JP2024072717A - Ophthalmologic composition - Google Patents

Abstract

To provide an ophthalmologic composition that can improve symptoms such as a sensation of foreign matter in the eye, eye mucus, blurry vision, and watery eyes.SOLUTION: An ophthalmologic composition for improving at least one symptom selected from the group consisting of a sensation of foreign matter in the eye, eye mucus, blurry vision, and watery eyes contains at least one selected from the group consisting of chondroitin sulfate and salts thereof. The total content of at least one selected from the group consisting of chondroitin sulfate and salts thereof is 1 w/v% relative to the total amount of the ophthalmologic composition.SELECTED DRAWING: None

Description

The present invention relates to an ophthalmic composition.

The cornea is the outermost tissue of the eyeball, and is made up of five layers: corneal epithelium, Bowman's membrane, corneal stroma, Descemet's membrane, and corneal endothelium. Because the cornea is in direct contact with the outside world, it is susceptible to the intrusion of various foreign substances, such as antigens, microorganisms, and dust.

Inflammatory and anti-inflammatory cytokines transmit information between cells and regulate immune function. However, if a foreign body enters the cornea, causing excessive secretion of inflammatory cytokines and upsetting the balance of immune function, symptoms such as a foreign body sensation in the eye, eye discharge, blurred vision, and watery eyes are induced. In order to alleviate these symptoms, ophthalmic compositions containing anti-inflammatory agents have been proposed.

Chondroitin sulfate or its salts have the effect of promoting energy metabolism, metabolism, and cellular respiration, as well as water retention, and are sometimes incorporated into ophthalmic compositions (for example, Patent Document 1).

However, nothing is known about the effects of chondroitin sulfate or its salts on the ocular foreign body sensation, eye discharge, blurred vision, and watery eyes, as well as the effects on the expression of inflammatory cytokines in corneal epithelial cells.

JP 2011-148791 A

The object of the present invention is to provide an ophthalmic composition that can improve symptoms such as foreign body sensation in the eye, eye discharge, blurred vision, and watery eyes.

The present inventors have unexpectedly discovered that an ophthalmic composition containing a specific amount of at least one selected from the group consisting of chondroitin sulfate and its salts suppresses gene expression of inflammatory cytokines in corneal epithelial cells and improves symptoms such as foreign body sensation in the eye, eye discharge, blurred vision, and watery eyes.

The present invention provides, for example, the following inventions.
[1]
An ophthalmic composition for improving, alleviating, treating, or preventing at least one symptom selected from the group consisting of foreign body sensation in the eye, eye discharge, blurred vision, and watery eyes, comprising at least one member selected from the group consisting of chondroitin sulfate and its salts, wherein the total content of the at least one member selected from the group consisting of chondroitin sulfate and its salts is 1 w/v % based on the total amount of the ophthalmic composition.
[2]
The ophthalmic composition according to [1], wherein the weight average molecular weight of at least one selected from the group consisting of chondroitin sulfate and its salts is 8,000 to 60,000.
[3]
The ophthalmic composition according to [1] or [2], which is an eye drop.

The present invention provides an ophthalmic composition that can improve symptoms such as foreign body sensation in the eye, eye discharge, blurred vision, and watery eyes.

The following describes in detail the embodiments of the present invention. However, the present invention is not limited to the following embodiments. In this specification, unless otherwise specified, the unit of content "%" means "w/v%" and is synonymous with "g/100 mL."

The ophthalmic composition according to this embodiment contains at least one component selected from the group consisting of chondroitin sulfate and its salts (also referred to simply as "component (A)").

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

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.

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

When chondroitin sulfate and its salts are included, they may be included as an active ingredient, or they may enhance the effects of other ingredients that improve symptoms such as a foreign body sensation in the eye, eye discharge, blurred vision, and watery eyes.

In this specification, the "weight average molecular weight" can be determined by using gel permeation chromatography in which a multi-angle light scattering detector (MALS detector) and a differential refractive index detector (RI detector) are connected online. Specifically, the following conditions are presented.
<Standard sample preparation>
10 mL of 0.1 M aqueous sodium nitrate 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 chromatography - multi-angle light scattering meter Detector: Differential refractive index detector (Optilab rEX, manufactured by Wyatt Technology)
Multi-angle light scattering detector (DAWN HELEOS, manufactured by Wyatt Technology)
Column: Shodex OHpak SB-806M HQ x 2 (φ7.8 mm x 30 cm, Showa Denko)
Solvent: 0.1 M sodium nitrate aqueous solution Flow rate: 0.7 mL/min
Column temperature: 23°C
Detector temperature: 23°C
Injection volume: 0.2 mL
Data processing: Wyatt Technology data processing system (ASTRA)

The molecular weight of chondroitin sulfate and its salts is not particularly limited as long as it is medicamentarily, pharmacologically (pharmaceutical), or physiologically acceptable, but examples of lower limits of the weight average molecular weight calculated by the above method include 8,000 or more, 10,000 or more, 15,000 or more, and 20,000 or more. Examples of upper limits of the weight average molecular weight calculated by the above method include 60,000 or less, 50,000 or less, 45,000 or less, 40,000 or less, 35,000 or less, and 30,000 or less. Examples of preferred weight average molecular weight ranges are 8,000 to 60,000, 20,000 to 45,000, and 20,000 to 30,000.

Chondroitin sulfate and its salts can be commercially available. Chondroitin sulfate and its salts can be used alone or in combination of two or more. Chondroitin sulfate and its salts can be used in combination with chondroitin sulfates and their salts having various weight-average molecular weights. For example, sodium chondroitin sulfate having a weight-average molecular weight of 56,000 can be used in combination with sodium chondroitin sulfate having a weight-average molecular weight of 25,000. When using such a combination, it is preferable to use chondroitin sulfate and its salts having a weight-average molecular weight of 8,000 to 60,000, preferably 9,000 to 45,000, more preferably 10,000 to 40,000 as raw materials.

The total content of the component (A) in the ophthalmic composition according to this embodiment is not particularly limited, and is appropriately set according to the type and content of other blended components, the formulation form of the ophthalmic composition, etc. The lower limit of the total content of the component (A) is, for example, preferably 0.7 w/v% or more, and more preferably 0.9 w/v% or more, from the viewpoint of more significantly achieving the effects of the present invention. The upper limit of the total content of the component (A) may be, for example, 1.2 w/v% or less, and preferably 1.1 w/v% or less, from the viewpoint of more significantly achieving the effects of the present invention. In addition, the total content of the component (A) in the ophthalmic composition according to this embodiment is particularly preferably 1.0 w/v% based on the total amount of the ophthalmic composition.

The ophthalmic composition according to this embodiment may further contain a buffering agent. When the ophthalmic composition further contains a buffering agent, the effect of the present invention is more pronounced. As the buffering agent, boric acid buffering agents (e.g., a combination of boric acid and borax, etc.), phosphate buffering agents (e.g., a combination of disodium hydrogen phosphate and sodium dihydrogen phosphate, etc.), and tris buffering agents (e.g., trometamol) are preferred, boric acid buffering agents and phosphate buffering agents are more preferred, boric acid and its salts are even more preferred, and a combination of boric acid and borax is even more preferred.

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 type and content of other blended ingredients, the intended use of the ophthalmic composition, the formulation form, etc. From the viewpoint of more significantly achieving the effects of the present invention, the content of the buffering agent is preferably 0.01 to 10 w/v%, more preferably 0.05 to 5 w/v%, and even more preferably 0.1 to 3 w/v%, based on the total amount of the ophthalmic composition.

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 type of the component (A) and the buffering agent, the type and content of other blended components, the intended use of the ophthalmic composition, the formulation form, etc. From the viewpoint of further enhancing the effect of the present invention, for example, the content ratio of the buffering agent relative to the component (A) is preferably 0.01 to 10 parts by mass, more preferably 0.05 to 5 parts by mass, and even more preferably 0.1 to 3 parts by mass, of the total content of the component (A) contained in the ophthalmic composition according to this embodiment.

The pH of the ophthalmic composition according to this embodiment is not particularly limited as long as it is within a medicamentously, 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, even more preferably 5.0 to 8.5, particularly preferably 5.0 to 8.0, and even more particularly preferably 5.5 to 8.0. It may also be 6.0 to 8.0, 6.5 to 8.0, 6.0 to 8.5, or 6.5 to 8.5.

The ophthalmic composition according to this embodiment can be adjusted to an osmotic pressure ratio within a range acceptable to the living body, if necessary. The appropriate osmotic pressure ratio can be appropriately set depending on the purpose, formulation, and method of use of the ophthalmic composition, and 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. It may also be 0.7 to 2.0, or 0.7 to 1.5. The osmotic pressure ratio is 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) based on the 17th Revised Japanese Pharmacopoeia, and the osmotic pressure is measured with reference to 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), and then accurately weighing out 0.900 g of it and dissolving it in purified water to make exactly 100 mL, or a commercially available standard solution for measuring osmolality ratios (0.9 w/v% sodium chloride aqueous solution) can be used.

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 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 1000 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, as measured at 20°C using a rotational viscometer (TV-20 type viscometer, manufactured by Toki Sangyo Co., Ltd., rotor: 1°34'×R24).

The ophthalmic composition according to the present embodiment may contain an appropriate amount of a combination of various pharmacologically active ingredients and physiologically active ingredients in addition to the above-mentioned ingredients, as long as the effect of the present invention is not impaired. The ingredients are not particularly limited, and examples thereof include active ingredients in ophthalmic drugs listed in the 2017 edition of the General Drug Manufacturing and Sales Approval Standards (supervised by the Japan Society of Regulatory Science). Specific examples of ingredients used in ophthalmic drugs include the following ingredients.
Antiallergic agents: for example, cromoglycic acid or a salt thereof (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), epinastine or a salt thereof (e.g., epinastine hydrochloride), and the like.
Steroids: for example, fluticasone propionate, fluticasone furoate, mometasone furoate, beclomethasone propionate, flunisolide, etc.
Decongestants: for example, epinephrine, epinephrine hydrochloride, ephedrine hydrochloride, phenylephrine hydrochloride, dl-methylephedrine hydrochloride, and the like.
Ocular muscle regulating drugs: for example, cholinesterase inhibitors having an active center similar to that of acetylcholine, specifically, tropicamide, helenien, atropine sulfate, pilocarpine 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, glycyrrhizic acid or a salt thereof (for example, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate), zinc sulfate, zinc lactate, etc.
Vitamins: for example, retinol acetate, retinol palmitate, tocopherol acetate, flavin adenine dinucleotide sodium, pyridoxine hydrochloride, panthenol, calcium pantothenate, ascorbic acid, sodium ascorbate, etc.
Amino acids: for example, L-arginine, glutamic acid, glycine, alanine, lysine, γ-aminobutyric acid, γ-aminovaleric acid, trimethylglycine, taurine, aspartic acid, and salts thereof.
Astringents: for example, zinc oxide.

In the ophthalmic composition according to the present embodiment, various additives may be appropriately selected according to the application and formulation form, and one or more additives may be used in combination in an appropriate amount according to the usual method, as long as the effect of the present invention is not impaired. Examples of such additives include various additives listed in the Pharmaceutical Additives Encyclopedia 2021 (edited by the Japan Pharmaceutical Additives Association). Representative components include the following additives.
Carrier: For example, an aqueous solvent such as water or aqueous ethanol.
Chelating agents: for example, (EDDA), ethylenediaminetriacetic acid, N-(2-hydroxyethyl)ethylenediaminetriacetic acid (HEDTA), diethylenetriaminepentaacetic acid (DTPA), and the like.
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: 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 dimethylaminoacetate betaine.
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-form.
Thickeners: for example, cellulose-based polymer compounds such as methylcellulose, ethylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose, etc.; guar gum; hydroxypropyl guar gum; gum arabic; karaya gum; xanthan gum; agar; alginic acid and its salts (sodium salt, etc.); heparinoids, 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: for example, borate buffers, phosphate buffers, citrate buffers, carbonate buffers, acetate buffers, lactate buffers, succinate buffers, Tris buffers, AMPD buffers, and the like.
Stabilizers: for example, sodium formaldehyde sulfoxylate (Rongalit), aluminum monostearate, glycerin monostearate, cyclodextrin, monoethanolamine, dibutylhydroxytoluene, sodium hydrogensulfite, sodium pyrosulfite, etc.
Preservatives: for example, alkyl polyaminoethyl glycine quaternary ammonium salts (e.g., benzalkonium chloride, benzethonium chloride, etc.), chlorhexidine gluconate, polydonium 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.
Isotonicity 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.

When the ophthalmic composition according to this embodiment contains water, the water content is, for example, 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, from the viewpoint of more significantly achieving the effects of the present invention.

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 17th edition of the Japanese Pharmacopoeia.

The ophthalmic composition according to this embodiment can be prepared by adding and mixing a desired amount of at least one selected from the group consisting of chondroitin sulfate and its salts, and other components as necessary, to a desired concentration. For example, it can be prepared by dissolving or dispersing those components in purified water, adjusting the pH and osmotic pressure to a predetermined level, and sterilizing the composition by filtration sterilization or the like.

The ophthalmic composition according to this embodiment can be in various formulation forms depending on the purpose. Examples of the formulation form include a liquid, a gel, a semi-solid (ointment, etc.), etc.

The ophthalmic composition according to the present 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. Eyewash includes eyewash that can be applied while wearing contact lenses), and contact lens compositions [contact lens wearing solution, contact lens care composition (contact lens disinfectant, contact lens preservative, contact lens cleaner, contact lens cleaning and preservative), contact lens packaging solution, etc.]. The term "contact lenses" includes hard contact lenses and soft contact lenses (including both ionic and non-ionic, and both silicone hydrogel contact lenses and non-silicone hydrogel contact lenses).

The ophthalmic composition according to this embodiment is preferably an eye drop (including an eye drop that can be applied while wearing contact lenses) because it can more significantly exert the effects of the present invention. When the ophthalmic composition according to this embodiment is an eye drop, the method of use and dosage are not particularly limited as long as it is effective and has few side effects. For example, for adults (15 years or older) and children aged 7 years 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, and 1 to 2 drops are preferably applied 4 times a day.

The ophthalmic composition according to the present embodiment is provided in any container. The container for containing the ophthalmic composition according to the present embodiment is not particularly limited, and may be made of glass or plastic, for example. Plastic is preferable. Examples of plastic include polyethylene terephthalate (PET), polyarylate, polyethylene naphthalate, polycarbonate, polyethylene, polypropylene, polyimide, copolymers of monomers constituting these, and mixtures of two or more of these. Polyethylene terephthalate is preferable. The container for containing the ophthalmic composition according to the present embodiment may be a transparent container that allows the inside of the container to be seen, or an opaque container that makes it difficult to see the inside of the container. A transparent container is preferable. Here, the "transparent container" includes both a colorless transparent container and a colored transparent container.

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 made of glass or plastic, for example. Plastic is preferable. 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 terephthalate.

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 a single use.

The ophthalmic composition according to this embodiment is preferably filled in a container having an internal volume of 4 to 30 mL, more preferably filled in a container having an internal volume of 5 to 20 mL, even more preferably filled in a container having an internal volume of 6 to 16 mL, and even more preferably filled in a container having an internal volume of 10 to 15 mL. It may also 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.

The ophthalmic composition according to this embodiment contains at least one selected from the group consisting of chondroitin sulfate and its salts, and as confirmed in the examples described below, significantly suppresses the gene expression of inflammatory cytokines, particularly IL-1α, IL-1β, IL-6 and IL-8, in corneal epithelial cells. Here, IL-1α, IL-1β (References: Am J Ophthalmol. 2011 Dec; 152(6): 900-909. and Invest Ophthalmol Vis Sci. 2009 Feb; 50(2): 597-603.) and IL-6 (References: Transl Vis Sci Technol. 2021 Jun 1; 10(7): 17.) are involved in the foreign body sensation in the eye. In addition, since reflex tearing occurs due to a foreign body sensation (Reference: Solved! Unspecified and Unknown Symptoms of Eyes and Vision (Kanehara Publishing)), IL-1α, IL-1β, and IL-6, which are involved in the foreign body sensation in the eyes, are also involved in watery eyes. IL-8 is involved in the development of eye discharge (Reference: J Leukoc Biol. 2019 Jun; 105(6): 1087-1098.), and is involved in the development of symptoms such as blurred vision associated with eye discharge. For these reasons, the ophthalmic composition according to this embodiment can be suitably used as an ophthalmic composition for improving, alleviating, treating, or preventing at least one symptom selected from the group consisting of foreign body sensation in the eyes, eye discharge, blurred vision, and watery eyes. In addition, as one embodiment of the present invention, a method for improving, alleviating, treating, or preventing at least one symptom selected from the group consisting of foreign body sensation in the eyes, eye discharge, blurred vision, and watery eyes, which comprises administering to a subject an ophthalmic composition containing at least one selected from the group consisting of chondroitin sulfate and a salt thereof, is provided. Furthermore, as one embodiment of the present invention, there is provided a use of at least one selected from the group consisting of chondroitin sulfate and its salts for the manufacture of an ophthalmic composition for improving, alleviating, treating, or preventing at least one symptom selected from the group consisting of foreign body sensation in the eye, eye discharge, blurred vision, and watery eyes.

Note that the symptoms referred to in this specification include eye symptoms caused by pollen, house dust, etc. Furthermore, in this specification, "foreign body sensation in the eye" includes a rolling sensation, and "blurred vision" includes blurred vision caused by a lot of eye discharge.

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

[Test Example 1: Anti-inflammatory effect on corneal epithelial cell line]
The corneal epithelial cell line was cultured on a cell culture dish coated with laminin 511E8 fragment (0.5 μg/cm ² ) until it became confluent. The differentiation medium used for the culture was DMEM/F-12 (2:1 (v/v)) medium (Life Technologies) containing 2% B27 Supplement (Life Technologies), 1% penicillin-streptomycin solution (Life Technologies), 20 ng/mL KGF (Keratinocyte Growth Factor) (Wako), and 10 μM Y-27632 (Wako). Subsequently, the cells were cultured overnight in a basal medium (DMEM/F-12 (2:1 (v/v)) medium containing 1% penicillin-streptomycin solution) to starve the cells. Thereafter, TNF was added (10 ng/mL) as an inflammation-inducing factor to the basal medium, and then sodium chondroitin sulfate having a weight-average molecular weight of about 25,000 was added to the basal medium to a concentration of 1.0 w/v%, and after 4 hours of culture, the cells were recovered using Maxwell RSC simpleRNA Tissue Kit (Promega). Thereafter, the cells were subjected to RT-qPCR to measure the gene expression levels of IL-1α, IL-1β, IL-6, and IL-8 relative to GAPDH. In addition, a culture condition in which neither TNF nor sodium chondroitin sulfate was added was used as a negative control, and a culture condition in which TNF was added but sodium chondroitin sulfate was not added was used as a positive control. The expression rate (%) of each gene following sodium chondroitin sulfate treatment relative to the negative control was calculated using the following formula 1.
Formula 1: Expression rate of each gene by TNF treatment or by TNF and sodium chondroitin sulfate treatment relative to the negative control=(expression level of each gene relative to GAPDH by TNF treatment or by addition of TNF and sodium chondroitin sulfate/expression level of each gene relative to GAPDH in the negative control)×100
The results are shown in Tables 1 to 4.

Tables 1 to 4 confirm that the addition of sodium chondroitin sulfate significantly reduces the mRNA expression levels of IL-1α, IL-1β, IL-6, and IL-8.

[Test Example 2: Sensory evaluation of eye drops]
[Preparation of eye drops (formulations A and B)]
An eye drop was prepared according to the standard method based on the formulation shown in Table 5. This sample was filled into an eye dropper bottle (container volume 14-14.5 mL, polyethylene terephthalate material) at 13 mL (filling rate 89.7-92.9%) to prepare an evaluation sample. The viscosity of formulation A was 2.1 mPa·s.
Formulations A and B were administered to the right eye of trained panelists (those with symptoms of eye discharge, foreign body sensation in the eye, blurred vision, or watery eyes) for four days at a dosage of 1 to 2 drops four times a day. Evaluation was performed using the VAS (Visual Analogue Scale) method, with subjective levels of eye discharge, foreign body sensation in the eye, blurred vision, and watery eyes marked in a straight line using a 10 cm line. Improvement values were calculated according to formula 2.
Formula 2: Improvement score = (mean VAS score before administration) - (mean VAS score after 4 days of administration)
The results are shown in Table 6.

From Table 6, it is clear that the improvement value of Formula A was higher than that of Formula B, making Formula A more effective than Formula B. Regarding blurred vision, the improvement value of Formula A was also higher than that of Formula B. This is consistent with the results of Test Example 1, and it was confirmed that 1 w/v% sodium chondroitin sulfate is effective in improving eye discharge, foreign body sensation in the eye, blurred vision, and watery eyes.

[Formulation example]
Ophthalmic compositions were prepared and filled into PET containers according to the formulations shown in Tables 7 to 9. In Tables 7 to 9, the units of each component are (w/v %).

Claims (3)

An ophthalmic composition for improving, alleviating, treating, or preventing at least one symptom selected from the group consisting of foreign body sensation in the eye, eye discharge, blurred vision, and watery eyes, containing at least one selected from the group consisting of chondroitin sulfate and its salts, wherein the total content of the at least one selected from the group consisting of chondroitin sulfate and its salts is 1 w/v% based on the total amount of the ophthalmic composition. The ophthalmic composition according to claim 1, wherein the weight average molecular weight of at least one selected from the group consisting of chondroitin sulfate and its salts is 8,000 to 60,000. The ophthalmic composition according to claim 1 or 2, which is an eye drop.