Ophthalmic composition

Abstract

The present invention pertains to an ophthalmic composition containing (A) at least one selected from the group consisting of chondroitin sulfate having a weight average molecular weight of 1000 to 20000 and a salt thereof, and (B) at least one selected from the group consisting of water-soluble vitamins, amino acids, and salts thereof.

Description

Ophthalmic composition

[0001] The present invention relates to ophthalmic compositions.

[0002] Chondroitin sulfate or its salts are a type of acidic mucopolysaccharide, and are known to be used to prevent corneal dryness due to their physiological viscosity (see, for example, Non-Patent Document 1).

[0003] Chondroitin sulfate preparation for ophthalmic use Chondron (registered trademark) eye drops 1% Chondron (registered trademark) eye drops 3% Package insert (revised November 2007)

[0004] An object of the present invention is to provide a novel ophthalmic composition containing sodium chondroitin sulfate having a specific weight-average molecular weight (1,000 to 20,000).

[0005] The present inventors have unexpectedly discovered that an ophthalmic composition containing sodium chondroitin sulfate having a weight-average molecular weight of 1,000 to 20,000 and a water-soluble vitamin or amino acid can reduce the elastic modulus of soft contact lenses. In particular, ophthalmic compositions that are OTC drugs are generally usable while wearing contact lenses. Ophthalmic compositions that are advantageous for contact lenses and their use are useful.

[0006] The present invention provides, for example, the following inventions. [1] An ophthalmic composition containing (A) at least one selected from the group consisting of chondroitin sulfate and salts thereof having a weight-average molecular weight of 1,000 to 20,000, and (B) at least one selected from the group consisting of water-soluble vitamins, amino acids, and salts thereof. [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 of [1] to [3], which is for use in soft contact lenses.

[0007] According to the present invention, a novel ophthalmic composition containing sodium chondroitin sulfate having a weight-average molecular weight of 1,000 to 20,000 can be provided.

[0008] Hereinafter, embodiments of the present invention will be described in detail, but 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 and salts thereof having a weight-average molecular weight of 1,000 to 20,000] The ophthalmic composition according to this embodiment contains at least one selected from the group consisting of chondroitin sulfate and salts thereof having a weight-average molecular weight of 1,000 to 20,000 (also simply referred to as "component (A)").

[0011] There are no particular limitations on the chondroitin sulfate and its salts, so long as they are medicamentally, pharmacologically (pharmaceutical) or physiologically acceptable.

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

[0013] As chondroitin sulfate and salts thereof, 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 or synthetic, but generally preferred are chondroitin sulfate and its salts derived from natural animals (preferably mammals, fish, mollusks, etc.; more preferably cattle, sharks, squid, rays, etc.), chondroitin sulfate and its salts derived from mushrooms such as wood ear mushrooms, and chondroitin sulfate and its salts derived from algae such as seaweed, with shark and / or ray-derived chondroitin sulfate and its salts being more preferred. Also preferred are chondroitin sulfate and its salts produced by fermentation using microorganisms such as lactic acid bacteria, Escherichia coli, and yeast.

[0015] Commercially available chondroitin sulfate and its salts can also be used. Chondroitin sulfate and its salts can be used singly or in combination of two or more. Furthermore, chondroitin sulfate and its salts having a weight-average molecular weight of 1,000 to 20,000 as defined herein can be used in combination with chondroitin sulfate and its salts having a weight-average molecular weight outside the range defined herein. For example, sodium chondroitin sulfate having a weight-average molecular weight of 16,000 can be used in combination with sodium chondroitin sulfate having a weight-average molecular weight of 25,000. When chondroitin sulfate and its salts having a weight-average molecular weight of 1,000 to 20,000 as defined herein are used in combination with chondroitin sulfate and its salts having a weight-average molecular weight outside the range defined herein, it is sufficient that chondroitin sulfate and its salts having a weight-average molecular weight of 1,000 to 20,000 are used as raw materials.

[0016] In this specification, the "weight average molecular weight" can be determined by using gel permeation chromatography with a multi-angle light scattering detector (MALS detector) and a refractive index detector (RI detector) connected online. Specifically, the following conditions are presented. <Standard sample preparation> 10 mL of 0.1 M sodium nitrate aqueous solution was added to 5 mg of chondroitin sulfate or a salt thereof, and the mixture was gently stirred at room temperature until completely dissolved. <Conditions for measuring weight-average molecular weight> Apparatus: Gel permeation chromatograph-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) Column: Two Shodex OHpak SB-806M HQ (φ7.8 mm × 30 cm, manufactured by Showa Denko) Solvent: 0.1 M aqueous sodium nitrate 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 1,000 to 20,000. Examples of lower limits of the weight-average molecular weight include 1,000 or more, 2,000 or more, 5,000 or more, 10,000 or more, 11,000 or more, 12,000 or more, and 14,000 or more. Examples of upper limits of the weight-average molecular weight include 20,000 or less, 19,500 or less, 19,000 or less, 18,000 or less, 17,000 or less, 15,000 or less, 14,000 or less, and 13,000 or less. Examples of ranges of the weight-average molecular weight include 1,000 to 20,000, 2,000 to 19,500, 5,000 to 19,000, 12,000 to 18,000, and 14,000 to 17,000. The weight-average molecular weight may also be in the range of 10,000 to 14,000.

[0018] The content of component (A) in the ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the types and contents of other blended components, the intended use of the ophthalmic composition, the formulation, etc. From the viewpoint of more significantly achieving the effects of the present invention, the content of component (A) is, for example, preferably 0.001 to 1 w / v%, more preferably 0.005 to 0.75 w / v%, and even more preferably 0.01 to 0.5 w / v%, based on the total amount of the ophthalmic composition. Furthermore, the content of component (A) may be 0.05 to 2 w / v%, 0.1 to 1 w / v%, 0.5 to 1 w / v%, or even 0.5 w / v%, or 1 w / v%.

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

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

[0021] As the water-soluble vitamin, commercially available products can also be used. The water-soluble vitamins may be used alone or in combination of two or more.

[0022] Examples of amino acids include aspartic acid, glutamic acid, asparagine, glutamine, arginine, lysine, glycine, alanine, γ-aminobutyric acid, γ-aminovaleric acid, trimethylglycine, ε-aminocaproic acid, aminoethylsulfonic acid (taurine), etc. Examples of amino acid salts include salts with inorganic acids (e.g., salts with hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc.), salts with organic acids (e.g., salts with acetic acid, succinic acid, fumaric acid, maleic acid, tartaric acid, citric acid, lactic acid, stearic acid, benzoic acid, methanesulfonic acid (mesylic acid), ethanesulfonic acid, p-toluenesulfonic acid, etc.), salts with inorganic bases (e.g., alkali metal salts such as sodium salt and potassium salt, alkaline earth metal salts such as calcium salt and magnesium salt, aluminum salt, ammonium salt), and salts with organic bases (e.g., salts with diethylamine, diethanolamine, meglumine, N,N-dibenzylethylenediamine, etc.). Commercially available amino acids and salts thereof can also be used. The amino acids and salts thereof may be any of L-, D-, and DL-isomers. Among the amino acids and salts thereof, aspartic acid or a salt thereof, ε-aminocaproic acid, and aminoethylsulfonic acid are preferred, with aminoethylsulfonic acid being more preferred, from the viewpoint of further enhancing the effects of the present invention.

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

[0024] The content ratio of component (B) relative to component (A) in the ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the types of components (A) and (B), the types and contents of other components, the intended use and formulation of the ophthalmic composition, and the like. From the viewpoint of further enhancing the effects of the present invention, the content ratio of component (B) relative to component (A) is, for example, preferably 0.0001 to 5,000 parts by mass, more preferably 0.0005 to 4,000 parts by mass, and even more preferably 0.001 to 3,000 parts by mass, relative to 1 part by mass of the total content of component (A) in the ophthalmic composition according to this embodiment. Furthermore, the total content of component (B) relative to 1 part by mass of the total content of component (A) may 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.

[0025] When component (B) is a water-soluble vitamin, from the viewpoint of more significantly exhibiting the effects of the present invention, 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 even more preferably 0.001 to 0.2 w / v%, based on the total amount of the ophthalmic composition according to this embodiment. Furthermore, 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 component (B) is a water-soluble vitamin, the content ratio of the water-soluble vitamin relative to component (A), from the viewpoint of further enhancing the effects of the present invention, is, for example, preferably 0.0001 to 500 parts by mass, more preferably 0.0005 to 300 parts by mass, and even more preferably 0.001 to 200 parts by mass, relative to 1 part by mass of the total content of component (A) in the ophthalmic composition according to this embodiment. Furthermore, when component (B) is a water-soluble vitamin, the total content of the water-soluble vitamin relative to 1 part by mass of the total content of component (A) may 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 component (B) is an amino acid and a salt thereof, from the viewpoint of more significantly achieving the effects of the present invention, for example, 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 even more preferably 0.05 to 3 w / v%, based on the total amount of the ophthalmic composition according to this embodiment. Furthermore, when component (B) is an amino acid and a salt thereof, the total content of the amino acid and its salt may be 0.1 to 2 w / v%, or 0.2 to 1 w / v%. Furthermore, when component (B) is aminoethylsulfonic acid, the content of aminoethylsulfonic acid is preferably 0.1 to 1 w / v%.

[0028] When component (B) is an amino acid and a salt thereof, the content ratio of the amino acid and the salt thereof relative to component (A), from the viewpoint of further enhancing the effects of the present invention, is, for example, preferably 0.0001 to 5000 parts by mass, more preferably 0.001 to 4000 parts by mass, and even more preferably 0.05 to 3000 parts by mass, relative to 1 part by mass of the total content of component (A) in the ophthalmic composition according to this embodiment. Furthermore, when component (B) is an amino acid and a salt thereof, the total content of the amino acid and the salt thereof may 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, relative to 1 part by mass of the total content of component (A).

[0029] [Buffering Agent] The ophthalmic composition according to this embodiment preferably further contains a buffering agent. When the ophthalmic composition further contains a buffering agent, the effects of the present invention are more pronounced. The buffering agent is not particularly limited as long as it is medicamentarily, pharmacologically (pharmaceutical), or physiologically acceptable. Examples of the buffering agent include inorganic buffering agents derived from inorganic acids, and organic buffering agents derived from organic acids or organic bases.

[0030] Examples of inorganic buffers include borate buffers, phosphate buffers, and carbonate buffers. Examples of borate buffers include boric acid or its salts (alkali metal borates, alkaline earth metal borates, etc.). Examples of phosphate buffers include phosphoric acid or its salts (alkali metal phosphates, alkaline earth metal phosphates, etc.). Examples of carbonate buffers include carbonic acid or its salts (alkali metal carbonates, alkaline earth metal carbonates, etc.). Furthermore, hydrates of borate, phosphate, or carbonate may be used as borate buffers, phosphate buffers, or carbonate buffers. More specific examples of the borate buffer include boric acid or a salt thereof (sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, borax, etc.); phosphate buffer includes phosphoric acid or a salt thereof (disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, trisodium phosphate, tripotassium phosphate, calcium monohydrogen phosphate, calcium dihydrogen phosphate, etc.); and carbonate buffer includes carbonic acid or a salt thereof (sodium hydrogen carbonate, sodium carbonate, ammonium carbonate, potassium carbonate, calcium carbonate, potassium hydrogen carbonate, magnesium carbonate, etc.).

[0031] Examples of organic buffers include citrate buffers, acetate buffers, lactate buffers, succinate buffers, Tris buffers, and AMPD buffers. Examples of citrate buffers include citric acid or salts thereof (alkali metal citrates, alkaline earth metal citrates, etc.). Examples of acetate buffers include acetic acid or salts thereof (alkali metal acetates, alkaline earth metal acetates, etc.). Examples of lactate buffers include lactic acid or salts thereof (alkali metal lactates, alkaline earth metal lactates, etc.). Examples of succinate buffers include succinic acid or salts thereof (alkali metal succinates, etc.). Furthermore, hydrates of citrate, acetate, lactate, or succinate may be used as citrate buffers, acetate buffers, lactate buffers, or succinate buffers. More specific examples of the citrate buffer include citric acid or a salt thereof (sodium citrate, potassium citrate, calcium citrate, sodium dihydrogen citrate, disodium citrate, etc.); acetic acid buffer includes acetic acid or a salt thereof (ammonium acetate, sodium acetate, potassium acetate, calcium acetate, etc.); lactic acid buffer includes lactic acid or a salt thereof (sodium lactate, potassium lactate, calcium lactate, etc.); and succinic acid buffer includes succinic acid or a salt thereof (monosodium succinate, disodium succinate, etc.). An example of a Tris buffer is trometamol or a salt thereof (trometamol hydrochloride, etc.). An example of an AMPD buffer is 2-amino-2-methyl-1,3-propanediol or a salt thereof.

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

[0033] The buffering agent may be a commercially available product. One type of buffering agent may be used alone, or two or more types may be used in combination.

[0034] The content of the buffering agent in the ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the type of buffering agent, the types and contents of other blended components, the intended use and formulation of the ophthalmic composition, etc. From the viewpoint of more significantly exhibiting the effects of the present invention, the content of the buffering agent is, for example, preferably 0.01 to 4 w / v %, more preferably 0.05 to 3 w / v %, and even more preferably 0.1 to 2 w / v %, based on the total amount of the ophthalmic composition.

[0035] The content ratio of the buffering agent relative to the component (A) in the ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the types of component (A) and buffering agent, the types and contents of other blended components, the intended use and formulation of the ophthalmic composition, etc. From the viewpoint of further enhancing the effects of the present invention, the content ratio of the buffering agent relative to the component (A) is, for example, preferably 0.01 to 4000 parts by mass, more preferably 0.05 to 3000 parts by mass, and even more preferably 0.1 to 2000 parts by mass, of the total content of the buffering agent relative to 1 part by mass of the total content of the component (A) contained in the ophthalmic composition according to this embodiment.

[0036] The pH of the ophthalmic composition according to this embodiment is not particularly limited as long as it is within a medicamentarily, pharmacologically (pharmaceutical), or physiologically acceptable range. The pH of the ophthalmic composition according to this embodiment may be, for example, 4.0 to 9.5, preferably 4.0 to 9.0, more preferably 4.5 to 9.0, even 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 according to this embodiment can be adjusted to have an osmotic pressure ratio within a range acceptable to the body, as needed. The appropriate osmotic pressure ratio can be appropriately set depending on the intended use, formulation, and method of use of the ophthalmic composition, but can be, for example, 0.4 to 5.0, preferably 0.6 to 3.0, more preferably 0.8 to 2.2, and even more preferably 0.8 to 2.0. The osmotic pressure ratio is defined as the ratio of the osmotic pressure of the sample to 286 mOsm (the osmotic pressure of a 0.9 w / v % sodium chloride aqueous solution) in accordance with the Japanese Pharmacopoeia, 17th Edition, and is measured with reference to the osmotic pressure measurement method (freezing point depression method) described in the Japanese Pharmacopoeia. The standard solution for measuring osmotic pressure ratios (0.9 w / v % aqueous sodium chloride solution) can be prepared by drying sodium chloride (Japanese Pharmacopoeia standard reagent) at 500 to 650°C for 40 to 50 minutes, allowing it to cool in a desiccator (silica gel), accurately weighing 0.900 g of the dried solution, and dissolving it in purified water to make exactly 100 mL; alternatively, a commercially available standard solution for measuring osmotic pressure ratios (0.9 w / v % aqueous sodium chloride solution) can be used.

[0038] The viscosity of the ophthalmic composition according to this embodiment is not particularly limited as long as it is within a medicamentarily, pharmacologically (pharmaceutical), or physiologically acceptable range. The viscosity of the ophthalmic composition according to this embodiment, as measured at 20°C using a rotational viscometer (TV-20 type viscometer, manufactured by Toki Sangyo Co., Ltd., rotor: 1°34' x 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] The ophthalmic composition according to this embodiment may contain, in addition to the above-mentioned components, an appropriate amount of a combination of components selected from various pharmacologically active components and physiologically active components, as long as the effects of the present invention are not impaired. The components are not particularly limited, and examples thereof include the active ingredients in ophthalmic drugs listed in the 2017 edition of the OTC Drug Manufacturing and Marketing Approval Standards (supervised by the Japan Society of Regulatory Science). Specific examples of components used in ophthalmic drugs include the following: Antiallergic agents: for example, sodium cromoglycate, tranilast, pemirolast potassium, ashitazanolast, amlexanox, ibudilast, etc. Antihistamines: for example, chlorpheniramine or a salt thereof (e.g., chlorpheniramine maleate), diphenhydramine or a salt thereof (e.g., diphenhydramine hydrochloride), iproheptine or a salt thereof (e.g., iproheptine hydrochloride), levocabastine or a salt thereof (e.g., levocabastine hydrochloride), ketotifen or a salt thereof (e.g., ketotifen fumarate), pemirolast potassium, olopatadine or a salt thereof (e.g., olopatadine hydrochloride), etc. Anti-inflammatory agents: for example, methyl salicylate, glycol salicylate, allantoin, tranexamic acid, lysozyme, lysozyme chloride, indomethacin, pranoprofen, ibuprofen, ibuprofen piconol, ketoprofen, felbinac, bendazac, piroxicam, bufexamac, butyl flufenamate, epsilon-aminocaproic acid, berberine chloride, berberine sulfate, sodium azulene sulfonate, glycyrrhizinic acid or a salt thereof (for example, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate), etc. Steroids: for example, fluticasone propionate, fluticasone furoate, mometasone furoate, beclomethasone propionate, flunisolide, etc. Decongestants: for example, tetrahydrozoline hydrochloride, tetrahydrozoline nitrate, naphazoline hydrochloride, naphazoline nitrate, epinephrine, epinephrine hydrochloride, ephedrine hydrochloride, phenylephrine hydrochloride, dl-methylephedrine hydrochloride, etc.Ocular muscle regulating drugs: for example, cholinesterase inhibitors having an active center similar to that of acetylcholine, specifically, neostigmine methylsulfate, tropicamide, helenien, atropine sulfate, pilocarpine hydrochloride, etc. Fat-soluble vitamins: for example, retinol acetate, retinol palmitate, tocopherol acetate, etc. Others: for example, sulfamethoxazole, sulfisoxazole, sulfisomidine and salts thereof, etc.

[0040] The ophthalmic composition according to this embodiment may contain one or more additives selected appropriately according to the intended use and formulation, in an appropriate amount, as long as the effects of the present invention are not impaired. Examples of such additives include those listed in the 2016 Pharmaceutical Additives Encyclopedia (edited by the Japan Pharmaceutical Additives Association). Representative components include the following: Carriers: aqueous solvents such as water and aqueous ethanol; Chelating agents: ethylenediaminediacetic acid (EDDA), ethylenediaminetriacetic acid, ethylenediaminetetraacetic acid (EDTA), N-(2-hydroxyethyl)ethylenediaminetriacetic acid (HEDTA), diethylenetriaminepentaacetic acid (DTPA), etc.; Bases: octyldodecanol, titanium oxide, potassium bromide, Plastibase, etc.; pH adjusters: hydrochloric acid, acetic acid, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, triethanolamine, monoethanolamine, diisopropanolamine, etc. Thickeners: for example, cellulose-based polymer compounds such as methylcellulose, ethylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, and carboxymethylcellulose sodium; polyvinyl-based polymer compounds such as polyvinylpyrrolidone and polyvinyl alcohol; carboxyvinyl polymers; guar gum; hydroxypropyl guar gum; gum arabic; karaya gum; xanthan gum; agar; alginic acid and its salts (sodium salt, etc.); mucopolysaccharides such as heparin-like substances, heparin, heparin sulfate, heparan sulfate, heparinoids, hyaluronic acid and its salts (sodium salt, etc.); starch; chitin and its derivatives; chitosan and its derivatives; carrageenan; monosaccharides such as glucose, etc. Stabilizers: for example, edetic acid, edetate salts (edetate disodium, edetate calcium disodium, edetate trisodium, edetate tetrasodium), sodium formaldehyde sulfoxylate (Rongalit), aluminum monostearate, glycerin monostearate, cyclodextrin, monoethanolamine, dibutylhydroxytoluene, sodium hydrogensulfite, sodium metabisulfite, etc.Preservatives: for example, alkylpolyaminoethylglycine quaternary ammonium salts (e.g., benzalkonium chloride, benzethonium chloride, etc.), chlorhexidine gluconate, polidronium chloride, zinc chloride, sodium benzoate, ethanol, chlorobutanol, sorbic acid, potassium sorbate, sodium dehydroacetate, methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, butyl parahydroxybenzoate, oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, biguanide compounds (specifically, polyhexanide hydrochloride (polyhexamethylene biguanide), alexidine, etc.), Gloquil (trade name, manufactured by Rhodia), etc. Isotonic agents: for example, potassium chloride, calcium chloride, sodium chloride, magnesium chloride, potassium acetate, sodium acetate, sodium bicarbonate, sodium carbonate, sodium thiosulfate, magnesium sulfate, glycerin, propylene glycol, sodium bisulfite, sodium sulfite, etc. Sugar alcohols: for example, xylitol, sorbitol, mannitol, glycerin, etc. These may be in the d-, l- or dl-form.

[0041] The ophthalmic composition according to this embodiment preferably does not contain POE sorbitan monolaurate, more preferably does not contain POE sorbitan monolaurate and polyoxyethylene hydrogenated castor oil, and further preferably does not contain a nonionic surfactant, because this allows the effects of the present invention to be more significantly exhibited.Examples of nonionic surfactants include POE sorbitan fatty acid esters such as POE (20) sorbitan monolaurate (polysorbate 20), POE (20) sorbitan monopalmitate (polysorbate 40), POE (20) sorbitan monostearate (polysorbate 60), POE (20) sorbitan tristearate (polysorbate 65), and POE (20) sorbitan monooleate (polysorbate 80); poloxamer 407, poloxamer 235, poloxamer 188, and poloxamer 403; POE POP glycols such as Poloxamer 237 and Poloxamer 124; POE hydrogenated castor oils such as POE hydrogenated castor oil 40, POE hydrogenated castor oil 50, POE hydrogenated castor oil 60, and POE hydrogenated castor oil 80; POE castor oils such as 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, and POE castor oil 50; polyethylene monostearate polyethylene glycol monostearate such as polyethylene glycol (2 E.O.), polyethylene glycol (4 E.O.), polyethylene glycol (9 E.O.), polyethylene glycol (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.) (Polyoxyl 40 stearate), polyethylene glycol monostearate (45 E.O.), polyethylene glycol monostearate (55 E.O.), polyethylene glycol monostearate (75 E.O.), and polyethylene glycol monostearate (140 E.O.); POE alkyl ethers such as POE(9) lauryl ether; POE-POP alkyl ethers such as POE(20) POP(4) cetyl ether; and POE alkyl phenyl ethers such as POE(10) nonylphenyl ether. In the compounds exemplified above, POE stands for polyoxyethylene, POP stands for polyoxypropylene, and the numbers in parentheses stand for the number of moles added.

[0042] The ophthalmic composition according to this embodiment preferably does not contain a terpenoid, since this allows the effects of the present invention to be more pronounced. Examples of terpenoids include menthol, camphor, borneol, and geraniol.

[0043] When the ophthalmic composition according to this embodiment contains water, the water content is, from the viewpoint of more significantly achieving the effects of the present invention, 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 even more preferably 90 w / v% or more and 99.2 w / v% or less, based on the total amount of the ophthalmic composition.

[0044] The water used in the ophthalmic composition according to this embodiment may be any water that is medicamentally, pharmacologically (pharmaceutical), or physiologically acceptable. Examples of such water include distilled water, tap water, purified water, sterile purified water, water for injection, and distilled water for injection. These definitions are based on the Japanese Pharmacopoeia, 17th Edition.

[0045] The ophthalmic composition according to this embodiment can be prepared by adding and mixing desired amounts of component (A), component (B), and, if necessary, other components to achieve desired concentrations. For example, the composition can be prepared by dissolving or dispersing these components in purified water, adjusting the pH and osmotic pressure to predetermined levels, and sterilizing the resulting mixture by filtration or other methods.

[0046] The ophthalmic composition according to this embodiment can be in various formulation forms depending on the purpose, such as a liquid, a gel, a semi-solid (e.g., ointment), etc.

[0047] The ophthalmic composition according to this embodiment can be used, for example, as eye drops (also called eye drops or eye drops; eye drops include eye drops that can be applied while wearing contact lenses), artificial tears, eyewash (also called eyewash or eyewash; eyewashes include eyewashes that can be used to wash the eyes while wearing contact lenses), and contact lens compositions [contact lens wetting solution, contact lens care compositions (contact lens disinfectants, contact lens preservatives, contact lens cleaners, contact lens cleaning and preservatives), contact lens packaging solution, etc.]. Note that "contact lenses" includes hard contact lenses and soft contact lenses (including both ionic and non-ionic contact lenses, and both silicone hydrogel contact lenses and non-silicone hydrogel contact lenses).

[0048] The ophthalmic composition according to this embodiment is preferably an eye drop (including an eye drop that can be applied while wearing contact lenses), as this allows the effects of the present invention to be more pronounced. When the ophthalmic composition according to this embodiment is an eye drop, the dosage and administration method are not particularly limited as long as they are effective and cause few side effects. For example, for adults (15 years of age or older) and children aged 7 years of age or older, 1 to 3 drops, 1 to 2 drops, or 2 to 3 drops are applied 2 to 4 times or 5 to 6 times a day.

[0049] The ophthalmic composition according to this embodiment is provided in any container. The container for containing the ophthalmic composition according to this embodiment is not particularly limited and may be made of, for example, glass or plastic. Plastic is preferred. Examples of plastic include polyethylene terephthalate (PET), polyarylate (PAR), polyethylene naphthalate (PEN), polycarbonate (PC), polyethylene (PE), polypropylene (PP), polyimide (PI), cyclic olefin copolymer (COC), copolymers of monomers constituting these, and mixtures of two or more of these. Polyethylene terephthalate (PET) is preferred. Furthermore, the container for containing the ophthalmic composition according to this embodiment may be a transparent container that allows the interior of the container to be seen, or an opaque container that makes it difficult to see the interior of the container. A transparent container is preferred. Here, the term "transparent container" includes both colorless transparent containers and colored transparent containers.

[0050] A nozzle may be attached to the container containing the ophthalmic composition according to this embodiment. The material of the nozzle is not particularly limited and may be, for example, glass or plastic. Plastic is preferred. Examples of plastic include polybutylene terephthalate (PBT), polyethylene (PE), polypropylene (PP), polyethylene terephthalate (PET), polyethylene naphthalate (PEN), copolymers of monomers constituting these, and mixtures of two or more of these. From the viewpoint of further enhancing the effects of the present invention, the nozzle is preferably made of polypropylene (PP), polyethylene (PE), polyethylene terephthalate (PET), polybutylene terephthalate (PBT), or polyethylene naphthalate (PEN), with polyethylene (PE) being more preferred.

[0051] The container that holds the ophthalmic composition according to this embodiment may be a multi-dose type that holds an amount for multiple uses, or a unit-dose type that holds an amount for single use.

[0052] The ophthalmic composition according to this embodiment is preferably filled in a container having an internal volume of 4 to 30 mL, more preferably in a container having an internal volume of 5 to 20 mL, even more preferably in a container having an internal volume of 10 to 18 mL, and even more preferably in a container having an internal volume of 15 to 18 mL. Alternatively, the ophthalmic composition may be filled in a container having an internal volume of 0.1 to 3 mL, or may be filled in a container having an internal volume of 0.2 to 1 mL.

[0053] As shown in the examples below, the ophthalmic composition according to this embodiment contains sodium chondroitin sulfate having a weight-average molecular weight of 1,000 to 20,000, and yet has the effect of significantly reducing the elastic modulus of soft contact lenses. Therefore, it is preferably an ophthalmic composition for soft contact lenses. The reduction in the elastic modulus of the soft contact lens makes the soft contact lens softer, thereby more effectively reducing discomfort due to a feeling of grittiness, stiffness, and poor wearing comfort when wearing and / or inserting the soft contact lens. Furthermore, one embodiment of the present invention provides a method for imparting the effect of reducing the elastic modulus of a soft contact lens to an ophthalmic composition, the method comprising blending (A) at least one selected from the group consisting of chondroitin sulfate and salts thereof having a weight-average molecular weight of 1,000 to 20,000 with (B) at least one selected from the group consisting of water-soluble vitamins, amino acids, and salts thereof.

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

[0055] The present invention will be specifically explained below based on test examples, but the present invention is not limited to these.

[0056] [Preparation of test solutions] The test solutions shown in Table 1 were prepared according to standard methods. The units of each component in Table 1 are g / 100 mL. The sodium chondroitin sulfate used in the following test examples is as follows: Sodium chondroitin sulfate, weight-average molecular weight of approximately 16,000: Maruha Nichiro Corporation: Non-prescription sodium chondroitin sulfate

[0057] Test Example 1: Evaluation of change in elastic modulus 4 mL of physiological saline (Otsuka Pharmaceutical Factory) was dispensed into a 12-well plate (BD Falcon, No. 35-3043), and one contact lens (Precision One: Alcon) was immersed in each well and allowed to stand at room temperature for at least 4 hours. 4 mL of each of the test solutions prepared above and listed in Table 1 was dispensed into another 12-well plate (BD Falcon, No. 35-3043), and the contact lenses, which had been lightly wiped to remove moisture with lint-free paper, were immersed in each well and allowed to stand at 34°C for 24 hours.

[0058] Using an MCR302 rheometer (manufactured by Anton Paar), a parallel plate PP12 / P12 (12 mm diameter, lattice pattern; 1 x 0.5, product number: 23935) and a cap plate P-PTD200 / 80-77 / SS / P2 (lattice pattern, product number: 7894) were used. The measurement temperature was 20°C, the frequency was 1 Hz, and the measurement time was set to "no time setting" mode. The shear stress (Pa) was measured for strains of 0.01 to 1%. Specifically, 0.5 mL of saline solution was dropped onto the cap plate, and the convex surface of a contact lens that had been wiped dry was placed on top of it (with the convex surface facing the cap plate). 0.5 mL of saline solution was then dropped onto the contact lens. The parallel plate was lowered and brought close to the cap plate, and the position was adjusted so that the contact lens was sandwiched between the two plates at a distance of 0.1 mm. Then, the shear stress (Pa) measurement was initiated. Measurements were made at five equally spaced intervals between 0.01 and 0.1% strain and five equally spaced intervals between 0.1 and 1% strain. The modulus of elasticity (Pa) was calculated using [Equation 1], where 0.0325% is the second measurement interval between 0.01 and 0.1% strain, and 1% is the measurement interval between 0.1 and 1% strain. Measurements were made three times, and the average value was taken as the average modulus of elasticity (Pa). [Equation 1] Modulus of elasticity (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, the elastic modulus reduction rate (%) relative to the corresponding Reference Example was calculated according to [Equation 2]: [Equation 2] Elastic modulus reduction rate (%) 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]

[0061] In Examples 1 to 3, which contained sodium chondroitin sulfate having a weight-average molecular weight of 16,000 and a water-soluble vitamin or an amino acid, the reduction in the elastic modulus of the soft contact lens was 16.6 to 31.9% compared to Reference Example 1, which contained no water-soluble vitamin or amino acid. This demonstrates that in ophthalmic compositions containing sodium chondroitin sulfate having a weight-average molecular weight of 1,000 to 20,000, the water-soluble vitamin or amino acid has the effect of softening hardened soft contact lenses.

[0062] Formulation Examples 1 to 16 were prepared according to the formulations shown in Tables 2 and 3 below. Formulation Examples 1 to 16 were filled into polyethylene terephthalate containers and fitted with nozzles made of low-density polyethylene, resulting in Formulation Examples 1 to 16. Formulation Examples 1 to 16 were filled into polyethylene terephthalate containers and fitted with nozzles made of polybutylene terephthalate on the entire wall surface that may come into contact with the content liquid when the cap is attached (during storage), resulting in Formulation Examples 17 to 32. Formulation Examples 1 to 16 were filled into polyethylene terephthalate containers and fitted with nozzles made of polyethylene terephthalate on part of the wall surface that may come into contact with the content liquid, resulting in Formulation Examples 33 to 48. Note that the units in the tables are w / v % unless otherwise specified.

[0063]

[0064]

Claims

1. An ophthalmic composition comprising: (A) at least one member selected from the group consisting of chondroitin sulfate and its salts having a weight-average molecular weight of 1,000 to 20,000; and (B) at least one member selected from the group consisting of water-soluble vitamins, amino acids, and their salts.

2. The ophthalmic composition according to claim 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 of claim 1, which does not contain a nonionic surfactant.

4. The ophthalmic composition according to claim 1, which is for use in soft contact lenses.

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