularly limited,
In the repeating unit (A), the proportion of the structural unit represented by the formula (2) is preferably from 0.01 to 50% by weight, particularly preferably from 0.1 to 25% by weight.
% By weight is desirable. The proportion of the structural unit represented by the formula (3) is preferably 0.01 to 50% by weight, and particularly preferably 0.1 to 25% by weight.
% By weight is desirable. In the structural unit represented by the formula (3) in the repeating unit (A), the ratio of the structural unit in which R ³ is a polysiloxanyl-containing bifunctional group is 0. 0 to the entire structural unit represented by the formula (3). It is preferably from 1 to 95% by weight, particularly preferably from 1 to 90% by weight. In this case, 0.
If the amount is less than 1% by weight, it may not be possible to impart the desirable properties represented by the polysiloxanyl group, while if it exceeds 95% by weight, the strength of the obtained block copolymer, such as tensile strength, may decrease. It is not preferable because there is a risk of doing so.

In the above-mentioned block copolymer, the arrangement of the structural units represented by the formulas (1) to (3) in the repeating unit (A) is not particularly limited. For example, -R ¹ -CO-NH-R ³ -NH-CO
—R ² —CO—NH—R ³ —NH—CO—R ¹ — and the like.

The copolymer such as the block copolymer of the present invention contains a polysiloxane component, a phospholipid-like component and a polyamide component. Both the polysiloxane component and the phospholipid-like component are components generally referred to as having high biocompatibility. In addition, the polysiloxane component and the polyamide component are hydrophobic, and the phospholipid-like component generally exhibits large hydrophilicity. The copolymer of the present invention further contains components having different properties such as polar and non-polar properties. At present, it is said that the size of a microdomain structure composed of a hydrophilic-hydrophobic component on the surface of a material plays an important role as one theory of molecular recognition in a living body. Based on this theory, it is considered that by precisely molecularly designing the copolymer of the present invention, a material having higher biocompatibility can be produced, and the material can be designed according to the intended use.

In order to produce the copolymer of the present invention, for example, to obtain a random copolymer, first, the above formula
The polymerizable monomer represented by (8) is mixed with a polymerization initiator having a reactive substituent such as a carboxyl group or an amino group or a chain transfer agent having a reactive substituent such as a carboxyl group or an amino group. A low-molecular-weight oligomer having a reactive group such as a carboxyl group or an amino group at both ends of the chain is synthesized by polymerizing by a known solution polymerization method, bulk polymerization method, suspension polymerization method or the like. Then, the above formulas (6) and (7)
Can be obtained by mixing a polymerizable monomer represented by the formula (1) with the obtained oligomer and polymerizing it by a known solution polymerization method, bulk polymerization method, direct polymerization method, or the like.

In order to produce the block copolymer of the present invention, for example, an azo group-containing polysiloxane-polyamide copolymer is obtained by polymerizing the polymerizable monomers represented by the above formulas (5) to (7). (Hereinafter, referred to as “first-stage reaction”), the resulting copolymer is polymerized with a phosphorylcholine analog-containing monomer represented by the above formula (8) (hereinafter, referred to as “second-stage reaction”). Reaction "). In the formulas (5) to (8), specific examples of R ^{1 to} R ⁸ include:
Preferable examples are the same as those described for the structural units represented by the above formulas (1) to (4).

As the polymerizable monomer represented by the formula (5),
What is necessary is just to be able to form the structural unit represented by the above formula (1), and examples thereof include ordinary azo-based initiators. For example,
4,4'-azobis (4-cyanopentanoic acid) or 4,4'-azobis (4-cyanopentanoic acid chloride) obtained by reacting a chlorinating agent, for example, thionyl chloride or the like, with the like are available. This is preferred from the viewpoint of These can be used alone or as a mixture when used.

The polymerizable compound represented by the formula (6) includes
Any carboxylic acid may be used as long as it can form the structural unit represented by the above formula (2). Linear aliphatic dicarboxylic acids such as acid and dodecane dicarboxylic acid; branched aliphatic dicarboxylic acids such as 2-methylglutaric acid and 3-methylglutaric acid; oxygen-containing acids such as diglycolic acid and α, ω-polyethylene glycol dicarboxylic acid 4, dicarboxylic acids having a hydrocarbon skeleton, isophthalic acid, terephthalic acid, phthalic acid;
4'-oxybisbenzoic acid, 3,4'-oxybisbenzoic acid, 4,4'-bisbenzoic acid, 3,4'-bisbenzoic acid, 4,4'-methylenebisbenzoic acid, 3,4'-methylenebisbenzoic acid Acid, 4,4′-ethylenebisbenzoic acid,
Aromatic dicarboxylic acids such as 3,4'-ethylenebisbenzoic acid, 4,4'-propylenebisbenzoic acid, and 3,4'-propylenebisbenzoic acid are exemplified. Also, for example,
Examples of the acid chloride include malonic dichloride, succinic dichloride, glutaric dichloride, adipic dichloride, pimelic dichloride, suberic dichloride, sebacic dichloride, decane dicarboxylic dichloride,
Linear aliphatic dicarboxylic acid dichloride such as dodecane dicarboxylic acid dichloride; 2-methylglutaric acid dichloride;
Branched aliphatic dicarboxylic acid dichloride such as 3-methylglutaric acid dichloride, diglycolyl dichloride, α, ω-
Dicarboxylic acid dichloride having an oxygen-containing hydrocarbon skeleton such as polyethylene glycol dicarboxylic acid dichloride, isophthaloyl chloride, terephthaloyl chloride, phthaloyl chloride, 4,4′-oxybisbenzoic acid chloride, 3,4′-oxybisbenzoic acid Chloride, 4,4 '
-Bisbenzoic acid chloride, 3,4'-bisbenzoic acid chloride, 4,4'-methylenebisbenzoic acid chloride, 3,
4'-methylenebisbenzoic acid chloride, 4,4'-ethylenebisbenzoic acid chloride, 3,4'-ethylenebisbenzoic acid chloride, 4,4'-propylenebisbenzoic acid chloride, 3,4'-propylenebisbenzoic acid And aromatic dicarboxylic acid dichloride such as chloride. These can be used alone or as a mixture when used.

The polymerizable compound represented by the formula (7) includes
What is necessary is just to be able to form the structural unit represented by the above formula (3). When R ³ in the formula (7) is a divalent organic group other than the polysiloxanyl group-containing bifunctional group, for example, methylene diamine, ethylene diamine, 1,3-diaminopropane, 1,4-diaminobutane, 1,5 Linear aliphatic diamines such as -diaminopentane, 1,6-diaminohexane, 1,8-diaminooctane, 1,10-diaminodecane and 1,12-diaminododecane; 1,3-diamino-
Branched aliphatic diamines such as 2-methylpropane; 2,2 ′
-(Oxybisethylamine), a diamine having an oxygen-containing hydrocarbon skeleton such as α, ω-polyethylene glycol diamine, 4,4′-diaminodiphenyl ether, 3,
4'-diaminodiphenyl ether, 4,4'-diaminobiphenyl, 3,4'-diaminobiphenyl, 4,
4′-diaminodiphenylmethylene, 3,4′-diaminodiphenylmethylene, 4,4′-diaminodiphenylethylene, 3,4′-diaminodiphenylethylene,
4,4'-diaminodiphenylpropylene, 3,4'-
And aromatic diamines such as diaminodiphenylpropylene. These can be used alone or as a mixture when used. On the other hand, when R ³ in the formula (7) is a polysiloxanyl group-containing bifunctional group, for example,
Monomer represented by (7a). In particular, the formula (7a ¹⁾
Are preferred. These can be used alone or as a mixture at the time of use, and are necessarily required as the polymerizable monomer represented by the formula (7).

[0026]

Embedded image (Wherein R ⁹ and R ¹⁰ are the same or different groups,
An alkyl group or a phenyl group having 1 to 6 carbon atoms, R ¹¹
And R ¹² are the same or different groups and represent a divalent organic group having 1 to 30 carbon atoms such as an alkylene group. x is 1 to
6 represents an integer, and y represents an integer of 10 to 200. )

The phosphorylcholine-like group-containing monomer represented by the formula (8) may be any monomer capable of forming the structural unit represented by the above formula (4). For example, 2- (meth) acryloyloxyethyl -2 '-(trimethylammonio)
Ethyl phosphate, 3- (meth) acryloyloxypropyl-2 ′-(trimethylammonio) ethyl phosphate, 4- (meth) acryloyloxy) butyl-2′-
(Trimethylammonio) ethyl phosphate, 5- (meth) acryloyloxypentyl-2 ′-(trimethylammonio) ethylphosphate, 6- (meth) acryloyloxyhexyl-2 ′-(trimethylammonio) ethylphosphate, 2- (Meth) acryloyloxyethyl-2 ′-(triethylammonio) ethyl phosphate,
2- (meth) acryloyloxyethyl-2 ′-(tripropylammonio) ethyl phosphate, 2- (meth) acryloyloxyethyl-2 ′-(tributylammonio) ethylphosphate, 2- (meth) acryloyloxypropyl- 2 ′-(trimethylammonio) ethyl phosphate, 2- (meth) acryloyloxybutyl-2 ′
-(Trimethylammonio) ethyl phosphate, 2-
(Meth) acryloyloxypentyl-2 '-(trimethylammonio) ethyl phosphate, 2- (meth) acryloyloxyhexyl-2'-(trimethylammonio)
Ethyl phosphate, 2- (vinyloxy) ethyl-2 '
-(Trimethylammonio) ethyl phosphate, 2-
(Allyloxy) ethyl-2 '-(trimethylammonio)
Ethyl phosphate, 2- (p-vinylbenzyloxy)
Ethyl-2 ′-(trimethylammonio) ethyl phosphate, 2- (p-vinylbenzoyloxy) ethyl-2 ′
-(Trimethylammonio) ethyl phosphate, 2-
(Styryloxy) ethyl-2 '-(trimethylammonio) ethylphosphate, 2- (p-vinylbenzyl) ethyl-2'-(trimethylammonio) ethylphosphate, 2- (vinyloxycarbonyl) ethyl-2'- (Trimethylammonio) ethyl phosphate, 2- (allyloxycarbonyl) ethyl-2 ′-(trimethylammonio) ethylphosphate, 2- (acryloylamino) ethyl-2 ′-(trimethylammonio) ethylphosphate, 2- ( Vinylcarbonylamino) ethyl-2 '-(trimethylammonio) ethylphosphate, 2- (allyloxycarbonylamino) ethyl-2'-(trimethylammonio) ethylphosphate, 2- (buteroyloxy) ethyl-2 '-(trimethyl Ammonio) ethyl phosphate, 2- (crotonoyloxy) ethyl-2'-
(Trimethylammonio) ethyl phosphate, ethyl-
(2'-trimethylammonioethyl phosphorylethyl)
Fumarate, butyl- (2'-trimethylammonioethylphosphorylethyl) fumarate, hydroxyethyl- (2'-trimethylammonioethylphosphorylethyl) fumarate, ethyl- (2'-trimethylammonioethylphosphorylethyl) fumarate, butyl- (2'-
Trimethylammonioethyl phosphorylethyl) fumarate, hydroxyethyl- (2'-trimethylammonioethyl phosphorylethyl) fumarate and the like. From the viewpoint of availability, 2-methacryloyloxyethyl-
Preferred is 2 '-(trimethylammonio) ethyl phosphate (hereinafter abbreviated as MPC). These can be used alone or as a mixture when used.

In the production method of the present invention, the amount of the polymerizable monomers represented by the formulas (5) to (7) when the first-stage reaction is carried out is defined as a total of 100% by weight. When you do
The charge ratio of the polymerizable monomers represented by the formulas (5) and (6) is 0.01 to 50% by weight, particularly 0.1 to 25% by weight.
Is preferable. The charge ratio of the polymerizable monomer represented by the formula (7) is preferably 1 to 90% by weight, particularly preferably 5 to 85% by weight. The charging ratio of the polymerizable monomer represented by the formula (5) is 0.1.
If the amount is less than 01% by weight, polysiloxane-polyamide copolymer molecules containing no azo group are not preferable, and if it exceeds 50% by weight, the repeating unit of polyamide is added to the finally obtained block copolymer of the present invention. Is not preferred because it is hardly contained. Equation (7)
In the polymerizable monomer represented by the formula, R ³ is a polysiloxanyl group-containing bifunctional group, the charged ratio of the monomer is represented by the formula (7)
With respect to the entire charged amount of the polymerizable monomer represented by 0.1,
-95% by weight, particularly preferably 1-90% by weight. In this case, if the amount is less than 0.1% by weight, it is difficult to obtain the preferable characteristics exhibited by the polysiloxanyl group, while if it exceeds 95% by weight, the obtained block copolymer of the present invention has a sufficient strength such as tensile strength. It is not preferable because it may not be obtained.

In the production method of the present invention, in the first-stage reaction, the number of moles of the polymerizable monomer represented by the formula (5) and the number of moles of the polymerizable monomer represented by the formula (6) are used. And the sum
When the number of moles of the polymerizable monomer represented by the formula (7) is equal to the number of moles, the degree of polymerization becomes highest. Therefore, based on this, the charged amount of each polymerizable monomer is calculated based on (the number of moles of the polymerizable monomer represented by the formula (5) and the mole of the polymerizable monomer represented by the formula (6)). It is preferable that (the sum of the numbers) / (the number of moles of the polymerizable monomer represented by the formula (7)) be selected from the range of 0.8 to 1.2.

The first-stage reaction may be a multi-stage reaction. For example, after mixing a polymerizable monomer represented by the formula (5) and a polymerizable monomer represented by the formula (7) in which R ³ is a divalent organic group other than the polysiloxanyl group-containing bifunctional group, , A polymerizable monomer represented by the following formula (6), and then R ³ is a polysiloxanyl group-containing bifunctional group.
A method of reacting a monomer containing a polymerizable monomer represented by the formula (7), or a polymerizable monomer represented by the formula (5) and a formula (7)
And then reacting the polymerizable monomer represented by the formula (6) with the polymerizable monomer represented by the formula (6).

In the first-stage reaction, a solvent can be used. Examples of the solvent include N, N-
Examples include dimethylformamide, N, N-dimethylacetamide, tetrahydrofuran, dioxane, diglyme, acetonitrile, dimethoxyethane, acetone, methyl ethyl ketone, methyl acetate, ethyl acetate, chloroform, and mixtures thereof. More preferable reaction conditions can be achieved by reducing the amount of water in the solvent by a known method and appropriately filling the solvent with dry nitrogen gas or dry air. The first-stage reaction conditions are as follows: -80 at normal pressure
It is preferable to carry out the reaction at a temperature of up to 80 ° C., but it is not limited to this.

In the first-stage reaction, an azo group-containing polysiloxane-polyamide copolymer is obtained. The weight average molecular weight of this copolymer is between 300 and 20
00000 is preferred, and more preferably 5000 to 50
0000. The azo group-containing polysiloxane-polyamide copolymer produced by the first-stage reaction can be purified by a known method. For example, water, an alcohol having 8 or less carbon atoms or a mixture thereof is precipitated and isolated by dropping the reaction solution, and water, the above alcohols, other organic solvents or a mixture thereof are added to the reaction solution. Examples of the method include a method of isolating the precipitate, a method of heating and cooling after the precipitation to increase the degree of purification, and the like. After the above-mentioned purification step, the purified product can be dried. Drying is performed under reduced pressure at -2
It is preferably carried out at 0 ° C. to 80 ° C., particularly at about room temperature to 40 ° C. The drying time is preferably 1 to 24 hours.

Next, in the second stage reaction, the azo group-containing polysiloxane-polyamide copolymer obtained above is polymerized with the phosphorylcholine analog-containing monomer represented by the formula (8). The charging ratio of the phosphorylcholine analog-containing monomer represented by the formula (8) is determined by the formula (5)
To the total amount of the polymerizable monomers represented by (7),
The range is preferably 0.1 to 95% by weight, particularly preferably 1 to 90% by weight. If the content is less than 0.1% by weight, preferable characteristics such as hydrophilicity, anti-blood cell adhesion, anti-protein adsorptivity, etc. exhibited by the phosphorylcholine-like group may not be obtained, which is not preferable. On the other hand, if the content exceeds 95% by weight, the tensile strength and the like of the molded product are undesirably reduced.

In the reaction of the second stage, the above formula (8)
In addition to the phosphorylcholine-like group-containing monomer represented by, another polymerizable monomer can be polymerized.
Other polymerizable monomers are not particularly limited, for example, (meth) acrylic acid, aconitic acid, itaconic acid, mesaconic acid, citraconic acid, fumaric acid, maleic acid, vinylsulfonic acid, acrylamide-2-methylpropanesulfone Acids, vinyl sulfonic acids, and various metal salts thereof;
N, N-dimethylaminopropyl (meth) acrylamide, N, N-dimethylaminoethyl (meth) acrylate, N, N-diethylaminoethyl (meth) acrylate, and various quaternary salts thereof; 2-vinylpyridine,
3-vinylpyridine, 4-vinylpyridine, 2-vinylimidazole, N-methyl-2-vinylimidazole,
N-vinylimidazole, (meth) acrylamide, N-
Methyl (meth) acrylamide, N, N-dimethyl (meth)
Acrylamide, N-ethyl (meth) acrylamide, N
-Isopropyl (meth) acrylamide, Nt-butyl
(Meth) acrylamide, 2-hydroxyethyl (meth) acrylate, monoglycerol methacrylate, N- (tris (hydroxymethyl) methyl) acrylamide, vinyl methyl ether, polyethylene glycol (meth) acrylate, N-vinylpyrrolidone, N- ( Various hydrophilic macromonomers such as (meth) acryloylpyrrolidone, acryloylmorpholine, maleic imide, and maleic anhydride; styrene monomers such as styrene, methylstyrene, chloromethylstyrene, and aminostyrene; methyl (meth) acrylate, ethyl ( (Meth) acrylate, butyl
(Meth) acrylate, dodecyl (meth) acrylate, cetyl (meth) acrylate, stearyl (meth) acrylate, cyclohexyl (meth) acrylate, various monoalkyl (meth) acrylates such as 2-ethylhexyl (meth) acrylate
Acrylate; glycidyl (meth) acrylate, (meth)
Reactive functional group-containing (meth) acrylates such as acryloyloxyethyltrimethoxysilane; 2- (meth) acryloyloxyethyl butyl urethane, 2- (meth) acryloyloxyethyl benzyl urethane, 2- (meth) acryloyloxyethyl phenyl urethane Urethane modification
(Meth) acrylate; various hydrophobic macromonomers such as ethyl vinyl ether, butyl vinyl ether, vinyl acetate, vinyl chloride, vinylidene chloride, ethylene, propylene, isobutylene, diethyl fumarate, diethyl malate, acrylonitrile, and vinylbenzylamine. . These can be used alone or as a mixture when used.

The second stage reaction is carried out by a known solution polymerization method,
It can be carried out according to a bulk polymerization method, an emulsion polymerization method, a suspension polymerization method and the like. The reaction can be carried out, if necessary, by substituting the polymerization system with an inert gas, for example, nitrogen, carbon dioxide, helium, or the like, or under an atmosphere, and starting the polymerization using various redox accelerators. You may. The polymerization temperature is preferably from 0 to 120C, and the polymerization time is preferably from 10 minutes to 48 hours.

Purification of the block copolymer obtained by the production method of the present invention can be carried out by a conventional reprecipitation method, dialysis method, ultrafiltration method or the like. In this purification step,
It is also possible to perform wet molding by solidifying while molding into a specific shape, for example, a fiber shape, a hollow fiber shape, a thread shape, or the like.

The copolymer such as the block copolymer of the present invention is excellent in film formability and moldability as compared with conventional natural phospholipids, and can be easily formed into a desired shape such as a film or fiber. It is possible. For example, a molded article can be easily formed by a very simple method such as a hot press or a solvent casting method. In particular, since heat molding is possible, various forms of molded articles can be obtained. Moreover, the resulting molded products such as films and fibers are superior in strength as compared to molded products molded from natural phospholipids. Furthermore, since the copolymer of the present invention contains a polysiloxane component, a phospholipid-like component and a polyamide component, by controlling the molecular weight and the like of each segment, the form can be changed to an oil, gel, or paste. , Elastomers, plastics and the like can be arbitrarily changed to desired properties. The copolymer of the present invention that can be in the above various forms,
Biocompatibility such as anti-thrombotic, anti-cell adhesion, anti-protein adhesion; gas permeability such as oxygen, etc., can be used for medical materials such as artificial organs; sensors such as biosensors; Ophthalmic materials such as lenses and intraocular lenses can be used in a wide range of fields such as gas separation membranes.
In particular, they are excellent in biocompatibility such as anti-cell adhesion and anti-protein adhesion, thermoplasticity, elasticity, etc., and thus are suitable as medical materials and ophthalmic materials.

[0038]

Since the copolymer of the present invention has a polysiloxane component, a polyamide component and a phospholipid-like component, it is excellent in biocompatibility and has a heat moldability and / or a certain degree of tensile strength after molding. . Also,
Hydrophilicity, water absorption and transparency can be imparted. Therefore, it is useful for various medical materials and ophthalmic materials. In the production method of the present invention, a block copolymer among the above copolymers can be easily obtained, and the molecular design of the obtained block copolymer is also easy. Obtainable.

[0039]

The present invention will be described below in more detail with reference to Examples and Comparative Examples, but the present invention is not limited thereto. Example 1 An average molecular weight of 1 as a polymerizable monomer represented by the formula (7)
54.7 g (33 mmol) of α, ω-bis (3-aminopropyl) polydimethylsiloxane of 680 and 3,4′-
8.4 g (42 mmol) of diaminodiphenyl ether
And 15.2 g (0.15 mol) of triethylamine and 250 ml of a mixed solvent of tetrahydrofuran-N, N-dimethylacetamide (2: 1 (volume ratio)) to prepare a mixed solution. On the other hand, 14.5 g (71.25 m) of isophthaloyl chloride as a polymerizable monomer represented by the formula (6) is used.
mol) and a polymerizable monomer represented by the formula (5):
4,4'-azobis (cyanopentanoic acid chloride) 1.2
g (3.75 mmol) and tetrahydrofuran-N, N
-Dimethylacetamide mixed solvent (2: 1 (volume ratio)) 25
0 ml was mixed and dissolved to prepare a mixed solution, and the mixture was dropped into the previously obtained mixed solution to cause a reaction. After completion of the reaction, the reaction mixture was filtered to remove by-product trimethylamine hydrochloride. A polymer was precipitated by dropping the obtained filtrate into water, and the precipitated polymer was washed with methanol and dried under reduced pressure. The yield of the obtained polymer is 7
0.3 g, and the yield was 95.9%. Further, the obtained polymer was analyzed by gel filtration high performance liquid chromatography, and the weight average molecular weight was determined to be 43,000 using polyethylene glycol as a standard substance.

With respect to the obtained polymer,¹H-NMR component
The analysis was performed. The results are shown below.¹ H-NMR δ: 0.079 (-Si (CH ₃ )_TwoO-), 0.6
(−Si (CH_Three)_TwoCH ₂ CH_TwoCH_TwoNH−), 0.9 (−N = N−C (CH ₃ ) (C
N) CH_TwoCH_Two−CONH−), 1.6 (−Si (CH_Three)_TwoCH_Two CH ₂ CH _TwoNH
−), 2.4 (−N = N−C (CH_Three) (CN) CH ₂ CH ₂ −CONH−),
3.3 (-Si (CH_Three)_TwoCH_TwoCH _TwoCH ₂ NH-), 6.6-8.6 (Yoshi
Aromatic H), 10.2-10.4 (amide H).¹ From the analysis results of H-NMR, the obtained polymer was as follows:
Azo group-containing polydimethylsiloxane having a structural unit
It was a polyamide copolymer. Where y in the formula is
Α, ω-bis (3-aminopropyl) polydimethyl
And an integer of 10 to 200 corresponding to siloxane.

[0041]

Embedded image

Next, 1 part by weight (5.0 g) of the obtained azo group-containing polydimethylsiloxane-polyamide copolymer was mixed with 1 part by weight of MPC as a phosphorylcholine analog-containing monomer represented by the formula (8). (5 g), and then mixed with a propanol-N, N-dimethylacetamide mixed solvent.
(1: 1 (volume ratio)) was dissolved in 50 ml. Subsequently, after degassing and sealing, a polymerization reaction was performed at 80 ° C. for 12 hours. After the polymerization reaction, the obtained reaction solution was poured into a dialysis tube, and dialyzed against water to purify the polymer. The yield and yield of the obtained purified polymer were measured. Furthermore, analysis was performed by gel filtration high performance liquid chromatography, and the weight average molecular weight was determined using polyethylene glycol as a standard substance. Table 1 shows the results. Further, the obtained polymer was heated and pressed under the conditions of 150 ° C. and 10 MPa to form a film having a thickness of 0.1 mm. The obtained membrane was immersed in ion-exchanged water, and the water absorption after 48 hours was calculated. The water absorption was determined based on the following equation. Table 1 shows the results. Water absorption (%) = ((weight of film after swelling−weight of dry film) / weight of film after swelling) × 100

Further, regarding the obtained polymer, ¹ H—N
MR analysis was performed. The results are shown below. ¹ H-NMR δ: 0.079 (-Si (C H ₃ ) ₂ O-), 0.6
_{(-Si (CH 3) 2 C} H 2 CH 2 CH 2 NH -), 1.6 (-Si (CH 3) 2 CH 2 C H 2
_{CH 2 NH -), 2.0 (} -CH 2 -C (C (= O)) (C H 3) -), 3.3
_{^{(-N + (C H 3)}} 3, -Si (CH 3) 2 CH 2 CH 2 C H 2 NH -), 3.7 (-OC
^{_{H 2 C H 2 -N + -}} ), 3.9-4.4 (-C (= O) O-C H 2 C H 2 O-P
_{O 2 -O-C H 2 CH} 2 -N + -), 6.6-8.6 ( aromatic H). ^{From the} result of ¹ H-NMR analysis, the obtained polymer was a block copolymer having the following structural units. Here, y in the formula represents an integer of 10 to 200 corresponding to α, ω-bis (3-aminopropyl) polydimethylsiloxane as a raw material. In addition, the composition was determined from this analysis result, and the equation
The content ratio of the unit corresponding to the structural unit shown in (1) to (4) was determined. Table 1 shows the results.

[0044]

Embedded image

[0045]Examples 2 to 7 Implemented except that the amount of MPC was changed as shown in Table 1.
A block copolymer was obtained in the same manner as in Example 1.
Various measurements were made. Table 1 shows the results. still, ¹H-N
Structures contained in the block copolymer obtained as a result of MR
The same as in Example 1 except that the content of the
It was like.

Comparative Example 1 A block copolymer was obtained in the same manner as in Example 1 except that the charged amount of each polymerizable monomer was changed as shown in Table 1.
Various measurements similar to those described above were performed. Table 1 shows the results. still,
As a result of ¹ H-NMR, the structural units contained in the obtained block copolymer were as follows. However, y in the formula is α, ω-bis (3-aminopropyl) as a raw material.
Shows an integer from 10 to 200 corresponding to polydimethylsiloxane.

[0047]

Embedded image

Comparative Example 2 5.0 g of MPC and 0.1 g of 4,4'-azobis (cyanopentanoic acid) were dissolved in 50 ml of a mixed solvent of propanol-N, N-dimethylacetamide (1: 1 (volume ratio)). After degassing and sealing, a polymerization reaction was carried out at 80 ° C. for 12 hours. The obtained polymerization solution was injected into a dialysis tube, and dialyzed against water to purify the polymer. For the obtained purified polymer, various measurements similar to those in Example 1 were performed. Table 1 shows the results. In addition, as a result of ¹ H-NMR, the structural units contained in the obtained block copolymer were as follows.

[0049]

Embedded image

[0050]

[Table 1]

Example 8 The average molecular weight of the polymerizable monomer represented by the formula (7) was 1
54.7 g (33 mmol) of α, ω-bis (3-aminopropyl) polydimethylsiloxane of 680 and 3,4′-
8.4 g (42 mmol) of diaminodiphenyl ether
And 15.2 g (0.15 mol) of triethylamine and 250 ml of a mixed solvent of tetrahydrofuran-N, N-dimethylacetamide (2: 1 (volume ratio)) to prepare a mixed solution. On the other hand, 13.7 g (67.5 mm) of isophthaloyl chloride as a polymerizable monomer represented by the formula (6) is used.
ol) and a polymerizable monomer represented by the formula (5):
4,4'-azobis (cyanopentanoic acid chloride) 2.4
g (7.5 mmol) and tetrahydrofuran-N, N-
Dimethylacetamide mixed solvent (2: 1 (volume ratio)) 250
and the mixture was dissolved by dissolution to prepare a mixed solution. The mixture was dropped into the previously obtained mixed solution to cause a reaction. After completion of the reaction, the reaction mixture was filtered to remove by-product trimethylamine hydrochloride. A polymer was precipitated by dropping the obtained filtrate into water, and the precipitated polymer was washed with methanol and dried under reduced pressure. The yield of the obtained polymer is 7
2.2 g, and the yield was 97.9%. Further, the obtained polymer was analyzed by gel filtration high performance liquid chromatography, and the weight average molecular weight was determined to be 39000 by using polyethylene glycol as a standard substance. The obtained polymer was subjected to ¹ H-NMR analysis. As a result, the obtained polymer was an azo group-containing polydimethylsiloxane-polyamide copolymer having the same structural units as in Example 1.

Next, 1 part by weight (5.0 g) of the obtained azo group-containing polydimethylsiloxane-polyamide copolymer was mixed with 1 part by weight of MPC as a phosphorylcholine analog-containing monomer represented by the formula (8). (5 g), and then mixed with a propanol-N, N-dimethylacetamide mixed solvent.
(1: 1 (volume ratio)) was dissolved in 50 ml. Subsequently, after degassing and sealing, a polymerization reaction was performed at 80 ° C. for 12 hours. After the polymerization reaction, the obtained reaction solution was poured into a dialysis tube, and dialyzed against water to purify the polymer. The same measurement as in Example 1 was performed on the obtained purified polymer. Table 2 shows the results. Further, about the obtained polymer, ¹ H-
NMR analysis was performed. As a result, the obtained polymer is
It was a block copolymer having the same constitutional units as in Example 1. Further, the composition was obtained from the analysis results, and the formulas (1) to
The content ratio of the unit corresponding to the structural unit shown in (4) was determined. Table 2 shows the results.

[0053]Examples 9 to 13 Implemented except that the amount of MPC was changed as shown in Table 2.
A block copolymer was obtained in the same manner as in Example 8, and was obtained in the same manner as in Example 1.
Various measurements were made. Table 2 shows the results. still, ¹H-N
Structures contained in the block copolymer obtained as a result of MR
The same as in Example 1 except that the content of the
It was like.

[0054]

[Table 2]

Example 14 The average molecular weight of the polymerizable monomer represented by the formula (7) was 1
54.7 g (33 mmol) of α, ω-bis (3-aminopropyl) polydimethylsiloxane of 680 and 3,4′-
8.4 g (42 mmol) of diaminodiphenyl ether
And 15.2 g (0.15 mol) of triethylamine and 250 ml of a mixed solvent of tetrahydrofuran-N, N-dimethylacetamide (2: 1 (volume ratio)) to prepare a mixed solution. On the other hand, 12.9 g (63.75 m) of isophthaloyl chloride as a polymerizable monomer represented by the formula (6) is used.
mol) and a polymerizable monomer represented by the formula (5):
4,4'-azobis (cyanopentanoic acid chloride) 3.6
g (11.25 mmol) and tetrahydrofuran-N,
N-dimethylacetamide mixed solvent (2: 1 (volume ratio)) 2
50 ml was mixed and dissolved to prepare a mixed solution, and the mixed solution obtained above was dropped and reacted. After completion of the reaction, the reaction mixture was filtered to remove by-product trimethylamine hydrochloride. A polymer was precipitated by dropping the obtained filtrate into water, and the precipitated polymer was washed with methanol and dried under reduced pressure. The yield of the obtained polymer was 69.9 g, and the yield was 94.2%. Also,
The obtained polymer was analyzed by gel filtration high performance liquid chromatography, and the weight average molecular weight was determined using polyethylene glycol as a standard substance.
Met. The obtained polymer was subjected to ¹ H-NMR analysis. As a result, the obtained polymer was an azo group-containing polydimethylsiloxane-polyamide copolymer having the same structural units as in Example 1.

Next, 1 part by weight of the obtained azo group-containing polydimethylsiloxane-polyamide copolymer (5.0 g) was added to 1 part by weight of MPC as a phosphorylcholine analog-containing monomer represented by the formula (8). (5 g), and then mixed with a propanol-N, N-dimethylacetamide mixed solvent.
(1: 1 (volume ratio)) was dissolved in 50 ml. Subsequently, after degassing and sealing, a polymerization reaction was performed at 80 ° C. for 12 hours. After the polymerization reaction, the obtained reaction solution was poured into a dialysis tube, and dialyzed against water to purify the polymer. The same measurement as in Example 1 was performed on the obtained purified polymer. Table 3 shows the results. Further, about the obtained polymer, ¹ H-
NMR analysis was performed. As a result, the obtained polymer is
It was a block copolymer having the same constitutional units as in Example 1. Further, the composition was obtained from the analysis results, and the formulas (1) to
The content ratio of the unit corresponding to the structural unit shown in (4) was determined. Table 3 shows the results.

Examples 15 to 20 A block copolymer was obtained in the same manner as in Example 14, except that the amount of MPC was changed as shown in Table 3, and various measurements were carried out in the same manner as in Example 1. Table 3 shows the results. In addition, ¹ H-
As a result of NMR, the structural units contained in the obtained block copolymer were the same as in Example 1 except for the content ratio.

[0058]

[Table 3]

Test Example 1 The polymers prepared in Examples 11 to 13, Examples 17 to 20 and Comparative Examples 1 and 2 were hot-pressed at 150 ° C. and 10 MPa to form a film having a thickness of 0.1 mm. Molded. In addition, since the polymer prepared in Comparative Example 2 was finely cracked when the molded body was peeled off from the press plate used in the heat molding, a film large enough to be used in the test could be obtained. Did not. The transparency of the obtained film after drying was visually observed, and evaluated based on the following four criteria. Table 4 shows the results. ◎; very good, ○; good, Δ; turbidity was observed, ×;
I can't see through. From the results in Table 4, Examples 11 to 13 and Examples 17 to 2 were obtained.
Since the polymer of No. 0 can be molded by heat and has transparency, it can be seen that it is useful for ophthalmic materials such as contact lenses.

[0060]

[Table 4]

Test Example 2 The block copolymers prepared in Examples 1 and 14 and Comparative Example 1 were hot-pressed at 150 ° C. and 10 MPa to form a film having a thickness of 0.1 mm. The resulting membrane was converted to a diameter of 14
A test piece was cut out into a circular shape of mm. The obtained test piece was put in each hole of a 24-well microplate, fixed with an O-ring made of silicone rubber, added with 700 μl of physiological saline, and equilibrated overnight. Thereafter, the physiological saline was removed, 700 µl of Hanks' buffer was added, and the mixture was allowed to stand for 1.5 hours, after which the buffer was removed. Next, citrated blood collected from a rabbit (Japanese white species, male) was collected at 4 ° C. and 1500 ° C.
Centrifuge at 15 rpm for 15 minutes.
et Rich Plasma (PRP) was recovered. 700 μl of the obtained PRP was added to each hole of the microplate, and left still at room temperature for 1 hour. Thereafter, the PRP was removed and washed three times with 1 ml of Hanks buffer. The platelets adhered to the surface of the test piece were fixed at 4 ° C. with a 2.5% by weight aqueous solution of glutaraldehyde, the surface was coated with Au by sputtering, and the number of adhered platelets was observed by a scanning electron microscope. The observation was performed three times for each test piece, and the evaluation was performed in a visual field (18.6 × 2) of an SEM image (3500 times).
7.1 μm) was determined by counting the number of adherent platelets
mm ² ), and the observation was performed by an average value of three times. Table 5 shows the results.

[0062]

[Table 5]

Test Example 3 The block copolymers prepared in Examples 2 to 5, 7 and Comparative Example 1 were hot-pressed at 150 ° C. and 10 MPa.
It was formed into a film having a thickness of 0.5 mm. 15 ×
A test piece cut out to 50 mm was prepared. Each of the obtained test pieces was set on a tensile strength tester (UNITRON UST-500 (Kamishima Seisakusho)), and the tensile breaking strength and the tensile breaking elongation were measured at a pulling speed of 10 mm / min. Table 6 shows the results
Shown in

[0064]

[Table 6]

Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat II (Reference) C08G 77/455 C08G 77/455 (71) Applicant 000244143 Mitsuru Akashi 2- 14-6 Kotokujidai, Kagoshima City, Kagoshima Prefecture (72 Inventor Kensaku Sonoda 2-17-14 Kasuga, Tsukuba City, Ibaraki Prefecture (72) Inventor Tajiro Shiino 2-26-2 Kasuga, Tsukuba City, Ibaraki Prefecture (72) Inventor Akio Hayashi 421-3 Nedo, Kashiwa City, Chiba Prefecture 72) Inventor Nobuo Nakabayashi 5-6-20 Koganehara, Matsudo City, Chiba Prefecture 2-14-6 Teradai F-term (reference) 4C076 EE12 EE26 EE27 EE49 4J001 DA01 DB02 DC10 EB05 EB06 EB07 EB08 EB09 EB35 EB36 EB37 EB44 EC04 EC05 EC06 EC07 EC08 EC09 EC13 EC24 EC44 EC81 EE12C EE16A JA4 ABA4J026 AC04 DB02 DB09 DB12 DB32 FA08 GA08 4J035 BA02 CA01N GA02 GA06 GB09 LA02 LA03 LA04 LB20

Claims (7)

[Claims] 1. A copolymer having structural units represented by the formulas (1) to (4) and having a structural unit represented by the formula (3) wherein R ³ is a polysiloxanyl group-containing bifunctional group. Embedded image (In the formulas (1) to (3), R ¹ , R ² and R ³ each independently represent a divalent organic group. In the formula (4), R ⁴ represents a hydrogen atom or a methyl group, R ⁵ , R ⁶ and R ⁷ are the same or different and represent a hydrogen atom, a hydrocarbon group having 1 to 6 carbon atoms or a hydroxy hydrocarbon group, m represents 0 or 1 and n represents
Represents an integer of 2 to 4. X represents a divalent organic group; Y represents an alkyleneoxy group having 1 to 6 carbon atoms;
Represents a hydrogen atom or a group represented by the following formula (here, R ⁸
Represents an alkyl group having 1 to 10 carbon atoms or a hydroxyalkyl group having 1 to 10 carbon atoms))). Embedded image 2. A repeating unit (A) having structural units represented by formulas (1) to (3) and a repeating unit (B) represented by formula (4)
Wherein the proportion of the repeating units (A) and (B) is from 5 to 99.9: 0.1 to 95 by weight, and the structural unit represented by the formula (1) in the repeating unit (A) 2. The block copolymer according to claim 1, wherein the ratio of the block copolymer is 0.01 to 50% by weight. 3. A compound of the formulas (5) to (3) comprising a polymerizable monomer represented by the formula (7), wherein R ³ is a polysiloxanyl group-containing bifunctional group.
After polymerizing the polymerizable monomer represented by (7) to obtain an azo group-containing polysiloxane-polyamide copolymer, the obtained copolymer is represented by the following formula: (In the formulas (5) to (7), A ¹ and A ² each independently represent a hydroxyl group or a chlorine atom, and R ^{1 to} R ^{3 each} represent a divalent organic group.) Phosphorylcholine represented by the formula (8) 3. The method for producing a block copolymer according to claim 2, wherein the monomer having a similar group is subjected to a polymerization reaction. Embedded image (In the formula, R ⁴ represents a hydrogen atom or a methyl group, and R ⁵ , R ⁶ and R ⁷ are the same or different groups, and represent a hydrogen atom, a hydrocarbon group having 1 to 6 carbon atoms or a hydroxy hydrocarbon group. M is 0 or 1, and n is an integer of 2 to 4.
X represents a divalent organic group, Y represents an alkyleneoxy group having 1 to 6 carbon atoms, Z represents a hydrogen atom or a group represented by the following formula (where R ⁸ represents 1 to 10 carbon atoms). Represents an alkyl group or a hydroxyalkyl group having 1 to 10 carbon atoms))). Embedded image 4. The phosphorylcholine analog-containing monomer represented by the formula (8) is 2-methacryloyloxyethyl-
The production method according to claim 3, wherein the production method is 2 '-(trimethylammonio) ethyl phosphate. 5. The polymerizable monomer represented by the formula (5) contains 4,4′-azobis (4-cyanopentanoic acid chloride), and the polymerizable monomer represented by the formula (6) is isophthaloyl. As a polymerizable monomer containing yl chloride and represented by the formula (7), 3,4′-diaminodiphenyl ether;
5. The process according to claim ³ , wherein R ³ in (7) comprises a polysiloxanyl group-containing bifunctional group and a monomer represented by the formula (7a ¹ ). Embedded image (Where x represents an integer of 1 to 6, and y represents an integer of 10 to 200). 6. A medical material comprising the copolymer according to claim 1 as an active ingredient. 7. An ophthalmic material comprising the copolymer according to claim 1 as an active ingredient.