WO2005111102A9 - 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 of polymer compound for preventing protein adhesion and composition containing the same

 [0001] The present invention relates to a protein adhesion-preventing polymer having excellent protein adhesion-preventing ability, and a composition comprising the same. More specifically, glass, ceramic, stainless steel, plastic, which is used as a material for medical devices, etc., and is feared to deteriorate the biocompatibility of the material due to adherence of biological substances such as proteins. It adheres to hard surfaces such as hair, soft surfaces such as hair and fibers, and gel surfaces, especially contact lens surfaces, even with low concentration and short-time treatment, and has excellent and durable protein adhesion. The present invention relates to a polymer compound for preventing protein adhesion that imparts a preventive ability and a composition containing the polymer compound.

 Background art

 [0002] It is used as a material for medical devices and the like, and there is a concern that the biocompatibility of the material may deteriorate due to the adhesion of biological materials such as proteins. Examples thereof include hard surfaces such as stainless steel and various plastics, soft surfaces such as hair and fibers, gel surfaces, and contact lens surfaces. Many of these are easily damaged by contact with special organic solvents. As a surface treating agent for treating these surfaces, water-soluble type products are desired. In addition, the surface treatment agent can be easily removed with water or rinsing water that comes into contact with it by normal use! There is a demand for a material that has such durability and can be used for a short period of time or a treatment agent with a concentration as low as possible. Furthermore, for applications where the human body comes into contact, it is desirable to consider safety.

[0003] As surface treatment agents, polymer compounds containing tertiary amino groups, cleaning compositions, antifouling compositions, and detersive antifouling compositions have been proposed (for example, Patent Document 1). : Japanese Patent Laid-Open No. 20 02-256030). Specifically, it is a polymer compound that has a polyoxyalkylene oxide-containing monomer as an essential component. By containing it in a contact lens cleaning agent, it prevents contamination of tear-derived proteins. Excellent effect It is what However, when it is limited to protein stains, there has been a demand for a further effect with respect to durability that remains without being washed away from the coated surface during long-term use. In addition, although it has excellent anti-adhesion properties against various pollutants, further effects are desired for the prevention of protein adhesion by short-time treatment or low concentration polymer compound solution treatment!

 [0004] Further, as a technique for preventing the adhesion of dirt to contact lenses, a polymer compound having 10 to 45 mol% of a quaternary amine functional group has been proposed (for example, Patent Document 2: Special Table 2000-510 186). (See the publication). Specifically, compositions and methods that inhibit protein accumulation in contact lenses have been proposed. However, since the content of the quaternary amine functional group is too high, it is adsorbed on the surface depending on the short-time treatment or the low-concentration polymer compound solution treatment with respect to the protein adhesion prevention targeted by the present invention. The ability to impart excellent protein adhesion prevention capability is not obtained.

 [0005] On the other hand, a polymer compound having an ionic property for use as a contact lens has been proposed (for example, see Patent Document 3: Japanese Patent Laid-Open No. 54-116947). Specifically, compositions and methods have been proposed in which the surface of an ionic outer lens is mainly coated with a polymer compound having a charge opposite to that of the surface and having a high water retention ability, thereby increasing the surface moisture. ing. However, with regard to the prevention of protein adhesion targeted by the present invention, the function of adsorbing to the surface and imparting excellent protein adhesion prevention ability even by treatment for a short time or treatment with a high molecular compound solution at a low concentration. Cannot be obtained.

 [0006] Further, a polymer compound having a cationic derivative of a vinyl polymer has been proposed (see Patent Document 4: Japanese Patent Laid-Open No. 150014), and lipid stains are adhered by hydrophilizing the lens with the polymer compound. Although difficult compositions and methods have been disclosed, regarding the prevention of protein adhesion targeted by the present invention, excellent adhesion prevention by adsorbing to the surface even by short-time treatment or low concentration polymer compound solution treatment is possible. The function to be granted cannot be obtained.

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

 Patent Document 2: Japanese Translation of Special Publication 2000-510186

 Patent Document 3: Japanese Patent Laid-Open No. 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 adherence of a biological substance such as protein. Excellent protein adhesion even with low concentration and short-time treatment on hard surfaces such as glass, ceramic, stainless steel, plastic, etc., soft surfaces such as hair and fibers, gel surfaces, contact lens surfaces, etc. An object of the present invention is to provide a protein adhesion-preventing polymer compound that has a preventive ability and is excellent in durability. Furthermore, an antifouling composition that is not easily washed away even by rinsing with water and that adsorbs on the target surface and exhibits antifouling properties, a decontaminating antifouling composition that has antifouling properties simultaneously with cleaning, and ophthalmic use It is an object to provide a composition and a composition for contact lenses.

 Means for solving the problem

 As a result of intensive investigations to achieve the above object, the present inventor has found that a monomer having a specific tertiary amino group and a monomer having Z or a specific quaternary ammonium group, and (meth) Polymeric compound strength obtained by copolymerizing acrylate monomer and nonionic water-soluble monomer in a specific amount, and having a weight average molecular weight of 5,000—1,000,000. It was found that the surface and gel surface have a durable ability to prevent protein adhesion even when treated at a low concentration for a short time. As a result of further intensive studies, by incorporating the above-mentioned polymer compound in the water-soluble composition, it has excellent protein adhesion preventing ability to be adsorbed on the target surface even at low concentration and for a short time treatment. It has been found that the copolymer is not washed away in a washing step involving rinsing and is adsorbed on the target surface as an active ingredient to exhibit antifouling properties, and the present invention has been made.

 [0010] Accordingly, the present invention comprises the following (A), (B) and (C) copolymerized, and has a weight average molecular weight.

5,000—1,000,000 protein adhesion-preventing polymer compound, and antifouling agent composition, cleansing antifouling agent composition, ophthalmic composition and contact comprising this high-molecular compound A lens composition is provided.

(A) (A-1) Monomer having tertiary amino group represented by the following general formula (1) 0.1-75% by mass and Z or (A-2) represented by the following general formula (2) Monomers with quaternary ammonium groups 0 [0011] [Chemical 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 1 to 14 carbon atoms, 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.

 [Chemical 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 independently a hydrogen atom or a linear or branched alkyl group having 1 to 14 carbon atoms, R ⁹ , R ^1Q and R ¹¹ independently represent a linear or branched alkyl group having 1 to 4 carbon atoms, n is 0, 1 or 2, X is halogen, OH, 1 / 2SO, HSO, 1 / (Indicates 3PO, HCO or CHCO)

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

(Wherein R ¹² is a hydrogen atom or a methyl group, and R ¹³ is a linear or branched alkyl group having 11 to 16 carbon atoms.)

 (C) (A), (B) Nonionic water-soluble monomers other than monomers 0.1—78.9% by mass of the invention

[0013] According to the present invention, a glass or ceramic that is used as a material for a medical device or the like and is concerned that the biocompatibility of the material is deteriorated due to adhesion of a biological substance such as protein. , Hard surfaces such as stainless steel and plastic, soft surfaces such as hair and fibers , A polymer compound for preventing protein adhesion, which is durable and excellent in protein adhesion prevention, and useful as an antifouling agent, even on a gel surface and contact lens surface even at low concentration and for a short time. An antifouling agent composition, a detersive antifouling agent composition, an ophthalmic composition and a contact lens composition containing the same can be provided.

 BEST MODE FOR CARRYING OUT THE INVENTION

 [0014] Hereinafter, the present invention will be described in more detail. The polymer compound of the present invention is obtained by blending the above monomers (A)-(C) with a specific proportion of each monomer with respect to the total monomer content (100% by mass) and copolymerizing them. 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 blending amount of each monomer at the time of copolymerization.

 [0015] The monomer (A) 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) the above general 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 independently a hydrogen atom or a straight chain having 1 to 4 carbon atoms. Alternatively, a branched alkyl group, R ⁴ and R ⁵ independently represent a linear or branched alkyl group having 1 to 4 carbon atoms, and m is 0, 1 or 2. Examples of the linear or branched alkyl group having 1 to 14 carbon atoms include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, a tbutyl group, and an isobutyl group.

Here, in the above 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 number 1 to 4 A linear or branched alkyl group, R ⁹ , R ^1Q and R ¹¹ independently represent a linear or branched alkyl group having 1 to 4 carbon atoms, n is 0, 1 or 2, and X is , Halogen, OH, 1 / 2SO

 4, HSO

 4, 1 / 3PO

 4, HCO or 2

CH CO is shown. 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.

[0018] (A-1) More specifically, as a monomer having a tertiary amino group, dimethylaminoethyl (meth) acrylate (hereinafter, (meth) acryl represents acrylic and methacrylic), (meth) (Meth) acrylic acid such as Jetylaminoethyl acrylate and Dipropylaminoethyl (meth) acrylate Examples thereof include dialkylaminoalkyl compounds, dimethylaminoethyl (meth) acrylamide, dimethylalkylaminoalkyl (meth) acrylamide compounds, preferably dimethylaminoethyl (meth) acrylate, and jetylamino (meth) acrylate. Ethyl, dialkylaminoalkyl (meth) acrylates such as dipropylaminoethyl (meth) acrylate, dimethylaminoethyl (meth) acrylamide, dimethylaminopropyl (meth) acrylamide, and jetylaminopropyl (meth) acrylamide And more preferably, dimethylaminoethyl (meth) acrylate, dimethylaminoethyl (meth) acrylate, dimethylaminopropyl (meth) acrylamide, and the like. And ethylaminopropyl (meth) acrylamide.

(A-2) Monomers having a quaternary ammonium group include (meth) acrylic acid dimethylaminoethyl methyl chloride, (meth) acrylic acid dimethylaminoethylethyl chloride, (meth) dimethyl acid acrylic acid Ethylethylsulfuric acid, (meth) acrylic acid dimethylaminoethyl methylphosphoric acid, (meth) acrylic acid dimethylaminoethylethyl phosphoric acid, (meth) acrylic acid dimethylaminoethyl methyl chloride, (meth) acrylic acid jetylamino Ethylethyl chloride, (meth) acrylic acid jetylaminoethylethylsulfuric acid, (meth) acrylic acid jetylamino aminoethyl methylphosphoric acid, (meth) acrylic acid jetylaminoethylethyl ethyl phosphoric acid, dimethylaminopropyl (meta) ) Acrylamide methyl chloride, dimethylaminopropyl (me Ta) acrylamidoethyl chloride, dimethylaminopropyl (meth) acrylamide ethyl sulfate, dimethylaminopropyl (meth) acrylamide methyl phosphate, dimethylaminopropyl (meth) acrylamide ethyl phosphate and the like. Among these, (meth) acrylic acid dimethylaminoethyl methyl chloride, (meth) acrylic acid dimethylaminoethylethyl chloride, (meth) acrylic acid dimethylaminoethylethyl sulfate, (meth) acrylic acid jetylaminoethyl methyl chloride, ( (Meth) acrylic acid jetylaminoethylethyl chloride, (meth) acrylic acid jetylaminoethylethyl sulfate, dimethylaminopropyl (meth) acrylamide methyl chloride, dimethylaminopropyl (meth) acrylamidoethyl chloride, dimethyl Aminopropyl (meth) acrylamidoethyl sulfate is preferred, (meth) acrylic acid dimethylaminoethyl methyl chloride, (meth) acrylic acid dimethylaminoethyl ethyl chloride, ( More preferred is methacrylic acid dimethylaminoethylethyl sulfate.

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

 [0021] The content of the monomer (A) is in the following range. (A) When the monomer content is too high, the solubility in water is high, so the performance in low concentration treatment and single time treatment with low durability is lowered. In addition, 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 single-time treatment with which durability is not achieved. The performance of is reduced.

 [0022] (A-1) When a monomer having a tertiary amino group is contained, the content thereof is 0.1 to 75% by mass, preferably 2-55% by mass, more preferably in all monomers. Is 3-35% by mass.

 [0023] (A-2) When a monomer having a quaternary ammonium group is contained, the content is 0.1-7% by mass, preferably 0.5-6, in the total monomer. % By mass, more preferably 115% by mass.

 [0024] The monomer (B) used in the present invention is a (meth) acrylate 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 a carbon number of 11 to 16, preferably ^{14 to 14.} is there.

[0026] As the monomer (B), more specifically, methyl (meth) acrylate, ethyl (meth) acrylate, propyl (meth) acrylate, isopropyl (meth) acrylate, (meth) Examples include butyl acrylate, t-butyl (meth) acrylate, isobutyl (meth) acrylate, hexyl (meth) acrylate, and the like. Among these, methacrylic acid (methyl) methacrylate, ethyl (meth) acrylate, propyl (meth) acrylate, isopropyl (meth) acrylate, butyl (meth) acrylate, and t-butyl (meth) acrylate are preferred. Methyl acid, ethyl methacrylate, propyl methacrylate, isopropyl methacrylate, butyl methacrylate, and t-butyl methacrylate are more preferable. These may be used alone or in 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 in the total monomers. (B) If the monomer content is less than 21% by mass, the ability to prevent protein adhesion due to low concentration treatment and short-time treatment will decrease, and if it exceeds 80% by mass, it will be difficult to obtain uniform solubility.

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

 [0029] (C) Monomers include (meth) acrylamide, dimethyl (meth) acrylamide, and N-bule.

 2 Examples include pyrrolidone, saccharide-related group-containing monomers, and polyalkylene oxide group-containing monomers represented by the following general formula (4).

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 or a phenyl group having 1 to 4 carbon atoms, 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.

[0030] Examples of the polyalkylene oxide group-containing monomer represented by the general formula (4) include polyalkylene glycol mono (meth) acrylate, polyethylene glycol polypropylene glycol mono (meth) acrylate, 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 Alkoxy polyalkylene glycol mono (meth) attalytes alkoxylated with alkyl groups having 1 to 3 carbon atoms such as polyalkylene glycol mono (meth) acrylates 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-bul-2-pyrrolidone, or methoxypolyethylene glycol mono (meth) acrylate, and more preferably N-bul 2 —Pyrrolidone, (CHO) methoxypolyethylene glycol having an average repeat number of 2-25

 twenty four

 It is a (meta) atelate. 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 0.1-77.9% by mass, preferably 15-73% by mass, and more preferably 30-65% by mass in the total monomers. . (C) If the monomer content is too low, the water solubility will decrease, and if it is too high, the adsorptivity to the target surface will be poor.

 [0033] The polymer compound of the present invention has a weight average molecular weight of 5,000 to 1,000,000, preferably <is 10,000 to 500,000, more preferably <is 10,000 to 400,000. 000. If the weight average molecular weight is too small, for example, when used on the surface of a gel, the pore size will be smaller than the pore size, and if it is too large, the viscosity of the polymer compound solution will be too high, which will limit the formulation design. In the present invention, the weight average molecular weight is a gel permeation chromatography, in which 0.5 mol ZL acetic acid and 0.5 mol ZL sodium acetate in water Z ethanol = 50Z 50 (νΖν%) solution is used as the 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 (ii)-(C) monomers can be produced. For example, solution polymerization, suspension polymerization, bulk polymerization It can be polymerized by. Industrially, a solution polymerization method is preferred even though radical polymerization by solution polymerization or suspension polymerization is preferred. The copolymer of the present invention may be a random copolymer or a block copolymer.

 [0035] When polymerized 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, hexane, and aliphatic Alternatively, various organic solvents such as heterocyclic compounds, ethyl acetate, acetone, and methyl ethyl ketone can be used. The polymerization concentration is not particularly limited, but it is usually preferable to polymerize at 10-50% by mass.

[0036] Examples of the polymerization initiator include persulfates such as ammonium persulfate, sodium persulfate, and persulfate strength, peroxides such as benzoyl peroxide and lauroyl peroxide, cumene hydride peroxide, Examples thereof include hydride peroxide such as hydride peroxide, and azo compounds such as azobisisobutyl thiol-tolyl. Polymerization initiator concentration Is usually preferably from 0.1 to 10 mol% based on the total amount of monomers used. Furthermore, 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, or a pH adjuster such as phosphoric acid, citrate, tartaric acid or lactic acid may be used. The polymerization temperature is appropriately determined depending on the solvent used and the polymerization initiator, but usually 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, dialysis membrane or the like. Examples of activated charcoal include generally used wood, coal, coconut shells, etc. activated with chemicals or steam, etc., and there are powder, crushed, fibrous, etc. It is not limited. As a material for the ultrafiltration membrane, polysulfone, polyethersulfone, polyvinylidene difluoride, cellulose acetate, nitrocellulose and the like can be used. Regarding the shape, a flat membrane shape, a hollow fiber shape and the like can be mentioned, but not particularly limited.

 [0038] The polymer compound for preventing protein adhesion according to the present invention is used as a material for a medical device or the like, and the biocompatibility of the material is deteriorated by adhesion of a biological substance represented by protein. Excellent anti-protein adhesion ability even at low concentrations and for a single time treatment on hard surfaces such as glass, ceramic, stainless steel, plastic, soft surfaces such as hair and fibers, gel surfaces, and contact lens surfaces Have. This 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 in an antifouling composition. In addition, the object can be washed and antifouling can be imparted, and even in a washing process involving rinsing with water, the polymer compound is not washed away and is adsorbed on the object surface. Therefore, it can be used in a detergency antifouling agent composition.

[0039] Further, the composition comprising the polymer compound for preventing protein adhesion of the present invention is suitable as an ophthalmic composition since it has 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 liquids, and eyewashes. Specific examples of the contact lens composition include a contact lens treatment solution, a cleaning solution, a storage solution, a cleaning storage solution, and a cleaning / disinfecting solution. [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%, based on the entire composition. 1 to 10% by mass, more preferably 0.005 to 5% by mass. If the content of the polymer compound is too low, its function may not be fully achieved, and if it is too high, there may be restrictions on the formulation design.

 [0041] When the polymer compound of the present invention is contained in various compositions, one or more low-molecular-weight surfactants having aionic properties, cationic properties, nonionic properties, and amphoteric properties can be used alone or in accordance with the application. 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 oxystearic acid tridalylide, such as HCO-60, manufactured by Nippon Surfactant Industrial Co., Ltd., polysorbate 80 (for example, TO 10M, manufactured by Nippon Surfactant Industrial Co., Ltd.), etc. And ethylene sonolebitan, polyoxyethylene polyoxypropylene block polymer, poloxamine (eg, TETRONIC 1107, manufactured by BASF Japan Ltd.), and the like.

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

[0043] Specifically, examples of the disinfectant include polyhexamethylene biguanide hydrochloride, salted polydrom and the like. As preservatives, salt benzalcoum, salt cetylpyridium, sorbic acid, potassium sorbate, methyl n-hydroxybenzoate, ethyl p-oxybenzoate, propyl n-oxybenzoate, p-oxybenzoic acid Examples include butyl. Enzymes include trypsin, chymotrypsin, pandareatin, papain, collagena, promelain, aminopeptidase, aspergillo.peptidase, pronase E, dispase, subtilisin A, subtilisin B, lipase, darcosidase, mutanase, α-amylase, dextran Examples thereof include enzymes. As buffer, boric acid, borax, trometamol, sodium dihydrogen phosphate, disodium hydrogen phosphate, citrate, sodium citrate, sodium bicarbonate, sodium carbonate, potassium L-aspartate, epsilon-aminocapri Acid, sodium glutamate and the like. As a stabilizer, α-cyclodextrin, Examples include sodium edetate, sodium hydrogen sulfite, and sodium thiosulfate. Examples of isotonic agents include aminoethylsulfonic acid, potassium salt, sodium salt, calcium salt, glycerin, glucose, D-mannitol and the like. Examples of the solubilizer include ethanol, urea, propylene glycol, polyethylene glycol such as Magrogol 4000, and monoethanolamine. Examples of the refreshing agent include wikiyou oil, dl camphor, geraol, heart force oil, bergamot oil, d-borneol, 1 menthol, and eucalyptus oil. Examples of the thickening agent include sodium chondroitin sulfate, hyaluronic acid and its salt, dextran 70, hydroxycellulose, polyvinyl alcohol, polyvinylpyrrolidone and the like. Further, if necessary, a lower alcohol, an antibacterial agent, a pigment, and a fragrance can be used singly or in 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 a medical device or the like, and the biocompatibility of the material is deteriorated due to adhesion of a biological substance represented by protein. When used on hard surfaces such as glass, ceramic, stainless steel, plastic, etc., soft surfaces such as hair and fibers, gel surfaces, and contact lens surfaces, water-soluble polymer compounds may be added. It may be preferable. Particularly when used on the surface of a contact lens, by combining the polymer compound of the present invention and a water-soluble polymer compound, for example, friction during scrubbing is reduced, and damage to the object is better prevented. be able to.

 [0045] Examples of the water-soluble polymer compound include cellulose-based polymer compounds such as hydroxycellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, and methylcellulose, and polybulls such as polybulol alcohol, polybululpyrrolidone, and carboxybulum polymer. -Based polymer compounds, mucopolysaccharides such as sodium chondroitin sulfate and hyaluronic acid, polyethylene glycol, dextran and the like. Among these, preferable water-soluble high molecular compounds are cellulose polymer compounds, polyvinyl polymer compounds, polyethylene glycol, and hyaluronic acid, and particularly preferable compounds are hydroxypropyl methylenorerose, hydroxyethylenorerose, polyvinylidene. Norenoreconole, polyvinylinopyrrolidone, polyethylene glycol, hyaluronic acid.

[0046] The blending amount of the water-soluble polymer compound 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 scrubbing the target surface.If the amount is too large, the viscosity becomes too high and the formulation design is limited. There is a case.

[0047] The dosage form, preparation method, and method of use of each composition of the present invention are not particularly limited, and each composition can be prepared according to a conventional method of each dosage form as a normal dosage form of each composition. By using the normal dose of the mold in the usual way, excellent antifouling properties and cleaning antifouling properties 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 that imparts excellent antifouling properties even if rinsed with water after the surface treatment. In addition, the above-described polymer compound is not detached by rinsing in the washing step with water, and a detersive antifouling agent composition that can be adsorbed on the target surface as an active ingredient to give excellent antifouling properties is obtained. It is done.

 Example

 [0049] Hereinafter, the present invention will be specifically described with reference to Examples and Comparative Examples, but the present invention is not limited to the following Examples.

 [0050] [Example 1]

 Into a separable flask equipped with a cooling reflux tube, dropping funnel, thermometer, nitrogen inlet tube and stirrer, 200 g of ethanol was charged, nitrogen gas was introduced with stirring, and heated to 78 ° C. , DM) 40. lg, methyl methacrylate (hereinafter abbreviated as MMA) 44.7 g, bull pyrrolidone (hereinafter abbreviated as VP) 65.2 g (DM 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, 2, 2-((azobis (2-methylbutyrate-tolyl))) The mixed solution of 78 g and 115 g of ethanol was continuously heated for 3 hours and further heated for 3 hours to obtain the polymer compound (copolymer) of Example 1 having the composition shown in Table 1. .

 [0051] [Example 2-25]

In Example 1 above, the type of monomer and the blending ratio were changed so that the composition shown in Table 1 was obtained. Except for the above, the polymer compound of Example 2-25 having the composition shown in Table 1 was obtained in the same manner as in Example 1.

 [0052] [Example 26]

A separable flask equipped with a cooling reflux tube, dropping funnel, thermometer, nitrogen inlet tube and stirring device was charged with 120 g of ethanol, and nitrogen gas was introduced while stirring to bring the internal temperature to 78. Caro heat to C, DM11.5g, MMA25.7g, VP42.4g, Methyl polyethylene glycol = f monomonomethacrylate (polyethylene average = 9) (hereinafter abbreviated as M—90G) 10.3g DM content in the body = 12.8 mass%, MMA content in all monomers = 28.6 mass%, VP content in all monomers = 47.1 mass%, 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 the mixture was further heated for 4 hours to conduct a polymerization reaction to obtain a copolymer. Add ion exchange water so that the solid content of the copolymer is 2% by mass, and at the same time add lmol% L hydrochloric acid aqueous solution and adjust the pH to 6, and regenerate cellulose dialysis tubing (UC36-32-100; (Viskase Companies, Inc.) and dialyzed for one week while changing the ion exchange water. The aqueous solution containing the polymer compound in the tube was dried using a freeze dryer to obtain the polymer compound of Example 26 (purified copolymer) having the composition shown in Table 3.

 [0053] [Example 27-62]

 In Example 26, except for changing the type and blending ratio of the monomers so that the composition shown in Table 3 was obtained, the compositions of Examples 27-62 having the compositions shown in Table 3 were prepared in the same manner as in Example 26 above. A molecular compound was obtained.

 [0054] [Comparative Examples 1 and 2]

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

 Comparative Example 1: Polybulurpyrrolidone (Polybutyrrolidone K 90): manufactured by BASF Corporation Comparative Example 2: Polyacrylic acid (Carbopol 934P): manufactured by Noveon

 [0055] [Comparative Example 3-9]

In Example 1 above, except that the type of monomer and the blending ratio were changed so that the composition shown in Table 2 was obtained, the composition of Comparative Example 3-9 shown in Table 2 was increased in the same manner as in Example 1 above. Min A child compound was obtained.

 [0056] With respect to the polymer compounds of Examples 1-25 and Comparative Example 1-9, the evaluation of antifouling property 1, antifouling property 2 and antifouling property 3 in 0.05% by mass aqueous solution was performed according to the following method. went. Regarding the evaluation of durability, the copolymer of Examples 1 and 25 above was evaluated with a 0.1% by mass aqueous solution, and Comparative Example 1-9 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 Examples 1 to 9, a 0.05 mass% aqueous solution was used.

 The antifouling property 4 and the cleaning property were evaluated according to the following methods. The results are also shown in Table 1-14.

 [0057] <Evaluation method of antifouling property 1>

 A stainless steel plate (10 cm × 10 cm) was immersed in 500 mL of a 0.05 mass% polymer compound solution or dispersion at room temperature for 1 hour. Take out the stainless steel plate, rinse it with ion-exchanged water, absorb moisture with clean soft paper, immerse the stainless steel plate in a solution of 0.6 g of fibrinogen, a kind of protein, in 500 mL of ion-exchanged water, Heated and shaken at 30 ° C for 1 hour. The stainless steel plate was taken out and blotted with clean soft paper. This stainless steel plate was stained with fibrinogen adhering to the stainless steel plate using a ninhydrin indicator, and the state of color development was evaluated according to the following evaluation criteria.

 [0058] <Evaluation criteria>

 5: Not dyed at all (corresponds to the colored state when the ninhydrin indicator is used without contacting the stainless steel plate with the fibrinogen solution)

 4: hardly dye

 3: Slightly dyed

 2: Pretty dyed

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

[0059] <Evaluation method of antifouling property 2>

Concentration of EMAA (ethylene 'methacrylic acid polymer) resin (lOcmX IOcm) (Mitsui's DuPont Poly Chemicals). It was immersed in 500 mL of a 05 mass% polymer compound solution or dispersion at room temperature for 1 hour. Remove EMAA oil and rinse with deionized water, clean and soft Moisture is absorbed with paper, and egg white lysozyme solution, a type of protein (Wako Pure Chemical Industries, Ltd.)

) After immersing EMAA resin in a solution of 0.60 g dissolved in 500 mL of ion-exchanged water, the mixture was heated and shaken at 30 ° C for 1 hour. EMAA oil was taken out, and water was absorbed with clean soft paper. This EMAA resin was stained with a ninhydrin indicator to stain the lysozyme adhering to the EMAA resin, and the color development was evaluated according to the following evaluation criteria.

[0060] <Evaluation criteria>

 5: Not dyed at all (corresponds to the colored state when ninhydrin indicator is used without contacting EMAA resin with egg white lysozyme solution)

 4: hardly dye

 3: Slightly dyed

 2: Pretty dyed

 1: Severely dyed (corresponds to the colored state when EMAA rosin is not treated with a polymer compound solution, but is contacted with egg white lysozyme solution, and -hydrin indicator is used)

 <0061 Evaluation Method for Antifouling Property 3>

 In the above evaluation method for antifouling property 2, replace EMAA resin with a soft contact lens [1DAY ACUVUE (manufactured by Johnson & Johnson)] as a lysozyme dyeing agent. The egg white lysozyme adhering to the soft contact lens was dyed by the same method as the antifouling property 2 evaluation method except that a thin aqueous solution was used, and the color development state was evaluated according to the following evaluation criteria.

 [0062] <Evaluation criteria>

 5: Completely uncolored ヽ (corresponds to the colored state when the soft contact lens is not in contact with the egg white lysozyme solution and the Elysin mouth solution is used V)

 4: hardly dye

 3: Slightly dyed

 2: Pretty dyed

 1: Staining vigorously (corresponds to the colored state when the soft contact lens is not treated with the polymer compound solution but is in contact with the egg white lysozyme solution and using the Ellis Mouth Sin aqueous solution)

[0063] <Durability Evaluation Method> A soft contact lens [1DAY ACUVUE (manufactured by Johnson & Johnson Co., Ltd.)] was prepared from the polymer compound solution of Examples 1-11 and Comparative Example 1-9 (Example 1-25 polymer compound 0. 1% by weight aqueous solution, Comparative Example 1-1 9 polymer compound 1.0% by weight aqueous solution) 50 OmU This was immersed for 1 hour at room temperature. Take out the soft contact lens, rinse with ion-exchanged water, absorb moisture with clean soft paper, and dissolve 0.6 g of egg white lysozyme solution (produced by Wako Pure Chemical Industries, Ltd.), a kind of protein, in 500 mL of ion-exchanged water. After the soft contact lens was immersed in the solution, it was shaken by heating at 30 ° C for 15 hours and 30 hours, respectively. The soft contact lens was taken out, and water was absorbed with clean soft paper. For this soft contact lens, lysozyme adhering to the lens was stained using a ninhydrin indicator, and the color development state was evaluated according to the following evaluation criteria.

<Evaluation criteria>

 5: Not dyed 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 dye

 3: Slightly dyed

 2: Pretty dyed

 1: Staining vigorously (corresponds to the colored state when the soft contact lens is not treated with the polymer compound solution but is contacted with the egg white lysozyme solution and the N-hydrin indicator is used)

<0065 Evaluation Method for Antifouling Property 4>

Soft contact lens [1DAY ACUVUE (manufactured by Johnson & Johnson Co., Ltd.)] The polymer compound solution of the above Example 26-62 and Comparative Example 1-9 (polymer compound concentration 0.05 mass%, salt Sodium 0.9 mass%) was immersed in 4 mL at room temperature for 4 hours. The soft contact lens was taken out and rinsed with ion exchange water, and moisture was absorbed with clean soft 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 soft Moisture was absorbed with paper. The soft contact lens was stained for protein adhering to the lens using a ninhydrin indicator, and the color development state was evaluated according to the following evaluation criteria.

 [0066] <Evaluation criteria>

 5: Not dyed 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 dye

 3: Slightly dyed

 2: Pretty dyed

 1: Staining vigorously (corresponds to the colored state when the soft contact lens is not treated with the polymer compound solution but is contacted with the egg white lysozyme solution and the N-hydrin indicator is used)

 [0067] <Evaluation method of detergency>

Soft contact lenses [1DAY ACUVUE (Johnson & Johnson Co., Ltd.)] were rinsed with ion-exchanged water, and water was blotted with clean soft paper. This soft contact lens was obtained by using egg white lysozyme (manufactured by Wako Pure Chemical Industries, Ltd.) 0.12 mass%, bovine serum albumin 0.388 mass ⁰ / "fraction V, manufactured by Nacalai Testa Co., Ltd.), γ-globulin 0. 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 And then shaken for 1 hour at 37 ° C. After removing the soft contact lens and blotting moisture with clean soft paper, the polymer compound solutions of Examples 26-62 and Comparative Examples 1-19 (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 indication Stained, and evaluate the state of the color in accordance with the following evaluation criteria.

 [0068] <Evaluation criteria>

 5: Not dyed at all (equivalent to the state where protein stains adhering to the used soft contact lens are almost washed)

4: hardly dye 3: Slightly dyed

2: Pretty dyed

1: Severely dyed (equivalent to almost no protein stains on the used contact lens)

2]

 Antifouling property Antifouling property Antifouling property

 Durability Polymer compound composition Weight average 1 2 3

(Material%) Molecular weight E AA So: 7 Contact 30 15 Stainless steel

 Resin Time Time Polyvinylpyrrolidone

 1 1 1 1 1 1 1 (K-90)

 2 Polyacryloleic 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

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 [0072] [Table 4]

[0073] [Examples 63-66, Comparative Examples 10 and 11]

 In accordance with the composition in Table 5, an antifouling agent composition and an antifouling detergent composition were prepared based on conventional methods. The obtained antifouling agent composition and antifouling detergent composition were subjected to the antifouling property 3 evaluation method described above, and 0.05% by mass of the polymer compound solution or dispersion was treated with the antifouling agent composition, Evaluation was made in the same manner except that the composition was changed to a soil cleaner. The results are also shown in Table 5.

[0074] [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 ― Polydonium chloride 0.011 ― 0.011

10% benzalkonium chloride solution-0-1-

 α-Silk σdextrin ― 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 Polysoto 80 0.05 ― ― 0.05

TETRONIC1107 0.3 0.3 0-3 0.3 0.3 0.3 New Pole 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 Trometamoe 0.3 ― 0.3 Sodium dihydrogen phosphate (dihydrate) ― 0.08 ― Sodium disodium phosphate (12 hydrate) 0.5-Chenic 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

 Sodium hydroxide

 Purified water lance

 100

 Η 7

 Anti-rust 3 5 5 5 5 1 1

 30 hours 5 5 5 5 1 1 Durability

 15 hours 5 5 5 5 1 1

Abbreviations in the table are shown below.

 • DM: Dimethylaminoethyl methacrylate

• DMA: Dimethylaminoethyl acrylate • DMAPAA: Dimethylaminopropyl Atalinoleamide

 • DMAPMA: Dimethylaminopropyl methacrylamide

 • DMC: Dimethylaminoethyl methyl chloride metathalate

 • MMA: methyl methacrylate

 • EMA: Ethyl methacrylate

 • BMA: n-butyl methacrylate

 • t-BMA: t-butyl methacrylate

• VP: Vinolelepyrrolidone

 • M—90G: Methoxypolyethylene glycol monometatalylate (Methoxypolyethylene glycol methacrylate) (Polyethylene average = 9) (Shin-Nakamura Chemical Co., Ltd.)

• M—230G: Methoxypolyethylene glycol monometatalylate (Methoxypolyethylene glycol methacrylate) (Polyethylene average = 23) (manufactured by Shin-Nakamura Engineering Co., Ltd.)

• HEMA: Hydroxyethyl methacrylate

AA: acrylic acid

 MAA: methacrylolic acid

 • TETORONIC 1107: Poloxamine (manufactured by BASF Japan)

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

Claims

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. (A) (A-1) Monomer having tertiary amino group represented by the following general formula (1) 0.1-75% by mass and Z or (A-2) represented by the following general formula (2) Monomers having quaternary ammonium groups 0.1 to 7% by mass

 [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 1 to 14 carbon atoms, 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.

 [Chemical 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 independently a hydrogen atom or a linear or branched alkyl group having 1 to 14 carbon atoms, R ⁹ , R ^1Q and R ¹¹ independently represent a linear or branched alkyl group having 1 to 4 carbon atoms, n is 0, 1 or 2, X is halogen, OH, 1 / 2SO, HSO, 1 / (Indicates 3PO, HCO or CHCO)

 4 4 4 2 3 2

(B) (Meth) acrylic acid ester monomer represented by the following general formula (3) 21—80 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 straight or branched chain having 1 to 16 carbon atoms. It is an alkyl group. )

 (C) (A), (B) Nonionic water-soluble monomer other than monomer 0.1-78.9 mass%

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

[3] A detersive antifouling agent 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 contact lenses comprising the polymer compound according to claim 1.