Ophthalmic components

Abstract

To provide an ophthalmic composition.SOLUTION: An ophthalmic composition has (A) at least one selected from the group consisting of epinastine and a salt thereof, (B) at least one selected from the group consisting of pranoprofen and a salt thereof, and (C) at least one selected from the group consisting of alcohol, water-soluble polymer, sugar, polyoxyethylene polyoxypropylene glycol, and polyethylene glycol fatty acid ester.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to an ophthalmic composition (or ophthalmic agent). [Background technology]

[0002] Epinastine hydrochloride is known as an antihistamine, and attempts are being made to use epinastine hydrochloride for ophthalmic purposes.

[0003] For example, Patent Document 1 (Japanese Patent No. 6134853) discloses an eye drop solution that contains only epinastine or a salt thereof at a concentration of more than 0.075% (w / v) as the active ingredient, and is substantially free of preservatives and ingredients with preservative properties. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Patent No. 6134853 (Claims, Examples) Summary of the Invention [Problem to be solved by the invention]

[0005] An object of the present invention is to provide a novel ophthalmic composition. [Means for solving the problem]

[0006] As described above, epinastine or a salt thereof is used as the sole active ingredient, and ophthalmic preparations in which epinastine or a salt thereof is combined with other active ingredients have not yet been developed.

[0007] Under these circumstances, the present inventors conducted extensive research to solve the above-mentioned problems, and as a result, discovered that a novel ophthalmic composition can be obtained by combining epinastine or a salt thereof with a specific active ingredient, that such ophthalmic compositions may cause precipitation or cloudiness, and that a specific ingredient can efficiently inhibit such precipitation. After further research, the present inventors completed the present invention.

[0008] That is, the present invention relates to the following inventions. [1] (A) one or more members selected from the group consisting of epinastine and salts thereof, (B) one or more members selected from the group consisting of pranoprofen and salts thereof, and (C) An ophthalmic composition comprising one or more members selected from the group consisting of alcohols, water-soluble polymers, sugars, polyoxyethylene polyoxypropylene glycols, and polyethylene glycol fatty acid esters. [2] The ophthalmic composition according to [1], wherein component (C) contains one or more selected from the group consisting of alkanols, alkane polyols, polyvinyl alcohols, polyethylene glycols, polyvinylpyrrolidones, oligosaccharides, polysaccharides, polyoxyethylene polyoxypropylene glycols, and polyoxyl stearates. [3] The ophthalmic composition according to [1] or [2], wherein the component (C) contains at least polyvinylpyrrolidone. [4] The ophthalmic composition according to any one of [1] to [3], which contains 0.005 to 0.5 w / v % of component (A). [5] The ophthalmic composition according to any one of [1] to [4], which contains 0.005 to 0.5 w / v % of component (B). [6] The ophthalmic composition according to any one of [1] to [5], wherein the proportion of the component (B) is 0.01 to 100 parts by mass per 1 part by mass of the component (A). [7] The ophthalmic composition according to any one of [1] to [6], which contains 0.001 to 20 w / v % of component (C). [8] The ophthalmic composition according to any one of [1] to [7], wherein the proportion of the (C) component is 0.005 parts by mass or more (e.g., 0.25 parts by mass or more) per part by mass of the (A) component, and 0.005 parts by mass or more (e.g., 0.25 parts by mass or more) per part by mass of the (B) component. [9] The ophthalmic composition according to any one of [1] to [8], which has a pH of 4 to 9.

[10] The component (C) comprises one or more selected from the group consisting of alkanols, alkane polyols, polyvinyl alcohols, polyethylene glycols, polyvinyl pyrrolidone, oligosaccharides, polysaccharides, polyoxyethylene polyoxypropylene glycols, and polyoxyl stearates, The proportion of component (A) is 0.01 to 0.1 w / v%, The proportion of component (B) is 0.01 to 0.1 w / v%, The proportion of component (C) is 0.01 to 10 w / v%, The proportion of the (B) component is 0.1 to 10 parts by mass per 1 part by mass of the (A) component, The ophthalmic composition according to any one of [1] to [9], which has a pH of 5 to 8.

[11] The ophthalmic composition according to any one of [1] to

[10] , which is free from precipitation.

[12] The ophthalmic composition according to any one of [1] to

[11] , which contains water in an amount of 90 mass % or more based on the total amount of the composition and is free from precipitation.

[13] (A) one or more members selected from the group consisting of epinastine and salts thereof, and A method for inhibiting precipitation in an ophthalmic composition containing (B) one or more members selected from the group consisting of pranoprofen and its salts, wherein the ophthalmic composition contains (C) one or more members selected from the group consisting of alcohols, water-soluble polymers, sugars, polyoxyethylene polyoxypropylene glycols, and polyethylene glycol fatty acid esters. [Effects of the Invention]

[0009] The present invention provides a novel ophthalmic composition. This ophthalmic composition contains pranoprofen and / or a salt thereof in addition to epinastine or a salt thereof, and is an ophthalmic composition of a novel combination type not found in conventional ophthalmic compositions.

[0010] In another aspect of the present invention, an ophthalmic composition capable of suppressing precipitation (cloudiness) can be provided. According to the investigations of the present inventors, precipitation may occur in a preparation containing a combination of epinastine and / or a salt thereof and pranoprofen and / or a salt thereof. However, the ophthalmic composition of the present invention, which contains a specific component selected from a wide variety of components in addition to these, can efficiently suppress such precipitation.

[0011] In another embodiment of the present invention, the precipitation suppression effect can be effectively exhibited even when other components (such as a pH adjuster or a buffer) are further contained or when a high proportion of water is contained.

[0012] In another embodiment of the present invention, the functions of specific components can be effectively exhibited without being impaired. For example, among the components (C), water-soluble polymers (polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, etc.) are also used as thickeners and dispersants, but even when the components (A) and (B) (and other components) are contained, they can effectively exhibit their functions as thickeners and dispersants.

[0013] Thus, the composition of the present invention is highly practical. DETAILED DESCRIPTION OF THE INVENTION

[0014] In this specification, the unit of content "w / v%" is synonymous with "g / 100 mL." Furthermore, in this specification, unless otherwise specified, the abbreviation "POE" means polyoxyethylene, and "POP" means polyoxypropylene.

[0015] [1. Ophthalmic composition] The ophthalmic composition of the present invention contains at least (A) epinastine and / or a salt thereof, and (B) pranoprofen or a salt thereof.

[0016] (A) Epinastine and / or its salt (Component (A)) Salts of epinastine are not particularly limited as long as they are pharmaceutically or physiologically acceptable, and examples thereof include organic acid salts [e.g., monocarboxylates (acetate, trifluoroacetate, butyrate, palmitate, stearate, etc.), polycarboxylates (fumarate, maleate, succinate, malonate, etc.), oxycarboxylates (lactate, tartrate, citrate, etc.), organic sulfonates (methanesulfonate, toluenesulfonate, tosylate, etc.)], inorganic acid salts (e.g., hydrochloride, sulfate, nitrate, hydrobromide, phosphate), etc.

[0017] Preferred epinastine and / or salts thereof include epinastine hydrochloride (monohydrochloride).

[0018] Epinastine and / or a salt thereof may be used alone or in combination of two or more kinds.

[0019] The content of component (A) in the composition may be, for example, about 0.0001 w / v% or more (e.g., 0.0003 to 5 w / v%), preferably 0.0005 w / v% or more (e.g., 0.001 to 1 w / v%), more preferably 0.003 w / v% or more (e.g., 0.005 to 0.5 w / v%), even more preferably 0.005 w / v% or more (e.g., 0.007 to 0.2 w / v%), still more preferably 0.008 w / v% or more (e.g., 0.01 to 0.1 w / v%), particularly preferably 0.02 w / v% or more (e.g., 0.03 to 0.1 w / v%), and most preferably 0.03 w / v% or more (e.g., 0.04 to 0.08 w / v%, 0.045 to 0.06 w / v%), relative to the total amount of the composition. Among these, 0.05 w / v %, 0.1 w / v %, etc. are preferred, with 0.05 w / v % being particularly preferred.

[0020] (B) Pranoprofen and / or its salt (ingredient (B)) The composition of the present invention contains pranoprofen and / or a salt thereof in addition to epinastine and / or a salt thereof. Even though the composition of the present invention contains multiple active ingredients, each of the active ingredients can efficiently exert its respective functions (pharmaceutical efficacy).

[0021] The salt of pranoprofen may be any pharmaceutically or physiologically acceptable salt, and examples thereof include salts with acids (e.g., salts with inorganic acids, salts with organic acids, and other salts exemplified in the section on component (A) above), as well as salts with bases {e.g., salts with organic bases (e.g., salts with organic amines such as methylamine, triethylamine, triethanolamine, morpholine, piperazine, pyrrolidine, tripyridine, picoline, etc.), salts with inorganic bases [e.g., ammonium salts; salts with alkali metals (sodium, potassium, etc.), alkaline earth metals (calcium, magnesium, etc.), aluminum, etc.], and the like}, such as sulfate, lactate, hydrochloride, chloride, sodium salt, and potassium salt. Preferred pranoprofen and / or salts thereof are pranoprofen and metal salts thereof, and pranoprofen is particularly preferred.

[0022] Pranoprofen and / or a salt thereof may be used alone or in combination of two or more kinds.

[0023] The content of component (B) in the composition may be, for example, about 0.0001 w / v% or more (e.g., 0.0003 to 5 w / v%), preferably 0.0005 w / v% or more (e.g., 0.001 to 1 w / v%), more preferably 0.003 w / v% or more (e.g., 0.005 to 0.5 w / v%), even more preferably 0.005 w / v% or more (e.g., 0.007 to 0.2 w / v%), still more preferably 0.008 w / v% or more (e.g., 0.01 to 0.1 w / v%), particularly preferably 0.02 w / v% or more (e.g., 0.03 to 0.1 w / v%), and most preferably 0.03 w / v% or more (e.g., 0.04 to 0.08 w / v%, 0.045 to 0.06 w / v%, etc.), relative to the total amount of the composition. Among these, 0.05 w / v %, 0.1 w / v %, etc. are preferred, with 0.05 w / v % being particularly preferred.

[0024] The proportion of the (B) component may be, for example, about 0.001 to 1000 parts by mass, preferably 0.005 to 200 parts by mass, more preferably 0.01 to 100 parts by mass, particularly preferably 0.05 to 20 parts by mass, and most preferably 0.1 to 10 parts by mass (e.g., 0.2 to 5 parts by mass, 0.3 to 3 parts by mass, 0.5 to 2 parts by mass, etc.), and particularly preferably 1 part by mass, per 1 part by mass of the (A) component.

[0025] (C) Specific component ((C) component) The composition of the present invention may contain a specific component (C). By combining components (A), (B) and (C), precipitation in the composition can be efficiently suppressed.

[0026] Examples of the component (C) include alcohols, water-soluble polymers, sugars, polyoxyethylene polyoxypropylene glycols, and polyethylene glycol fatty acid esters. Examples of alcohols include monools (e.g., alkanols (e.g., lower alkanols such as ethanol)), polyols (polyhydric alcohols) {e.g., diols (e.g., alkanediols (e.g., ethylene glycol, butanediol), polyalkanediols (e.g., diethylene glycol)), polyols having three or more hydroxyl groups (e.g., triols (e.g., alkanetriols such as glycerin), tetraols (e.g., alkanetetraols such as erythritol), pentaols (e.g., alkanepentaols such as xylitol), and hexaols (e.g., alkanehexaols such as mannitol and sorbitol)), and tri- to hexaols}, and aminoalcohols (e.g., alkanolamines (compounds having a hydroxyl group and an amino group in an alkane skeleton, e.g., mono- or poly(hydroxyalkyl)amines (e.g., diethanolamine, triethanolamine, triisopropanolamine), hydroxyalkylaminoalkanes (e.g., trometamol), and the like). The alcohol may be water-soluble (water-miscible).

[0027] Examples of the water-soluble polymer include water-soluble synthetic polymers {for example, hydroxy group-containing polymers (e.g., polyvinyl alcohol), acid group-containing polymers [for example, acrylic acid-based polymers (e.g., polyacrylic acid or a salt thereof, carboxyvinyl polymer), etc.], oxyalkylene group-containing polymers [for example, polyethylene glycols (e.g., macrogols such as macrogol 200, 400, 1500, 4000, 6000), etc.], lactam polymers [for example, polyvinylpyrrolidone (e.g., polyvinylpyrrolidone K25, K30, K90)], etc.}, and water-soluble cellulose derivatives (e.g., methyl cellulose, ethyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, sodium carboxymethyl cellulose, etc.).

[0028] The term "sugar (saccharides)" may be a concept that includes all of sugars or their derivatives and salts. Examples of sugars (saccharides) include monosaccharides (e.g., glucose), oligosaccharides {e.g., disaccharides (e.g., maltose, trehalose, sucrose), trisaccharides (e.g., maltotriose), fructooligosaccharides, galactooligosaccharides, maltooligosaccharides, isomaltooligosaccharides, cyclic oligosaccharides [e.g., cyclodextrins (e.g., α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin)], and the like}, amino sugars (e.g., glucosamine, galactosamine, etc.), polysaccharides (polysaccharides) [for example, glucose-derived polysaccharides (for example, dextran, dextrin, starch, etc.), mucopolysaccharides (for example, heparinoids, heparin, heparin sulfate, heparan sulfate, heparinoid, hyaluronic acid, hyaluronate (sodium salt, etc.), etc.), alginic acid, chondroitin, chondroitin sulfate, chitosan, chitin, derivatives thereof, etc.]. The sugar (such as a polysaccharide) may be water-soluble (water-miscible).

[0029] Examples of polyoxyethylene polyoxypropylene glycols include poloxamer 407, poloxamer 235, poloxamer 188, poloxamer 403, poloxamer 237, and poloxamer 124.

[0030] Examples of polyethylene glycol fatty acid esters include polyethylene glycol linear fatty acid esters such as polyoxyl stearate [or polyoxyethylene monostearate or polyethylene glycol stearate, for example, polyethylene glycol monostearate (2 E.O.), polyethylene glycol monostearate (4 E.O.), polyethylene glycol monostearate (9 E.O.), polyethylene glycol monostearate (10 E.O.), polyethylene glycol monostearate (23 E.O.), polyethylene glycol monostearate (25 E.O.), polyethylene glycol monostearate (32 E.O.), polyethylene glycol monostearate (40 E.O., polyoxyl 40 stearate), polyethylene glycol monostearate (45 E.O.), polyethylene glycol monostearate (55 E.O.), polyethylene glycol monostearate (75 E.O.), polyethylene glycol monostearate (140 E.O.)].

[0031] Of these components (C), alkanols (e.g., ethanol), alkane polyols (e.g., glycerin), polyvinyl alcohol, polyethylene glycol, polyvinylpyrrolidone, oligosaccharides (e.g., cyclodextrin), polysaccharides (e.g., glucose-derived polysaccharides), polyoxyethylene polyoxypropylene glycol, polyoxyl stearate, etc. are preferred, and polyvinylpyrrolidone is particularly preferred.

[0032] Therefore, the component (C) may contain at least these components.

[0033] Component (C) may be used alone or in combination of two or more types.

[0034] When the component (C) is combined, components of the same type (same classification) may be combined, or components of different types (different classifications) may be combined.

[0035] When component (C) is contained, the content of component (C) in the composition may be, for example, 0.001 w / v% or more (e.g., 0.001 to 20 w / v%), preferably 0.005 w / v% or more (e.g., 0.007 to 15 w / v%), more preferably 0.01 w / v% or more (e.g., 0.03 to 10 w / v%), and particularly preferably 0.05 w / v% or more (e.g., 0.1 to 5 w / v%), relative to the total amount of the composition.

[0036] When component (C) contains an alcohol, the content of the alcohol in the composition may be, for example, 0.01 w / v% or more (e.g., 0.01 to 15 w / v%), preferably 0.05 w / v% or more (e.g., 0.05 to 12.5 w / v%), more preferably 0.075 w / v% or more (e.g., 0.075 to 10 w / v%), and particularly preferably 0.1 w / v% or more (e.g., 0.1 to 8.0 w / v%), relative to the total amount of the composition.

[0037] When component (C) contains a water-soluble polymer, the content of the water-soluble polymer in the composition may be, for example, 0.01 w / v% or more (e.g., 0.01 to 10 w / v%), preferably 0.05 w / v% or more (e.g., 0.05 to 7.5 w / v%), more preferably 0.075 w / v% or more (e.g., 0.075 to 5.0 w / v%), and particularly preferably 0.1 w / v% or more (e.g., 0.1 to 3.0 w / v%), relative to the total amount of the composition.

[0038] When component (C) contains a sugar, the sugar content in the composition may be, for example, 0.01 w / v% or more (e.g., 0.01 to 3.0 w / v%), preferably 0.05 w / v% or more (e.g., 0.05 to 2.0 w / v%), more preferably 0.75 w / v% or more (e.g., 0.75 to 1.5 w / v%), and particularly preferably 0.1 w / v% or more (e.g., 0.1 to 1.0 w / v%), relative to the total amount of the composition.

[0039] When component (C) contains polyoxyethylene polyoxypropylene glycol, the content of polyoxyethylene polyoxypropylene glycol in the composition may be, for example, 0.01 w / v% or more (e.g., 0.03 to 20 w / v%), preferably 0.05 w / v% or more (e.g., 0.05 to 15 w / v%), more preferably 0.075 w / v% or more (e.g., 0.075 to 12 w / v%), and particularly preferably 0.1 w / v% or more (e.g., 0.2 to 10 w / v%), or may be 0.5 w / v% or more (e.g., 0.7 w / v% or more, 0.8 w / v% or more, 0.9 w / v% or more, 1 w / v% or more, 5 w / v% or more, 1 to 10 w / v%, etc.) relative to the total amount of the composition.

[0040] When component (C) contains a polyethylene glycol fatty acid ester, the content of the polyethylene glycol fatty acid ester in the composition may be, for example, 0.01 w / v% or more (e.g., 0.03 to 20 w / v%), preferably 0.05 w / v% or more (e.g., 0.05 to 15 w / v%), more preferably 0.075 w / v% or more (e.g., 0.075 to 12 w / v%), and particularly preferably 0.1 w / v% or more (e.g., 0.2 to 10 w / v%), or may be 0.5 w / v% or more (e.g., 0.7 w / v% or more, 0.8 w / v% or more, 0.9 w / v% or more, 1 w / v% or more, 5 w / v% or more, 1 to 10 w / v%, etc.) relative to the total amount of the composition.

[0041] When component (C) is contained, the proportion of component (C) relative to 1 part by mass of component (A) may be, for example, 0.005 part by mass or more (e.g., 0.0075 part by mass or more, 0.01 part by mass or more, 0.02 part by mass or more, 0.03 part by mass or more, etc.), or may be about 0.25 part by mass or more (e.g., 0.25 to 200 parts by mass), preferably 0.5 part by mass or more (e.g., 0.5 to 175 parts by mass), more preferably 0.75 part by mass or more (e.g., 0.75 to 150 parts by mass), particularly preferably 1.0 part by mass or more (e.g., 1.0 to 125 parts by mass), and most preferably 1.5 parts by mass or more (e.g., 1.5 to 100 parts by mass).

[0042] When component (C) contains an alcohol, the proportion of the alcohol may be, per 1 part by mass of component (A), for example, 1.0 part by mass or more (e.g., 1.0 to 200 parts by mass), preferably 1.5 parts by mass or more (e.g., 1.5 to 150 parts by mass), more preferably 1.75 parts by mass or more (e.g., 1.75 to 120 parts by mass), particularly preferably 2.0 parts by mass or more (e.g., 2.0 to 100 parts by mass), and most preferably 2.25 parts by mass or more (e.g., 2.25 to 80 parts by mass).

[0043] When component (C) contains a water-soluble polymer, the proportion of the water-soluble polymer may be, per 1 part by mass of component (A), for example, 0.25 parts by mass or more (e.g., 0.25 to 200 parts by mass), preferably 0.5 parts by mass or more (e.g., 0.5 to 175 parts by mass), more preferably 0.75 parts by mass or more (e.g., 0.75 to 150 parts by mass), particularly preferably 1.0 parts by mass or more (e.g., 1.0 to 125 parts by mass), and most preferably 1.5 parts by mass or more (e.g., 1.5 to 100 parts by mass).

[0044] When component (C) contains sugar, the proportion of sugar may be, for example, about 0.5 parts by mass or more (e.g., 0.5 to 150 parts by mass), preferably 0.75 parts by mass or more (e.g., 0.75 to 125 parts by mass), more preferably 1.0 parts by mass or more (e.g., 1.0 to 100 parts by mass), particularly preferably 1.25 parts by mass or more (e.g., 1.25 to 75 parts by mass), and most preferably 1.5 parts by mass or more (e.g., 1.5 to 50 parts by mass) per part by mass of component (A).

[0045] When component (C) contains polyoxyethylene polyoxypropylene glycol, the proportion of polyoxyethylene polyoxypropylene glycol may be, for example, 0.2 parts by mass or more (e.g., 0.6 to 400 parts by mass), preferably 1 part by mass or more (e.g., 1 to 300 parts by mass), more preferably 1.5 parts by mass or more (e.g., 1.5 to 240 parts by mass), and particularly preferably 2 parts by mass or more (e.g., 4 to 200 parts by mass), or may be about 10 parts by mass or more (e.g., 14 parts by mass or more, 16 parts by mass or more, 18 parts by mass or more, 20 parts by mass or more, 100 parts by mass or more, 20 to 200 parts by mass, etc.), per part by mass of component (A).

[0046] When component (C) contains a polyethylene glycol fatty acid ester, the proportion of the polyethylene glycol fatty acid ester may be, per 1 part by mass of component (A), for example, 0.2 parts by mass or more (e.g., 0.6 to 400 parts by mass), preferably 1 part by mass or more (e.g., 1 to 300 parts by mass), more preferably 1.5 parts by mass or more (e.g., 1.5 to 240 parts by mass), and particularly preferably 2 parts by mass or more (e.g., 4 to 200 parts by mass), or may be about 10 parts by mass or more (e.g., 14 parts by mass or more, 16 parts by mass or more, 18 parts by mass or more, 20 parts by mass or more, 100 parts by mass or more, 20 to 200 parts by mass, etc.).

[0047] When component (C) is contained, the proportion of component (C) relative to 1 part by mass of component (B) may be, for example, 0.005 parts by mass or more (e.g., 0.0075 parts by mass or more, 0.01 parts by mass or more, 0.02 parts by mass or more, 0.03 parts by mass or more, etc.), or may be about 0.25 parts by mass or more (e.g., 0.25 to 200 parts by mass), preferably 0.5 parts by mass or more (e.g., 0.5 to 175 parts by mass), more preferably 0.75 parts by mass or more (e.g., 0.75 to 150 parts by mass), particularly preferably 1.0 part by mass or more (e.g., 1.0 to 125 parts by mass), and most preferably 1.5 parts by mass or more (e.g., 1.5 to 100 parts by mass).

[0048] When component (C) contains an alcohol, the proportion of the alcohol may be, per 1 part by mass of component (B), for example, 1.0 part by mass or more (e.g., 1.0 to 200 parts by mass), preferably 1.5 parts by mass or more (e.g., 1.5 to 150 parts by mass), more preferably 1.75 parts by mass or more (e.g., 1.75 to 120 parts by mass), particularly preferably 2.0 parts by mass or more (e.g., 2.0 to 100 parts by mass), and most preferably 2.25 parts by mass or more (e.g., 2.25 to 80 parts by mass).

[0049] When component (C) contains a water-soluble polymer, the proportion of the water-soluble polymer may be, for example, about 0.25 parts by mass or more (e.g., 0.25 to 200 parts by mass), preferably 0.5 parts by mass or more (e.g., 0.5 to 175 parts by mass), more preferably 0.75 parts by mass or more (e.g., 0.75 to 150 parts by mass), particularly preferably 1.0 parts by mass or more (e.g., 1.0 to 125 parts by mass), and most preferably about 1.5 parts by mass or more (e.g., 1.5 to 100 parts by mass) per part by mass of component (B).

[0050] When component (C) contains sugar, the proportion of sugar may be, for example, about 0.5 parts by mass or more (e.g., 0.5 to 150 parts by mass), preferably 0.75 parts by mass or more (e.g., 0.75 to 125 parts by mass), more preferably 1.0 parts by mass or more (e.g., 1.0 to 100 parts by mass), particularly preferably 1.25 parts by mass or more (e.g., 1.25 to 75 parts by mass), and most preferably 1.5 parts by mass or more (e.g., 1.5 to 50 parts by mass) per part by mass of component (B).

[0051] When component (C) contains polyoxyethylene polyoxypropylene glycol, the proportion of polyoxyethylene polyoxypropylene glycol may be, for example, 0.2 parts by mass or more (e.g., 0.6 to 400 parts by mass), preferably 1 part by mass or more (e.g., 1 to 300 parts by mass), more preferably 1.5 parts by mass or more (e.g., 1.5 to 240 parts by mass), and particularly preferably 2 parts by mass or more (e.g., 4 to 200 parts by mass), or may be about 10 parts by mass or more (e.g., 14 parts by mass or more, 16 parts by mass or more, 18 parts by mass or more, 20 parts by mass or more, 100 parts by mass or more, 20 to 200 parts by mass, etc.) per part by mass of component (B).

[0052] When component (C) contains a polyethylene glycol fatty acid ester, the proportion of the polyethylene glycol fatty acid ester may be, for example, 0.2 parts by mass or more (e.g., 0.6 to 400 parts by mass), preferably 1 part by mass or more (e.g., 1 to 300 parts by mass), more preferably 1.5 parts by mass or more (e.g., 1.5 to 240 parts by mass), and particularly preferably 2 parts by mass or more (e.g., 4 to 200 parts by mass), or may be about 10 parts by mass or more (e.g., 14 parts by mass or more, 16 parts by mass or more, 18 parts by mass or more, 20 parts by mass or more, 100 parts by mass or more, 20 to 200 parts by mass, etc.), per part by mass of component (B).

[0053] When component (C) is contained, the proportion of component (C) per part by mass of the total amount of components (A) and (B) may be, for example, about 0.005 parts by mass or more (e.g., 0.0075 parts by mass or more, 0.01 parts by mass or more, 0.02 parts by mass or more, 0.04 parts by mass or more), or about 0.5 parts by mass or more (e.g., 0.5 to 400 parts by mass), preferably 1.0 parts by mass or more (e.g., 1.0 to 350 parts by mass), more preferably 1.5 parts by mass or more (e.g., 1.5 to 300 parts by mass), particularly preferably 1.25 parts by mass or more (e.g., 1.25 to 200 parts by mass), and most preferably about 2.0 parts by mass or more (e.g., 2.0 to 200 parts by mass).

[0054] When component (C) contains an alcohol, the proportion of the alcohol may be, per part by mass of the total amount of components (A) and (B), for example, 2.0 parts by mass or more (e.g., 2.0 to 400 parts by mass), preferably 3.0 parts by mass or more (e.g., 3.0 to 300 parts by mass), more preferably 3.5 parts by mass or more (e.g., 3.5 to 240 parts by mass), particularly preferably 4.0 parts by mass or more (e.g., 4.0 to 200 parts by mass), and most preferably 4.5 parts by mass or more (e.g., 4.5 to 160 parts by mass).

[0055] When component (C) contains a water-soluble polymer, the proportion of the water-soluble polymer may be, per 1 part by mass of components (A) and (B), for example, 0.5 parts by mass or more (e.g., 0.5 to 400 parts by mass), preferably 1.0 parts by mass or more (e.g., 1.0 to 350 parts by mass), more preferably 1.5 parts by mass or more (e.g., 1.5 to 300 parts by mass), particularly preferably 2.0 parts by mass or more (e.g., 2.0 to 250 parts by mass), and most preferably about 3.0 parts by mass or more (e.g., 3.0 to 200 parts by mass).

[0056] When component (C) contains a sugar, the proportion of the sugar may be, for example, 1.0 part by mass or more (e.g., 1.0 to 300 parts by mass), preferably 1.5 parts by mass or more (e.g., 1.5 to 250 parts by mass), more preferably 2.0 parts by mass or more (e.g., 2.0 to 200 parts by mass), particularly preferably 2.5 parts by mass or more (e.g., 2.5 to 150 parts by mass), and most preferably about 3.0 parts by mass or more (e.g., 3.0 to 100 parts by mass) per part by mass of the total amount of components (A) and (B).

[0057] When component (C) contains polyoxyethylene polyoxypropylene glycol, the proportion of polyoxyethylene polyoxypropylene glycol per 1 part by mass of the total amount of components (A) and (B) may be, for example, 0.1 parts by mass or more (e.g., 0.3 to 200 parts by mass), preferably 0.5 parts by mass or more (e.g., 0.5 to 150 parts by mass), more preferably 0.75 parts by mass or more (e.g., 0.75 to 120 parts by mass), and particularly preferably 1 part by mass or more (e.g., 2 to 100 parts by mass), or may be about 5 parts by mass or more (e.g., 7 parts by mass or more, 8 parts by mass or more, 9 parts by mass or more, 10 parts by mass or more, 50 parts by mass or more, 10 to 100 parts by mass, etc.).

[0058] When component (C) contains a polyethylene glycol fatty acid ester, the proportion of the polyethylene glycol fatty acid ester, relative to 1 part by mass of the total amount of components (A) and (B), may be, for example, 0.1 parts by mass or more (e.g., 0.3 to 200 parts by mass), preferably 0.5 parts by mass or more (e.g., 0.5 to 150 parts by mass), more preferably 0.75 parts by mass or more (e.g., 0.75 to 120 parts by mass), and particularly preferably 1 part by mass or more (e.g., 2 to 100 parts by mass), or may be about 5 parts by mass or more (e.g., 7 parts by mass or more, 8 parts by mass or more, 9 parts by mass or more, 10 parts by mass or more, 50 parts by mass or more, 10 to 100 parts by mass, etc.).

[0059] By setting the ratio as described above, precipitation can be efficiently suppressed.

[0060] [Other ingredients] The composition of the present invention may further contain other components. In the present invention, even if other components are contained, the effects of the present invention can often be ensured. In addition, by containing other components, the effects of the present invention can sometimes be realized more effectively.

[0061] The other component may be one corresponding to the above component (C).

[0062] Amino acids The composition of the present invention may contain amino acids. The amino acid includes, for example, an amino acid or a salt thereof, and an amino acid analogue, and also includes a compound having an amino group and a carboxyl group or a sulfone group in the molecule, or a derivative thereof.

[0063] Specific examples include amino acids or salts thereof, and mucopolysaccharides or salts thereof. Among amino acids, examples of amino acids or salts thereof include monoaminomonocarboxylic acids such as glycine, alanine, aminobutyric acid, aminovaleric acid, and aminocaproic acid; monoaminodicarboxylic acids such as aspartic acid and glutamic acid or salts thereof; diaminomonocarboxylic acids such as arginine and lysine or salts thereof; and derivatives of aminoethylsulfonic acid (taurine) and salts thereof.

[0064] Among amino acids, mucopolysaccharides or derivatives or salts thereof include, for example, acidic mucopolysaccharides such as derivatives of chondroitin sulfate, hyaluronic acid, alginic acid, etc., or salts thereof.

[0065] Specific amino acids and mucopolysaccharides include glycine, alanine, γ-aminobutyric acid, γ-aminovaleric acid, epsilon aminocaproic acid, aspartic acid, glutamic acid, arginine, aminoethylsulfonic acid, chondroitin sulfate, hyaluronic acid, alginic acid, and salts thereof.

[0066] Chondroitin sulfate is a sugar chain in which D-glucuronic acid and N-acetylglucosamine are repeated, with sulfate ester bonds to some or all of the hydroxyl groups. The position and number of sulfate bonds vary, and chondroitin sulfate also has derivatives (e.g., those in which all or some of the N-acetylglucosamines are replaced with iduronic acid). Such chondroitin sulfate may have any structure. Examples include chondroitin 4-sulfate (chondroitin sulfate A), chondroitin 6-sulfate (chondroitin sulfate C), and chondroitin sulfate E in which the 4- and 6-positions of N-acetylglucosamine are sulfated. Chondroitin sulfate may also be extracted from animals.

[0067] The salts of amino acids or salts of mucopolysaccharides include pharmaceutically, pharmacologically or physiologically acceptable salts. Examples of such salts include salts with organic acids [for example, monocarboxylates (acetate, trifluoroacetate, butyrate, palmitate, stearate, etc.), polycarboxylates (fumarate, maleate, etc.), oxycarboxylates (lactate, tartrate, citrate, succinate, malonate, etc.), organic sulfonates (methanesulfonate, toluenesulfonate, tosylate, etc.)], salts with inorganic acids (for example, hydrochloride, sulfate, nitrate, hydrobromide, phosphate), salts with organic bases (for example, salts with organic amines such as methylamine, triethylamine, triethanolamine, morpholine, piperazine, pyrrolidine, tripyridine, picoline, etc.), salts with inorganic bases [for example, ammonium salts; salts with metals such as alkali metals (sodium, potassium, etc.), alkaline earth metals (calcium, magnesium, etc.), aluminum, etc.], and the like, and the salts are appropriately selected depending on the compound.

[0068] Specific salts include salts of aspartic acid (sodium aspartate, potassium aspartate, magnesium aspartate, magnesium-potassium aspartate mixture, etc.), salts of glutamic acid (sodium glutamate, magnesium glutamate, etc.), sodium chondroitin sulfate, sodium hyaluronate, etc.

[0069] The amino acids may be in the D-, L- or DL-form.

[0070] Preferred amino acids include aminoethylsulfonic acid (taurine) or its salts, sodium chondroitin sulfate, aspartates (e.g., potassium L-aspartate, magnesium potassium L-aspartate), epsilon-aminocaproic acid or its salts, hyaluronic acid or its salts (such as sodium hyaluronate), and the like. Among these, hyaluronic acid or its salts (such as sodium hyaluronate), aminoethylsulfonic acid (taurine) and / or its salts, and sodium chondroitin sulfate are preferred.

[0071] The amino acids may be used alone or in combination of two or more kinds.

[0072] When the composition contains amino acids, the content of the amino acids in the composition may be, for example, 0.001 w / v% or more, preferably 0.01 to 20 w / v%, more preferably 0.03 to 10 w / v%, even more preferably 0.05 to 5 w / v%, even more preferably 0.1 to 3 w / v%, and particularly preferably about 0.15 to 2 w / v%, and may usually be 0.001 to 10 w / v% [e.g., 0.005 to 10 w / v%, preferably 0.01 to 5 w / v%, and even more preferably 0.05 to 3 w / v% (e.g., 0.1 to 1 w / v%)] relative to the total amount of the composition.

[0073] Cooling agent The compositions of the present invention may also include a cooling agent. The combination of components (A), (B), and (C) may reduce or impair the feel when used, but the use of a freshener can improve or enhance this feel when used. For example, while increasing the pH of the composition may be advantageous in terms of solubility, the higher the pH of the composition, the more unpleasant the feeling when used and the worse the feel when used. However, the use of a freshener can alleviate this unpleasant feeling and efficiently improve the feel when used.

[0074] The cooling agent is not particularly limited, but examples thereof include terpenoids such as menthol, anethole, eugenol, camphor, geraniol, cineole, borneol, limonene, and rhubarb. These may be in the d-, l-, or dl-isomer. Other examples include essential oils such as peppermint oil, cool mint oil, spearmint oil, peppermint oil, fennel oil, cinnamon oil, bergamot oil, eucalyptus oil, and rose oil.

[0075] Of these, terpenoids are preferred, and among these, menthol, camphor, geraniol, cineol, borneol, and rhododendron are preferred, with menthol, camphor, and borneol being more preferred, menthol and borneol being even more preferred, and menthol being most preferred.

[0076] The cooling agent may be used alone or in combination of two or more. In particular, the cooling agent preferably contains one or more selected from the group consisting of menthol, borneol, and camphor, and when two or more types are combined, it is preferable to combine at least these (for example, a combination of menthol, borneol, and camphor).

[0077] When the composition contains a cooling agent, the proportion of the cooling agent may be, for example, 0.00001 w / v% or more, 0.00005 w / v% or more, 0.0001 w / v% or more, 0.0003 w / v% or more, 0.0005 w / v% or more, 0.0007 w / v% or more, 0.0008 w / v% or more, 0.0009 w / v% or more, or 0.001 w / v% or more relative to the total amount of the composition.

[0078] The proportion of the cooling agent may be 5 w / v% or less, 3 w / v% or less, 2 w / v% or less, 1.5 w / v% or less, 1.2 w / v% or less, 1 w / v% or less, 0.9 w / v% or less, 0.8 w / v% or less, 0.7 w / v% or less, or 0.6 w / v% or less relative to the total amount of the composition.

[0079] In particular, when the composition of the present invention contains menthol, the proportion of menthol may be, for example, about 0.00001 w / v% or more (e.g., 0.00005 to 2 w / v%), preferably about 0.0001 to 0.2 w / v% (e.g., 0.0003 to 0.1 w / v%), and more preferably about 0.0005 to 0.05 w / v% (e.g., 0.001 to 0.02 w / v%) relative to the total amount of the composition.

[0080] In particular, when the composition of the present invention contains borneol, the proportion of borneol may be, for example, 0.00001 w / v% or more (e.g., 0.00005 to 3 w / v%), preferably 0.0001 to 2 w / v% (e.g., 0.0003 to 1 w / v%), and more preferably about 0.0005 to 0.8 w / v% (e.g., 0.001 to 0.5 w / v%) relative to the total amount of the composition.

[0081] In particular, when the composition of the present invention contains camphor, the proportion of camphor may be, for example, 0.00001 w / v% or more (e.g., 0.00005 to 1 w / v%), preferably 0.0001 to 0.1 w / v% (e.g., 0.0003 to 0.05 w / v%), and more preferably about 0.0005 to 0.02 w / v% (e.g., 0.001 to 0.01 w / v%) relative to the total amount of the composition.

[0082] Fat-soluble antioxidants The compositions of the present invention may also contain a fat-soluble antioxidant.

[0083] Examples of fat-soluble antioxidants include butyl-containing phenols such as dibutylhydroxytoluene (BHT) and butylhydroxyanisole (BHA); nordihydroguaiaretic acid (NDGA); ascorbic acid esters such as ascorbyl palmitate, ascorbyl stearate, aminopropyl ascorbyl phosphate, tocopherol ascorbyl phosphate, ascorbyl triphosphate, and ascorbyl phosphate palmitate; gallic acid esters such as ethyl gallate, propyl gallate, octyl gallate, and dodecyl gallate; propyl gallate; 3-butyl-4-hydroxyquinolin-2-one; carotenoids such as lutein and astaxanthin; polyphenols such as anthocyanins, catechin, tannin, and curcumin; and CoQ10.

[0084] Of these, dibutylhydroxytoluene is preferred.

[0085] The fat-soluble antioxidants may be used alone or in combination of two or more kinds.

[0086] When the composition contains a fat-soluble antioxidant, the content of the fat-soluble antioxidant in the composition may be, for example, about 0.0001 to 0.1 w / v%, preferably 0.0005 to 0.01 w / v%, more preferably 0.0007 to 0.009 w / v%, even more preferably 0.001 to 0.008 w / v%, still more preferably 0.003 to 0.007 w / v%, and most preferably 0.0045 to 0.006 w / v%, relative to the total amount of the composition.

[0087] anti-allergy drugs The composition of the present invention may also contain an anti-allergic agent.

[0088] Examples of antiallergic agents include tranilast, cromoglycate, ibudilast, azanolast, tazanolast, suplatast, pemirolast, amlexanox, oxatomide, and salts thereof.

[0089] Examples of the salts include the salts exemplified above, such as alkali metal or alkaline earth metal salts (sodium cromoglycate, potassium cromoglycate, magnesium cromoglycate, calcium cromoglycate, etc.), inorganic acid salts (e.g., hydrochloride, sulfate, etc.), and organic acid salts (e.g., tosylate, fumarate, etc.).

[0090] Of these, tranilast, cromoglycic acid and salts thereof are preferred, and tranilast and sodium cromoglycate are more preferred.

[0091] The antiallergic agents may be used alone or in combination of two or more.

[0092] When the composition contains an antiallergic agent, the content of the antiallergic agent in the composition may be, for example, about 0.1 to 10 w / v%, preferably 0.2 to 8 w / v%, more preferably 0.3 to 5 w / v%, even more preferably 0.5 to 3 w / v%, particularly preferably 0.7 to 2 w / v%, even more particularly preferably 0.8 to 1.5 w / v%, and most preferably 0.9 to 1.2 w / v%, relative to the total amount of the composition.

[0093] antihistamines The compositions of the present invention may also include an antihistamine. The antihistamine (antihistamine other than epinastine and its salts) is not particularly limited as long as it is a substance having antihistamine action, and examples thereof include chlorpheniramine, diphenhydramine, ketotifen, olopatadine, levocabastine, iproheptine, and salts thereof.

[0094] The salt may be any pharmaceutically or physiologically acceptable salt, for example, an inorganic acid salt (e.g., hydrochloride, sulfate, etc.), an organic acid salt (e.g., tosylate, fumarate, etc.),

[0095] Specific salts include, for example, diphenhydramine hydrochloride, iproheptine hydrochloride, chlorpheniramine maleate, and the like.

[0096] Antihistamines may be used alone or in combination of two or more.

[0097] When the composition contains an antihistamine, the content of the antihistamine in the composition may be, for example, 0.0001 w / v% or more, preferably 0.001 to 10 w / v%, more preferably 0.003 to 5 w / v%, even more preferably 0.005 to 1 w / v%, still more preferably 0.01 to 0.5 w / v%, particularly preferably 0.015 to 0.3 w / v% (e.g., 0.02 to 0.1 w / v%), and most preferably about 0.025 to 0.05 w / v% (e.g., 0.03 w / v%), and typically about 0.01 to 0.05 w / v%, relative to the total amount of the composition.

[0098] anti-inflammatory agents The compositions of the present invention may also include an anti-inflammatory agent. The anti-inflammatory agent (anti-inflammatory agent other than pranoprofen and its salts) is not particularly limited as long as it is a substance having anti-inflammatory activity, and examples thereof include indomethacin, allantoin, berberine, azulene sulfonic acid, diclofenac, bromfenac, glycyrrhizinic acid, zinc, silver, tranexamic acid, lysozyme, and salts thereof.

[0099] Examples of the salt include the above-mentioned exemplified salts such as salts with inorganic acids, salts with organic acids, salts with inorganic bases, and salts with organic bases, and examples thereof include sulfate salts, lactate salts, hydrochloride salts, chloride salts, sodium salts, and potassium salts.

[0100] Specific salts include berberine sulfate, berberine chloride, dipotassium glycyrrhizinate, sodium azulene sulfonate, diclofenac sodium, bromfenac sodium, zinc sulfate, zinc lactate, silver nitrate, and lysozyme chloride.

[0101] The anti-inflammatory agents may be used alone or in combination of two or more.

[0102] When the composition contains an anti-inflammatory agent, the content of the anti-inflammatory agent in the composition may be, for example, about 0.001 w / v% or more (e.g., 0.02 w / v%), preferably 0.005 to 10 w / v% (e.g., 5 w / v%), more preferably 0.01 to 1 w / v%, even more preferably 0.1 to 0.5 w / v% (e.g., 0.3 w / v%), and particularly preferably about 0.2 to 0.3 w / v% (e.g., 0.25 w / v%), relative to the total amount of the composition.

[0103] The composition of the present invention may contain various ingredients (for example, ingredients that do not belong to the categories of ingredients described above). Examples of such ingredients (additives) include surfactants, preservatives, buffers, pH adjusters, isotonicity agents, thickeners or viscosifiers, stabilizers, oils, sugars, polymeric compounds, polyhydric alcohols, inorganic salts, and fat-insoluble antioxidants (or water-soluble antioxidants).

[0104] The additives may be used alone or in combination of two or more thereof. In addition, each additive may be used alone or in combination of two or more thereof.

[0105] Specific examples of the additives are given below.

[0106] surfactants The composition of the present invention may contain a surfactant, such as a nonionic surfactant.

[0107] Nonionic surfactants include polysorbates (POE sorbitan fatty acid esters) such as POE (20) sorbitan monolaurate (polysorbate 20), POE (20) sorbitan monopalmitate (polysorbate 40), POE (20) sorbitan monostearate (polysorbate 60), POE (20) sorbitan tristearate (polysorbate 65), and POE (20) sorbitan monooleate (polysorbate 80); POE hydrogenated castor oil 40, POE hydrogenated castor oil 50, POE hydrogenated castor oil 60, and POE hydrogenated castor oil 80. Examples of suitable POE castor oils include POE hydrogenated castor oil, POE castor oil 3, POE castor oil 4, POE castor oil 6, POE castor oil 7, POE castor oil 10, POE castor oil 13.5, POE castor oil 17, POE castor oil 20, POE castor oil 25, POE castor oil 30, POE castor oil 35, and POE castor oil 50; POE alkyl ethers such as POE(9) lauryl ether; POE-POP alkyl ethers such as POE(20)POP(4) cetyl ether; and POE alkylphenyl ethers such as POE(10) nonylphenyl ether. In the compounds exemplified above, POE stands for polyoxyethylene, POP stands for polyoxypropylene, and the numbers in parentheses indicate the number of moles added.

[0108] Among these, POE sorbitan fatty acid esters; POE·POP glycols; POE hydrogenated castor oil; and POE castor oil are preferred, with Polysorbate 80, POE hydrogenated castor oil 40, POE hydrogenated castor oil 60, POE castor oil 3, POE castor oil 10, POE castor oil 35, and polyoxyl stearate 40 being more preferred, Polysorbate 80 and POE hydrogenated castor oil 60 being even more preferred, and Polysorbate 80 being particularly preferred.

[0109] The surfactants may be used alone or in combination of two or more.

[0110] When the composition of the present invention contains a surfactant (particularly, a nonionic surfactant), the proportion of the surfactant may be, for example, 0.001 w / v% or more, preferably 0.005 w / v% or more, more preferably 0.01 w / v% or more, and particularly preferably 0.05 w / v% or more, relative to the total amount of the composition.

[0111] The proportion of the surfactant may be, for example, 5 w / v % or less, preferably 1 w / v % or less, based on the total amount of the composition.

[0112] preservatives The compositions of the present invention may also contain a preservative. Examples of preservatives include polydronium chloride, alkylpolyaminoethylglycines (e.g., alkyldiaminoethylglycine hydrochloride), sodium benzoate, ethanol, quaternary ammonium salts (e.g., benzalkonium chloride, benzethonium chloride), chlorhexidine gluconate, chlorobutanol, sorbic acid, potassium sorbate, sodium dehydroacetate, parahydroxybenzoic acid esters (e.g., methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, butyl parahydroxybenzoate), oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, biguanide compounds (e.g., polyhexanide hydrochloride), and Gloquil (manufactured by Rhodia).

[0113] Among these, alkyl polyaminoethyl glycines (e.g., alkyl diaminoethyl glycine hydrochloride), sodium benzoate, ethanol, quaternary ammonium salts, chlorhexidine gluconate, chlorobutanol, sorbic acid, potassium sorbate, parahydroxybenzoic acid esters, and biguanide compounds are preferred, with quaternary ammonium salts, chlorhexidine gluconate, chlorobutanol, and biguanide compounds being more preferred, and benzalkonium chloride and polyhexanide hydrochloride being even more preferred.

[0114] When the composition contains a preservative, the proportion of the preservative in the composition may be, for example, 0.000001 w / v% or more, preferably 0.00001 w / v% or more, preferably 0.00005 w / v% or more, preferably 0.001 w / v% or more, preferably 0.005 w / v% or more, based on the total amount of the composition. The total amount of the preservative may be 1 w / v% or less, preferably 0.1 w / v% or less, preferably 0.05 w / v% or less, preferably 0.03 w / v% or less, preferably 0.025 w / v% or less, based on the total amount of the composition.

[0115] buffer The compositions of the present invention may also contain a buffering agent. Examples of the buffer include borate buffer, phosphate buffer, carbonate buffer, citrate buffer, acetate buffer, and the like.

[0116] Components of the borate buffer include boric acid, borate salts (sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, borax, etc.), etc. The borate salts may be hydrated.

[0117] Components of phosphate buffers include phosphoric acid and phosphate salts (disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, trisodium phosphate, dipotassium phosphate, calcium monohydrogen phosphate, calcium dihydrogen phosphate, etc.). The phosphate salts may be hydrates.

[0118] Components of carbonate buffers include carbonic acid, carbonates (potassium carbonate, sodium carbonate, calcium carbonate, potassium bicarbonate, sodium bicarbonate, magnesium carbonate, etc.), etc. The carbonates may be hydrated.

[0119] Components of citrate buffers include citric acid, citrate salts (sodium citrate, potassium citrate, calcium citrate, sodium dihydrogen citrate, disodium citrate, etc.), etc. Citrate salts may be hydrates.

[0120] Components of acetate buffers include acetic acid, acetate salts (ammonium acetate, potassium acetate, calcium acetate, sodium acetate, etc.), etc. Acetate salts may be hydrates.

[0121] Among these, boric acid buffers are preferred from the viewpoint of preservative effectiveness, etc., and phosphate buffers are more preferred from the viewpoint of low cytotoxicity, etc., with boric acid buffers being more preferred. As the boric acid buffer, a combination of boric acid and its salts is preferred, a combination of boric acid and an alkali metal salt and / or an alkaline earth metal salt of boric acid is more preferred, a combination of boric acid and an alkali metal salt of boric acid is even more preferred, and a combination of boric acid and borax is even more preferred.

[0122] When a buffer is added to the composition of the present invention, the amount of buffer added varies depending on the type of buffer and the types and amounts of other ingredients, and cannot be uniformly defined, but examples thereof include a total amount of buffer of 0.001 w / v% or more, preferably 0.01 w / v% or more, preferably 0.05 w / v% or more, and preferably 0.1 w / v% or more relative to the total amount of the composition. Also, the total amount of buffer of 10 w / v% or less, preferably 5 w / v% or less, preferably 3 w / v% or less, preferably 2.5 w / v% or less, and preferably 2 w / v% or less relative to the total amount of the composition.

[0123] In particular, when a boric acid buffer is used, the proportion of the buffer in the composition may be about 0.01 to 10 w / v%, preferably 0.05 to 5 w / v%, more preferably 0.1 to 4 w / v%, and even more preferably 0.2 to 3 w / v%, based on the total composition.

[0124] pH adjuster Examples of pH adjusters include hydrochloric acid, sulfuric acid, polyphosphoric acid, organic acids (propionic acid, oxalic acid, gluconic acid, fumaric acid, lactic acid, tartaric acid, malic acid, succinic acid, etc.), sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, triethanolamine, monoethanolamine, and diisopropanolamine. The pH adjusters may be used alone or in combination of two or more.

[0125] Isotonic agent Examples of isotonic agents include sodium chloride, potassium chloride, calcium chloride, magnesium chloride, potassium acetate, sodium acetate, magnesium sulfate, glycerin, and propylene glycol. The isotonicity agents may be used alone or in combination of two or more kinds.

[0126] Thickeners or thickeners The ophthalmic compositions of the present invention may include a viscosity increasing or thickening agent.

[0127] Examples of thickening agents or viscosifying agents include guar gum, hydroxypropyl guar gum, cellulose-based polymer compounds (e.g., methylcellulose, ethylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, sodium carboxymethylcellulose, etc.), gum arabic, karaya gum, xanthan gum, agar, alginic acid, α-cyclodextrin, dextrin, dextran, mucopolysaccharides (e.g., heparinoids, heparin, heparin, heparin sulfate, heparan sulfate, heparinoid, hyaluronic acid, hyaluronate (sodium salt, etc.), etc.), starch, chitin and derivatives thereof, chitosan and derivatives thereof, carrageenan, sorbitol ... Examples of suitable acrylic acid surfactants include tallow, polyvinyl polymer compounds (such as polyvinylpyrrolidone, polyvinyl alcohol, and carboxyvinyl polymers), alkali metal salts of polyacrylic acid (such as sodium and potassium salts), amine salts of polyacrylic acid (such as monoethanolamine salts, diethanolamine salts, and triethanolamine salts), casein, gelatin, collagen, pectin, elastin, ceramide, liquid paraffin, glycerin, polyethylene glycol, macrogol, polyethyleneimine alginate (such as sodium salts), alginate esters (such as propylene glycol esters), powdered tragacanth, and triisopropanolamine. The thickening or viscosifying agents may be used alone or in combination of two or more.

[0128] stabilizers Stabilizers include, for example, hydroxyalkylamines (or aminoalkanols or alkanolamines, such as monoethanolamine, diethanolamine, triethanolamine, trometamol, etc.), sodium formaldehyde sulfoxylate (Rongalit), aluminum monostearate, and glycerin monostearate. The stabilizers may be used alone or in combination of two or more kinds.

[0129] oil Examples of oils include animal oils such as squalane and refined lanolin, mineral oils such as liquid paraffin and white petrolatum, and vegetable oils such as castor oil and sesame oil.

[0130] sugars Examples of sugars include monosaccharides and oligosaccharides (disaccharides, etc.), and specific examples include glucose, maltose, trehalose, sucrose, cyclodextrin, xylitol, sorbitol, and mannitol.

[0131] Polyhydric alcohol Examples of polyhydric alcohols include polyethylene glycol, glycerin, propylene glycol, xylitol, diethylene glycol, mannitol, sorbitol, and polyvinyl alcohol.

[0132] inorganic salts Examples of inorganic salts include potassium chloride, sodium chloride, calcium chloride, magnesium chloride, sodium bicarbonate, sodium carbonate (including dry sodium carbonate), potassium bicarbonate, potassium carbonate, magnesium sulfate, sodium hydrogen phosphate, potassium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, sodium hydrogen sulfite, sodium sulfite, potassium acetate, sodium acetate, and sodium thiosulfate. Among these, potassium chloride, sodium chloride, calcium chloride, sodium hydrogen carbonate, sodium carbonate (including dry sodium carbonate), magnesium sulfate, sodium hydrogen phosphate, sodium dihydrogen phosphate, and potassium dihydrogen phosphate are preferred, potassium chloride, sodium chloride, calcium chloride, sodium hydrogen phosphate, and sodium dihydrogen phosphate are more preferred, and potassium chloride and sodium chloride are even more preferred.

[0133] Water-soluble antioxidant Examples of water-soluble antioxidants include ascorbic acid, ascorbic acid derivatives (such as disodium ascorbyl 2-sulfate, sodium ascorbate, magnesium ascorbyl 2-phosphate, and sodium ascorbyl 2-phosphate), sodium hydrogen sulfite, sodium sulfite, sodium pyrosulfite, sodium thiosulfate, and edetic acid or salts thereof (such as disodium edetate and tetrasodium edetate).

[0134] The composition of the present invention may further contain ingredients having pharmacological or physiological activity.

[0135] The pharmacologically active ingredient or physiologically active ingredient can be used alone or in combination of two or more kinds.

[0136] Examples of such pharmacologically active ingredients and physiologically active ingredients include the active ingredients in various pharmaceuticals listed in the 2017 edition of the Guide to Manufacturing and Marketing Approval Standards and Application Practices for Prescription and Non-prescription Drugs (supervised by the Japan Society of Regulatory Science). Examples include decongestants, ocular muscle regulating agents, astringents, vitamins, amino acids, antibacterial agents or disinfectants, local anesthetic ingredients, soothing agents, and sulfonamides. Specific examples of these drugs are listed below.

[0137] Decongestants (vasoconstrictors) Decongestants include, for example, α-adrenergic agonists, specifically imidazoline decongestants such as oxymetazoline, tetrahydrozoline, naphazoline, or salts thereof such as hydrochlorides and nitrates, epinephrine, epinephrine hydrochloride, ephedrine hydrochloride, phenylephrine hydrochloride, methylephedrine hydrochloride, epinephrine bitartrate, etc. These may be in any of the d-, l-, or dl-isomers.

[0138] To explain imidazoline vasoconstrictors in more detail, the salt of an imidazoline vasoconstrictor may be any pharmaceutically or physiologically acceptable salt, and examples thereof include organic acid salts such as maleate and fumarate; inorganic acid salts such as hydrochloride and sulfate; metal salts, etc. Among the salts, inorganic acid salts are preferred, hydrochloride or nitrate are more preferred, and hydrochloride (e.g., tetrahydrozoline hydrochloride) is particularly preferred.

[0139] Among decongestants (vasoconstrictors), imidazoline vasoconstrictors are preferred, tetrahydrozoline, naphazoline, or a salt thereof is more preferred, and tetrahydrozoline or a salt thereof is even more preferred.

[0140] Ocular muscle adjusters Examples of eye muscle adjusters include cholinesterase inhibitors having an active center similar to that of acetylcholine, specifically neostigmine methylsulfate, tropicamide, helenien, and atropine sulfate.

[0141] Vitamins Examples of vitamins include flavin adenine dinucleotide or a salt thereof (e.g., flavin adenine dinucleotide sodium), cobalamin or a salt thereof (e.g., cyanocobalamin, methylcobalamin), retinol, a salt thereof, or a derivative thereof (e.g., retinol acetate, retinol palmitate), pyridoxine or a salt thereof (e.g., pyridoxine hydrochloride), panthenol, pantothenic acid or a salt thereof (e.g., sodium pantothenate, potassium pantothenate, calcium pantothenate, magnesium pantothenate), tocopherol, a salt thereof, or a derivative thereof (e.g., tocopherol acetate, tocopherol succinate, tocopherol nicotinate), pyridoxal or a salt thereof (e.g., pyridoxal phosphate), and ascorbic acid or a salt thereof (e.g., sodium ascorbate, calcium ascorbate).

[0142] Among these, flavin adenine dinucleotide or a salt thereof (particularly, flavin adenine dinucleotide sodium), cobalamin or a salt thereof (particularly, cyanocobalamin), retinol, a salt thereof or a derivative thereof (particularly, retinol acetate and retinol palmitate), pyridoxine or a salt thereof (particularly, pyridoxine hydrochloride), panthenol, pantothenic acid or a salt thereof (particularly, sodium pantothenate and calcium pantothenate), tocopherol, a salt thereof or a derivative thereof (particularly, tocopherol acetate) are preferred, and pyridoxine hydrochloride and tocopherol acetate are more preferred. The composition of the present invention may not contain pyridoxine or a salt thereof.

[0143] Antibacterial or disinfectant Examples of antibacterial or disinfectant agents include sulfa drugs such as sulfamethoxazole, sulfisoxazole, sulfamethoxazole sodium, sulfisoxazole diethanolamine, sulfisoxazole monoethanolamine, sulfisomazole sodium, and sulfisomidine sodium, alkylpolyaminoethylglycine, chloramphenicol, ofloxacin, norfloxacin, levofloxacin, and lomefloxacin hydrochloride.

[0144] Local anesthetic ingredients Examples of local anesthetic ingredients include procaine hydrochloride and lidocaine hydrochloride.

[0145] Base or carrier The compositions of the present invention may contain a base or carrier. Compositions containing such bases or carriers can be prepared, for example, by mixing each of the above-mentioned components with a pharmaceutically acceptable base or carrier, using a conventional method, for example, as described in the 17th Edition of the Japanese Pharmacopoeia.

[0146] Examples of bases or carriers include water, polar solvents (particularly water-soluble solvents) such as ethanol, oily bases, etc. The bases or carriers can be used alone or in combination of two or more.

[0147] In particular, the composition of the present invention may be an aqueous composition (for example, a composition containing water or a mixed solvent of water and a water-soluble solvent).

[0148] Properties The state of the composition of the present invention is not particularly limited and may be any state, such as a liquid, fluid, gel, or semi-solid state. It also includes compositions that are prepared just before use and are in a liquid, fluid, gel, or semi-solid state. A semi-solid state refers to a state that has plasticity that can be deformed by applying force, such as an ointment.

[0149] Furthermore, as described above, the composition may be an aqueous composition (mainly containing an aqueous or hydrophilic base or carrier), an oily composition (mainly containing an oily or hydrophobic base or carrier), or in particular an aqueous composition.

[0150] In the case of an aqueous composition, the water content is preferably 50% by mass or more, more preferably 75% by mass or more, and even more preferably 90% by mass or more, based on the total amount of the composition (or formulation). It may also be 95% by mass or more, or 98% by mass or more. The base or carrier may also consist solely of water.

[0151] In the case of an oily composition, the water content is preferably less than 50% by mass, more preferably 30% by mass or less, and even more preferably 20% by mass or less, based on the total amount of the composition (or preparation).

[0152] pH The pH of the composition of the present invention is preferably 3 or higher (e.g., 4 or higher), more preferably 5 or higher (e.g., 5.5 or higher), and even more preferably 6 or higher. The pH is preferably 10 or lower, more preferably 9 or lower, and even more preferably 8.5 or lower.

[0153] The pH of the composition of the present invention may be, for example, 4 to 9, preferably 4.5 to 8.5, more preferably 5 to 8, or may be 5.5 to 8, 6 to 8, 6 to 7.5, or 6.5 to 7.5. In the present invention, even at the above pH, the effects of the present invention (such as the effect of inhibiting precipitation) can be efficiently achieved.

[0154] Osmotic pressure The osmotic pressure ratio of the composition of the present invention is, for example, preferably 0.4 or more, more preferably 0.5 or more, and even more preferably 0.6 or more, and is preferably 5 or less, more preferably 3 or less, and even more preferably 2 or less.

[0155] The osmolality ratio is the ratio of the osmolality of the sample to the osmolality of 286 mOsm (0.9 w / v% sodium chloride solution) according to the 17th edition of the Japanese Pharmacopoeia. Osmolality is measured according to the freezing-point depression method described in the 17th edition of the Japanese Pharmacopoeia. The standard solution for measuring the osmolality ratio (0.9 w / v% sodium chloride solution) is 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, dissolving it in purified water, and preparing a solution of exactly 100 mL. Alternatively, a commercially available standard solution for measuring the osmolality ratio (0.9 w / v% sodium chloride solution) can be used.

[0156] Dosage form The dosage form (dosage form, shape, structure) of the composition of the present invention is not particularly limited, and examples thereof include eye drops (also called eye drops or eye drops; eye drops include those that can be applied while wearing contact lenses), eyewash, eye ointment (water-soluble eye ointment, oil-soluble eye ointment), contact lens wetting solution, intraocular injection (e.g., intravitreal injection), contact lens solution (cleaning solution, storage solution, disinfectant solution, multi-purpose solution, packaged solution), preservatives for excised eye tissues such as corneas for transplantation, and surgical irrigation solutions. Eye drops, eyewash, and eye ointments also include those used while wearing contact lenses.

[0157] 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).

[0158] Preferred dosage forms of the composition of the present invention include eye drops, eye washes, eye ointments (water-soluble eye ointments, oil-soluble eye ointments), contact lens wetting solutions, contact lens solutions (cleaning solutions, storage solutions, disinfectants, multi-purpose solutions, packaging solutions), etc., more preferred are eye drops, eye washes, contact lens wetting solutions, contact lens solutions (cleaning solutions, storage solutions, disinfectants, multi-purpose solutions), even more preferred are eye drops and eye washes, and particularly preferred are eye drops.

[0159] The composition of the present invention may be a single-use unit dose or a reusable multi-dose, or may be packaged and used in a multi-dose form.

[0160] container The composition of the present invention may be contained (filled, injected, or sealed) in a container. The container may be any packaging material having a part (surface) that comes into contact with the composition (formulation), and may be composed of, for example, a container body that contains the composition (e.g., a liquid composition), a part that includes the container's extraction port (nozzle, inner plug), a suction tube, a cap, etc.

[0161] The material constituting the container can be selected from a wide range of materials, and examples include plastics (e.g., olefin-based resins, styrene-based resins, acrylic-based resins, polyester-based resins, polycarbonate-based resins, fluororesins, chlorine-based resins (such as polyvinyl chloride), polyamide-based resins, polyacetal-based resins, polyphenylene ether-based resins (such as modified polyphenylene ether), polyarylates, polysulfones, polyimide-based resins, cellulose-based resins (such as cellulose acetate), hydrocarbon-based resins which may be substituted with halogen atoms), metals (such as aluminum), and the like, at least partly or entirely in the portion that comes into contact with the composition.

[0162] The container may be made of a single material or two or more materials.

[0163] Examples of olefin-based resins include ethylene-based resins [for example, polyethylene (including high-density polyethylene, low-density polyethylene, very-low-density polyethylene, linear low-density polyethylene, and ultra-high-molecular-weight polyethylene), ethylene-propylene copolymers, etc.], propylene-based resins [for example, polypropylene (PP) (including isotactic polypropylene, syndiotactic polypropylene, and atactic polypropylene), propylene-ethylene copolymers, etc.], and methylpentene-based resins (for example, polymethylpentene, etc.).

[0164] Examples of styrene-based resins include polystyrene and acrylonitrile-containing styrene-based resins (such as acrylonitrile-styrene copolymers (AS resins), acrylonitrile-butadiene-styrene copolymers (ABS resins)).

[0165] Examples of acrylic resins include resins containing, as a polymerization component, an acrylic acid ester such as methyl acrylate, or a methacrylic acid ester such as methyl methacrylate, cyclohexyl methacrylate, or t-butylcyclohexyl methacrylate.

[0166] Examples of polyester-based resins include aromatic polyester-based resins [e.g., resins having alkylene terephthalate units (alkylene terephthalate-based resins: e.g., polyethylene terephthalate (PET), polytrimethylene terephthalate, polybutylene terephthalate (PBT)), etc.), and resins having alkylene naphthalate units (e.g., polyethylene naphthalate (PEN), polybutylene naphthalate, etc.)].

[0167] Examples of fluororesins include fluorine-substituted polyethylene (polytetrafluoroethylene, polychlorotrifluoroethylene, etc.), polyvinylidene fluoride, polyvinyl fluoride, perfluoroalkoxy fluororesin, tetrafluoroethylene-hexafluoropropylene copolymer, ethylene-tetrafluoroethylene copolymer, and ethylene-chlorotrifluoroethylene copolymer.

[0168] Examples of polyacetal resins include those consisting only of oxymethylene units, as well as those containing oxyethylene units in part.

[0169] The modified polyphenylene ether may include polystyrene-modified polyphenylene ether.

[0170] The polyarylate may include amorphous polyarylate.

[0171] Examples of polyimide resins include aromatic polyimides, such as those obtained by polymerizing pyromellitic dianhydride and 4,4'-diaminodiphenyl ether.

[0172] Examples of cellulose acetate include cellulose diacetate and cellulose triacetate.

[0173] As the material for the container, plastics such as olefin-based resins, styrene-based resins, and polyester-based resins (i.e., plastic containers) are preferred, with ethylene-based resins, propylene-based resins, alkylene terephthalate-based resins, and polystyrene being more preferred, with polypropylene, polyethylene terephthalate, and polystyrene being even more preferred, and polyethylene terephthalate being even more preferred.

[0174] The container material may be a polymer blend with a polymer other than the above-mentioned polymer. When the container material for storing the ophthalmic composition of the present invention is a blend polymer with the above-mentioned polymer, the mixing ratio of the above-mentioned polymer to the other polymer is not particularly limited as long as the effects of the present invention are achieved, but the total weight of the polymers relative to the total amount of all constituent materials is preferably 30 w / w% or more, more preferably 50 w / w% or more, even more preferably 65 w / w% or more, and particularly preferably 80 w / w% or more.

[0175] At least a part of the surface of the container that comes into contact with the composition of the present invention may be made of the above material. For example, a layer or film made of the above material may be formed on the inner surface of the container, or the container itself may be molded from the above material. From the viewpoint of significantly achieving the effects of the present invention, it is preferable that the container itself be molded from the above material.

[0176] Furthermore, the parts that make up the container (the container body, the part including the container's extraction port (nozzle, inner plug), suction tube, cap, etc.) may be made of the above materials, or the entire container may be made of the above materials. In particular, from the viewpoint of significantly achieving the effects of the present invention, it is preferable that the container body be made of the above materials, and it is more preferable that the entire container body be made of the above materials (a state in which some layers that make up the container body are not made of the above materials).

[0177] Target disease (use) The target disease (use) of the composition of the present invention is not particularly limited as long as it is for ophthalmic use. For example, the composition is useful for alleviating, improving, suppressing, or treating allergic symptoms, itchy eyes, eye pain, eye inflammation, blepharitis, blurred vision, bloodshot eyes, foreign body sensation (gritty sensation, etc.), corneal damage, corneal injury, watery eyes (epiphora), palpebral conjunctival follicles, eye discharge (eye mucus), etc., as well as for enhancing, normalizing, and protecting the cornea's barrier function.

[0178] Watery eyes are a symptom that occurs when the tear drainage pathways from the lacrimal puncta to the lacrimal canaliculi, lacrimal sac, and nasolacrimal duct become blocked by eye discharge or when excessive tears are produced due to irritation.

[0179] As used herein, "alleviation" includes alleviation of symptoms and inhibition of progression of symptoms, and "improvement," "suppression," and "treatment" include alleviation of symptoms, inhibition of progression of symptoms, cure, or complete recovery.

[0180] In particular, the composition of the present invention is suitable for alleviating, improving, suppressing, or treating allergic symptoms (allergic symptoms of the eye).

[0181] The allergens causing allergic symptoms are not particularly limited, but may include pollen (cedar pollen, cypress pollen, etc.), house dust (indoor dust), and the like.

[0182] In another embodiment, the composition of the present invention is suitable for alleviating, improving, suppressing, or treating symptoms such as itchy eyes, eye pain, eye inflammation, blepharitis, blurred vision, bloodshot eyes, watery eyes, foreign body sensation, corneal damage, corneal injury, watery eyes (epiphora), palpebral conjunctival follicles, eye discharge (eye mucus), etc. These symptoms may or may not be caused by allergic symptoms.

[0183] How to use The method of use (mode of use) of the composition of the present invention can be appropriately selected depending on its properties and the like.

[0184] For example, when the composition of the present invention is a preparation to be applied to the eyes, such as eye drops, eyewash, or eye ointment, the dosage varies depending on the target symptoms, but can be, for example, one or more, two or more, three or more, four or more, five or more, or six or more times per day. Also, the dosage can be nine or fewer, eight or fewer, seven or fewer, six or fewer, five or fewer, or four or fewer times per day. Administration four times per day is particularly preferred.

[0185] When the composition of the present invention is an eye drop, for example, 1 to 3 drops, 1 to 2 drops, or 2 to 3 drops may be administered at one time. Preferably, 1 to 2 drops are administered. One drop may also be administered. The amount of one drop administered may preferably be 30 to 50 μL.

[0186] When the composition of the present invention is an eyewash, for example, 1 to 30 mL, preferably 1 to 20 mL, and more preferably 4 to 6 mL may be used for each eyewash.

[0187] When the composition of the present invention is an eye ointment, for example, 0.001 to 5 g may be applied to the eye each time.

[0188] When the composition of the present invention is a contact lens wetting solution, it may be applied, for example, 1 to 3 drops, preferably 1 to 2 drops, to one and / or both sides of the contact lens each time it is put on or taken off, to wet the lens before wearing, and it is preferable to wet both sides of the contact lens before wearing.

[0189] [2. Suppression of precipitation and cloudiness] The ophthalmic composition according to this embodiment exhibits the effect of being able to suppress precipitation (clouding) in the ophthalmic composition (or being able to improve or enhance the dissolution stability).

[0190] Thus, as one embodiment of the present invention, the following method is provided.

[0191] A method for suppressing precipitation (cloudiness) in an ophthalmic composition (a method for improving or enhancing dissolution stability), the method comprising adding (C) one or more selected from the group consisting of alcohols, water-soluble polymers, sugars, polyoxyethylene polyoxypropylene glycols, and polyethylene glycol fatty acid esters to an ophthalmic composition containing (A) one or more selected from the group consisting of epinastine and salts thereof, and (B) one or more selected from the group consisting of pranoprofen and salts thereof.

[0192] Furthermore, as one embodiment of the present invention, the following agent is provided.

[0193] An agent for suppressing precipitation (cloudiness) in an ophthalmic composition (or an agent for improving or enhancing dissolution stability) comprising (A) one or more members selected from the group consisting of epinastine and its salts, and (B) one or more members selected from the group consisting of pranoprofen and its salts, and (C) one or more members selected from the group consisting of alcohols, water-soluble polymers, sugars, polyoxyethylene polyoxypropylene glycols, and polyethylene glycol fatty acid esters.

[0194] In each of the above embodiments, the types and contents of the components (A) to (C), 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]

[0195] The present invention will be explained in more detail below by way of examples, but the present invention is not limited to these examples, and many modifications can be made by those skilled in the art within the technical spirit of the present invention.

[0196] Aqueous ophthalmic compositions (eye drops) having the compositions shown in the table below were prepared, and precipitation was evaluated as follows.

[0197] 200 g (200 cm) of the prepared composition 3 ) was filled into 10 mL glass screw bottles and stored at room temperature for 1 hour, after which the presence and extent of precipitation (cloudiness) was visually confirmed.

[0198] The degree of precipitation for Test Example 1 was evaluated according to the following criteria.

[0199] ○: No precipitation △: The degree of precipitation is the same as that of Test Example 1 ×: More precipitation than in Test Example 1

[0200] The results are shown in the table below. Note that in the aqueous ophthalmic compositions in the table below, the unit of each component is (w / v %).

[0201] [Table 1]

[0202] As is clear from the results in the table above, it was surprisingly found that although precipitation does not occur when epinastine hydrochloride or pranoprofen is contained alone, precipitation does occur when epinastine hydrochloride and pranoprofen are combined (Test Examples 1 to 3).

[0203] Such precipitation could be effectively suppressed by using specific components (Test Examples 4 to 19). Normally, the use of surfactants can often suppress such precipitation, but a common surfactant not only had no effect on suppressing precipitation, but actually increased precipitation (Test Example 20), so these results were quite unexpected.

[0204] The properties and the like of the compositions of Test Examples 4 to 19, in which the deposition suppression effect was confirmed, were further investigated.

[0205] First, all of these compositions could be filled into eye drop containers (made of PET, 6 mm diameter) without any problems, and were excellent in filling properties.

[0206] Furthermore, when the compositions were dropped from an eye dropper, they all drained well, demonstrating that the resulting compositions were all compositions that were less likely to drip.

[0207] Furthermore, each composition was dropped onto a colorless, transparent plastic film, and the water was allowed to evaporate. Visual inspection of the state after evaporation revealed that no or very little white residue (whitening or precipitation due to non-volatile components) was observed in any of the compositions. Thus, it was confirmed that all of the obtained compositions could be efficiently formulated. In fact, when filling the eye drop containers, none of the compositions left any white residue on the production line (nozzles, etc.).

[0208] Furthermore, in each composition, the function of component (c) was effectively exhibited. For example, in Test Example 5, concentrated glycerin was used, but the function as an isotonic agent was exhibited without being impaired.

[0209] [Formulation example] Ophthalmic compositions were prepared according to the formulations shown in the following table, where the units of each component are (w / v%).

[0210] [Table 2] [Industrial Applicability]

[0211] The present invention can provide an ophthalmic composition useful as an eye drop or the like.

Claims

1. (A) one or more selected from the group consisting of epinastine and salts thereof; (B) one or more selected from the group consisting of pranoprofen and salts thereof, and (C) An ophthalmic composition containing a water-soluble cellulose derivative.

2. (A) one or more selected from the group consisting of epinastine and salts thereof, (B) one or more selected from the group consisting of pranoprofen and salts thereof, and (C) an ophthalmic composition containing one or more selected from the group consisting of alkanols, alkane polyols, polyvinyl alcohols, polyethylene glycols, polyvinylpyrrolidones, water-soluble cellulose derivatives, oligosaccharides, polysaccharides, polyoxyethylene polyoxypropylene glycols, and polyoxyl stearates; The ophthalmic composition further comprises at least one selected from the group consisting of a surfactant, a buffer, a pH adjuster, and a tonicity agent.

3. (A) one or more selected from the group consisting of epinastine and salts thereof, (B) one or more selected from the group consisting of pranoprofen and salts thereof, and (C) an ophthalmic composition containing one or more selected from the group consisting of alkanols, alkane polyols, polyvinyl alcohols, polyethylene glycols, polyvinylpyrrolidones, water-soluble cellulose derivatives, oligosaccharides, polysaccharides, polyoxyethylene polyoxypropylene glycols, and polyoxyl stearates; An ophthalmic composition containing 0.0001 w / v% or more of component (A).

4. (A) one or more selected from the group consisting of epinastine and salts thereof, (B) one or more selected from the group consisting of pranoprofen and salts thereof, and (C) an ophthalmic composition containing one or more selected from the group consisting of alkanols, alkane polyols, polyvinyl alcohols, polyethylene glycols, polyvinylpyrrolidones, water-soluble cellulose derivatives, oligosaccharides, polysaccharides, polyoxyethylene polyoxypropylene glycols, and polyoxyl stearates; An ophthalmic composition containing 0.0001 w / v% or more of component (B).

5. (A) one or more selected from the group consisting of epinastine and salts thereof, (B) one or more selected from the group consisting of pranoprofen and salts thereof, and (C) an ophthalmic composition containing one or more selected from the group consisting of alkanols, alkane polyols, polyvinyl alcohols, polyethylene glycols, polyvinylpyrrolidones, water-soluble cellulose derivatives, oligosaccharides, polysaccharides, polyoxyethylene polyoxypropylene glycols, and polyoxyl stearates; An ophthalmic composition in which the ratio of component (B) is 0.001 to 1000 parts by mass per part by mass of component (A).

6. (A) one or more selected from the group consisting of epinastine and salts thereof, (B) one or more selected from the group consisting of pranoprofen and salts thereof, and (C) an ophthalmic composition containing one or more selected from the group consisting of alkanols, alkane polyols, polyvinyl alcohols, polyethylene glycols, polyvinylpyrrolidones, water-soluble cellulose derivatives, oligosaccharides, polysaccharides, polyoxyethylene polyoxypropylene glycols, and polyoxyl stearates; An ophthalmic composition containing 0.001 w / v% or more of component (C).

7. (A) one or more selected from the group consisting of epinastine and salts thereof, (B) one or more selected from the group consisting of pranoprofen and salts thereof, and (C) an ophthalmic composition containing one or more selected from the group consisting of alkanols, alkane polyols, polyvinyl alcohols, polyethylene glycols, polyvinylpyrrolidones, water-soluble cellulose derivatives, oligosaccharides, polysaccharides, polyoxyethylene polyoxypropylene glycols, and polyoxyl stearates; An ophthalmic composition, wherein the proportion of component (C) is 0.005 parts by mass or more per 1 part by mass of component (A) and 0.005 parts by mass or more per 1 part by mass of component (B).

8. (A) one or more selected from the group consisting of epinastine and salts thereof, (B) one or more selected from the group consisting of pranoprofen and salts thereof, and (C) an ophthalmic composition containing one or more selected from the group consisting of alkanols, alkane polyols, polyvinyl alcohols, polyethylene glycols, polyvinylpyrrolidones, water-soluble cellulose derivatives, oligosaccharides, polysaccharides, polyoxyethylene polyoxypropylene glycols, and polyoxyl stearates; An ophthalmic composition having a pH of 4 or higher.

9. (A) one or more selected from the group consisting of epinastine and salts thereof, (B) one or more selected from the group consisting of pranoprofen and salts thereof, and (C) an ophthalmic composition containing one or more selected from the group consisting of alkanols, alkane polyols, polyvinyl alcohols, polyethylene glycols, polyvinylpyrrolidones, water-soluble cellulose derivatives, oligosaccharides, polysaccharides, polyoxyethylene polyoxypropylene glycols, and polyoxyl stearates; The proportion of component (A) is 0.001 to 1 w / v %, The proportion of component (B) is 0.0003 to 5 w / v%, The proportion of component (C) is 0.001 to 20 w / v%, The proportion of the (B) component is 0.005 to 200 parts by mass per 1 part by mass of the (A) component, An ophthalmic composition having a pH of 4 to 9.

10. The ophthalmic composition according to any one of claims 1 to 9, which is free from precipitation.

11. 11. The ophthalmic composition according to claim 1, which contains water in an amount of 90% by mass or more based on the total amount of the composition and is free from precipitation.

12. (A) one or more selected from the group consisting of epinastine and salts thereof, and A method for inhibiting precipitation in an ophthalmic composition containing (B) one or more members selected from the group consisting of pranoprofen and salts thereof, comprising incorporating (C) a water-soluble cellulose derivative into the ophthalmic composition.

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