JP2010057691A - Medical instrument - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a medical instrument which is indwelt in a living body and suppresses blood clot formation, restenosis, and the like by platelet, blood coagulation factors, and adsorption of proteins which occur by indwelling in the body without using a bioactive medical agent. <P>SOLUTION: The medical instrument has at least one layer containing a hydrophilic polymer on the surface of base material. The hydrophilic polymer contains 30% mol or more of structural unit including a hydrophilic group. Moreover, the contact angle of water droplet in air obtained by measuring the surface of the medical instrument at 20°C is 15° or narrower. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a medical instrument used for the purpose of indwelling in a body, and more particularly to a stent that is placed in a stenosis or occlusion in a lumen in a living body and maintains the patency of the lumen. .

As a treatment method for ischemic heart disease caused by stenosis of coronary arteries such as angina pectoris and myocardial infarction, coronary intervention has rapidly spread in recent years in place of highly invasive coronary artery bypass surgery.
A typical coronary intervention is a percutaneous transluminal coronary angioplasty (PTCA) in which a catheter with an inflatable balloon at the tip is inflated at the stenosis of the coronary artery to expand the lumen of the blood vessel. ) However, with PTCA alone, restenosis occurred at a high frequency of about 40% after the operation, and retreatment was necessary, so the mental and physical distress given to the patient was great.
In order to solve this problem, in recent years, a so-called stent placement technique in which a substantially cylindrical support called a stent made of a metal or plastic coil or mesh is expanded and placed in a stenotic site has been widely performed. As a result, the incidence of vascular restenosis was halved. However, although stent placement can prevent elastic recoil and vascular remodeling, it is difficult to completely prevent vascular restenosis in the chronic phase. In-stent restenosis (ISR: In- Stent Restenosis) occurs with a probability of about 20% after the operation, and it is known that the incidence of ISR is high particularly in diabetic patients. The above-mentioned ISR is considered to occur due to the vascular wall becoming inflamed by placement of a stent, and as a result, smooth muscle cells migrate to the intima side and the intima is hyperplastic.

  Therefore, in recent years, attempts have been made to reduce the restenosis rate by causing a stent to carry a drug and releasing the drug locally over a predetermined period at the indwelling site. The usefulness of drugs such as tranilast, paclitaxel, probucol, cilostazol, and rapamycin has been suggested, and stents that coat them with various polymers have been reported, but have not yet been fully satisfactory.

  In addition, a stent using a compound that inactivates α1-protease inhibitor or α2-macroglobulin as an anti-vascular restenosis drug has also been proposed (Patent Document 1 and Patent Document 2). In order to reduce the restenosis rate by releasing the drug locally over a predetermined period of time at the indwelling site, the present inventors have prepared the outer peripheral surface and / or the inner peripheral surface of the pretreated stent substrate, A coated stent that is coated with a polyamide elastomer containing a blood vessel restenosis prevention agent and further has a topcoat layer has been proposed (Patent Document 3). However, these drugs are highly reactive, and it has been difficult to release the drugs locally at the indwelling site over a predetermined period.

Furthermore, as a method for producing a stent coated with a therapeutic substance, a method of coating a stent together with a bioabsorbable polymer and a biostable polymer is known (Patent Document 4 and Patent Document 5). However, in the method of Patent Document 4 using a solution containing a solvent, a polymer dissolved in the solvent, and a drug dispersed in the solvent, the water-insoluble drug is dispersed in the solvent in which the polymer is dissolved. It is difficult to select a solvent to apply to the body. Further, in the method of Patent Document 5, the operation of applying or immersing the stent in a solution in which a drug is dissolved or suspended in a biocompatible polymer and / or biodegradable polymer solution and drying is repeated a plurality of times. become.
International Publication No. 03/043656 Pamphlet JP 2003-221347 A JP 2005-170801 A Japanese Patent No. 3673973 Japanese Patent No. 3476604

  The present invention is a medical device that can suppress thrombus formation, restenosis, etc. caused by adsorption of platelets, blood coagulation factors, and proteins, which may occur when placed in the body, without using a drug. The object is to provide a medical instrument.

Cross-linked silicone superhydrophilic materials are considered biocompatible, especially foreign bodies in the body, and there is a concern that platelets, blood coagulation factors, and proteins will be adsorbed, and are expected to be effective in suppressing thrombus formation and restenosis thrombus could not.
However, as a result of intensive studies, the present inventors have covered the base material with a hydrophilic polymer so that the contact angle of airborne drops on the surface of a medical device such as a stent is 15 degrees or less (measurement temperature 20 ° C.). Discovered that thrombus and restenosis are less likely to occur even after the medical device is placed in the body, suppressing adsorption of proteins such as platelets, blood coagulation factors, and fibrin (proteins involved in blood coagulation). . In addition, it has been found that by containing silicon in the hydrophilic polymer, a strong film excellent in crosslinking density can be formed on the surface of the medical device.
The present invention is based on the above findings and is as follows.

(1) A medical device having at least one layer containing a hydrophilic polymer on a base material, wherein the hydrophilic polymer contains 30 mol% or more of a structural unit containing a hydrophilic group and silicon. Furthermore, the medical device is characterized in that the contact angle of water droplets measured on the surface of the medical device at 20 ° C. is 15 degrees or less.
(2) The medical device, wherein the hydrophilic polymer is crosslinked by hydrolysis and condensation of a hydrolyzable silyl group.
(3) The hydrophilic polymer (I), the general formulas (II-1) and (II) in which the layer containing the hydrophilic polymer includes a structure represented by the following general formulas (I-1) and (I-2) -2) A composition containing either the hydrophilic polymer (II) having a structure represented by formula (III) or the hydrophilic polymer (III) having a structure represented by formulas (III-1) and (III-2) The medical device according to (1), wherein the medical device is a layer formed of an object.

In the general formulas (I-1) and (I-2), R ^{101 to} R ¹⁰⁸ each independently represents a hydrogen atom or a hydrocarbon group. p represents an integer of 1 to 3, and L ¹⁰¹ and L ¹⁰² each represents a single bond or a polyvalent organic linking group. x and y represent a composition ratio, x represents a number satisfying 0 <x <100 and y represents 0 <y <100. A ¹⁰¹ is —OH, —OR _a , —COR _a , —CO ₂ R _e , —CON (R _a ) (R _b ), —N (R _a ) (R _b ), —NHCOR _d , —NHCO ₂ R _{a, -OCON (R a) (} R b), - NHCON (R a) (R b), - SO 3 R e, -OSO 3 R e, -SO 2 R d, -NHSO 2 R d, -SO ₂ N (R _a ) (R _b ), —N (R _a ) (R _b ) (R _c ), —N (R _a ) (R _b ) (R _c ) (R _g ), —PO ₃ (R _e ) (R _f ), —OPO ₃ (R _e ) (R _f ), or —PO ₃ (R _d ) (R _e ). Here, R _a , R _b and R _c each independently represent a hydrogen atom or a linear, branched or cyclic alkyl group, R _d represents a linear, branched or cyclic alkyl group, R _e and R _f independently represents a hydrogen atom or a linear, branched or cyclic alkyl group, an alkali metal, an alkaline earth metal, or onium, and R _g represents a halogen ion, an inorganic anion, or an organic anion.

In the general formula (II-1) and (II-2), each represent R ²⁰¹ to R ²⁰⁵ independently represent a hydrogen atom or a hydrocarbon group. q represents an integer of 1 to 3, and L ²⁰¹ and L ²⁰² each represents a single bond or a polyvalent organic linking group. A ²⁰¹ is _{-OH, -OR a, -COR a,} -CO 2 R e, -CON (R a) (R b), - N (R a) (R b), - NHCOR d, -NHCO 2 R _{a, -OCON (R a) (} R b), - NHCON (R a) (R b), - SO 3 R e, -OSO 3 R e, -SO 2 R d, -NHSO 2 R d, -SO ₂ N (R _a ) (R _b ), —N (R _a ) (R _b ) (R _c ), —N (R _a ) (R _b ) (R _c ) (R _g ), —PO ₃ (R _e ) (R _f ), —OPO ₃ (R _e ) (R _f ), or —PO ₃ (R _d ) (R _e ). Here, R _a , R _b and R _c each independently represent a hydrogen atom or a linear, branched or cyclic alkyl group, R _d represents a linear, branched or cyclic alkyl group, R _e and R _f independently represents a hydrogen atom or a linear, branched or cyclic alkyl group, an alkali metal, an alkaline earth metal, or onium, and R _g represents a halogen ion, an inorganic anion, or an organic anion.
Formula (III)

In general formulas (III-1) and (III-2), R ^{301 to} R ³¹¹ each independently represents a hydrogen atom or a hydrocarbon group. r represents an integer of 1 to 3, and L ^{301 to} L ³⁰³ each represents a single bond or a polyvalent organic linking group. x and y represent a composition ratio, x represents a number satisfying 0 <x <100 and y represents 0 <y <100. A ³⁰¹ represents —OH, —OR _a , —COR _a , —CO ₂ R _e , —CON (R _a ) (R _b ), —N (R _a ) (R _b ), —NHCOR _d , —NHCO ₂ R _{a, -OCON (R a) (} R b), - NHCON (R a) (R b), - SO 3 R e, -OSO 3 R e, -SO 2 R d, -NHSO 2 R d, -SO ₂ N (R _a ) (R _b ), —N (R _a ) (R _b ) (R _c ), —N (R _a ) (R _b ) (R _c ) (R _g ), —PO ₃ (R _e ) (R _f ), —OPO ₃ (R _e ) (R _f ), or —PO ₃ (R _d ) (R _e ). Here, R _a , R _b and R _c each independently represent a hydrogen atom or a linear, branched or cyclic alkyl group, R _d represents a linear, branched or cyclic alkyl group, R _e and R _f independently represents a hydrogen atom or a linear, branched or cyclic alkyl group, an alkali metal, an alkaline earth metal, or onium, and R _g represents a halogen ion, an inorganic anion, or an organic anion.
(4) The layer containing the hydrophilic polymer is a layer formed by a composition containing the hydrophilic polymer (IV) or (V) having a structure represented by the following general formula (IV) or (V). It is characterized by that.

In general formulas (IV) and (V), R ^{401 to} R ⁴⁰⁴ and R ^{501 to} R ⁵⁰² each independently represent a hydrogen atom or a hydrocarbon group, and R ⁵⁰³ represents a hydrogen atom or a monovalent nonmetallic atomic group. . x, y and z each independently represents an integer of 0 to 2, and L ⁴⁰¹ , L ⁴⁰² and L ⁵⁰¹ each independently represents an atom selected from a carbon atom, a hydrogen atom, an oxygen atom, a nitrogen atom and a sulfur atom. It represents a divalent linking group having three or more types. m and n represent an integer of 3 to 25,000.
(5) The medical device according to any one of (1) to (3), which contains a physiologically active substance.
(6) The medical device according to any one of (1) to (4), wherein the base material is a stent body, and the medical device is a stent.

  The medical device of the present invention has a structure in which the surface of the medical device is covered with a hydrophilic polymer that forms a strong film so that the contact angle of water droplets is 15 degrees or less (measurement temperature: 20 ° C.). Therefore, for example, in a stent, it is possible to suppress thrombus formation and restenosis caused by platelets and blood coagulation factors and proteins without using a bioactive agent even after being placed in the body. .

Hereinafter, the present invention will be described in more detail.
The medical device according to the present invention is a medical device having at least one layer containing a hydrophilic polymer on a substrate, wherein the hydrophilic polymer contains 30 mol% or more of structural units containing a hydrophilic group and silicon. Furthermore, the contact angle of the water droplets measured at 20 ° C. on the surface of the medical instrument is 15 degrees or less.

[Air drop contact angle]
The contact angle of water droplets in the air means “the angle between the liquid surface and the solid surface (the angle inside the liquid) where the free surface of the stationary liquid (water droplet) in the air is in contact with the solid wall (base material)” And quantifies the degree of wetting. The aerial water droplet contact angle of the present invention is preferably measured using a droplet method such as the θ / 2 method, the tangent method, or the curve fitting method.
[Medical equipment]
The medical device is not particularly limited as long as it is a medical device to be placed in the body, but an artificial heart, artificial blood vessel, artificial tooth, artificial joint, artificial lens, suture thread, blood transfusion filter, catheter, and stent are preferable. A stent is particularly preferable.

[Hydrophilic polymer]
The hydrophilic polymer contained in a composition (also referred to as a hydrophilic composition) for forming a layer containing a hydrophilic polymer (also referred to as a hydrophilic layer) on a substrate contains 30 mol of a structural unit containing a hydrophilic group. % Or more, and preferably has at least one hydrolyzable silyl group.

  The main chain structure of the hydrophilic polymer is not particularly limited. Preferred main chain structures include acrylic resin, methacrylic resin, polyvinyl acetal resin, polyurethane resin, polyurea resin, polyimide resin, polyamide resin, epoxy resin, polystyrene resin, novolac type phenol resin, polyester resin, synthetic rubber, natural rubber, etc. An acrylic resin and a methacrylic resin are particularly preferable. The hydrophilic polymer may be a copolymer, and the copolymer may be any of a random copolymer, a block copolymer, and a graft copolymer.

The hydrolyzable silyl group is a group that reacts with water to produce silanol (Si—OH), and is preferably represented by the following general formula (a).
Formula (a): —Si (R ² ) _a (OR ¹ ) _3-a
In general formula (a), R ¹ is a hydrogen atom or an alkyl group, R ² is a monovalent hydrocarbon group selected from a hydrogen atom or an alkyl group, an aryl group and an aralkyl group, and a is an integer of 0 to 2. . When a plurality of R ¹ or R ² are present, they may be the same or different from each other.

When R ¹ represents an alkyl group, an alkyl group having 1 to 10 carbon atoms is preferable, when R ² represents an alkyl group, an alkyl group having 1 to 10 carbon atoms is preferable, and when R ² represents an aryl group, 6 alkyl atoms are represented. An aryl group having ˜25 is preferred, and an aralkyl group having 7 to 12 carbon atoms is preferred when it represents an aralkyl group.

The hydrolyzable silyl group is preferably a hydrolyzable silyl group bonded to a carbon atom.
One or more hydrolyzable silyl groups may be present at the end of the polymer main chain, or one or more may be present at the side chain. When two or more hydrolyzable silyl groups are included, the two or more hydrolyzable silyl groups may be the same as or different from each other.

The hydrolyzable silyl group can form a chemical bond by reacting with a hydrolyzed polycondensate of an alkoxide (also referred to as a metal alkoxide) containing an element selected from Si, Ti, Zr, and Al described later. Moreover, hydrolyzable silyl groups may form a chemical bond. The hydrophilic polymer is preferably water-soluble, and preferably becomes water-insoluble by reacting with a hydrolysis or polycondensate of a metal alkoxide. The chemical bond in this case includes a covalent bond, an ionic bond, a coordination bond, and a hydrogen bond in the same manner as usual. The chemical bond is preferably a covalent bond.
The hydrophilic polymer is preferably crosslinked by hydrolysis and condensation of a hydrolyzable silyl group.

  The hydrophilic group is preferably a carboxyl group, an alkali metal salt of a carboxyl group, a sulfonic acid group, an alkali metal salt of a sulfonic acid group, a hydroxyl group, an amide group, a carbamoyl group, a sulfonamide group, a sulfamoyl group, or a functional group. Can be mentioned. These groups may be present at any position in the polymer. A polymer structure in which a plurality of polymers are bonded directly from a polymer main chain or via a linking group, or bonded to a polymer side chain or a graft side chain, is preferred.

  Further, the hydrophilic polymer used in the present invention is preferably a polymer having a metal alkoxide and a group that forms a bond by the action of a catalyst or the like. As the group that forms a bond with the metal alkoxide compound by the action of the catalyst, in addition to the hydrolyzable silyl group represented by the general formula (a), a carboxyl group, an alkali metal salt of a carboxy group, a carboxylic anhydride group, Amino group, hydroxy group, epoxy group, methylol group, mercapto group, isocyanate group, block isocyanate group, alkoxysilyl group, alkoxytitanate group, alkoxyaluminate group, alkoxyzirconate group, ethylenically unsaturated group, ester group And reactive groups such as a tetrazole group.

  A linking group is preferably interposed between the repeating unit containing a hydrophilic group and the hydrolyzable silyl group, or between the repeating unit containing a hydrophilic group and the main chain.

  The layer containing a hydrophilic polymer is a hydrophilic polymer (I) having a structure represented by the following general formulas (I-1) and (I-2), general formulas (II-1) and (II-2). It is preferable to contain either hydrophilic polymer (II) containing the structure represented, or hydrophilic polymer (III) containing the structure represented by general formula (III-1) and (III-2).

[Hydrophilic polymer (I) having a structure represented by general formulas (I-1) and (I-2)]

In the general formulas (I-1) and (I-2), R ^{101 to} R ¹⁰⁸ each independently represents a hydrogen atom or a hydrocarbon group. p represents an integer of 1 to 3, and L ¹⁰¹ and L ¹⁰² each represents a single bond or a polyvalent organic linking group. x and y represent a composition ratio, x represents a number satisfying 0 <x <100 and y represents 0 <y <100. A ¹⁰¹ is —OH, —OR _a , —COR _a , —CO ₂ R _e , —CON (R _a ) (R _b ), —N (R _a ) (R _b ), —NHCOR _d , —NHCO ₂ R _{a, -OCON (R a) (} R b), - NHCON (R a) (R b), - SO 3 R e, -OSO 3 R e, -SO 2 R d, -NHSO 2 R d, -SO ₂ N (R _a ) (R _b ), —N (R _a ) (R _b ) (R _c ), —N (R _a ) (R _b ) (R _c ) (R _g ), —PO ₃ (R _e ) (R _f ), —OPO ₃ (R _e ) (R _f ), or —PO ₃ (R _d ) (R _e ). Here, R _a , R _b and R _c each independently represent a hydrogen atom or a linear, branched or cyclic alkyl group, R _d represents a linear, branched or cyclic alkyl group, R _e and R _f independently represents a hydrogen atom or a linear, branched or cyclic alkyl group, an alkali metal, an alkaline earth metal, or onium, and R _g represents a halogen ion, an inorganic anion, or an organic anion.

In the formula (I-1) and ^{(I-2), R 101} ~R 108 each independently represent a hydrogen atom or a hydrocarbon group. Examples of the hydrocarbon group include an alkyl group and an aryl group, and a linear, branched or cyclic alkyl group having 1 to 8 carbon atoms is preferable. Specifically, methyl group, ethyl group, propyl group, butyl group, pentyl group, hexyl group, heptyl group, octyl group, isopropyl group, isobutyl group, s-butyl group, t-butyl group, isopentyl group, neopentyl group 1-methylbutyl group, isohexyl group, 2-ethylhexyl group, 2-methylhexyl group, cyclopentyl group and the like. R ^{101 to} R ¹⁰⁸ are preferably a hydrogen atom, a methyl group or an ethyl group from the viewpoints of effects and availability.

  These hydrocarbon groups may further have a substituent. When the alkyl group has a substituent, the substituted alkyl group is constituted by a bond between a substituent and an alkylene group, and a monovalent nonmetallic atomic group excluding hydrogen is used as the substituent. Preferred examples include halogen atoms (-F, -Br, -Cl, -I), hydroxyl groups, alkoxy groups, aryloxy groups, mercapto groups, alkylthio groups, arylthio groups, alkyldithio groups, aryldithio groups, amino groups, N-alkylamino group, N, N-diarylamino group, N-alkyl-N-arylamino group, acyloxy group, carbamoyloxy group, ア ル キ ル -alkylcarbamoyloxy group, N-arylcarbamoyloxy group, N, N-dialkyl Carbamoyloxy group, N, N-diarylcarbamoyloxy group, N-alkyl-N-reelcarbamoyloxy group, alkylsulfoxy group, arylsulfoxy group, acylthio group, acylamino group, N-alkylacylamino group, N-aryl Acylamino group, ureido group, N'- Rukyureido group, N ′, N′-dialkylureido group, N′-arylureido group, N ′, N′-diarylureido group, N′-alkyl-N′-arylureido group, N-alkylureido group, N— Arylureido group, N′-alkyl-N-alkylureido group, N′-alkyl-N-arylureido group, N ′, N′-dialkyl-N-alkylureate group, N ′, N′-dialkyl-N -Arylureido group, N'-aryl-Ν-alkylureido group, N'-aryl-N-arylureido group, N ', N'-diaryl-N-alkylureido group, N', N'-diaryl-N -Arylureido group, N'-alkyl-N'-aryl-N-alkylureido group, N'-alkyl-N'-aryl-N-arylureido group, alkoxycarbonylamino group, Ryloxycarbonylamino group, N-alkyl-N-alkoxycarbonylamino group, N-alkyl-N-aryloxycarbonylamino group, N-aryl-N-alkoxycarbonylamino group, N-aryl-N-aryloxycarbonylamino Group, formyl group, acyl group, carboxyl group, alkoxycarbonyl group,

Aryloxycarbonyl group, carbamoyl group, N-alkylcarbamoyl group, N, N-dialkylcarbamoyl group, N-arylcarbamoyl group, N, N-diarylcarbamoyl group, N-alkyl-N-arylcarbamoyl group, alkylsulfinyl group, Arylsulfinyl group, alkylsulfonyl group, arylsulfonyl group, sulfo group (—SO ₃ H) and its conjugate base group (hereinafter referred to as sulfonate group), alkoxysulfonyl group, aryloxysulfonyl group, sulfinamoyl group, N-alkyls Rufinamoyl group, N, N-dialkylsulfinamoyl group, N-arylsulfinamoyl group, N, N-diarylsulfinamoyl group, N-alkyl-N-arylsulfinamoyl group, sulfamoyl group, N-alkyl Sulfa Yl group, N, N- dialkylsulfamoyl group, N- aryl sulfamoyl group, N, N- diaryl sulfamoyl group, N- alkyl -N- arylsulfamoyl group phosphono group (-PO ₃ H ₂ ) And conjugated base groups thereof (hereinafter referred to as phosphonate groups), dialkyl phosphono groups (—PO ₃ (alkyl) ₂ ), diaryl phosphono groups (—PO ₃ (aryl) ₂ ), alkylaryl phosphono groups (— PO ₃ (alkyl) (aryl)), monoalkyl phosphono group (-PO ₃ H (alkyl)) and its conjugated base group (hereinafter referred to as alkyl phosphonophenyl group), monoaryl phosphono group (-PO ₃ H (aryl)) and its conjugated base group (hereinafter referred to as aryl phosphonophenyl group), Oyo phosphonooxy group (-OPO ₃ H ₂₎ A conjugated base group thereof (hereinafter referred to as phosphonophenyl group), dialkyl phosphonooxy group (-OPO ₃ (alkyl) _2), diaryl phosphonooxy group (-OPO ₃ (aryl) _2), alkylaryl phosphonooxy aryloxy Group (—OPO (alkyl) (aryl)), monoalkylphosphonooxy group (—OPO ₃ H (alkyl)) and its conjugate base group (hereinafter referred to as alkylphosphonatooxy group), monoarylphosphonooxy group (—OPO ₃ H (aryl)) and its conjugate base group (hereinafter referred to as arylphosphonateoxy group), morpholino group, cyano group, nitro group, aryl group, alkenyl group, and alkynyl group.

Specific examples of the alkyl group in these substituents are the same as those of R ^{1 to} R ⁸ , and specific examples of the aryl group include a phenyl group, a biphenyl group, a naphthyl group, a tolyl group, Xylyl, mesityl, cumenyl, chlorophenyl, bromophenyl, chloromethylphenyl, hydroxyphenyl, methoxyphenyl, ethoxyphenyl, phenoxyphenyl, acetoxyphenyl, benzoyloxyphenyl, methylthiophenyl , Phenylthiophenyl group, methylaminophenyl group, dimethylaminophenyl group, acetylaminophenyl group, carboxyphenyl group, methoxycarbonylphenyl group, ethoxyphenylcarbonyl group, phenoxycarbonylphenyl group, N-phenylcarbamoy Phenyl group include a phenyl group, cyanophenyl group, sulfophenyl group, sulfonatophenyl group, phosphonophenyl phenyl group, a phosphonophenyl phenyl group. Examples of alkenyl groups include vinyl, 1-propenyl, 1-butenyl, cinnamyl, 2-chloro-1-ethenyl, etc. Examples of alkynyl include ethynyl, 1-butenyl, A propynyl group, a 1-butynyl group, a trimethylsilylethynyl group, etc. are mentioned. Examples of G ¹ in the acyl group (G ¹ CO—) include hydrogen and the above alkyl groups and aryl groups.

  Among these substituents, more preferred are halogen atoms (—F, —Br, —Cl, —I), alkoxy groups, aryloxy groups, alkylthio groups, arylthio groups, N-alkylamino groups, N, N-dialkyls. Amino group, acyloxy group, N-alkylcarbamoyloxy group, N-arylcarbamoyloxy group, acylamino group, formyl group, acyl group, carboxyl group, alkoxycarbonyl group, aryloxycarbonyl group, carbamoyl group, N-alkylcarbamoyl group N, N-dialkylcarbamoyl group, N-arylcarbamoyl group, N-alkyl-N-arylcarbamoyl group, sulfo group, sulfonate group, sulfamoyl group, N-alkylsulfamoyl group, N, N-dialkylsulfamoyl group Group, N-arylsulfamoy Group, N-alkyl-N-arylsulfamoyl group, phosphono group, phosphonate group, dialkyl phosphono group, diaryl phosphono group, monoalkyl phosphono group, alkyl phosphonate group, monoaryl phosphono group, aryl phosphonate group Group, phosphonooxy group, phosphonatooxy group, aryl group, and alkenyl group.

  On the other hand, the alkylene group in the substituted alkyl group is preferably a divalent organic residue obtained by removing any one of the hydrogen atoms on the alkyl group having 1 to 20 carbon atoms. Preferably, it is a straight chain having 1 to 12 carbon atoms, more preferably a straight chain having 1 to 8 carbon atoms, more preferably a branched structure having 3 to 12 carbon atoms, still more preferably 3 to 8 carbon atoms, and More preferable examples include cyclic alkylene groups having 5 to 10 carbon atoms, and further preferably 5 to 8 carbon atoms. Preferable specific examples of the substituted alkyl group obtained by combining the substituent and the alkylene group include a chloromethyl group, a bromomethyl group, a 2-chloroethyl group, a trifluoromethyl group, a hydroxymethyl group, a methoxymethyl group, and a methoxyethoxy group. Ethyl group, allyloxymethyl group, phenoxymethyl group, methylthiomethyl group, tolylthiomethyl group, ethylaminoethyl group, diethylaminopropyl group, morpholinopropyl group, acetyloxymethyl group, benzoyloxymethyl group, N-cyclohexylcarbamoyloxyethyl Group, N-phenylcarbamoyloxyethyl group, acetylaminoethyl group, N-methylbenzoylaminopropyl group, 2-oxyethyl group, 2-oxypropyl group, carboxypropyl group, methoxycarbonyl group Group, allyloxycarbonyl butyl group,

  Chlorophenoxycarbonylmethyl group, carbamoylmethyl group, N-methylcarbamoylethyl group, N, N-dipropylcarbamoylmethyl group, N- (methoxyphenyl) carbamoylethyl group, N-methyl-N- (sulfophenyl) carbamoyl Methyl group, sulfobutyl group, sulfonatobutyl group, sulfamoylbutyl group, N-ethylsulfamoylmethyl group, N, N-dipropylsulfamoylpropyl group, N-tolylsulfamoylpropyl group, N-methyl-N- (Phosphonophenyl) sulfamoyloctyl group, phosphonobutyl group, phosphonatohexyl group, diethylphosphonobutyl group, diphenylphosphonopropyl group, methylphosphonobutyl group, methylphosphonatobutyl group, tolylphosphonohexyl group, Torilho Phonatohexyl group, phosphonooxypropyl group, phosphonatoxybutyl group, benzyl group, phenethyl group, α-methylbenzyl group, 1-methyl-1-phenylethyl group, p-methylbenzyl group, cinnamyl group, allyl group 1-propenylmethyl group, 2-butenyl group, 2-methylallyl group, 2-methylpropenylmethyl group, 2-propynyl group, 2-butynyl group, 3-butynyl group and the like.

  Of these, a hydroxymethyl group is preferred from the viewpoint of hydrophilicity.

L ^{101 to} L ¹⁰³ represent a single bond or an organic linking group. Here, the single bond means that the polymer main chain and X are directly bonded without a linking chain.
When L ^{101 to} L ¹⁰³ represent an organic linking group, L ^{101 to} L ¹⁰³ represent a polyvalent linking group composed of a non-metallic atom, 0 to 60 carbon atoms, and 0 to 10 nitrogen atoms. It consists of atoms, 0 to 50 oxygen atoms, 0 to 100 hydrogen atoms, and 0 to 20 sulfur atoms. Specifically, it is preferably selected from -N <, an aliphatic group, an aromatic group, a heterocyclic group, and combinations thereof, -O-, -S-, -CO-, -NH-, or A combination containing -O- or -S- or -CO- or -NH- is preferably a divalent linking group.
More specific examples of the linking group include the following structural units or those formed by combining them.

In the general formula (I-1), L ¹⁰¹ represents a single bond, or, -CONH -, - NHCONH -, - OCONH -, - 1 one structure selected from the group consisting of - SO ₂ NH- and -SO ₃ A linking group having the above is preferable.
L ¹⁰² is _{-CH 2 CH 2 CH 2 S -} , - CH 2 S -, - CONHCH (CH 3) CH 2 -, - CONH -, - CO -, - from the group consisting of - CO ₂ - and -CH ₂ A linking group having one or more selected structures is preferred.

In the general formula (I-2), A ¹⁰¹ is —OH, —OR _a , —COR _a , —CO ₂ R _e , —CON (R _a ) (R _b ), —N (R _a ) (R _b ). , —NHCOR _d , —NHCO ₂ R _a , —OCON (R _a ) (R _b ), —NHCON (R _a ) (R _b ), —SO ₃ R _e , —OSO ₃ R _e , —SO ₂ R _d , —NHSO ₂ R _d , —SO ₂ N (R _a ) (R _b ), —N (R _a ) (R _b ) (R _c ), —N (R _a ) (R _b ) (R _c ) ( _{R g), - PO 3 (} R e) (R f), - OPO 3 (R e) (R f), or -PO ₃ represents an _{(R d) (R e)} . Here, R _a , R _b and R _c each independently represent a hydrogen atom or a linear, branched or cyclic alkyl group (preferably having 1 to 8 carbon atoms), and R _d is a linear, branched or cyclic group. alkyl group (preferably having from 1 to 8 carbon atoms) represents, R _e and R _f each independently represents a hydrogen atom or a straight, branched or cyclic alkyl group (preferably having from 1 to 8 carbon atoms), an alkali metal, an alkaline earth metal or an onium,, R _g represents a halogen ion, an inorganic anion or an organic anion. In addition, —CON (R _a ) (R _b ), —N (R _a ) (R _b ), —OCON (R _a ) (R _b ), —NHCON (R _a ) (R _b ), —SO ₂ N (R _a ) (R _b ), —N (R _a ) (R _b ) (R _c ), —N (R _a ) (R _b ) (R _c ) (R _g ), —PO ₃ (R _e ) R _{a to} R _g may be bonded to each other to form a ring for (R _f ), —OPO ₃ (R _e ) (R _f ), or —PO ₃ (R _d ) (R _e ), The formed ring may be a heterocycle containing a heteroatom such as an oxygen atom, a sulfur atom or a nitrogen atom. R _{a to} R _g may further have a substituent, and the substituents that can be introduced here are the same as those exemplified as the substituents that can be introduced when R ^{1 to} R ⁸ are alkyl groups. Can be listed.

Specific examples of the linear, branched or cyclic alkyl group in R _{a to} R _f include a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group, a hexyl group, a heptyl group, an octyl group, and an isopropyl group. , Isobutyl group, s-butyl group, t-butyl group, isopentyl group, neopentyl group, 1-methylbutyl group, isohexyl group, 2-ethylhexyl group, 2-methylhexyl group, cyclopentyl group and the like.
In addition, in R _{a to} R _g , preferable examples of the alkali metal include lithium, sodium, and potassium, the alkaline earth metal includes barium, and the onium includes ammonium, iodonium, sulfonium, and the like.
In addition, examples of halogen ions include fluorine ions, chlorine ions, bromine ions, inorganic anions include nitrate anions, sulfate anions, tetrafluoroborate anions, hexafluorophosphate anions, and organic anions include methanesulfone. Preferable examples include an acid anion, trifluoromethanesulfonic acid anion, nonafluorobutanesulfonic acid anion, p-toluenesulfonic acid anion, and the like.

The A ^101, _{specifically, -NHCOCH 3, -CONH 2, -CON} (CH 3) 2, -COOH, -SO 3 - NMe 4 +, -SO 3 - K +, - (CH 2 CH 2 O) _n H, morpholyl group and the like are preferable. More _{preferably, -NHCOCH 3, -CONH 2, -CON} (CH 3) 2, -SO 3 - K +, - (CH 2 CH 2 O) n H, is. In the above, n preferably represents an integer of 1 to 100.

  p represents an integer of 1 to 3, preferably 2 to 3, and more preferably 3.

  In the hydrophilic polymer including the structures represented by the general formulas (I-1) and (I-2), x and y are the structures represented by the general formula (I-1) in the (A) specific hydrophilic polymer. The composition ratio of the unit and the structural unit represented by the general formula (I-2) is represented. x is 0 <x <100, and y is 0 <y <100. x is preferably in the range of 1 <x <90, and more preferably in the range of 1 <x <50. y is preferably in the range of 10 <y <99, and more preferably in the range of 50 <y <99.

  The copolymerization ratio of the hydrophilic polymer (I) including the structures represented by the general formulas (I-1) and (I-2) is such that the amount of the general formula (I-2) having a hydrophilic group is within the above range. Can be set arbitrarily. Preferably, the molar ratio (y) of the structural unit of the general formula (I-2) and the molar ratio (x) of the structural unit of the general formula (I-1) having a hydrolyzable silyl group amount are y / x = The range of 30/70 to 99/1 is preferable, y / x = 40/60 to 98/2 is more preferable, and y / x = 50/50 to 97/3 is most preferable. If y / x is 30/70 or more, the hydrophilicity is not insufficient. On the other hand, if y / x = 99/1 or less, the hydrolyzable silyl group amount is sufficient and sufficient curing is obtained. The film strength is also sufficient.

  The mass average molecular weight of the polymer containing the structures represented by the general formulas (I-1) and (I-2) is preferably 1,000 to 1,000,000, more preferably 1,000 to 500,000, 1,000 to 200,000 is most preferred.

  Specific examples of the hydrophilic polymer including the structures represented by the general formulas (I-1) and (I-2) are shown below together with their mass average molecular weights (MW). It is not limited to. In addition, the polymer of the specific example shown below means that each structural unit described is a random copolymer or a block copolymer contained in the described molar ratio.

Each compound for synthesizing the hydrophilic polymer including the structures represented by the general formulas (I-1) and (I-2) is commercially available, and can be easily synthesized.
Any conventionally known method can be used as the radical polymerization method for synthesizing the hydrophilic polymer containing the structures represented by the general formulas (I-1) and (I-2).
Specifically, general radical polymerization methods include, for example, New Polymer Experiments 3 (1996, Kyoritsu Shuppan), Polymer Synthesis and Reaction 1 (Polymer Society of Japan, 1992, Kyoritsu Shuppan), New Experiment Chemistry Lecture 19 (1978, Maruzen), Polymer Chemistry (I) (Edited by The Chemical Society of Japan, 1996, Maruzen), Synthetic Polymer Chemistry (Materials Engineering Lecture, 1995, Tokyo Denki University Press) These can be applied.
[Hydrophilic polymer (II) including structures represented by general formulas (II-1) and (II-2)]

In the general formula (II-1) and (II-2), each represent R ²⁰¹ to R ²⁰⁵ independently represent a hydrogen atom or a hydrocarbon group. q represents an integer of 1 to 3, and L ²⁰¹ and L ²⁰² each represents a single bond or a polyvalent organic linking group. A ²⁰¹ represents —OH, —OR _a , —COR _a , —CO ₂ R _e , —CON (R _a ) (R _b ), —N (R _a ) (R _b ), —NHCOR _d , —NHCO ₂ R _{a, -OCON (R a) (} R b), - NHCON (R a) (R b), - SO 3 R e, -OSO 3 R e, -SO 2 R d, -NHSO 2 R d, -SO ₂ N (R _a ) (R _b ), —N (R _a ) (R _b ) (R _c ), —N (R _a ) (R _b ) (R _c ) (R _g ), —PO ₃ (R _e ) (R _f ), —OPO ₃ (R _e ) (R _f ), or —PO ₃ (R _d ) (R _e ). Here, R _a , R _b and R _c each independently represent a hydrogen atom or a linear, branched or cyclic alkyl group, R _d represents a linear, branched or cyclic alkyl group, R _e and R _f independently represents a hydrogen atom or a linear, branched or cyclic alkyl group, an alkali metal, an alkaline earth metal, or onium, and R _g represents a halogen ion, an inorganic anion, or an organic anion.

  The hydrophilic polymer (II) including the structures represented by the general formulas (II-1) and (II-2) has a structural unit represented by the following general formula (II-2) and has a polymer chain. It preferably has a partial structure represented by the following general formula (II-1) at the end of

In the general formulas (II-1) and (II-2), R ^{201 to} R ²⁰⁵ each independently represents a hydrogen atom or a hydrocarbon group, and hydrocarbons in the case where R ^{201 to} R ²⁰⁵ represent a hydrocarbon group. Examples of the group include an alkyl group and an aryl group, and a linear, branched or cyclic alkyl group having 1 to 8 carbon atoms is preferable. Specifically, there may be mentioned the same ones as mentioned in R ¹⁰¹ to R ¹⁰⁸ in the general formula (I-1) and (I-2).
L ²⁰¹ and L ²⁰² each independently represents a single bond or a polyvalent organic linking group. Here, the single bond means that the main chain of the polymer is directly bonded to the A ²⁰¹ and Si atoms without a connecting chain. When L ²⁰¹ and L ²⁰² represent a polyvalent organic linking group, specific examples and preferred examples thereof may be the same as those described for L ¹⁰¹ in the general formula (I-1).
A ²⁰¹ represents —OH, —OR _a , —COR _a , —CO ₂ R _e , —CON (R _a ) (R _b ), —N (R _a ) (R _b ), —NHCOR _d , —NHCO ₂ R _{a, -OCON (R a) (} R b), - NHCON (R a) (R b), - SO 3 R e, -OSO 3 R e, -SO 2 R d, -NHSO 2 R d, -SO ₂ N (R _a ) (R _b ), —N (R _a ) (R _b ) (R _c ), —N (R _a ) (R _b ) (R _c ) (R _g ), —PO ₃ (R _e ) (R _f ), —OPO ₃ (R _e ) (R _f ), or —PO ₃ (R _d ) (R _e ). Specific examples and preferred examples of A ²⁰¹ include the same examples as those described for A ¹⁰¹ in formula (I-2).
q represents an integer of 1 to 3. Preferably it is 2-3, More preferably, it is 3.

L ²⁰¹ and L ²⁰² are —CH ₂ CH ₂ CH ₂ S—, —CH ₂ S—, —CONHCH (CH ₃ ) CH ₂ —, —CONH—, —CO—, —CO ₂ — and —CH ₂ —. A linking group having at least one structure selected from the group consisting of

  The hydrophilic polymer containing the structure represented by the general formulas (II-1) and (II-2) is, for example, a chain transfer agent (described in the radical polymerization handbook (NTS, Mikiji Tsunoike, Go Endo)). And Iniferter (described in Macromolecules 1986, 19, p287- (Otsu)) can be synthesized by radical polymerization of a hydrophilic monomer (eg, potassium salt of acrylamide, acrylic acid, 3-sulfopropyl methacrylate). Examples of chain transfer agents include 3-mercaptopropionic acid, 2-aminoethanethiol hydrochloride, 3-mercaptopropanol, 2-hydroxyethyl disulfide, 3-mercaptopropyltrimethoxysilane. Alternatively, a hydrophilic monomer (eg, acrylamide) may be radically polymerized using a radical polymerization initiator having a reactive group without using a chain transfer agent.

  The hydrophilic polymer including the structures represented by the general formulas (II-1) and (II-2) is represented by the following general formula (i) and a radically polymerizable monomer represented by the following general formula (i). In the radical polymerization, it can be synthesized by radical polymerization using a silane coupling agent having chain transfer ability. Since the silane coupling agent (ii) has chain transfer ability, it is possible to synthesize a polymer in which a silane coupling group is introduced at the end of the polymer main chain in radical polymerization.

In the above formula (i) and ^{(ii), R 201 ~R 205} , L 201, L 202, A 201, q is the same as defined in the general formula (II-1). These compounds are commercially available and can also be easily synthesized. The radically polymerizable monomer represented by the general formula (i) has a hydrophilic group ^A201 , and this monomer becomes one structural unit in the hydrophilic polymer.

  In the hydrophilic polymer (II) including the structures represented by the general formulas (II-1) and (II-2), the number of moles of the structural unit of the general formula (II-1) having a hydrolyzable silyl group amount. On the other hand, the number of moles of the structural unit of the general formula (II-2) is preferably in the range of 1000 to 10 times, more preferably 500 to 20 times, and most preferably 200 to 30 times. If it is 30 times or more, the hydrophilicity is not insufficient. On the other hand, if it is 200 times or less, the amount of hydrolyzable silyl groups is sufficient, sufficient curing is obtained, and the film strength is also sufficient.

  The weight average molecular weight of the hydrophilic polymer (II) including the structures represented by the general formulas (II-1) and (II-2) is preferably 1,000 to 1,000,000, and 1,000 to 500,000. 000 is more preferable, and 1,000 to 200,000 is most preferable.

  Specific examples of the hydrophilic polymer (II) that can be suitably used in the present invention are shown below, but the present invention is not limited thereto.

[Hydrophilic polymer (III) including structures represented by general formulas (III-1) and (III-2)]
The hydrophilic polymer (III) includes structures represented by the following general formulas (III-1) and (III-2). The hydrophilic polymer (III) is preferably a hydrophilic graft polymer obtained by introducing a side chain having a hydrophilic group into a trunk polymer having a reactive group.

In general formulas (III-1) and (III-2), R ^{301 to} R ³¹¹ each independently represents a hydrogen atom or a hydrocarbon group. r represents an integer of 1 to 3, and L ^{301 to} L ³⁰³ each represents a single bond or a polyvalent organic linking group. x and y represent a composition ratio, x represents a number satisfying 0 <x <100 and y represents 0 <y <100. A ³⁰¹ represents —OH, —OR _a , —COR _a , —CO ₂ R _e , —CON (R _a ) (R _b ), —N (R _a ) (R _b ), —NHCOR _d , —NHCO ₂ R _{a, -OCON (R a) (} R b), - NHCON (R a) (R b), - SO 3 R e, -OSO 3 R e, -SO 2 R d, -NHSO 2 R d, -SO ₂ N (R _a ) (R _b ), —N (R _a ) (R _b ) (R _c ), —N (R _a ) (R _b ) (R _c ) (R _g ), —PO ₃ (R _e ) (R _f ), —OPO ₃ (R _e ) (R _f ), or —PO ₃ (R _d ) (R _e ). Here, R _a , R _b and R _c each independently represent a hydrogen atom or a linear, branched or cyclic alkyl group, R _d represents a linear, branched or cyclic alkyl group, R _e and R _f independently represents a hydrogen atom or a linear, branched or cyclic alkyl group, an alkali metal, an alkaline earth metal, or onium, and R _g represents a halogen ion, an inorganic anion, or an organic anion.

In the general formulas (III-1) and (III-2), R ^{301 to} R ³¹¹ each independently represents a hydrogen atom or a hydrocarbon group, and hydrocarbons in the case where R ^{301 to} R ³¹¹ represent a hydrocarbon group. Examples of the group include an alkyl group and an aryl group, and a linear, branched or cyclic alkyl group having 1 to 8 carbon atoms is preferable. Specifically, the same as those mentioned for R ^{101 to} R ¹⁰⁸ in the general formulas (I-1) and (I-2) can be given, and preferred ranges are also the same.
L ³⁰¹ , L ³⁰² and L ³⁰³ each independently represents a single bond or a polyvalent organic linking group. Here, the single bond means that the main chain of the polymer and A ³⁰¹ , the side chain, and the Si atom are directly bonded without a connecting chain. When L ³⁰¹ , L ³⁰² and L ³⁰³ represent a polyvalent organic linking group, specific examples and preferred examples are the same as those described for L ¹⁰¹ in the general formula (I-1). Can do.
A ³⁰¹ represents —OH, —OR _a , —COR _a , —CO ₂ R _e , —CON (R _a ) (R _b ), —N (R _a ) (R _b ), —NHCOR _d , —NHCO ₂ R _{a, -OCON (R a) (} R b), - NHCON (R a) (R b), - SO 3 R e, -OSO 3 R e, -SO 2 R d, -NHSO 2 R d, -SO ₂ N (R _a ) (R _b ), —N (R _a ) (R _b ) (R _c ), —N (R _a ) (R _b ) (R _c ) (R _g ), —PO ₃ (R _e ) (R _f ), —OPO ₃ (R _e ) (R _f ), or —PO ₃ (R _d ) (R _e ). Specific examples and preferred examples of A ²⁰¹ include the same examples as those described for A ¹⁰¹ in formula (I-2).
r represents an integer of 1 to 3. Preferably it is 2-3, More preferably, it is 3.

  This hydrophilic graft polymer can be prepared using a method generally known as a method for synthesizing a graft polymer. Specifically, a general method for synthesizing a graft polymer is described in “Graft Polymerization and its Applications” by Fumio Ide, published in 1977, “Polymer Publications”, and “New Polymer Experiments 2, Polymer Synthesis / The reaction is described in “Polymer Society” edited by Kyoritsu Shuppan Co., Ltd. 1995, and these can be applied.

  As a synthesis method of the graft polymer, basically, 1. 1. Polymerize the branch monomer from the trunk polymer. 2. Link the branch polymer to the trunk polymer. It can be divided into three methods of copolymerizing a branch polymer with a trunk polymer (macromer method). Any of these three methods can be used to produce the hydrophilic graft polymer used in the present invention, but “3. Macromer method” is particularly excellent from the viewpoint of production suitability and control of the membrane structure. ing.

  The synthesis of a graft polymer using a macromonomer is described in the above-mentioned "New Polymer Experiment 2, Polymer Synthesis / Reaction" edited by Polymer Society, Kyoritsu Publishing Co., Ltd. 1995. It is also described in detail in Yu Yamashita et al. “Chemical Monomer Chemistry and Industry”, IPC, 1989. The graft polymer used in the present invention is obtained by first copolymerizing a hydrophilic macromonomer (corresponding to a precursor of a hydrophilic polymer side chain) synthesized by the above method and a monomer having a reactive group. Can be synthesized.

  Particularly useful among the hydrophilic macromonomers are macromonomers derived from carboxyl group-containing monomers such as acrylic acid and methacrylic acid, 2-acrylamido-2-methylpropanesulfonic acid, vinylstyrene sulfonic acid, and salts thereof Sulfonic acid macromonomer derived from the monomer of amide, amide macromonomer such as acrylamide and methacrylamide, amide macromonomer derived from N-vinylcarboxylic amide monomer such as N-vinylacetamide and N-vinylformamide, Macromonomers derived from hydroxyl-containing monomers such as hydroxyethyl methacrylate, hydroxyethyl acrylate, glycerol monomethacrylate, methoxyethyl acrylate, methoxypolyethylene glycol acrylic Over bets, a macromonomer derived from alkoxy group or ethylene oxide group-containing monomers such as polyethylene glycol acrylate. A monomer having a polyethylene glycol chain or a polypropylene glycol chain can also be usefully used as the macromonomer of the present invention. Among these macromonomers, the useful polymer has a mass average molecular weight (hereinafter simply referred to as molecular weight) in the range of 400 to 100,000, preferably 1000 to 50,000, and particularly preferably 1500 to 20,000. . If the molecular weight is 400 or more, effective hydrophilicity is obtained, and if it is 100,000 or less, the polymerizability with the copolymerization monomer forming the main chain tends to be high, both of which are preferable.

  In the hydrophilic polymer (III) including the structures represented by the general formulas (III-1) and (III-2), x is preferably in the range of 1 <x <90, and in the range of 1 <x <50. More preferably. y is preferably in the range of 10 <y <99, and more preferably in the range of 50 <y <99.

  The copolymerization ratio of the hydrophilic polymer (III) can be arbitrarily set so that the amount of the general formula (III-2) having a hydrophilic group is within the above range. Preferably, the molar ratio (y) of the structural unit of the general formula (III-2) and the molar ratio (x) of the structural unit of the general formula (III-1) having a hydrolyzable silyl group amount are y / x = The range of 30/70 to 99/1 is preferable, y / x = 40/60 to 98/2 is more preferable, and y / x = 50/50 to 97/3 is most preferable. If y / x is 30/70 or more, the hydrophilicity is not insufficient. On the other hand, if y / x = 99/1 or less, the hydrolyzable silyl group amount is sufficient and sufficient curing is obtained. The film strength is also sufficient.

  The hydrophilic polymer (III) may be a copolymer with other monomers described later, in which case the structural units represented by the general formulas (III-1) and (III-2) are represented by the hydrophilic polymer. It is preferable to contain 20 mol%-99 mol% in (III), and it is more preferable to contain 50 mol%-99 mol%.

  The hydrophilic polymer (III) preferably has a mass average molecular weight of 1,000,000 or less, and has a molecular weight of 1,000 to 1,000,000, more preferably 20,000 to 100,000. When the molecular weight is 1,000,000 or less, there is a problem in handling properties, such as the ability to form a uniform coating film without lowering the solubility in a solvent when preparing a coating solution for forming a hydrophilic coating film, without lowering the solubility in the solvent. This is preferable.

  Specific examples of the hydrophilic polymer (III) including the structures represented by the general formulas (III-1) and (III-2) are shown below together with their mass average molecular weights (MW). The invention is not limited to these examples. In addition, the polymer of the specific example shown below means that each structural unit described is a random copolymer or a block copolymer contained in the described molar ratio.

The hydrophilic polymer (I), (II) or (III) may be a copolymer with another monomer. Examples of other monomers used include acrylic esters, methacrylic esters, acrylamides, methacrylamides, vinyl esters, styrenes, acrylic acid, methacrylic acid, acrylonitrile, maleic anhydride, maleic imide, etc. These known monomers are also included. By copolymerizing such monomers, various physical properties such as film forming property, film strength, hydrophilicity, hydrophobicity, solubility, reactivity, and stability can be improved.

  Specific examples of acrylic esters include methyl acrylate, ethyl acrylate, (n- or i-) propyl acrylate, (n-, i-, sec- or t-) butyl acrylate, amyl acrylate, 2-ethylhexyl acrylate, Dodecyl acrylate, chloroethyl acrylate, 2-hydroxyethyl acrylate, 2-hydroxypropyl acrylate, 2-hydroxypentyl acrylate, cyclohexyl acrylate, allyl acrylate, trimethylolpropane monoacrylate, pentaerythritol monoacrylate, benzyl acrylate, methoxybenzyl acrylate, chloro Benzyl acrylate, hydroxybenzyl acrylate, hydroxyphenethyl acrylate, dihydroxyphene Chill acrylate, furfuryl acrylate, tetrahydrofurfuryl acrylate, phenyl acrylate, hydroxyphenyl acrylate, chlorophenyl acrylate, sulfamoylphenyl acrylate, 2- (hydroxyphenyl carbonyloxy) ethyl acrylate.

  Specific examples of methacrylic acid esters include methyl methacrylate, ethyl methacrylate, (n- or i-) propyl methacrylate, (n-, i-, sec- or t-) butyl methacrylate, amyl methacrylate, 2-ethylhexyl methacrylate, Dodecyl methacrylate, chloroethyl methacrylate, 2-hydroxyethyl methacrylate, 2-hydroxypropyl methacrylate, 2-hydroxypentyl methacrylate, cyclohexyl methacrylate, allyl methacrylate, trimethylolpropane monomethacrylate, pentaerythritol monomethacrylate, benzyl methacrylate, methoxybenzyl methacrylate, chloro Benzyl methacrylate, hydroxybenzyl methacrylate, hydroxy E phenethyl methacrylate, dihydroxyphenethyl methacrylate, furfuryl methacrylate, tetrahydrofurfuryl methacrylate, phenyl methacrylate, hydroxyphenyl methacrylate, chlorophenyl methacrylate, sulfamoylphenyl methacrylate, 2- (hydroxyphenyl carbonyloxy) ethyl methacrylate.

  Specific examples of acrylamides include acrylamide, N-methylacrylamide, N-ethylacrylamide, N-propylacrylamide, N-butylacrylamide, N-benzylacrylamide, N-hydroxyethylacrylamide, N-phenylacrylamide, and N-tolylacrylamide. N- (hydroxyphenyl) acrylamide, N- (sulfamoylphenyl) acrylamide, N- (phenylsulfonyl) acrylamide, N- (tolylsulfonyl) acrylamide, N, N-dimethylacrylamide, N-methyl-N-phenylacrylamide , N-hydroxyethyl-N-methylacrylamide and the like.

  Specific examples of methacrylamides include methacrylamide, N-methylmethacrylamide, N-ethylmethacrylamide, N-propylmethacrylamide, N-butylmethacrylamide, N-benzylmethacrylamide, N-hydroxyethylmethacrylamide, N -Phenylmethacrylamide, N-tolylmethacrylamide, N- (hydroxyphenyl) methacrylamide, N- (sulfamoylphenyl) methacrylamide, N- (phenylsulfonyl) methacrylamide, N- (tolylsulfonyl) methacrylamide, N , N-dimethylmethacrylamide, N-methyl-N-phenylmethacrylamide, N-hydroxyethyl-N-methylmethacrylamide and the like.

Specific examples of vinyl esters include vinyl acetate, vinyl butyrate, vinyl benzoate and the like.
Specific examples of styrenes include styrene, methyl styrene, dimethyl styrene, trimethyl styrene, ethyl styrene, propyl styrene, cyclohexyl styrene, chloromethyl styrene, trifluoromethyl styrene, ethoxymethyl styrene, acetoxymethyl styrene, methoxy styrene, dimethoxy styrene. Chlorostyrene, dichlorostyrene, bromostyrene, iodostyrene, fluorostyrene, carboxystyrene and the like.

  The ratio of these other monomers used for the synthesis of the copolymer needs to be an amount sufficient for improving various physical properties, but the function as a hydrophilic film is sufficient, and the specific hydrophilic polymer (I ), In order to obtain the advantage of adding the specific hydrophilic polymer (II) and / or the specific hydrophilic polymer (III), it is preferable that the ratio is not too large. Accordingly, the preferred total proportion of the other monomers in the specific hydrophilic polymer (I), the specific hydrophilic polymer (II) and / or the specific hydrophilic polymer (III) is preferably 80% by mass or less, more preferably It is 50 mass% or less.

The copolymerization ratio of the hydrophilic polymer (I), (II) or (III) can be measured by preparing a calibration curve with a nuclear magnetic resonance apparatus (NMR) or a standard substance and measuring with an infrared spectrophotometer. it can.

In the hydrophilic composition in the present invention, the hydrophilic polymers (I), (II) or (III) may be used alone or in combination of two or more.
The hydrophilic polymer (I), (II) or (III) is preferably used in an amount of 20 to 99.5% by mass based on the total solid content of the hydrophilic composition from the viewpoint of curability and hydrophilicity. More preferably, ˜99.5% by mass is used.

  The above-mentioned hydrophilic polymer forms a crosslinked film in a state where it is mixed with a hydrolysis and polycondensate of metal alkoxide. The hydrophilic polymer, which is an organic component, is involved in the film strength and film flexibility. In particular, the hydrophilic polymer has a viscosity of 0.1 to 100 mPa · s (5% aqueous solution, measured at 20 ° C.), preferably When it is in the range of 0.5 to 70 mPa · s, more preferably 1 to 50 mPa · s, good film properties are provided.

  In the present invention, the hydrophilic polymer is preferably a hydrophilic polymer having a structure represented by the following general formula (IV) or (V).

In the general formulas (IV) and (V), R ^{401 to} R ⁴⁰⁴ and R ^{501 to} R ⁵⁰² each independently represent a hydrogen atom or a hydrocarbon group having 8 or less carbon atoms, and R ⁵⁰³ represents a hydrogen atom or a monovalent non-valent group. Represents a metal atomic group. x, y and z each independently represents an integer of 0 to 2, and L ⁴⁰¹ , L ⁴⁰² and L ⁵⁰¹ each independently represents an atom selected from a carbon atom, a hydrogen atom, an oxygen atom, a nitrogen atom and a sulfur atom. It represents a divalent linking group having three or more types. m and n represent an integer of 3 to 25,000.

Examples of the hydrocarbon group when R ^{401 to} R ⁴⁰⁴ and R ^{501 to} R ⁵⁰² represent a hydrocarbon group include an alkyl group and an aryl group, and a linear, branched or cyclic alkyl group having 1 to 8 carbon atoms. Is preferred. Specifically, methyl group, ethyl group, propyl group, butyl group, pentyl group, hexyl group, heptyl group, octyl group, isopropyl group, isobutyl group, s-butyl group, t-butyl group, isopentyl group, neopentyl group 1-methylbutyl group, isohexyl group, 2-ethylhexyl group, 2-methylhexyl group, cyclopentyl group and the like.
R ^{401 to} R ⁴⁰⁴ and R ^{501 to} R ⁵⁰² are preferably a hydrogen atom, a methyl group or an ethyl group from the viewpoints of effects and availability.

  These hydrocarbon groups may further have a substituent. When the alkyl group has a substituent, the substituted alkyl group is constituted by a bond between a substituent and an alkylene group, and a monovalent nonmetallic atomic group excluding hydrogen is used as the substituent. Preferred examples include halogen atoms (-F, -Br, -Cl, -I), hydroxyl groups, alkoxy groups, aryloxy groups, mercapto groups, alkylthio groups, arylthio groups, alkyldithio groups, aryldithio groups, amino groups, N-alkylamino group, N, N-diarylamino group, N-alkyl-N-arylamino group, acyloxy group, carbamoyloxy group, ア ル キ ル -alkylcarbamoyloxy group, N-arylcarbamoyloxy group, N, N-dialkyl Carbamoyloxy group, N, N-diarylcarbamoyloxy group, N-alkyl-N-reelcarbamoyloxy group, alkylsulfoxy group, arylsulfoxy group, acylthio group, acylamino group, N-alkylacylamino group, N-aryl Acylamino group, ureido group, N'- Rukyureido group, N ′, N′-dialkylureido group, N′-arylureido group, N ′, N′-diarylureido group, N′-alkyl-N′-arylureido group, N-alkylureido group, N— Arylureido group, N′-alkyl-N-alkylureido group, N′-alkyl-N-arylureido group, N ′, N′-dialkyl-N-alkylureate group, N ′, N′-dialkyl-N -Arylureido group, N'-aryl-Ν-alkylureido group, N'-aryl-N-arylureido group, N ', N'-diaryl-N-alkylureido group, N', N'-diaryl-N -Arylureido group, N'-alkyl-N'-aryl-N-alkylureido group, N'-alkyl-N'-aryl-N-arylureido group, alkoxycarbonylamino group, Ryloxycarbonylamino group, N-alkyl-N-alkoxycarbonylamino group, N-alkyl-N-aryloxycarbonylamino group, N-aryl-N-alkoxycarbonylamino group, N-aryl-N-aryloxycarbonylamino Group, formyl group, acyl group, carboxyl group, alkoxycarbonyl group,

Aryloxycarbonyl group, carbamoyl group, N-alkylcarbamoyl group, N, N-dialkylcarbamoyl group, N-arylcarbamoyl group, N, N-diarylcarbamoyl group, N-alkyl-N-arylcarbamoyl group, alkylsulfinyl group, Arylsulfinyl group, alkylsulfonyl group, arylsulfonyl group, sulfo group (—SO ₃ H) and its conjugate base group (hereinafter referred to as sulfonate group), alkoxysulfonyl group, aryloxysulfonyl group, sulfinamoyl group, N-alkyls Rufinamoyl group, N, N-dialkylsulfinamoyl group, N-arylsulfinamoyl group, N, N-diarylsulfinamoyl group, N-alkyl-N-arylsulfinamoyl group, sulfamoyl group, N-alkyl Sulfa Yl group, N, N- dialkylsulfamoyl group, N- aryl sulfamoyl group, N, N- diaryl sulfamoyl group, N- alkyl -N- arylsulfamoyl group phosphono group (-PO ₃ H ₂ ) And conjugated base groups thereof (hereinafter referred to as phosphonate groups), dialkyl phosphono groups (—PO ₃ (alkyl) ₂ ), diaryl phosphono groups (—PO ₃ (aryl) ₂ ), alkylaryl phosphono groups (— PO ₃ (alkyl) (aryl)), monoalkyl phosphono group (-PO ₃ H (alkyl)) and its conjugated base group (hereinafter referred to as alkyl phosphonophenyl group), monoaryl phosphono group (-PO ₃ H (aryl)) and its conjugated base group (hereinafter referred to as aryl phosphonophenyl group), Oyo phosphonooxy group (-OPO ₃ H ₂₎ A conjugated base group thereof (hereinafter referred to as phosphonophenyl group), dialkyl phosphonooxy group (-OPO ₃ (alkyl) _2), diaryl phosphonooxy group (-OPO ₃ (aryl) _2), alkylaryl phosphonooxy aryloxy Group (—OPO (alkyl) (aryl)), monoalkylphosphonooxy group (—OPO ₃ H (alkyl)) and its conjugate base group (hereinafter referred to as alkylphosphonatooxy group), monoarylphosphonooxy group (—OPO ₃ H (aryl)) and its conjugate base group (hereinafter referred to as arylphosphonateoxy group), morpholino group, cyano group, nitro group, aryl group, alkenyl group, and alkynyl group.

Specific examples of the alkyl group in these substituents are the same as those of R ^{401 to} R ⁴⁰⁴ and R ^{501 to} R ⁵⁰² , and specific examples of the aryl group include a phenyl group, a biphenyl group, Naphthyl group, tolyl 2 group, xylyl group, mesityl group, cumenyl group, chlorophenyl group, bromophenyl group, chloromethylphenyl group, hydroxyphenyl group, methoxyphenyl group, ethoxyphenyl group, phenoxyphenyl group, acetoxyphenyl group, benzoy Loxyphenyl group, methylthiophenyl group, phenylthiophenyl group, methylaminophenyl group, dimethylaminophenyl group, acetylaminophenyl group, carboxyphenyl group, methoxycarbonylphenyl group, ethoxyphenylcarbonyl group, phenoxycarbonylphenyl group, - it can be exemplified phenylcarbamoyl phenyl group, a phenyl group, cyanophenyl group, sulfophenyl group, sulfonatophenyl group, phosphonophenyl phenyl group, a phosphonophenyl phenyl group. Examples of alkenyl groups include vinyl, 1-propenyl, 1-butenyl, cinnamyl, 2-chloro-1-ethenyl, etc. Examples of alkynyl include ethynyl, 1-butenyl, A propynyl group, a 1-butynyl group, a trimethylsilylethynyl group, etc. are mentioned. Examples of G ¹ in the acyl group (G ¹ CO—) include hydrogen and the above alkyl groups and aryl groups.

  Among these substituents, more preferred are halogen atoms (—F, —Br, —Cl, —I), alkoxy groups, aryloxy groups, alkylthio groups, arylthio groups, N-alkylamino groups, N, N-dialkyls. Amino group, acyloxy group, N-alkylcarbamoyloxy group, N-arylcarbamoyloxy group, acylamino group, formyl group, acyl group, carboxyl group, alkoxycarbonyl group, aryloxycarbonyl group, carbamoyl group, N-alkylcarbamoyl group N, N-dialkylcarbamoyl group, N-arylcarbamoyl group, N-alkyl-N-arylcarbamoyl group, sulfo group, sulfonate group, sulfamoyl group, N-alkylsulfamoyl group, N, N-dialkylsulfamoyl group Group, N-arylsulfamoy Group, N-alkyl-N-arylsulfamoyl group, phosphono group, phosphonate group, dialkyl phosphono group, diaryl phosphono group, monoalkyl phosphono group, alkyl phosphonate group, monoaryl phosphono group, aryl phosphonate group Group, phosphonooxy group, phosphonatooxy group, aryl group, and alkenyl group.

  On the other hand, examples of the alkylene group in the substituted alkyl group include divalent organic residues obtained by removing any one of the hydrogen atoms on the alkyl group having 1 to 20 carbon atoms. Can include linear alkylene groups having 1 to 12 carbon atoms, branched chains having 3 to 12 carbon atoms, and cyclic alkylene groups having 5 to 10 carbon atoms. Preferable specific examples of the substituted alkyl group obtained by combining the substituent and the alkylene group include chloromethyl group, bromomethyl group, 2-chloroethyl group, trifluoromethyl group, methoxymethyl group, methoxyethoxyethyl group, allyl group. Oxymethyl group, phenoxymethyl group, methylthiomethyl, tolylthiomethyl group, ethylaminoethyl group, diethylaminopropyl group, morpholinopropyl group, acetyloxymethyl group, benzoyloxymethyl group, N-cyclohexylcarbamoyloxyethyl group, N- Phenylcarbamoyloxyethyl group, acetylaminoethyl group, N-methylbenzoylaminopropyl group, 2-oxyethyl group, 2-oxypropyl group, carboxypropyl group, methoxycarbonylethyl group, allyloxy Rubonirubuchiru group,

Chlorophenoxycarbonylmethyl group, carbamoylmethyl group, N-methylcarbamoylethyl group, N, N-dipropylcarbamoylmethyl group, N- (methoxyphenyl) carbamoylethyl group, N-methyl-N- (sulfophenyl) carbamoylmethyl group , Sulfobutyl group, sulfonatobutyl group, sulfamoylbutyl group, N-ethylsulfamoylmethyl group, N, N-dipropylsulfamoylpropyl group, N-tolylsulfamoylpropyl group, N-methyl-N- (phos Phonophenyl) sulfamoyloctyl group, phosphonobutyl group, phosphonatohexyl group, diethylphosphonobutyl group, diphenylphosphonopropyl group, methylphosphonobutyl group, methylphosphonatobutyl group, tolylphosphonohexyl group, tolylphos Onatohexyl group, phosphonooxypropyl group, phosphonatoxybutyl group, benzyl group, phenethyl group, α-methylbenzyl group, 1-methyl-1-phenylethyl group, p-methylbenzyl group, cinnamyl group, allyl group, 1 -Propenylmethyl group, 2-butenyl group, 2-methylallyl group, 2-methylpropenylmethyl group, 2-propynyl group, 2-butynyl group, 3-butynyl group and the like can be mentioned.
x, y and z each independently represents 0, 1 or 2, and among them, 0 is preferable.

Examples of the monovalent nonmetallic atomic group represented by R ⁵⁰³ include the monovalent nonmetallic atomic groups listed as specific examples of R ^{401 to} R ⁴⁰⁴ and R ^{501 to} R ⁵⁰² , specifically, a methyl group , Ethyl group, propyl group, butyl group, pentyl group, hexyl group, heptyl group, octyl group, isopropyl group, isobutyl group, s-butyl group, t-butyl group, isopentyl group, neopentyl group, 1-methylbutyl group, isohexyl Preferred examples include a group, 2-ethylhexyl group, 2-methylhexyl group, cyclopentyl group, halogen atom, hydroxyl group and the like. From the viewpoint of improving hydrophilicity and availability, a hydrogen atom, a methyl group and a hydroxyl group are preferable.

L ⁴⁰¹ , L ⁴⁰² and L ⁵⁰¹ each independently represent a divalent linking group having three or more atoms selected from a carbon atom, a hydrogen atom, an oxygen atom, a nitrogen atom and a sulfur atom. From 0 to 60 carbon atoms, 0 to 10 nitrogen atoms, 0 to 50 oxygen atoms, 1 to 100 hydrogen atoms, and 0 to 20 sulfur atoms. It holds. That is, the linking group does not include a divalent linking group such as an unsubstituted alkylene group consisting of only a carbon atom and a hydrogen atom. In addition, as a more specific linking group, one composed of the following structural units other than the structural unit consisting of only two types of atoms, or a combination of a plurality of structural units shown below is combined. Mention can be made.

  The molecular weight of the general formulas (IV) and (V) is preferably 100 to 1,000,000, more preferably 200 to 500,000, and most preferably 300 to 200,000. What is necessary is just to select the structure of the terminal alkoxysilyl group, the numerical value of m, n, etc. so that this preferable molecular weight may be adapted.

  Although the preferable specific example of general formula (IV) and (V) is given to the following, this invention is not limited to these. First, specific examples of the structure represented by the general formula (IV) [Exemplary compounds (IV-1) to (IV-34)] are shown together with their weight average molecular weights (MW). For some compounds, the exemplary compounds are indicated by the compounds introduced at the terminals of the copolymer obtained by polymerizing the monomers when the composition ratio of the monomers constituting the compounds represents the molar ratio. It represents that the exemplary compounds are constituted by these. Those in which only one type of compound is introduced at the ends indicates that the compound is introduced at both ends.

  Next, specific examples of the structure represented by the general formula (V) [Exemplary compounds (V-1) to (V-34)] are shown. In addition, about some compounds, an exemplary compound is displayed with the monomer which comprises this compound, and the compound introduce | transduced into the terminal of the copolymer obtained by polymerizing the monomer, exemplary compound Is constituted by these. Two types of compounds introduced at the terminal are described, each indicating that it is introduced at one terminal.

  The hydrophilic polymers (IV) and (V) can be synthesized by the method described in JP-A-2007-70088 and the like.

  In the present invention, it is preferable to use the hydrophilic polymer (II), (IV) or (V) as the hydrophilic polymer having a structure difficult to adsorb such as platelets, blood coagulation factors, proteins and the like. More preferably, a hydrophilic polymer (IV) or (V) containing a polyethylene glycol structure in the structure is used.

The hydrophilic composition in the present invention may contain one or more of the hydrophilic polymers (I), (II), (III), (IV) or (V).
The hydrophilic polymer (I), (II), (III), (IV) or (V) is preferably used in an amount of 20 to 99.5% by mass relative to the total solid content of the hydrophilic composition, More preferably, 99.5% by mass is used.

  A preferred mass ratio when the hydrophilic composition contains the hydrophilic polymer (II), (IV) or (V) and the hydrophilic polymer (I) or (III) is (hydrophilic polymer (II), (IV) or (V) / the hydrophilic polymer (I) or (III)) is 50/50 to 5/95.

  The hydrophilic polymer (I), (II), (III), (IV) or (V) forms a crosslinked film in a state where it is mixed with a hydrolysis or polycondensate of a metal alkoxide. The hydrophilic polymer, which is an organic component, is involved in the film strength and film flexibility. In particular, the viscosity measured at 20 ° C. of a 5% aqueous solution of the hydrophilic polymer is 0.1 to 100 mPa · s, preferably When it is in the range of 0.5 to 70 mPa · s, more preferably 1 to 50 mPa · s, good film properties are provided. The viscosity can be measured with an E-type viscometer (trade name: RE80L, manufactured by Tokyo Keiki Co., Ltd.).

Solvents used when synthesizing a hydrophilic polymer containing 30 mol% or more of a structural unit containing a hydrophilic group and containing at least one hydrolyzable silyl group are tetrahydrofuran, ethylene dichloride, cyclohexanone, methyl ethyl ketone, acetone, methanol. , Ethanol, propanol, acetonitrile, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, 2-methoxyethyl acetate, diethylene glycol dimethyl ether, 1-methoxy-2-propanol, 1-methoxy-2-propyl acetate, N, N-dimethylformamide N, N-dimethylacetamide, N-methylpyrrolidone, toluene, ethyl acetate, methyl lactate, ethyl lactate, dimethyl sulfoxide, water and the like. These solvents are used alone or in combination of two or more.
As the radical polymerization initiator used for synthesizing the hydrophilic polymer, known compounds such as an azo initiator, a peroxide initiator, and a redox initiator can be used.

[Crosslinking agent]
When the hydrophilic composition contains the hydrophilic polymer (II) (IV) or (V), it is preferable to contain a crosslinking agent in order to obtain good curability. Further, when the hydrophilic composition (I) or (III) containing the structure represented above is contained in the hydrophilic composition, good curability can be obtained even when the crosslinking agent is not contained. In order to obtain a coating film having very excellent strength, a crosslinking agent may be contained.
As the crosslinking agent, an alkoxide compound (also referred to as a metal alkoxide) containing an element selected from Si, Ti, Zr, and Al is particularly preferable. A metal alkoxide is a hydrolyzable polymerizable compound having a functional group capable of being hydrolyzed and polycondensed in its structure and serving as a cross-linking agent, and has a cross-linked structure due to polycondensation of metal alkoxides. A strong cross-linked film can be formed and further chemically bonded to the hydrophilic polymer. The metal alkoxide can be represented by general formula (V-1) or general formula (V-2), in which R ²⁰ represents a hydrogen atom, an alkyl group or an aryl group, and R ²¹ represents an alkyl group or an aryl group. Z represents Si, Ti or Zr, and m represents an integer of 0-2. The carbon number when R ²⁰ and R ²¹ represent an alkyl group is preferably 1 to 4. The alkyl group or aryl group may have a substituent, and examples of the substituent that can be introduced include a halogen atom, an amino group, and a mercapto group. This compound is a low molecular compound and preferably has a molecular weight of 2000 or less.

_{^{(R 20) m -Z- (OR}} 21) 4-m (V-1)
Al- (OR ²² ) ₃ (V-2)

Specific examples of the metal alkoxide represented by the general formula (V-1) or the general formula (V-2) are shown below, but are not limited thereto.
When Z is Si, that is, the hydrolyzable compound containing silicon includes, for example, trimethoxysilane, tetramethoxysilane, tetraethoxylane, tetrapropoxysilane, methyltrimethoxysilane, dimethyldimethoxysilane, γ- Examples include chloropropyltriethoxysilane, γ-mercaptopropyltrimethoxysilane, γ-aminopropyltriethoxysilane, phenyltrimethoxysilane, diphenyldimethoxysilane, and the like. Among these, particularly preferred are trimethoxysilane, tetramethoxysilane, tetraethoxysilane, methyltrimethoxysilane, dimethyldimethoxysilane, phenyltrimethoxysilane and the like.

When Z is Ti, i.e., including titanium, for example, trimethoxy titanate, tetramethoxy titanate, triethoxy titanate, tetraethoxy titanate, tetrapropoxy titanate, chlorotrimethoxy titanate, chlorotriethoxy titanate, ethyl Examples include trimethoxy titanate, methyl triethoxy titanate, ethyl triethoxy titanate, diethyl diethoxy titanate, phenyl trimethoxy titanate, and phenyl triethoxy titanate. When Z is Zr, that is, the one containing zirconium can include, for example, zirconates corresponding to the compounds exemplified as those containing titanium.
In the case where the central metal is Al, that is, examples of the hydrolyzable compound containing aluminum include, for example, trimethoxy aluminate, triethoxy aluminate, tripropoxy aluminate, triisopropoxy aluminate and the like. be able to.

  Among the above, tetramethoxysilane, tetraethoxysilane, methyltrimethoxysilane, and methyltriethoxysilane are particularly preferable.

  When the hydrophilic polymer (II), (IV) or (V) is used, the metal alkoxide compound selected from Si, Ti, Zr, and Al is 1 to 80 with respect to the total solid content of the hydrophilic composition. It is preferably used in an amount of 5% by mass, more preferably 5 to 70% by mass. When the hydrophilic polymer (I) or (III) containing the structure represented above is used, it is preferably used in an amount of 0 to 80% by mass, based on the total solid content of the hydrophilic composition, 0 to 70% by mass. % Is more preferably used.

[Curing catalyst]
In the hydrophilic composition, a hydrolyzable silyl group-containing hydrophilic polymer and a cross-linking agent such as a metal alkoxide compound are dissolved in a solvent and stirred well, so that these components are hydrolyzed and polycondensed. An inorganic composite sol solution is formed, and a hydrophilic film having high hydrophilicity and high film strength is formed by the sol solution. In preparing the organic / inorganic composite sol solution, it is preferable to use a curing catalyst in order to promote hydrolysis and polycondensation reaction.
As the curing catalyst, it is preferable to use an acidic catalyst, a basic catalyst, or a metal complex.

  As the curing catalyst, a curing catalyst that promotes a reaction that causes hydrolysis and polycondensation of a crosslinking agent such as the metal alkoxide compound to cause a bond with a hydrolyzable silyl group-containing hydrophilic polymer is selected. The compound is used as it is, or an acid or a compound in which a basic compound is dissolved in a solvent such as water or alcohol (hereinafter collectively referred to as an acidic catalyst and a basic catalyst, respectively) is used. The concentration at which the acid or basic compound is dissolved in the solvent is not particularly limited, and may be appropriately selected according to the characteristics of the acid or basic compound used, the desired content of the curing catalyst, and the like. Here, when the concentration of the acid or basic compound constituting the curing catalyst is high, the hydrolysis and polycondensation rates tend to increase. However, when a basic catalyst with a high concentration is used, a precipitate may be generated in the sol solution. Therefore, when a basic catalyst is used, the concentration is preferably 1 N or less in terms of concentration in an aqueous solution.

The type of the acidic catalyst or the basic catalyst is not particularly limited. However, when it is necessary to use a catalyst having a high concentration, a catalyst composed of an element that hardly remains in the coating film after drying is preferable. Specifically, the acid catalyst is represented by hydrogen halide such as hydrochloric acid, nitric acid, sulfuric acid, sulfurous acid, hydrogen sulfide, perchloric acid, hydrogen peroxide, carbonic acid, carboxylic acid such as formic acid or acetic acid, and its R ³⁰ COOH. is the structural formula substituted carboxylic acid was replaced by an R ³⁰ other element or substituent, and sulfonic acids such as benzenesulfonic acid. Examples of the basic catalyst include an ammoniacal base such as aqueous ammonia, ethylamine and aniline, etc. And amines.

The curing catalyst is particularly preferably a metal complex.
The metal complex catalyst can promote hydrolysis and polycondensation of a metal alkoxide compound selected from Si, Ti, Zr, and Al, and can cause a bond with a hydrophilic polymer. Particularly preferred metal complex catalysts include metal elements selected from groups 2A, 3B, 4A and 5A of the periodic table and β-diketones, ketoesters, hydroxycarboxylic acids or esters thereof, amino alcohols, and enolic active hydrogen compounds. Metal complexes composed of selected oxo or hydroxy oxygen containing compounds.
Among the constituent metal elements, 2A group elements such as Mg, Ca, Sr and Ba, 3B group elements such as Al and Ga, 4A group elements such as Ti and Zr, and 5A group elements such as V, Nb and Ta are preferable. , Each forming a complex with excellent catalytic effect. Among them, complexes obtained from Zr, Al and Ti are excellent and preferred.

  In the present invention, the oxo- or hydroxy-oxygen-containing compound constituting the ligand of the metal complex is a β diketone such as acetylacetone (2,4-pentanedione) or 2,4-heptanedione, methyl acetoacetate, acetoacetic acid Ketoesters such as ethyl and butyl acetoacetate, lactic acid, methyl lactate, salicylic acid, ethyl salicylate, phenyl salicylate, malic acid, tartaric acid, methyl tartrate and other hydroxycarboxylic acids and esters thereof, 4-hydroxy-4-methyl-2-pentanone , 4-hydroxy-2-pentanone, 4-hydroxy-4-methyl-2-heptanone, ketoalcohols such as 4-hydroxy-2-heptanone, monoethanolamine, N, N-dimethylethanolamine, N-methyl- Monoethanolamine, diethanol Amino alcohols such as amine and triethanolamine, methylol melamine, methylol urea, methylol acrylamide, enol active compounds such as malonic acid diethyl ester, methyl group, methylene group or carbonyl carbon of acetylacetone (2,4-pentanedione) The compound which has a substituent is mentioned.

  A preferred ligand is acetylacetone or an acetylacetone derivative. In the present invention, the acetylacetone derivative refers to a compound having a substituent on the methyl group, methylene group or carbonyl carbon of acetylacetone. Substituents for substitution on the methyl group of acetylacetone are all linear or branched alkyl groups having 1 to 3 carbon atoms, acyl groups, hydroxyalkyl groups, carboxyalkyl groups, alkoxy groups, alkoxyalkyl groups, and acetylacetone As a substituent for substituting the methylene group, a carboxyl group, each of which is a linear or branched carboxyalkyl group and hydroxyalkyl group having 1 to 3 carbon atoms, and as a substituent for substituting the carbonyl carbon of acetylacetone, Is an alkyl group of 1 to 3, and in this case, a hydrogen atom is added to the carbonyl oxygen to form a hydroxyl group.

Specific examples of preferable acetylacetone derivatives include ethylcarbonylacetone, n-propylcarbonylacetone, i-propylcarbonylacetone, diacetylacetone, 1-acetyl-1-propionyl-acetylacetone, hydroxyethylcarbonylacetone, hydroxypropylcarbonylacetone, acetoacetic acid. , Acetopropionic acid, diacetacetic acid, 3,3-diacetpropionic acid, 4,4-diacetbutyric acid, carboxyethylcarbonylacetone, carboxypropylcarbonylacetone, diacetone alcohol.
Of these, acetylacetone and diacetylacetone are particularly preferred. The complex of the above acetylacetone derivative and the above metal element is a mononuclear complex in which one to four molecules of the acetylacetone derivative are coordinated per metal element, and the coordinateable bond of the acetylacetone derivative is a coordinateable bond of the acetylacetone derivative. When the number of hands is larger than the total number of hands, ligands commonly used for ordinary complexes such as water molecules, halogen ions, nitro groups, and ammonio groups may coordinate.

  Examples of preferred metal complexes include tris (acetylacetonato) aluminum complex, di (acetylacetonato) aluminum / aco complex, mono (acetylacetonato) aluminum / chloro complex, di (diacetylacetonato) aluminum complex, ethylacetate Acetate aluminum diisopropylate, aluminum tris (ethylacetoacetate), cyclic aluminum oxide isopropylate, tris (acetylacetonato) barium complex, di (acetylacetonato) titanium complex, tris (acetylacetonato) titanium complex, di-i -Propoxy bis (acetylacetonato) titanium complex salt, zirconium tris (ethyl acetoacetate), zirconium tris (benzoic acid) complex salt, etc. are mentioned. These are excellent in stability in aqueous coating solutions and in gelation promotion effect in sol-gel reaction during heat drying, but in particular, ethyl acetoacetate aluminum diisopropylate, aluminum tris (ethyl acetoacetate), di ( Acetylacetonato) titanium complex and zirconium tris (ethylacetoacetate) are preferred.

  Although the description of the counter salt of the metal complex described above is omitted in this specification, the type of the counter salt is arbitrary as long as it is a water-soluble salt that maintains the neutrality of the charge as the complex compound, such as nitrate, Salt forms such as halogenates, sulfates, phosphates, etc., that ensure stoichiometric neutrality are used. For the behavior of the metal complex in the silica sol-gel reaction, see J.A. Sol-Gel. Sci. and Tec. There is a detailed description in 16.209 (1999). The following scheme is estimated as the reaction mechanism. That is, in the coating solution, the metal complex has a coordinated structure and is stable, and in the dehydration condensation reaction that starts in the heat drying process after coating, it is considered that crosslinking is promoted by a mechanism similar to an acid catalyst. In any case, the use of this metal complex has led to satisfying the improvement of coating solution aging stability and film surface quality, and high hydrophilicity and high durability.

In addition to the above metal complex catalyst, the acidic catalyst and the basic catalyst may be used in combination.
The above metal complex catalyst can be easily obtained as a commercial product, and can also be obtained by a known synthesis method, for example, reaction of each metal chloride with an alcohol.

  It is preferable that 0.1-20 mass% is used for a curing catalyst with respect to the total solid of a hydrophilic composition, and it is more preferable that 1-10 mass% is used.

[Inorganic fine particles]
The hydrophilic composition may contain inorganic fine particles in order to improve hydrophilicity, prevent cracking of the film, and improve film strength. Inorganic fine particles are particularly preferred because of their high hydrophilicity. As the inorganic fine particles, for example, silica, alumina, magnesium oxide, titanium oxide, magnesium carbonate, calcium alginate or a mixture thereof can be preferably mentioned.
The inorganic fine particles preferably have an average particle size of 10 nm to 10 μm, and more preferably 0.05 to 3 μm. Within the above range, it is possible to form a coating film that is stably dispersed in the coating film, sufficiently maintains the film strength of the coating film, and has high durability and excellent hydrophilicity.
Among the inorganic fine particles as described above, a colloidal silica dispersion is particularly preferable and can be easily obtained as a commercial product.
The content of the inorganic fine particles is preferably 80% by mass or less, and more preferably 50% by mass or less, based on the total solid content of the hydrophilic composition.

[Surfactant]
A surfactant may be added to the hydrophilic composition.
Examples of the surfactant include those described in JP-A Nos. 62-173463 and 62-183457. For example, anionic surfactants such as dialkylsulfosuccinates, alkylnaphthalenesulfonates, fatty acid salts, polyoxyethylene alkyl ethers, polyoxyethylene alkyl allyl ethers, acetylene glycols, polyoxyethylene / polyoxypropylene blocks Nonionic surfactants such as copolymers, and cationic surfactants such as alkylamine salts and quaternary ammonium salts. An organic fluoro compound may be used in place of the surfactant. The organic fluoro compound is preferably hydrophobic. Examples of the organic fluoro compounds include fluorine surfactants, oily fluorine compounds (eg, fluorine oil) and solid fluorine compound resins (eg, tetrafluoroethylene resin). No. (columns 8 to 17) and those described in JP-A Nos. 62-135826.
The addition amount of the surfactant is appropriately selected according to the purpose, but is preferably 0.001 to 10% by mass, and 0.01 to 5% by mass with respect to the total solid content of the hydrophilic composition. More preferably.

[solvent]
It is also effective to appropriately add an organic solvent to the hydrophilic composition in order to ensure the formation of a uniform coating film on the substrate during the formation of the coating film with the hydrophilic composition.
Examples of the solvent include ketone solvents such as acetone, methyl ethyl ketone, and diethyl ketone, alcohol solvents such as methanol, ethanol, 2-propanol, 1-propanol, 1-butanol, and tert-butanol, and chlorine such as chloroform and methylene chloride. Solvents, aromatic solvents such as benzene and toluene, ester solvents such as ethyl acetate, butyl acetate and isopropyl acetate, ether solvents such as diethyl ether, tetrahydrofuran and dioxane, glycols such as ethylene glycol monomethyl ether and ethylene glycol dimethyl ether And ether solvents.
In this case, it is effective to add in a range that does not cause a problem in relation to VOC (volatile organic solvent), and the amount is preferably 0 to 50% by mass, more preferably 0 to 30% with respect to the entire hydrophilic composition. It is the range of mass%.

[Polymer compound]
In order to adjust the physical properties of the coating film, various polymer compounds can be added to the hydrophilic composition as long as the hydrophilicity is not impaired. High molecular compounds include acrylic polymer, polyvinyl alcohol resin, polyvinyl butyral resin, polyurethane resin, polyamide resin, polyester resin, epoxy resin, phenol resin, polycarbonate resin, polyvinyl formal resin, shellac, vinyl resin, acrylic resin. Rubber resins, waxes and other natural resins can be used. Two or more of these may be used in combination. Of these, vinyl copolymers obtained by copolymerization of acrylic monomers are preferred. Furthermore, a copolymer containing “carboxyl group-containing monomer”, “methacrylic acid alkyl ester”, or “acrylic acid alkyl ester” as a structural unit is also preferably used as the copolymer composition of the polymer binder.
The addition amount of the polymer compound is appropriately selected according to the purpose, but is preferably 0.001 to 20% by mass, and 0.01 to 15% by mass with respect to the total solid content of the hydrophilic composition. It is more preferable that

In addition to this, if necessary, for example, leveling additives, matting agents, waxes for adjusting film physical properties, tackifiers within the range that does not impair hydrophilicity in order to improve adhesion to the substrate. Etc. can be contained.
As the tackifier, specifically, a high molecular weight adhesive polymer described in JP-A-2001-49200, 5-6p (for example, (meth) acrylic acid and an alkyl group having 1 to 20 carbon atoms). An ester with an alcohol having, an ester of (meth) acrylic acid with an alicyclic alcohol having 3 to 14 carbon atoms, a copolymer comprising an ester of (meth) acrylic acid with an aromatic alcohol having 6 to 14 carbon atoms) And a low molecular weight tackifying resin having a polymerizable unsaturated bond.

[Medical device with hydrophilic surface]
Hereinafter, regarding a medical device in which at least one hydrophilic layer is formed on a substrate using the hydrophilic composition described above (that is, the surface is hydrophilized) and a manufacturing method thereof, the case where the medical device is a stent is described below. This will be described as an example. Here, the base material corresponds to the main stent body.
In the present invention, a hydrophilic layer may be formed directly on the body substrate of the medical device, or a primer layer (undercoat layer) for improving adhesion is provided in advance, and a hydrophilic layer is formed thereon. May be. Further, the hydrophilic layer may be composed of at least one layer or may be composed of a plurality of layers.

(Undercoat layer)
In the present invention, one or more undercoat layers can be provided between the substrate and the hydrophilic layer.
The undercoat layer is preferably obtained by hydrolysis and polycondensation of a composition having at least an alkoxide compound containing an element selected from Si, Ti, Zr and Al and a nonvolatile catalyst.
An undercoat layer obtained by hydrolysis and polycondensation of a composition having at least an alkoxide compound containing an element selected from Si, Ti, Zr, and Al and a nonvolatile catalyst has a crosslinked structure. In the present invention, a crosslinked structure formed by hydrolysis and condensation polymerization of a compound is appropriately referred to as a sol-gel crosslinked structure.

  Examples of the alkoxide compound containing an element selected from Si, Ti, Zr and Al include those described above. Among these, Si alkoxides are preferable from the viewpoint of reactivity and availability, and specifically, compounds used for silane coupling agents can be suitably used.

Nonvolatile catalysts used in the undercoat layer are those other than those having a boiling point of less than 20 ° C., in other words, those having a boiling point of 20 ° C. or higher, or those having no boiling point in the first place (such as thermal decomposition, Including those that do not cause changes).
Although it does not specifically limit as a non-volatile catalyst used for this invention, A metal complex (it is also called a metal chelate compound) and a silane coupling agent are mentioned. In addition, although an acid or an alkali is used suitably as a catalyst in this industry, if these also have a boiling point of 20 degreeC or more, they are applicable without a restriction | limiting especially. For example, hydrochloric acid having a boiling point of −83 ° C. is excluded, but nitric acid having a boiling point of 121 ° C. or phosphoric acid having a decomposition temperature of 213 ° C. is applied as a nonvolatile catalyst in the present invention.
Examples of the metal complex include those described above.

  The silane coupling agent used as the non-volatile catalyst is not particularly limited, and examples thereof include those having a functional group showing acidity or alkalinity, and more specifically, peroxo acid, carboxylic acid, carbohydrazone acid, carboximide A functional group showing acidity such as acid, sulfonic acid, sulfinic acid, sulfenic acid, selenonic acid, selenic acid, selenic acid, telluronic acid and the above alkali metal salts, or a basic functional group showing amino group, etc. The silane coupling agent which has is mentioned.

The undercoat layer is formed by applying a composition having at least the above alkoxide compound and a non-volatile catalyst on a base material, heating, and drying the composition, whereby the composition is hydrolyzed and polycondensed. Can be formed. The heating temperature and heating time for forming the undercoat layer are not particularly limited as long as the solvent and the time in which the solvent in the sol solution is removed and a strong film can be formed. It is preferably 150 ° C. or lower, and the heating time is preferably within 1 hour.
The undercoat layer can be prepared by a known coating method, and is not particularly limited. For example, spray coating method, dip coating method, flow coating method, spin coating method, roll coating method, film applicator method, screen printing Methods such as coating, bar coating, brush coating, and sponge coating are applicable. Among these, the dip coating method is particularly preferable.

  The subbing layer thus obtained contains a non-volatile catalyst without losing its activity, and is also present on the surface of the subbing layer and the hydrophilic layer. The adhesion at the interface is extremely high.

  The undercoat layer can be further improved in adhesion at the interface between the undercoat layer and the hydrophilic layer by providing fine irregularities by mixing plasma etching or metal particles.

As the material for the undercoat layer, a hydrophilic resin or water-dispersible latex can be used.
Examples of hydrophilic resins include polyvinyl alcohol (PVA), cellulose resins [methyl cellulose (MC), hydroxyethyl cellulose (HEC), carboxymethyl cellulose (CMC), etc.], chitins, chitosans, starch, and ether bonds. Examples thereof include resins [polyethylene oxide (PEO), polyethylene glycol (PEG), polyvinyl ether (PVE), etc.], resins having a carbamoyl group [polyacrylamide (PAAM), polyvinyl pyrrolidone (PVP), etc.], and the like. Moreover, the polyacrylic acid salt which has a carboxyl group, maleic acid resin, alginate, gelatins, etc. can also be mentioned.
Among these, at least one selected from polyvinyl alcohol resins, cellulose resins, resins having an ether bond, resins having a carbamoyl group, resins having a carboxyl group, and gelatins is preferable, and in particular, polyvinyl alcohol (PVA) Of these, gelatin resins are preferred.

Examples of the water-dispersible latex include acrylic latex, polyester latex, NBR resin, polyurethane latex, polyvinyl acetate latex, SBR resin, polyamide latex and the like. Among these, acrylic latex is preferable.
The above hydrophilic resin and water-dispersible latex may be used alone or in combination of two or more, or a hydrophilic resin and a water-dispersible latex may be used in combination.
Moreover, you may use the crosslinking agent which bridge | crosslinks the said hydrophilic polymer and water-dispersible latex.
As a cross-linking agent applicable to the present invention, a cross-linking agent that forms a cross-link by known heat can be used. General thermal crosslinking agents include those described in “Crosslinking agent handbook” by Shinzo Yamashita, Tosuke Kaneko, published by Taiseisha (1981). The number of functional groups of the crosslinking agent used in the present invention is not particularly limited as long as it is 2 or more and can be effectively crosslinked with a hydrophilic resin or water-dispersible latex. Specific thermal crosslinking agents include polycarboxylic acids such as polyacrylic acid, amine compounds such as polyethyleneimine, ethylene or propylene glycol diglycidyl ether, tetraethylene glycol diglycidyl ether, nonaethylene glycol diglycidyl ether, polyethylene or polypropylene Polyepoxy compounds such as glycol glycidyl ether, neopentyl glycol diglycidyl ether, 1,6-hexanediol diglycidyl ether, trimethylolpropane triglycidyl ether, sorbitol polyglycidyl ether, polyaldehyde compounds such as glyoxal and terephthalaldehyde, tolylene diene Isocyanate, hexamethylene diisocyanate, diphenylmethane isocyanate, xylylene diiso Polyisocyanate compounds such as anate, polymethylene polyphenyl isocyanate, cyclohexyl diisocyanate, cyclohexane phenylene diisocyanate, naphthalene-1,5-diisocyanate, isopropylbenzene-2,4-diisocyanate, polypropylene glycol / tolylene diisocyanate addition reaction product, block polyisocyanate Examples thereof include compounds, silane coupling agents such as tetraalkoxysilane, metal cross-linking agents such as acetylacetonate of aluminum, copper and iron (III), and polymethylol compounds such as trimethylolmelamine and pentaerythritol. Among these thermal cross-linking agents, a water-soluble cross-linking agent is preferable from the viewpoint of easy preparation of the coating solution and prevention of a decrease in hydrophilicity of the produced hydrophilic layer.
Wherein at least one of the hydrophilic resin and water-dispersible latex, the total amount of the undercoat layer is preferably from ^{0.01~20g / m 2, 0.1~10g / m} 2 is more preferable.

[Stent]
The surface-hydrophilized stent in the present invention comprises a tubular base material (stent body) and a hydrophilic layer covering the base material. FIG. 1 is a side view of an example of a surface hydrophilized stent according to the present invention, and FIG. 2 is an enlarged cross-sectional view taken along line AA of FIG. As shown in FIG. 2, the stent 1 of FIG. 1 has a hydrophilic layer 3 formed on the surface of the linear member 2 constituting the stent body 23 so as to cover the linear member 2.
A stent retains the inner diameter of a blood vessel after dilating the stenosis of the blood vessel, and is generally cylindrical and has a slot, oval, circular, or other shaped passageway drilled therein. The stent may also be composed of a spirally wound or tortuous wire. Furthermore, a stent may be a flat or perforated structure wound to form a tubular or cylindrical structure, which may be woven, wound, perforated, etched or cut to form a passage. The stent has a self-expanding type or a balloon-expanding type as an expansion mechanism, but in the present invention, either a self-expanding type or a balloon-expanding type may be used.

  Examples of the material of the stent body include polymer materials, metal materials, carbon fibers, ceramics, etc., and these materials may be used alone or in appropriate combination, and have a certain degree of rigidity and elasticity. If it is, there will be no restriction | limiting in particular, However, It is preferable that it is a material which has biocompatibility, and a metal, a polymer material, and carbon fiber are still more preferable.

  Specifically, examples of polymer materials include polyolefins such as polyethylene and polypropylene, aromatic polyesters such as polyethylene terephthalate, aliphatic polyesters such as polylactic acid and polyglycolic acid, and cellulose polymers such as cellulose acetate and cellulose nitrate. Fluorine-containing polymers such as polytetrafluoroethylene and tetrafluoroethylene-ethylene copolymer are preferred.

  As the metal material, for example, stainless steel, tantalum, titanium, nickel titanium alloy, tantalum titanium alloy, nickel aluminum alloy, inconel, gold, platinum, iridium, tungsten, cobalt-based alloy and the like are preferable. Among stainless steels, SUS316L, which has the best corrosion resistance, is preferable. Among the cobalt-based alloys, MP35N, L605 and the like are preferable.

  The main stent body can be suitably formed from the above-exemplified materials by a material appropriately selected according to the application location or expansion means. For example, when the stent body is formed of a metal material, the metal material is excellent in strength, so that the stent can be surely placed in the lesion. When the stent body is formed of a polymer material, the polymer material is excellent in flexibility, and thus exhibits an excellent effect in terms of reachability (delivery property) to the lesioned portion of the stent.

  In addition, when the stent body is made of a biodegradable polymer such as polylactic acid, the stent itself degrades and absorbs into the living body after fulfilling its function as a stent, that is, after suppressing vascular occlusion and restenosis in the acute phase. Since it disappears, it has an excellent effect in that the risk of restenosis and thrombotic complications in the late period is low.

  In addition, when the stent is self-expanding, a restoring force to the original shape is required, so a superelastic alloy such as titanium nickel is preferable. When the stent is balloon-expandable, shape recovery after expansion is unlikely to occur. Since stainless steel is preferable, stainless steel or the like is preferable.

  In addition, when the stent body is made of carbon fiber, it has an excellent effect in that it has high strength and excellent flexibility and high safety in vivo.

  What is necessary is just to select the magnitude | size of a stent main body suitably according to an application location. For example, when used for the coronary artery of the heart, the outer diameter before expansion is usually 1.0 to 3.0 mm, and the length is preferably 5 to 50 mm. As shown in FIG. 1, when the stent body 1 is composed of the linear member 2, the length in the width direction of the linear member that configures the stent body to have a large number of notches is preferably 0.01. It is -0.5mm, More preferably, it is 0.05-0.2mm.

  The manufacturing method of the stent body is not particularly limited, and may be appropriately selected from commonly used manufacturing methods according to the structure and material of the stent. For example, an etching technique such as laser etching or chemical etching, and a manufacturing method using a laser cut technique can be selected.

  Moreover, in order to improve the adhesiveness with the hydrophilic layer, the entire surface or a part of the surface of the stent body of the present invention may be pretreated. Examples of the pretreatment include a method in which the surface of the stent body is coated with a material having a high affinity for both the stent body and the hydrophilic layer as a primer. Although various materials can be used as the primer material, the most preferable one is a silane coupling agent having a hydrolyzable group and an organic functional group. Silanol groups generated by the decomposition of hydrolyzable groups (for example, alkoxy groups) of the silane coupling agent can be bonded to the metal stent body and the hydrophilic polymer in the hydrophilic layer through chemical bonds. Specific examples of the silane coupling agent include tetramethoxysilane, methyltrimethoxysilane, γ-aminopropylethoxysilane, γ-glycidoxypropylmethyldimethoxysilane, and the like. Examples of primer materials other than silane coupling agents include, for example, organic titanium coupling agents such as tetraethyl orthotitanate, aluminum coupling agents, chromium coupling agents, organic phosphoric acid coupling agents, polyparaxylene, etc. Organic vapor deposition film, cyanoacrylate adhesive, polyurethane paste resin, and the like.

  Further, as another adhesion improving means, a surface hydrophilization treatment can be applied to one or both surfaces of the base material by an oxidation method, a roughening method, or the like as desired. Examples of the oxidation method include corona discharge treatment, glow discharge treatment, chromic acid treatment (wet), flame treatment, hot air treatment, ozone / ultraviolet irradiation treatment, and the like. As a roughening method, it can also be mechanically roughened by sandblasting, brush polishing or the like.

[Bioactive substances]
The hydrophilic layer of the stent of the present invention may contain a physiologically active substance. However, it is not always necessary for the hydrophilic layer to cover the entire surface of the linear member 2 constituting the stent body, as long as it covers at least a part of the surface of the linear member 2 constituting the stent body. Accordingly, only the upper surface of the outer surface 21 having a cross-sectional shape as shown in FIG. 2 (the inner surface 22 forms a short arc and the outer surface 21 forms a slightly longer arc) is covered with the hydrophilic layer. It may be a thing. When the hydrophilic layer is in such a formed form, the physiologically active substance is locally released from the stent surface to the living tissue, so that effective treatment can be performed.

  The physiologically active substance in the present invention is not particularly limited as long as it suppresses stenosis and occlusion of the vascular system that can occur when the stent of the present invention is placed in a lesion, and can be arbitrarily selected. For example, anticancer agents, immunosuppressive agents, antibiotics, antirheumatic agents, antithrombotic agents, HMG-CoA reductase inhibitors, ACE inhibitors, calcium antagonists, antihyperlipidemic agents, integrin inhibitors, antiallergic agents, From the group consisting of antioxidants, GPIIbIIIa antagonists, retinoids, flavonoids, carotenoids, lipid improvers, DNA synthesis inhibitors, tyrosine kinase inhibitors, antiplatelet drugs, anti-inflammatory drugs, biological materials, interferons, and NO production promoters At least one selected is preferable in that the lesion can be treated by controlling the behavior of cells in the lesion tissue.

  Preferred examples of the anticancer agent include vincristine, vinblastine, vindesine, irinotecan, pirarubicin, paclitaxel, docetaxel, and methotrexate.

  Examples of the immunosuppressant include sirolimus, everolimus, pimecrolimus, sirolimus derivatives such as ABT-578, AP23573, and CCI-779, tacrolimus, azathioprine, cyclosporine, cyclophosphamide, mycophenolate mofetil, gusperimus, mizoribine, and the like. preferable.

  As the antibiotic, for example, mitomycin, adriamycin, doxorubicin, actinomycin, daunorubicin, idarubicin, pirarubicin, aclarubicin, epirubicin, pepromycin, dinostatin styramer and the like are preferable.

  As the anti-rheumatic agent, for example, methotrexate, sodium thiomalate, penicillamine, lobenzalit and the like are preferable.

  As the antithrombotic agent, for example, heparin, aspirin, antithrombin preparation, ticlopidine, hirudin and the like are preferable.

  Preferred examples of the HMG-CoA reductase inhibitor include cerivastatin, cerivastatin sodium, atorvastatin, rosuvastatin, pitavastatin, fluvastatin, fluvastatin sodium, simvastatin, lovastatin, pravastatin and the like.

  As the ACE inhibitor, for example, quinapril, perindopril erbumine, trandolapril, cilazapril, temocapril, delapril, enalapril maleate, lisinopril, captopril and the like are preferable.

  As the calcium antagonist, for example, hifedipine, nilvadipine, diltiazem, benidipine, nisoldipine and the like are preferable.

  As the antihyperlipidemic agent, for example, probucol is preferable.

  As the integrin inhibitor, for example, AJM300 is preferable.

  As the antiallergic agent, for example, tranilast is preferable.

  As said antioxidant, (alpha) -tocopherol is preferable, for example.

  As the GPIIbIIIa antagonist, for example, abciximab is preferable.

  As the retinoid, for example, all-trans retinoic acid is preferable.

  As the flavonoid, for example, epigallocatechin, anthocyanin, and proanthocyanidin are preferable.

  As the carotenoid, for example, β-carotene and lycopene are preferable.

  As the lipid improving agent, for example, eicosapentaenoic acid is preferable.

  As the DNA synthesis inhibitor, for example, 5-FU is preferable.

  As the tyrosine kinase inhibitor, for example, genistein, tyrphostin, arbustatin, staurosporine and the like are preferable.

  As the antiplatelet drug, for example, ticlopidine, cilostazol, and clopidogrel are preferable.

  As the anti-inflammatory drug, for example, steroids such as dexamethasone and prednisolone are preferable.

  Examples of the bio-derived material include EGF (epidemal growth factor), VEGF (basic endowment growth factor), HGF (hepatocyte growth factor), PDGF (platelet growth factor), and PDGF (platelet growth factor).

  As the interferon, for example, interferon-γ1a is preferable.

  As the NO production promoting substance, for example, L-arginine is preferable.

  The hydrophilic layer may contain only one kind of the above-exemplified physiologically active substances, or may contain two or more different physiologically active substances. When two or more types of physiologically active substances are included, the combination may be appropriately selected from the physiologically active substances exemplified above as necessary. Also, when a physiologically active substance is contained in a medical device other than a stent, the hydrophilic layer may contain the physiologically active substance.

[Method for imparting hydrophilic layer]
(Agitation of hydrophilic composition)
It is preferable to stir the hydrophilic composition before applying it to the substrate for the purpose of improving the hydrolysis / condensation rate of the alkoxysilyl group. The stirring time is preferably 10 minutes to 10 hours, more preferably 15 minutes to 2 hours.
More preferably, the curing catalyst is added to the composition containing the hydrophilic polymer and stirred for the above time.

  The surface-hydrophilized stent of the present invention can be obtained by applying onto a stent body which is an untreated or primer-treated substrate, and heating and drying to form a hydrophilic layer. The heating temperature and heating time for forming the hydrophilic layer are not particularly limited as long as the solvent and the time in which the solvent in the sol solution is removed and a strong film can be formed, but from the viewpoint of improving the production suitability and the condensation rate. The heating temperature is preferably 20 to 200 ° C, more preferably 60 to 150 ° C. The heating time is preferably 10 seconds to 2 hours, more preferably 30 seconds to 1 hour.

  The surface-hydrophilized stent of the present invention can be prepared by a known application method, and is not particularly limited. For example, a spray coating method, a dip coating method, a flow coating method, a spin coating method, a roll coating method, Methods such as a film applicator method, a screen printing method, a bar coater method, brush coating, and sponge coating can be applied. Among these, the dip coating method is particularly preferable.

  The said coating method can apply | coat to the stent main body surface by means, such as brush coating, spray coating, roller coating, dip coating, for example. The coating amount is not particularly limited, but generally it is considered that a range of about 0.05 to 500 μm is sufficient. Conditions for drying the coating film can be selected according to the type of the hydrophilic composition. For example, when an aqueous coating material containing a base resin containing a hydrolyzable silyl group, a hydroxyl group and an epoxy group as essential functional group components and a metal chelate compound is used, it is about 1 to 72 hours at room temperature or when heated. Drying can be performed at 40 ° C. to 200 ° C. for about 1 minute to 24 hours.

  Specifically, in the method for producing a stent having a hydrophilic surface according to the present invention, at least one layer made of the hydrophilic polymer is formed on the surface of a stent body as a base material. However, the layer is not necessarily formed so as to cover the entire surface of the stent body, and may be formed so as to cover at least a part of the surface of the stent body. Therefore, only the outer surface of the cylindrical stent body may be covered with a layer, or only the inner surface may be covered with a layer. When the physiologically active substance is contained in the hydrophilic layer, specifically, the physiologically active substance is mixed in a solvent such as acetone, ethyl acetate, ethanol, chloroform, tetrahydrofuran, etc. at a ratio as described above, and the solution concentration is 0. An aqueous dispersion obtained by dissolving in an amount of 001 to 20% by mass, preferably 0.01 to 10% by mass, and emulsifying and dispersing in a coating solution for the hydrophilic layer may be used. The coating solution containing the hydrophilic polymer is applied to the entire surface or a part of the linear member constituting the stent body using the above-described coating method, preferably a spray or a dispenser that can be dispensed in a small amount or an inkjet. And then the solvent may be volatilized. Alternatively, it is also preferable to volatilize the solvent after immersing (dipping) the stent body in the solution as described above. The number of sprays and dippings may be one, but a method of performing a plurality of times is usually used in order to adjust the thickness of the coating layer according to the solution concentration or the like.

  As a specific method of spraying and dipping, a mixed solution containing a hydrophilic polymer and a physiologically active substance is spray-applied to a stent body which is a base material, or the stent body is immersed in the solution and taken out. C., preferably at 70 to 80.degree. C., for about 5 to 60 minutes, preferably for 10 to 30 minutes, to volatilize the solvent. The concentration of the spray solution is 0.01 wt% to 5 wt%, preferably 0.05 wt% to 3 wt%, and the spray flow rate is 0.01 to 0.1 ml / min, preferably 0.02 to 0.05 ml. / Min. When applied by dipping, the concentration of the solution is 0.01 wt% to 5 wt%, preferably 0.05 wt% to 3 wt%, and the dipping time is 1 to 30 seconds, preferably 5 to 10 seconds.

  The expanding means of the stent manufactured by such a method is the same as that of a normal stent and is not particularly limited. For example, it may be of a self-expanding type, that is, a type that expands in the radial direction by its own restoring force by removing the force holding the thin and small folded stent. However, the stent of the present invention is preferably of a balloon expandable type, that is, a type in which the balloon is expanded from the inside of the stent body and the stent is radially expanded by the external force.

[Physical properties of hydrophilic layer]
(Water drop contact angle)
The hydrophilicity is generally measured by a water droplet contact angle. The surface of the medical device having a hydrophilic surface according to the present invention has a contact angle of airborne water droplets measured at 20 ° C. of 15 ° or less, preferably 10 ° or less.

  The thickness of the hydrophilic layer is preferably 0.01 μm to 100 μm, more preferably 0.05 μm to 50 μm, and most preferably 0.1 μm to 20 μm. When the film thickness is 0.01 μm or more, sufficient hydrophilicity and durability can be obtained, and when the film thickness is 100 μm or less, there is no problem in film forming properties such as cracking, which is preferable.

  EXAMPLES Hereinafter, the present invention will be described in detail with reference to examples, but the present invention is not limited thereto.

1. Preparation of stent [Example 1]
A linear member 2 (width: 0.1 mm) constituting a stent body (material: SUS316L) having a cylindrical shape with an outer diameter of 2.0 mm, a thickness of 100 μm, and a length of 30 mm shown in FIG. The first layer coating solution (1) having the following composition is applied to the surface of the substrate using a micro-dispenser and oven-dried at 100 ° C. for 10 minutes to form a first layer having a dry coating amount of 1.0 g / m ² . did. After sufficiently cooling at room temperature, the hydrophilic layer coating solution (1) is applied as a second layer on the first layer coating surface using a micro dispenser, oven dried at 150 ° C. for 30 minutes, and a dry coating amount of 3.0 g. A second layer of / m ² was formed to obtain a stent having a hydrophilic surface.

<First layer coating solution (1)>
Colloidal silica dispersion 20% by mass aqueous solution (Snowtex C, Nissan Chemical Industries, Ltd., average particle size 10-20 nm) 100 g
・ 500g of the following sol-gel preparation (1)
・ 30 g of 5% by weight aqueous solution of the following anionic surfactant
・ Purified water 450g

<Sol-gel preparation liquid (1)>
16 g of tetramethoxysilane (manufactured by Tokyo Chemical Industry Co., Ltd.) was mixed in 400 g of ethyl alcohol, 20 g of acetylacetone, 20 g of tetraethyl orthotitanate, and 200 g of purified water, and the mixture was stirred at room temperature for 2 hours to prepare.

<Hydrophilic layer coating solution (1)>
・ 500g of the following sol-gel preparation (2)
-5.0 g of 5% by weight aqueous solution of the above anionic surfactant

<Sol-gel preparation liquid (2)>
The following hydrophilic polymer <1> 30 g was mixed in 200 g of ethyl alcohol, 0.25 g of acetylacetone, 0.3 g of tetraethyl orthotitanate, and 300 g of purified water, and the mixture was stirred at room temperature for 2 hours to prepare.

  After mounting this stent on the balloon of the delivery catheter and expanding the balloon to an outer diameter of 3.0 mm, the surface of the stent was observed with a CCD camera. Damaged parts such as peeling from the main body were not confirmed.

[Example 2]
A stent having a hydrophilic surface was obtained in the same manner as in Example 1 except that the hydrophilic layer coating solution (1) was changed to the hydrophilic layer coating solution (2).

<Hydrophilic layer coating solution (2)>
・ 500g of the following sol-gel preparation (3)
-5.0 g of 5% by weight aqueous solution of the above anionic surfactant

<Sol-gel preparation liquid (3)>
The following hydrophilic polymer <2> 27 g and tetramethoxysilane 3 g were mixed in 200 g of ethyl alcohol, 0.25 g of acetylacetone, 0.3 g of tetraethyl orthotitanate, and 300 g of purified water, and the mixture was prepared by stirring at room temperature for 2 hours.

Example 3
A linear member 2 (width: 0.1 mm) constituting a stent body (material: SUS316L) having a cylindrical shape with an outer diameter of 2.0 mm, a thickness of 100 μm, and a length of 30 mm shown in FIG. A first layer coating solution (2) having the following composition was dip coated on the surface of the substrate, and oven dried at 100 ° C. for 10 minutes to form a first layer having a dry coating amount of 0.1 g / m ² . After sufficiently cooling at room temperature, the hydrophilic layer coating solution (1) used in Example 1 was applied as a second layer on the first layer coating surface as a second layer, oven dried at 150 ° C. for 30 minutes, and the dry coating amount was 0. A second layer of 0.5 g / m ² was formed, and a stent having a hydrophilic surface was obtained.

<First layer coating solution (2)>
・ 500g of the following sol-gel preparation (4)
・ 30 g of 5% by weight aqueous solution of the above anionic surfactant
・ Purified water 450g

<Sol-gel preparation liquid (4)>
In 200 g of ethyl alcohol, 10 g of acetylacetone, 10 g of tetraethyl orthotitanate and 100 g of purified water, 4 g of tetramethoxysilane (manufactured by Tokyo Chemical Industry Co., Ltd.) and 4 g of methyltrimethoxysilane (manufactured by Tokyo Chemical Industry Co., Ltd.) are mixed. Stir at room temperature for 2 hours to prepare.

Example 4
A stent having a hydrophilic surface was obtained in the same manner as in Example 3 except that the hydrophilic layer coating solution (1) was changed to the hydrophilic layer coating solution (3).

<Hydrophilic layer coating solution (3)>
・ 500g of the following sol-gel preparation (5)
-5.0 g of 5% by weight aqueous solution of the above anionic surfactant

<Sol-gel preparation solution (5)>
In 200 g of ethyl alcohol, 0.25 g of acetylacetone, 0.3 g of tetraethyl orthotitanate, and 300 g of purified water, the following hydrophilic polymer <1> 15 g and the following hydrophilic polymer <2> 15 g are mixed and stirred at room temperature for 2 hours. And prepared.

[Examples 5 to 9]
A linear member 2 (width: 0.1 mm) constituting a stent body (material: SUS316L) having a cylindrical shape with an outer diameter of 2.0 mm, a thickness of 100 μm, and a length of 30 mm shown in FIG. A first layer coating solution (3) having the following composition was dip coated on the surface of the substrate, and oven-dried at 100 ° C. for 2 minutes to form a layer having a dry coating amount of 0.5 g / m ² . The water droplet contact angle of the first layer was 80 °. Further the first layer coating solution having the following composition on the first layer (4) and dip coating, 100 ° C., and 10 minutes oven dried to form a layer having a dry coating amount of 0.5 g / m ^2, 2 A first layer having a layer structure was formed. The water droplet contact angle of the layer formed from the first layer coating solution (4) was 10 °. Subsequently, on the first layer of the two-layer structure, the hydrophilic polymer in the hydrophilic layer coating liquid (3) and the drying conditions were changed in the same manner as in Example 3 except that the drying conditions were changed as shown in Table 1. A stent having two layers formed and having a hydrophilic surface was obtained.

<First layer coating solution (3)>
・ Epicoat 1009 (manufactured by Shell Chemicals Japan) 100g
・ Takenate D110N (manufactured by Takeda Pharmaceutical, solid content 10%) 100g
・ Methyl ethyl ketone 1200g

<First layer coating solution (4)>
-PVA105 aqueous solution (Kuraray, solid content 6%) 130g
・ Glyoxal aqueous solution (Tokyo Kasei, solid content 40%) 50g
・ Ethylene glycol diglycidyl ether (Tokyo Kasei) 10g
・ Methanol silica (Nissan Chemical, solid content 30%) 30g
・ 20 g of 5% by weight aqueous solution of the above anionic surfactant
・ Water 7600g

Example 10
A stent having a hydrophilic surface was obtained in the same manner as in Example 3 except that the hydrophilic layer coating solution (1) was changed to the hydrophilic layer coating solution (4).

<Hydrophilic layer coating solution (4)>
・ 500 g of the sol-gel preparation (5)
-623 g of the following bioactive substance dispersion (1)

<Bioactive substance dispersion (1)>
An ultrasonic disperser (Strain of 23,000 g of sirolimus (Rapamycin, manufactured by SIGMA) dissolved in 20 g of methyl ethyl ketone in 1000 g of a 5% by weight aqueous solution of the anionic surfactant dissolved in 20 mL of methyl ethyl ketone. ) Manufactured by SMT Co., Ltd.).

[Comparative Example 1]
A stainless steel stent (material: SUS316L, outer diameter 1.8 mm, length 15 mm, thickness 80 μm) was prepared for the purpose of comparing the therapeutic effect with a stent having no hydrophilic layer.

[Comparative Example 2]
A stent was prepared according to Examples 2 and 3 of JP2007-97706.

2. Stent evaluation (hydrophilicity evaluation)
Float plate glass (thickness 2 mm), which is the most common transparent plate glass, was prepared, and the surface of the plate glass was hydrophilized by UV / O ₃ treatment for 10 minutes, and then produced in Examples 1 to 10. The sample which apply | coated the 1st layer coating liquid and the hydrophilic layer coating liquid by the same procedure as above was produced, and the contact angle of distilled water was measured at 20 degreeC using Kyowa Interface Science DROP MASTER 500.

[Evaluation of stenosis rate]
As a pathological evaluation, an implantation test of the stent produced in Examples 1 to 10 in a porcine coronary artery was performed. A stent mounted on the balloon of the delivery catheter is inserted from the right carotid artery of the pig and delivered to a site of about 3 mm in diameter of the porcine coronary artery so that the ratio of dilatation balloon diameter / contrast vessel diameter becomes about 1.1 The balloon was expanded by applying a water pressure of 10 atm to the balloon, and the stent was implanted in the porcine coronary artery. There was no problem in the followability and delivery performance of the above-mentioned stent to the bending artery. The stenosis rate after 1 month and 6 months was evaluated. The results of the above evaluation are collectively shown in Table 2.

  From Table 2, Examples 1-10 of this invention form a hydrophilic surface with a small contact angle of water compared with the comparative example 1 which does not have a hydrophilic layer, and the comparative example 2 containing a bioactive substance, and are narrowed It is clear that the rate is small. In Example 11 where a physiologically active substance was contained in the hydrophilic layer, it was found that the stenosis rate was further reduced.

It is a side view of an example of the surface hydrophilized stent in this invention. FIG. 2 is an enlarged cross-sectional view taken along line AA in FIG. 1.

Explanation of symbols

1. 1. Stent (surface hydrophilic treatment) Linear member
3. Hydrophilic layer
21. Outer surface
22. Inner surface
23. Stent body

Claims (6)

  A medical device having at least one layer containing a hydrophilic polymer on a substrate, wherein the hydrophilic polymer contains 30 mol% or more of a structural unit containing a hydrophilic group and silicon, A medical instrument, wherein the contact angle of the water droplet measured on the surface of the medical instrument at 20 ° C is 15 degrees or less.   A medical device, wherein the hydrophilic polymer is crosslinked by hydrolysis and condensation of a hydrolyzable silyl group. The hydrophilic polymer (I) containing the structure represented by the following general formulas (I-1) and (I-2), the general formulas (II-1) and (II-2) Formed by a composition containing either the hydrophilic polymer (II) having a structure represented by formula (III) or the hydrophilic polymer (III) having a structure represented by formulas (III-1) and (III-2) The medical device according to claim 1, wherein the medical device is a layer to be formed.

In the general formulas (I-1) and (I-2), R ^{101 to} R ¹⁰⁸ each independently represents a hydrogen atom or a hydrocarbon group. p represents an integer of 1 to 3, and L ¹⁰¹ and L ¹⁰² each represents a single bond or a polyvalent organic linking group. x and y represent a composition ratio, x represents a number satisfying 0 <x <100 and y represents 0 <y <100. A ¹⁰¹ is —OH, —OR _a , —COR _a , —CO ₂ R _e , —CON (R _a ) (R _b ), —N (R _a ) (R _b ), —NHCOR _d , —NHCO ₂ R _{a, -OCON (R a) (} R b), - NHCON (R a) (R b), - SO 3 R e, -OSO 3 R e, -SO 2 R d, -NHSO 2 R d, -SO ₂ N (R _a ) (R _b ), —N (R _a ) (R _b ) (R _c ), —N (R _a ) (R _b ) (R _c ) (R _g ), —PO ₃ (R _e ) (R _f ), —OPO ₃ (R _e ) (R _f ), or —PO ₃ (R _d ) (R _e ). Here, R _a , R _b and R _c each independently represent a hydrogen atom or a linear, branched or cyclic alkyl group, R _d represents a linear, branched or cyclic alkyl group, R _e and R _f independently represents a hydrogen atom or a linear, branched or cyclic alkyl group, an alkali metal, an alkaline earth metal, or onium, and R _g represents a halogen ion, an inorganic anion, or an organic anion.

In the general formula (II-1) and (II-2), each represent R ²⁰¹ to R ²⁰⁵ independently represent a hydrogen atom or a hydrocarbon group. q represents an integer of 1 to 3, and L ²⁰¹ and L ²⁰² each represents a single bond or a polyvalent organic linking group. A ²⁰¹ represents —OH, —OR _a , —COR _a , —CO ₂ R _e , —CON (R _a ) (R _b ), —N (R _a ) (R _b ), —NHCOR _d , —NHCO ₂ R _{a, -OCON (R a) (} R b), - NHCON (R a) (R b), - SO 3 R e, -OSO 3 R e, -SO 2 R d, -NHSO 2 R d, -SO ₂ N (R _a ) (R _b ), —N (R _a ) (R _b ) (R _c ), —N (R _a ) (R _b ) (R _c ) (R _g ), —PO ₃ (R _e ) (R _f ), —OPO ₃ (R _e ) (R _f ), or —PO ₃ (R _d ) (R _e ). Here, R _a , R _b and R _c each independently represent a hydrogen atom or a linear, branched or cyclic alkyl group, R _d represents a linear, branched or cyclic alkyl group, R _e and R _f independently represents a hydrogen atom or a linear, branched or cyclic alkyl group, an alkali metal, an alkaline earth metal, or onium, and R _g represents a halogen ion, an inorganic anion, or an organic anion.

In general formulas (III-1) and (III-2), R ^{301 to} R ³¹¹ each independently represents a hydrogen atom or a hydrocarbon group. r represents an integer of 1 to 3, and L ^{301 to} L ³⁰³ each represents a single bond or a polyvalent organic linking group. x and y represent a composition ratio, x represents a number satisfying 0 <x <100 and y represents 0 <y <100. A ³⁰¹ represents —OH, —OR _a , —COR _a , —CO ₂ R _e , —CON (R _a ) (R _b ), —N (R _a ) (R _b ), —NHCOR _d , —NHCO ₂ R _{a, -OCON (R a) (} R b), - NHCON (R a) (R b), - SO 3 R e, -OSO 3 R e, -SO 2 R d, -NHSO 2 R d, -SO ₂ N (R _a ) (R _b ), —N (R _a ) (R _b ) (R _c ), —N (R _a ) (R _b ) (R _c ) (R _g ), —PO ₃ (R _e ) (R _f ), —OPO ₃ (R _e ) (R _f ), or —PO ₃ (R _d ) (R _e ). Here, R _a , R _b and R _c each independently represent a hydrogen atom or a linear, branched or cyclic alkyl group, R _d represents a linear, branched or cyclic alkyl group, R _e and R _f independently represents a hydrogen atom or a linear, branched or cyclic alkyl group, an alkali metal, an alkaline earth metal, or onium, and R _g represents a halogen ion, an inorganic anion, or an organic anion. The layer containing the hydrophilic polymer is a layer formed by a composition containing the hydrophilic polymer (IV) or (V) having a structure represented by the following general formula (IV) or (V). The medical instrument according to claim 1.

In general formulas (IV) and (V), R ^{401 to} R ⁴⁰⁴ and R ^{501 to} R ⁵⁰² each independently represent a hydrogen atom or a hydrocarbon group, and R ⁵⁰³ represents a hydrogen atom or a monovalent nonmetallic atomic group. . x, y and z each independently represents an integer of 0 to 2, and L ⁴⁰¹ , L ⁴⁰² and L ⁵⁰¹ each independently represents an atom selected from a carbon atom, a hydrogen atom, an oxygen atom, a nitrogen atom and a sulfur atom. It represents a divalent linking group having three or more types. m and n represent an integer of 3 to 25,000.   The medical device according to any one of claims 1 to 4, comprising a physiologically active substance.   The medical device according to any one of claims 1 to 5, wherein the base material is a stent body, and the medical device is a stent.

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