Ophthalmic composition

Abstract

To provide an ophthalmic composition that causes less wetting of a resin comprising polybutylene terephthalate.SOLUTION: An ophthalmic composition has (A) pranoprofen or salt thereof, and (B) at least one selected from the group consisting of nonionic surface active components, antiallergic components, anti-inflammatory components, preservatives, polysaccharides, vinyl compounds, vitamins, amino acids, refreshing agents, antioxidants, hyperemia removers, oil contents, and inorganic salts, wherein, the ophthalmic composition is stored in a container that has a portion in contact with the ophthalmic composition wholly or partially formed of a resin comprising polybutylene terephthalate.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to ophthalmic compositions. [Background technology]

[0002] Pranoprofen is known as a non-steroidal anti-inflammatory agent that has excellent anti-inflammatory, analgesic, and antipyretic effects, and is also highly safe, so it is incorporated into many ophthalmic pharmaceutical preparations.

[0003] Known containers for storing ophthalmic pharmaceutical preparations include containers made of polyethylene terephthalate, polyethylene naphthalate, polypropylene, polyarylate, polybutylene terephthalate, polycarbonate, and glass (for example, Patent Document 1). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2014-214085 Summary of the Invention [Problem to be solved by the invention]

[0005] The present inventors have discovered a new problem in that an ophthalmic composition containing (A) pranoprofen or a salt thereof has a small dynamic contact angle with a resin containing polybutylene terephthalate and thus is easily wetted. If the ophthalmic composition is easily wetted with a container formed of a resin containing polybutylene terephthalate, liquid may remain or the liquid may not drain easily, which may lead to a deterioration in the quality and usability of the ophthalmic composition.

[0006] An object of the present invention is to provide an ophthalmic composition that is inhibited from wetting a resin containing polybutylene terephthalate. [Means for solving the problem]

[0007] The present inventors have found that an ophthalmic composition containing (A) pranoprofen or a salt thereof in combination with (B) one or more selected from the group consisting of nonionic surfactants, antiallergic ingredients, anti-inflammatory ingredients, preservatives, polysaccharides, vinyl compounds, vitamins, amino acids, antioxidants, cooling agents, decongestants, oils, and inorganic salts has a larger dynamic contact angle (i.e., suppressed wetting) with a resin containing polybutylene terephthalate (hereinafter also referred to as a "polybutylene terephthalate-containing resin" or a "PBT-containing resin") than an ophthalmic composition containing (A) pranoprofen or a salt thereof alone. The present invention is based on this finding and provides the following inventions.

[0008] [1] An ophthalmic composition containing (A) pranoprofen or a salt thereof and (B) one or more selected from the group consisting of a nonionic surfactant, an antiallergic component, an anti-inflammatory component, a preservative, a polysaccharide, a vinyl compound, a vitamin, an amino acid, an antioxidant, a cooling agent, a decongestant, an oil, and an inorganic salt, wherein the ophthalmic composition is contained in a container, part or all of which comes into contact with the ophthalmic composition, and is formed from a resin containing polybutylene terephthalate. [2] the nonionic surfactant component is at least one selected from the group consisting of polyoxyethylene-polyoxypropylene block copolymers, polyoxyethylene castor oil derivatives, polyethylene glycol monostearate, polyhydric alcohols, and salts thereof; the antiallergic ingredient is one or more selected from the group consisting of tranilast, ketotifen, cromoglycic acid, and salts thereof; The anti-inflammatory component is at least one selected from the group consisting of azulene sulfonic acid, glycyrrhizinic acid, epsilon-aminocaproic acid, and salts thereof; the preservative is at least one selected from the group consisting of benzalkonium, a biguanide compound, sorbic acid, chlorobutanol, alkylpolyaminoethylglycine, parahydroxybenzoic acid ester, sulfamethoxazole, and salts thereof; the polysaccharide is at least one selected from the group consisting of acidic polysaccharides, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, and salts thereof; the vinyl compound is at least one selected from the group consisting of polyvinylpyrrolidone and salts thereof, the vitamin is one or more selected from the group consisting of cyanocobalamin, flavin adenine dinucleotide, panthenol, pyridoxine, retinol, tocopherol, and salts thereof; The amino acids are at least one selected from the group consisting of aspartic acid, taurine, and salts thereof, the refreshing agent is one or more selected from the group consisting of menthol, camphor, borneol, and geraniol; the antioxidant is at least one selected from the group consisting of butylhydroxyanisole and salts thereof; the decongestant is one or more selected from the group consisting of tetrahydrozoline, naphazoline, and salts thereof; The oil is one or more selected from the group consisting of vegetable oils, and The ophthalmic composition according to [1], wherein the inorganic salt is one or more selected from the group consisting of sodium chloride, calcium chloride, and zinc chloride. [3] (C) The ophthalmic composition according to [1] or [2], further comprising one or more selected from the group consisting of chlorpheniramine, edetic acid, dibutylhydroxytoluene, polysorbate 80, and salts thereof. [4] A method for imparting to an ophthalmic composition a wetting-inhibiting effect to a resin containing polybutylene terephthalate, the method comprising blending (A) pranoprofen or a salt thereof and (B) one or more selected from the group consisting of a nonionic surfactant, an antiallergic component, an anti-inflammatory component, a preservative, a polysaccharide, a vinyl compound, a vitamin, an amino acid, a cooling agent, an antioxidant, a decongestant, an oil, and an inorganic salt into the ophthalmic composition.

[0009] The present invention also provides the following inventions. [2-1] An ophthalmic composition containing (A) pranoprofen or a salt thereof and (B-1) one or more selected from the group consisting of a nonionic surfactant, an antiallergic component, an anti-inflammatory component, a preservative, a polysaccharide, a vinyl compound, an amino acid, a cooling agent, an antioxidant, a decongestant, an oil, and an inorganic salt, wherein the ophthalmic composition is contained in a container, part or all of which comes into contact with the ophthalmic composition, and is formed from a resin containing polybutylene terephthalate. [2-2] the nonionic surfactant component is at least one selected from the group consisting of polyoxyethylene-polyoxypropylene block copolymer, polyoxyethylene castor oil, polyethylene glycol monostearate, polyethylene glycol, sorbitol, xylitol, tyloxapol, and salts thereof; the antiallergic ingredient is one or more selected from the group consisting of tranilast, diphenhydramine, and salts thereof; the anti-inflammatory component is one or more selected from the group consisting of epsilon-aminocaproic acid, berberine, lysozyme, and salts thereof; the preservative is at least one selected from the group consisting of chlorhexidine, chlorobutanol, benzethonium, alkylpolyaminoethylglycine, paraben, sulfamethoxazole, phenylethyl alcohol, monoethanolamine, ethanol, and salts thereof; the polysaccharide is one or more selected from the group consisting of gellan gum, dextran, hydroxyethyl cellulose, carboxymethyl cellulose, and salts thereof; the vinyl compound is at least one selected from the group consisting of polyvinyl alcohol, carboxyvinyl polymer, and salts thereof; the amino acids are at least one selected from the group consisting of glycine, glutamic acid, taurine, and salts thereof; the cooling agent is one or more selected from the group consisting of borneol, geraniol, eucalyptus oil, and bergamot oil; the antioxidant is at least one selected from the group consisting of butylhydroxyanisole and salts thereof; the decongestant is one or more selected from the group consisting of tetrahydrozoline, naphazoline, and salts thereof; The oil is one or more selected from the group consisting of sesame oil, castor oil, petrolatum, paraffin, and lanolin; and The ophthalmic composition according to [2-1], wherein the inorganic salt is at least one selected from the group consisting of sodium chloride, calcium chloride, zinc chloride, and magnesium sulfate. [2-3] The ophthalmic composition according to [2-2], wherein the total content of taurine or a salt thereof is 0.25 w / v% or more based on the total amount of the ophthalmic composition. [2-4] (C) The ophthalmic composition according to any one of [2-1] to [2-3], further comprising one or more selected from the group consisting of chlorpheniramine, edetic acid, dibutylhydroxytoluene, polysorbate 80, and salts thereof.

[0010] The present invention also provides the following inventions. [3-1] An ophthalmic composition containing (A) pranoprofen or a salt thereof, (B-2) one or more anti-allergic ingredients selected from the group consisting of cromoglycic acid, ketotifen, tranilast and salts thereof, and (C-1) chlorpheniramine or a salt thereof, wherein the ophthalmic composition is contained in a container in which part or all of the part that comes into contact with the ophthalmic composition is formed of a resin containing polybutylene terephthalate. [3-2] The ophthalmic composition according to [3-1], further comprising one or more selected from the group consisting of (B-3) nonionic surfactants, mannitol, azulene sulfonic acid, glycyrrhizinic acid, epsilon-aminocaproic acid, allantoin, sorbic acid, chlorhexidine, hyaluronic acid, alginic acid, hydroxypropyl methylcellulose, polyvinylpyrrolidone, tocopherol acetate, cyanocobalamin, panthenol, taurine, aspartic acid, camphor, and salts thereof, and (C-2) polysorbate 80 and salts thereof. [3-3] The ophthalmic composition according to [3-2], wherein the nonionic surfactant component is propylene glycol, glycerin, polyoxyethylene hydrogenated castor oil, or a salt thereof. [3-4] The ophthalmic composition according to [3-2] or [3-3], wherein the total content of aspartic acid or a salt thereof is 0.25 w / v% or more based on the total amount of the ophthalmic composition. [3-5] Contains at least polysorbate 80, The ophthalmic composition according to any one of [3-2] to [3-4], further comprising (B-4) one or more selected from the group consisting of pyridoxine, polyhexamethylene biguanide, and salts thereof. [3-6] The ophthalmic composition according to any one of [3-2] to [3-4], which contains at least polyoxyethylene hydrogenated castor oil and tocopherol acetate. [3-7] Contains at least polyoxyethylene hydrogenated castor oil, The ophthalmic composition according to any one of [3-2] to [3-4], further comprising (B-5) one or more members selected from the group consisting of chondroitin sulfate, menthol, benzalkonium, and salts thereof. [3-8] The ophthalmic composition according to [3-7], wherein the total content of chondroitin sulfate or a salt thereof is 0.25 w / v% or more based on the total amount of the ophthalmic composition. [3-9] The component (B-2) contains at least tranilast or a salt thereof, The ophthalmic composition according to [3-1] further contains one or more selected from the group consisting of (B-6) nonionic surfactants, mannitol, azulene sulfonic acid, glycyrrhizinic acid, epsilon-aminocaproic acid, allantoin, sorbic acid, chlorhexidine, polyhexamethylene biguanide, chondroitin sulfate, hyaluronic acid, alginic acid, hydroxypropyl methylcellulose, polyvinylpyrrolidone, tocopherol acetate, cyanocobalamin, panthenol, taurine, aspartic acid, menthol, camphor, benzalkonium, and salts thereof, and (C-3) edetic acid, dibutylhydroxytoluene, polysorbate 80, and salts thereof. [3-10] The ophthalmic composition according to [3-9], wherein the nonionic surfactant component is propylene glycol, glycerin, polyoxyethylene hydrogenated castor oil, or a salt thereof.

[0011] The present invention also provides the following inventions. [4-1] An ophthalmic composition comprising (A) pranoprofen or a salt thereof and (C-1) chlorpheniramine or a salt thereof, The total content of chlorpheniramine or a salt thereof is 0.02 w / v% or more based on the total amount of the ophthalmic composition; The ophthalmic composition is contained in a container, the part of which that comes into contact with the ophthalmic composition being partly or entirely made of a resin containing polybutylene terephthalate. [4-2] (B-7) The ophthalmic composition according to [4-1], further comprising one or more selected from the group consisting of propylene glycol, glycerin, azulene sulfonic acid, sorbic acid, polyhexamethylene biguanide, polyoxyethylene hydrogenated castor oil, mannitol, glycyrrhizinic acid, allantoin, chlorhexidine, paraben, hyaluronic acid, alginic acid, hydroxypropyl methylcellulose, polyvinylpyrrolidone, pyridoxine, tocopherol acetate, cyanocobalamin, panthenol, taurine, aspartic acid, camphor, and salts thereof. [4-3] Contains at least polyoxyethylene hydrogenated castor oil, The ophthalmic composition according to [4-2], further comprising one or more selected from the group consisting of (B-8) chondroitin sulfate, benzalkonium, menthol and salts thereof, and (C-4) edetic acid, dibutylhydroxytoluene and salts thereof.

[0012] The present invention also provides the following inventions. [5-1] An ophthalmic composition containing (A) pranoprofen or a salt thereof and (B-9) one or more anti-inflammatory components selected from the group consisting of glycyrrhizinic acid, allantoin, azulene sulfonic acid, and salts thereof, wherein the ophthalmic composition is contained in a container, part or all of which comes into contact with the ophthalmic composition being formed from a resin containing polybutylene terephthalate. [5-2] Contains at least one or more anti-inflammatory components selected from the group consisting of glycyrrhizinic acid and salts thereof, The ophthalmic composition according to [5-1] further contains one or more selected from the group consisting of (B-10) sorbic acid, polyhexamethylene biguanide, chlorhexidine, paraben, benzalkonium, polyoxyethylene hydrogenated castor oil, mannitol, chondroitin sulfate, hyaluronic acid, alginic acid, hydroxypropyl methylcellulose, polyvinylpyrrolidone, pyridoxine, tocopherol acetate, cyanocobalamin, panthenol, taurine, aspartic acid, camphor, menthol, propylene glycol, glycerin, and salts thereof, and (C-5) chlorpheniramine, edetic acid, and salts thereof. [5-3] Contains at least one or more anti-inflammatory components selected from the group consisting of allantoin and salts thereof, The ophthalmic composition according to [5-1] further contains one or more selected from the group consisting of (B-11) sorbic acid, polyhexamethylene biguanide, chlorhexidine, paraben, benzalkonium, polyoxyethylene hydrogenated castor oil, mannitol, chondroitin sulfate, hyaluronic acid, alginic acid, polyvinylpyrrolidone, pyridoxine, tocopherol acetate, cyanocobalamin, panthenol, taurine, aspartic acid, camphor, menthol, propylene glycol, glycerin, neostigmine methylsulfate and salts thereof, and (C-5) chlorpheniramine, edetic acid and salts thereof. [5-4] Contains at least one or more anti-inflammatory components selected from the group consisting of azulene sulfonic acid and its salts, The ophthalmic composition according to [5-1], further comprising (B-12) one or more selected from the group consisting of sorbic acid, chlorhexidine, benzalkonium, polyoxyethylene hydrogenated castor oil, alginic acid, tocopherol acetate, cyanocobalamin, panthenol, camphor, propylene glycol, and salts thereof. [5-5] The ophthalmic composition according to [5-4], further comprising (B-13) one or more selected from the group consisting of polyhexamethylene biguanide, chondroitin sulfate, pyridoxine, taurine, aspartic acid, menthol, neostigmine methylsulfate, and salts thereof, and (C) chlorpheniramine, edetic acid, dibutylhydroxytoluene, polysorbate 80, and salts thereof. [5-6] The ophthalmic composition according to [5-5], which contains at least polyoxyethylene hydrogenated castor oil.

[0013] The present invention also provides the following inventions. [6-1] An ophthalmic composition comprising (A) pranoprofen or a salt thereof, (B-14) one or more selected from the group consisting of pyridoxine, tocopherol, cyanocobalamin, panthenol, flavin adenine dinucleotide, retinol, derivatives thereof, and salts thereof, and (B-15) one or more selected from the group consisting of taurine, aspartic acid, and salts thereof, wherein the ophthalmic composition is contained in a container, part or all of which comes into contact with the ophthalmic composition, and is formed from a resin containing polybutylene terephthalate. [6-2] The ophthalmic composition according to [6-1], wherein the component (B-15) comprises two or more selected from the group consisting of taurine, aspartic acid, and salts thereof. [6-3] The ophthalmic composition according to [6-1] or [6-2] further contains (B-16) one or more selected from the group consisting of cromoglycic acid, polyoxyethylene hydrogenated castor oil, camphor, sorbic acid, chlorhexidine, paraben, benzalkonium, mannitol, hyaluronic acid, alginic acid, polyvinylpyrrolidone, propylene glycol, glycerin, and salts thereof. [6-4] Contains at least aspartic acid or a salt thereof, The total content of aspartic acid or a salt thereof is 0.3 w / v% or more based on the total amount of the ophthalmic composition; The ophthalmic composition according to any one of [6-1] to [6-3], further comprising (B-17) one or more selected from the group consisting of cromoglycic acid, polyoxyethylene hydrogenated castor oil, camphor, and salts thereof. [6-5] The ophthalmic composition according to any one of [6-1] to [6-4], wherein the component (B-14) comprises two or more selected from the group consisting of pyridoxine, tocopherol, cyanocobalamin, panthenol, flavin adenine dinucleotide, retinol, derivatives thereof, and salts thereof. [6-6] The ophthalmic composition according to [6-5], further comprising (B-17) one or more selected from the group consisting of cromoglycic acid, polyoxyethylene hydrogenated castor oil, camphor, and salts thereof.

[0014] The present invention also provides the following inventions. [7-1] An ophthalmic composition comprising (A) pranoprofen or a salt thereof, (B-18) chondroitin sulfate or a salt thereof, and (B-19) one or more selected from the group consisting of taurine, cyanocobalamin, panthenol, polyhexamethylene biguanide, hydroxypropyl methylcellulose, and salts thereof, The total content of chondroitin sulfate or a salt thereof is 0.35 w / v% or more based on the total amount of the ophthalmic composition; The ophthalmic composition is contained in a container, the part of which that comes into contact with the ophthalmic composition being partly or entirely made of a resin containing polybutylene terephthalate. [7-2] The ophthalmic composition according to [7-1], further comprising (B-20) one or more selected from the group consisting of polyoxyethylene hydrogenated castor oil, tocopherol acetate, pyridoxine, flavin adenine dinucleotide, and salts thereof. [Effects of the Invention]

[0015] The ophthalmic composition of the present invention contains a combination of components (A) and (B), and therefore exhibits the effect of increasing the dynamic contact angle with a resin containing polybutylene terephthalate (reducing wetting) compared to an ophthalmic composition containing component (A) alone. This reduces residual liquid and improves drainage, even when the ophthalmic composition is contained in a container where part or all of the surface in contact with the ophthalmic composition is formed from a resin containing polybutylene terephthalate. This also prevents deterioration in the quality and usability of the ophthalmic composition. DETAILED DESCRIPTION OF THE INVENTION

[0016] Hereinafter, embodiments of the present invention will be described in detail, but the present invention is not limited to the following embodiments.

[0017] In this specification, unless otherwise specified, the unit of content "%" means "w / v%" and is synonymous with "g / 100 mL." In this specification, unless otherwise specified, the abbreviation "POE" means polyoxyethylene, and the abbreviation "POP" means polyoxypropylene.

[0018] [1. Ophthalmic composition] The ophthalmic composition of this embodiment contains (A) pranoprofen or a salt thereof (also simply referred to as "component (A)") and (B) one or more selected from the group consisting of nonionic surfactants, antiallergic components, anti-inflammatory components, preservatives, polysaccharides, vinyl compounds, vitamins, amino acids, cooling agents, antioxidants, decongestants, oils, and inorganic salts (also simply referred to as "component (B)").

[0019] <Component (A)> Pranoprofen is a known compound that is also called (2RS)-2-(10H-9-oxa-1-azaanthracen-6-yl)-propanoic acid or α-methyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetic acid, and may be synthesized by a known method or may be commercially available.

[0020] The salt of pranoprofen is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutical), or physiologically acceptable. Specific examples of such salts include salts with inorganic bases [e.g., ammonium salts; salts with metals such as alkali metals (sodium, potassium, etc.), alkaline earth metals (calcium, magnesium, etc.), and aluminum], and salts with organic bases [e.g., salts with organic amines such as methylamine, triethylamine, diethylamine, triethanolamine, morpholine, piperazine, pyrrolidine, tripyridine, and picoline]. Pranoprofen or its salts also include hydrates.

[0021] Pranoprofen or a salt thereof may be used alone or in combination of two or more.

[0022] The content of component (A) in the ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the type of component (A), 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 component (A) is, for example, preferably 0.0001 to 0.4 w / v%, more preferably 0.0005 to 0.3 w / v%, even more preferably 0.001 to 0.2 w / v%, and particularly preferably 0.01 to 0.1 w / v%, based on the total amount of the ophthalmic composition.

[0023] <(B) component> Component (B) is one or more selected from the group consisting of nonionic surfactants, antiallergic components, anti-inflammatory components, preservatives, polysaccharides, vinyl compounds, vitamins, amino acids, cooling agents, antioxidants, decongestants, oils, and inorganic salts. Component (B) is not particularly limited as long as it is medicamentarily, pharmacologically (pharmaceutical), or physiologically acceptable.

[0024] The nonionic surface active component (B) includes a nonionic surfactant and a polyhydric alcohol (excluding the component (C) Polysorbate 80). The nonionic surface active component can be appropriately selected from known nonionic surface active components.

[0025] Specific 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), and POE (20) sorbitan tristearate (polysorbate 65); POE castor oil derivatives such as POE (40) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 40), POE (60) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 60), and POE (100) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 100); POE (3) castor oil (polyoxyethylene castor oil 3), POE (10) castor oil (polyoxyethylene castor oil POE castor oils such as POE (35) castor oil (polyoxyethylene castor oil 35), POE (70) castor oil (polyoxyethylene castor oil 70); POE alkyl ethers such as POE (9) lauryl ether; POE-POP alkyl ethers such as POE (20) POP (4) cetyl ether; POE (20) POP (20) glycol (Pluronic L44), POE (54) POP (39) glycol (Pluronic P85), POE (120) POP (40) glycol (Pluronic F87), POE (160) POP (30) glycol (Poloxamer 188, Pluronic F68), POE (196) POP (67) glycol (Poloxamer 407, Pluronic F127), POE (200) POP (70) glycol (Lutrol F127) and other POE·POP block copolymers; polyethylene glycol monostearate such as polyoxyl 10 stearate and polyoxyl 40 stearate; and tyloxapol. In the compounds exemplified above, the numbers in parentheses indicate the number of moles added.

[0026] Examples of polyhydric alcohols include alcohols having two or more hydroxyl groups in the molecule and salts thereof. Specific examples of polyhydric alcohols include aliphatic polyhydric alcohols (aliphatic alcohols having two or more hydroxyl groups in the molecule) such as glycerin, propylene glycol, ethylene glycol, diethylene glycol, and polyethylene glycol (300, 400, 4000, 6000), sugar alcohols such as glucose, lactose, maltose, fructose, sorbitol, maltitol, mannitol, xylitol, and trehalose, and salts thereof.

[0027] Preferred nonionic surfactants are POE-POP block copolymers, POE castor oil derivatives, polyethylene glycol monostearate, tyloxapol, and polyhydric alcohols, more preferred are POE-POP block copolymers, POE castor oil derivatives, polyethylene glycol monostearate, tyloxapol, aliphatic polyhydric alcohols, and sugar alcohols, and even more preferred are poloxamer 188, poloxamer 407, polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil, polyoxyl stearate, tyloxapol, propylene glycol, polyethylene glycol (particularly 400, 4000, and 6000), glycerin, sorbitol, and xylitol.

[0028] The nonionic surfactant component may be a commercially available product. One type of nonionic surfactant component may be used alone, or two or more types may be used in combination.

[0029] The antiallergic component (B) is a compound having an antiallergic effect and its salt (excluding chlorpheniramine and its salt (C)). The antiallergic component can be appropriately selected from known antiallergic components such as chemical mediator release inhibitors and histamine receptor antagonists.

[0030] Specific examples of the antiallergic ingredient include tranilast, ketotifen, diphenhydramine, cromoglycate, pemirolast, amlexanox, ibudilast, ashitazanolast, levocabastine, and salts thereof.

[0031] As the antiallergic component, tranilast, ketotifen, diphenhydramine, cromoglycic acid and salts thereof are preferred, and tranilast, ketotifen fumarate, diphenhydramine hydrochloride and sodium cromoglycate are more preferred.

[0032] The antiallergic component may be a commercially available product. One type of antiallergic component may be used alone, or two or more types may be used in combination.

[0033] The anti-inflammatory component (B) is a compound having anti-inflammatory or anti-inflammatory activity, or a salt thereof (excluding pranoprofen and its salts (A)). The anti-inflammatory component can be appropriately selected from known anti-inflammatory components.

[0034] Specific examples of anti-inflammatory ingredients include berberine, azulenes (azulene, azulene sulfonic acid, kamaazulene, guaiazulene, etc.), allantoin, zinc sulfate, lysozyme, glycyrrhizinic acid, epsilon-aminocaproic acid, celecoxib, rofecoxib, indomethacin, diclofenac, bromfenac, piroxicam, meloxicam, methyl salicylate, ibuprofen, ibuprofen piconol, bufexamac, butyl flufenamate, bendazac, ketoprofen, felbinac, and salts thereof.

[0035] As the anti-inflammatory component, berberine, azulene sulfonic acid, lysozyme, glycyrrhizinic acid, epsilon-aminocaproic acid, and salts thereof are preferred, and berberine, sodium azulene sulfonate, lysozyme, dipotassium glycyrrhizinate, and epsilon-aminocaproic acid are more preferred.

[0036] The anti-inflammatory component may be a commercially available product. One type of anti-inflammatory component may be used alone, or two or more types may be used in combination.

[0037] The preservative of component (B) is a compound having a bactericidal or bacteriostatic action, or a salt thereof. The preservative can be appropriately selected from known preservatives or antibacterial agents.

[0038] Specific examples of preservatives include alkylpolyaminoethylglycine, benzoic acid, benzalkonium, benzethonium, chlorobutanol, sorbic acid, dehydroacetic acid, parabens (e.g., parahydroxybenzoic acid esters such as methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, and butyl parahydroxybenzoate), oxyquinoline, phenylethyl alcohol, benzyl alcohol, biguanide compounds (e.g., biguanide, chlorhexidine, polyhexanide, and polyhexamethylene biguanide), polyquaterniums, Gloquil (trade name, manufactured by Rhodia), sulfisoxazole, sulfamethoxazole, monoethanolamine, ethanol, and salts thereof. Specific examples of salts of preservatives include alkyldiaminoethylglycine hydrochloride, sodium benzoate, benzalkonium chloride, benzethonium chloride, chlorhexidine gluconate, potassium sorbate, sodium dehydroacetate, oxyquinoline sulfate, polyhexanide hydrochloride, and sodium sulfamethoxazole.

[0039] Preferable preservatives include benzalkonium, benzethonium, biguanide compounds, sorbic acid, chlorobutanol, alkylpolyaminoethylglycine, parabens (particularly, parahydroxybenzoates), sulfamethoxazole, phenylethyl alcohol, monoethanolamine, ethanol, and salts thereof; more preferable preservatives are benzalkonium, chlorhexidine gluconate, potassium sorbate, chlorobutanol, alkyldiaminoethylglycine hydrochloride, chlorobutanol, parabens (particularly, propyl parahydroxybenzoate or methyl parahydroxybenzoate), polyhexamethylene biguanide, benzalkonium chloride, sodium sulfamethoxazole, phenylethyl alcohol, monoethanolamine, and ethanol.

[0040] Commercially available preservatives can also be used. One type of preservative may be used alone, or two or more types may be used in combination.

[0041] The polysaccharides of component (B) include dextran, acidic polysaccharides, cellulose-based polymer compounds, and salts thereof. The polysaccharides can be appropriately selected from known polysaccharides.

[0042] Specific examples of dextran include dextran 40 and dextran 70.

[0043] Acidic polysaccharides are polysaccharides having an acidic group. Specific examples of acidic polysaccharides include acidic mucopolysaccharides such as hyaluronic acid, chondroitin sulfate, chitosan, heparin, heparan, alginic acid, and derivatives thereof (e.g., acetylated forms), xanthan gum, and gellan gum.

[0044] The cellulose-based polymer compound can be cellulose or a polymer compound in which the hydroxyl groups of cellulose are substituted with other functional groups. Examples of functional groups that substitute the hydroxyl groups of cellulose include methoxy groups, ethoxy groups, hydroxymethoxy groups, hydroxyethoxy groups, hydroxypropoxy groups, carboxymethoxy groups, and carboxyethoxy groups. Specific examples of the cellulose-based polymer compound include methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose (hypromellose), carboxymethyl cellulose, and carboxyethyl cellulose.

[0045] As polysaccharides, dextran, acidic polysaccharides, cellulose-based polymer compounds, and salts thereof are preferred, dextran, acidic polysaccharides, hydroxyethyl cellulose, hydroxypropyl methylcellulose, carboxymethyl cellulose, and salts thereof are more preferred, dextran, acidic mucopolysaccharides, xanthan gum, gellan gum, hydroxyethyl cellulose, hydroxypropyl methylcellulose, carboxymethyl cellulose, and salts thereof are even more preferred, and dextran, chondroitin sulfate, hyaluronic acid, xanthan gum, gellan gum, hydroxyethyl cellulose, hydroxypropyl methylcellulose, carboxymethyl cellulose, and salts thereof are particularly preferred.

[0046] The polysaccharides may be commercially available. One type of saccharide may be used alone, or two or more types may be used in combination.

[0047] The vinyl compound of component (B) includes a vinyl polymer compound and a salt thereof. The vinyl compound can be appropriately selected from known vinyl compounds.

[0048] Specific examples of vinyl compounds include vinyl alcohol polymers such as polyvinyl alcohol (completely or partially saponified), vinylpyrrolidone polymers such as polyvinylpyrrolidone, carboxyvinyl polymers, and salts thereof.

[0049] As the vinyl compound, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymers, and salts thereof are preferred, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymers, and salts thereof are more preferred, polyvinyl alcohol, polyvinylpyrrolidone K17, polyvinylpyrrolidone K25, polyvinylpyrrolidone K30, polyvinylpyrrolidone K90, carboxyvinyl polymers, and salts thereof are even more preferred, and polyvinyl alcohol, polyvinylpyrrolidone K30, polyvinylpyrrolidone K90, carboxyvinyl polymers, and salts thereof are particularly preferred.

[0050] The vinyl compound may be a commercially available one. One vinyl compound may be used alone, or two or more vinyl compounds may be used in combination.

[0051] The vitamin that is component (B) can be appropriately selected from known vitamins.

[0052] Specific examples of vitamins include fat-soluble vitamins such as vitamin E (d-α-tocopherol, dl-α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, etc.), vitamin A (retinal, retinol, retinoic acid, carotene, dehydroretinal, lycopene, etc.), derivatives thereof, and salts thereof; and water-soluble vitamins such as vitamin B1, vitamin B2 (flavin adenine dinucleotide), niacin (nicotinic acid and nicotinamide), pantothenic acid, panthenol, vitamin B6 (pyridoxine, pyridoxal, and pyridoxamine), biotin, folic acid, and vitamin B12 (cyanocobalamin, hydroxocobalamin, methylcobalamin, and adenosylcobalamin), and salts thereof. Specific examples of vitamin salts include flavin adenine dinucleotide sodium, pyridoxine hydrochloride, calcium pantothenate, sodium pantothenate, etc. Specific examples of vitamin derivatives include tocopherol acetate, retinol acetate, and retinol palmitate.

[0053] Preferred vitamins include cyanocobalamin, flavin adenine dinucleotide, panthenol, pyridoxine, retinol, tocopherol, and derivatives thereof, and salts thereof, and more preferred are cyanocobalamin, flavin adenine dinucleotide sodium, panthenol, pyridoxine hydrochloride, retinol palmitate, and tocopherol acetate.

[0054] Commercially available vitamins can also be used. Vitamins can be used alone or in combination of two or more.

[0055] The amino acids of component (B) are compounds having an amino group and a carboxyl group in the molecule, derivatives thereof, and salts thereof. The amino acids can be appropriately selected from known amino acids.

[0056] Examples of amino acids include amino acids and their salts, and amino acid derivatives and their salts. Specific examples of amino acids and their salts include monoaminomonocarboxylic acids such as glycine, alanine, aminobutyric acid, and aminovaleric acid, monoaminodicarboxylic acids such as aspartic acid and glutamic acid, and diaminomonocarboxylic acids such as arginine and lysine, as well as salts thereof. Specific examples of amino acid derivatives and their salts include amino acid derivatives such as aminoethylsulfonic acid (taurine) and their salts. Amino acids may be in the D-, L-, or DL-form.

[0057] As the amino acids, monoaminodicarboxylic acids, amino acid derivatives, and salts thereof are preferred, glycine, aspartic acid, glutamic acid, arginine, taurine, and salts thereof are more preferred, and glycine, potassium aspartate, sodium glutamate, arginine, and taurine are even more preferred.

[0058] Commercially available amino acids can also be used. The amino acids may be used alone or in combination of two or more.

[0059] The refreshing agent of component (B) is a compound or a salt thereof that has the effect of providing a refreshing or cool feeling to the eyes. The refreshing agent can be appropriately selected from known refreshing agents.

[0060] Examples of refreshing agents include terpenoids and essential oils containing terpenoids. Examples of terpenoids include menthol, menthone, camphor, borneol (rhubarb), geraniol, cineole, citronellol, carvone, anethole, eugenol, limonene, linalool, and linalyl acetate. Examples of essential oils containing terpenoids include eucalyptus oil, bergamot oil, peppermint oil, fennel oil, rose oil, cinnamon oil, spearmint oil, camphor oil, cool mint, and peppermint oil. Terpenoids may be in the d-, l-, or dl-form, and examples include l-menthol, d-menthol, dl-menthol, dl-camphor, d-camphor, dl-borneol, and d-borneol. However, some terpenoids, such as geraniol and cineole, do not have optical isomers.

[0061] As the refreshing agent, menthol, camphor, borneol, geraniol, and essential oils containing any of these are preferred, and menthol, camphor, borneol, geraniol, eucalyptus oil, and bergamot oil are more preferred.

[0062] The cooling agent may be a commercially available product. One cooling agent may be used alone, or two or more cooling agents may be used in combination.

[0063] The antioxidant, component (B), is a compound that inhibits harmful reactions involving oxygen, or a salt thereof (excluding dibutylhydroxytoluene and its salt, component (C)). Any known antioxidant can be appropriately selected and used.

[0064] Specific examples of antioxidants include butylhydroxyanisole, ascorbic acid, and salts thereof.

[0065] As the antioxidant, butylhydroxyanisole and salts thereof are preferred, and butylhydroxyanisole is more preferred.

[0066] The antioxidant may be a commercially available product. One type of antioxidant may be used alone, or two or more types may be used in combination.

[0067] The decongestant of component (B) is a compound having an effect of suppressing congestion, or a salt thereof. The decongestant can be appropriately selected from known decongestants such as imidazoline decongestants.

[0068] Specific examples of decongestants include tetrahydrozoline, naphazoline, oxymetazoline, xylometazoline, and salts thereof.

[0069] Preferred decongestants are tetrahydrozoline, naphazoline, and salts thereof, with naphazoline hydrochloride and tetrahydrozoline hydrochloride being more preferred.

[0070] The decongestant may be a commercially available product. One type of decongestant may be used alone, or two or more types may be used in combination.

[0071] The oil component (B) includes vegetable oils derived from plants, animal oils derived from animals, and natural or synthetic mineral oils. The oil component can be appropriately selected from known oil components.

[0072] Specific examples of oils include vegetable oils such as soybean oil, rice oil, rapeseed oil, cottonseed oil, sesame oil, safflower oil, almond oil, castor oil, olive oil, cacao oil, camellia oil, sunflower oil, palm oil, flax oil, perilla oil, shea oil, coconut oil, jojoba oil, grapeseed oil, and avocado oil; animal oils such as lanolin (refined lanolin, etc.), orange roughy oil, squalane, and horse oil; and mineral oils such as petrolatum (white petrolatum, yellow petrolatum, etc.) and liquid paraffin.

[0073] As the oil, vegetable oil, animal oil and mineral oil are preferred, and sesame oil, castor oil, lanolin, vaseline and liquid paraffin are more preferred.

[0074] The oil may be a commercially available product. One type of oil may be used alone, or two or more types may be used in combination.

[0075] The inorganic salt of component (B) is an ionic bond between an anion derived from an inorganic acid and a cation derived from an inorganic base. The inorganic salt can be appropriately selected from known inorganic salts.

[0076] Specific examples of inorganic salts include metal chlorides such as calcium chloride, magnesium chloride, sodium chloride, potassium chloride, ammonium chloride, and zinc chloride; metal sulfates such as calcium sulfate, magnesium sulfate, sodium sulfate, potassium sulfate, and ammonium sulfate; metal sulfites such as sodium hydrogen sulfite and sodium sulfite; metal carbonates such as sodium hydrogen carbonate and sodium carbonate; and metal phosphates such as disodium hydrogen phosphate, sodium dihydrogen phosphate, and potassium dihydrogen phosphate.

[0077] As the inorganic salt, metal chlorides and metal sulfates are preferred, sodium chloride, potassium chloride, calcium chloride, zinc chloride and magnesium sulfate are more preferred, and sodium chloride, calcium chloride, zinc chloride and magnesium sulfate are even more preferred.

[0078] Commercially available inorganic salts can also be used. The inorganic salts can be used alone or in combination of two or more.

[0079] The "salt" in component (B) is not particularly limited as long as it is medicamentally, pharmacologically (pharmaceutical), or physiologically acceptable. Specific examples include basic salts such as salts with inorganic bases, such as alkali metal salts and alkaline earth metal salts, and salts with organic bases, including salts with sodium, potassium, calcium, magnesium, ammonium, diethanolamine, ethylenediamine, etc. Furthermore, salts with amines, such as ammonia, methylamine, dimethylamine, trimethylamine, dicyclohexylamine, tris(hydroxymethyl)aminomethane, N,N-bis(hydroxyethyl)piperazine, 2-amino-2-methyl-1-propanol, ethanolamine, N-methylglucamine, and L-glucamine; and salts with basic amino acids, such as lysine, δ-hydroxylysine, and arginine, may also be used. Furthermore, it may be a salt with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc.; a salt with organic acids such as methanesulfonic acid, benzenesulfonic acid, paratoluenesulfonic acid, acetic acid, propionic acid, tartaric acid, fumaric acid, maleic acid, malic acid, oxalic acid, succinic acid, citric acid, benzoic acid, mandelic acid, cinnamic acid, lactic acid, glycolic acid, glucuronic acid, ascorbic acid, nicotinic acid, salicylic acid, gluconic acid, palmitic acid, etc.; or a salt with acidic amino acids such as aspartic acid, glutamic acid, etc. The "salt" of component (B) includes solvates and hydrates of the salt.

[0080] 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 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 component (B) is, for example, preferably 0.00001 to 10 w / v%, more preferably 0.00005 to 8 w / v%, even more preferably 0.0001 to 7 w / v%, and particularly preferably 0.0001 to 6 w / v%, based on the total amount of the ophthalmic composition.

[0081] From the viewpoint of more significantly achieving the effects of the present invention, the total content of the nonionic surfactant component (B) in the ophthalmic composition of this embodiment is preferably 0.00005 to 10 w / v%, more preferably 0.0001 to 8 w / v%, even more preferably 0.0001 to 5 w / v%, and particularly preferably 0.005 to 5 w / v%, based on the total amount of the ophthalmic composition.

[0082] From the viewpoint of more significantly achieving the effects of the present invention, the total content of the antiallergic component (B) in the ophthalmic composition according to this embodiment is preferably 0.00001 to 6 w / v%, more preferably 0.0005 to 4 w / v%, even more preferably 0.0005 to 2 w / v%, and particularly preferably 0.005 to 2 w / v%, based on the total amount of the ophthalmic composition.

[0083] From the viewpoint of more significantly achieving the effects of the present invention, the total content of the anti-inflammatory component (B) in the ophthalmic composition according to this embodiment is preferably 0.00001 to 3 w / v%, more preferably 0.00005 to 1.5 w / v%, even more preferably 0.0001 to 1.0 w / v%, and particularly preferably 0.0001 to 0.6 w / v%, based on the total amount of the ophthalmic composition.

[0084] From the viewpoint of more significantly achieving the effects of the present invention, the total content of the preservative (B) in the ophthalmic composition according to this embodiment is preferably 0.00001 to 6 w / v%, more preferably 0.00005 to 6 w / v%, even more preferably 0.00005 to 5 w / v%, and particularly preferably 0.0001 to 5 w / v%, based on the total amount of the ophthalmic composition.

[0085] When polyhexamethylene biguanide or a salt thereof is used as component (B), the content of polyhexamethylene biguanide or a salt thereof is preferably 0.0000001 to 0.001 w / v%, more preferably 0.000001 to 0.0005 w / v%, even more preferably 0.00001 to 0.0005 w / v%, and particularly preferably 0.00001 to 0.0002 w / v%, based on the total amount of the ophthalmic composition, in order to more significantly exhibit the effects of the present invention.

[0086] From the viewpoint of more significantly achieving the effects of the present invention, the total content of the (B) polysaccharides in the ophthalmic composition according to this embodiment is preferably 0.0001 to 6 w / v%, more preferably 0.0005 to 5 w / v%, even more preferably 0.001 to 4 w / v%, and particularly preferably 0.001 to 3 w / v%, based on the total amount of the ophthalmic composition.

[0087] From the viewpoint of more significantly achieving the effects of the present invention, the total content of the (B) vinyl compound in the ophthalmic composition according to this embodiment is preferably 0.0005 to 10 w / v%, more preferably 0.0005 to 5 w / v%, even more preferably 0.001 to 5 w / v%, and particularly preferably 0.001 to 3 w / v%, based on the total amount of the ophthalmic composition.

[0088] From the viewpoint of more significantly achieving the effects of the present invention, the total content of vitamin (B) in the ophthalmic composition of this embodiment is preferably 0.00001 to 1.6 w / v%, more preferably 0.0005 to 0.8 w / v%, even more preferably 0.0005 to 0.4 w / v%, and particularly preferably 0.0005 to 0.3 w / v%, based on the total amount of the ophthalmic composition.

[0089] When retinol or a derivative thereof, or a salt thereof is used as component (B), the content of retinol or a derivative thereof, or a salt thereof is, for example, preferably 10,000 to 500,000 IU / 100 mL, more preferably 500,000 to 300,000 IU / 100 mL, even more preferably 1,000 to 300,000 IU / 100 mL, and particularly preferably 500 to 200,000 IU / 100 mL, based on the total volume of the ophthalmic composition. The term "IU" refers to the international unit determined by the method described in the Vitamin A Quantitation Method in the Sixteenth Edition of the Japanese Pharmacopoeia.

[0090] From the viewpoint of more significantly achieving the effects of the present invention, the total content of (B) amino acids in the ophthalmic composition of this embodiment is preferably 0.0001 to 5 w / v%, more preferably 0.0005 to 3 w / v%, even more preferably 0.001 to 3 w / v%, and particularly preferably 0.001 to 2 w / v%, based on the total amount of the ophthalmic composition.

[0091] From the viewpoint of more significantly achieving the effects of the present invention, the total content of the (B) refreshing agent in the ophthalmic composition according to this embodiment is preferably 0.00001 to 0.8 w / v%, more preferably 0.00005 to 0.7 w / v%, even more preferably 0.0001 to 0.6 w / v%, and particularly preferably 0.0001 to 0.5 w / v%, based on the total amount of the ophthalmic composition.

[0092] From the viewpoint of more significantly exhibiting the effects of the present invention, the total content of the decongestant (B) in the ophthalmic composition according to this embodiment is preferably 0.0001 to 0.1 w / v%, more preferably 0.0001 to 0.08 w / v%, even more preferably 0.0005 to 0.08 w / v%, and particularly preferably 0.0005 to 0.05 w / v%, based on the total amount of the ophthalmic composition.

[0093] From the viewpoint of more significantly achieving the effects of the present invention, the total content of the (B) oil component in the ophthalmic composition according to this embodiment is preferably 0.00001 to 6 w / v%, more preferably 0.00005 to 3 w / v%, even more preferably 0.0001 to 1 w / v%, and particularly preferably 0.0001 to 0.5 w / v%, based on the total amount of the ophthalmic composition.

[0094] From the viewpoint of more significantly achieving the effects of the present invention, the total content of (B) inorganic salt in the ophthalmic composition according to this embodiment is preferably 0.00001 to 5 w / v%, more preferably 0.00005 to 3 w / v%, even more preferably 0.0001 to 3 w / v%, and particularly preferably 0.0001 to 2 w / v%, based on the total amount of the ophthalmic composition.

[0095] The content ratio of component (B) 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 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 component (B) to component (A) is, for example, preferably 0.0001 to 10,000 parts by mass, more preferably 0.0001 to 1,000 parts by mass, even more preferably 0.0005 to 500 parts by mass, and particularly preferably 0.001 to 200 parts by mass, of the total content of component (B) per part by mass of the total content of component (A) contained in the ophthalmic composition according to this embodiment.

[0096] <(C) component> The ophthalmic composition according to this embodiment may further contain (C) one or more selected from the group consisting of chlorpheniramine, edetic acid, dibutylhydroxytoluene, polysorbate 80, and salts thereof (also simply referred to as "component (C)"). When the ophthalmic composition further contains component (C), the wetting suppression effect on polybutylene terephthalate-containing resins is more significantly exhibited.

[0097] The "salt" in component (C) is not particularly limited as long as it is medicamentarily, pharmacologically (pharmaceutical), or physiologically acceptable. Specific examples include basic salts such as salts with inorganic bases, such as alkali metal salts and alkaline earth metal salts, and salts with organic bases, including salts with sodium, potassium, calcium, magnesium, ammonium, diethanolamine, ethylenediamine, etc. Furthermore, salts with amines, such as ammonia, methylamine, dimethylamine, trimethylamine, dicyclohexylamine, tris(hydroxymethyl)aminomethane, N,N-bis(hydroxyethyl)piperazine, 2-amino-2-methyl-1-propanol, ethanolamine, N-methylglucamine, and L-glucamine; and salts with basic amino acids, such as lysine, δ-hydroxylysine, and arginine, may also be used. Furthermore, salts with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc.; salts with organic acids such as methanesulfonic acid, benzenesulfonic acid, paratoluenesulfonic acid, acetic acid, propionic acid, tartaric acid, fumaric acid, maleic acid, malic acid, oxalic acid, succinic acid, citric acid, benzoic acid, mandelic acid, cinnamic acid, lactic acid, glycolic acid, glucuronic acid, ascorbic acid, nicotinic acid, salicylic acid, gluconic acid, palmitic acid, etc.; and salts with acidic amino acids such as aspartic acid, glutamic acid, etc. The "salt" of component (C) includes solvates and hydrates of the salt.

[0098] Specific examples of component (C) include chlorpheniramine, chlorpheniramine maleate, edetic acid, sodium edetate and its hydrate, dibutylhydroxytoluene, and polysorbate 80. Of these, chlorpheniramine maleate, sodium edetate hydrate, dibutylhydroxytoluene, and polysorbate 80 are preferred.

[0099] The content of component (C) in the ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the type of component (C), 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 component (C) is, for example, preferably 0.00001 to 3 w / v%, more preferably 0.00005 to 2 w / v%, even more preferably 0.0001 to 1.5 w / v%, and particularly preferably 0.0001 to 1 w / v%, based on the total amount of the ophthalmic composition.

[0100] From the viewpoint of more significantly achieving the effects of the present invention, the total content of (C) chlorpheniramine or a salt thereof in the ophthalmic composition of this embodiment is preferably 0.00001 to 0.5 w / v%, more preferably 0.0005 to 0.1 w / v%, even more preferably 0.0005 to 0.08 w / v%, and particularly preferably 0.0005 to 0.05 w / v%, based on the total amount of the ophthalmic composition.

[0101] From the viewpoint of more significantly achieving the effects of the present invention, the total content of (C) edetic acid or a salt thereof in the ophthalmic composition according to this embodiment is preferably 0.00001 to 1 w / v%, more preferably 0.0005 to 0.6 w / v%, even more preferably 0.001 to 0.6 w / v%, and particularly preferably 0.001 to 0.5 w / v%, based on the total amount of the ophthalmic composition.

[0102] From the viewpoint of more significantly exhibiting the effects of the present invention, the total content of (C) dibutylhydroxytoluene or a salt thereof in the ophthalmic composition according to this embodiment is preferably 0.00001 to 0.01 w / v%, more preferably 0.00005 to 0.005 w / v%, even more preferably 0.00005 to 0.001 w / v%, and particularly preferably 0.0001 to 0.001 w / v%, based on the total amount of the ophthalmic composition.

[0103] From the viewpoint of more significantly exhibiting the effects of the present invention, the total content of (C) polysorbate 80 or a salt thereof in the ophthalmic composition according to this embodiment is preferably 0.00001 to 2 w / v%, more preferably 0.0001 to 1.5 w / v%, even more preferably 0.001 to 1 w / v%, and particularly preferably 0.005 to 1 w / v%, based on the total amount of the ophthalmic composition.

[0104] The content ratio of component (C) to 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 component (C), etc. From the viewpoint of further enhancing the effects of the present invention, the content ratio of component (C) to component (A) is, for example, preferably 0.0001 to 10,000 parts by mass, more preferably 0.0005 to 1,000 parts by mass, even more preferably 0.001 to 500 parts by mass, and particularly preferably 0.01 to 200 parts by mass, of the total content of component (C) per 1 part by mass of the total content of component (A) contained in the ophthalmic composition according to this embodiment.

[0105] 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, and even more preferably 5.0 to 8.5.

[0106] 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, Sixteenth 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.

[0107] 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 (RE550 type viscometer, manufactured by Tosangyo Co., Ltd., rotor: 1°34' x R24), is preferably 0.01 to 10,000 mPa s, more preferably 0.05 to 8,000 mPa s, and even more preferably 0.1 to 1,000 mPa s.

[0108] 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:

[0109] Steroids: for example, fluticasone propionate, fluticasone furoate, mometasone furoate, beclomethasone propionate, flunisolide, etc. Astringents: zinc oxide, zinc lactate, etc. Local anesthetics: for example, lidocaine, procaine, etc. Others: For example, ofloxacin, norfloxacin, levofloxacin, lomefloxacin and their salts.

[0110] 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 2007 (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, N-(2-hydroxyethyl)ethylenediaminetriacetic acid (HEDTA), diethylenetriaminepentaacetic acid (DTPA), etc. Bases: for example, octyldodecanol, titanium oxide, potassium bromide, plastibase, etc. pH adjusters: hydrochloric acid, acetic acid, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, triethanolamine, diisopropanolamine, etc. Stabilizers: sodium formaldehyde sulfoxylate (Rongalit), sodium hydrogen sulfite, sodium pyrosulfite, aluminum monostearate, glycerin monostearate, cyclodextrin, etc. Anionic surfactants: polyoxyethylene alkyl ether phosphates, polyoxyethylene alkyl ether sulfates, alkylbenzene sulfonates, alkyl sulfates, N-acyltaurine salts, etc. Amphoteric surfactants: lauryl dimethylaminoacetic acid betaine, etc.

[0111] 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 16th edition of the Japanese Pharmacopoeia.

[0112] The ophthalmic composition according to the present 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 the desired levels, and sterilizing the mixture by filtration or other methods.

[0113] 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.

[0114] 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 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), etc.]. The term "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).

[0115] The ophthalmic composition according to this embodiment contains pranoprofen or a salt thereof, and is therefore effective in preventing bloodshot eyes, itchy eyes, blurred vision, eye fatigue, and the like.

[0116] When the ophthalmic composition according to the present embodiment is an eye drop, the dosage and administration method are not particularly limited as long as they are effective and have few side effects. For example, for adults (15 years of age or older) and children 7 years of age or older, one to two drops may be instilled into the eyes four times a day, or two to three drops may be instilled into the eyes five to six times a day.

[0117] <Container> The ophthalmic composition of this embodiment is preferably contained in a container (also referred to as a "PBT-containing resin container") in which part or all of the part that comes into contact with the ophthalmic composition is formed from a resin containing polybutylene terephthalate.

[0118] The PBT-containing resin may contain only a polymer obtained by polycondensation of terephthalic acid and 1,4-butanediol, or may contain a polymer obtained by polycondensation of an ester-forming derivative of terephthalic acid and 1,4-butanediol. An example of an ester-forming derivative of terephthalic acid is dimethyl terephthalate. The polymer obtained by polycondensation of terephthalic acid or its ester-forming derivative with 1,4-butanediol may contain other monomers as constituent components of the polymer.

[0119] The PBT-containing resin may also contain other polymers such as polycarbonate, (meth)acrylic acid polymer, polystyrene (PS), polyethylene naphthalate (PEN), polyethylene terephthalate (PET), polyethylene (PE), polyarylate, and polypropylene (PP).

[0120] In the PBT-containing resin according to this embodiment, the content of the polymer obtained by polycondensation of terephthalic acid or an ester-forming derivative thereof with 1,4-butanediol is preferably 50% by mass or more, more preferably 60% by mass or more, and even more preferably 70% by mass or more, based on the total amount of polymers contained in the PBT-containing resin.

[0121] The PBT-containing resin may contain additives such as stabilizers, etc. The PBT-containing resin may also be reinforced by including a reinforcing agent such as glass fiber.

[0122] The PBT-containing resin may be any commercially available product without particular limitation, such as Novaduran (registered trademark) 5010R5 (manufactured by Mitsubishi Engineering Plastics Corporation), Valox (registered trademark) 315 (SABIC Japan LLC), and Valox (registered trademark) 195 (SABIC Japan LLC).

[0123] Examples of containers for storing ophthalmic compositions include eye drop containers, eyewash containers, containers for contact lens wetting solution, containers for contact lens care solutions (including containers for contact lens cleaning solution, containers for contact lens storage solution, containers for contact lens disinfecting solution, containers for contact lens multi-purpose solution, etc.), etc. Examples of parts of containers for storing ophthalmic compositions that come into contact with the ophthalmic composition include inner stoppers, perforated inner stoppers, and the inner surface of the container (the innermost layer if the container has a structure consisting of multiple layers).

[0124] In the PBT-containing resin container according to this embodiment, a part or all of the part that comes into contact with the ophthalmic composition is formed of a PBT-containing resin. For example, when the PBT-containing resin container has a perforated inner stopper (nozzle), only the perforated inner stopper part may be formed of a PBT-containing resin, or the storage part other than the perforated inner stopper may be formed of a PBT-containing resin, or the entire container may be formed of a PBT-containing resin.

[0125] The PBT-containing resin container may have only a portion of its surface that comes into contact with the ophthalmic composition formed from the PBT-containing resin, but from the viewpoint of achieving the effects of the present invention more significantly, it is preferable that the entire surface that comes into contact with the ophthalmic composition be formed from the PBT-containing resin. When only a portion of the container is formed from the PBT-containing resin, the type of resin that forms the other portions is not particularly limited, and may contain, for example, one or more polymers selected from the group consisting of polyethylene terephthalate (PET), polystyrene (PS), acrylonitrile butadiene styrene (ABS), polycarbonate, polyethylene (PE), polypropylene (PP), polymethyl methacrylate, ethylene-vinyl acetate copolymer, and ethylene-vinyl alcohol copolymer as constituent components.

[0126] The shape and capacity of the PBT-containing resin container are not particularly limited and may be appropriately determined depending on the application. For example, when the PBT-containing resin container is a container for storing eye drops or contact lens wetting solution, the capacity may be, for example, 0.1 mL to 50 mL, preferably 2 mL to 40 mL, and more preferably 4 mL to 25 mL. Furthermore, when the PBT-containing resin container is a container for storing eyewash or contact lens care solution, the capacity may be, for example, 40 mL to 600 mL.

[0127] The type of PBT-containing resin container may be a container commonly used in the field of ophthalmology, and specifically may be, for example, an eye drop container, an eyewash container, a container for holding contact lens wetting solution, or a container for holding contact lens care solution (including a container for holding contact lens cleaning solution, a container for holding contact lens storage solution, a container for holding contact lens disinfecting solution, a container for holding contact lens multi-purpose solution, etc.). The type of PBT-containing resin container is preferably an eye drop container, a container for holding contact lens wetting solution, or a container for holding contact lens care solution. 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).

[0128] The PBT-containing resin container may be a multi-dose type that contains an amount for multiple uses, or a unit-dose type that contains an amount for single use.

[0129] The ophthalmic composition according to this embodiment may also be provided as an ophthalmic composition contained in a PBT-containing resin container. The present invention can also be understood as an ophthalmic product (e.g., eye drops, eyewash, contact lens-related products) containing the ophthalmic composition of the present invention contained in a PBT-containing resin container.

[0130] The ophthalmic composition according to this embodiment may be an ophthalmic composition containing any combination of the above-described various components. Particularly preferred combinations of components to be incorporated into the ophthalmic composition according to this embodiment are exemplified below. Note that the above-described embodiments can be applied to matters not specifically mentioned below.

[0131] An ophthalmic composition according to one embodiment (hereinafter also referred to as the "first ophthalmic composition") comprises (A) pranoprofen or a salt thereof and (B-1) one or more selected from the group consisting of nonionic surfactants, antiallergic ingredients, anti-inflammatory ingredients, preservatives, polysaccharides, vinyl compounds, amino acids, cooling agents, antioxidants, decongestants, oils, and inorganic salts, and is housed in a container, part or all of which comes into contact with the ophthalmic composition, and is formed from a resin containing polybutylene terephthalate.

[0132] In a first ophthalmic composition, the nonionic surfactant component is at least one selected from the group consisting of polyoxyethylene-polyoxypropylene block copolymer, polyoxyethylene castor oil, polyethylene glycol monostearate, polyethylene glycol, sorbitol, xylitol, tyloxapol, and salts thereof; the antiallergic component is at least one selected from the group consisting of tranilast, diphenhydramine, and salts thereof; the anti-inflammatory component is at least one selected from the group consisting of epsilon-aminocaproic acid, berberine, lysozyme, and salts thereof; the preservative is at least one selected from the group consisting of chlorhexidine, chlorobutanol, benzethonium, alkylpolyaminoethylglycine, paraben, sulfamethoxazole, phenylethyl alcohol, monoethanolamine, ethanol, and salts thereof; and the polysaccharide is at least one selected from the group consisting of gellan gum, dextran, hydroxyethylcellulose, the vinyl compound is one or more selected from the group consisting of polyvinyl alcohol, carboxyvinyl polymers and salts thereof; the amino acids are one or more selected from the group consisting of glycine, glutamic acid, taurine and salts thereof; the freshening agent is one or more selected from the group consisting of borneol, geraniol, eucalyptus oil and bergamot oil; the antioxidant is one or more selected from the group consisting of butylhydroxyanisole and salts thereof; the decongestant is one or more selected from the group consisting of tetrahydrozoline, naphazoline and salts thereof; the oil is one or more selected from the group consisting of sesame oil, castor oil, petrolatum, paraffin and lanolin; and the inorganic salt is one or more selected from the group consisting of sodium chloride, calcium chloride, zinc chloride and magnesium sulfate.

[0133] When taurine or a salt thereof is used as component (B-1) in the first ophthalmic composition, the content of taurine or a salt thereof is, in addition to the range exemplified for (B) amino acids, preferably 0.25 w / v% or more, more preferably 0.25 to 5 w / v%, even more preferably 0.25 to 3 w / v%, even more preferably 0.25 to 2 w / v%, and particularly preferably 0.25 to 1 w / v%, based on the total amount of the ophthalmic composition.

[0134] It is preferable that the first ophthalmic composition further contains (C) one or more selected from the group consisting of chlorpheniramine, edetic acid, dibutylhydroxytoluene, polysorbate 80, and salts thereof.

[0135] An ophthalmic composition according to one embodiment (hereinafter also referred to as the "second ophthalmic composition") comprises (A) pranoprofen or a salt thereof, (B-2) one or more anti-allergic ingredients selected from the group consisting of cromoglycic acid, ketotifen, tranilast and salts thereof, and (C-1) chlorpheniramine or a salt thereof, and is contained in a container in which part or all of the part that comes into contact with the ophthalmic composition is formed of a resin containing polybutylene terephthalate.

[0136] It is preferable that the second ophthalmic composition further contains one or more selected from the group consisting of (B-3) nonionic surfactants, mannitol, azulene sulfonic acid, glycyrrhizinic acid, epsilon-aminocaproic acid, allantoin, sorbic acid, chlorhexidine, hyaluronic acid, alginic acid, hydroxypropyl methylcellulose, polyvinylpyrrolidone, tocopherol acetate, cyanocobalamin, panthenol, taurine, aspartic acid, camphor and salts thereof, and (C-2) polysorbate 80 and salts thereof.

[0137] In the second ophthalmic composition, the nonionic surfactant component is preferably propylene glycol, glycerin, polyoxyethylene hydrogenated castor oil, or a salt thereof.

[0138] When aspartic acid or a salt thereof is used as component (B-3) in the second ophthalmic composition, the content of aspartic acid or a salt thereof is, in addition to the range exemplified for (B) amino acids, preferably 0.25 w / v% or more, more preferably 0.25 to 5 w / v%, more preferably 0.25 to 3 w / v%, even more preferably 0.25 to 2 w / v%, and particularly preferably 0.25 to 1 w / v%, based on the total amount of the ophthalmic composition.

[0139] The second ophthalmic composition preferably contains at least polysorbate 80 as component (C-2) (note that in this case, the second ophthalmic composition may also contain other components (B-3) and (C-2)), and further contains one or more members selected from the group consisting of pyridoxine, polyhexamethylene biguanide, and salts thereof (B-4).

[0140] The second ophthalmic composition preferably contains at least polyoxyethylene hydrogenated castor oil and tocopherol acetate as component (B-3), and in this case, the second ophthalmic composition may contain other components (B-3) and (C-2).

[0141] The second ophthalmic composition also preferably contains at least polyoxyethylene hydrogenated castor oil as component (B-3) (note that in this case, the second ophthalmic composition may contain other components (B-3) and (C-2)), and further contains (B-5) one or more selected from the group consisting of chondroitin sulfate, menthol, benzalkonium, and salts thereof.

[0142] When chondroitin sulfate or a salt thereof is used as component (B-3) in the second ophthalmic composition, the content of chondroitin sulfate or a salt thereof is, in addition to the range exemplified for (B) polysaccharide, preferably 0.25 w / v% or more, more preferably 0.25 to 6 w / v%, more preferably 0.25 to 5 w / v%, even more preferably 0.25 to 4 w / v%, even more preferably 0.25 to 3 w / v%, and particularly preferably 0.25 to 0.5 w / v%, based on the total amount of the ophthalmic composition.

[0143] The second ophthalmic composition contains at least tranilast or a salt thereof as the component (B-2) (note that in this case, the second ophthalmic composition may contain other (B-2) components), and preferably further contains one or more selected from the group consisting of (B-6) nonionic surfactants, mannitol, azulene sulfonic acid, glycyrrhizinic acid, epsilon-aminocaproic acid, allantoin, sorbic acid, chlorhexidine, polyhexamethylene biguanide, chondroitin sulfate, hyaluronic acid, alginic acid, hydroxypropyl methylcellulose, polyvinylpyrrolidone, tocopherol acetate, cyanocobalamin, panthenol, taurine, aspartic acid, menthol, camphor, benzalkonium and salts thereof, and (C-3) edetic acid, dibutylhydroxytoluene, polysorbate 80 and salts thereof.

[0144] An ophthalmic composition according to one embodiment (hereinafter also referred to as the "third ophthalmic composition") comprises (A) pranoprofen or a salt thereof and (C-1) chlorpheniramine or a salt thereof, wherein the total content of chlorpheniramine or a salt thereof is 0.02 w / v% or more based on the total amount of the ophthalmic composition, and the ophthalmic composition is contained in a container, part or all of which comes into contact with the ophthalmic composition, formed of a resin containing polybutylene terephthalate.

[0145] In addition to the range exemplified for (C) chlorpheniramine or a salt thereof, the content of (C-1) chlorpheniramine or a salt thereof in the third ophthalmic composition is, for example, based on the total amount of the ophthalmic composition, preferably a total content of chlorpheniramine or a salt thereof of 0.02 w / v% or more, more preferably 0.02 to 0.5 w / v%, more preferably 0.02 to 0.3 w / v%, even more preferably 0.02 to 0.1 w / v%, even more preferably 0.02 to 0.08 w / v%, even more preferably 0.02 to 0.05 w / v%, and particularly preferably 0.02 to 0.03 w / v%.

[0146] It is preferable that the third ophthalmic composition further contains (B-7) one or more selected from the group consisting of propylene glycol, glycerin, azulene sulfonic acid, sorbic acid, polyhexamethylene biguanide, polyoxyethylene hydrogenated castor oil, mannitol, glycyrrhizinic acid, allantoin, chlorhexidine, paraben, hyaluronic acid, alginic acid, hydroxypropyl methylcellulose, polyvinylpyrrolidone, pyridoxine, tocopherol acetate, cyanocobalamin, panthenol, taurine, aspartic acid, camphor, and salts thereof.

[0147] The third ophthalmic composition preferably contains at least polyoxyethylene hydrogenated castor oil as component (B-7) (note that in this case, the third ophthalmic composition may contain other (B-7) components), and further contains one or more selected from the group consisting of (B-8) chondroitin sulfate, benzalkonium, menthol and salts thereof, and (C-4) edetic acid, dibutylhydroxytoluene and salts thereof.

[0148] An ophthalmic composition according to one embodiment (hereinafter also referred to as the "fourth ophthalmic composition") comprises (A) pranoprofen or a salt thereof and (B-9) one or more anti-inflammatory components selected from the group consisting of glycyrrhizinic acid, allantoin, azulene sulfonic acid, and salts thereof, and is contained in a container in which part or all of the part that comes into contact with the ophthalmic composition is formed of a resin containing polybutylene terephthalate.

[0149] When the fourth ophthalmic composition contains one or more anti-inflammatory ingredients selected from the group consisting of glycyrrhizinic acid and its salts as component (B-9), it preferably further contains one or more ingredients selected from the group consisting of (B-10) sorbic acid, polyhexamethylene biguanide, chlorhexidine, paraben, benzalkonium, polyoxyethylene hydrogenated castor oil, mannitol, chondroitin sulfate, hyaluronic acid, alginic acid, hydroxypropyl methylcellulose, polyvinylpyrrolidone, pyridoxine, tocopherol acetate, cyanocobalamin, panthenol, taurine, aspartic acid, camphor, menthol, propylene glycol, glycerin and salts thereof, and (C-5) chlorpheniramine, edetic acid and salts thereof (ophthalmic composition No. 4-1).

[0150] When the fourth ophthalmic composition contains at least one or more anti-inflammatory ingredients selected from the group consisting of allantoin and its salts as component (B-9), it preferably further contains one or more ingredients selected from the group consisting of (B-11) sorbic acid, polyhexamethylene biguanide, chlorhexidine, paraben, benzalkonium, polyoxyethylene hydrogenated castor oil, mannitol, chondroitin sulfate, hyaluronic acid, alginic acid, polyvinylpyrrolidone, pyridoxine, tocopherol acetate, cyanocobalamin, panthenol, taurine, aspartic acid, camphor, menthol, propylene glycol, glycerin, neostigmine methylsulfate and salts thereof, and (C-5) chlorpheniramine, edetic acid and salts thereof (ophthalmic composition No. 4-2).

[0151] When the fourth ophthalmic composition contains one or more anti-inflammatory components selected from the group consisting of azulene sulfonic acid and its salts as component (B-9), it preferably further contains (B-12) one or more components selected from the group consisting of sorbic acid, chlorhexidine, benzalkonium, polyoxyethylene hydrogenated castor oil, alginic acid, tocopherol acetate, cyanocobalamin, panthenol, camphor, propylene glycol, and salts thereof (4-3 ophthalmic composition).

[0152] The ophthalmic composition No. 4-3 preferably further contains (B-13) one or more selected from the group consisting of polyhexamethylene biguanide, chondroitin sulfate, pyridoxine, taurine, aspartic acid, menthol, neostigmine methylsulfate, and salts thereof, and (C) chlorpheniramine, edetic acid, dibutylhydroxytoluene, polysorbate 80, and salts thereof. When the ophthalmic composition No. 4-3 contains these additional components, it preferably contains at least polyoxyethylene hydrogenated castor oil as component (B-12) (note that in this case, the ophthalmic composition No. 4-3 may contain other (B-12) components).

[0153] An ophthalmic composition according to one embodiment (hereinafter also referred to as the "fifth ophthalmic composition") comprises (A) pranoprofen or a salt thereof, (B-14) one or more selected from the group consisting of pyridoxine, tocopherol, cyanocobalamin, panthenol, flavin adenine dinucleotide, retinol, and derivatives thereof, and salts thereof, and (B-15) one or more selected from the group consisting of taurine, aspartic acid, and salts thereof, and is housed in a container in which part or all of the portion that comes into contact with the ophthalmic composition is formed of a resin containing polybutylene terephthalate.

[0154] In the fifth ophthalmic composition, the component (B-15) preferably contains two or more members selected from the group consisting of taurine, aspartic acid, and salts thereof.

[0155] It is preferable that the fifth ophthalmic composition further contains (B-16) one or more selected from the group consisting of cromoglycic acid, polyoxyethylene hydrogenated castor oil, camphor, sorbic acid, chlorhexidine, paraben, benzalkonium, mannitol, hyaluronic acid, alginic acid, polyvinylpyrrolidone, propylene glycol, glycerin, and salts thereof.

[0156] The fifth ophthalmic composition preferably contains at least aspartic acid or a salt thereof as component (B-15) (note that in this case, the fifth ophthalmic composition may contain other (B-15) components), and the total content of aspartic acid or a salt thereof is 0.3 w / v% or more based on the total amount of the ophthalmic composition, and further contains (B-17) one or more selected from the group consisting of cromoglycic acid, polyoxyethylene hydrogenated castor oil, camphor, and salts thereof.

[0157] When aspartic acid or a salt thereof is used as component (B-15) in the fifth ophthalmic composition, the content of aspartic acid or a salt thereof is, in addition to the range exemplified for (B) amino acids, preferably 0.3 w / v% or more, more preferably 0.3 to 5 w / v%, more preferably 0.3 to 3 w / v%, even more preferably 0.3 to 2 w / v%, and particularly preferably 0.3 to 1 w / v%, based on the total amount of the ophthalmic composition.

[0158] In the fifth ophthalmic composition, the component (B-14) preferably contains two or more selected from the group consisting of pyridoxine, tocopherol, cyanocobalamin, panthenol, flavin adenine dinucleotide, retinol, derivatives thereof, and salts thereof.

[0159] The fifth ophthalmic composition preferably further contains (B-17) one or more selected from the group consisting of cromoglycic acid, polyoxyethylene hydrogenated castor oil, camphor, and salts thereof.

[0160] An ophthalmic composition according to one embodiment (hereinafter also referred to as the "sixth ophthalmic composition") comprises (A) pranoprofen or a salt thereof, (B-18) chondroitin sulfate or a salt thereof, and (B-19) one or more selected from the group consisting of taurine, cyanocobalamin, panthenol, polyhexamethylene biguanide, hydroxypropyl methylcellulose, and salts thereof, wherein the total content of chondroitin sulfate or a salt thereof is 0.35 w / v% or more based on the total amount of the ophthalmic composition, and the ophthalmic composition is contained in a container, part or all of which comes into contact with the ophthalmic composition, formed from a resin containing polybutylene terephthalate.

[0161] The sixth ophthalmic composition preferably further contains (B-20) one or more selected from the group consisting of polyoxyethylene hydrogenated castor oil, tocopherol acetate, pyridoxine, flavin adenine dinucleotide, and salts thereof.

[0162] [2. Suppression of wetting of PBT-containing resins] The ophthalmic composition according to this embodiment has suppressed wetting of a resin containing polybutylene terephthalate. Accordingly, one embodiment of the present invention provides a method for imparting an ophthalmic composition with an inhibitory effect on a resin containing polybutylene terephthalate, the method comprising blending (A) pranoprofen or a salt thereof and (B) one or more selected from the group consisting of a nonionic surfactant, an antiallergic component, an anti-inflammatory component, an antiseptic, a polysaccharide, a vinyl compound, a vitamin, an amino acid, a cooling agent, a decongestant, an oil, and an inorganic salt into the ophthalmic composition.

[0163] In this embodiment, the types and contents of the (A) component and the (B) component, the types and contents of other components, the formulation form and use of the ophthalmic composition, etc. are as described in [1. Ophthalmic composition]. [Example]

[0164] The present invention will be specifically explained below based on test examples, but the present invention is not limited to these.

[0165] [Test method: Dynamic contact angle (advancing angle) measurement method] The dynamic contact angle (advancing angle) of each test liquid was measured using a contact angle meter DM-501 (manufactured by Kyowa Interface Science Co., Ltd.) according to the measurement procedure of the expansion / contraction method of the contact angle meter. The dynamic contact angle (advancing angle) is the contact angle when the interface between a solid and a liquid moves.

[0166] Specifically, a plate-shaped PBT-containing resin (product name: PBT Natural, manufactured by Aram Co.) (a square prism with sides of 50 mm and a thickness of approximately 2 mm) was placed on the stage of the contact angle meter, and the test liquid was set in the dispenser. At room temperature, a 1 μL droplet of the test liquid was dropped onto the PBT-containing resin plate, causing it to settle in a hemispherical shape. Next, the tip of the dispenser's liquid ejection part was quickly placed on the top of the hemisphere. In this state, the test liquid was continuously ejected at a rate of 6 μL / sec, and the shape of the droplet was photographed from the side 15 times every 0.1 sec. To match the measurement conditions, the test liquids paired when calculating the rate of change in dynamic contact angle were measured consecutively using the same PBT-containing resin plate under the same temperature conditions (room temperature).

[0167] Next, the left and right contact angles for each image were determined using the contact angle meter's analysis software, FAMAS. Here, the contact angle refers to the angle between the tangent line drawn from the contact point P between the surface of the PBT-containing resin plate, the test liquid, and air to the test liquid and the tangent line drawn to the surface of the PBT-containing resin plate, the angle on the side containing the test liquid. There were two contact points P for each droplet, one on the left and one on the right. As the droplet expanded following the ejection of the test liquid, the contact angle changed and then became almost constant. Therefore, the average left and right contact angles for each image were calculated, and the average values were arranged in the order in which the images were taken. The first average value at which the standard deviation of the five average values fell below 2.5° (the average left and right contact angles for the image taken earliest among the five average values) was used as the measured dynamic contact angle. For all test liquids, no standard deviations greater than 2.5° were observed after the initial standard deviation fell below 2.5°. Even when the contact angle did not change during the droplet spreading process, the dynamic contact angle measurement was obtained according to the above criteria.

[0168] The above procedure was repeated three times for each test liquid, and the average of the three measurements was taken as the dynamic contact angle of the test liquid. The standard deviation of the three measurements was 2.0° or less for all test liquids.

[0169] Test Example 1: Evaluation of dynamic contact angle (advancing angle) of formulation containing only component (A) Each formulation (component (A) solution and component (B) solution) shown in Table 1 was prepared by a standard method and used as a test solution. The units of content in Table 1 are w / v %. The component (A) solution in each test was a formulation containing the component (A) shown in Table 1 in the content shown in Table 1, and adjusted to the pH shown in Table 1 with appropriate amounts of hydrochloric acid and sodium hydroxide (the balance being purified water). Similarly, the component (B) solution was a formulation containing the component (B) shown in Table 1 in the content shown in Table 1, and adjusted to the pH shown in Table 1 with appropriate amounts of hydrochloric acid and sodium hydroxide (the balance being purified water).

[0170] The dynamic contact angle of each test liquid was determined (average of three measurements) according to the procedure described in the test method above. The rate of change in the dynamic contact angle of the component (A) liquid relative to the component (B) liquid was then calculated using the following formula (1). The calculated results are shown in Table 1. [Equation 1] Dynamic contact angle change rate (%) = {(dynamic contact angle of each (A) component liquid / corresponding dynamic contact angle of (B) component liquid) - 1} × 100 The corresponding component (B) liquid is the component (B) liquid listed in the same test number column in Table 1.

[0171] For Tests No. 2, No. 15, and No. 26, both component (A) and component (B) solutions were heat-treated before being used to measure the dynamic contact angle. The heat treatment involved filling 5 mL of each test solution into a 10 mL glass headspace vial after preparation and leaving it at 60°C for 7 days, which corresponds to storage at room temperature for approximately 3 years. Tests were conducted immediately after preparation for the other test solutions.

[0172] [Table 1]

[0173] As shown in Table 1, it can be seen that the dynamic contact angle of component (A) liquid was smaller than that of component (B) liquid in all tests conducted under different conditions. In other words, it was revealed that the composition containing pranoprofen (A) has a small dynamic contact angle with respect to the resin containing polybutylene terephthalate, and is prone to wetting.

[0174] [Test Example 2: Evaluation of Dynamic Contact Angle (Advancing Angle)] Each ophthalmic composition shown in Tables 2 to 6 and a corresponding component (A) solution were prepared by a standard method and used as a test solution. The units of each component in Tables 2 to 6 are w / v %. The corresponding component (A) solution is a formulation obtained by removing all components other than component (A) from the formulation of each test solution and adjusting the pH with appropriate amounts of hydrochloric acid and sodium hydroxide (the remainder being purified water). For example, the component (A) solution corresponding to the test solution in Example 1-1 contains 0.05 w / v % of (A) pranoprofen and has a pH of 7.5.

[0175] The dynamic contact angle of each test liquid was determined (average of three measurements) according to the procedure described in the test method above. The rate of change in the dynamic contact angle of each test liquid relative to the corresponding component (A) liquid was then calculated using the following [Equation 2]. [Equation 2] Dynamic contact angle change rate (%) = {(dynamic contact angle of each test liquid / dynamic contact angle of corresponding component (A) liquid) - 1} × 100

[0176] Furthermore, Examples 2-1 to 2-3, 15, and 26 were subjected to heat treatment together with the corresponding component (A) liquid, followed by measurement of the dynamic contact angle. The heat treatment involved filling 5 mL of the test liquid into 10 mL glass headspace vials after preparation and leaving the liquid at 60°C for 7 days, which corresponds to storage at room temperature for approximately 3 years. The other test liquids were tested immediately after preparation. [Table 2]

[0177] [Table 3]

[0178] [Table 4]

[0179] [Table 5]

[0180] [Table 6]

[0181] As shown in Tables 2 to 6, compared to a component (A) solution containing only component (A), an ophthalmic composition containing a combination of component (A) and component (B) has a larger dynamic contact angle, and can suppress wetting of polybutylene terephthalate-containing resins. Furthermore, as shown in Tables 2 to 4, an ophthalmic composition containing component (C) in addition to components (A) and (B) has an even larger dynamic contact angle, and can further suppress wetting of polybutylene terephthalate-containing resins. Furthermore, even heat-treated ophthalmic compositions have a larger dynamic contact angle, and can suppress wetting of polybutylene terephthalate-containing resins even after long-term storage.

[0182] [Test Example 3: Evaluation of Dynamic Contact Angle (Advancing Angle)] Each ophthalmic composition shown in Tables 7 to 10 was prepared by a conventional method and used as a test solution. The unit of each component in Tables 7 to 10 is w / v %. The dynamic contact angle was measured in the same manner as in the test method above, except that the average value of the left and right contact angles for each image was calculated, and the average values were arranged in the order in which the images were taken. Five consecutive images were selected, and the first average value when the standard deviation of the five average values was 2.0° or less (the average value of the left and right contact angles for the image taken earliest among the five average values) was used as the measured value of the dynamic contact angle. For all test solutions, no standard deviation greater than 2.0° was observed after the standard deviation first reached 2.0° or less.

[0183] From the dynamic contact angle (average value of three measured values) of each test liquid obtained, the rate of change in the dynamic contact angle of each test liquid relative to the corresponding test liquid (Test Liquid 1 or Test Liquid 2 in Table 7) was calculated using the following [Equation 3]. [Equation 3] Dynamic contact angle change rate (%) = {(dynamic contact angle of each test liquid / dynamic contact angle of test liquid 1 or test liquid 2) - 1} × 100

[0184] The corresponding test solution is a formulation obtained by removing all components other than component (A) from the formulation of each test solution and adjusting the pH to the same level with hydrochloric acid and an appropriate amount of sodium hydroxide (the remainder being purified water). In Tables 7 to 10, the test solution corresponding to Examples 37 to 39 and 42 is Test Solution 2, and the test solution corresponding to the other Examples is Test Solution 1.

[0185] Furthermore, Example 44 was subjected to heat treatment together with the corresponding test liquid (Test Liquid 1) before being subjected to measurement of the dynamic contact angle. The heat treatment involved filling 5 mL of the test liquid into 10 mL glass headspace vials after preparation and leaving them at 60°C for 7 days, which corresponds to storage at room temperature for approximately 3 years. The other test liquids were tested immediately after preparation.

[0186] [Table 7]

[0187] [Table 8]

[0188] [Table 9]

[0189] [Table 10]

[0190] As shown in Tables 7 to 10, compared to test solutions containing only component (A), ophthalmic compositions containing component (A) in combination with component (B) and / or component (C) have larger dynamic contact angles and can suppress wetting of polybutylene terephthalate-containing resins. Furthermore, even heat-treated ophthalmic compositions have larger dynamic contact angles, and can suppress wetting of polybutylene terephthalate-containing resins even after long-term storage.

[0191] Test Example 4: Evaluation of Dynamic Contact Angle (Advancing Angle) Each ophthalmic composition shown in Tables 11 to 17 was prepared by a conventional method and used as a test solution. The unit of each component in Tables 11 to 17 is w / v %. The dynamic contact angle was measured in the same manner as in Test Example 3. For all test solutions, after the standard deviation initially reached 2.0° or less, no standard deviation greater than 2.0° was observed.

[0192] From the dynamic contact angle (average value of three measurements) of each test liquid obtained, the rate of change in the dynamic contact angle of each test liquid relative to the corresponding test liquid was calculated using the following [Equation 4]. [Equation 4] Dynamic contact angle change rate (%) = {(dynamic contact angle of each test liquid / dynamic contact angle of corresponding test liquid) - 1} × 100

[0193] The corresponding test solutions are as follows: Examples 10-1, 10-3, and 10-9 are test solution 10-1; Examples 10-2, 10-4 to 10-8, and 10-10 to 10-11 are test solution 10-2 (Table 11); Examples 10-12 to 10-21 are test solution 10-2 (Table 12); Example 10-24 is test solution 10-1; Examples 10-22 and 10-23 are test solution 10-2; and Examples 10-25 to 10-27 are test solution 10-1. -3 (Table 13), Examples 10-28 and 10-29 are test liquid 10-2, Examples 10-30 and 10-31 are test liquid 10-4 (Table 14), Examples 10-32 to 10-37 are test liquid 10-5, Examples 10-38 to 10-42 are test liquid 10-6 (Table 15), Examples 11-1 to 11-11 are test liquid 10-7 (Table 16), and Examples 11-12 to 11-16 are test liquid 10-7 (Table 17). After each test liquid was prepared, the test was carried out immediately.

[0194] [Table 11]

[0195] [Table 12]

[0196] [Table 13]

[0197] [Table 14]

[0198] [Table 15]

[0199] [Table 16]

[0200] [Table 17]

[0201] As shown in Tables 11 to 17, compared to the test solution containing component (A) in combination with (B-2) one or more anti-allergic components selected from the group consisting of cromoglycic acid, tranilast, and salts thereof, and (C-1) chlorpheniramine or a salt thereof, the ophthalmic compositions containing various components (B) and / or (C) in combination have significantly larger dynamic contact angles and can further suppress wetting of polybutylene terephthalate-containing resins.

[0202] Test Example 5: Evaluation of Dynamic Contact Angle (Advancing Angle) Each ophthalmic composition shown in Tables 18 to 22 was prepared by a conventional method and used as a test solution. The unit of each component in Tables 18 to 22 is w / v %. The dynamic contact angle was measured in the same manner as in Test Example 3. For all test solutions, after the standard deviation initially reached 2.0° or less, no standard deviation greater than 2.0° was observed.

[0203] From the dynamic contact angle (average value of three measurements) of each test liquid obtained, the rate of change in the dynamic contact angle of each test liquid relative to the corresponding test liquid was calculated using the following [Equation 5]. [Equation 5] Dynamic contact angle change rate (%) = {(dynamic contact angle of each test liquid / dynamic contact angle of corresponding test liquid) - 1} × 100

[0204] The corresponding test solutions are as follows: Examples 20-A to 20-D are test solution 20-A (Table 18), Examples 20-1 and 20-3 are test solution 20-1, Examples 20-2 and 20-4 to 20-7 are test solution 20-2 (Table 19), Examples 20-8 to 20-10, 20-13 to 20-15, and 20-17 to 20-18 are test solution 20-1, Examples 20-11 to 20-12, and 20-16 are test solution 20-2 (Table 20), Examples 20-19 to 20-29 are test solution 20-1 (Table 21), and Examples 20-30 to 20-34 are test solution 20-3 (Table 22). Each test solution was tested immediately after preparation.

[0205] [Table 18]

[0206] [Table 19]

[0207] [Table 20]

[0208] [Table 21]

[0209] [Table 22]

[0210] As shown in Tables 18 to 21, compared to test solutions containing only component (A), ophthalmic compositions containing component (A) in combination with various components (B) and (C) chlorpheniramine or a salt thereof have larger dynamic contact angles and are able to suppress wetting of polybutylene terephthalate-containing resins. Also, as shown in Table 22, compared to test solutions containing component (A) and (C) chlorpheniramine or a salt thereof, ophthalmic compositions further containing polyoxyethylene hydrogenated castor oil in combination with various components (B) have larger dynamic contact angles and are able to suppress wetting of polybutylene terephthalate-containing resins.

[0211] [Test Example 6: Evaluation of Dynamic Contact Angle (Advancing Angle)] Each ophthalmic composition shown in Tables 23 to 30 was prepared by a conventional method and used as a test solution. The unit of each component in Tables 23 to 30 is w / v %. The dynamic contact angle was measured in the same manner as in Test Example 3. For all test solutions, once the standard deviation initially reached 2.0° or less, no standard deviation greater than 2.0° was observed.

[0212] From the dynamic contact angle (average value of three measurements) of each test liquid obtained, the rate of change in the dynamic contact angle of each test liquid relative to the corresponding test liquid was calculated using the following [Equation 6]. [Equation 6] Dynamic contact angle change rate (%) = {(dynamic contact angle of each test liquid / dynamic contact angle of corresponding test liquid) - 1} × 100

[0213] The corresponding test solutions are as follows: Examples 30-1 to 30-2, 30-4 to 30-8, and 30-10 to 30-11 are test solution 30-1; Examples 30-3 and 30-9 are test solution 30-2 (Table 23); Examples 30-12 to 30-16 and 30-18 to 30-21 are test solution 30-1; Example 30-17 is test solution 30-2 (Table 24); Examples 30-22 to 30-27 are test solution 30-1; Examples 30-28 to 30-32 are test solution 30-3 (Table 25); and Examples 30-33 to 30-34, 30-36 to 30-37 are test solution 30-4 (Table 26). Examples 30-40 and 30-42 to 30-43 are test solution 30-3, Examples 30-35 and 30-41 are test solution 30-4 (Table 26), Examples 30-44 to 30-53 are test solution 30-3 (Table 27), Example 30-54 is test solution 30-5, Example 30-55 is test solution 30-6 (Table 28), Examples 30-56 to 30-62 and 30-64 to 30-65 are test solution 30-7, Example 30-63 is test solution 30-8 (Table 29), and Examples 30-66 to 30-76 are test solution 30-9 (Table 30). Each test solution was tested immediately after preparation.

[0214] [Table 23]

[0215] [Table 24]

[0216] [Table 25]

[0217] [Table 26]

[0218] [Table 27]

[0219] [Table 28]

[0220] [Table 29]

[0221] [Table 30]

[0222] As shown in Tables 22 to 30, compared to the test solution containing component (A) in combination with one or more anti-inflammatory components selected from the group consisting of (B-9) glycyrrhizinic acid, allantoin, azulene sulfonic acid, and their salts, the ophthalmic compositions containing various components (B) and / or (C) in combination have a significantly larger dynamic contact angle, and are able to further suppress wetting of polybutylene terephthalate-containing resins.

[0223] Test Example 7: Evaluation of Dynamic Contact Angle (Advancing Angle) Each ophthalmic composition shown in Tables 31 to 40 was prepared by a conventional method and used as a test solution. The unit of each component in Tables 31 to 40 is w / v %. The dynamic contact angle was measured in the same manner as in Test Example 3. For all test solutions, once the standard deviation initially reached 2.0° or less, no standard deviation greater than 2.0° was observed.

[0224] From the dynamic contact angle (average value of three measurements) of each test liquid obtained, the rate of change in the dynamic contact angle of each test liquid relative to the corresponding test liquid was calculated using the following [Equation 7]. [Equation 7] Dynamic contact angle change rate (%) = {(dynamic contact angle of each test liquid / dynamic contact angle of corresponding test liquid) - 1} × 100

[0225] The corresponding test solutions are as follows: Examples 40-1 to 40-2 and 40-4 to 40-8 are test solution 40-1, Example 40-3 is test solution 40-2, Examples 40-9 and 40-10 are test solution 40-3 (Table 31), Examples 40-11 to 40-12 and 40-15 to 40-19 are test solution 40-4, Examples 40-13 to 40-14 are test solution 40-5 (Table 32), and Example 40-2 Examples 40-0 to 40-21 and 40-24 to 40-27 are test solution 40-6, Examples 40-22 to 40-23 are test solution 40-7, Examples 40-28 to 40-29 are test solution 40-8 (Table 33), Examples 40-30 to 40-34 are test solution 40-9 (Table 34), Examples 40-35 to 40-39 are test solution 40-10, and Examples 40-40 to 40-41 are test solution 40-11, Example 40-42 corresponds to test solution 40-12 (Table 35), Examples 40-43 to 40-46 correspond to test solution 40-13, Examples 40-47 to 40-51 correspond to test solution 40-14 (Table 36), Examples 40-52 to 40-55 correspond to test solution 40-15, Examples 40-56 to 40-59 correspond to test solution 40-16 (Table 37), Examples 40-60 to 40-62 correspond to test solution 40-17, and Examples Examples 40-63 to 40-65 correspond to test solution 40-18 (Table 38), Examples 40-66 to 40-70 correspond to test solution 40-19, Examples 40-71 to 40-73 correspond to test solution 40-20 (Table 39), Examples 40-74 to 40-75 correspond to test solution 40-21, Examples 40-76 to 40-77 correspond to test solution 40-22, and Examples 40-78 to 40-79 correspond to test solution 40-23 (Table 40). Each test solution was tested immediately after preparation.

[0226] [Table 31]

[0227] [Table 32]

[0228] [Table 33]

[0229] Table 34

[0230] Table 35

[0231] Table 36

[0232] Table 37

[0233] Table 38

[0234] Table 39

[0235] Table 40

[0236] As shown in Tables 31 to 40, compared to the test solution containing component (A) in combination with (B-14) one or more selected from the group consisting of pyridoxine, tocopherol, cyanocobalamin, panthenol, flavin adenine dinucleotide, retinol and their derivatives, and their salts, and (B-15) one or more selected from the group consisting of taurine, aspartic acid and their salts, the ophthalmic compositions containing various components (B) and / or (C) in combination have significantly larger dynamic contact angles and can further suppress wetting of polybutylene terephthalate-containing resins.

[0237] Test Example 8: Evaluation of Dynamic Contact Angle (Advancing Angle) Each ophthalmic composition shown in Tables 41 to 42 was prepared by a conventional method and used as a test solution. The unit of each component in Tables 41 to 42 is w / v %. The dynamic contact angle was measured in the same manner as in Test Example 3. For all test solutions, once the standard deviation initially reached 2.0° or less, no standard deviation greater than 2.0° was observed.

[0238] From the dynamic contact angle (average value of three measurements) of each test liquid obtained, the rate of change in the dynamic contact angle of each test liquid relative to the corresponding test liquid was calculated using the following [Equation 8]. [Equation 8] Dynamic contact angle change rate (%) = {(dynamic contact angle of each test liquid / dynamic contact angle of corresponding test liquid) - 1} × 100

[0239] The corresponding test solutions are as follows: Test solution 50-1 for Examples 50-1 to 50-3 and 50-6 to 50-7, Test solution 50-2 for Examples 50-4 to 50-5 (Table 41), Test solution 50-3 for Examples 50-8 to 50-17, and Test solution 50-4 for Examples 50-18 to 50-19 (Table 42). After each test solution was prepared, it was immediately subjected to testing.

[0240] [Table 41]

[0241] [Table 42]

[0242] As shown in Tables 41 to 42, compared to the test solution containing a combination of component (A) and (B) chondroitin sulfate or a salt thereof, the ophthalmic composition containing a combination of various (B) components further exhibited a significantly larger dynamic contact angle, thereby further suppressing wetting of the polybutylene terephthalate-containing resin.

[0243] Test Example 9: Eye Drop Test Each formulation shown in Table 43 was prepared by standard methods and filled into a 14.2 mL polyethylene terephthalate eye dropper container at a volume of 13 mL (the units of each ingredient in Table 43 are w / v%). After filling, a polybutylene terephthalate nozzle was attached to the eye dropper container. Immediately after preparation, each test solution was subjected to an eye drop test. Four subjects with the symptoms shown in Table 43 were evaluated for each symptom by instilling one of the corresponding eye drops into the right eye and the other into the left eye, or by instilling one of the corresponding eye drops into the right eye and the other into the left eye. The eye drops were administered four times a day, with one drop administered per eye. The post-instillation efficacy for each symptom was evaluated using a visual analog scale (VAS) one hour after the fourth instillation. More specifically, the left end of a horizontal line was designated 0% (no symptoms felt at all) and the right end was designated 100% (the most severe symptoms ever experienced). Each subject was asked to mark a point on the line representing the intensity of their symptoms, and the length from the left end to that point was measured to evaluate the percentage (VAS score). The ease of instillation, an evaluation item shown in Table 43, was scored as 0% if the subject felt it was easy to instill the test solution from the eye dropper container into their eye, and 100% if the subject felt the operation was difficult. Examples of difficult operation include poor drainage of the test solution from the container, feeling that it took a long time to instill the solution into the eye, feeling that excessive grip strength was required, or failure to instill the solution into the eye.

[0244] The rate of change in VAS value in Table 43 was calculated using the following formula. VAS value change rate (%) = {(VAS score of each test solution - VAS score of corresponding test solution) / VAS score of corresponding test solution} × 100 The corresponding test liquid is the test liquid designated by a lowercase letter. For example, the corresponding test liquid for test liquid A is test liquid a.

[0245] As shown in Table 43, the ophthalmic compositions containing the combination of component (A) and each component showed a larger change in VAS value and improved symptoms compared to the corresponding test solutions. Furthermore, the compositions were also found to be easier to dispense from an eye dropper. [Table 43]

[0246] Test Example 10: Evaluation of Dynamic Contact Angle (Advancing Angle) Each ophthalmic composition shown in Tables 44 to 48 was prepared by a conventional method and used as a test solution. The unit of each component in Tables 44 to 48 is w / v %. The dynamic contact angle was measured in the same manner as in Test Example 3. For all test solutions, once the standard deviation initially reached 2.0° or less, no standard deviation greater than 2.0° was observed.

[0247] From the dynamic contact angle (average value of three measurements) of each test liquid obtained, the rate of change in the dynamic contact angle of each test liquid relative to the corresponding test liquid was calculated using the following [Equation 9]. [Equation 9] Dynamic contact angle change rate (%) = {(dynamic contact angle of each test liquid / dynamic contact angle of corresponding test liquid) - 1} × 100 The corresponding test solution is the "corresponding test example" listed in the same table.

[0248] The osmotic pressure ratio of each test solution was calculated as the ratio of the osmotic pressure of the test solution to 286 mOsm (the osmotic pressure of a 0.9 w / v% sodium chloride aqueous solution) in accordance with the 16th Edition of the Japanese Pharmacopoeia. Specifically, measurements were performed using the osmotic pressure measurement method (freezing point depression method) described in the Japanese Pharmacopoeia. A commercially available standard solution (0.9 w / v% sodium chloride aqueous solution) for measuring the osmotic pressure ratio was used.

[0249] [Table 44]

[0250] [Table 45]

[0251] [Table 46]

[0252] [Table 47]

[0253] [Table 48]

[0254] As shown in Tables 44 to 48, when the osmotic pressure ratio of the ophthalmic composition of the present invention is in the range of 0.8 to 2.2, the dynamic contact angle becomes significantly larger, and wetting of the polybutylene terephthalate-containing resin can be further suppressed.

Claims

[Claim 1] An ophthalmic composition comprising (A) pranoprofen or a salt thereof and (B) one or more components selected from the group consisting of a nonionic surfactant, an antiallergic component, an anti-inflammatory component, a preservative, a polysaccharide, a vinyl compound, a vitamin, an amino acid, an antioxidant, a cooling agent, a decongestant, an oil, and an inorganic salt, the ophthalmic composition being contained in a container, a part or all of which comes into contact with the ophthalmic composition being formed from a resin containing polybutylene terephthalate.

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