阅读说明：本技术 含有地夸磷索及阳离子性聚合物的眼科用组合物 (Ophthalmic composition containing diquafosol and cationic polymer ) 是由 高桥恭平 浅田博之 神村明日香 森岛健司 桃川雄介 远藤健一 于 2019-02-27 设计创作，主要内容包括：眼科用组合物,其是含有地夸磷索或其盐、以及阳离子性聚合物的眼科用组合物,该阳离子性聚合物为选自由壳聚糖、壳聚糖衍生物、阳离子性(甲基)丙烯酸酯共聚物、阳离子性有机硅聚合物、二烯丙基季铵盐·丙烯酰胺共聚物、阳离子性水解角蛋白、阳离子性水解丝、阳离子性水解胶原蛋白、阳离子性水解酪蛋白、阳离子性水解大豆蛋白、阳离子性乙烯基吡咯烷酮共聚物、聚乙烯基吡咯烷酮、二甲基二烯丙基氯化铵的均聚物、己二酸·二甲氨基羟丙基二亚乙基三胺共聚物、己二酸·环氧丙基二亚乙基三胺共聚物及丙烯酰胺·β-甲基丙烯酰氧基乙基三甲基铵甲基硫酸盐共聚物组成的组中的至少一种。(An ophthalmic composition comprising diquafosol or a salt thereof and a cationic polymer, the cationic polymer is at least one selected from the group consisting of chitosan, chitosan derivatives, cationic (meth) acrylate copolymers, cationic silicone polymers, diallyl quaternary ammonium salt/acrylamide copolymers, cationic hydrolyzed keratin, cationic hydrolyzed silk, cationic hydrolyzed collagen, cationic hydrolyzed casein, cationic hydrolyzed soy protein, cationic vinylpyrrolidone copolymers, polyvinylpyrrolidone, homopolymers of dimethyldiallylammonium chloride, copolymers of adipic acid/dimethylaminopropyl diethylenetriamine, copolymers of adipic acid/glycidyl diethylenetriamine and copolymers of acrylamide/β -methacryloyloxyethyl trimethylammoniumethylmethanesulfate.)

1. An ophthalmic composition comprising diquafosol or a salt thereof and a cationic polymer, the cationic polymer is at least one selected from the group consisting of chitosan, chitosan derivatives, cationic (meth) acrylate copolymers, cationic silicone polymers, diallyl quaternary ammonium salt/acrylamide copolymers, cationic hydrolyzed keratin, cationic hydrolyzed silk, cationic hydrolyzed collagen, cationic hydrolyzed casein, cationic hydrolyzed soy protein, cationic vinylpyrrolidone copolymers, polyvinylpyrrolidone, homopolymers of dimethyldiallylammonium chloride, copolymers of adipic acid/dimethylaminopropyl diethylenetriamine, copolymers of adipic acid/glycidyl diethylenetriamine and copolymers of acrylamide/β -methacryloyloxyethyl trimethylammoniumethylmethanesulfate.

2. The ophthalmic composition according to claim 1, wherein the cationic polymer is at least one selected from the group consisting of chitosan, a chitosan derivative, a diallyl quaternary ammonium salt-acrylamide copolymer, and polyvinylpyrrolidone.

3. An ophthalmic composition according to claim 1 or 2, wherein the cationic polymer is polyvinylpyrrolidone.

4. An ophthalmic composition according to any one of claims 1 to 3, comprising polyvinylpyrrolidone having a K value of 17 or more.

5. An ophthalmic composition according to any one of claims 1 to 4, comprising polyvinylpyrrolidone having a K value of 17 to 90.

6. An ophthalmic composition according to any one of claims 1 to 5, comprising a polyvinylpyrrolidone having a K value of 30.

7. An ophthalmic composition according to any one of claims 1 to 6, comprising a polyvinylpyrrolidone having a K value of 90.

8. The ophthalmic composition according to claim 1 or 2, wherein the cationic polymer is at least one selected from the group consisting of chitosan and chitosan derivatives.

9. An ophthalmic composition according to any one of claims 1 to 8, wherein the concentration of the cationic polymer is 0.00001 to 10% (w/v).

10. The ophthalmic composition according to any one of claims 1 to 9, wherein the concentration of the diquafosol or the salt thereof is 0.0001 to 10% (w/v).

11. An ophthalmic composition according to any one of claims 1 to 10, wherein the concentration of diquafosol or a salt thereof is 0.01 to 5% (w/v).

12. An ophthalmic composition according to any one of claims 1 to 11, wherein the concentration of diquafosol or a salt thereof is 1 to 5% (w/v).

13. An ophthalmic composition according to any one of claims 1 to 12, wherein the diquafosol or a salt thereof is present at a concentration of 3% (w/v).

14. An ophthalmic composition according to any one of claims 1 to 13, which is an eye drop.

15. An ophthalmic composition according to any one of claims 1 to 14, which is aqueous.

16. An ophthalmic composition according to any one of claims 1 to 15, which is of the suspension or dissolution type.

17. An ophthalmic composition according to any one of claims 1 to 16, having a viscosity of from 1 to 500 mPa-s at 25 ℃.

18. An ophthalmic composition according to any one of claims 1 to 17, having a viscosity of from 1 to 100 mPa-s at 25 ℃.

19. An ophthalmic composition according to any one of claims 1 to 18, wherein the salt of diquafosol is sodium diquafosol.

20. An ophthalmic composition according to any one of claims 1 to 19, for use in the prevention or treatment of dry eye.

21. An ophthalmic composition according to any one of claims 1 to 20, wherein the ophthalmic composition is administered in the form of 1 to 5 drops per 1 to 6 times a day in an eye drop manner.

22. An ophthalmic composition according to any one of claims 1 to 21, wherein the ophthalmic composition is administered in the form of 1 to 2 drops per time in an eye drop manner 2 to 4 times a day.

23. An ophthalmic composition according to any one of claims 1 to 22, wherein the ophthalmic composition is administered in the form of eye drops 1 to 2 drops 3 or 4 times per day.

24. An ophthalmic composition comprising diquafosol or a salt thereof, and polyvinylpyrrolidone.

25. The ophthalmic composition according to claim 24, comprising polyvinylpyrrolidone having a K value of 17 or more.

26. An ophthalmic composition according to claim 24 or 25, comprising a polyvinylpyrrolidone having a K-value of 17 to 90.

27. An ophthalmic composition according to any one of claims 24 to 26, comprising a polyvinylpyrrolidone having a K-value of 30.

28. An ophthalmic composition according to any one of claims 24 to 27, comprising a polyvinylpyrrolidone having a K-value of 90.

Technical Field

The present invention relates to an ophthalmic composition containing diquafosol or a salt thereof and a cationic polymer.

Background

Diquafosol is also known as P¹,P⁴-bis (uridine-5') tetraphosphate or purine receptor agonist of Up4U, has lacrimal secretion promoting effect, and is used as eye drop (product name: DIQUAS) containing diquafosol tetrasodium salt with concentration of 3% (w/v)^{(registered trademark)}Eye drops 3%) and used for the treatment of dry eye (patent document 1, non-patent document 1). Diquafosol tetrasodium salt is very soluble in water, DIQUAS^{(registered trademark)}Eye drops are colorless clear sterile aqueous eye drops (non-proprietary) in 3%Patent document 1).

On the other hand, a cationic polymer is a polymer containing 1 or more substituents which become cationic when dissolved in water, and is used in various applications. For example, japanese patent application laid-open No. 2006-321757 (patent document 2) describes the following: the cationic polymer exerts an effect of preventing a dry feeling, a sticky feeling, and a knotting in a stage of hair wetting from rinsing the whole hair material cleanser to drying the hair by a shampoo treatment or the like, and also contributes to an effect of imparting gloss, a soft feeling, a smooth feeling, a moist feeling, an easy-to-finish property, and the like to the hair during drying.

In addition, polyvinylpyrrolidone, which is one kind of cationic polymer, is used as, for example, a suspending agent, a solubilizer for a poorly soluble compound, and the like in the field of ophthalmic compositions (patent document 3).

Disclosure of Invention

Problems to be solved by the invention

The present invention addresses the problem of finding a novel ophthalmic composition containing diquafosol or a salt thereof.

Means for solving the problems

The present inventors have conducted intensive studies and as a result, found that an ophthalmic composition containing diquafosol or a salt thereof and a cationic polymer selected from the group consisting of chitosan, a chitosan derivative, a cationic (meth) acrylate copolymer, a cationic silicone polymer, a diallyl quaternary ammonium salt/acrylamide copolymer, a cationic hydrolyzed keratin, a cationic hydrolyzed silk, a cationic hydrolyzed collagen, a cationic hydrolyzed casein, a cationic hydrolyzed soy protein, a cationic vinylpyrrolidone copolymer, polyvinylpyrrolidone, a homopolymer of dimethyldiallylammonium chloride, an adipic acid/dimethylamino-hydroxypropyltriamine copolymer, an adipic acid/epoxypropyl diethylenetriamine copolymer, and an acrylamide/β -methacryloyloxyethyl tristriamide has a high tear fluid volume increasing effect At least one kind of copolymer of methyl ammonium methyl sulfate, and the cationic polymer has been found to have the metabolic stability effect of diquafosol or a salt thereof. Moreover, the inventors of the present application found that: an ophthalmic composition containing diquafosol or a salt thereof and polyvinylpyrrolidone which is one kind of cationic polymer does not show nerve irritation, can improve the comfort of eye drops, and has a high tear volume increasing effect. Hereinafter, these ophthalmic compositions are also referred to as "the present compositions". That is, the present invention relates to the following.

The composition is an ophthalmic composition containing diquafosol or a salt thereof and a cationic polymer, the cationic polymer is at least one selected from the group consisting of chitosan, chitosan derivatives, cationic (meth) acrylate copolymers, cationic silicone polymers, diallyl quaternary ammonium salt/acrylamide copolymers, cationic hydrolyzed keratin, cationic hydrolyzed silk, cationic hydrolyzed collagen, cationic hydrolyzed casein, cationic hydrolyzed soy protein, cationic vinylpyrrolidone copolymers, polyvinylpyrrolidone, homopolymers of dimethyldiallylammonium chloride, copolymers of adipic acid/dimethylaminohydroxypropyl diethylenetriamine, copolymers of adipic acid/epoxypropyl diethylenetriamine, and copolymers of acrylamide/beta-methacryloyloxyethyl trimethylammonium methyl sulfate.

In the present composition, the cationic polymer is preferably at least one selected from the group consisting of chitosan, chitosan derivatives, diallyl quaternary ammonium salt/acrylamide copolymers, and polyvinylpyrrolidone.

In the present composition, the cationic polymer is preferably polyvinylpyrrolidone.

The present composition preferably comprises polyvinylpyrrolidone having a K value of 17 or more.

The composition preferably contains polyvinylpyrrolidone with a K value of 17-90.

The present compositions preferably comprise polyvinylpyrrolidone having a K-value of 30.

The present compositions preferably comprise polyvinylpyrrolidone having a K value of 90.

In the present composition, the cationic polymer is more preferably at least one selected from the group consisting of chitosan and chitosan derivatives.

In the present composition, the concentration of the cationic polymer is preferably 0.00001 to 10% (w/v).

In the present composition, the concentration of the diquafosol or the salt thereof is preferably 0.0001 to 10% (w/v).

In the present composition, the concentration of the diquafosol or the salt thereof is more preferably 0.01 to 5% (w/v).

In the present composition, the concentration of the diquafosol or the salt thereof is more preferably 1 to 5% (w/v).

In the present composition, the concentration of the above diquafosol or a salt thereof is more preferably 3% (w/v).

The present composition is preferably an eye drop.

The present composition is preferably aqueous.

The present composition is preferably in a suspended or dissolved form.

The viscosity of the composition is preferably 1 to 500 mPas at 25 ℃.

The viscosity of the present composition is more preferably 1 to 100 mPas at 25 ℃.

In the present composition, the salt of diquafosol is preferably sodium diquafosol.

The present composition is preferably a composition for the prevention or treatment of dry eye.

The composition is preferably applied in the form of eye drops 1 to 6 times per 1 day, 1 to 5 drops per time.

The present composition is more preferably applied in the form of eye drops 1 to 2 drops at a time 2 to 4 times a day.

The present composition is further preferably administered in the form of eye drops by 3 or 4 times per 1 to 2 drops per day.

The present invention also provides an ophthalmic composition containing diquafosol or a salt thereof and polyvinylpyrrolidone.

The present composition preferably comprises polyvinylpyrrolidone having a K value of 17 or more.

The composition preferably contains polyvinylpyrrolidone with a K value of 17-90.

The present compositions preferably comprise polyvinylpyrrolidone having a K-value of 30.

The present compositions preferably comprise polyvinylpyrrolidone having a K value of 90.

The present invention also provides a dry eye therapeutic agent containing diquafosol or a salt thereof and a cationic polymer. Here, the cationic polymer is at least one selected from the group consisting of chitosan, chitosan derivatives, cationic (meth) acrylate copolymers, cationic silicone polymers, diallyl quaternary ammonium salt/acrylamide copolymers, cationic hydrolyzed keratin, cationic hydrolyzed silk, cationic hydrolyzed collagen, cationic hydrolyzed casein, cationic hydrolyzed soy protein, cationic vinylpyrrolidone copolymers, polyvinylpyrrolidone, homopolymers of dimethyldiallylammonium chloride, copolymers of adipic acid and dimethylamino hydroxypropyl diethylenetriamine, copolymers of adipic acid and glycidyl diethylenetriamine, and copolymers of acrylamide and β -methacryloyloxyethyl trimethylammonium methyl sulfate.

The present invention also provides a dry eye therapeutic agent containing diquafosol or a salt thereof and polyvinylpyrrolidone.

The present invention also provides a method for preventing or treating dry eye, which comprises the step of administering to a patient an ophthalmic composition containing diquafosol or a salt thereof and a cationic polymer. Here, the cationic polymer is at least one selected from the group consisting of chitosan, chitosan derivatives, cationic (meth) acrylate copolymers, cationic silicone polymers, diallyl quaternary ammonium salt/acrylamide copolymers, cationic hydrolyzed keratin, cationic hydrolyzed silk, cationic hydrolyzed collagen, cationic hydrolyzed casein, cationic hydrolyzed soy protein, cationic vinylpyrrolidone copolymers, polyvinylpyrrolidone, homopolymers of dimethyldiallylammonium chloride, copolymers of adipic acid and dimethylamino hydroxypropyl diethylenetriamine, copolymers of adipic acid and glycidyl diethylenetriamine, and copolymers of acrylamide and β -methacryloyloxyethyl trimethylammonium methyl sulfate.

The present invention also provides a method for preventing or treating dry eye, which comprises administering to a patient an ophthalmic composition containing diquafosol or a salt thereof and polyvinylpyrrolidone.

The present invention also provides an ophthalmic composition containing diquafosol or a salt thereof and a cationic polymer, which is used for preventing or treating dry eye. Here, the cationic polymer is at least one selected from the group consisting of chitosan, chitosan derivatives, cationic (meth) acrylate copolymers, cationic silicone polymers, diallyl quaternary ammonium salt/acrylamide copolymers, cationic hydrolyzed keratin, cationic hydrolyzed silk, cationic hydrolyzed collagen, cationic hydrolyzed casein, cationic hydrolyzed soy protein, cationic vinylpyrrolidone copolymers, polyvinylpyrrolidone, homopolymers of dimethyldiallylammonium chloride, copolymers of adipic acid and dimethylaminohydroxypropyl diethylenetriamine, copolymers of adipic acid and epoxypropyl diethylenetriamine, and copolymers of acrylamide and β -methacryloyloxyethyl trimethylammonium methyl sulfate.

The present invention also provides an ophthalmic composition containing diquafosol or a salt thereof and polyvinylpyrrolidone, which is used for preventing or treating dry eye.

The present invention also provides a use of an ophthalmic composition containing diquafosol or a salt thereof and a cationic polymer for the production of a pharmaceutical for preventing or treating dry eye. Here, the cationic polymer is at least one selected from the group consisting of chitosan, chitosan derivatives, cationic (meth) acrylate copolymers, cationic silicone polymers, diallyl quaternary ammonium salt/acrylamide copolymers, cationic hydrolyzed keratin, cationic hydrolyzed silk, cationic hydrolyzed collagen, cationic hydrolyzed casein, cationic hydrolyzed soy protein, cationic vinylpyrrolidone copolymers, polyvinylpyrrolidone, homopolymers of dimethyldiallylammonium chloride, copolymers of adipic acid and dimethylamino hydroxypropyl diethylenetriamine, copolymers of adipic acid and glycidyl diethylenetriamine, and copolymers of acrylamide and β -methacryloyloxyethyl trimethylammonium methyl sulfate.

The present invention also provides a use of an ophthalmic composition containing diquafosol or a salt thereof and polyvinylpyrrolidone for the production of a pharmaceutical for preventing or treating dry eye.

Effects of the invention

From the test results described below, it is also clear that: the composition has high tear increasing effect. The cationic polymer contained in the composition has the effect of improving the metabolic stability of diquafosol or a salt thereof. Therefore, the composition is compared with the existing DIQUAS applied by eye drops^{(registered trademark)}In the case of eye drops, a stronger therapeutic effect on dry eye can be expected. Additionally, existing DIQUAS^{(registered trademark)}The eye drops require 6 times of eye dropping for 1 day, and there are patients who cannot obtain the expected effect due to poor eye drop compliance (adherence), but the present composition has a sufficient therapeutic effect on dry eye, and the number of eye drops is reduced, and improvement of eye drop compliance is expected. Furthermore, the existing DIQUAS^{(registered trademark)}The eye drops contain diquafosol tetrasodium salt at a concentration of 3% (w/v), and the present composition is expected to exhibit a therapeutic effect for dry eye at a lower concentration of the same level or more. In addition, the ophthalmic composition contains diquafosol or a salt thereof and polyvinylpyrrolidone as one kind of cationic polymerThe compound does not exhibit nerve irritation, and therefore can improve the comfort of the eye drops.

Drawings

Fig. 1 is a graph showing the maximum fluorescence intensity (RFUmax) after adding diquafosol sodium.

Detailed Description

The present invention will be described in more detail.

In the present specification, "(w/v)%" means the mass (g) of the subject component contained in 100mL of the ophthalmic composition of the present invention.

"Diquafosol" is a compound represented by the following chemical structural formula.

[ chemical formula 1]

The "salt of diquafosol" is not particularly limited as long as it is a salt acceptable as a pharmaceutical, and includes metal salts formed with lithium, sodium, potassium, calcium, magnesium, zinc, and the like; salts with inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, sulfuric acid, phosphoric acid, etc.; salts with organic acids such as acetic acid, fumaric acid, maleic acid, succinic acid, citric acid, tartaric acid, adipic acid, gluconic acid, glucoheptonic acid, glucuronic acid, terephthalic acid, methanesulfonic acid, lactic acid, hippuric acid, 1, 2-ethanedisulfonic acid, isethionic acid, lactobionic acid, oleic acid, pamoic acid (pamoic acid), polygalacturonic acid, stearic acid, tannic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, lauryl sulfate, dimethyl sulfate, naphthalenesulfonic acid, and sulfosalicylic acid; quaternary ammonium salts with methyl bromide, methyl iodide, etc.; salts with halogen ions such as bromide ion, chloride ion, and iodide ion; salts with ammonia; salts with organic amines such as triethylenediamine, 2-aminoethanol, 2-iminobis (ethanol), 1-deoxy-1- (methylamino) -2-D-sorbitol, 2-amino-2- (hydroxymethyl) -1, 3-propanediol, procaine, and N, N-bis (phenylmethyl) -1, 2-ethylenediamine; and so on.

In the present invention, "diquafosol or a salt thereof" also includes a hydrate and an organic solvate of diquafosol (free form) or a salt thereof.

When a polymorph or a polymorph group (polymorph system) exists in diquafosol or a salt thereof, the polymorph or the polymorph group (polymorph system) is also included in the scope of the present invention. The "polymorph group (polymorph system)" herein means each crystal form and the whole process thereof in each stage when the crystal form changes according to the conditions and states of the above-mentioned crystals such as preparation, crystallization and storage.

The "diquafosol or a salt thereof" in the present invention is preferably a sodium salt of diquafosol, and particularly preferably a diquafosol tetrasodium salt (also referred to simply as "diquafosol sodium" in the present specification) represented by the following chemical formula.

[ chemical formula 2]

The diquafosol or a salt thereof can be produced by the method disclosed in Japanese patent application laid-open No. 2001-510484.

The composition may contain an active ingredient other than diquafosol or a salt thereof, but preferably contains diquafosol or a salt thereof as the only active ingredient.

The concentration of diquafosol or a salt thereof in the present composition is not particularly limited, and is, for example, preferably 0.0001 to 10% (w/v), more preferably 0.001 to 5% (w/v), still more preferably 0.01 to 5% (w/v), yet more preferably 0.1 to 5% (w/v), still more preferably 1 to 5% (w/v), and particularly preferably 3% (w/v). More specifically, it is preferably 0.001% (w/v), 0.002% (w/v), 0.003% (w/v), 0.004% (w/v), 0.005% (w/v), 0.006% (w/v), 0.007% (w/v), 0.008% (w/v), 0.009% (w/v), 0.01% (w/v), 0.02% (w/v), 0.03% (w/v), 0.04% (w/v), 0.05% (w/v), 0.06% (w/v), 0.07% (w/v), 0.08% (w/v), 0.09% (w/v), 0.1% (w/v), 0.2% (w/v), 0.3% (w/v), 0.4% (w/v), 0.5% (w/v), 0.6% (w/v), 0.7% (w/v), 0.8% (w/v), 0.9% (w/v), 1% (w/v), 1.5% (w/v), 2% (w/v), 2.5% (w/v), 3% (w/v), 3.5% (w/v), 4% (w/v), 4.5% (w/v), or 5% (w/v).

In the present invention, the "cationic polymer" refers to a polymer containing 1 or more substituents which become cationic when dissolved in water.

In the cationic polymer, the substituent which becomes a cation when dissolved in water is not particularly limited, and examples thereof include a primary amino group, a secondary or tertiary amino group, an imino group, an imide group, an amide group and a quaternary ammonium group.

The cationic polymer is not particularly limited, and includes at least one selected from the group consisting of chitosan, chitosan derivatives, cationic (meth) acrylate copolymers, cationic silicone polymers, diallyl quaternary ammonium salt/acrylamide copolymers, cationic hydrolyzed keratin, cationic hydrolyzed silk, cationic hydrolyzed collagen, cationic hydrolyzed casein, cationic hydrolyzed soybean protein, cationic vinylpyrrolidone copolymers, polyvinylpyrrolidone, homopolymers of dimethyldiallylammonium chloride, copolymers of adipic acid/dimethylaminohydroxypropyl diethylenetriamine, copolymers of adipic acid/epoxypropyl diethylenetriamine, and copolymers of acrylamide/β -methacryloyloxyethyl trimethylammonium methyl sulfate. Among these, the cationic polymer in the present composition is preferably at least one selected from the group consisting of chitosan, a chitosan derivative, a diallyl quaternary ammonium salt/acrylamide copolymer, and polyvinylpyrrolidone, and more preferably at least one selected from the group consisting of chitosan, a chitosan derivative, and polyvinylpyrrolidone.

Chitosan is a polysaccharide substantially composed of (a) a monomer β (1 → 4) -D-glucosamine linkage unit and (B) a monomer β (1 → 4) -N-acetyl-D-glucosamine linkage unit. The ratio of the amounts of (A) and (B) is preferably from about 50 to about 99% for (A) and from about 1 to about 50% for (B). Here, the ratio of the amount of (a) is also referred to as "degree of deacetylation". The viscosity evaluation value of a 1% aqueous solution of chitosan is preferably about 1 to about 3,000 mPas.

Chitosan also contains chitosan salts such as hydrochloride.

Examples of the chitosan derivative include chitosan-N-acetylcysteine and the like.

Examples of the cationic (meth) acrylate copolymer include a vinylpyrrolidone/dialkylamino alkyl (meth) acrylate copolymer, a quaternized derivative of a vinylpyrrolidone/dimethylamino methacrylate copolymer and dimethyl sulfate, and an aminoethyl acrylate phosphate- (meth) acrylate copolymer.

Examples of the cationic silicone polymer include cationic silicone derivatives.

Examples of the diallyl quaternary ammonium salt/acrylamide copolymer include a dimethyldiallylammonium chloride/acrylamide copolymer.

Examples of the cationic hydrolyzed keratin include N- [ 2-hydroxy-3 (trimethyl) propyl ] ammonium chloride hydrolyzed keratin and the like.

Examples of the cationic hydrolyzed yarn include hydrolyzed yarn of N- [ 2-hydroxy-3- (cocoalkyldimethyl) propyl ] ammonium chloride.

Examples of the cationic hydrolyzed collagen include hydrolyzed collagen of N- [ 2-hydroxy-3- (cocoalkyldimethyl) propyl ] ammonium chloride, and the like.

Examples of the cationic hydrolyzed casein include N- [ 2-hydroxy-3- (cocoalkyldimethyl) propyl ] ammonium chloride hydrolyzed casein.

Examples of the cationic hydrolyzed soybean protein include N- [ 2-hydroxy-3- (cocoalkyldimethyl) propyl ] ammonium chloride hydrolyzed soybean protein and the like.

Examples of the cationic vinylpyrrolidone copolymer include copolymers of vinylpyrrolidone/imidazole and a quaternary ammonium salt.

The present composition may contain one kind of cationic polymer or two or more kinds of cationic polymers, but preferably contains only 1 kind of cationic polymer.

The concentration of the cationic polymer in the present composition is not particularly limited, and is, for example, preferably 0.00001 to 10% (w/v), more preferably 0.0001 to 5% (w/v), still more preferably 0.001 to 5% (w/v), yet more preferably 0.01 to 5% (w/v), and yet more preferably 0.01 to 3% (w/v).

In the present invention, polyvinylpyrrolidone refers to a polymer compound obtained by polymerizing N-vinyl-2-pyrrolidone, and is one type of cationic polymer. The K value of the polyvinylpyrrolidone used in the present invention is preferably 17 or more, more preferably 17 to 90, further preferably 25 to 90, and further preferably 30 to 90. Examples thereof include polyvinylpyrrolidone K17, polyvinylpyrrolidone K25, polyvinylpyrrolidone K30, polyvinylpyrrolidone K40, polyvinylpyrrolidone K50, polyvinylpyrrolidone K60, polyvinylpyrrolidone K70, polyvinylpyrrolidone K80, polyvinylpyrrolidone K85, polyvinylpyrrolidone K90 and polyvinylpyrrolidone K120. The K value of polyvinylpyrrolidone is a viscosity characteristic value relating to molecular weight, and is a value calculated by applying a relative viscosity value (25 ℃) measured by a capillary viscometer to the following formula (1) of Fikentscher.

[ mathematical formula 1]

In formula (1), η_relC is a polyvinylpyrrolidone concentration (%) in the aqueous polyvinylpyrrolidone solution, which is a relative viscosity of the aqueous polyvinylpyrrolidone solution with respect to water.

In the present invention, one kind of polyvinylpyrrolidone may be used alone, or two or more kinds of polyvinylpyrrolidone having different K values may be used in combination as desired.

The concentration of the polyvinylpyrrolidone in the present composition is not particularly limited, and is, for example, preferably 0.0001 to 10% (w/v), more preferably 0.001 to 5% (w/v), still more preferably 0.01 to 5% (w/v), yet more preferably 0.01 to 3% (w/v), and particularly preferably 0.1 to 3% (w/v).

In the present composition, pharmaceutically acceptable additives can be further added as needed using a general technique. For example: buffers such as sodium phosphate, sodium hydrogen phosphate, sodium dihydrogen phosphate, sodium acetate, and aminocaproic acid; calcium chloride, sodium chloride, potassium chloride, concentrated glycerin, and the like; stabilizers such as sodium edetate; surfactants such as polysorbates; antioxidants such as ascorbic acid; benzalkonium chloride, chlorhexidine gluconate and other preservatives; pH regulators such as hydrochloric acid and sodium hydroxide; and so on. These additives may be used singly or in combination of two or more kinds as desired.

The pH of the present composition is not limited to a specific value as long as it is within a range allowable as a pharmaceutical. However, the pH of the present composition is preferably 8 or less, more preferably in the range of 4 to 8, still more preferably in the range of 5 to 8, still more preferably in the range of 6 to 8, and particularly preferably about 7.

In the present invention, the "ophthalmic composition" refers to a composition for use in the prevention and/or treatment of an ocular disease or the like. Examples of the dosage form include eye drops, eye ointment, injection, ointment (for example, it can be applied to eyelid skin), and the like, and eye drops are preferred. Here, the term "eye drops" is used as the same meaning as eye drops or eye drops, and the definition of eye drops is also included in eye drops for contact lenses.

The present composition is preferably an aqueous ophthalmic composition using water as a solvent (base), and more preferably an aqueous eye drop.

The present composition may be a soluble eye drop or a suspension eye drop depending on the nature, content, and the like of the active ingredient and the additive.

The viscosity of the present composition is adjusted so as to be in the range of preferably 1 to 500 mPas, more preferably 1 to 100 mPas, still more preferably 1 to 50 mPas, still more preferably 1 to 30 mPas, and particularly preferably 1 to 20 mPas, using a rotational viscometer (25 ℃ C.; 50 s)^-1Shear rate of (d) was measured.

The osmotic pressure of the present composition is not limited to a specific value as long as it is within a range allowable as a pharmaceutical. However, the osmotic pressure of the present composition is preferably 2 or less, more preferably in the range of 0.5 to 2, still more preferably in the range of 0.7 to 1.6, still more preferably in the range of 0.8 to 1.4, and particularly preferably in the range of 0.9 to 1.2.

The composition can be stored in a container made of various materials. For example, containers made of polyethylene, polypropylene, or the like can be used. When the present composition is an eye drop, it is contained in an eye drop container, more specifically, a "multi-dose type eye drop container" or a "unit-dose type eye drop container".

In the present invention, the term "multi-dose type eye drop container" refers to an eye drop container comprising a container body and a lid body attachable to the container body, wherein the lid body of the eye drop container can be freely opened and resealed. In this multi-dose type eye drop container, a plurality of doses of eye drops are stored, which are generally used for a certain period of time. On the other hand, the "unit dose type eye drop container" refers to an eye drop container for the following purpose: the cap is welded and sealed to the bottle mouth portion, and the welded portion between the cap and the bottle-shaped body is broken and opened for use. The unit dose type eye drop container contains a single dose or a plurality of doses of eye drops.

The method of use of the present composition can be appropriately changed depending on the dosage form, the weight, age, body weight, judgment of a doctor, and the like of a patient to be administered, and for example, in the case of selecting an eye drop as a dosage form, the administration of eye drops can be performed 1 to 5 drops, preferably 1 to 3 drops, more preferably 1 to 2 drops, particularly preferably 1 drop, 1 to 6 times a day, preferably 1 to 4 times a day, more preferably 1 to 2 times a day, and daily to weekly. More specifically, the number of eye drops is, for example, preferably 1 day 6, 1 day 5, 1 day 4, 1 day 3, 1 day 2 or 1 day 1, more preferably 1 day 6, 1 day 4, 1 day 3 or 1 day 2, still more preferably 1 day 4 or 1 day 3, and particularly preferably 1 day 3.

In addition, when the concentration of diquafosol or a salt thereof in the present composition is 3% (w/v), the diquafosol or a salt thereof can be administered by eye drop administration in a manner of 1 dose of 1 to 5 drops, preferably 1 to 3 drops, more preferably 1 to 2 drops, particularly preferably 1 drop, 1 day 6, 1 day 5, 1 day 4, 1 day 3, 1 day 2 or 1 day 1, preferably 1 day 6, 1 day 4, 1 day 3 or 1 day 2, more preferably 1 day 4 or 1 day 3, particularly preferably 1 day 3.

Further, the 1 drop is preferably about 0.1 to 30. mu.L, more preferably about 0.5 to 20. mu.L, and further preferably about 1 to 15. mu.L.

The present composition is effective for the prevention or treatment of dry eye. Dry eye is defined as "chronic diseases of tears and keratoconjunctival epithelium due to various factors, and is a disease accompanied by eye discomfort and abnormal vision", and keratoconjunctivitis sicca (KCS) is included in dry eye. In the present invention, the generation of dry eye symptoms due to the wearing of soft contact lenses is also included in dry eye.

The symptoms of dry eye include subjective symptoms such as dry eye, eye discomfort, eye fatigue, heaviness, photophobia, ophthalmalgia, and blurred vision (cloudiness), as well as objective manifestations such as hyperemia and corneal/conjunctival epithelial injury.

There are many unclear points about the causes of dry eye, but the following reasons have been reported: huggeren's syndrome (Sjogren's syndrome); congenital lacrimal disorder; sarcoidosis; graft Versus Host Disease (GVHD: Graft Versus Host Disease) due to bone marrow transplantation; ocular pemphigus (ocular pemphigoid); duffins-Johnson syndrome (Stevens-Johnson syndrome); lacrimal obstruction due to trachoma and the like; diabetes mellitus; a decrease in reflex secretion caused by corneal refractive correction surgery (LASIK: Laser (-assisted) in Situ Keratiomarieuss) or the like; meibomian gland dysfunction; reduction of oil layer due to blepharitis, etc.; blink dysfunction or eyelid closure dysfunction due to eyeball protrusion, rabbit eye, and the like; decreased mucin secretion from embryonic cells; VDT (visual Display terminals) operations; and so on.

The composition can be applied to the eyes of a patient with dry eye who wears soft contact lenses. Here, the term "eye-dropping the eye of a dry eye patient wearing a soft contact lens" means that an eye drop is dropped in a state where the soft contact lens is worn on the cornea of the dry eye patient.