Ophthalmic components

Abstract

This invention relates to an ophthalmic composition comprising: (A) at least one of chondroitin sulfate and its salts selected from the group consisting of chondroitin sulfate and its salts having a weight average molecular weight of 0.1 to 20,000; and (B) at least one of the group consisting of water-soluble vitamins, amino acids and their salts.

Description

Technical Field

[0001] The present invention relates to an ophthalmic composition. Prior Art

[0002] It is known that chondroitin sulfate or its salt is one of acidic mucopolysaccharides and is used to prevent corneal dryness by physiological viscosity. (For example, Non-Patent Document 1). Prior Art Documents Non-Patent Documents

[0003] Non-Patent Document 1: Ophthalmic Chondroitin Sulfate Preparation Chondron (registered trademark) Eye Drops 1% Chondron (registered trademark) Eye Drops 3% Attachment (revised November 2007) Summary of the Invention

[0004] [Problems to be Solved by the Invention] An object of the present invention is to provide a novel ophthalmic composition containing sodium chondroitin sulfate having a specific weight average molecular weight (10,000 to 20,000). [Technical Means for Solving the Problems]

[0005] The present inventors have found that an ophthalmic composition blended with sodium chondroitin sulfate having a weight average molecular weight of 10,000 to 20,000 and a water-soluble vitamin or an amino acid can unexpectedly reduce the elastic modulus of soft contact lenses. In particular, an ophthalmic composition as an OTC pharmaceutical can generally be used when wearing contact lenses. It is useful as an ophthalmic composition having an advantage in contact lenses or during their wearing.

[0006] The present invention provides, for example, the following inventions. [1] An ophthalmic composition comprising: (A) at least one selected from the group consisting of chondroitin sulfate and its salts having a weight average molecular weight of 10,000 to 20,000; and (B) at least one selected from the group consisting of water-soluble vitamins, amino acids, and their salts. [2] The ophthalmic composition according to [1], wherein the content of component (A) is 0.001 to 1 w / v% based on the total amount of the ophthalmic composition. [3] The ophthalmic composition according to [1] or [2], which does not contain a nonionic surfactant. [4] The ophthalmic composition according to any one of [1] to [3], which is used for soft contact lenses. [Effects of the Invention]

[0007] According to the present invention, a novel ophthalmic composition containing sodium chondroitin sulfate having a weight average molecular weight of 0.1×10⁴ to 2×10⁴ can be provided. Embodiment

[0008] Hereinafter, the embodiments of the present invention will be described in detail. However, the present invention is not limited to the following embodiments.

[0009] In this specification, unless otherwise specified, the unit of content “%” means “w / v%” and is synonymous with “g / 100 mL”.

[0010] [(A) At least one selected from the group consisting of chondroitin sulfate having a weight average molecular weight of 0.1×10⁴ to 2×10⁴ and its salts] The ophthalmic composition of the present embodiment contains at least one selected from the group consisting of chondroitin sulfate having a weight average molecular weight of 0.1×10⁴ to 2×10⁴ and its salts (also simply referred to as “component (A)”).

[0011] Chondroitin sulfate and its salts are not particularly limited as long as they are pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable.

[0012] Examples of the salts of chondroitin sulfate include alkali metal salts and alkaline earth metal salts. Examples of the alkali metal salts include sodium salts and potassium salts. Examples of the alkaline earth metal salts include magnesium salts and calcium salts.

[0013] As chondroitin sulfate and its salts, chondroitin sulfate and alkali metal salts of chondroitin sulfate are preferred, chondroitin sulfate and sodium chondroitin sulfate are more preferred, and sodium chondroitin sulfate is even more preferred.

[0014] Chondroitin sulfate and its salts may be natural products or synthetic products. Generally, chondroitin sulfate and its salts derived from animals (preferably mammals, fish, mollusks, etc.; more preferably cows, sharks, cuttlefish, rays, etc.), chondroitin sulfate and its salts derived from mushrooms such as Auricularia auricula, and chondroitin sulfate and its salts derived from algae such as seaweeds are preferably used as natural products. Chondroitin sulfate and its salts derived from sharks and / or rays can be more preferably used. Also, “chondroitin sulfate and its salts produced by fermentation using microorganisms such as lactic acid bacteria, Escherichia coli, and yeast” can be preferably used.

[0015] Commercially available chondroitin sulfate and its salts can also be used. Chondroitin sulfate and its salts can be used alone or in combination of two or more. Also, chondroitin sulfate and its salts with a weight-average molecular weight of 0.1×10⁴ to 2×10⁴ as specified in this specification and chondroitin sulfate and its salts with a weight-average molecular weight outside the range specified in this specification can be used in combination. For example, sodium chondroitin sulfate with a weight-average molecular weight of 1.6×10⁴ and sodium chondroitin sulfate with a weight-average molecular weight of 2.5×10⁴ can be used in combination. When chondroitin sulfate and its salts with a weight-average molecular weight of 0.1×10⁴ to 2×10⁴ as specified in this specification and chondroitin sulfate and its salts with a weight-average molecular weight outside the range specified in this specification are used in combination, it is sufficient that chondroitin sulfate and its salts with a weight-average molecular weight of 0.1×10⁴ to 2×10⁴ are contained as raw materials.

[0016] In this specification, the "weight-average molecular weight" can be determined by gel permeation chromatography using a multi-angle light scattering detector (MALS detector) and a differential refractive index detector (RI detector) connected in series. Specifically, the following conditions are shown. <Standard sample preparation> Prepared by adding 5 mg of chondroitin sulfate or its salt to 10 mL of 0.1 M sodium nitrate aqueous solution and slowly stirring at room temperature to completely dissolve them. <Measurement conditions for weight-average molecular weight> Apparatus: Gel permeation chromatography - multi-angle light scattering meter Detector: Differential refractive index detector (Optilab rEX manufactured by Wyatt Technology) Multi-angle light scattering detector (DAWN HELEOS manufactured by Wyatt Technology) Columns: 2 Shodex OHpak SB-806M HQ (ϕ7.8 mm×30 cm, manufactured by Showa Denko) Solvent: 0.1 M sodium nitrate aqueous solution Flow rate: 0.7 mL / min Column temperature: 23°C Detector temperature: 23°C Injection volume: 0.2 mL Data processing: Data processing system (ASTRA) manufactured by Wyatt Technology

[0017] The weight-average molecular weight of chondroitin sulfate and its salts calculated by the above method is not particularly limited as long as it is in the range of 10,000 to 20,000. As the lower limit of the weight-average molecular weight, examples include 10,000 or more, 20,000 or more, 50,000 or more, 100,000 or more, 110,000 or more, 120,000 or more, and 140,000 or more. As the upper limit of the weight-average molecular weight, examples include 20,000 or less, 195,000 or less, 190,000 or less, 180,000 or less, 170,000 or less, 150,000 or less, 140,000 or less, and 130,000 or less. As the range of the weight-average molecular weight, examples include 10,000 to 20,000, 20,000 to 195,000, 50,000 to 190,000, 120,000 to 180,000, and 140,000 to 170,000. Also, as the range of the weight-average molecular weight, it can also be 100,000 to 140,000.

[0018] The content of component (A) in the ophthalmic composition of the present embodiment is not particularly limited and is appropriately set according to the types and contents of other blended components, the uses and dosage forms of the ophthalmic composition, etc. From the viewpoint of more significantly exerting the effects of the present invention, based on the total amount of the ophthalmic composition, the content of component (A) is preferably, for example, 0.001 to 1 w / v%, more preferably 0.005 to 0.75 w / v%, and still more preferably 0.01 to 0.5 w / v%. Also, the content of component (A) can also be 0.05 to 2 w / v%, 0.1 to 1 w / v%, 0.5 to 1 w / v%, and can also be 0.5 w / v%, 1 w / v%.

[0019] [(B) is at least one selected from the group consisting of water-soluble vitamins, amino acids, and their salts] The ophthalmic composition of the present embodiment contains at least one selected from the group consisting of water-soluble vitamins, amino acids, and their salts (also simply referred to as "component (B)"). The water-soluble vitamins, amino acids, or their salts are not particularly limited as long as they are pharmaceutically, pharmacologically (pharmaceutically), or physiologically acceptable.

[0020] As water-soluble vitamins, examples include: flavin adenine dinucleotide and its salts (such as sodium flavin adenine dinucleotide), cobalamins (such as cyanocobalamin, methylcobalamin, etc.), pantothenic acid and its salts (such as sodium pantothenate, potassium pantothenate, calcium pantothenate, magnesium pantothenate, etc.), panthenol, pyridoxol or its salts (such as pyridoxol hydrochloride), pyridoxal and its salts (such as pyridoxal phosphate), etc., which are vitamin B groups; ascorbic acid and its salts (such as sodium ascorbate), etc., which are vitamin C. Among water-soluble vitamins, from the viewpoint of further enhancing the effects of the present invention, vitamin B groups are preferred, and panthenol, pyridoxol or its salts, flavin adenine dinucleotide or its salts, and cyanocobalamin are more preferred, and panthenol, pyridoxol or its salts are even more preferred.

[0021] As water-soluble vitamins, commercially available ones can also be used. Water-soluble vitamins can be used alone or in combination of two or more.

[0022] As amino acids, examples include: aspartic acid, glutamic acid, asparagine, glutamine, arginine, lysine, glycine, alanine, γ-aminobutyric acid, γ-aminovaleric acid, trimethylglycine, ε-aminocaproic acid, taurine (aminoethanesulfonic acid), etc. As salts of amino acids, examples include salts with inorganic acids (such as salts with hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc.), salts with organic acids (such as salts with acetic acid, succinic acid, fumaric acid, maleic acid, tartaric acid, citric acid, lactic acid, stearic acid, benzoic acid, mesylic acid, ethanesulfonic acid, p-toluenesulfonic acid, etc.), salts with inorganic bases (such as alkali metal salts such as sodium salts and potassium salts, alkaline earth metal salts such as calcium salts and magnesium salts, aluminum salts, ammonium salts), and salts with organic bases (such as salts with diethylamine, diethanolamine, meglumine, N,N-dibenzylethylenediamine, etc.). Amino acids and their salts can also be commercially available ones. As amino acids and their salts, they can be any of L-form, D-form, and DL-form. Among amino acids and their salts, from the viewpoint of further enhancing the effects of the present invention, aspartic acid or its salts, ε-aminocaproic acid, and taurine are preferred, and taurine is more preferred.

[0023] The content of component (B) in the ophthalmic composition of the present embodiment is not particularly limited and is appropriately set according to the type of component (B), the types and contents of other blended components, the dosage form, etc. From the viewpoint of more significantly exerting the effects of the present invention, for example, based on the total amount of the ophthalmic composition of the present embodiment, the total content of component (B) is preferably 0.0001 to 5 w / v%, more preferably 0.0005 to 4 w / v%, and still more preferably 0.001 to 3 w / v%. Also, the total content of component (B) may be 0.005 to 1 w / v%, 0.01 to 0.1 w / v%.

[0024] The content ratio of component (B) to component (A) in the ophthalmic composition of the present embodiment is not particularly limited and is appropriately set according to the types of components (A) and (B), the types and contents of other blended components, the use of the ophthalmic composition, the dosage form, etc. From the viewpoint of further enhancing the effects of the present invention, for example, relative to 1 part by mass of the total content of component (A) contained in the ophthalmic composition of the present embodiment, the total content of component (B) is preferably 0.0001 to 5000 parts by mass, more preferably 0.0005 to 4000 parts by mass, and still more preferably 0.001 to 3000 parts by mass. Also, relative to 1 part by mass of the total content of component (A), the total content of component (B) may be 0.001 to 20 parts by mass, 0.01 to 5 parts by mass, 0.01 to 1 part by mass, 0.02 to 2 parts by mass.

[0025] When component (B) is a water-soluble vitamin, from the viewpoint of more significantly exerting the effects of the present invention, for example, based on the total amount of the ophthalmic composition of the present embodiment, the total content of the water-soluble vitamin is preferably 0.0001 to 0.5 w / v%, more preferably 0.0005 to 0.3 w / v%, and still more preferably 0.001 to 0.2 w / v%. Also, when component (B) is a water-soluble vitamin, the total content of the water-soluble vitamin may be 0.01 to 0.1 w / v%.

[0026] When the component (B) is a water-soluble vitamin, from the viewpoint of further enhancing the effects of the present invention, for example, with respect to 1 part by mass of the total content of the component (A) contained in the ophthalmic composition of the present embodiment, the total content of the water-soluble vitamin is preferably 0.0001 to 500 parts by mass, more preferably 0.0005 to 300 parts by mass, and still more preferably 0.001 to 200 parts by mass. Further, when the component (B) is a water-soluble vitamin, with respect to 1 part by mass of the total content of the component (A), the total content of the water-soluble vitamin may also be 0.001 to 20 parts by mass, 0.01 to 5 parts by mass, 0.01 to 1 part by mass, or 0.02 to 2 parts by mass.

[0027] When the component (B) is an amino acid and its salt, from the viewpoint of more significantly exerting the effects of the present invention, for example, based on the total amount of the ophthalmic composition of the present embodiment, the total content of the amino acid and its salt is preferably 0.0001 to 5 w / v%, more preferably 0.001 to 4 w / v%, and still more preferably 0.05 to 3 w / v%. Further, when the component (B) is an amino acid and its salt, the total content of the amino acid and its salt may also be 0.1 to 2 w / v% or 0.2 to 1 w / v%. Furthermore, when the component (B) is taurine, the content of taurine is preferably 0.1 to 1 w / v%.

[0028] When the component (B) is an amino acid and its salt, from the viewpoint of further enhancing the effects of the present invention, for example, with respect to 1 part by mass of the total content of the component (A) contained in the ophthalmic composition of the present embodiment, the total content of the amino acid and its salt is preferably 0.0001 to 5000 parts by mass, more preferably 0.001 to 4000 parts by mass, and still more preferably 0.05 to 3000 parts by mass. Further, when the component (B) is an amino acid and its salt, with respect to 1 part by mass of the total content of the component (A), the total content of the amino acid and its salt may also be 0.001 to 20 parts by mass, 0.01 to 5 parts by mass, 0.01 to 1 part by mass, or 0.02 to 2 parts by mass.

[0029] 〔Buffer〕 The ophthalmic composition of the present embodiment preferably further contains a buffer. By further containing a buffer in the ophthalmic composition, the effects of the present invention are more significantly exerted. The buffer is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Examples of the buffer include inorganic buffers as buffers derived from inorganic acids and organic buffers as buffers derived from organic acids or organic bases.

[0030] As inorganic buffers, examples include: boric acid buffers, phosphate buffers, carbonate buffers, etc. As boric acid buffers, examples include: boric acid or its salts (alkali metal borates, alkaline earth metal borates, etc.). As phosphate buffers, examples include: phosphoric acid or its salts (alkali metal phosphates, alkaline earth metal phosphates, etc.). As carbonate buffers, examples include: carbonic acid or its salts (alkali metal carbonates, alkaline earth metal carbonates, etc.). Also, as boric acid buffers, phosphate buffers or carbonate buffers, hydrates of borates, phosphates or carbonates can also be used. Regarding more specific examples, as boric acid buffers, examples include: boric acid or its salts (sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, borax, etc.); as phosphate buffers, examples include: phosphoric acid or its salts (disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, trisodium phosphate, tripotassium phosphate, calcium hydrogen phosphate, calcium dihydrogen phosphate, etc.); as carbonate buffers, examples include: carbonic acid or its salts (sodium hydrogen carbonate, sodium carbonate, ammonium carbonate, potassium carbonate, calcium carbonate, potassium hydrogen carbonate, magnesium carbonate, etc.).

[0031] As organic buffers, examples include: citrate buffers, acetate buffers, lactate buffers, succinate buffers, Tris buffers, AMPD buffers, etc. As citrate buffers, examples include: citric acid or its salts (alkali metal citrates, alkaline earth metal citrates, etc.). As acetate buffers, examples include: acetic acid or its salts (alkali metal acetates, alkaline earth metal acetates, etc.). As lactate buffers, examples include: lactic acid or its salts (alkali metal lactates, alkaline earth metal lactates, etc.). As succinate buffers, examples include: succinic acid or its salts (alkali metal succinates, etc.). Also, as citrate buffers, acetate buffers, lactate buffers or succinate buffers, hydrates of citrates, acetates, lactates or succinates can also be used. Regarding more specific examples, as citrate buffers, examples include: citric acid or its salts (sodium citrate, potassium citrate, calcium citrate, sodium dihydrogen citrate, disodium citrate, etc.); as acetate buffers, examples include: acetic acid or its salts (ammonium acetate, sodium acetate, potassium acetate, calcium acetate, etc.); as lactate buffers, examples include: lactic acid or its salts (sodium lactate, potassium lactate, calcium lactate, etc.); as succinate buffers, examples include: succinic acid or its salts (monosodium succinate, disodium succinate, etc.). As Tris buffers, examples include: trometamol or its salts (trometamol hydrochloride, etc.). As AMPD buffers, examples include: 2-amino-2-methyl-1,3-propanediol or its salts.

[0032] As the buffer, a boric acid buffer (such as a combination of boric acid and borax, etc.) is preferred, a boric acid and its salts are more preferred, and a combination of boric acid and borax is even more preferred.

[0033] Commercially available buffers can also be used. One type of buffer can be used alone, or two or more types can be used in combination.

[0034] The content of the buffer in the ophthalmic composition of the present embodiment is not particularly limited and is appropriately set according to the type of buffer, the types and contents of other blended components, the use and dosage form of the ophthalmic composition, etc. Regarding the content of the buffer, from the viewpoint of more significantly exerting the effects of the present invention, for example, based on the total amount of the ophthalmic composition, the total content of the buffer is preferably 0.01 to 4 w / v%, more preferably 0.05 to 3 w / v%, and still more preferably 0.1 to 2 w / v%.

[0035] The content ratio of the buffer in the ophthalmic composition of the present embodiment to the component (A) is not particularly limited and is appropriately set according to the types of the component (A) and the buffer, the types and contents of other blended components, the use and dosage form of the ophthalmic composition, etc. Regarding the content ratio of the buffer to the component (A), from the viewpoint of further enhancing the effects of the present invention, for example, relative to 1 part by mass of the total content of the component (A) contained in the ophthalmic composition of the present embodiment, the total content of the buffer is preferably 0.01 to 4000 parts by mass, more preferably 0.05 to 3000 parts by mass, and still more preferably 0.1 to 2000 parts by mass.

[0036] The pH of the ophthalmic composition of the present embodiment is not particularly limited as long as it is within the range acceptable in medicine, pharmacology (pharmaceutics), or physiology. As the pH of the ophthalmic composition of the present embodiment, for example, it can be 4.0 to 9.5, preferably 4.0 to 9.0, more preferably 4.5 to 9.0, still more preferably 4.5 to 8.5, still more preferably 5.0 to 8.5, and particularly preferably 5.0 to 8.0.

[0037] The ophthalmic composition of the present embodiment can be adjusted as needed to an osmotic pressure ratio within the allowable range of the living body. The appropriate osmotic pressure ratio can be appropriately set according to the use, formulation form, method of use, etc. of the ophthalmic composition. For example, it can be set to 0.4 to 5.0, preferably set to 0.6 to 3.0, more preferably set to 0.8 to 2.2, and even more preferably set to 0.8 to 2.0. The osmotic pressure ratio is based on the seventeenth revised edition of the Japanese Pharmacopoeia, and is the ratio of the osmotic pressure of the sample to the osmotic pressure of 286 mOsm (the osmotic pressure of a 0.9 w / v% sodium chloride aqueous solution). The osmotic pressure is measured with reference to the osmotic pressure measurement method (cryoscopic method) described in the Japanese Pharmacopoeia. Furthermore, the standard solution (0.9 w / v% sodium chloride aqueous solution) for measuring the osmotic pressure ratio is prepared as follows: After drying sodium chloride (Japanese Pharmacopoeia standard reagent) at 500 to 650 °C for 40 to 50 minutes, it is placed in a desiccant (silica gel) to cool, and 0.900 g of it is accurately weighed and dissolved in purified water to accurately prepare 100 mL; alternatively, a commercially available standard solution (0.9 w / v% sodium chloride aqueous solution) for measuring the osmotic pressure ratio can be used.

[0038] The viscosity of the ophthalmic composition of the present embodiment is not particularly limited as long as it is within the range pharmaceutically, pharmacologically (pharmaceutically), or physiologically acceptable. As the viscosity of the ophthalmic composition of the present embodiment, for example, the viscosity at 20 °C measured using a rotational viscometer (TV-20 type viscometer, manufactured by Toki Sangyo Co., Ltd., rotor: 1°34'×R24) is preferably 1 to 10,000 mPa·s, more preferably 1 to 8,000 mPa·s, even more preferably 1 to 1,000 mPa·s, even more preferably 1 to 100 mPa·s, particularly preferably 1 to 20 mPa·s, and most preferably 1.5 to 10 mPa·s.

[0039] As long as it is within the range that does not damage the effects of the present invention, the ophthalmic composition of the present embodiment may also contain, in combination and in an appropriate amount, components selected from various pharmacologically active ingredients and physiologically active ingredients other than the above-mentioned components. There is no particular limitation on this component. For example, the active ingredients in ophthalmic drugs described in the 2017 edition of the General Standards for the Manufacture and Sale of Pharmaceuticals for General Use (supervised by the Regulatory Science Society, Incorporated Association) can be exemplified. As the components that can be used in ophthalmic drugs, specifically, the following components can be exemplified. Antihistamines: For example, sodium cromoglycate, tranilast, potassium pemirolast, acitazanolast, amlexanox, ibudilast, etc. Antihistamines: such as chlorpheniramine or its salts (e.g., chlorpheniramine maleate), diphenhydramine or its salts (e.g., diphenhydramine hydrochloride), iproheptine or its salts (e.g., iproheptine hydrochloride), levocabastine or its salts (e.g., levocabastine hydrochloride), ketotifen or its salts (e.g., ketotifen fumarate), potassium pemirolast, olopatadine or its salts (e.g., olopatadine hydrochloride), etc. Anti-inflammatory agents: such as methyl salicylate, ethylene glycol salicylate, allantoin, tranexamic acid, lysozyme, lysozyme chloride, indometacin, pranoprofen, ibuprofen, ibuprofen piconol, ketoprofen, felbinac, bendazac, piroxicam, bufexamac, butyl flufenamate, ε-aminocaproic acid, berberine chloride, berberine sulfate, sodium azulene sulfonate, glycyrrhizic acid or its salts (e.g., dipotassium glycyrrhizate, monammonium glycyrrhizate), etc. Steroid agents: such as fluticasone propionate, fluticasone furoate, mometasone furoate, beclomethasone propionate, flunisolide, etc. Decongestants: such as tetrahydrozoline hydrochloride, tetrahydrozoline nitrate, naphazoline hydrochloride, naphazoline nitrate, adrenaline, adrenaline hydrochloride, ephedrine hydrochloride, norepinephrine hydrochloride, dl-methylephedrine hydrochloride, etc. Ocular accommodation agents: such as cholinesterase inhibitors having an active center similar to acetylcholine, specifically, neostigmine methylsulfate, tropicamide, helenien, atropine sulfate, pilocarpine hydrochloride, etc. Fat-soluble vitamins: such as retinol acetate, retinol palmitate, tocopherol acetate, etc. Others: such as sulfamethoxazole, sulfisoxazole, sulfisomidine, and their salts, etc. In the ophthalmic composition of this embodiment, within the range of not impairing the effects of the present invention, various additives can also be appropriately selected according to their uses and dosage forms according to conventional methods, and one or more kinds can be used in combination and contain an appropriate amount. As such additives, for example, various additives described in the Pharmaceutical Additives Dictionary 2016 (edited by the Japan Pharmaceutical Additives Association) can be exemplified. As representative components, the following additives can be cited.

[0040] Vehicles: such as aqueous solvents such as water and hydrous ethanol. Chelating agents: such as ethylenediaminediacetic acid (EDDA), ethylenediaminetriacetic acid, ethylenediaminetetraacetic acid (EDTA), N-(2-hydroxyethyl)ethylenediaminetriacetic acid (HEDTA), diethylenetriaminepentaacetic acid (DTPA), etc. Bases: such as octyldodecanol, titanium oxide, potassium bromide, plastibase, etc. pH adjusters: such as hydrochloric acid, acetic acid, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, triethanolamine, monoethanolamine, diisopropanolamine, etc. Viscosity increasing agents: such as cellulose-based polymer compounds such as methylcellulose, ethylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, sodium carboxymethylcellulose; polyethylene-based polymer compounds such as polyvinylpyrrolidone and polyvinyl alcohol; carboxyvinyl polymer; guar gum; hydroxypropyl guar gum; gum arabic; karaya gum; tragacanth gum; agar; alginic acid and its salts (such as sodium salt, etc.); mucopolysaccharides such as heparin analogs, heparin, heparan sulfate, heparinoid, hyaluronic acid and its salts (such as sodium salt, etc.); starch; chitin and its derivatives; chitosan and its derivatives; carrageenan; monosaccharides such as glucose, etc. Stabilizers: such as ethylenediaminetetraacetic acid, ethylenediaminetetraacetate salts (disodium ethylenediaminetetraacetate, calcium disodium ethylenediaminetetraacetate, trisodium ethylenediaminetetraacetate, tetrasodium ethylenediaminetetraacetate), rongalite, aluminum monostearate, glyceryl monostearate, cyclodextrin, monoethanolamine, dibutylhydroxytoluene, sodium bisulfite, sodium metabisulfite, etc. ​Preservatives: such as alkyl polyaminoethyl glycine quaternary ammonium salts (such as benzalkonium chloride, benzethonium chloride, etc.), loceryl gluconate, polidronium chloride, zinc chloride, sodium benzoate, ethanol, chlorobutanol, sorbic acid, potassium sorbate, sodium dehydroacetate, methyl paraben, ethyl paraben, propyl paraben, butyl paraben, hydroxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, biguanide compounds (specifically, polyhexamethylene biguanide hydrochloride (polyhexamethylene biguanide), alexidine, etc.), Glokill (trade name, manufactured by Rhodia Japan, Ltd.), etc. Isotonic agents: such as potassium chloride, calcium chloride, sodium chloride, magnesium chloride, potassium acetate, sodium acetate, sodium bicarbonate, sodium carbonate, sodium thiosulfate, magnesium sulfate, glycerol, propylene glycol, sodium bisulfite, sodium sulfite, etc. Sugar alcohols: such as xylitol, sorbitol, mannitol, glycerol, etc. They can be any one of the d-form, l-form or dl-form.

[0041] In terms of being able to more significantly exhibit the effects of the present invention, the ophthalmic composition of the present embodiment preferably does not contain POE sorbitan monolaurate, more preferably does not contain POE sorbitan monolaurate and polyoxyethylene hydrogenated castor oil, and still more preferably does not contain nonionic surfactants. Examples of nonionic surfactants include: POE(20) sorbitan monolaurate (polysorbate 20), POE(20) sorbitan monopalmitate (polysorbate 40), POE(20) sorbitan monostearate (polysorbate 60), POE(20) sorbitan tristearate (polysorbate 65), POE(20) sorbitan monooleate (polysorbate 80) and other POE sorbitan fatty acid esters; poloxamer 407, poloxamer 235, poloxamer 188, poloxamer 403, poloxamer 237, poloxamer 124 and other POE·POP diols; POE hydrogenated castor oil 40, POE hydrogenated castor oil 50, POE hydrogenated castor oil 60, POE hydrogenated castor oil 80 and other POE hydrogenated castor oils; POE castor oil 3, POE castor oil 4, POE castor oil 6, POE castor oil 7, POE castor oil 10, POE castor oil 13.5, POE castor oil 17, POE castor oil 20, POE castor oil 25, POE castor oil 30, POE castor oil 35, POE castor oil 50 and other POE castor oils; polyethylene glycol monostearate (2 E.O.), polyethylene glycol monostearate (4 E.O.), polyethylene glycol monostearate (9 E.O.), polyethylene glycol monostearate (10 E.O.), polyethylene glycol monostearate (23 E.O.), polyethylene glycol monostearate (25 E.O.), polyethylene glycol monostearate (32 E.O.), polyethylene glycol monostearate (40 E.O.) (polyethylene glycol 40 stearate), polyethylene glycol monostearate (45 E.O.), polyethylene glycol monostearate (55 E.O.), polyethylene glycol monostearate (75 E.O.), polyethylene glycol monostearate (140 E.O.) and other polyethylene glycol monostearates; POE(9) lauryl ether and other POE alkyl ethers; POE(20)POP(4) hexadecyl ether and other POE-POP alkyl ethers; POE(10) nonylphenyl ether and other POE alkyl phenyl ethers. Furthermore, in the above-exemplified compounds, POE represents polyoxyethylene, POP represents polyoxypropylene, and the numbers in parentheses represent the number of moles of addition.

[0042] In terms of being able to more significantly exhibit the effects of the present invention, the ophthalmic composition of the present embodiment preferably does not contain terpenoids. Examples of terpenoids include: menthol, camphor, borneol, geraniol.

[0043] When the ophthalmic composition of the present embodiment contains water, from the viewpoint of more significantly exhibiting the effects of the present invention, for example, based on the total amount of the ophthalmic composition, the water content is preferably 80 w / v% or more and less than 100 w / v%, more preferably 85 w / v% or more and 99.5 w / v% or less, and still more preferably 90 w / v% or more and 99.2 w / v% or less.

[0044] The water used in the ophthalmic composition of the present embodiment only needs to be pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Examples of such water include distilled water, ordinary water, purified water, sterilized purified water, water for injection, and distilled water for injection. Their definitions are based on the 17th revised edition of the Japanese Pharmacopoeia.

[0045] The ophthalmic composition of the present embodiment can be prepared by adding the required amounts of component (A), component (B), and other components as needed to a desired concentration and mixing them. For example, it can be prepared by dissolving or dispersing these components in purified water, adjusting to a specified pH and osmotic pressure, and performing a sterilization treatment such as filtration sterilization.

[0046] The ophthalmic composition of the present embodiment can adopt various dosage forms according to the purpose. Examples of dosage forms include liquid agents, gel agents, semi-solid agents (such as ointments), etc.

[0047] The ophthalmic composition of the present embodiment can be used, for example, as eye drops (also known as eye drops or eye medications. Also, eye drops include eye drops that can be instilled when wearing contact lenses), artificial tears, eye washes (also known as eye wash solutions or eye wash medications. Also, eye washes include eye washes that can be used for eye washing when wearing contact lenses), contact lens compositions [contact lens wearing solutions, contact lens care compositions (contact lens disinfectants, contact lens preservatives, contact lens cleaners, contact lens cleaning preservatives), contact lens packaging solutions, etc.]. Furthermore, "contact lenses" include hard contact lenses and soft contact lenses (including both ionic and non-ionic types, including both silicone hydrogel contact lenses and non-silicone hydrogel contact lenses).

[0048] In terms of being able to more significantly exhibit the effects of the present invention, the ophthalmic composition of the present embodiment is preferably an eye drop (including an eye drop that can be instilled when wearing contact lenses). When the ophthalmic composition of the present embodiment is an eye drop, regarding its usage and dosage, as long as it is a usage and dosage that can exhibit effects with fewer side effects, there is no particular limitation. For example, in the case of adults (15 years old and above) and children 7 years old and above, a method of instilling 1 to 3 drops, 1 to 2 drops, or 2 to 3 drops once, and 2 to 4 times or 5 to 6 times a day can be exemplified.

[0049] The ophthalmic composition of the present embodiment is provided in an arbitrary container. The container for accommodating the ophthalmic composition of the present embodiment is not particularly limited. For example, it can be made of glass, and it can also be made of plastic. It is preferably made of plastic. As the plastic, for example, polyethylene terephthalate (PET), polyarylate (PAR), polyethylene naphthalate (PEN), polycarbonate (PC), polyethylene (PE), polypropylene (PP), polyimide (PI), cyclic olefin copolymer (COC), copolymers of monomers constituting them, and mixtures of two or more of them can be exemplified. It is preferably polyethylene terephthalate (PET). Further, the container for accommodating the ophthalmic composition of the present embodiment can be a transparent container that allows visual recognition of the inside of the container, or an opaque container that makes it difficult to visually recognize the inside of the container. It is preferably a transparent container. Here, the "transparent container" includes both a colorless transparent container and a colored transparent container.

[0050] A nozzle can also be installed on the container for accommodating the ophthalmic composition of the present embodiment. The material of the nozzle is not particularly limited. For example, it can be made of glass, and it can also be made of plastic. It is preferably made of plastic. As the plastic, for example, polybutylene terephthalate (PBT), polyethylene (PE), polypropylene (PP), polyethylene terephthalate (PET), polyethylene naphthalate (PEN), and copolymers of monomers constituting them, and mixtures of two or more of them can be exemplified. From the viewpoint of further improving the effects of the present invention, the material of the nozzle is preferably polypropylene (PP), polyethylene (PE), polyethylene terephthalate (PET), polybutylene terephthalate (PBT), polyethylene naphthalate (PEN), and more preferably polyethylene (PE).

[0051] The container for accommodating the ophthalmic composition of the present embodiment can be a multi-dose type that accommodates a plurality of usage amounts, or a single-dose type that accommodates a single usage amount.

[0052] The ophthalmic composition of the present embodiment is preferably filled in a container with an internal volume of 4 to 30 mL, more preferably filled in a container with an internal volume of 5 to 20 mL, still more preferably filled in a container with an internal volume of 10 to 18 mL, and even more preferably filled in a container with an internal volume of 15 to 18 mL. Also, it can be filled in a container with an internal volume of 0.1 to 3 mL, and can also be filled in a container with an internal volume of 0.2 to 1 mL.

[0053] As shown in the examples described later, the ophthalmic composition of the present embodiment contains sodium chondroitin sulfate having a weight average molecular weight of 0.1×10⁴ to 2×10⁴, and has the effect of significantly reducing the elastic modulus of soft contact lenses. Therefore, it is preferably an ophthalmic composition for soft contact lenses. If the elastic modulus of the soft contact lens is reduced, the soft contact lens becomes softer, whereby it is possible to more effectively reduce the foreign body friction or stiffness during and / or when wearing the soft contact lens, and the discomfort caused by poor wearing feeling. Also, as an embodiment of the present invention, there is provided a method for imparting the effect of reducing the elastic modulus of a soft contact lens to an ophthalmic composition, which includes: blending (B) at least one selected from the group consisting of water-soluble vitamins, amino acids, and their salts in an ophthalmic composition containing (A) at least one selected from the group consisting of chondroitin sulfate having a weight average molecular weight of 0.1×10⁴ to 2×10⁴ and its salts.

[0054] In the above embodiment, the ratio of reducing the elastic modulus of the soft contact lens (hereinafter, also referred to as "reduction rate of elastic modulus") is not particularly limited, and the reduction rate of the elastic modulus of the soft contact lens is preferably 10 to 50%. Here, the reduction rate of the elastic modulus of the soft contact lens in the present embodiment is calculated by the following formula. Furthermore, in this specification, the "elastic modulus of the soft contact lens" means the value measured by using an MCR302 rheometer manufactured by Anton Paar and using a parallel plate PP12 / P12. [Formula] Reduction rate of elastic modulus (%) = (Elastic modulus of comparative composition (Pa) - Elastic modulus of the agent of the present embodiment (Pa)) / Elastic modulus of comparative composition (Pa) × 100 Here, the comparative composition is a composition having the same composition as the ophthalmic composition of the present embodiment except that it does not contain (B) at least one selected from the group consisting of water-soluble vitamins, amino acids, and their salts. Examples

[0055] Hereinafter, the present invention will be specifically described based on test examples, but the present invention is not limited thereto.

[0056] 〔Preparation of Test Solution〕 Prepare the test solutions shown in Table 1 according to a conventional method. Furthermore, the unit of each component in Table 1 is g / 100 mL. Also, the sodium chondroitin sulfate used in the following test examples is as described below. Sodium chondroitin sulfate Weight-average molecular weight of approximately 16,000: MARUHA NICHIRO Corporation: Sodium chondroitin sulfate according to the Japanese Pharmaceutical Codex

[0057] 〔Test Example 1: Evaluation of Elastic Modulus Change〕 Dispense physiological saline (manufactured by Otsuka Pharmaceutical Factory, Inc.) into a 12-well plate (BD Falcon, No. 35-3043) at 4 mL per well, and immerse 1 contact lens (PRECISION 1: manufactured by ALCON) in each well, and let stand at room temperature for 4 hours or more. Dispense each of the test solutions described in Table 1 prepared above into another 12-well plate (BD Falcon, No. 35-3043) at 4 mL per well, and immerse 1 contact lens whose moisture has been gently wiped off with lint free paper in each well, and let stand at 34 °C for 24 hours.

[0058] Use an MCR302 rheometer (manufactured by Anton Paar), and set it to parallel plate PP12 / P12 (diameter 12 mm, grid processing; 1×0.5, product number: 23935), cover plate P-PTD200 / 80-77 / SS / P2 (grid processing, product number: 7894), measurement temperature 20 °C, frequency 1 Hz, measurement time "no time setting" mode, and measure the shear stress (Pa) corresponding to a strain of 0.01 to 1%. Specifically, add 0.5 mL of physiological saline to the cover plate, place the convex surface of the contact lens from which the moisture has been wiped (place the convex surface of the lens facing the cover plate side) on it, and add 0.5 mL of physiological saline to the contact lens. Lower the parallel plate to approach the cover plate, and set the position so that the contact lens is sandwiched at a distance of 0.1 mm between the two plates, and start measuring the shear stress (Pa). Regarding the measurement interval, measurements are made at 5 points evenly dividing the strain of 0.01 to 0.1% and 5 points evenly dividing the strain of 0.1 to 1%. The second point of the measurement interval of the strain of 0.01 to 0.1%, i.e., 0.0325%, and 1% of the measurement interval of the strain of 0.1 to 1% are used in [Equation 1] to calculate the elastic modulus (Pa). The measurement is performed 3 times, and the average value is set as the average elastic modulus (Pa). [Equation 1] Elastic modulus (Pa) = Shear stress / Strain = (Shear stress at 1% strain) - (Shear stress at 0.0325% strain) / (1 - 0.0325)

[0059] Using the average elastic modulus (Pa) in Examples 1 to 3, calculate the reduction rate (%) of the elastic modulus relative to the corresponding reference example according to [Equation 2]. [Equation 2] Reduction rate (%) of the elastic modulus relative to the corresponding reference example = (Average elastic modulus (Pa) of the corresponding reference example - Average elastic modulus (Pa) of the example) / Average elastic modulus (Pa) of the corresponding reference example × 100 The reference example corresponding to Examples 1 to 3 is Reference Example 1.

[0060] [Table 1] Example 1 Example 2 Example 3 Reference Example 1 Sodium chondroitin sulfate (Weight average molecular weight: 16,000) 0.5 0.5 0.5 0.5 Pyridoxine hydrochloride 0.1 - - - Panthenol - 0.1 - - Taurine - - 1.0 - Boric acid 1.2 1.2 1.2 1.2 Borax 0.1 0.1 0.1 0.1 Purified water Remainder Remainder Remainder Remainder Total amount 100 mL 100 mL 100 mL 100 mL pH 7 7 7 7 Elastic modulus reduction rate (%) relative to Reference Example 1 17.0 16.6 31.9

[0061] For Examples 1 to 3 containing sodium chondroitin sulfate with a weight average molecular weight of 16,000 and water-soluble vitamins or amino acids, compared to Reference Example 1 without water-soluble vitamins or amino acids, the elastic modulus reduction rate of the soft contact lenses was 16.6 to 31.9%, indicating that in the ophthalmic composition containing sodium chondroitin sulfate with a weight average molecular weight of 10,000 to 20,000, water-soluble vitamins or amino acids have the effect of softening the hardened soft contact lenses.

[0062] [Formulation Example] Prepare Formulation Examples 1 to 16 according to the formulations described in Tables 2 and 3 below. Those in which Formulation Examples 1 to 16 are filled into containers made of polyethylene terephthalate and equipped with nozzles made of low-density polyethylene are designated as Formulation Examples 1 to 16. Those in which Formulation Examples 1 to 16 are filled into containers made of polyethylene terephthalate and equipped with nozzles made of polybutylene terephthalate on the entire wall surface where contact with the content liquid may occur when the lid is installed (during storage) are designated as Formulation Examples 17 to 32. Those in which Formulation Examples 1 to 16 are filled into containers made of polyethylene terephthalate and equipped with nozzles made of polyethylene terephthalate on a part of the wall surface where contact with the content liquid may occur are designated as Formulation Examples 33 to 48. Furthermore, the units in the table are w / v% unless otherwise specified.

[0063] [Table 2] Component name Formulation Example 1 Formulation Example 2 Formulation Example 3 Formulation Example 4 Formulation Example 5 Formulation Example 6 Formulation Example 7 Formulation Example 8 Formulation Example 9 Formulation Example 10 Sodium chondroitin sulfate (Weight average molecular weight: 16,000) 0.5 1 0.1 0.25 0.1 0.5 0.25 0.4 0.2 0.15 Sodium flavin adenine dinucleotide - - 0.05 - - - - 0.01 0.05 - Cyanocobalamin - 0.01 - - - - 0.020 - - - Pyridoxine hydrochloride - 0.05 0.1 - 0.01 0.08 - - 0.01 - Panthenol 0.05 - - 0.1 - 0.025 - - - 0.05 Potassium L-aspartate 0.5 0.5 0.5 - 0.8 - - 0.1 1 - Potassium magnesium L-aspartate - - - 0.800 - - 1 - 2 - Taurine 0.5 0.5 1 0.5 1 - 0.5 0.1 1 - ε-Aminocaproic acid - 1 1 - 2.5 - - - 1 - Tetrahydrozoline hydrochloride 0.01 0.03 0.1 0.01 0.01 0.02 - - - 0.02 Neostigmine Methylsulfate - 0.005 - 0.005 0.005 - - - - 0.0025 Allantoin 0.1 - - - - - 0.1 - - - Dipotassium Glycyrrhizinate - 0.1 0.25 - - 0.25 0.1 - - 0.25 Sodium Azelate - - - 0.01 - - - 0.02 - - Berberine Chloride - - - - - 0.01 - 0.01 - - Zinc sulfate - 0.05 - - - - 0.1 - - 0.1 Chlorpheniramine maleate - 0.03 0.03 0.03 0.03 0.02 0.01 0.03 - - Potassium chloride - 0.008 - - - - - - - - Sodium chloride - - - - - - 0.1 - - - Benzalkonium chloride - 0.01 - - - - - - - - Loceryl gluconate - - - - - - - - 0.005 - Polyhexamethylene guanidine hydrochloride 1 ppm - 1 ppm - - - - - - - Chlorobutanol 0.1 0.2 0.1 - - - 0.2 - - - Zinc chloride - - - - - - - - - 0.001 Sodium ethylenediaminetetraacetate 0.01 0.05 0.01 0.05 0.05 - 0.01 0.01 0.05 0.05 Boric acid 1.2 0.2 0.3 0.1 0.5 0.3 0.1 1 0.4 0.1 Borax 0.3 0.1 0.05 0.025 - - 0.01 0.1 0.1 0.2 Sodium hydrogen phosphate - - - - - - - - - 0.15 Sodium dihydrogen phosphate - - - - - - - - - 0.2 Citric acid - - - - - - - - 0.1 - Tromethamine - - - - 0.3 - - - - - Propylene Glycol - - - - 0.2 - - - - - Concentrated Glycerol 0.1 - - - - - - - - - Sodium Hyaluronate 0.005 0.002 - - - - - - - 0.01 Dextran - - - 0.05 - - - - - - L-Arginine - - - - - - - - - 0.1 Polyvinylpyrrolidone - - - - - - 0.1 - - - Hydroxyethyl cellulose - - 0.1 - - - - - - - Hydroxypropyl methyl cellulose 0.1 - - - - - 0.2 - 0.01 - Hydrochloric acid Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Sodium hydroxide Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Purified water The balance The balance The balance The balance The balance The balance The balance Remainder Remainder Remainder Total amount 100 mL 100 mL 100 mL 100 mL 100 mL 100 mL 100 mL 100 mL 100 mL 100 mL pH 5.8 6.0 5.7 6.2 5.8 5.8 5.3 5.7 6.5 5.5

[0064] [Table 3] Component name Formulation Example 11 Formulation Example 12 Formulation Example 13 Formulation Example 14 Formulation Example 15 Formulation Example 16 Sodium chondroitin sulfate (Weight average molecular weight: 16,000) 0.2 1 0.5 0.3 0.25 0.5 Potassium L-aspartate - - 1 - 0.5 0.5 Potassium magnesium L-aspartate 2 1 - - 0.5 - Taurine - 0.5 - 1 - 0.5 ε-Aminocaproic acid - - - - 1 - Potassium chloride - - 0.08 - - 0.05 Sodium chloride 0.1 0.4 0.1 0.3 0.2 0.4 Benzalkonium chloride - 0.01 - - - - Loceryl gluconate - - - - 0.02 - Polyhexamethylene biguanide hydrochloride 1 ppm - 1 ppm - - - Chlorobutanol 0.15 - - - - - Zinc chloride - - - - - 0.0001 Sodium ethylenediaminetetraacetate - 0.005 0.05 0.02 0.01 0.05 Boric acid 1 1 0.4 1 - 1 Borax - 0.1 0.1 0.2 - 0.2 Sodium hydrogen phosphate - - - - 0.15 - Sodium dihydrogen phosphate - - - - 0.1 - Citric acid - - 0.1 - - 0.1 Concentrated glycerol - - - - - 0.1 Sodium hyaluronate - 0.02 - - - - L-Arginine - 0.5 - - - - Polyvinylpyrrolidone - - 0.5 0.1 - - Hydroxyethyl cellulose 0.07 - - - 0.2 - Hydroxypropyl methylcellulose - - 0.1 - 0.2 0.3 Hydrochloric acid Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Sodium hydroxide Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Purified water The balance The balance The balance The balance The balance The balance Total amount 100 mL 100 mL 100 mL 100 mL 100 mL 100 mL pH 6.5 7.2 6.8 7.0 7.5 6.2

Claims

1. An ophthalmic composition comprising: (A) at least one of chondroitin sulfate and its salts selected from the group consisting of chondroitin sulfate and its salts having a weight-average molecular weight of 0.1 to 20,000; and (B) at least one of the group consisting of water-soluble vitamins, amino acids and their salts, wherein the content of component (A) is 0.01 to 0.5 w / v based on the total amount of the ophthalmic composition.

2. The ophthalmic composition of claim 1 does not contain nonionic surfactants.

3. The ophthalmic composition of claim 1, used in soft contact lenses.