Ophthalmic composition for soft contact lenses

Abstract

To provide a new ophthalmic composition that can prevent dry eye.SOLUTION: A ophthalmic composition for soft contact lenses contains (A) vitamin A and (B) at least two selected from the group consisting of neostigmine methylsulfate, chlorpheniramine maleate, an amino acid and a salt thereof, and chondroitin sulfate sodium.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to an ophthalmic composition for soft contact lenses. [Background technology]

[0002] Soft contact lenses are widely used because they contain a lot of water and are softer and more comfortable to wear than hard contact lenses. However, wearing soft contact lenses is known to cause discomfort such as eye inflammation, itching, and pain, as well as eye fatigue, blurred vision, and dry eyes. It has also been reported that soft contact lenses have a particular problem in that they tend to adsorb terpenoids (see, for example, Patent Document 1). [Prior art documents] [Patent documents]

[0003] [Patent Document 1] International Publication No. 2007 / 145344 Summary of the Invention [Problem to be solved by the invention]

[0004] When an active ingredient contained in an ophthalmic preparation that can be used while wearing a soft contact lens is adsorbed onto the soft contact lens, the medicinal effect of the active ingredient cannot be fully exerted, which is a problem.

[0005] An object of the present invention is to provide an ophthalmic composition for soft contact lenses in which the adsorption of an active ingredient to soft contact lenses is suppressed. [Means for solving the problem]

[0006] The present inventors have unexpectedly discovered that by adding a specific amount of vitamin A to an ophthalmic composition containing specific amounts of at least two active ingredients selected from the group consisting of neostigmine methylsulfate, chlorpheniramine maleate, amino acids, and sodium chondroitin sulfate, adsorption of the active ingredients to soft contact lenses is suppressed.

[0007] The present invention provides, for example, the following inventions. [1] An ophthalmic composition for soft contact lenses, comprising (A) a vitamin A compound and (B) at least two members selected from the group consisting of neostigmine methylsulfate, chlorpheniramine maleate, amino acids and their salts, and sodium chondroitin sulfate. [2] The ophthalmic composition according to [1], comprising neostigmine methylsulfate and chlorpheniramine maleate as component (B). [3] The ophthalmic composition according to [1], comprising, as component (B), at least one selected from the group consisting of amino acids and salts thereof, and sodium chondroitin sulfate. [4] The ophthalmic composition according to [1], comprising, as component (B), at least one selected from the group consisting of neostigmine methylsulfate, chlorpheniramine maleate, amino acids and salts thereof, and sodium chondroitin sulfate. [5] The ophthalmic composition according to any one of [1] to [4], wherein the content of vitamin A is 45,000 IU / 100 mL to 65,000 IU / 100 mL based on the total amount of the ophthalmic composition, the content of neostigmine methylsulfate is 0.0045 w / v% to 0.0055 w / v% based on the total amount of the ophthalmic composition, the content of chlorpheniramine maleate is 0.027 w / v% to 0.033 w / v% based on the total amount of the ophthalmic composition, the content of amino acids and salts thereof is 0.9 w / v% to 1.1 w / v% based on the total amount of the ophthalmic composition, and the content of sodium chondroitin sulfate is 0.45 w / v% to 0.55 w / v% based on the total amount of the ophthalmic composition. [Effects of the Invention]

[0008] According to the present invention, it is possible to provide an ophthalmic composition for soft contact lenses in which adsorption of an active ingredient to a soft contact lens is suppressed. DETAILED DESCRIPTION OF THE INVENTION

[0009] DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The following describes in detail the embodiments of the present invention, but the present invention is not limited to the following embodiments.

[0010] In this specification, unless otherwise specified, the unit of content "%" means "w / v%" and is synonymous with "g / 100 mL".

[0011] The ophthalmic composition for soft contact lenses according to this embodiment contains (A) a vitamin A group (also referred to simply as "component (A)"), and (B) at least two members selected from the group consisting of neostigmine methylsulfate, chlorpheniramine maleate, amino acids and their salts, and sodium chondroitin sulfate (also referred to simply as "component (B)").

[0012] [Component (A)] The vitamin A is not particularly limited as long as it is medicamentarily, pharmacologically (pharmaceutical), or physiologically acceptable. Specific examples of vitamin A include retinol, retinal, retinoic acid, and derivatives thereof, and salts thereof.

[0013] Examples of derivatives of vitamin A include esters with monocarboxylic acids such as retinol palmitate, retinol acetate, retinol butyrate, retinol propionate, retinol octylate, retinol laurate, retinol oleate, and retinol linoleate.

[0014] Salts of vitamin A include, for example, organic acid salts (e.g., monocarboxylates (acetate, trifluoroacetate, butyrate, palmitate, stearate, etc.), polycarboxylates (fumarate, maleate, succinate, malonate, etc.), hydroxycarboxylates (lactate, tartrate, citrate, etc.), organic sulfonates (methanesulfonate, toluenesulfonate, tosylate, etc.), inorganic acid salts (e.g., hydrochloride, sulfate, nitrate, hydrobromide, phosphate), salts with organic bases (e.g., salts with organic amines such as methylamine, triethylamine, triethanolamine, morpholine, piperazine, pyrrolidine, tripyridine, picoline, etc.), and salts with inorganic bases (e.g., ammonium salts; salts with alkali metals (sodium, potassium, etc.), alkaline earth metals (calcium, magnesium, etc.), aluminum, etc.).

[0015] As vitamin A, derivatives of retinol are preferred, esters of retinol and monocarboxylic acids are more preferred, retinol palmitate and retinol acetate are even more preferred, and retinol palmitate is even more preferred.

[0016] As vitamin A, synthetic products or extracts obtained from natural products (e.g., vitamin A oil) may be used. Vitamin A oil is a fatty oil obtained from animal tissues containing retinol, or a concentrate thereof, or a product obtained by appropriately adding vegetable oil to either of these. Commercially available vitamin A products can also be used. Vitamin A may be used alone or in combination of two or more types.

[0017] The content of vitamin A in the ophthalmic composition according to this embodiment may be, for example, 35,000 IU / 100 mL to 100,000 IU / 100 mL, 40,000 IU / 100 mL to 80,000 IU / 100 mL, 45,000 IU / 100 mL to 65,000 IU / 100 mL, 47,000 IU / 100 mL to 63,000 IU / 100 mL, 48,000 IU / 100 mL to 62,000 IU / 100 mL, 49,000 IU / 100 mL to 61,000 IU / 100 mL, or 50,000 IU / 100 mL, based on the total volume of the ophthalmic composition, from the viewpoint of more significantly exhibiting the effects of the present invention. Here, "IU" refers to the international unit determined by the method described in the Vitamin A Quantitation Method in the Seventeenth Edition of the Japanese Pharmacopoeia, etc. For example, the 17th Edition of the Japanese Pharmacopoeia states in its drug monographs that retinol acetate contains more than 2.5 million units of vitamin A per gram, and retinol palmitate contains more than 1.5 million units of vitamin A per gram.

[0018] [(B) component] (Neostigmine methylsulfate) Neostigmine methylsulfate is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutical), or physiologically acceptable.

[0019] Neostigmine methylsulfate is a known compound also known as (3-dimethylcarbamoyloxyphenyl)trimethylammonium methylsulfate.

[0020] From the viewpoint of more significantly exhibiting the effects of the present invention, the content of neostigmine methylsulfate in the ophthalmic composition according to this embodiment may be, for example, 0.0005 w / v% to 0.05 w / v%, 0.001 w / v% to 0.01 w / v%, 0.0045 w / v% to 0.0055 w / v%, 0.0047 w / v% to 0.0053 w / v%, or 0.005 w / v%, based on the total amount of the ophthalmic composition.

[0021] (Chlorpheniramine maleate) There are no particular limitations on the chlorpheniramine maleate, so long as it is pharmaceutically, pharmacologically (pharmaceutical), or physiologically acceptable.

[0022] Chlorpheniramine maleate is a known compound that is also called (3RS)-3-(4-chlorophenyl)-N,N-dimethyl-3-pyridin-2-ylpropylamine monomaleate.

[0023] From the viewpoint of more significantly exhibiting the effects of the present invention, the content of chlorpheniramine maleate in the ophthalmic composition according to this embodiment may be, for example, 0.01 w / v% to 0.05 w / v%, 0.027 w / v% to 0.033 w / v%, 0.028 w / v% to 0.032 w / v%, or 0.03 w / v% based on the total amount of the ophthalmic composition.

[0024] (Amino acids and their salts) There are no particular limitations on the amino acids and salts thereof, so long as they are medicamentally, pharmacologically (pharmaceutical) or physiologically acceptable.

[0025] Examples of amino acids and salts thereof include L-aspartic acid or salts thereof (e.g., potassium L-aspartate, sodium L-aspartate, magnesium L-aspartate, calcium L-aspartate, magnesium·potassium L-aspartate (a mixture of equal parts of magnesium L-aspartate and potassium L-aspartate)), aminoethylsulfonic acid or salts thereof, L-arginine, glutamic acid, glycine, alanine, lysine, γ-aminobutyric acid, γ-aminovaleric acid, trimethylglycine, and salts thereof. Commercially available amino acids and salts thereof can also be used. The amino acids and salts thereof may be in the L-, D-, or DL-form, and examples thereof include potassium L-aspartate, magnesium L-aspartate, and a mixture of equal parts of magnesium·potassium L-aspartate. Among the amino acids and salts thereof, aspartic acid, aminoethylsulfonic acid, and salts thereof are preferred, with aminoethylsulfonic acid being particularly preferred, from the viewpoint of further enhancing the effects of the present invention.

[0026] From the viewpoint of more significantly achieving the effects of the present invention, the content of the amino acid and its salt in the ophthalmic composition of this embodiment may be, for example, 0.001 w / v% to 5 w / v%, 0.01 w / v% to 2 w / v%, 0.1 w / v% to 1.5 w / v%, 0.9 w / v% to 1.1 w / v%, or 1 w / v% based on the total amount of the ophthalmic composition.

[0027] (Sodium chondroitin sulfate) Sodium chondroitin sulfate is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutical), or physiologically acceptable. The molecular weight of sodium chondroitin sulfate is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutical), or physiologically acceptable, but typically, sodium chondroitin sulfate with a weight-average molecular weight of about 1,000 to 100,000, preferably about 5,000 to 50,000, and more preferably about 10,000 to 40,000 can be used.

[0028] From the viewpoint of more significantly achieving the effects of the present invention, the content of sodium chondroitin sulfate in the ophthalmic composition of this embodiment may be, for example, 0.05 w / v% to 1 w / v%, 0.1 w / v% to 0.8 w / v%, 0.45 w / v% to 0.55 w / v%, 0.47 w / v% to 0.53 w / v%, or 0.5 w / v% based on the total amount of the ophthalmic composition.

[0029] Component (B) may contain two, three, or four types selected from the group consisting of neostigmine methylsulfate, chlorpheniramine maleate, amino acids and salts thereof, and sodium chondroitin sulfate. From the viewpoint of more significantly exhibiting the effects of the present invention, component (B) preferably contains at least one selected from the group consisting of neostigmine methylsulfate, chlorpheniramine maleate, amino acids and salts thereof, and sodium chondroitin sulfate, and more preferably contains at least one selected from the group consisting of neostigmine methylsulfate, chlorpheniramine maleate, amino acids and salts thereof, and sodium chondroitin sulfate.

[0030] It is known that continuous wear of soft contact lenses can cause corneal damage and inflammation, so it is desirable for ophthalmic preparations that can be used while wearing soft contact lenses to have the effect of protecting corneal epithelial cells or repairing corneal tissue.

[0031] An ophthalmic composition according to one embodiment of the present invention, which contains component (A) and, as component (B), at least one selected from the group consisting of amino acids and salts thereof and a predetermined amount of sodium chondroitin sulfate, has an excellent effect of protecting corneal epithelial cells, as is clear from the test examples described below. Furthermore, the protection of corneal epithelial cells results in repair of corneal tissue. Therefore, according to the present invention, it is possible to provide an ophthalmic composition for soft contact lenses that has both the effect of protecting corneal epithelial cells and / or the effect of repairing corneal tissue.

[0032] It is also known that wearing soft contact lenses can cause discomfort, pain, or stinging in the eyes due to corneal damage or inflammation, dry eyes, etc. (pain so severe that it becomes difficult to keep the eyes open when the dryness of the eyes progresses, or a sharp, tingling pain when removing soft contact lenses). Therefore, it is desirable for an ophthalmic preparation that can be used while wearing soft contact lenses to also have the effect of suppressing discomfort, pain, and stinging in the eyes.

[0033] An ophthalmic composition according to one embodiment of the present invention, which contains predetermined amounts of neostigmine methylsulfate and chlorpheniramine maleate as components (A) and (B), has the effect of suppressing discomfort, pain, and / or stinging caused by wearing soft contact lenses, as is clear from the test examples described below. Thus, according to the present invention, it is possible to provide an ophthalmic composition for soft contact lenses which has the effects of suppressing discomfort, discomfort, pain, and / or stinging caused by wearing soft contact lenses.

[0034] 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, and may be, for example, 4.0 to 9.5, 4.0 to 9.0, 4.5 to 9.0, 4.5 to 8.5, 5.0 to 8.5, 5.0 to 8.0, 5.5 to 7.5, or 6.0 to 7.0.

[0035] The ophthalmic composition according to this embodiment can be adjusted to have an osmotic pressure ratio within a biologically acceptable range, as needed. The appropriate osmotic pressure ratio can be appropriately determined 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 using the osmotic pressure measurement method (freezing point depression method) described in the Japanese Pharmacopoeia. The standard solution for measuring osmolality ratios (0.9 w / v% sodium chloride aqueous solution) can be prepared by drying sodium chloride (Japanese Pharmacopoeia standard reagent) at 500-650°C for 40-50 minutes, allowing it to cool in a desiccator (silica gel), accurately weighing 0.900 g of the solution, and dissolving it in purified water to make exactly 100 mL; alternatively, a commercially available standard solution for measuring osmolality ratios (0.9 w / v% sodium chloride aqueous solution) can be used.

[0036] 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 may be, for example, 1 to 10,000 mPa·s, 1 to 8,000 mPa·s, 1 to 1,000 mPa·s, 1 to 100 mPa·s, 1 to 20 mPa·s, or 1 to 10 mPa·s as measured at 20°C using a rotational viscometer (TV-20 type viscometer, manufactured by Toki Sangyo Co., Ltd., rotor: 1°34'×R24).

[0037] The ophthalmic composition according to this embodiment may contain, in addition to the above-mentioned components, a combination of various pharmacologically active components and physiologically active components in appropriate amounts, as long as the effects of the present invention are not impaired. The components are not particularly limited, and examples thereof include active ingredients in ophthalmic drugs listed in the 2012 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, 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 (e.g., 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 agents: For example, cholinesterase inhibitors having an active center similar to that of acetylcholine, specifically tropicamide, helenien, atropine sulfate, pilocarpine hydrochloride, etc. Vitamins: for example, tocopherol acetate, flavin adenine dinucleotide sodium, cyanocobalamin, pyridoxine hydrochloride, panthenol, calcium pantothenate, ascorbic acid, sodium ascorbate, etc. Astringents: for example, zinc oxide, zinc lactate, zinc sulfate, etc. Others: For example, sulfamethoxazole, sulfisoxazole, sulfisomidine and their salts.

[0038] The ophthalmic composition according to this embodiment may contain one or more additives selected appropriately in a conventional manner depending on the intended use and formulation, as long as the effects of the present invention are not impaired. Examples of such additives include those listed in the Pharmaceutical Additives Dictionary 2016 (edited by the Japan Pharmaceutical Additives Association). Representative additives include the following: Carrier: For example, an aqueous solvent such as water or aqueous ethanol. Chelating agents: for example, ethylenediaminediacetic acid (EDDA), ethylenediaminetriacetic acid, ethylenediaminetetraacetic acid (EDTA), N-(2-hydroxyethyl)ethylenediaminetriacetic acid (HEDTA), diethylenetriaminepentaacetic acid (DTPA), etc. Bases: for example, octyldodecanol, titanium oxide, potassium bromide, plastibase, etc. pH adjusters: for example, hydrochloric acid, acetic acid, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, triethanolamine, monoethanolamine, diisopropanolamine, etc. Surfactants include, for example, nonionic surfactants such as tyloxapol, polyoxyethylene sorbitan fatty acid esters, polyoxyl stearates, polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, and poloxamers; anionic surfactants such as polyoxyethylene alkyl ether phosphates, polyoxyethylene alkyl ether sulfates, alkylbenzene sulfonates, alkyl sulfates, and N-acyltaurine salts; and zwitterionic surfactants such as lauryl dimethylaminoacetic acid betaine. Of these, from the viewpoint of more significantly exhibiting the effects of the present invention, polyoxyethylene sorbitan fatty acid esters, polyoxyl stearates, polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, and poloxamers are preferred. Fragrances or freshening agents: for example, menthol, menthone, camphor, borneol, geraniol, cineole, citronellol, carvone, anethole, eugenol, limonene, linalool, linalyl acetate, thymol, cymene, terpineol, pinene, camphene, isoborneol, fenchene, nerol, myrcene, myrcenol, linalool acetate, lavandulol, eucalyptus oil, bergamot oil, peppermint oil, cool mint oil, spearmint oil, peppermint oil, fennel oil, cinnamon oil, rose oil, camphor oil, etc. These may be in the d-, l-, or dl-isomer. 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. Buffers include, for example, borate buffers, phosphate buffers, carbonate buffers, acetate buffers, lactate buffers, succinate buffers, citrate buffers, Tris buffers, and AMPD buffers. Among these, borate buffers and phosphate buffers are preferred, with borate buffers being particularly preferred, from the viewpoint of more significantly achieving the effects of the present invention. Specifically, from the viewpoint of more significantly achieving the effects of the present invention, the total content of the buffers is preferably 0.01 w / v% to 5 w / v%, more preferably 0.1 w / v% to 3 w / v%, and particularly preferably 0.5 w / v% to 1.5 w / v%, based on the total amount of the ophthalmic composition. 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, polidonium 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 hydrogen carbonate, sodium carbonate, sodium thiosulfate, magnesium sulfate, glycerin, propylene glycol, sodium hydrogen sulfite, sodium sulfite, etc. Sugar alcohols: for example, xylitol, sorbitol, mannitol, glycerin, etc. These may be in the d-, l- or dl-form. Oils: for example, vegetable oils such as sesame oil, castor oil, soybean oil, olive oil, etc.; animal oils such as squalane, etc.; mineral oils such as liquid paraffin, Vaseline, etc.

[0039] From the viewpoint of being able to significantly exhibit the effects of the present invention, the ophthalmic composition according to this embodiment preferably does not contain at least three selected from the group consisting of epsilon-aminocaproic acid, allantoin, berberine chloride or berberine sulfate, sodium azulene sulfonate, dipotassium glycyrrhizinate, and zinc sulfate or zinc lactate, and more preferably does not contain a combination of epsilon-aminocaproic acid, allantoin, and dipotassium glycyrrhizinate; a combination of allantoin, berberine chloride, and zinc sulfate; a combination of allantoin, dipotassium glycyrrhizinate, and zinc sulfate; a combination of epsilon-aminocaproic acid, berberine chloride, and dipotassium glycyrrhizinate; and a combination of allantoin, sodium azulene sulfonate, and dipotassium glycyrrhizinate.

[0040] When the ophthalmic composition of this embodiment contains water, the water content may be, for example, 80 w / v% or more but less than 100 w / v%, 85 w / v% or more but 99.5 w / v% or less, or 90 w / v% or more but 99.2 w / v% or less, based on the total amount of the ophthalmic composition, from the viewpoint of more significantly achieving the effects of the present invention.

[0041] 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.

[0042] The ophthalmic composition of 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, it can be prepared by dissolving or dispersing these components in purified water, adjusting the pH and osmotic pressure to the desired level, and sterilizing the mixture by filtration or other methods. When component (B) is neostigmine methylsulfate, the amount of neostigmine methylsulfate relative to component (A) may be 0.0002 g to 0.0015 g, 0.00069 g to 0.0012 g, 0.00075 g to 0.0011 g, or 0.001 g per 100 mL of vitamin A complex (10,000 IU / 100 mL). When component (B) is chlorpheniramine maleate, the amount of chlorpheniramine maleate may be 0.002 g to 0.009 g, 0.0043 g to 0.007 g, 0.0046 g to 0.0067 g, or 0.006 g per 10,000 IU of vitamin A. When component (B) is an amino acid and a salt thereof, the amount of amino acid and a salt thereof may be 0.02 g to 1 g, 0.1 g to 0.4 g, 0.14 g to 0.24 g, 0.16 g to 0.22 g, or 0.2 g per 10,000 IU of vitamin A. When component (B) is sodium chondroitin sulfate, the amount of sodium chondroitin sulfate may be 0.01 g to 0.2 g, 0.02 g to 0.16 g, 0.069 g to 0.12 g, 0.075 g to 0.11 g, or 0.1 g per 10,000 IU / 100 mL of vitamin A.

[0043] The ophthalmic composition according to the present embodiment can be in various formulation forms depending on the purpose. Examples of the formulation form include a liquid, a gel, a semi-solid (e.g., ointment), etc. Among these, a liquid is preferred from the viewpoint of more significantly exhibiting the effects of the present invention.

[0044] The ophthalmic composition according to this embodiment is a composition for use in contact with a soft contact lens. Examples include soft contact lens eye drops, which can be used while wearing soft contact lenses; soft contact lens eyewashes, which can be used while wearing soft contact lenses; soft contact lens wetting solutions; and soft contact lens solutions (cleaning solutions, storage solutions, disinfecting solutions, multi-purpose solutions). Among these, the ophthalmic composition is particularly suitable for use as soft contact lens eye drops. Soft contact lens eye drops and soft contact lens eyewashes can be used even when soft contact lenses are not being worn, but are suitable for use while wearing or wearing soft contact lenses.

[0045] Soft contact lenses can be classified into four types, Groups I to IV, based on their water content and whether they are ionic. Group I soft contact lenses have a water content of less than 50% and the molar percentage of anionic monomers among the constituent monomers of the raw material polymer is less than 1%. Group II soft contact lenses have a water content of 50% or more and the molar percentage of the above monomers is less than 1%. Group III soft contact lenses have a water content of less than 50% and the molar percentage of the above monomers is 1% or more. Group IV soft contact lenses have a water content of 50% or more and the molar percentage of the above monomers is 1% or more. The ophthalmic composition according to this embodiment can be applied to soft contact lenses of any group, but Groups II and IV are preferred, with Group IV being more preferred.

[0046] Soft contact lenses include silicone hydrogel contact lenses and hydrogel contact lenses. Silicone hydrogel contact lenses are made of a material containing silicone, such as a polymer of silicone and acrylate, copolymerized with a hydrophilic monomer, such as hydroxyethyl methacrylate or dimethylacrylamide. The ophthalmic composition according to this embodiment can be used for both silicone hydrogel contact lenses and hydrogel contact lenses.

[0047] The ophthalmic composition according to this embodiment is preferably an eye drop for soft 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 or older, 1 to 3 drops, 1 to 2 drops, or 2 to 3 drops are instilled into the eyes 2 to 4 times a day, or 5 to 6 times a day.

[0048] The ophthalmic composition according to this embodiment is provided in any container. The container for storing 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, polyarylate, polyethylene naphthalate, polycarbonate, polyethylene, polypropylene, polyimide, copolymers of monomers constituting these, and mixtures of two or more of these. Polyethylene terephthalate is preferred. Furthermore, the container for storing 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.

[0049] A nozzle may be attached to the container that contains 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, polyethylene, polypropylene, polyethylene terephthalate, polyethylene naphthalate, 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 material is preferably polypropylene, polyethylene, polyethylene terephthalate, polybutylene terephthalate, or polyethylene naphthalate, and more preferably polyethylene or polyethylene naphthalate.

[0050] 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.

[0051] 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 6 to 18 mL, and even more preferably in a container having an internal volume of 10 to 16 mL. Alternatively, it 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. [Example]

[0052] The present invention will be specifically explained below based on test examples, but the present invention is not limited to these.

[0053] [Test Example 1: Evaluation of suppression of component adsorption onto soft contact lenses (1)] Ophthalmic compositions of each formulation example were prepared according to the compositions shown in Tables 1 and 2 in accordance with conventional methods. Soft contact lenses (Johnson & Johnson, 2-week Acuvue, Group IV) were washed with saline (Otsuka saline). 4 mL of saline was dispensed into each well of a 12-well plate (Falcon, product number 353043), and each soft contact lens was immersed in the solution for at least 4 hours at room temperature. After immersion, the solution adhering to the soft contact lens was wiped off with a nonwoven wiper (Bencotto, PS-2, Ozu Sangyo). Next, 10 mL of each ophthalmic composition prepared above for each formulation example was poured into a PFA bottle (Sanplatec, product number SAN13905), and one soft contact lens was immersed in the solution. The bottle was then shaken at 120 rpm and 34°C for 24 hours. Next, for each formulation, the neostigmine methylsulfate and chlorpheniramine maleate contained in the sample ophthalmic composition (in which a soft contact lens was soaked) and the blank ophthalmic composition (in which a soft contact lens was not soaked and stored at 4°C for 24 hours) were quantified by HPLC, and the difference was taken as the amount of neostigmine methylsulfate and chlorpheniramine maleate adsorbed to the soft contact lens. Next, the adsorption rate of each formulation was calculated using the following formula 1, assuming the adsorption rate of the reference formulation to be 100%. The results are shown in Tables 1 and 2. For prescription examples 1-2 and 1-3, the reference prescription example is 1-1, for prescription examples 1-5 and 1-6, the reference prescription example is 1-4, for prescription example 1-8, the reference prescription example is 1-7, and for prescription example 1-10, the reference prescription example is 1-9. (Equation 1): Adsorption rate (%) relative to the standard formulation example = (adsorption amount of the formulation example / adsorption amount of the standard formulation example) × 100

[0054] [Table 1]

[0055] [Table 2]

[0056] In the ophthalmic compositions of Prescription Examples 1-2 and 1-5, which were prepared by blending vitamin A and chlorpheniramine maleate into the ophthalmic compositions of Prescription Examples 1-1 and 1-4, each of which contained only neostigmine methylsulfate as an active ingredient, adsorption of neostigmine methylsulfate to soft contact lenses was significantly suppressed compared to the ophthalmic compositions of Prescription Examples 1-1 and 1-4. Furthermore, in the ophthalmic compositions of Prescription Examples 1-3 and 1-6, which were prepared by blending vitamin A, chlorpheniramine maleate, aminoethylsulfonic acid, and sodium chondroitin sulfate into the ophthalmic compositions of Prescription Examples 1-1 and 1-4, adsorption of neostigmine methylsulfate to soft contact lenses was even more significantly suppressed compared to the ophthalmic compositions of Prescription Examples 1-1 and 1-4.

[0057] In the ophthalmic compositions of Formulation Examples 1-8 and 1-10, which were formulated with vitamin A, neostigmine methylsulfonate, aminoethylsulfonic acid, and sodium chondroitin sulfate in addition to the ophthalmic compositions of Formulation Examples 1-7 and 1-9, which contained only chlorpheniramine maleate as an active ingredient, the adsorption of chlorpheniramine maleate to soft contact lenses was suppressed compared to the ophthalmic compositions of Formulation Examples 1-7 and 1-9.

[0058] Test Example 2: Evaluation of suppression of diameter change of soft contact lenses Ophthalmic compositions for soft contact lenses are required not to affect the physical properties (color, shape, hardness, fragility, etc.) of soft contact lenses, and changes in the lens properties (diameter, base curve, etc.) affect fitting, causing a foreign body sensation or discomfort in the eye and making the soft contact lens more likely to come off. Therefore, an ophthalmic composition that can suppress changes in the diameter of soft contact lenses is evaluated as being able to suppress the foreign body sensation and / or discomfort in the eye caused by wearing soft contact lenses.

[0059] (method) Ophthalmic compositions of each formulation example were prepared according to the compositions shown in Tables 3 to 5 in accordance with conventional methods. Soft contact lens 1 (Alcon, Focus Dailies, Group II, diameter manufacturer's standard: 13.80 mm) and soft contact lens 2 (Johnson & Johnson, 2-week Acuvue, Group IV, diameter manufacturer's standard: 14.00 mm) were washed with saline (Otsuka saline). Four milliliters of saline was dispensed into each well of a 12-well plate (Falcon, product number 353043), and each soft contact lens was immersed in the solution for at least four hours at room temperature. After immersion, the solution adhering to the soft contact lens was wiped off with a nonwoven wiper (Bencotto, PS-2, Ozu Sangyo). Next, 10 mL of the ophthalmic composition of each formulation example prepared above was poured into a PFA bottle (Sanplatec, product number SAN13905), and one soft contact lens was immersed in the solution. The solution was then shaken at 120 rpm and 34°C for 24 hours. Next, each soft contact lens was immersed in the ophthalmic composition of each prescription example, and the temperature was kept constant at 20°C, and the diameter of the soft contact lens was measured using a universal projector (Nikon, V-12B). The difference between the measured diameter and the manufacturer's standard value for the diameter of the soft contact lens was then taken as the diameter change, and the diameter change rate for each prescription example was calculated according to the following formula 2, assuming that the diameter change for the reference prescription example was 100%. The results are shown in Tables 3 to 5. For prescription example 2-2, the reference prescription example is 2-1, for prescription example 2-4, the reference prescription example is 2-3, for prescription example 2-6, the reference prescription example is 2-5, and for prescription example 2-8, the reference prescription example is 2-7. (Equation 2): Diameter change rate (%) relative to the reference prescription example = (diameter change of prescription example / diameter change of reference prescription example) × 100

[0060] [Table 3]

[0061] [Table 4]

[0062] [Table 5]

[0063] The ophthalmic compositions of Prescription Examples 2-2 and 2-4, which were formulated by compounding vitamin A, neostigmine methylsulfonate, aminoethylsulfonic acid, and sodium chondroitin sulfate with the ophthalmic compositions of Prescription Examples 2-1 and 2-3, each containing only chlorpheniramine maleate as an active ingredient, suppressed the rate of change in diameter of soft contact lenses compared to the ophthalmic compositions of Prescription Examples 2-1 and 2-3, respectively.

[0064] The ophthalmic compositions of Prescription Examples 2-6 and 2-8, which were formulated with vitamin A, chlorpheniramine maleate, aminoethylsulfonic acid, and sodium chondroitin sulfate in addition to the ophthalmic compositions of Prescription Examples 2-5 and 2-7, each containing only neostigmine methylsulfate as the active ingredient, suppressed the rate of change in diameter of the soft contact lens compared to the ophthalmic compositions of Prescription Examples 2-5 and 2-7, respectively.

[0065] [Test Example 3: Nav1.7 Current Measurement Test] It has been reported that when the phosphorylation and expression of ion channels involved in pain sensation, including Nav1.7, are enhanced by wearing soft contact lenses, etc., nerve excitability increases, inducing eye pain (e.g., The Ocular Surface, Vol. 16(1), January 2018, pp. 31-44). Therefore, an ophthalmic composition that can inhibit Nav1.7 current is evaluated as being able to suppress the sense of incongruity, discomfort, pain, and / or stinging in the eyes caused by wearing soft contact lenses.

[0066] (method) Test solutions for each formulation example were prepared according to the compositions shown in Table 6 in a conventional manner. hNav1.7-expressing CHO cells were seeded on glass coverslips. Under voltage clamp, Nav1.7 current across the cell membrane was recorded using the whole-cell patch clamp technique. The holding potential was set at -100 mV, and 30-msec depolarizing pulses of -20 mV were applied to the cells once every 10 seconds. After the peak inward Nav1.7 current stabilized in the extracellular solution, the test solution of each formulation was applied to the cells for 5 minutes. Nav1.7 current was measured using a patch clamp amplifier (Axopatch 200B, Molecular Devices LLC, California, USA), and the resulting electrical signals were recorded on a computer using patch clamp recording analysis software (pCLAMP 10, Molecular Devices LLC, California, USA). The peak Nav1.7 current was measured, and the percentage change in Nav1.7 current after application of each formulation relative to the Nav1.7 current before application (Nav1.7 current inhibition rate) was calculated. The inhibition rate of Formulation Example 3-2 was calculated based on the following formula 3, assuming that the inhibition rate of Formulation Example 3-1 was 100. The results are shown in Table 6. (Equation 3): Nav1.7 current suppression rate for the reference formulation = (Nav1.7 current suppression rate for each formulation / Nav1.7 current suppression rate for formulation example 3-1) × 100 The extracellular fluid used was an aqueous solution having the following composition to which DMSO was added so as to make a concentration of 0.5 w / v %. NaCl: 140mmol / L, KCl: 4mmol / L, CaCl2: 2mmol / L, MgCl2: 1mmol / L, HEPES: 10mmol / L, D(+)-glucose: 10mmol / L (adjusted to pH 7.35 with 1mol / L NaOH)

[0067] [Table 6]

[0068] It was confirmed that Formulation Example 3-2, which contains vitamin A, neostigmine methylsulfate, and chlorpheniramine maleate as active ingredients, suppresses the Nav1.7 current by about 2.8 times compared to Formulation Example 3-1, which contains only vitamin A as the active ingredient. Therefore, the ophthalmic composition according to this embodiment can significantly suppress the discomfort, pain, and / or stinging sensation in the eyes caused by wearing soft contact lenses.

[0069] Test Example 4: Corneal epithelial cell proliferation test Test solutions for each formulation example were prepared according to the compositions shown in Table 7 in a conventional manner. Immortalized human corneal epithelial cells (HCE-T) (RIKEN) were cultured at 6 × 10 3 Cells were seeded into a 96-well plate (Corning 3340) at 100 cells / well and cultured for 3 days at 37°C, 5% CO2, and 90% humidity. Each test solution prepared above was added to the cells after removing the culture supernatant, and the cells were cultured for another 3 days at 37°C, 5% CO2, and 90% humidity. The culture supernatant was removed, and a solution of Cell Counting Kit 8 (DOJINDO) diluted 10-fold with culture medium was added to the cells. After 1 hour, the absorbance at 450 nm was measured. The test solution (Formulation Example 4-1) containing no vitamin A, sodium chondroitin sulfate, or aminoethylsulfonic acid was used as a control group. The cell viability of each formulation was evaluated based on the following formula 4, with the cell viability of the control group being set at 100%. In formula 4, "blank" refers to the absorbance at 450 nm of the WST-8 solution without cells seeded. The results are shown in Table 7. (Equation 4) Cell viability (%) for the reference formulation = {(absorbance at 450 nm for each formulation - blank) / (absorbance at 450 nm for formulation example 4-1 - blank)} x 100 The culture medium used was DMEM / F-12 (Dulbecco's Modified Eagle Medium / Nutrient Mixture F-12, Gibco) supplemented with insulin (5 μg / mL), hEGF (10 μg / mL), sterile DMSO (0.5%), and FBS (5%).

[0070] [Table 7]

[0071] In Formulation Example 4-2, which contained only vitamin A as the active ingredient, the cell viability was almost unchanged compared to the control Formulation Example 4-1. On the other hand, in Formulation Example 4-3, which contained vitamin A, sodium chondroitin sulfate, and aminoethylsulfonic acid as active ingredients, the cell viability was significantly higher than that of the control Formulation Example 4-1 (p<0.05, Dunnett's test). Therefore, it was confirmed that the ophthalmic composition according to this embodiment has an excellent protective effect on corneal epithelial cells.

[0072] Test Example 5: Evaluation of suppression of adsorption of ingredients to soft contact lenses (2) Ophthalmic compositions of each formulation example were prepared according to the compositions shown in Tables 8 to 10 in accordance with conventional methods. Soft contact lens 3 (Johnson & Johnson, 2-week Acuvue, Group IV) and soft contact lens 4 (Alcon, Focus Dailies, Group II) were washed with saline (Otsuka saline). 4 mL of saline was dispensed into each well of a 12-well plate (Falcon, product number 353043), and each soft contact lens was immersed in the solution for at least 4 hours at room temperature. After immersion, the solution adhering to the soft contact lens was wiped off with a nonwoven wiper (Bencotto, PS-2, Ozu Sangyo). Next, 10 mL of each of the ophthalmic compositions prepared above was poured into a 10 mL glass headspace vial (GL Sciences), and one soft contact lens was immersed in the solution. The solution was then shaken at 120 rpm and 34°C for 24 hours. Next, for each formulation, the neostigmine methylsulfate and chlorpheniramine maleate contained in the sample ophthalmic composition (in which a soft contact lens was soaked) and the blank ophthalmic composition (in which a soft contact lens was not soaked and stored at 4°C for 24 hours) were quantified by HPLC, and the difference was taken as the amount of neostigmine methylsulfate and chlorpheniramine maleate adsorbed to the soft contact lens. The adsorption rate of each formulation was then calculated using the following formula 1, assuming the adsorption rate of the reference formulation to be 100%. The results are shown in Tables 8 to 10. The reference prescription example for prescription examples 5-2 to 5-5 is prescription example 5-1, the reference prescription example for prescription examples 5-7 to 5-10 is prescription example 5-6, and the reference prescription example for prescription examples 5-12 to 5-14 is prescription example 5-11. (Equation 1): Adsorption rate (%) relative to the standard formulation example = (adsorption amount of the formulation example / adsorption amount of the standard formulation example) × 100

[0073] [Table 8]

[0074] [Table 9]

[0075] [Table 10]

[0076] When soft contact lens 3 was used, the amount of neostigmine methylsulfate adsorbed to the soft contact lens was significantly increased in the ophthalmic composition of Prescription Example 5-2, which further contained vitamin A (50,000 IU / 100 mL) in addition to the ophthalmic composition of Prescription Example 5-1, which contained only neostigmine methylsulfate as the active ingredient, compared to the ophthalmic composition of Prescription Example 5-1. In contrast, the ophthalmic composition of Prescription Example 5-3, which further contained vitamin A (40,000 IU / 100 mL) and chlorpheniramine maleate (0.01 w / v%) in addition to the ophthalmic composition of Prescription Example 5-1, suppressed adsorption of neostigmine methylsulfate to soft contact lenses compared to the ophthalmic composition of Prescription Example 5-1, and the ophthalmic composition of Prescription Example 5-4, which further contained vitamin A (50,000 IU / 100 mL) and chlorpheniramine maleate (0.03 w / v%) in addition to the ophthalmic composition of Prescription Example 5-1, significantly suppressed adsorption of neostigmine methylsulfate to soft contact lenses compared to the ophthalmic composition of Prescription Example 5-1. Furthermore, the ophthalmic composition of Formulation Example 5-5, which further contained vitamin A (50,000 IU / 100 mL), chlorpheniramine maleate (0.03 w / v%), aminoethylsulfonic acid, and sodium chondroitin sulfate in addition to the ophthalmic composition of Formulation Example 5-1, showed a more significant inhibition of adsorption of neostigmine methylsulfate to soft contact lenses compared to the ophthalmic composition of Formulation Example 5-1.

[0077] When soft contact lens 3 was used, the ophthalmic compositions of Prescription Examples 5-7 and 5-8, which further contained vitamin A (50,000 IU / 100 mL) or neostigmine methylsulfate (0.005 w / v%) in addition to the ophthalmic composition of Prescription Example 5-6 containing only chlorpheniramine maleate as the active ingredient, showed adsorption of chlorpheniramine maleate to the soft contact lens to the same extent as the ophthalmic composition of Prescription Example 5-6. In contrast, the ophthalmic composition of Formulation Example 5-9, which further contained vitamin A (40,000 IU / 100 mL), neostigmine methylsulfonate (0.001 w / v%), aminoethylsulfonic acid (0.1 w / v%), and sodium chondroitin sulfate (0.05 w / v%) in addition to the ophthalmic composition of Formulation Example 5-6, suppressed adsorption of chlorpheniramine maleate to soft contact lenses compared to the ophthalmic composition of Formulation Example 5-6. The ophthalmic composition of Formulation Example 5-10, which further contained vitamin A (50,000 IU / 100 mL), neostigmine methylsulfonate (0.005 w / v%), aminoethylsulfonic acid (1 w / v%), and sodium chondroitin sulfate (0.5 w / v%) in addition to the ophthalmic composition of Formulation Example 5-6, significantly suppressed adsorption of chlorpheniramine maleate to soft contact lenses compared to the ophthalmic composition of Formulation Example 5-6.

[0078] When soft contact lens 4 was used, the ophthalmic composition of Prescription Example 5-12, which further contained neostigmine methylsulfate in addition to the ophthalmic composition of Prescription Example 5-11 containing only chlorpheniramine maleate as an active ingredient, showed adsorption of chlorpheniramine maleate to the soft contact lens to the same extent as the ophthalmic composition of Prescription Example 5-11. However, the ophthalmic composition of Prescription Example 5-13, which further contained vitamin A, neostigmine methylsulfonic acid, aminoethylsulfonic acid, and sodium chondroitin sulfate in addition to the ophthalmic composition of Prescription Example 5-11, showed significantly reduced adsorption of chlorpheniramine maleate to the soft contact lens compared to the ophthalmic composition of Prescription Example 5-11.

[0079] [Formulation example] Eye drops for soft contact lenses are prepared by a conventional method according to the formulation shown in the following Table 11. The unit of the amount of each component in the following Table 11 is w / v % unless otherwise specified in the table.

[0080] [Table 11]

Claims

1. Vitamin A and at least one selected from the group consisting of aminoethylsulfonic acid, potassium L-aspartate, magnesium L-aspartate, and potassium magnesium L-aspartate; Sodium chondroitin sulfate, and at least one selected from the group consisting of neostigmine methylsulfate and chlorpheniramine maleate, the content of the vitamin A group is 3.5 to 50,000 IU / 100 mL based on the total amount of the ophthalmic composition; the content of the aminoethylsulfonic acid is 0.9 to 1.1 w / v % based on the total amount of the ophthalmic composition; the content of the potassium L-aspartate is 0.9 to 1.1 w / v % based on the total amount of the ophthalmic composition; the content of the magnesium L-aspartate is 0.01 to 2 w / v % based on the total amount of the ophthalmic composition; the content of the potassium magnesium L-aspartate is 0.01 to 2 w / v % based on the total amount of the ophthalmic composition; the content of the sodium chondroitin sulfate is 0.5 to 1 w / v % based on the total amount of the ophthalmic composition; The content of the neostigmine methylsulfate is 0.0 based on the total amount of the ophthalmic composition. 0.045 to 0.0055 w / v%, The ophthalmic composition has a content of chlorpheniramine maleate of 0.01 to 0.05 w / v % based on the total amount of the ophthalmic composition.

2. The vitamin A compound is retinol palmitate, The ophthalmic composition according to claim 1, wherein the content of retinol palmitate is 50,000 IU / 100 mL based on the total volume of the ophthalmic composition.

3. the content of the aminoethylsulfonic acid is 1 w / v % based on the total amount of the ophthalmic composition; the content of the potassium L-aspartate is 1 w / v% based on the total amount of the ophthalmic composition; the content of the magnesium L-aspartate is 1 w / v% based on the total amount of the ophthalmic composition; 3. The ophthalmic composition according to claim 1, wherein the content of the potassium magnesium L-aspartate is 2 w / v % based on the total amount of the ophthalmic composition.

4. The ophthalmic composition according to any one of claims 1 to 3, wherein the content of the neostigmine methylsulfate is 0.005 w / v % based on the total amount of the ophthalmic composition.

5. The ophthalmic composition according to any one of claims 1 to 4, wherein the content of the chlorpheniramine maleate is 0.03 w / v % based on the total amount of the ophthalmic composition.

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