WO2005111102A1 - Polymer for preventing protein adhesion and composition containing the same - Google Patents

Abstract

[MEANS FOR SOLVING PROBLEMS] A polymer for preventing protein adhesion obtained by copolymerizing a monomer having a specific tertiary amino group and/or a monomer having a specific quaternary ammonium group with a (meth)acrylic ester monomer and a nonionic water-soluble monomer in specific amounts. [EFFECTS] The polymer for preventing protein adhesion, even when used in a low-concentration short-time treatment, has the excellent long-lasting ability to prevent protein from adhering to hard surfaces of, e.g., glasses, ceramics, stainless steel, and plastics, soft surfaces of, e.g., hairs and fibers, gel surfaces, and contact lens surfaces.

Description

 Specification

 TECHNICAL FIELD The present invention relates to a polymer compound for preventing protein adhesion and a composition containing the same.

 The present invention relates to a polymer compound for preventing protein adhesion having an excellent ability to prevent protein adhesion, and a composition containing the same. More specifically, glass, ceramic, stainless steel, plastic, and the like, which are used as materials for medical devices and the like, and there is a concern that the biocompatibility of the material may be impaired by the attachment of biological substances such as proteins. Adhesion to hard surfaces such as skin, soft surfaces such as hair and fibers, and gel surfaces, especially contact lens surfaces, even when treated at low concentration and for a short time, and durable and excellent protein adhesion The present invention relates to a polymer compound for preventing protein adhesion imparting a protective ability and a composition containing the polymer compound.

 Background art

 [0002] Glass, ceramics, ceramics, and the like are used as materials for medical devices and the like, and there is a concern that the biocompatibility of the material may be degraded due to the attachment of a biological substance represented by a protein. Examples include hard surfaces of stainless steel and various plastics, soft surfaces such as hair and fibers, gel surfaces, contact lens surfaces, and the like. In many cases, such substances easily damage the surface when they come into contact with special organic solvents. As surface treating agents for treating these surfaces, products of a water-soluble type are desired. In addition, the surface treatment agent cannot be easily removed with the water or rinsing water that comes into contact with normal use! It is desired to have durability that is as long as possible, and that the good effect can be obtained even with a short-time treatment or a treatment agent with the lowest possible concentration. Further, for applications in which the human body comes into contact, it is desired that safety is considered.

[0003] As a surface treatment agent, a polymer compound containing a tertiary amino group, a detergent composition, an antifouling agent composition, and a cleaning antifouling agent composition have been proposed (for example, Patent Document 1). : See JP-A-2002-256030). Specifically, it is a polymer compound containing a polyoxyalkylene oxide-containing monomer as an essential component, and contains a detergent for contact lenses to prevent contamination of tear-derived proteins. Excellent effect It is what is done. However, in the case of protein stains only, a further effect has been desired with respect to durability such that it remains without being washed off from the coated surface during long-term use. In addition, although it has excellent anti-adhesion properties against various contaminants, it is desired to further prevent protein adhesion by short-time treatment or low-concentration polymer compound solution treatment!

 [0004] As a technique for preventing adhesion of dirt to contact lenses, a polymer compound having a quaternary amine functional group in an amount of 10 to 45 mol% has been proposed (for example, Patent Document 2: JP-T-2000-510186). Gazette). Specifically, compositions and methods for inhibiting the accumulation of proteins in contact lenses have been proposed. However, since the content of the quaternary amine functional group is too high, in order to prevent protein adhesion, which is the object of the present invention, it may be adsorbed on the surface by short-time treatment or treatment with a low-concentration polymer solution. And a function of imparting an excellent protein adhesion prevention ability cannot be obtained.

 [0005] On the other hand, ionic polymer compounds for use in contact lenses have been proposed (see, for example, Patent Document 3: JP-A-54-116947). Specifically, a composition and a method have been proposed which increase the surface moisture by coating the surface of the ionic contour lens with a polymer compound having a charge opposite to that of the surface and having a high water retention ability. ing. However, with regard to the prevention of protein adhesion targeted by the present invention, the function of adsorbing to the surface even by short-time treatment or treatment with a low-concentration polymer compound solution to impart excellent protein adhesion prevention ability. Cannot be obtained.

 [0006] Furthermore, a polymer compound having a cationic derivative of a vinyl polymer has been proposed (Patent Document 4: Japanese Patent Application Laid-Open No. 150014/1993), and lipid dirt adheres by making the lens hydrophilic with the polymer compound. Although difficult compositions and methods have been disclosed, the present invention aims to prevent protein adhesion by adsorbing to the surface even by short-time treatment or treatment with a low-concentration polymer compound solution. The function to be given cannot be obtained.

 [0007] Patent Document 1: Japanese Patent Application Laid-Open No. 2002-256030

 Patent Document 2: JP-T-2000-510186

 Patent Document 3: JP-A-54-116947

Patent Document 4: JP-A-1-50014 Disclosure of the invention

 Problems to be solved by the invention

 [0008] The present invention has been made in view of the above circumstances, and is used as a material for medical devices and the like, and the biocompatibility of the material is poor due to the attachment of a biological substance such as a protein. Excellent protein adherence to hard surfaces such as glass, ceramics, stainless steel, and plastics, soft surfaces such as hair and fibers, gel surfaces, and contact lens surfaces, etc., which may cause danger, even when treated at low concentration and for a short time. An object of the present invention is to provide a polymer compound for preventing protein adhesion, which has an inhibitory ability and has an excellent durability. Furthermore, an antifouling agent composition that is not easily washed away even by rinsing with water and is adsorbed on the target surface and exhibits antifouling properties, a cleaning antifouling composition that has antifouling properties simultaneously with cleaning, and ophthalmic use It is intended to provide compositions and compositions for contact lenses.

 Means for solving the problem

 As a result of intensive studies to achieve the above object, the present inventors have found that a monomer having a specific tertiary amino group and a monomer having Z or a specific quaternary ammonium group, A polymer compound obtained by copolymerizing an acrylic acid ester monomer and a nonionic water-soluble monomer in a specific amount and having a weight average molecular weight of 5,000 to 1,000,000. It has been found that even when the surface and the gel surface are treated at a low concentration for a short time, the gel has a durable protein adhesion preventing ability. As a result of further intensive studies, it was found that the inclusion of the above-mentioned polymer compound in the water-soluble composition allows it to be adsorbed on the target surface even at low concentration and for a short period of time, and has an excellent ability to prevent protein adhesion. The present inventors have found that the copolymer is not washed out in a washing step involving rinsing, and is adsorbed on an object surface as an active ingredient to exhibit antifouling properties, and the present invention has been accomplished.

 Therefore, the present invention is obtained by copolymerizing the following (A), (B) and (C), and has a weight average molecular weight

A polymer compound for preventing protein adhesion of 5,000 to 1,000,000, and an antifouling agent composition, a cleaning antifouling agent composition, an ophthalmic composition, and a contact containing the high molecular compound A composition for a lens is provided.

(A) (A-1) 0.1 to 75% by mass of a monomer having a tertiary amino group represented by the following general formula (1) and Z or (A-2) represented by the following general formula (2) Monomer having a quaternary ammonium group 0 [0011] [Formula 1]

(1)

(Wherein, R ¹ is a hydrogen atom or a methyl group, A is an oxygen atom or NH, RR ³ is independently a hydrogen atom or a linear or branched alkyl group having 14 to 14 carbon atoms, and R ⁴ and R ⁵ are Independently, it represents a linear or branched alkyl group having 1 to 4 carbon atoms, and m is 0, 1 or 2.)

 [Formula 2]

(Wherein, R ⁶ is a hydrogen atom or a methyl group, A is an oxygen atom or NH, R ⁷ and R ⁸ are each independently a hydrogen atom or a linear or branched alkyl group having 14 to 14 carbon atoms, R ⁹ , R ^1Q and R ^{11 each} independently represent a linear or branched alkyl group having 14 to 14 carbon atoms, n is 0, 1 or 2, and X is halogen, OH, 1 / 2SO, HSO, 1 / 3 Indicates PO, HCO or CH CO.)

(B) (meth) acrylic acid ester monomer represented by the following general formula (3) 21-80% by mass CH = C (R ¹² ) COOR ¹³ (3)

(In the formula, R ¹² is a hydrogen atom or a methyl group, and R ¹³ is a linear or branched alkyl group having ¹⁶ carbon atoms.)

 (C) Nonionic water-soluble monomers other than (A) and (B) monomers 0.1 to 78.9% by mass Effect of the Invention

[0013] According to the present invention, there is a concern that the biocompatibility of a material may be deteriorated due to the attachment of a biological substance such as a protein when used as a material for a medical device or the like. Hard surface of steel, stainless steel, plastic etc., soft surface of hair, fiber etc. A polymer compound for preventing protein adhesion, which is durable and has an excellent protein adhesion preventing ability even when treated at a low concentration and for a short time on a gel surface and a contact lens surface, and is useful as an antifouling agent. An antifouling agent composition, a cleaning antifouling agent composition, an ophthalmic composition and a contact lens composition containing the same can be provided.

 BEST MODE FOR CARRYING OUT THE INVENTION

 Hereinafter, the present invention will be described in more detail. The polymer compound of the present invention is obtained by mixing and copolymerizing the monomers (A) and (C) in a specific ratio with respect to the total amount of the monomers (100% by mass). It is. Therefore, the content of the structural unit composed of each monomer in the copolymer of the present invention is the same as the compounding amount of each monomer at the time of copolymerization.

 [0015] The (A) monomer used in the present invention includes (A-1) a monomer having a tertiary amino group represented by the above general formula (1) and Z or (A-2) It has a quaternary ammonium group represented by the formula (2).

Here, in the general formula (1), R ¹ is a hydrogen atom or a methyl group, A is an oxygen atom or NH, R ² and R ³ are each independently a hydrogen atom or a straight chain having 14 carbon atoms. Alternatively, R ⁴ and R ^{5 each} independently represent a linear or branched alkyl group having 14 to 14 carbon atoms, and m is 0, 1 or 2. Examples of the linear or branched alkyl group having 14 to 14 carbon atoms include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, a t-butyl group and an isobutyl group.

In the general formula (2), R ⁶ is a hydrogen atom or a methyl group, A is an oxygen atom or NH, R ⁷ and R ⁸ are independently a hydrogen atom or a carbon atom R ⁹ , R ^1Q and R ^{11 each} independently represent a linear or branched alkyl group having 14 to 14 carbon atoms, n is 0, 1 or 2, and X is , Halogen, OH, 1 / 2SO

 4, HSO

 4, 1 / 3PO

 4, HCO or 2

Indicates CH CO. As a linear or branched alkyl group having 1 to 4 carbon atoms, methyl

3 2

 Group, ethyl group, propyl group, isopropyl group, butyl group, t-butyl group and isobutyl group.

(A-1) More specifically, monomers having a tertiary amino group include dimethylaminoethyl (meth) acrylate (hereinafter, (meth) acryl represents acryl and methacryl), and (meth) (Meth) acrylic acid such as getylaminoethyl acrylate, dipropylaminoethyl (meth) acrylate Dialkylaminoalkyl compounds, dimethylaminoethyl (meth) acrylamide, dimethylalkylaminoalkyl (meth) acrylamidide conjugates and the like are preferred, and dimethylaminoethyl (meth) acrylate, getylamino (meth) acrylate are preferred. Ethyl, dialkylaminoalkyl (meth) acrylates such as dipropylaminoethyl (meth) acrylate, dimethylaminoethyl (meth) acrylamide, dimethylaminopropyl (meth) acrylamide, getylaminopropyl (meth) acrylamide And more preferably dimethylaminoethyl (meth) acrylate, getylaminoethyl (meth) acrylate, and dimethylaminopropyl (meth) acrylamide. And methylaminopropyl (meth) acrylamide.

(A-2) As monomers having a quaternary ammonium group, dimethylaminoethyl methyl chloride (meth) acrylate, dimethylaminoethyl ethyl chloride (meth) acrylate, dimethylamino (meth) acrylate Ethyl ethyl sulfate, dimethylaminoethyl methyl methacrylate (meth) acrylate, dimethylaminoethylethyl methacrylate (meth) acrylate, ethylaminoethyl methyl methacrylate, getylamino methacrylate Ethylethyl chloride, getylaminoethylethyl methacrylate (meth) acrylate, getylaminoethylmethyl phosphate (meth) acrylate, getylaminoethylethyl phosphate (meth) acrylate, dimethylaminopropyl (meth) acrylate ) Acrylamide methyl chloride, dimethylaminopropyl (T) acrylamidoethyl chloride, dimethylaminopropyl (meth) acrylamidoethylsulfate, dimethylaminopropyl (meth) acrylamidomethylphosphoric acid, dimethylaminopropyl (meth) acrylamidoethylphosphoric acid and the like. Among them, dimethylaminoethyl methyl chloride (meth) acrylate, dimethylaminoethylethyl chloride (meth) acrylate, dimethylaminoethylethyl sulphate (meth) acrylate, getylaminoethyl methyl chloride (meth) acrylate, (Meth) acrylic acid ethyl ethyl ethyl chloride, (meth) acrylic acid ethyl ethyl ethyl ethyl sulfate, dimethylaminopropyl (meth) acrylamide methyl chloride, dimethylaminopropyl (meth) acrylamidoethyl chloride, dimethyl Aminopropyl (meth) acrylamidoethyl sulfate is preferred, and dimethylaminoethyl methyl methacrylate, dimethylaminoethyl ethyl methacrylate, Dimethylaminoethylethyl methacrylate) is more preferred.

 [0020] The monomer (A-1) and the monomer (A-2) may be used alone or in combination. These monomers can be used alone or in an appropriate combination of two or more. In the present invention, it is preferable to use one or more (A-1) monomers in view of the ease of preparation and durability of the composition.

 [0021] The content of the monomer (A) is in the following range. (A) If the content of the monomer is too large, the solubility in water is high, so that the performance in the low-concentration treatment and the one-hour treatment with low durability is deteriorated. On the other hand, if the content of the monomer (A) is too small, the monomer (A) does not function as an adsorption site in the polymer compound, and the low-concentration treatment and the single-hour treatment, which have poor durability, cannot be performed. Performance is reduced.

 (A-1) When a monomer having a tertiary amino group is contained, its content is 0.1 to 75% by mass, preferably 2-55% by mass, more preferably 2 to 55% by mass of all monomers. Is 3-35% by mass.

 (A-2) When a monomer having a quaternary ammonium group is contained, its content is 0.1 to 7% by mass, preferably 0.5 to 6% by mass in the whole monomer. %, More preferably 115% by mass.

 [0024] The (B) monomer used in the present invention is a (meth) acrylate ester monomer represented by the following general formula (3).

CH = C (R ¹² ) COOR ¹³ (3)

 2

Here, in the general formula (3), R ¹² is a hydrogen atom or a methyl group, and R ¹³ is a linear or branched alkyl group having 116, preferably 114 carbon atoms. is there.

[0026] More specifically, as the (B) monomer, methyl (meth) acrylate, ethyl (meth) acrylate, propyl (meth) acrylate, isopropyl (meth) acrylate, (meth) Butyl acrylate, t-butyl (meth) acrylate, isobutyl (meth) acrylate, hexyl (meth) acrylate and the like. Of these, methacrylic acid is preferably methyl (meth) acrylate, ethyl (meth) acrylate, propyl (meth) acrylate, isopropyl (meth) acrylate, butyl (meth) acrylate, and t-butyl (meth) acrylate. Methyl acrylate, ethyl methacrylate, propyl methacrylate, isopropyl methacrylate, butyl methacrylate, and t-butyl methacrylate are more preferred. These may be used alone or in an appropriate combination of two or more. [0027] The content of the monomer (B) is 21 to 80% by mass, preferably 22 to 55% by mass, and particularly preferably 23 to 50% by mass based on all the monomers. (B) If the content of the monomer is less than 21% by mass, the ability to prevent protein adhesion by low-concentration treatment and short-time treatment decreases, and if it exceeds 80% by mass, it is difficult to obtain uniform solubility.

 [0028] The (C) monomer used in the present invention is a nonionic water-soluble monomer other than the (A) and (B) monomers. By copolymerizing a nonionic water-soluble monomer other than the monomers (A) and (B), the water solubility of the polymer compound can be improved without lowering the ability to prevent protein adhesion. When a composition containing the polymer compound of the present invention is used, problems such as precipitation of insolubles can be prevented.

 [0029] (C) Monomers include (meth) acrylamide, dimethyl (meth) acrylamide, N-butyl

 2 Pyrrolidone, a saccharide-related group-containing monomer, a polyalkylene oxide group-containing monomer represented by the following general formula (4), and the like.

CH = C (R ¹⁴ ) COO (CHO) R ¹⁵ (4)

 2 p 2p q

(In the formula, R "is a hydrogen atom or a methyl group, R ¹⁵ is a hydrogen atom, an alkyl group having 1 to 14 carbon atoms or a phenyl group. P is an integer of 2 to 4, and q is 2 — 250, and there may be two or more alkylene oxide groups with different p in the molecule.)

Examples of the polyalkylene oxide group-containing monomer represented by the general formula (4) include polyalkylene glycol mono (meth) acrylates, polyethylene glycol polypropylene glycol mono (meth) acrylates, and the like. (Meth) acrylate, methoxy polyethylene glycol mono (meth) acrylate, methoxy polyethylene glycol-propylene glycol mono (meth) acrylate, ethoxy polyethylene glycol (meth) acrylate, ethoxy polyethylene glycol polypropylene glycol mono (meth) acrylate , Such as polyalkylene glycol mono (meth) acrylates, etc., alkoxypolyalkylene glycol mono (meth) acrylates alkoxylated with an alkyl group having 13 carbon atoms Over DOO, Hue Roh alkoxy polyethylene glycol mono (meth) Atari rate, phenoxyethanol polyethylene glycol polypropylene glycol mono (meth) Atari rate, and the like.

[0031] Preferably, the (C) monomer is (meth) acrylamide, N-butyl-2-pyrrolidone, methoxypolyethylene glycol mono (meth) atalylate, and more preferably N-butyl 2 —Methoxypolyethylene glycol with an average number of repetitions of 2 to 25 for pyrrolidone and (CHO)

 twenty four

 No (meta) atarilate. The monomer (C) is not limited to the above compounds, and may be used alone or in combination of two or more.

 [0032] The content of the monomer (C) is 0.1 to 78.9% by mass, preferably 15 to 73% by mass, more preferably 30 to 65% by mass, based on all the monomers. . (C) If the content of the monomer is too small, the water solubility is reduced, and if the content is too large, the adsorptivity to the target surface is poor.

 [0033] The polymer compound of the present invention has a weight average molecular weight of 5,000-1,000,000, preferably <10,000-500,000, and more preferably <10,000-400, 000. If the weight average molecular weight is too small, for example, when used on a gel surface, it will be smaller than its pore size, and if it is too large, the viscosity of the polymer compound solution will be too high, thus limiting the design of the formulation. In the present invention, the weight average molecular weight is gel permeation chromatography, 0.5 mol ZL acetic acid, 0.5 mol ZL sodium acetate in water Z ethanol = 50 Z 50 (νΖν%) solution is used as a mobile phase, and polyethylene glycol is used. It can be obtained as a standard.

 [0034] The method for producing the polymer compound of the present invention is not particularly limited as long as a copolymer obtained by copolymerizing the above (上 記)-(C) monomers can be produced. Examples thereof include solution polymerization, suspension polymerization, and bulk polymerization. Can be polymerized. Industrially, a method based on solution polymerization is preferred, even though radical polymerization based on solution polymerization or suspension polymerization is preferred. In addition, the copolymer of the present invention may be a random copolymer or a block copolymer.

 [0035] In the case of performing polymerization by solution polymerization, examples of the solvent include water, lower alcohols such as methyl alcohol, ethyl alcohol, and isopropyl alcohol; aromatics such as benzene, toluene, xylene, cyclohexane, and hexane; Alternatively, various organic solvents such as heterocyclic compounds, ethyl acetate, acetone, and methyl ethyl ketone can be used. Although the polymerization concentration is not particularly limited, it is usually preferable to carry out the polymerization at 10 to 50% by mass.

[0036] Examples of the polymerization initiator include persulfates such as ammonium persulfate, sodium persulfate, and persulfuric acid potassium, peroxides such as benzoyl peroxide and lauroyl peroxide, cumenehydroxide, and the like. Examples thereof include a peroxide at the mouth such as a peroxide at the mouth, and an azoi conjugate such as azobis isopti-tolyl. Polymerization initiator concentration Is usually preferably 0.1 to 10 mol% based on the total amount of the monomers used. Further, in order to regulate the molecular weight, a chain transfer agent such as an alkyl mercaptan, a polymerization accelerator such as a Lewis acid compound, and a pH adjuster such as phosphoric acid, citric acid, tartaric acid, and lactic acid may be used. The polymerization temperature is appropriately determined depending on the solvent and the polymerization initiator to be used, but usually, the room temperature is preferably 150 ° C.

 [0037] Low molecular weight impurities such as residual monomers contained in the obtained polymer compound can be removed and purified by treatment using activated carbon, ultrafiltration, a dialysis membrane or the like. Examples of activated carbon include commonly used wood, coal, coconut shells and the like activated with chemicals and steam, and the shape of the activated carbon is also powder, crushed, fibrous, etc. Not limited. As the material of the ultrafiltration membrane, polysulfone, polyethersulfone, polyvinylidene difluoride, cellulose acetate, nitrocellulose and the like can be used. The shape may be a flat membrane shape, a hollow fiber shape or the like, but is not particularly limited.

 [0038] The polymer compound for preventing protein adhesion of the present invention is used as a material for medical devices and the like, and the biocompatibility of the material is degraded by the attachment of a biological substance represented by a protein. It has excellent anti-protein-adhesion ability even at low concentration for a single hour on hard surfaces such as glass, ceramics, stainless steel, and plastic, soft surfaces such as hair and fibers, gel surfaces, and contact lens surfaces. Have. The polymer compound is adsorbed on these surfaces to impart antifouling properties, and is not easily washed away by rinsing with water, so that it can be used as an antifouling composition. In addition, the object can be washed and imparted with antifouling properties. Even in a washing step involving rinsing with water, the polymer compound is not washed away by the rinsing, but is adsorbed on the object surface. Since the antifouling agent exhibits antifouling properties, it can be used for a cleaning antifouling agent composition.

Further, the composition containing the polymer compound for preventing protein adhesion of the present invention is suitable as an ophthalmic composition because of having the above-mentioned properties, and is particularly suitable as a contact lens. Examples of the ophthalmic composition include general eye drops, antibacterial eye drops, artificial tears, contact lens mounting solutions, eyewashes, and the like. Specific examples of the contact lens composition include a treatment solution for a contact lens, a cleaning solution, a preservative solution, a cleaning preservative solution, a cleaning disinfecting solution, and the like. [0040] The content of the polymer compound of the present invention in each of the above compositions is not particularly limited, but is usually 0.0001 to 20% by mass, preferably 0.001% by mass based on the whole of each composition. One 10% by mass, more preferably 0.005-5% by mass. If the content of the polymer compound is too small, its function may not be sufficiently exhibited, and if it is too large, there may be a limitation in formulation design.

 When the polymer compound of the present invention is contained in various compositions, an aionic, cationic, nonionic or amphoteric low-molecular-weight surfactant may be used alone or in accordance with the intended use. Two or more kinds may be used in combination. Examples of such low molecular weight surfactants include alkylbenzene sulfonate, alkyl polyoxyethylene sulfate, alkyl polyoxyethylene ether, fatty acid diethanolamide, N alkylene betaine, polyoxyethylene hydrogenated castor oil 60 ( For example, polyoxyethylene oxocystearate tridalicelide such as HCO-60, manufactured by Nippon Surfatatanto Kogyo Co., Ltd., and polyoxymonooleate polyoxylates, such as polysoribate 80 (for example, TO 10M, manufactured by Nippon Surfatatanto Kogyo Co., Ltd.). Ethylene sonorevitan, polyoxyethylene polyoxypropylene block polymer, poloxamine (for example, TETRONIC1107, BASF Japan Ltd.) and the like.

 [0042] In addition to the above-mentioned components, various compositions may include one kind of disinfectant, preservative, enzyme, buffer, stabilizer, isotonic sizing agent, solubilizer, freshener, thickener, and the like. They may be used alone or in combination of two or more.

[0043] Specifically, examples of the disinfectant include polyhexamethylene biguanide hydrochloride, Shiridani polydrodium, and the like. As preservatives, Shiridani benzalco-pam, Shiridani cetyl pyrididium, sorbic acid, potassium sorbate, methyl noroxybenzoate, ethyl parahydroxybenzoate, propyl nonoxybenzoate, propyloxybenzoate Butyl and the like. Enzymes include trypsin, chymotrypsin, pandaleatin, papain, colavenase, promelain, aminopeptidase, aspergillus peptidase, pronase E, dispase, subtilisin A, subtilisin B, lipase, dalcosidase, mutanase, α-amylase, dextra And the like. Buffers include boric acid, borax, trometamol, sodium dihydrogen phosphate, disodium hydrogen phosphate, citric acid, sodium citrate, sodium hydrogen carbonate, sodium carbonate, potassium L-aspartate, epsilon-aminocapri Acid, sodium glutamate and the like. Α-cyclodextrin, Sodium edetate, sodium bisulfite, sodium thiosulfate and the like. Examples of the isotonic sizing agent include aminoethylsulfonic acid, potassium sulphite, sodium chloride, sulphite calcium, glycerin, glucose, D-mantol and the like. Examples of solubilizers include ethanol, urea, propylene glycol, polyethylene glycol such as Magrogol 4000, and monoethanolamine. Examples of fresheners include fennel oil, dl camphor, gerol, heart-strength oil, bergamot oil, d-borneol, 1 menthol, eucalyptus oil and the like. Examples of the thickener include sodium chondroitin sulfate, hyaluronic acid and salts thereof, dextran 70, hydroxycellulose, polyvinyl alcohol, polyvinyl pyrrolidone and the like. If necessary, a lower alcohol, an antibacterial agent, a dye, a fragrance and the like can be used alone or in an appropriate combination of two or more.

[0044] In particular, the composition containing the polymer compound of the present invention is used as a material for medical devices and the like, and the biocompatibility of the material is deteriorated due to the attachment of a biological substance represented by a protein. When used on hard surfaces such as glass, ceramics, stainless steel, and plastics, soft surfaces such as hair and fibers, gel surfaces, and contact lens surfaces that may cause danger, a water-soluble polymer compound may be added. May be preferred. In particular, when used on the surface of a contact lens, the combination of the polymer compound of the present invention and a water-soluble polymer compound reduces friction during scrubbing, for example, and better prevents damage to the object. be able to.

 [0045] Examples of the water-soluble polymer compound include cellulosic polymer compounds such as hydroxycellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, and methylcellulose; and polybutyl such as polybutyl alcohol, polybutylpyrrolidone, and carboxybutyl polymer. Examples include mucopolysaccharides such as a series polymer compound, sodium chondroitin sulfate, and hyaluronic acid, polyethylene glycol, and dextran. Among these, preferred water-soluble high-molecular compounds are cellulose-based polymer compounds, polyvinyl-based polymer compounds, polyethylene render glycols, and hyaluronic acid, and particularly preferred compounds are hydroxypropyl methinoresenolerose, hydroxyethenoresenorelose, and polyvinyl alcohol. Noreanolone, polyvinylinolepyrrolidone, polyethylene glycol and hyaluronic acid.

[0046] The amount of the water-soluble polymer compound to be added is not particularly limited! 0. for the entire Narubutsu 0001- 20 mass _^0/0, preferably from 0.5 001 10 mass _^0/0, more rather preferably is 0.5 005- 5 wt%. If the amount of the water-soluble polymer compound is too small, the object may be damaged due to friction when the target surface is scrubbed.If the amount is too large, the viscosity becomes too high and there is a restriction in the formulation design. There are cases.

[0047] The dosage form, preparation method, and usage method of each composition of the present invention are not particularly limited, and each composition can be prepared as a normal dosage form according to a conventional method of each dosage form. By using the usual amount of the mold in the usual way of use, excellent antifouling property and cleaning antifouling property can be exhibited.

 [0048] When the above-mentioned various compositions are prepared by blending the polymer compound of the present invention, when prepared as an aqueous composition, an antifouling agent imparting excellent antifouling properties even after rinsing with water after surface treatment. In the washing step with water, the above-mentioned polymer compound is not desorbed by rinsing, but is adsorbed on the target surface as an active ingredient to give a cleantable antifouling agent composition capable of imparting excellent antifouling properties. Can be

 Example

 Hereinafter, the present invention will be described in detail with reference to Examples and Comparative Examples, but the present invention is not limited to the following Examples.

 [Example 1]

 200 g of ethanol was charged into a separable flask equipped with a cooling reflux tube, a dropping funnel, a thermometer, a nitrogen inlet tube and a stirrer, and nitrogen gas was introduced with stirring, heated to 78 ° C, and dimethylaminoethyl methacrylate (hereinafter referred to as dimethylaminoethyl methacrylate). , DM) 40. lg, methyl methacrylate (hereinafter abbreviated as MMA) 44.7 g, bulpyrrolidone (hereinafter abbreviated as VP) 65.2 g (DM content in total monomer = 27% by mass, MMA content in all monomers = 30% by mass, VP content in all monomers = 43% by mass), and a mixed solution of 35 g of ethanol and 2,2- (azobis (2-methylbutymouth-tolyl)) A mixed solution of 0.78 g and 115 g of ethanol was continuously calored over 3 hours, and further heated for 3 hours to obtain a polymer compound (copolymer) of Example 1 having the composition shown in Table 1. .

 [Example 2-25]

In Example 1 above, the types and blending ratios of the monomers were changed so that the compositions shown in Table 1 were obtained. Except for the above, the polymer of Examples 2 to 25 having the composition shown in Table 1 was obtained in the same manner as in Example 1 above.

 [Example 26]

120 g of ethanol was charged into a separable flask equipped with a cooling reflux tube, a dropping funnel, a thermometer, a nitrogen inlet tube and a stirrer, and nitrogen gas was introduced with stirring to adjust the internal temperature to 78. Heat calorie to C, DM11.5g, MMA25.7g, VP42.4g, methoxypolyethylene glycol = monomethyl methacrylate (polyethylene average = 9) (hereinafter abbreviated as M-90G) 10.3g (total single amount) DM content in body = 12.8% by weight, MMA content in all monomers = 28.6% by weight, VP content in all monomers = 47.1% by weight, M in all monomers 90G = 11. a mixed solution of 5 mass _^0/0) and ethanol 41 g, 2, 2- (Azobisu (2 Mechirubuchi port - tolyl).) 0. 71 g and ethanol 49 continuously 2 and mixed solution of lg It was added over a period of time, and further heated for 4 hours to carry out a polymerization reaction to obtain a copolymer. At the same time, ion-exchanged water was added so that the solid content of the copolymer was 2% by mass, and at the same time, an aqueous solution of hydrochloric acid of 1 mol% L was added to adjust the pH to 6, and a regenerated cellulose dialysis tube (UC36-32-100; Viskase Companies, Inc.) and dialyzed for 1 week while replacing the ion-exchanged water. The aqueous solution containing the polymer compound in the tube was dried using a freeze dryer to obtain a polymer compound (purified copolymer) of Example 26 having the composition shown in Table 3.

 [Example 27-62]

 In Example 26 above, except that the kind and the mixing ratio of the monomers were changed so as to obtain the composition shown in Table 3, the composition of Examples 27 to 62 having the composition shown in Table 3 was obtained in the same manner as in Example 26. A molecular compound was obtained.

 [Comparative Examples 1 and 2]

 The following commercially available polymer compounds were used as Comparative Examples 1 and 2.

 Comparative Example 1: Polyvinylpyrrolidone (Polyvinylpyrrolidone K90): BASF Corporation Comparative Example 2: Polyacrylic acid (Carbopol 934P): Noveon

 [Comparative Examples 3-9]

In Comparative Example 3-9 having the composition shown in Table 2, the same method as in Example 1 was used, except that the types and the proportions of the monomers were changed so as to obtain the composition shown in Table 2. Minute A child compound was obtained.

 For the polymer compounds of Example 125 and Comparative Example 119, the antifouling property 1, the antifouling property 2 and the antifouling property 3 in a 0.05% by mass aqueous solution were evaluated according to the following methods. went. Regarding the evaluation of durability, the copolymer of Example 125 above was evaluated with a 0.1% by mass aqueous solution, and that of Comparative Example 119 with a 1.0% by mass aqueous solution according to the following method. went. Further, with respect to the polymer compounds of Examples 26 to 62 and Comparative Example 19, a 0.05% by mass aqueous solution was used.

 The antifouling property of 4, and detergency were evaluated according to the following methods. The results are shown in Table 1-4.

 <Evaluation method for antifouling property 1>

 A stainless plate (10 cm × 10 cm) was immersed in 500 mL of a 0.05% by mass polymer solution or dispersion for 1 hour at room temperature. Remove the stainless steel plate, rinse with ion-exchanged water, absorb moisture with clean soft paper, immerse the stainless steel plate in a solution of 0.60 g of fibrinogen, a kind of protein, in 500 mL of ion-exchanged water, The mixture was heated and shaken at 30 ° C for 1 hour. The stainless steel plate was removed and water was absorbed with clean soft paper. The stainless plate was stained with fibrinogen attached to the stainless plate using a ninhydrin indicator, and the state of color development was evaluated according to the following evaluation criteria.

 <Evaluation criteria>

 5: Does not stain at all (corresponds to the colored state when using a ninhydrin indicator without contacting the stainless steel plate with the fibrinogen solution)

 4: hardly stained

 3: Slightly stained

 2: Dyed considerably

 1: Intense staining (corresponds to the colored state when a stainless steel plate is not treated with a polymer compound solution but is brought into contact with a fibrinogen solution and a -hydrin indicator is used)

<Evaluation method of antifouling property 2>

EMAA (ethylene methacrylic acid polymer) resin (10 cmX IOcm) (Mitsui DuPont Polychemical Co., Ltd.) concentration. It was immersed in 500 mL of a 0.05% by mass polymer solution or dispersion at room temperature for 1 hour. Take out the EMAA fat and rinse with ion exchanged water, clean and soft Egg white lysozyme solution (a type of protein) made by absorbing and absorbing moisture with paper (manufactured by Wako Pure Chemical Industries, Ltd.)

EMAA resin was immersed in a solution of 0.60 g in 500 mL of ion-exchanged water, and heated and shaken at 30 ° C for 1 hour. The EMAA 榭 fat was removed and water was absorbed with clean soft paper. This EMAA resin was stained for lysozyme attached to the EMAA resin using a ninhydrin indicator, and the state of color development was evaluated according to the following evaluation criteria.

[0060] <Evaluation criteria>

 5: Not stained at all (equivalent to colored state when EMAA fat is not brought into contact with egg white lysozyme solution and ninhydrin indicator is used)

 4: hardly stained

 3: Slightly stained

 2: Dyed considerably

 1: Intense staining (equivalent to the colored state when EMAA 榭 fat is not treated with a polymer compound solution but is brought into contact with an egg white lysozyme solution and a -hydrin indicator is used)

 <Evaluation method for antifouling property 3>

 In the above method for evaluating antifouling property 2, EMAA resin was replaced with a soft contact lens [1DAY ACUVUE (manufactured by Johnson & Johnson Co.)], and 0.05% by mass of Eris mouth was used as a lysozyme stain. The egg white lysozyme adhered to the soft contact lens was stained in the same manner as in the evaluation method of the antifouling property 2 except that the aqueous solution of syn was used, and the state of color development was evaluated according to the following evaluation criteria.

 [0062] <Evaluation criteria>

 5: Does not stain at all ヽ (Equivalent to the colored state when a soft contact lens is not in contact with the egg white lysozyme solution and an aqueous solution of erythrocyte is used V)

 4: hardly stained

 3: Slightly stained

 2: Pretty dyed

 1: Intense staining (corresponds to the colored state when using a solution of erythrocycin in contact with an egg white lysozyme solution without treating the soft contact lens with a polymer compound solution)

<Durability Evaluation Method> The soft contact lens [1DAY ACUVUE (manufactured by Johnson & Johnson Co., Ltd.)] was added to the polymer compound solution of Example 125 and Comparative Example 119 (the polymer compound of Example 125). 1% by mass aqueous solution, Comparative Example 11: High molecular weight compound of 1.0 1.0% by mass aqueous solution) 50 OmU, and immersed at room temperature for 1 hour. Remove the soft contact lens, rinse with ion-exchanged water, absorb the moisture with clean soft paper, and dissolve 0.60 g of egg white lysozyme solution (a product of Wako Pure Chemical Industries, Ltd.) in 500 mL of ion-exchanged water. After immersing the soft contact lens in the solution, the mixture was heated and shaken at 30 ° C for 15 hours and 30 hours, respectively. I took out the soft contact lens and absorbed the moisture with clean soft paper. For this soft contact lens, lysozyme attached to the lens was stained with a ninhydrin indicator, and the state of color development was evaluated according to the following evaluation criteria.

[0064] <Evaluation criteria>

 5: No staining at all (corresponds to the colored state when using a ninhydrin indicator without contacting the soft contact lens with the egg white lysozyme solution)

 4: hardly stained

 3: Slightly stained

 2: Pretty dyed

 1: Intense staining (corresponds to the colored state when a soft contact lens is not treated with a polymer compound solution but is in contact with an egg white lysozyme solution and a -hydrin indicator is used)

<Evaluation method for antifouling property 4>

The soft contact lens [1DAY ACUVUE (manufactured by Johnson & Johnson Co., Ltd.)] was used as the polymer compound solution of the above Examples 26-62 and Comparative Example 119 (polymer compound concentration: 0.05% by mass, (0.9% by mass of sodium) in 4 mL at room temperature for 4 hours. The soft contact lens was taken out, rinsed with ion-exchanged water, and wiped clean and soft with paper. The soft contact lenses, egg white (manufactured by Wako Pure Chemical Co.) Lysozyme 0.12 mass _^0/0, bovine blood Kiyoshi albumin 0.388 mass _^0/0 (fraction V, Nacalai Tester Co.), .gamma. globulin 0.161 mass _^0/0 (bovine, Cohn F- 2, Nacalai tester Co.), egg white were mixed Shioi匕sodium 0.9 wt% and disodium hydrogen phosphate 0.045 mass _^0/0 It was immersed in 2 mL of lysozyme solution and heated and shaken at 37 ° C for 1 hour. Take out the soft contact lens, clean and soft Moistened paper with a wet paper. With respect to this soft contact lens, a protein attached to the lens was stained with a ninhydrin indicator, and the state of color development was evaluated according to the following evaluation criteria.

 [0066] <Evaluation criteria>

 5: No staining at all (corresponds to the colored state when using a ninhydrin indicator without contacting the soft contact lens with the egg white lysozyme solution)

 4: hardly stained

 3: Slightly stained

 2: Pretty dyed

 1: Intense staining (corresponds to the colored state when a soft contact lens is not treated with a polymer compound solution but is in contact with an egg white lysozyme solution and a -hydrin indicator is used)

 <Evaluation Method for Detergency>

A soft contact lens [1DAY ACUVUE (manufactured by Johnson & Johnson)] was rinsed with ion-exchanged water, and moisture was absorbed with clean soft paper. 0.12% by mass of egg white lysozyme (manufactured by Wako Pure Chemical Industries, Ltd.), 0.388% by mass of bovine serum albumin ⁰ / "fraction V, manufactured by Nakarai Testa Co., Ltd." 161 mass _{^{0/0 (bovine, cohn F-}} 2, Nacalai tester Co.), dipped in egg white lysozyme solution 2mL were mixed Shioi匕sodium 0.9 wt% and disodium hydrogen 0.045 wt% phosphoric acid After heating and shaking for 1 hour at 37 ° C, the soft contact lens was taken out, the moisture was absorbed with clean soft paper, and then the polymer solution of Examples 26-62 and Comparative Example 19-19 was obtained. (polymerized compound concentration 0.05 wt%, Shioi匕sodium 0.9 mass _^0/0) were the scrubbed with 3 mL Dzu' dropwise per contact lens one side. this soft contact lenses, ninhydrin finger Protein attached to the lens using an indicator Stained, and evaluate the state of the color in accordance with the following evaluation criteria.

 <Evaluation criteria>

 5: No staining (equivalent to almost all protein stains on used soft contact lenses have been washed)

4: hardly stained 3: Slightly stain

2: fairly stained

1: Intense staining (corresponds to almost no removal of protein stains from used contact lenses)

2]

 Antifouling properties Antifouling properties Antifouling properties

 Durability Polymer compound composition Weight average 1 2 3

(Quality%) Molecular weight E AA S: 7 Contact 30 15 Stainless steel

 Resin Time Time Polyvinylpyrrolidone

 1 1 1 1 1 1 1 (K-90)

 2 Polyacrinoleic acid 1 1 1 1 1

3 DM / AA / MMA-25 / 70/5 95,000 2 1 1 1 1

4 D / AA / HE A = 0.1 / 35 / 64.9 70,000 2 1 1 1 1 Ratio

Comparison 5 MAA / AA = 40/60 78,000 1 1 1 1 1 Example

 6 M- 230G / AA-20 / 80 89,000 2 1 1 1 1

7 DMC / EMA / VP = 0.8 / 22 / 77.2 2,000 2 1 2 1 1

8 DMC / iVlAA / MA / VP-0.1 / 20/2 / 77.9 34,000 1 1 1 1 1

9 DMC / MAA / M— 230G = 15/82/3 22,000 1 1 1 1 1

^ ¾0071 [Table 4]

[Examples 63-66, Comparative Examples 10, 11]

 An antifouling agent composition and an antifouling cleaning composition were prepared according to a conventional method according to the compositions shown in Table 5. The obtained antifouling agent composition and antifouling detergent composition were subjected to the above-mentioned method for evaluating antifouling property 3 by adding 0.05% by mass of a polymer compound solution or dispersion to the antifouling agent composition and the antifouling composition. Evaluation was made in the same manner except that the composition was changed to a soil cleaning composition. The results are shown in Table 5.

[Table 5]

Example Comparative Example Composition (% by mass)

 63 64 65 66 10 11 Example 1 0.03--Example 2 0.03-Polymer-Example 3-0.03-Compound Example 55-0.03

 Comparative Example 1 ― L0 Comparative Example 2 ― ― 1.0 Polyhexamethylene biguanide hydrochloride 0.0001 0.00007 0.0001 0.0001 ― Polydmium chloride 0.011 ― 0.011

10% benzalkonium chloride solution-0-1-

 α-sig σ dextrin ― 0.1-Subtilisin A 0.005 0.005 0.005 0.005 0.005 0.005 Polyoxyethylene hydrogenated castor oil 60 0.1 0-1 ― 0-1 Polysolute 80 0.05 ― ― 0.05

TETRONIC1107 0.3 0.3 0-3 0.3 0.3 0.3 Newpol PE68 0.5 0.5 0.5 0.5 0.5 0.5 Boric acid 0.3 ― One 0.3 0.3 Borax 0,05 0.05 0.05 Tromethamore 0.3 ― 0.3 Sodium dihydrogen phosphate (dihydrate) ― 0.08 ― Disodium hydrogen phosphate (decahydrate) 0.5-Cuenoic acid 0.05 0.05 0.05 0.05 0.05 0.05 Sodium edetate 0.01 0.01 0.01 0.01 0.01 0.01 Sodium chloride 0.1--0.1 0.1 Glycerin 0.1 0.1 0.1 Manni 1, 1 0.1-

 Propylene glycol 0.2 0.2 0.2 0.2 0.2 0-2

1-menthol, 0.002 0.002 0.002 0.002 0.002 0.002

Potassium L-aspartate 0.25 0.25 0.25 0.25 0.25 0.25 aminoethylsulfonic acid 1.0 1.0 1.0 1.0 1.0 1.0

Sodium L-glutamate 0.1 0.1 0.1 0.1 0Λ 0.1 Dilute hydrochloric acid qs

 Sodium hydroxide appropriate amount

 Purified water lance

 100

 Η 7

 3 5 5 5 5 1 1

 30 hours 5 5 5 5 1 1 Durability

 15 hours 5 5 5 5 1 1

The abbreviations in the table are shown below.

 • DM: Dimethylaminoethyl methacrylate

• DMA: dimethylaminoethyl acrylate • DMAPAA: Dimethylaminopropyl atalinoleamide

 • DMAPMA: dimethylaminopropyl methacrylamide

 • DMC: dimethylaminoethyl methyl methacrylate chloride

 • MMA: Methyl methacrylate

 • EMA: Ethyl methacrylate

 • BMA: n-butyl methacrylate

 • t-BMA: t-butyl methacrylate

• VP: Vininolepyrrolidone

 • M-90G: Methoxypolyethylene glycol monomethacrylate (methoxypolyethylene glycol methacrylate) (polyethylene average = 9) (Shin-Nakamura Chemical Co., Ltd.)

• M-230G: Methoxy polyethylene glycol monomethacrylate (methoxypolyethylene glycol methacrylate) (polyethylene average = 23)

• HEMA: hydroxyethyl methacrylate

• AA: acrylic acid

 MAA: Methacryloleic acid

 • TETORONIC 1107: Poloxamine (manufactured by BASF Japan Ltd.)

• New Pole PE68: Pull mouth nick type nonionic surfactant (manufactured by Sanyo Chemical Co., Ltd.)

The scope of the claims

 [1] A polymer compound for preventing protein adhesion, which is obtained by copolymerizing the following (A), (B) and (C) and has a weight average molecular weight of 5,000 to 1,000,000, 000.

 (A) (A-1) 0.1 to 75% by mass of a monomer having a tertiary amino group represented by the following general formula (1) and Z or (A-2) represented by the following general formula (2) 0.1 to 7% by mass of a monomer having a quaternary ammonium group

 [Chemical 1]

(Wherein, R ¹ is a hydrogen atom or a methyl group, A is an oxygen atom or NH, RR ³ is independently a hydrogen atom or a linear or branched alkyl group having 14 to 14 carbon atoms, and R ⁴ and R ⁵ are Independently, it represents a linear or branched alkyl group having 1 to 4 carbon atoms, and m is 0, 1 or 2.)

 [Formula 2]

(Wherein, R ⁶ is a hydrogen atom or a methyl group, A is an oxygen atom or NH, R ⁷ and R ⁸ are each independently a hydrogen atom or a linear or branched alkyl group having 14 to 14 carbon atoms, R ⁹ , R ^1Q and R ^{11 each} independently represent a linear or branched alkyl group having 14 to 14 carbon atoms, n is 0, 1 or 2, and X is halogen, OH, 1 / 2SO, HSO, 1 / 3 Indicates PO, HCO or CH CO.)

 4 4 4 2 3 2

(B) (meth) acrylic acid ester monomer represented by the following general formula (3) 21-80% by mass CH = C (R ¹² ) COOR ¹³ (3)

 2

(Wherein, R ¹² is a hydrogen atom or a methyl group, and R ¹³ is a linear or branched chain having ¹⁶ carbon atoms. Is an alkyl group. )

 (C) Nonionic water-soluble monomers other than (A) and (B) monomers 0.1—78.9 mass%

[2] An antifouling composition comprising the polymer compound according to claim 1.

[3] A cleaning antifouling composition comprising the polymer compound according to claim 1.

 [4] An ophthalmic composition comprising the polymer compound according to claim 1.

[5] A composition for a contact lens, comprising the polymer compound according to claim 1.

Claims

[Summary] (A) Monomer represented by (1) and monomer represented by Z or (2)

 [Formula 1]

(R ¹ is hydrogen or methyl group, A is oxygen or NH,

R ³ is hydrogen or an alkyl group, R ⁴ and R ⁵ are alkyl groups)

[Formula 2]

(R ⁶ is hydrogen or methyl group, A is oxygen or NH, RR ⁸ is hydrogen or alkyl group, R ⁹ , R ^w and R ¹¹ are alkyl groups, n is 0, 1 or 2, X is halogen)

 (B) the monomer represented by (3)

CH = C (R ¹² ) COOR ¹³ (3)

 2

(R ¹² is hydrogen or methyl group, R ¹³ is alkyl group)

 (C) Nonionic water-soluble monomer

And a polymer compound for preventing protein adhesion.

[Effect] Durable and excellent protein adhesion to hard surfaces such as glass, ceramics, stainless steel, plastics, etc., soft surfaces such as hair and fibers, gel surfaces and contact lens surfaces even at low concentration and for a short time. A polymer compound for preventing protein adhesion having an inhibitory ability, and containing the same A composition comprising: [Selection diagram] None