JPH09183819A - Copolymer having phospholipid-like structure and medical material - Google Patents

Abstract

(57) Abstract: A copolymer having a phospholipid-like structure capable of forming a coating layer having high durability and biocompatibility on a substrate surface by a simple operation, and a medical product coated with the copolymer. Provide materials for use. A _{(3) (W ;-( CH 2} ) k + 1 -, - COO (C
_{H 2) k -, - CONH-} (CH) k -, - C 6 H 4 (CH 2) k - or _{-C 6 H 4 CH 2 NH (} CH 2) k -, X; 2 Ataizanmoto, Y ; C1
~ 6 alkyleneoxy group, Z; H or R ² OCO-, k =
0-4, m = 0-10, R ¹ ; H or a methyl group, R ² ; C1
-10 alkyl group or hydroxyalkyl group, R ³ R
⁴ R ⁵ ; H or C 1-6 (hydroxy) hydrocarbon group, R ⁶ ;
C1-10 alkoxy group or C6～14 aryloxy group, R ⁷ R ^8; (halogen-containing) C1-10 alkoxy group, (halogen-containing) C6～14 aryloxy groups, C
1-10 alkyl group, O-containing C1-10 alkyl group or N-containing C1-10 alkyl group, R ⁹ ; H or methyl group), and the number average molecular weight 50 in which units a and b are uniformly distributed.
A copolymer of 00 to 300,000 and a: b = 95: 5 to 50:50 is provided. Embedded image

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a copolymer having a phosphorylcholine group-containing monomer and a silyl group-containing monomer as constituents and having a phospholipid-like structure, and a medical material obtained by coating the polymer.

[0002]

BACKGROUND OF THE INVENTION Phosphorylcholine group-containing polymers have biocompatibility such as blood compatibility, complement deactivation, nonadsorption of biological substances and antithrombotic property due to the phospholipid-like structure derived from biological membranes. It is known that it has excellent properties such as antifouling property, moisture retention property, etc., and research and development on polymer synthesis and its use for the purpose of developing biomaterials making the best use of their respective functions have been conducted. It is active.

Particularly, a substrate such as glass, ceramics or metal which can be easily processed and molded and has sufficient strength is coated with a phosphorylcholine group-containing polymer as a stable layer easily and without impairing the above-mentioned excellent properties. Is required to do. In order to achieve this purpose, various coating materials have been studied, physical adsorption, immobilization by ionic bonding, a method of incorporating reactive functional groups into the coating material and covalently bonding to the substrate, and reaction active sites on the substrate surface. Various coating methods have been proposed, such as a method of graft copolymerizing a phosphorylcholine group-containing monomer.

For example, JP-A-3-39309 discloses that a copolymer of 2- (methacryloyloxy) ethyl-2 '-(trimethylammonio) ethyl phosphate and a methacrylic acid ester maintains biocompatibility and It is disclosed that it has excellent mechanical properties and moldability.
Further, JP-A-7-502053 discloses that a comonomer having a functional group capable of physical adsorption, covalent bond or ionic bond on the surface of a substrate is copolymerized as an adhesion-imparting component, and the obtained phosphorylcholine group is obtained. It has been shown that when the surface of the substrate is coated with the contained copolymer, a medical material excellent in properties such as protein non-adsorption and biocompatibility can be obtained. In this case, it is also shown that a small amount of (3-trimethoxysilyl) propyl methacrylate can be used as a cross-linking component between the polymers, in addition to the comonomer that enhances the adhesion to the surface of the substrate. In addition, JP-A-7-5135
No. 5, gazette discloses 2- (methacryloyloxy) ethyl-
2 '-(trimethylammonio) ethyl phosphate 8
0 mol%, (3-methacryloyloxypropyl) trichlorosilane 5 mol%, and methyl methacrylate 15
A terpolymer consisting of mol% is exemplified, and it is shown that blood compatibility is maintained for a long period of time. Further, in JP-A-6-510322, an excellent biocompatible material is obtained by treating a stainless steel surface with (3-methacryloyloxypropyl) trimethoxysilane and then graft-copolymerizing a phosphorylcholine group-containing monomer. It is disclosed that it can be obtained. Further, JP-A-7-83923 discloses that a phosphorylcholine group-containing polymer can be used as a protein adsorption inhibitor.

[0005]

As described above, various efforts have been made to improve the adhesion to the surface of the base material.
It has not been possible to obtain a polymer which has a durability sufficient for practical use for a long period of time while maintaining functions such as biocompatibility and antifouling property. In particular, it is currently extremely difficult to stably coat a polymer containing a highly hydrophilic and chemically unstable phosphorylcholine group onto the surface of an inorganic metal, ceramics or glass while maintaining the above function. Difficult to do. That is, a sufficiently stable coating layer cannot be obtained by physical adsorption, and in the method of immobilizing by ionic bond, the exchange of an ionic substance existing in an aqueous medium or the adsorption of a biological substance due to surface charge easily occurs,
It is not possible to obtain a coating layer having both the above-mentioned functions such as antifouling property and biocompatibility and practical durability. In addition, the method of containing a reactive functional group in the coating material and covalently bonding to the base material does not provide sufficient adhesion and durability to the base material if the functional group is small, and if the quantity is large, the function expression will occur. There is a problem that it becomes insufficient and side reactions occur. In particular, unreacted reactive functional groups often adversely affect the function, and if unreacted reactive functional groups are reduced to make reaction conditions severe, unstable phosphorylcholine groups deteriorate. In particular, the use of a comonomer having a large amount of chlorosilyl group not only causes the highly reactive chlorosilyl group to react, but also causes hydrogen chloride produced during polymerization and storage to act on an unstable phosphorylcholine group for hydrolysis and transesterification. However, it adversely affects gelation and the like, and causes coating unevenness and a marked deterioration in blood compatibility. Further, in the method of graft-copolymerizing a phosphorylcholine group-containing monomer by forming reaction-active points on the surface of the substrate, it is necessary to make the reaction atmosphere oxygen-free in order to carry out the graft copolymerization, and also pretreat it. However, there is a problem that the reaction process is complicated, such as that

Therefore, the first object of the present invention is to solve the above-mentioned problems, and particularly to combine high durability and high biocompatibility on the surface of a base material such as glass, ceramics or metal by a simple operation. Another object of the present invention is to provide a copolymer having a phospholipid-like structure capable of forming a coating layer having the same.

A second object of the present invention is to provide a medical material having both high durability and high biocompatibility by being coated with the copolymer.

[0008]

According to the present invention, the general formula (1)

[0009]

Embedded image

(In the formula, X is a divalent residue, and Y is a carbon number 1
The 6 alkyleneoxy group, also Z represents ² -O-CO- hydrogen atom or R, m is an integer of 0, R ¹
Is a hydrogen atom or a methyl group, and R ² has 1 to 10 carbon atoms.
Represents an alkyl group or a hydroxyalkyl group of
³ , R ⁴ and R ⁵ are the same or different groups and are a hydrogen atom or a hydrocarbon group having 1 to 6 carbon atoms or 1 to 6 carbon atoms.
6 shows a hydroxyhydrocarbon group. ) At least one phosphorylcholine group-containing monomer represented by the general formula (2)

[0011]

Embedded image

(In the formula, W is-(CH ₂ ) _k- , -CO-O- (C
_{H 2) k -, - CO} -NH- (CH) k -, - C 6 H 4 - (CH 2)
_k -, or _{-C 6 H 4 -CH 2 -NH- (} CH 2) k - represents any. k is an integer of 0 to 4, R ⁹ is a hydrogen atom or a methyl group, R ⁶ is an alkoxy group having 1 to 10 carbon atoms or an aryloxy group having 6 to 14 carbon atoms, and R ⁷ and R ⁸ are the same or Different groups, which may have a halogen atom, have an alkoxy group having 1 to 10 carbon atoms, an aryloxy group having 6 to 14 carbon atoms, which may contain a halogen atom, an alkyl group having 1 to 10 carbon atoms, and an oxygen atom. Containing 1 to 10 carbon atoms
Or an alkyl group having 1 to 10 carbon atoms containing a nitrogen atom. ), Which is obtained by random or alternating copolymerization with at least one silyl group-containing monomer represented by the following general formula (3)

[0013]

[Chemical 6]

(Wherein W, X, Y, Z, k, m, R ¹ ,
R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ and R ⁹ are represented by the formula (1)
And the same as described in (2). ), And each monomer structural unit (a,
b) is evenly distributed and has a number average molecular weight of 5,000 to 3
And the composition ratio of a and b is 95: 5
A copolymer having a phospholipid-like structure of 50:50 is provided.

Further, according to the present invention, there is provided a medical material, the surface of which is coated with the above-mentioned copolymer having a phospholipid-like structure.

[0016]

BEST MODE FOR CARRYING OUT THE INVENTION The copolymer of the present invention contains a first monomer represented by the general formula (1) and a second monomer represented by the general formula (2) as constituent units.

The first monomer is a phosphorylcholine group-containing monomer represented by the above general formula (1). In the general formula (1), examples of the divalent residue X include the divalent residues exemplified below. However, in the formula, n represents an integer of 0 to 10.

[0018]

Embedded image

Specific examples of the first monomer include, for example,
2- (methacryloyloxy) ethyl-2 '-(trimethylammonio) ethyl phosphate, 3- (methacryloyloxy) propyl-2'-(trimethylammonio) ethyl phosphate, 4- (methacryloyloxy) butyl-2 '-( Trimethylammonio) ethyl phosphate, 5- (methacryloyloxy) pentyl-
2 '-(trimethylammonio) ethyl phosphate,
6- (methacryloyloxy) hexyl-2 '-(trimethylammonio) ethyl phosphate, 2- (methacryloyloxy) ethyl-2'-(triethylammonio) ethyl phosphate, 2- (methacryloyloxy) ethyl-2 '-( Tripropylammonio) ethyl phosphate, 2- (methacryloyloxy) ethyl-
2 '-(tributylammonio) ethyl phosphate,
2- (methacryloyloxy) ethyl-2 '-(tricyclohexylammonio) ethyl phosphate, 2-
(Methacryloyloxy) ethyl-2 '-(triphenylammonio) ethyl phosphate, 2- (methacryloyloxy) ethyl-2'-(trihydroxymethylammonio) ethyl phosphate, 2- (methacryloyloxy) propyl-2'- (Trimethylammonio) ethyl phosphate, 2- (methacryloyloxy) butyl-2 '-(trimethylammonio) ethyl phosphate, 2- (methacryloyloxy) pentyl-2'-
(Trimethylammonio) ethyl phosphate, 2-
(Methacryloyloxy) hexyl-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) ethyl phosphate, 2- (p-vinylbenzyloxy) ethyl-2'-
(Trimethylammonio) ethyl phosphate, 2-
(Vinyloxycarbonyl) ethyl-2 '-(trimethylammonio) ethylphosphate, 2- (allyloxycarbonyl) ethyl-2'-(trimethylammonio) ethylphosphate, 2- (acryloylamino)
Ethyl-2 '-(trimethylammonio) ethyl phosphate, 2- (vinylcarbonylamino) ethyl-2'
-(Trimethylammonio) ethyl phosphate, 2-
(Allyloxycarbonylamino) ethyl-2 '-(trimethylammonio) ethyl phosphate, ethyl-
(2'-Trimethylammonioethylphosphorylethyl) fumarate, butyl- (2'-trimethylammonioethylphosphorylethyl) fumarate, hydroxyethyl- (2'-trimethylammonioethylphosphorylethyl) fumarate, ethyl- (2'- Trimethylammonioethylphosphorylethyl) malate, butyl-
Examples thereof include (2′-trimethylammonioethylphosphorylethyl) malate and hydroxyethyl- (2′-trimethylammonioethylphosphorylethyl) malate. When used, they can be used alone or as a mixture.

The first monomer is as described in JP-A-54-63025.
JP-A-58-154591, JP-A-63
-222183, JP-A-5-107511, JP-A-6-41157 and JP-A-7-5020
It can be produced by a known method disclosed in Japanese Patent No. 53, or the like.

The second monomer is a silyl group-containing monomer represented by the general formula (2). The second monomer further comprises a compound in which R ^{6 to} R ⁸ are only an alkyl group having 1 to 10 carbon atoms, an alkoxy group having 1 to 10 carbon atoms or an aryloxy group having 6 to 14 carbon atoms, and a carbon atom containing an oxygen atom. It can be classified into a compound containing an alkyl group of 1 to 10 or a compound containing an alkyl group of 1 to 10 carbon atoms containing a nitrogen atom.

Specific examples of the second monomer belonging to the above are, for example, methoxydimethylvinylsilane, trimethoxyvinylsilane, (3-methacryloyloxypropyl) methoxydimethylsilane, (3-methacryloyloxypropyl) dimethoxymethylsilane and (3-vinyl). Benzylaminopropyl) trimethoxysilane, (3-
Methacryloyloxypropyl) trimethoxysilane and other methoxysilanes, ethoxydimethylvinylsilane,
Ethoxysilanes such as triethoxyvinylsilane, allyltriethoxysilane, (3-vinylbenzylaminopropyl) triethoxysilane, dimethylisobutoxyvinylsilane, dimethylisopentyloxyvinylsilane, tris (2-methoxyethoxy) vinylsilane, triisopropoxyvinylsilane. And the like, alkenyloxysilanes such as allyloxydimethylvinylsilane, and phenoxysilanes such as triphenoxyvinylsilane.

Specific examples of the second monomer belonging to the above include (2- (2-ethoxyethoxy) ethoxy) dimethylvinylsilane, diacetoxymethylvinylsilane, triacetoxyvinylsilane and the like.

Specific examples of the second monomer belonging to the above include (3-aminophenoxy) dimethylvinylsilane and (4-aminophenoxy) dimethylvinylsilane.

Among these silyl group-containing monomers,
Trialkoxysilane is most preferable because it can exhibit sufficient performance in terms of adhesion to substrates and durability. This is because a strong adhesion can be achieved by the cross-linking of silyl groups between polymer molecules by the interposition of three highly reactive alkoxy groups, the bonding of silyl groups within the same polymer molecule, or their strong interaction. It is considered that this is because a bond or a strong interaction between the polymer and the surface of the material is stimulated, and a stable layer of silane can be formed on the surface of the material. On the other hand, when conventional chlorosilanes such as vinyltrichlorosilane and allyltrichlorosilane are used, not only the reaction of highly reactive chlorosilyl group but also hydrogen chloride produced during polymerization and storage is unstable phosphorylcholine group. It also acts on silyl groups and adversely affects hydrolysis, transesterification, gelation, etc.

The copolymer of the present invention may contain, as a constituent unit, other radically copolymerizable monomer in addition to the first monomer and the second monomer. Other monomers are not particularly limited as long as they do not impair the effects of the present invention, and include, for example, styrene, methylstyrene, (o
-, M- or p-) chloromethylstyrene, methyl acrylate, methyl methacrylate, ethyl acrylate, ethyl methacrylate, butyl acrylate, butyl methacrylate, acrylic acid, methacrylic acid, acrylic acid amide, methacrylic acid amide, 2-hydroxyethyl acrylate, 2-hydroxyethyl methacrylate, ethyl vinyl ether, butyl vinyl ether, N
-Vinylpyrrolidone, vinyl chloride, vinylidene chloride, ethylene, propylene, isobutylene, acrylonitrile, or a mixture thereof can be preferably mentioned. In order not to impair the effects of the present invention, it is desirable that the content of the various other monomers be less than 70% by weight, and more preferably less than 50% by weight in the entire constitutional unit.

The copolymer of the present invention has a repeating unit represented by the above formula (3), which is obtained by random copolymerization or alternating copolymerization of the first monomer and the second monomer, as an essential constitutional unit. , A copolymer in which the respective monomer structural units (a, b) are uniformly distributed. On this occasion,
The fact that the monomer structural units (a, b) are uniformly distributed can be determined by, for example, a run number described later.

For such a copolymer, it is necessary to select an appropriate combination and an appropriate polymerization method from the first monomer and the second monomer so that each structural unit can be uniformly distributed when the copolymer is obtained. Can be obtained.

Suitable combinations of the first monomer and the second monomer generally include monomers having good copolymerizability, that is, conjugated monomers having a conjugated double bond, and non-conjugated double bonds. Conjugated monomers,
Or each combination of alternating copolymerizable monomers in a molar ratio close to equimolar can be mentioned. With these combinations, the optimum combination of random copolymerization or alternating copolymerization can be obtained.

Examples of combinations of conjugated monomers having conjugated double bonds include 2- (methacryloyloxy) ethyl-2 '-(trimethylammonio) ethyl phosphate and (3-methacryloyloxypropyl) trimethoxysilane. And the like. Examples of the combination of non-conjugated monomers having a non-conjugated double bond include a combination of 2- (allyloxy) ethyl-2 ′-(trimethylammonio) ethyl phosphate and trimethoxyvinylsilane. Examples of the combination of the alternating copolymerizable monomers include ethyl-
Examples include a combination of (2′-trimethylammonioethylphosphorylethyl) malate and trimethoxyvinylsilane.

As an index for more quantitative selection of these combinations, the monomer reactivity ratio, which is a parameter expressing copolymerizability, can be used. That is, each reaction represented by the following formulas (a) to (d) at the time of copolymerization M ₁ · + M ₁ → M ₁ · (a) M ₁ · + M ₂ → M ₂ · (b) M ₂ Each reaction represented by + M ₁ → M ₁ · (c) M ₂ · + M ₂ → M ₂ · (d) (wherein M ₁ and M ₂ represent the first monomer and the second monomer, respectively) the rate constants, respectively k ₁₁ of, k _12, k _21, and when the k _22, monomer reactivity ratios r ₁ and r _{2 are, r 1 = k 11 / k} 12 , respectively, r ₂ = k
₂₂ / k ₂₁ . In the copolymerization reaction of the first monomer and the second monomer, when the value of r ₁ × r ₂ is close to 1 (the above or in the case), random copolymerization is likely to occur. Also,
When the value of r ₁ × r ₂ is close to 0 (in the above case), alternating copolymerization is likely to occur.

As a suitable method for polymerizing the first monomer and the second monomer, when a combination of the first monomer which is difficult to copolymerize and the second monomer having high reactivity is selected, one of the monomers is used as a reaction system. A method of performing polymerization while constantly increasing the concentration of the monomer in the system by gradually dropping it into the system, or a procedure in which the reaction is quickly completed at the same time as the mixture of the first monomer and the second monomer that is difficult to copolymerize is dropped. Any method commonly used for obtaining a uniform copolymer can be used, such as a method of repeating

Whether or not each monomer structural unit is uniformly distributed in the copolymer obtained by the above-mentioned appropriate copolymerization can be confirmed by analyzing the microstructure of the copolymer. In particular, as one of the indicators of whether or not it has sufficient homogeneity to obtain the effect of the present invention, ru
n number (R) can be mentioned. A run is a continuous chain of the same monomers existing in the copolymer, and the value R of the run number is defined as the number of all runs existing per 100 monomer constitutional units in the copolymer. To be done. For example, R = 100 in the case of a perfect alternating copolymer, and R = 2 in the case of an AB type block copolymer. That is, the run number is an index of the number of bonds between the first monomer and the second monomer, which is a portion showing the alternating property of the copolymer.

The run number correlates with the monomer reactivity ratio and can be obtained by the formula (e) in the low conversion rate in the initial stage of polymerization, and in the high conversion state as the reaction proceeds. The average value (R) can be obtained by f). In the copolymer of the present invention, run numb is used as an index for uniformly distributing the monomer structural units (a, b).
When er is used, an R value of 8 or more, particularly 10 or more is preferable in order to simultaneously satisfy the functions such as biocompatibility and antifouling property and the functions such as adhesion and durability.

[0035]

[Equation 1]

[0036]

[Equation 2]

In the formulas (e) and (f), F ₁ represents the mole fraction of the first monomer in the copolymer, and m represents the polymerization rate (edited by the Society of Polymer Science, "Copolymerization 1-Reaction Analysis"). Baifukan (1
975)).

The copolymer of the present invention has a number average molecular weight of 50.
It is 00-300000. When the number average molecular weight is less than 5,000, the concentration of silyl group per molecule decreases and the physical adsorption effect also decreases, resulting in insufficient adhesion and durability with a substrate or the like. The number average molecular weight is 30
When it exceeds 0000, the solution viscosity becomes high and it becomes difficult to handle and to prepare a thin coating layer.

In the copolymer of the present invention, the molar ratio of the first monomer to the second monomer is 95: 5 to 50:
50, preferably 90:10 to 70:30. First
When the molar ratio of the monomers is less than 50%, the functions such as biocompatibility and antifouling property are likely to deteriorate. If the molar ratio of the second monomer is less than 5%, the adhesion and durability will be insufficient, and if it exceeds 50%, the functions such as biocompatibility and antifouling property will be likely to deteriorate, and polysilane will be further added during the polymerization. To form gelation easily.

The reaction operation for producing the copolymer of the present invention is not particularly limited as long as the above-mentioned copolymer structure and the effects of the present invention are not impaired, but solution polymerization, suspension polymerization,
The methods used in ordinary radical polymerization such as emulsion polymerization and bulk polymerization can be used, and solution polymerization is particularly preferable.

A polymerization initiator may be added during the polymerization reaction. The polymerization initiator is not particularly limited, and a usual polymerization initiator for radical polymerization can be used. Specifically, benzoyl peroxide, t-butylperoxy-2-ethylhexanoate, succinyl peroxide, glutarperoxide, succinylperoxyglutarate, t-butylperoxymalate, t
-Butyl peroxypivalate, di-2-ethoxyethyl peroxy carbonate, 3-hydroxy-1,1-
Organic peroxides such as dimethylbutyl peroxypivalate; azobisisobutyronitrile, dimethyl-2,2 '
-Azobisisobutyrate, 1-((1-cyano-1-
Methylethyl) azo) formamide, 2,2'-azobis (2-methyl-N-phenylpropionamidin) dihydrochloride, 2,2'-azobis (2-methyl-N- (2-hydroxyethyl) -propion Amide), 2,2'-azobis (2-methylpropionamide) dihydrate, 4,4'-azobis (4-cyanopentanoic acid), 2,2'-azobis (2- (hydroxymethyl) propionitrile), etc. The azo compound and the like can be used, and when used, they can be used alone or as a mixture.

Examples of the solvent for carrying out the solution polymerization include methanol, ethanol, propanol, butanol, ethylene glycol, glycerin, tetrahydrofuran, acetone, methyl ethyl ketone, diethyl ketone, acetonitrile, nitrobenzene, and mixtures thereof. You can When alcohols are used as the polymerization solvent, the alcohols may substitute with the alkoxy group or aryloxy group bonded to the silyl group, and the silyl group charged with the silyl group in the resulting polymer is used. The chemical structure with the contained monomer may change.

In the polymerization reaction, when a large amount of water is present in the solvent, the silyl group is hydrolyzed to a silanol group, which may bind to a container such as glass or metal or form polysilane, which is not preferable. Therefore, in such a case, it is preferable that the solvent is dehydrated before the polymerization.

The polymerization conditions for carrying out the above polymerization reaction are preferably a polymerization temperature of 5 to 100 ° C. and a polymerization time of 10 minutes to 20 hours. The monomer and the polymerization initiator may be dissolved from the beginning or may be added sequentially or continuously afterwards. Further, a chain transfer agent may be used to control the molecular weight of the resulting copolymer. The amount of the polymerization initiator used is 100 parts by weight of the monomer component,
It is preferably 0.01 to 20 parts by weight, and more preferably 0.1 to 10 parts by weight.

After completion of the polymerization reaction, the obtained product is purified to remove residual monomers and the like, whereby the copolymer of the present invention can be obtained. As a method for purification, usual methods such as reprecipitation and ultrafiltration can be used, but since silyl groups are hydrolyzed to silanol groups in the presence of water, it is preferable to perform purification in an atmosphere without water. .

Depending on the polymerization conditions, the polymerization conversion rate may be high and it may not be necessary to remove the residual monomer. In such a case, after the reaction is completed, the reaction solution can be directly subjected to coating without purification to produce the medical material of the present invention described later. Alternatively, the reaction solution after completion of the reaction may be directly dissolved or dispersed in water or alcohol to give a coating solution.

The medical material of the present invention has a surface of a substrate coated with the copolymer of the present invention.

The base material is not particularly limited,
Glass, ceramics, metal or the like can be used.

Examples of the glass include silicate glass which is usually used industrially, and glass which is used as biomedical glass. For example, bioinert biomedical glass such as aluminosilicate glass; or amorphous glass or crystalline glass containing calcium oxide and phosphorus pentoxide, hydroxyapatite, tricalcium phosphate porous body, calcium oxide-alumina-5 There are bioactive bio-glasses that cause decomposition, absorption, reaction, precipitation, etc. in the living body, such as phosphorus oxide-based porous bodies, glass fibers containing calcium oxide and phosphorus pentoxide, and the like. It also includes porous glass used as oxygen carriers, separation membranes, adsorbents, and the like.

As the above-mentioned ceramics, in addition to the products conventionally produced in the ceramic industry, new ceramics,
A wide range of materials, such as those called fine ceramics or advanced ceramics, are included, but medical ceramics used in the biological field are most preferable. Medical ceramics include bio-inert ceramics such as alumina, zirconia, carbon, silicon nitride, and silicon carbide that hardly change in the living body; or in living bodies such as hydroxyapatite, tricalcium phosphate, tetracalcium phosphate, and living glass. Examples thereof include bioactive ceramics that undergo decomposition, absorption, reaction and the like.

As the metal, stainless steel, Co--
There are Cr alloys, titanium and titanium alloys, Ni-Ti alloys, tantalum, etc., and those usually called medical metal materials are preferable.

As a coating method, a coating solution is prepared by dissolving or dispersing 0.1 to 60% by weight of the copolymer of the present invention in water, which is applied to a substrate for 1 minute to
The method of contacting for 1 hour is mentioned. At this time, the coating can be efficiently performed by heating the coating solution to 60 ° C. or higher or acidifying the coating solution with acetic acid or the like to a pH of about 3 to 5. After coating, lightly wash with water and then at room temperature for 12 ~
It is preferable to dry for 24 hours, 50 to 70 ° C. for 6 to 12 hours, or 90 to 120 ° C. for 1 to 4 hours.

As another method for coating, a coating solution is prepared by adding 0.5 to 50% by weight of water to a solution or dispersion of 0.1 to 60% by weight of the copolymer of the present invention in alcohol. Then, a method of bringing this into contact with the substrate for 1 minute to 1 hour can be mentioned. The water added when preparing the coating solution is preferably added in an equimolar amount or more of the silyl group in the solution in order to hydrolyze the silyl group. When coating, add 6 parts of coating solution.
Coating can be efficiently performed by heating to 0 ° C. or higher or by making the coating solution acidic with acetic acid or the like at a pH of about 3 to 5. After coating, lightly clean with alcohol and then at room temperature for 12-24
It is preferable to dry for 6 hours to 12 hours at 50 to 70 ° C. or 30 minutes to 4 hours at 90 to 120 ° C.

Yet another method of coating is as follows:
A method in which 0.1 to 80% by weight of the copolymer of the present invention is dissolved or dispersed in water or an organic solvent to form a coating solution, which is directly applied to a substrate and dried. As a method of directly applying the coating solution, in addition to a usual method of applying with a brush, a roller, a blade, etc., a method of spraying, a spin coating,
A technique such as dip coating can be used.

The medical material of the present invention can be used in, for example, instruments and devices that come into contact with biological substances. The bio-related substances are proteins such as enzymes and antibodies, peptides such as glutathione, various blood-derived substances including various blood cells such as platelets and leukocytes, and various floating cells.

There are no particular restrictions on the instruments and devices that come into contact with biological substances, and various instruments and devices that are preferably highly biocompatible can be mentioned. Specifically, for example, artificial organs, blood circuits, artificial heart-lung circuits, reaction vessels such as various clinical test instruments or clinical test instruments used in clinical tests, injection needles, cannulas, catheters, guide wires, slants, fiberscopes, sensors , Nozzles, stirring devices, glass beads, metal fine particles, magnetic fine particles, bioreactors, gel filtration columns, capillary columns and the like.

The medical material of the present invention has a highly hydrophilic surface because it has a polymer surface layer containing a phosphorylcholine group. Therefore, the medical material of the present invention can also be used as a medical material having effects such as prevention of fogging and dew condensation.

[0058]

INDUSTRIAL APPLICABILITY The copolymer of the present invention is coated with a copolymer having a phospholipid-like structure chemically bonded to the surface of a substrate by a very simple operation of bringing it into contact with an apparatus or device for coating and drying it. Layers can be formed. Further, since this coating layer contains a silyl group and a phosphorylcholine group in an appropriate composition and in a uniformly distributed state, the silyl group portion is formed by firmly bonding to the material surface or between the silyl groups. ,
In addition, the surface thereof has a high water solubility and a phosphorylcholine group portion excellent in biocompatibility has a multiphase structure forming a surface layer, and has both high durability and high biocompatibility. Therefore, the copolymer of the present invention is useful as a coating material or the like that can easily form a coating layer having high durability and high biocompatibility on a substrate.

Further, the medical material of the present invention has high durability and high biocompatibility at the same time because the coating material is coated on the surface thereof.

[0060]

The present invention will be described in more detail with reference to the following examples.
The present invention is not limited to these. In the following examples, the polymerization rate, the monomer reactivity ratio, and the mole fraction were calculated by the following equations.

Polymerization rate The reaction mixture was sampled at regular intervals of 270M.
It was determined by measuring the monomer concentration by proton NMR of Hz.

A value such that r ₁ and r ₂ are optimized by a computer by a relational expression (g) between the monomer reactivity specific polymerization rate m and the mole fraction f ₁ of the first monomer in the reaction system is calculated by a computer. I asked.

[0063]

(Equation 3)

Molar Fraction of First Monomer of Copolymer F
₁ (calculated value) Calculated from the relational expression (h) between the monomer composition and the copolymer composition.

[0065]

(Equation 4)

[0066] The value R of the run number The the run number The was calculated from the equation (e).

Examples 1-1a to 1-1b Copolymer of 2- (methacryloyloxy) ethyl-2 '-(trimethylammonio) ethyl phosphate and 3- (methacryloyloxypropyl) trimethoxysilane 2- ( Methacryloyloxy) ethyl-2 '-(trimethylammonio) ethyl phosphate (hereinafter abbreviated as MPC) and 3- (methacryloyloxypropyl)
Monomer mixture 2 composed of trimethoxysilane (hereinafter abbreviated as M3MS) adjusted to an MPC mole fraction of 0.6
Ethanol (60 g) was added to 0 g to form a uniform solution, and the atmosphere was sufficiently replaced with nitrogen. Then, 0.4 g of t-butylperoxypivalate was further added as a polymerization initiator, and copolymerization was performed at 60 ° C. Sampling is performed at regular intervals, each monomer concentration is measured by proton NMR, the polymerization rate m and the mole fraction f ₁ of the first monomer in the reaction system are determined, and further, by the relational expression (g), r ₁ A value was calculated by a computer such that r and r ₂ were optimized. The polymerization rate is 27%
The reaction solution at that time was added dropwise to methyl ethyl ketone to precipitate a copolymer, which was filtered and then vacuum dried to obtain a white powder. I
When R and GPC measurements were performed, the following results were obtained,
It was confirmed that the obtained product was a copolymer of MPC and M3MS.

IR: 970 cm ^-1 (N ⁺ (CH ₃ ) ₃ ),
1090 cm ^-1 (C-O-C), 1170 cm ^-1 (Si
-O), 1240 cm ^-1 (P-O), 1720 cm
^-1 (C = O) GPC: number average molecular weight; 58,000, weight average molecular weight;
145000 Furthermore, the molar fraction of the MPC constitutional unit in the copolymer measured by measuring the amount of nitrogen by Kjeldahl analysis was 0.
It was 61.

Further, the polymerization was carried out in the same manner except that the charged mole fraction of MPC monomer was changed to 0.9. The results of the two cases obtained are shown in Examples 1-1a and 1-1b, respectively.
Are shown in Table 1.

Examples 1-2a to 1-2b Copolymer of 2- (allyloxy) ethyl-2 '-(trimethylammonio) ethyl phosphate and trimethoxyvinylsilane 2- (allyloxy) ethyl-instead of MPC 2'-
(Trimethylammonio) ethyl phosphate (hereinafter, referred to as
Example 1-1a, except that trimethoxyvinylsilane (hereinafter abbreviated as V3MS) was used instead of M3MS, and 0.4 g of t-butylperoxypivalate was set to 1.6 g. Polymerization was performed in the same manner as in 1-1b. The results of the two obtained examples are shown in Table 1 as Examples 1-2a and 1-2b, respectively. The IR measurement results of the obtained copolymer were as follows.

IR: 970 cm ^-1 (N ⁺ (CH ₃ ) ₃ ),
1090 cm ^-1 (C-O-C), 1170 cm ^-1 (Si
-O), 1240 cm ^-1 (P-O), 1720 cm
^-1 (C = O) Examples 1-3a to 1-3b Copolymer of ethyl- (2'-trimethylammonioethylphosphoryl) fumarate and trimethoxyvinylsilane Ethyl- (2'-trimethyl instead of MPC Ammonioethylphosphoryl) fumarate (hereinafter abbreviated as EPF), V3MS was used instead of M3MS, and 0.4 g of t-butylperoxypivalate was added to 1.2 g.
Polymerization was performed in the same manner as in Examples 1-1a and 1-1b, except that g was used. The results of the two obtained examples are shown in Table 1 as Examples 1-3a and 1-3b, respectively. The IR measurement results of the obtained copolymer were as follows.

IR: 970 cm ^-1 (N ⁺ (CH ₃ ) ₃ ),
1090 cm ^-1 (C-O-C), 1170 cm ^-1 (Si
-O), 1240 cm ^-1 (P-O), 1720 cm
^-1 (C = O) Examples 1-4a to 1-4b 2- (p-vinylbenzyl) ethyl-2 '-(trimethylammonio) ethyl phosphate and (3-methacryloyloxypropyl)
Copolymer with trimethoxysilane 2- (p-vinylbenzyl) ethyl-instead of MPC
Example 1-Aside from using 2 '-(trimethylammonio) ethyl phosphate (hereinafter abbreviated as VPC)
Polymerization was performed in the same manner as in 1a to 1-1b. The results of the two obtained examples are shown in Table 1 as Examples 1-4a and 1-4b, respectively. The IR measurement results of the obtained copolymer were as follows.

IR: 970 cm ^-1 (N ⁺ (CH ₃ ) ₃ ),
1090 cm ^-1 (C-O-C), 1170 cm ^-1 (Si
-O), 1240 cm ^-1 (P-O), 1720 cm
^-1 (C = O) Examples 1-5a to 1-5b 2- (methacryloyloxy) ethyl-2 '-(trimethylammonio) ethyl phosphate and (3-methacryloyloxypropyl)
Copolymer with dimethoxymethylsilane The procedure was the same as in Examples 1-1a to 1-1b except that (3-methacryloyloxypropyl) dimethoxymethylsilane (hereinafter abbreviated as M2MS) was used instead of M3MS. Polymerization was carried out. The results of the two obtained examples are shown in Table 1 as Examples 1-5a and 1-5b, respectively. The IR measurement results of the obtained copolymer were as follows.

IR: 970 cm ^-1 (N ⁺ (CH ₃ ) ₃ ),
1090 cm ^-1 (C-O-C), 1170 cm ^-1 (Si
-O), 1240 cm ^-1 (P-O), 1720 cm
^-1 (C = O) Examples 1-6a to 1-6b 2- (methacryloyloxy) ethyl-2 '-(trimethylammonio) ethyl phosphate and (3-methacryloyloxypropyl)
Copolymer with methoxydimethylsilane The same operation as in Examples 1-1a to 1-1b except that (3-methacryloyloxypropyl) methoxydimethylsilane (hereinafter abbreviated as M1MS) was used instead of M3MS. Polymerization was carried out. The results of the two obtained examples are shown in Table 1 as Examples 1-6a and 1-6b, respectively. The IR measurement results of the obtained copolymer were as follows.

IR: 970 cm ^-1 (N ⁺ (CH ₃ ) ₃ ),
1090 cm ^-1 (C-O-C), 1170 cm ^-1 (Si
-O), 1240 cm ^-1 (P-O), 1720 cm
^-1 (C = O) Comparative Examples 1-1a to 1-1b Copolymer of 2- (methacryloyloxy) ethyl-2 '-(trimethylammonio) ethyl phosphate and trimethoxyvinylsilane V3MS was used instead of M3MS. Polymerization was performed in the same manner as in Examples 1-1a and 1-1b, except that t-butyl peroxypivalate was used in an amount of 0.4 g and 0.8 g. The results of the two obtained examples are shown in Table 1 as Comparative Examples 1-1a and 1-1b, respectively. The IR measurement results of the obtained copolymer were as follows.

IR: 970 cm ^-1 (N ⁺ (CH ₃ ) ₃ ),
1090 cm ^-1 (C-O-C), 1170 cm ^-1 (Si
-O), 1240 cm ^-1 (P-O), 1720 cm
^-1 (C = O) Comparative Examples 1-2a to 1-2b Copolymer of 2- (allyloxy) ethyl-2 '-(trimethylammonio) ethyl phosphate and 3- (methacryloyloxypropyl) trimethoxysilane Polymerization was performed in the same manner as in Examples 1-1a and 1-1b, except that APC was used instead of MPC, and 0.4 g of t-butylperoxypivalate was changed to 1.6 g. The results of the two cases obtained are shown in Comparative Examples 1-2a and 1-2, respectively.
It is shown in Table 1 as b. In addition, the IR of the obtained copolymer
The measurement results of were as follows.

IR: 970 cm ^-1 (N ⁺ (CH ₃ ) ₃ ),
1090 cm ^-1 (C-O-C), 1170 cm ^-1 (Si
-O), 1240 cm ^-1 (P-O), 1720 cm
^-1 (C = O)

[0078]

[Table 1]

In Table 1, the abbreviations for the first and second monomers are as follows.

MPC: 2- (methacryloyloxy) ethyl-2 '-(trimethylammonio) ethyl phosphate APC: 2- (allyloxy) ethyl-2'-(trimethylammonio) ethyl phosphate EPF: ethyl- (2'- Trimethylammonioethylphosphoryl) fumarate VPC: 2- (p-vinylbenzyl) ethyl-2'-
(Trimethylammonio) ethyl phosphate M3MS: 3- (methacryloyloxypropyl) trimethoxysilane V3MS: trimethoxyvinylsilane M2MS: (3-methacryloyloxypropyl) dimethoxymethylsilane M1MS: (3-methacryloyloxypropyl) methoxydimethylsilane Example 1-7a to 1-7c After adding 60 g of ethanol to 20 g of a monomer mixture prepared from MPC (first monomer) and M3MS (second monomer) and having an MPC mole fraction of 0.6, a nitrogen gas was thoroughly replaced with nitrogen. , T-butyl peroxypivalate 0.
4 g was added and copolymerized at 60 ° C. for 10 hours. After completion of the reaction, the state of the reaction solution (whether or not gel was formed) was visually observed, and then the reaction solution was added dropwise to methyl ethyl ketone to precipitate a copolymer, followed by filtration and vacuum drying to obtain a white powder in a yield of 85%.
I got it. IR and GPC measurements were performed, and the result was M
It was confirmed to be a copolymer of PC and M3MS. The measured number average molecular weight was 58,000 and the weight average molecular weight was 110,000. Furthermore, the molar fraction of the MPC structural unit in the copolymer was 0.61 which was measured by measuring the amount of nitrogen by the Kjeldahl analysis method.

Further, polymerization was carried out in the same manner except that the charged mole fractions of MPC monomer were changed to 0.9 and 0.95. The results of the three cases obtained are shown in Example 1-7.
It shows in Table 2 as a, 1-7b, and 1-7c.

Comparative Examples 1-3a to 1-3b The molar ratio of the MPC monomer charged was 0.15 and 0.9.
Polymerization was performed in the same manner as in Example 1-7 except that the number was changed to 8. The results of the two obtained examples are shown in Table 2 as Comparative Examples 1-3a and 1-3b, respectively.

Examples 1-8a to 1-8b 20 g of a monomer mixture composed of VPC (first monomer) and M3MS (second monomer) and adjusted to a BPC mole fraction of 0.5 was added to t-butylperoxypivalate. 0.4 g
Was added, and 60 g of ethanol was further added to form a uniform solution, which was sufficiently replaced with nitrogen, and then copolymerized at 60 ° C. for 10 hours. After completion of the reaction, the reaction solution was added dropwise to methyl ethyl ketone to precipitate a copolymer, which was filtered and vacuum dried to obtain a white powder in a yield of 8
Obtained at 0%. IR and GPC measurements were performed, and it was confirmed that the obtained product was a copolymer of BPC and M3MS. The measured number average molecular weight was 53,000 and the weight average molecular weight was 98,000. Furthermore, the molar fraction of the MPC structural unit in the copolymer was 0.51, which was measured by measuring the amount of nitrogen by the Kjeldahl analysis method.

Further, the polymerization was carried out in the same manner except that the charged mole fraction of the VPC monomer was 0.95. The results of the two obtained examples are shown in Examples 1-8a and 1-8, respectively.
It is shown in Table 2 as b.

Comparative Examples 1-4a to 1-4b VPC monomer charge mole fractions of 0.25 and 0.9.
Polymerization was performed in the same manner as in Example 1-8 except that the number was changed to 8. The results of the two obtained examples are shown in Table 2 as Comparative Examples 1-4a and 1-4b, respectively.

[0086]

[Table 2]

Comparative Example 1-5 Polymerization was performed in the same manner as in Example 1-7c except that (3-methacryloyloxypropyl) trichlorosilane was used instead of M3MS. As a result, the yield is 75%
Thus, a copolymer of MPC having a number average molecular weight of 75,000 and (3-methacryloyloxypropyl) trichlorosilane was obtained.

Comparative Example 1-6 Polymerization was performed in the same manner as in Example 1-7a except that (3-methacryloyloxypropyl) trichlorosilane was used instead of M3MS. As a result, a gel was formed during the polymerization.

Examples 1-9 ( Ternary Copolymer) Instead of the monomer mixture composed of MPC and M3MS and having an MPC mole fraction of 0.6, the molar ratio of MPC, M3MS and n-butyl methacrylate was 4%. Polymerization was performed in the same manner as in Example 1-7, except that the monomer mixture prepared to be 3: 3 was used. As a result, a terpolymer of MPC, M3MS and n-butyl methacrylate having a number average molecular weight of 53,000 with a yield of 85% was obtained. The IR measurement results of the obtained copolymer were as follows.

IR: 970 cm ^-1 (N ⁺ (CH ₃ ) ₃ ),
1090 cm ^-1 (C-O-C), 1170 cm ^-1 (Si
-O), 1240 cm ^-1 (P-O), 1720 cm
^-1 (C = O) Example 1-10 ( Ternary Copolymer) Instead of the monomer mixture prepared from MPC and M3MS to have an MPC mole fraction of 0.6, the molar ratio of MPC, M3MS and styrene was changed. Polymerization was performed in the same manner as in Example 1-7 except that the monomer mixture prepared to be 4: 3: 3 was used. As a result, a terpolymer of MPC, M3MS and styrene having a number average molecular weight of 55,000 was obtained with a yield of 83%. The IR measurement results of the obtained copolymer were as follows.

IR: 970 cm ^-1 (N ⁺ (CH ₃ ) ₃ ),
1090 cm ^-1 (C-O-C), 1170 cm ^-1 (Si
-O), 1240 cm ^-1 (P-O), 1720 cm
^-1 (C = O) Example 2 15 wt% copolymer solution 15 prepared by dissolving the copolymer obtained in Examples 1-1a to 1-8b in ethanol
0.5 parts by weight of water and 0.1 parts by weight of acetic acid were added to the parts by weight to prepare a coating solution. In each coating solution, a cover glass previously washed with a 1N sodium hydroxide aqueous solution is immersed for 10 minutes to perform coating,
After lightly washing with ethanol, it was dried at 70 ° C. for 6 hours.
These coated cover glasses were subjected to the following protein adsorption test to determine the protein adsorption amount. The results are shown in Table 3.

Further, the phosphorus content on the surface of the cover glass immediately after coating and the phosphorus content on the surface of the cover glass after holding in flowing water having a strong flow for 100 hours were measured by an X-ray photoelectron spectrometer, and both were compared. By doing so, the durability of the coating layer was measured. That is, the degree of peeling of the coating layer was evaluated by measuring the intensity of the photoelectron peak (2p; 134 ev) proportional to the phosphorus content on the surface of the coated cover glass as well as the relative intensity. Table 3 shows the peak intensities Ia measured by the X-ray photoelectron spectrometer immediately after the measured coating, the peak intensities Ib measured after holding in flowing water having a strong flow for 100 hours, and the relative intensities Ib / Ia. The smaller the value of Ib / Ia, the larger the amount of peeling, indicating that the adhesion strength of the copolymer to the cover glass is poor.

Protein Adsorption Amount Measurement Test A fluorescent substance, fluorescein isothiocyanate (hereinafter abbreviated as FITC) was modified into a goat antibody to prepare a FITC-labeled antibody. 0.2 mg of this FITC-labeled antibody
/ Ml Dissolve a test plate such as a cover glass coated in a dissolved phosphate buffer (pH 7.4) at 4 ° C
The protein was adsorbed by incubating for 24 hours. Alternatively, when measuring a coated cell, 0.2 mg / m 2 of the FITC-labeled antibody is added to the cell.
The solution was filled with the dissolved phosphate buffer and incubated at 4 ° C. for 24 hours to adsorb the protein. After that, wash the test plate, cell, etc. on which the protein is adsorbed lightly with water and
The adsorbed protein was eluted with 1% sodium dodecylsulfate solution. The amount of protein adsorbed was evaluated by measuring the fluorescence intensity of the protein eluate and comparing it with a calibration curve prepared in advance.

[0094]

[Table 3]

Comparative Example 2 The copolymers obtained in Comparative Examples 1-1a to 1-5 and MP
Example 2 except that a homopolymer of C (homo MPC) was used.
The same procedure was followed to measure the amount of adsorbed protein and the durability of each coating layer. In addition, the amount of protein adsorbed and the durability of the cover glass without coating were also measured. Table 4 shows the results.

[0096]

[Table 4]

Example 3-1 A glass optical cell having a capacity of 1 ml, which was washed with a 1N aqueous solution of sodium hydroxide in advance, was used as a coating solution using a 10% by weight aqueous solution of the copolymer obtained in Example 1-1b.
It was immersed in the coating solution heated to 0 ° C. for 5 minutes. After coating, lightly wash the cell with water, and
Let dry for hours. The amount of protein adsorbed on the coating layer and the Ib / Ia value of the coated cell were measured in the same manner as in Example 2 and found to be 3 ng / c.
m ^2, was 1.01.

Comparative Example 3-1 Example 3-Aside from using the copolymer obtained in Comparative Example 1-1b instead of the copolymer obtained in Example 1-1b.
The cell was coated in the same manner as in No. 1, and the protein adsorption amount and Ib / Ia value of the coating layer were measured and found to be 55 ng / cm ² and 0.21, respectively.

Example 3-2 A 10% by weight aqueous solution of the copolymer obtained in Example 1-1b was used as a coating solution, and a stainless steel plate (10 mm × 25 mm) was previously washed with 1N aqueous sodium hydroxide solution.
The coated stainless steel plate was prepared by applying the solution to the above and drying at room temperature for 24 hours. When the amount of adsorbed protein on this coated stainless plate was measured in the same manner as in Example 2, it was 6 ng /
cm ² .

For comparison, an uncoated stainless steel plate was washed with sodium hydroxide and then with ethanol, and the amount of adsorbed protein was measured in the same manner.
/ Cm ² .

Example 3-3 A 10% by weight aqueous solution of the copolymer obtained in Example 1-1b was used as a coating solution, and a glass plate (18 mm × 18 mm) previously washed with 1N aqueous sodium hydroxide solution was used.
Immerse in the coating solution for 10 minutes. After coating, lightly wash the glass plate with ethanol, and
Let dry for hours. The amount of protein adsorbed on the coating layer of the coated glass plate was measured in the same manner as in Example 2, and it was 8 ng / cm ² .

For comparison, after washing the uncoated glass plate with sodium hydroxide, the amount of adsorbed protein was similarly measured and found to be 61 ng / cm ² .

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Kenshiro Suto, 3-7-1 Hanafata, Tsukuba City, Ibaraki Prefecture Sanrif Seki III No. 202 (72) Inventor Kazuo Matsuyama 16-7 Kitahama, Katahara Town, Gamagori City, Aichi Prefecture (72) ) Inventor Shujiro Sakaki 2-20-3 Kasuga, Tsukuba-shi, Ibaraki (72) Inventor Koji Kamenono 2-17-14 Kasuga, Tsukuba-shi, Ibaraki (72) Nobuo Nakabayashi 5, Koganehara, Matsudo-shi, Chiba No. 6-20 (72) Inventor Kazuhiko Ishihara 6-5-9-201 Kamimizuhoncho, Kodaira-shi, Tokyo

Claims (3)

[Claims] 1. A compound of the general formula (1) (In the formula, X represents a divalent residue, Y represents an alkyleneoxy group having 1 to 6 carbon atoms, and Z represents a hydrogen atom or R ² —O—.
CO-, m is an integer of 0 to 10, R ¹ is a hydrogen atom or a methyl group, R ² is an alkyl group or a hydroxyalkyl group having 1 to 10 carbon atoms, and R ³ , R ⁴ and R ⁵ 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 having 1 to 6 carbon atoms. ) And at least one type of phosphorylcholine group-containing monomer represented by the general formula (2) (Wherein, W is _{- (CH 2) k -,} - CO-O- (CH 2) k -, - C
_{O-NH- (CH) k -} , - C 6 H 4 - (CH 2) k -, or -C ₆ H
_{4 -CH 2 -NH- (CH 2)} k - represents any. k is 0
4, R ⁹ is a hydrogen atom or a methyl group, R ⁶ is an alkoxy group having 1 to 10 carbon atoms or an aryloxy group having 6 to 14 carbon atoms, and R ⁷ and R ⁸ are the same or different groups. An alkoxy group having 1 to 10 carbon atoms which may contain a halogen atom, and a carbon number 6 which may contain a halogen atom.
To 14 aryloxy groups, C1-10 alkyl groups, oxygen atom-containing C1-10 alkyl groups, or nitrogen atom-containing C1-10 alkyl groups. )
Which is obtained by random or alternating copolymerization with at least one silyl group-containing monomer represented by the following general formula (3): (In the formula, W, X, Y, Z, k, m, R ¹ , R ² , R ³ ,
R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ and R ⁹ are represented by the formulas (1) and (2)
It is the same as that described in. ), The number average molecular weight of each monomer structural unit (a, b) uniformly distributed is 5,000 to 300,000.
And the composition ratio of a and b is 95: 5 to 50:50.
Is a copolymer having a phospholipid-like structure. 2. The copolymer according to claim 1, wherein the run number of the copolymer is 8 or more. 3. A medical material in which the copolymer having the phospholipid-like structure according to claim 1 or 2 is coated on the surface.