JP5927045B2 - Ophthalmic aqueous composition - Google Patents

Description

  The present invention relates to an aqueous ophthalmic composition.

  In order to improve the physical properties of the ophthalmic aqueous composition, attempts have been made to mix various components. For example, Patent Document 1 discloses, as a method for stabilizing the viscosity of a composition, hyaluronic acid or a salt thereof, castor oil, sesame oil, olive oil, soybean oil, peanut oil, almond oil, wheat germ oil, camellia oil, Disclosed is a mucosa-applied composition containing at least one vegetable oil selected from corn oil, rapeseed oil, sunflower oil, cottonseed oil or coconut oil. Further, it is known that a nonionic surfactant is blended in an aqueous ophthalmic composition for the purpose of assisting dissolution of other blended components.

JP 2006-117656 A

  The present inventors have repeatedly investigated the physical properties of an ophthalmic aqueous composition containing one or more vegetable oils selected from the group consisting of sesame oil, castor oil and soybean oil, and a nonionic surfactant. The ophthalmic aqueous composition obtained a completely new finding that it easily causes discoloration and turbidity over time.

  The present invention provides an aqueous ophthalmic composition that can be stably stored for a long period of time, even when the above-mentioned specific vegetable oil and nonionic surfactant are contained, and discoloration and turbidity over time are suppressed. Objective. Another object of the present invention is to provide a method for suppressing discoloration and turbidity over time in an ophthalmic aqueous composition containing the specific vegetable oil and nonionic surfactant.

  The present invention comprises (a) one or more vegetable oils selected from the group consisting of sesame oil, castor oil and soybean oil, (b) a nonionic surfactant, and (c) diphenhydramine hydrochloride, (C) The ophthalmic aqueous composition whose content of a component is 0.1-50 mass parts with respect to 1 mass part of said (a) component is provided.

  The aqueous ophthalmic composition of the present invention contains the component (a) and the component (b), and includes the component (c) at a specific ratio with respect to the component (a). Discoloration and turbidity are suppressed, and can be stored stably for a long time.

  The ophthalmic aqueous composition preferably further contains at least one selected from the group consisting of boric acid and salts thereof, phosphoric acid and salts thereof, and citric acid and salts thereof.

  By using at least one selected from the group consisting of boric acid and its salts, phosphoric acid and its salts, and citric acid and its salts, discoloration and turbidity over time are further suppressed, and it is stored more stably for a long time. can do. It is also advantageous in enhancing the storage efficacy of the aqueous ophthalmic composition of the present invention.

  The present invention also provides an aqueous ophthalmic composition comprising (a) one or more vegetable oils selected from the group consisting of sesame oil, castor oil and soybean oil, and (b) a nonionic surfactant. c) Provided is a method for suppressing discoloration of an aqueous ophthalmic composition, wherein diphenhydramine hydrochloride is blended so that the component (c) is in the range of 0.1 to 50 parts by mass with respect to 1 part by mass of the component (a). .

  The present invention further provides an aqueous ophthalmic composition comprising (a) one or more vegetable oils selected from the group consisting of sesame oil, castor oil and soybean oil, and (b) a nonionic surfactant. c) Provided is a method for suppressing turbidity of an aqueous ophthalmic composition, wherein diphenhydramine hydrochloride is blended so that the component (c) is in the range of 0.1 to 50 parts by mass with respect to 1 part by mass of the component (a). .

  According to the ophthalmic aqueous composition of the present invention, diphenhydramine hydrochloride (component (c)) is added to the specific vegetable oil (component (a)) and nonionic surfactant (component (b)). a) By blending at a specific ratio with respect to the component, discoloration and turbidity over time are suppressed and high transparency is maintained, so that the properties of the aqueous ophthalmic composition can be stably maintained even after long-term storage. It is possible to maintain.

  Furthermore, the ophthalmic aqueous composition of the present invention contains the specific vegetable oil (component (a)), a nonionic surfactant (component (b)), and diphenhydramine hydrochloride (component (c)), and By containing the component (c) at a specific ratio with respect to the component (a), it is possible to exhibit excellent storage efficacy, suppress the growth of microorganisms in the aqueous ophthalmic composition, or microorganisms Can be reduced. Therefore, the ophthalmic aqueous composition can be used more safely, and can be stably used safely for a long time even after the ophthalmic aqueous composition is opened.

  In the present specification, the unit “%” of the content ratio or the blending ratio means “w / v%” and is synonymous with “g / 100 mL”.

  In the present specification, unless otherwise specified, the abbreviation “POE” means polyoxyethylene.

  In this specification, unless otherwise specified, the abbreviation “POP” means polyoxypropylene.

[1. Ophthalmic aqueous composition)
The aqueous ophthalmic composition of the present invention contains (a) one or more vegetable oils selected from the group consisting of sesame oil, castor oil and soybean oil (sometimes simply referred to as “(a) component”). To do.

  The sesame oil in the present invention refers to a vegetable oil obtained from seeds of a plant belonging to the genus Sesameaceae (Sesamumindicum Linne (Pedaliaceae)). The sesame oil that can be blended in the aqueous ophthalmic composition of the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Those obtained from seeds using a purification method or those commercially available can be used. In particular, sesame oil that conforms to the 15th revised Japanese Pharmacopoeia standard is suitably used from the viewpoint that the effect of suppressing discoloration or turbidity over time of the ophthalmic aqueous composition is more remarkable.

  The castor oil in the present invention refers to a vegetable oil obtained from seeds of plants belonging to the genus Euphorbiaceae (Ricinus communis Linne (Euforbiaceae), etc.). The castor oil that can be blended in the aqueous ophthalmic composition of the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Those obtained from seeds using the purification method described above or those commercially available can be used. In particular, castor oil that conforms to the standard of the 15th revised Japanese pharmacopoeia is suitably used from the viewpoint of more prominently suppressing the discoloration or turbidity of the ophthalmic aqueous composition over time.

  The soybean oil in the present invention refers to a vegetable oil obtained from the seed of a plant of the leguminous soybean genus (Glycinemax Merrill (Leguminosae), etc.). The soybean oil that can be blended in the ophthalmic aqueous composition of the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Those obtained from seeds using the purification method described above or those commercially available can be used. In particular, soybean oil that conforms to the standards of the 15th revised Japanese Pharmacopoeia is suitably used from the viewpoint that the effect of suppressing discoloration or turbidity over time of the ophthalmic aqueous composition is more remarkable.

  The vegetable oil selected from the group consisting of these sesame oil, castor oil and soybean oil can be used alone or in combination of two or more. Among them, sesame oil and castor oil are preferable, and sesame oil is particularly preferable.

  About the content rate of the said (a) component in the ophthalmic aqueous composition of this invention, according to the kind of (a) component, the kind and content rate of another compounding component, the formulation form of the ophthalmic aqueous composition, etc. suitably Can be set. As an example of the content ratio of the component (a), the total amount of the component (a) is generally 0.001 to 5%, preferably 0.001 to 1%, more preferably, with respect to the total amount of the ophthalmic aqueous composition. 0.001 to 0.5%, more preferably about 0.001 to 0.1% is exemplified.

  The aqueous ophthalmic composition of the present invention contains (b) a nonionic surfactant (sometimes simply referred to as “component (b)”).

  The component (b) in the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. For example, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil, polyoxyethylene-polyoxypropylene block copolymer, polyoxyethylene-polyoxypropylene block copolymer adduct, polyoxyethylene-polyoxy One or more selected from the group consisting of propylene alkyl ether and polyoxyethylene alkylphenyl ether can be used.

  Specific examples of the component (b) used in the present invention include the following components. For example, POE sorbitan fatty acid ester includes monolauric acid POE (20) sorbitan (polysorbate 20), monooleic acid POE (20) sorbitan (polysorbate 80), POE sorbitan monostearate (polysorbate 60), POE sorbitan tristearate. (Polysorbate 65) and the like; POE hydrogenated castor oil 5, POE hydrogenated castor oil 10, POE hydrogenated castor oil 20, POE hydrogenated castor oil 40, POE hydrogenated castor oil 50, POE hydrogenated castor oil 60, POE Hardened castor oil 100, etc .; POE castor oil includes POE castor oil 3, POE castor oil 10, POE castor oil 20, POE castor oil 35, POE castor oil 40, POE castor oil 50, POE castor oil 60, etc .; polyoxy ethylene Examples of the polyoxypropylene block copolymer (hereinafter also referred to as “polyoxyethylene polyoxypropylene copolymer”) include poloxamer 407, poloxamer 235, poloxamer 188, etc .; examples of the POE-POP block copolymer adduct of ethylenediamine include poloxamine POE alkyl ethers include POE (9) lauryl ether; POE / POP alkyl ethers include POE (20) POP (4) cetyl ether; POE alkyl phenyl ethers include POE (10) nonyl phenyl ether; And so on. The numbers in parentheses indicate the number of added moles.

  (B) A component can be used 1 type or in combination of 2 or more types. The component (b) is preferably POE sorbitan fatty acid ester, POE hydrogenated castor oil, POE castor oil, polyoxyethylene-polyoxypropylene block copolymer, and particularly preferably polysorbate 80, POE hydrogenated castor oil 60, POE castor oil 10, POE castor oil 35, and poloxamer 407. Among these, polysorbate 80 conforming to the 15th revised Japanese Pharmacopoeia standard, from the viewpoint of more effectively exhibiting the effect of suppressing discoloration or turbidity over time of the ophthalmic aqueous composition and enhancing the storage efficacy, or A polyoxyethylene hydrogenated castor oil 60 conforming to the pharmaceutical additive standard 2003 is preferably used.

  The content ratio of the component (b) in the ophthalmic aqueous composition can be appropriately set according to the type of the component (b), the type and content ratio of other compounding components, the formulation form of the ophthalmic aqueous composition, and the like. As an example of the content ratio of the component (b), the component (b) is a total amount with respect to the total amount of the aqueous ophthalmic composition, and is usually 0.001 to 5%, preferably 0.001 to 4%, more preferably. Examples are 0.002 to 3%, more preferably 0.005 to 2%, and still more preferably about 0.01 to 1%. If the blending amount of the nonionic surfactant is within the above range, the ophthalmic aqueous composition can more effectively exhibit the effect of suppressing discoloration or turbidity over time or the effect of enhancing the preservation effect, and is more irritating to the eyes. It is also preferable from the viewpoint of being kept low.

  In the ophthalmic aqueous composition of the present invention, the content ratio of the component (b) to the component (a) is not particularly limited, but the effect of suppressing discoloration or turbidity with time of the aqueous ophthalmic composition is more remarkable. In view of the above, with respect to 1 part by mass of the total amount of the component (a), the component (b) is 0.1 to 1000 parts by mass, preferably 0.1 to 300 parts by mass, more preferably 1 to 30 parts by mass. It is preferable to be within the range.

  The aqueous ophthalmic composition of the present invention comprises (c) diphenhydramine hydrochloride (sometimes simply referred to as “(c) component”) with respect to 1 part by mass of the total amount of (a) component, It is contained at a ratio of 0.1 to 50 parts by mass in total. As described above, the component (c) is contained together with the components (a) and (b), and is blended into the ophthalmic aqueous composition at a specific ratio with respect to the component (a). Color change or turbidity with time can be suppressed, and the effect of enhancing the storage effect can be exhibited.

  Diphenhydramine is a known compound also referred to as 2-benzhydryloxy-N, N-dimethylethanamine. Diphenhydramine hydrochloride is the hydrochloride salt of diphenhydramine. The diphenhydramine hydrochloride used in the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable, and is synthesized by a known method or commercially available. Things can be used. Among diphenhydramine hydrochlorides, diphenhydramine hydrochloride conforming to the 15th revised Japanese Pharmacopoeia standard is more effective in suppressing the discoloration or turbidity of the ophthalmic aqueous composition over time and enhancing the storage efficacy. Preferably used.

  The content ratio of the component (c) in the ophthalmic aqueous composition can be appropriately set according to the type and content ratio of other compounding components, the formulation form of the ophthalmic aqueous composition, and the like. As an example of the content ratio of the component (c), the total amount of the component (c) is usually 0.0001 to 1.0%, preferably 0.001 to 0.5% with respect to the total amount of the aqueous ophthalmic composition. More preferably, about 0.01 to 0.05% is exemplified.

  In the ophthalmic aqueous composition of the present invention, the content ratio of the component (c) to the component (a) is generally 0.07 to 0.07 to (c) component in total with respect to 1 part by mass of the total component (a). The total amount of the component (a) may be within the range of 75 parts by mass, from the viewpoint of more prominently suppressing the discoloration or turbidity with time of the aqueous ophthalmic composition and further enhancing the storage efficacy. The component (c) is a total amount with respect to 1 part by mass, preferably 0.1 to 50 parts by mass, more preferably 0.2 to 20 parts by mass, and still more preferably 0.2 to 10 parts by mass. Is done.

  In addition, the component (c) can effectively suppress discoloration or turbidity over time of the aqueous ophthalmic composition produced by containing both the component (a) and the component (b). The component c) is an ophthalmic aqueous composition containing one or more vegetable oils selected from the group consisting of sesame oil, castor oil, and soybean oil, and a nonionic surfactant. Can be used to suppress. The component (c) is a discoloration inhibitor in an aqueous ophthalmic composition containing one or more vegetable oils selected from the group consisting of sesame oil, castor oil and soybean oil, and a nonionic surfactant. Or it can also be used as a turbidity inhibitor.

  The aqueous ophthalmic composition of the present invention preferably further contains at least one selected from the group consisting of boric acid and salts thereof, phosphoric acid and salts thereof, and citric acid and salts thereof, Containing at least one selected from the group consisting of salts thereof, at least one selected from the group consisting of phosphoric acid and salts thereof, or at least one selected from the group consisting of citric acid and salts thereof. More preferred. Thus, by containing at least one selected from the group consisting of boric acid and its salts, phosphoric acid and its salts, and citric acid and its salts, it is expected that the effects of the present invention will be further improved. The Examples of boric acid and its salts include boric acid and borates such as alkali metal borate and alkaline earth metal borate. Moreover, you may use the borate hydrate as boric acid and its salt. More specific examples include boric acid, sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, borax and the like as boric acid and its salts. Boric acid and its salt can be used alone or in combination of two or more. As preferred specific examples of boric acid and its salt, a combination of boric acid and its salt; preferably a combination of boric acid and an alkali metal salt of boric acid, a combination of boric acid and an alkaline earth metal salt, A combination of boric acid with an alkali metal salt and an alkaline earth metal salt of boric acid; more preferably a combination of boric acid with an alkali metal salt of boric acid; particularly preferably a combination of boric acid and borax. Illustrated. Examples of phosphoric acid and salts thereof include phosphoric acid and phosphates such as alkali metal phosphate and alkaline earth metal phosphate. Moreover, you may use the hydrate of a phosphate as phosphoric acid and its salt. As more specific examples, phosphoric acid and its salts include disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, trisodium phosphate, dipotassium phosphate, calcium monohydrogen phosphate and phosphoric acid. Examples include calcium dihydrogen. Phosphoric acid and its salt can be used alone or in combination of two or more. As a suitable specific example of phosphoric acid and a salt thereof, a combination of disodium hydrogen phosphate and sodium dihydrogen phosphate is exemplified. Examples of citric acid and its salts include citric acid, and alkali metal citrate and alkaline earth metal citrate. More specific examples include citric acid and its salts such as sodium citrate, potassium citrate, calcium citrate, sodium dihydrogen citrate and disodium citrate. Citric acid and its salt can be used alone or in combination of two or more. A suitable example of citric acid and its salt is a combination of citric acid and sodium citrate.

  When the ophthalmic aqueous composition of the present invention contains at least one selected from the group consisting of boric acid and its salts, phosphoric acid and its salts, and citric acid and its salts, the content is used. According to at least one kind selected from the group consisting of boric acid and its salt, phosphoric acid and its salt, citric acid and its salt, the kind and amount of other compounding ingredients, use of the aqueous ophthalmic composition, etc. However, for example, with respect to the total amount of the ophthalmic aqueous composition, the total amount is 0.01 to 10 w / v%, preferably 0.05 to 5 w / v%. Preferably about 0.1-2 w / v% is illustrated.

  The aqueous ophthalmic composition of the present invention may further contain a buffer. The buffer that can be incorporated into the aqueous ophthalmic composition is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Examples of such buffers include carbonate buffer, acetate buffer, Tris buffer, epsilon-aminocaproic acid, aspartic acid, aspartate and the like. These buffering agents may be used in combination. Examples of the carbonate buffer include carbonates or carbonates such as alkali metal carbonates and alkaline earth metal carbonates. Carbonic acid or a salt thereof (sodium hydrogen carbonate, sodium carbonate, ammonium carbonate, potassium carbonate, calcium carbonate, potassium hydrogen carbonate, magnesium carbonate, etc.); as an acetic acid buffer, acetic acid or a salt thereof (ammonium acetate, potassium acetate) Tris (hydroxymethyl) aminomethane or a salt thereof (hydrochloride, acetate, sulfonate, etc.); aspartic acid or a salt thereof (sodium aspartate, magnesium aspartate) And potassium aspartate). These buffering agents may be used alone or in any combination of two or more.

  The pH of the ophthalmic aqueous composition of the present invention is not particularly limited as long as it is within a pharmaceutically, pharmacologically (pharmaceutical) or physiologically acceptable range. As an example of a suitable pH, 4.0 to 9.5, preferably 4.5 to 9.0, and more preferably 4.5 to 8. 5, More preferably, the range which becomes 4.5-8.0 is mentioned.

  The aqueous ophthalmic composition of the present invention can be further adjusted to an osmotic pressure ratio within a range acceptable for a living body, if necessary. The appropriate osmotic pressure ratio varies depending on the application site, dosage form, etc., but is usually in the range of 0.7 to 5.0, more preferably 0.8 to 3.0, still more preferably 0.9 to 2.0. It is done. The osmotic pressure can be adjusted by a known method in the technical field using an inorganic salt, a polyhydric alcohol, or the like. The osmotic pressure ratio here is the ratio of the osmotic pressure of the sample to the osmotic pressure of 286 mOsm (0.9 w / v sodium chloride aqueous solution) based on the 15th revised Japanese Pharmacopoeia, and the osmotic pressure is the 15th revised Measured according to the osmotic pressure measurement method (freezing point depression method) described in the Japanese Pharmacopoeia. The standard solution for measuring the osmotic pressure ratio (0.9 w / v% sodium chloride aqueous solution) was dried in sodium chloride (Japanese Pharmacopoeia standard reagent) at 500 to 650 ° C. for 40 to 50 minutes, and then in a desiccator (silica gel). The mixture is allowed to cool and 0.900 g is accurately weighed and dissolved in purified water to make exactly 100 mL, or a commercially available standard solution for osmotic pressure ratio measurement (0.9 w / v% sodium chloride aqueous solution) is used.

  The aqueous ophthalmic composition of the present invention contains various pharmacologically active ingredients and physiologically active ingredients in addition to the above ingredients according to conventional methods according to its use and formulation form, as long as the effects of the present invention are not impaired. An appropriate amount may be selected and one or more may be used in combination. Examples of these pharmacologically active components and physiologically active components include active ingredients in various pharmaceuticals described in the generic drug manufacture (import) approval standard 2000 edition (supervised by the Pharmaceutical Affairs Research Committee).

Specific examples of the pharmacologically active component or physiologically active component include the following components.
Antihistamine or antiallergic agent: for example, ketotifen fumarate, iproheptin, chlorpheniramine maleate, sodium cromoglycate, tranilast, pemirolast potassium and the like.
Decongestant: For example, tetrahydrozoline hydrochloride, naphazoline hydrochloride, naphazoline sulfate, epinephrine hydrochloride, ephedrine hydrochloride, methylephedrine hydrochloride, and the like.
Bactericides: for example, acrinol, cetylpyridinium, benzalkonium chloride, benzethonium chloride, chlorhexidine hydrochloride, chlorhexidine gluconate, alkyldiaminoethylglycine hydrochloride, etc.
Vitamins: For example, pyridoxine hydrochloride, flavin adenine dinucleotide sodium, cyanocobalamin, retinol acetate, retinol palmitate, panthenol, calcium pantothenate, tocopherol acetate and the like.
Amino acids: For example, potassium aspartate, magnesium aspartate, aminoethylsulfonic acid and the like.
Anti-inflammatory agent: for example, dipotassium glycyrrhizinate, azulene sulfonic acid, allantoin, tranexamic acid, epsilon-aminocaproic acid, berberine, lysozyme and the like.
Astringent: For example, zinc white, zinc lactate, zinc sulfate and the like.
Other: For example, sodium hyaluronate, sulfamethoxazole, sulfamethoxazole sodium, pranoprofen and the like.

In addition, in the aqueous ophthalmic composition of the present invention, various additives can be appropriately selected according to conventional methods according to the use and formulation form, as long as the effects of the present invention are not impaired. An appropriate amount may be added in combination. Examples of these additives include various additives described in Pharmaceutical Additives Encyclopedia 2007 (edited by Japan Pharmaceutical Additives Association). Typical additives include the following additives.
Thickener: For example, carboxyvinyl polymer, hydroxyethylcellulose, hydroxypropylmethylcellulose, methylcellulose, sodium carboxymethylcellulose, alginic acid, polyvinyl alcohol (completely or partially saponified product), polyvinylpyrrolidone, macrogol, sodium chondroitin sulfate, sodium hyaluronate, etc. .
Sugars: for example, glucose, cyclodextrin and the like.
Sugar alcohols: For example, xylitol, sorbitol, mannitol and the like. These may be d-form, l-form or dl-form.
Preservatives, bactericides or antibacterial agents: for example, alkyldiaminoethylglycine hydrochloride, sodium benzoate, ethanol, benzalkonium chloride, benzethonium chloride, chlorhexidine gluconate, chlorobutanol, sorbic acid, potassium sorbate, sodium dehydroacetate, paraoxy Methyl benzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate, oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, Glow Kill (trade name, manufactured by Rhodia) and the like.
pH adjuster: for example, hydrochloric acid, boric acid, aminoethylsulfonic acid, epsilon-aminocaproic acid, citric acid, acetic acid, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, sodium bicarbonate, sodium carbonate, boro Sand, triethanolamine, diisopropanolamine, sulfuric acid, phosphoric acid, polyphosphoric acid, propionic acid, oxalic acid, gluconic acid, fumaric acid, lactic acid, tartaric acid, malic acid, succinic acid, gluconolactone, ammonium acetate and the like.
Stabilizers: For example, dibutylhydroxytoluene, trometamol, sodium formaldehyde sulfoxylate (Longalite), tocopherol, sodium pyrosulfite, aluminum monostearate, glyceryl monostearate and the like.
Chelating agents: for example, ethylenediaminediacetic acid (EDDA), ethylenediaminetriacetic acid, ethylenediaminetetraacetic acid (edetic acid, EDTA), N- (2-hydroxyethyl) ethylenediaminetriacetic acid (HEDTA), diethylenetriaminepentaacetic acid (DTPA), and the like.
Perfume or refreshing agent: for example, menthol, anethole, eugenol, camphor, geraniol, cineol, borneol, limonene, ryuno and the like. These may be either d-form, l-form or dl-form, and are formulated as essential oils (mint oil, cool mint oil, spearmint oil, peppermint oil, fennel oil, cinnamon oil, bergamot oil, eucalyptus oil, rose oil, etc.) May be.

  In this specification, the ophthalmic aqueous composition means an ophthalmic composition containing water, and usually contains 80 w / v% or more of water, more preferably 90 w / v% or more, and still more preferably 95 w / v. % Or more, particularly preferably 97 w / v% or more. The water contained in the ophthalmic aqueous composition of the present invention may be any pharmaceutical, pharmacologically (pharmaceutically) or physiologically acceptable. For example, distilled water, normal water, purified water, sterilized purified water, water for injection, distilled water for injection, and the like can be used. These definitions are based on the 15th revision Japanese Pharmacopoeia.

  The aqueous ophthalmic composition of the present invention is obtained by adding desired amounts of the above-mentioned component (a), component (b), and component (c), and other compounding components as required to obtain a desired concentration. It is prepared and can be in various forms depending on the purpose. For example, a liquid agent, a gel agent, etc. are mentioned as a form of the ophthalmic aqueous composition of this invention. From the viewpoint that the effect of suppressing discoloration and turbidity with time is more remarkably exhibited, a liquid agent is more preferable.

  Specific examples of the preparation form of the aqueous ophthalmic composition of the present invention include eye drops (including eye drops that can be instilled while wearing contact lenses), eye wash (eye drops that can be washed while wearing contact lenses). A contact lens mounting liquid, a contact lens care agent, and the like. From the viewpoint that a high preservative effect is required as a pharmaceutical product, it is preferably an eye wash or an eye drop, and from the viewpoint that an eye drop nozzle is easily in contact with the eye and the periphery of the eye for consumers, and a particularly high preservative effect is desired. Particularly preferred are eye drops. The contact lenses include all contact lenses such as hard contact lenses, oxygen permeable hard contact lenses, soft contact lenses, and silicone hydrogel contact lenses.

  Further, particularly when the aqueous ophthalmic composition of the present invention is a pharmaceutical product such as eye drops, eye wash, etc., a package that allows easy visual recognition of the contents, that is, a package having a transparent portion, from the formulation and usage characteristics. Need to be filled. According to the ophthalmic aqueous composition of the present invention, since the temporal change in appearance such as discoloration and turbidity is suppressed even when filled in a package having such a transparent portion, the consumer can feel at ease. Can be used, leading to improved compliance. Thus, the ophthalmic aqueous composition of the present invention can be provided as a containerized ophthalmic aqueous composition by filling a highly transparent plastic container. Examples of the material for such a plastic container include polycarbonate, polyethylene terephthalate, polyarylate, and polyethylene naphthalate. In particular, a polyethylene terephthalate container is preferred.

  Specific examples of ophthalmic aqueous compositions in containers include eye drops (including eye drops that can be instilled while wearing contact lenses), eye wash (including eye drops that can be washed while wearing contact lenses), and contact lenses. Examples include products in which liquids, contact lens care agents, and the like are at least partially filled in light transmissive containers.

  The aqueous ophthalmic composition of the present invention is useful for the treatment of dry eyes, tired eyes, conjunctival hyperemia, eye inflammation, itchy eyes and blurred vision. Moreover, since it can also exhibit an antihistamine action based on the component (c), it is useful as a preventive or alleviating agent for allergic symptoms.

[2. Method for suppressing discoloration of aqueous ophthalmic composition]
As described above, the occurrence of discoloration in the aqueous ophthalmic composition containing the components (a) and (b) described above, the component (c) described above with respect to 1 part by mass of the component (a) It becomes possible to suppress by making it contain so that it may become the range of 0.1-50 mass parts.

  Accordingly, the present invention provides an ophthalmology comprising (a) one or more vegetable oils selected from the group consisting of sesame oil, castor oil, and soybean oil, and (b) a nonionic surfactant. (C) diphenhydramine hydrochloride is added to the aqueous composition for use so that the component (c) is in the range of 0.1 to 50 parts by mass with respect to 1 part by mass of the component (a). A method for suppressing discoloration of the aqueous ophthalmic composition is provided.

  Moreover, the method for suppressing discoloration of the aqueous ophthalmic composition includes (a) one or more vegetable oils selected from the group consisting of sesame oil, castor oil and soybean oil, and (b) a nonionic surfactant. The ophthalmic aqueous composition contains (c) diphenhydramine hydrochloride so that the component (c) is in the range of 0.1 to 50 parts by mass with respect to 1 part by mass of the component (a). It can also be called the method for suppressing discoloration of the aqueous ophthalmic composition.

  Further, the method for suppressing discoloration of the aqueous ophthalmic composition includes (a) one or more vegetable oils selected from the group consisting of sesame oil, castor oil and soybean oil, (b) a nonionic surfactant, and (c The above ophthalmic aqueous composition is characterized by containing diphenhydramine hydrochloride so that the component (c) is in the range of 0.1 to 50 parts by mass with respect to 1 part by mass of the component (a). It can also be called a discoloration suppressing method.

  In addition, in the said discoloration suppression method, the kind of component (a)-(c) to be used, a compounding ratio, a content ratio, a compounding ratio, a content ratio, etc., the kind of other component mix | blended, a compounding ratio, a content ratio, compounding Regarding the formulation form and use of the ophthalmic aqueous composition, such as the ratio and content ratio, the types and content ratios of each component, the content ratio, the ophthalmic formulation form, and eye drops in the above-mentioned “1. Ophthalmic aqueous composition” This is the same as the use of the agent.

[3. Method for suppressing turbidity of aqueous ophthalmic composition]
As described above, the occurrence of turbidity in the aqueous ophthalmic composition containing the components (a) and (b) described above, the component (c) with respect to 1 part by mass of the component (c) It becomes possible to suppress by making it contain so that it may become the range of 0.1-50 mass parts.

  Accordingly, the present invention provides an ophthalmology comprising (a) one or more vegetable oils selected from the group consisting of sesame oil, castor oil, and soybean oil, and (b) a nonionic surfactant. (C) diphenhydramine hydrochloride is added to the aqueous composition for use so that the component (c) is in the range of 0.1 to 50 parts by mass with respect to 1 part by mass of the component (a). A method for suppressing turbidity of the aqueous ophthalmic composition is provided.

  Further, the method for suppressing turbidity of the aqueous ophthalmic composition includes (a) one or more vegetable oils selected from the group consisting of sesame oil, castor oil, and soybean oil, and (b) a nonionic surfactant. The ophthalmic aqueous composition contains (c) diphenhydramine hydrochloride so that the component (c) is in the range of 0.1 to 50 parts by mass with respect to 1 part by mass of the component (a). A method for suppressing turbidity of the aqueous ophthalmic composition is also provided.

  Moreover, the turbidity suppression method of the said ophthalmic aqueous composition comprises: (a) one or more vegetable oils selected from the group consisting of sesame oil, castor oil and soybean oil; (b) a nonionic surfactant; The above ophthalmic aqueous composition is characterized by containing diphenhydramine hydrochloride so that the component (c) is in the range of 0.1 to 50 parts by mass with respect to 1 part by mass of the component (a). It can also be called a turbidity suppression method.

  In addition, in the said turbidity suppression method, the kind of component (a)-(c) to be used, a compounding ratio, a content ratio, a compounding ratio, a content ratio, etc., the kind of other component mix | blended, a compounding ratio, a content ratio, compounding Regarding the formulation form and use of the ophthalmic aqueous composition, such as the ratio and content ratio, the types and content ratios of each component, the content ratio, the ophthalmic formulation form, and eye drops in the above-mentioned “1. Ophthalmic aqueous composition” This is the same as the use of the agent.

[4. Method for enhancing the storage efficacy of an ophthalmic aqueous composition]
As described above, the components (a), (b), and (c) are added in the range of 0.1 to 50 parts by mass of the component (c) with respect to 1 part by mass of the component (a). By containing, the preservative efficacy of the ophthalmic aqueous composition can be enhanced, and the growth of microorganisms in the ophthalmic aqueous composition can be suppressed.

  Accordingly, the present invention provides, from another viewpoint, (a) one or more vegetable oils selected from the group consisting of sesame oil, castor oil and soybean oil, (b) a nonionic surfactant, and (c) hydrochloric acid. Diphenhydramine is blended so that the component (c) is in the range of 0.1 to 50 parts by mass with respect to 1 part by mass of the component (a), and the preservation efficacy of the ophthalmic aqueous composition is enhanced. A method is also provided.

  The method for enhancing the preservation efficacy of the aqueous ophthalmic composition includes (a) one or more vegetable oils selected from the group consisting of sesame oil, castor oil, and soybean oil, and (b) a nonionic surfactant. c) An aqueous ophthalmic composition comprising diphenhydramine hydrochloride so that the component (c) is in the range of 0.1 to 50 parts by mass with respect to 1 part by mass of the component (a). A method for enhancing storage efficacy is also provided.

  The method for enhancing the preservative efficacy of the ophthalmic aqueous composition includes (c) one or more selected from the group consisting of (a) sesame oil, castor oil and soybean oil in the ophthalmic aqueous composition containing diphenhydramine hydrochloride. The vegetable oil of (b) and (b) the nonionic surfactant are contained so that the component (a) is in the range of 0.02 to 10 parts by mass with respect to 1 part by mass of the component (c). It can also be referred to as a method for enhancing the storage efficacy of an aqueous ophthalmic composition.

  In addition, in the said preservation | save efficacy enhancement method, the kind of component (a)-(c) to be used, a compounding ratio, a compounding ratio, a content rate, a content ratio, etc., the kind of other component mix | blended, a compounding ratio, a compounding ratio, About the formulation form and use etc. of the aqueous ophthalmic composition such as the content ratio, the content ratio, etc., the type and content ratio of each component, the content ratio, the formulation form of the eye drop in the above-mentioned “1. This is the same as the use of eye drops.

  EXAMPLES The present invention will be described in detail below based on examples, but the present invention is not limited to these examples. In addition, storage for about 7 to 10 days at 70 ° C. is considered to correspond to storage for about 3 years at room temperature.

[Test Example 1-1: Discoloration and turbidity suppression test]
Eye drops were prepared according to the formulation described in Table 1 below (Examples 1 to 7 and Control 1). Note that sesame oil and diphenhydramine hydrochloride were used in accordance with the 15th revised Japanese Pharmacopoeia, and polyoxyethylene hydrogenated castor oil 60 was used in compliance with the Pharmaceutical Additives Standard 2003. Immediately after the preparation, the absorbance (A420) of each ophthalmic aqueous composition at a wavelength of 420 nm was measured using a spectrophotometer (Hitachi “U-3300”) (starting A420). Thereafter, each ophthalmic aqueous composition was filled in an eye drop container made of PET and stored for 1 week in a thermostat at 70 ° C., and then the absorbance of each ophthalmic aqueous composition at a wavelength of 420 nm was again obtained using the above spectrophotometer. (A420) was measured (after storage, A420). From the measured values obtained, the A420 change rate (change rate of absorbance) before and after storage was calculated according to the following formula (I). A420 can be used as a parameter for coloring (yellowness) in the solution, and the larger A420, the more severe the color change (yellow). In addition, as a result of the calculation of the following formula (I), the larger the change rate of the absorbance (A420), the more the color change with time is suppressed.
A420 change rate (%) = (1− (after storage A420 / starting A420)) × 100 (I)

Based on the A420 change rate of each Example and Control calculated above, the improvement degree of discoloration by diphenhydramine hydrochloride was calculated based on the following formula (II). The greater the degree of improvement in discoloration, the more discoloration is suppressed compared to the comparative example. In addition, the prescription of control 1 is the same as that of Examples 1-7 except not mix | blending diphenhydramine hydrochloride.
Degree of improvement in discoloration (%) = A420 rate of change in example (%) − A420 rate of change in control (%) (II)

Similarly to the above, immediately after the preparation, the absorbance (A660) of each ophthalmic aqueous composition at a wavelength of 660 nm was measured using the spectrophotometer (starting A660). Thereafter, each ophthalmic aqueous composition was filled in an eye drop container made of PET, and stored for one week in a thermostat at 70 ° C., and then the absorbance of each ophthalmic aqueous composition at a wavelength of 660 nm again using the spectrophotometer. (A660) was measured (after storage, A660). From the obtained measured value, the A660 change rate (change rate of absorbance) before and after storage was calculated according to the following formula (III). A660 can be used as a parameter of the degree of turbidity (low transparency) of the solution, and the larger A660 means the more turbidity is. Further, as a result of calculation of the following formula (III), it means that the turbidity with time is suppressed as the change rate of the absorbance (A660) is larger.
A660 change rate (%) = (1− (A660 after storage / A660 at start)) × 100 (III)

Based on the A660 change rate of each Example and Control calculated above, the improvement in turbidity due to diphenhydramine hydrochloride was calculated based on the following formula (IV). It means that turbidity is suppressed compared with control, so that the improvement degree of turbidity is large. In addition, the prescription of control 1 is the same as that of Examples 1-7 except not mix | blending diphenhydramine hydrochloride.
Turbidity improvement rate (%) = A660 change rate (%) of Example-A660 change rate (%) of control (IV)

  The results are also shown in Table 1. Examples 1 to 7 in which the ratio of (c) component (diphenhydramine hydrochloride) to component (a) (sesame oil) is 0.1 to 50 parts by mass of (c) component to 1 part by mass of component (a) By blending diphenhydramine, discoloration and turbidity over time of eye drops containing sesame oil and polyoxyethylene hydrogenated castor oil 60 were suppressed.

[Test Example 1-2: Discoloration and turbidity suppression test]
Eye drops were prepared according to the formulations described in Table 3 below (Comparative Examples 1 to 5 and Controls 2 and 3). Note that sesame oil and diphenhydramine hydrochloride were used in accordance with the 15th revised Japanese Pharmacopoeia, and polyoxyethylene hydrogenated castor oil 60 was used in compliance with the Pharmaceutical Additives Standard 2003. The test was conducted in the same manner as in Test Example 1-1, and the degree of improvement in discoloration and the degree of improvement in turbidity were calculated. In addition, about the calculation of Formula (II) and (IV), "Example" in a formula was read as "Comparative example", and it calculated. The combinations of the comparative examples and the corresponding controls are as shown in Table 2 below.

  The prescription for Control 2 is the same as Comparative Example 1 except that diphenhydramine hydrochloride is not blended, and the prescription for Control 3 is the same as Comparative Example 4 except that diphenhydramine hydrochloride is not blended. The formulation of Control 1 in Table 1 is the same as Comparative Examples 2, 3 and 5 in Table 3 except that diphenhydramine hydrochloride is not blended. As the control 1, the value of Control 1 in Table 1 is used. The calculation was done.

  The results are also shown in Table 3. Comparative Examples 1 to 5 in which the ratio of (c) component (diphenhydramine hydrochloride) to component (a) (sesame oil) is outside the range of 0.1 to 50 parts by mass of (c) component to 1 part by mass of component (a) In the eye drops containing sesame oil and polyoxyethylene hydrogenated castor oil 60, discoloration and turbidity over time were not suppressed.

[Test Example 2: Discoloration and turbidity suppression test]
Eye drops were prepared according to the formulation described in Table 4 below (Examples 8 and 9 and Control 4). The sesame oil, diphenhydramine hydrochloride, and polysorbate 80 were used in accordance with the 15th revised Japanese Pharmacopoeia. The test was conducted in the same manner as in Test Example 1-1 (however, storage in a thermostatic chamber was 60 ° C. for 1 week or 70 ° C. for 1 week), and the degree of improvement in discoloration and the degree of improvement in turbidity were calculated. The formulation of Control 4 is the same as in Examples 8 and 9 except that diphenhydramine hydrochloride is not blended.

  The results are also shown in Table 4. Examples 8 and 9 wherein the ratio of (c) component (diphenhydramine hydrochloride) to component (a) (sesame oil) is in the range of 0.1 to 50 parts by mass of (c) component to 1 part by mass of component (a). By adding diphenhydramine hydrochloride, discoloration and turbidity of eye drops containing sesame oil and polysorbate 80 over time were suppressed.

[Test Example 3: Discoloration and turbidity suppression test]
Eye drops were prepared according to the formulation described in Table 5 below (Example 10 and Control 5). The sesame oil, diphenhydramine hydrochloride, and polysorbate 80 were used in accordance with the 15th revised Japanese Pharmacopoeia. The test was conducted in the same manner as in Test Example 1-1 (however, storage in a thermostatic chamber was 60 ° C. for 1 week), and the degree of improvement in discoloration and the degree of improvement in turbidity were calculated. The formulation of Control 5 is the same as Example 10 except that diphenhydramine hydrochloride is not blended.

  The results are also shown in Table 5. (A) Example 10 which is in the range of 0.1 to 50 parts by mass of component (c) with respect to 1 part by mass of component is that of ophthalmic solution containing sesame oil and polysorbate 80 by blending diphenhydramine hydrochloride over time. Discoloration and turbidity were suppressed.

[Test Example 4: Discoloration and turbidity suppression test]
Eye drops were prepared according to the formulation described in Table 6 below (Example 11 and Control 6). The sesame oil, diphenhydramine hydrochloride, and polysorbate 80 were used in accordance with the 15th revised Japanese Pharmacopoeia. The test was performed in the same manner as in Test Example 1-1 (however, storage in a thermostatic chamber was 70 ° C. for 1 week for the discoloration test and 70 ° C. for 1 day for the turbidity test), and the improvement degree of discoloration and the improvement degree of turbidity were calculated. The formulation of Control 6 is the same as that of Example 11 except that diphenhydramine hydrochloride is not blended.

  The results are also shown in Table 6. Example 11 which is in the range of 0.1 to 50 parts by mass of component (c) with respect to 1 part by mass of component (a) is the time course of eye drops containing sesame oil and polysorbate 80 by blending diphenhydramine hydrochloride. Discoloration and turbidity were suppressed.

[Test Example 5: Discoloration and turbidity suppression test]
Eye drops were prepared according to the formulation described in Table 7 below (Example 12 and Control 7). In addition, castor oil, diphenhydramine hydrochloride, and polysorbate 80 were used in accordance with the 15th revised Japanese Pharmacopoeia. The test was conducted in the same manner as in Test Example 1-1 (however, storage in a thermostatic chamber was 60 ° C. for 1 week or 70 ° C. for 1 week), and the degree of improvement in discoloration and the degree of improvement in turbidity were calculated. The formulation of Control 7 is the same as Example 12 except that diphenhydramine hydrochloride is not blended.

  The results are also shown in Table 7. (A) Example 12 which is in the range of 0.1 to 50 parts by mass of component (c) with respect to 1 part by mass of component is the time of ophthalmic solution containing castor oil and polysorbate 80 by blending diphenhydramine hydrochloride. Discoloration and turbidity were suppressed.

[Test Example 6: Test for suppressing discoloration and turbidity]
Eye drops were prepared according to the formulations described in Table 9 below (Comparative Examples A and B). The sesame oil, castor oil, polysorbate 80, and chlorpheniramine maleate were used in accordance with the 15th revised Japanese Pharmacopoeia, and the polyoxyethylene hydrogenated castor oil 60 was used in accordance with the pharmaceutical additive standard 2003. Tested in the same manner as in Test Example 1-1 (however, storage in a thermostatic chamber was 70 ° C. for 1 week in Comparative Example A and 60 ° C. for 1 week in Comparative Example B), and the degree of improvement in discoloration and the improvement rate in turbidity were calculated. . In addition, about the calculation of Formula (II) and (IV), "Example" in a formula was read as "Comparative example", and it calculated. Further, combinations of each comparative example and the corresponding control are as shown in Table 8 below.

  The results are also shown in Table 9. Comparative examples A and B containing chlorpheniramine maleate instead of diphenhydramine hydrochloride contain component (a) (sesame oil or castor oil) and component (b) (polyoxyethylene hydrogenated castor oil 60 or polysorbate 80). Discoloration and turbidity over time of the eye drops were not suppressed.

[Test Example 7: Turbidity suppression test]
Eye drops were prepared according to the formulation described in Table 10 below (Examples A and B and Controls A and B). The sesame oil, diphenhydramine hydrochloride, and polysorbate 80 were used in accordance with the 15th revised Japanese Pharmacopoeia. The test was conducted in the same manner as in Test Example 1-1 (however, storage in a thermostatic chamber was 70 ° C. for 1 day), and the improvement in turbidity was calculated. The formulation of Control A is the same as Example A except that diphenhydramine hydrochloride is not blended, and the formulation of Control B is the same as Example B except that diphenhydramine hydrochloride is not blended.

  The results are also shown in Table 10. Even when disodium hydrogen phosphate and sodium dihydrogen phosphate are blended in place of boric acid and borax (Example A), or when sodium citrate and citric acid are blended (Example B), diphenhydramine hydrochloride The ocular turbidity containing the component (a) (sesame oil) and the component (b) (polysorbate 80) was suppressed over time.

[Test Example 8: Turbidity (haze value) suppression test 1]
Eye drops were prepared according to the formulation described in Table 12 below (Examples 13 to 15 and Controls 8 to 10). Note that sesame oil, castor oil, soybean oil, diphenhydramine hydrochloride each used a product conforming to the 15th revised Japanese Pharmacopeia, and polyoxyethylene hydrogenated castor oil 60 used a product compliant with the Pharmaceutical Additives Standard 2003. Immediately after the preparation, the haze value was measured (measuring instrument: turbidimeter (manufactured by Nippon Denshoku Industries Co., Ltd., NDH-300A)). From the obtained measured value, the improvement degree of the haze value was calculated based on the following formula (V). The haze value can be used as a parameter for the degree of turbidity (low transparency). The larger the haze value, the more turbidity is. Further, as a result of the calculation of the following formula (V), the larger the improvement degree of the haze value, the more turbidity is suppressed as compared with the control.
Improvement rate of haze value (%) = (1− (haze value of example / haze value of control)) × 100 (V)

Further, combinations of each example and the corresponding control are as shown in Table 11 below.

  The formulation of Control 8 is the same as that of Example 13 except that diphenhydramine hydrochloride is not blended. The formulation of Control 9 is the same as that of Example 14 except that diphenhydramine hydrochloride is not blended. The formulation of is the same as Example 15 except that diphenhydramine hydrochloride is not blended.

  The results are also shown in Table 12. (A) Examples 13-15 which are in the range of 0.1-50 mass parts of (c) component with respect to 1 mass part of component are vegetable oil (sesame oil, castor oil, or soybean oil) by mix | blending diphenhydramine hydrochloride. Moreover, the turbidity immediately after preparation of the eye drop containing the polyoxyethylene hydrogenated castor oil 60 could be suppressed.

[Test Example 9: Preservative efficacy test]
1. Tests on products immediately after preparation:
An aqueous ophthalmic composition was prepared according to the formulation described in Table 13 below, filtered through a 0.2 μm membrane filter, filled into sterilized eye drops, and used as eye drops (Comparative Examples 2-1 and 2). -2). The sesame oil, diphenhydramine hydrochloride, and polysorbate 80 were used in accordance with the 15th revised Japanese Pharmacopoeia. Immediately after preparation, a viable cell count test was performed according to the method defined in the Japanese Pharmacopoeia (15th revision) to evaluate the antiseptic properties (preservative efficacy) of eye drops. Specifically, Escherichia coli (ATCC8739 strain) was inoculated on the surface of a soy bean casein digest agar plate medium and cultured at 33 ° C. for 24 hours. The cultured cells were aseptically collected with a platinum loop and suspended in an appropriate amount of sterilized physiological saline to prepare a bacterial suspension containing about 3 × 10 ⁷ CFU / mL viable bacteria. An appropriate amount of each eye drop shown in Table 13 was added to this bacterial suspension, and then allowed to stand at 25 ° C. for a predetermined period. Each eye drop was added so that the number of living Escherichia coli was about 3 × 10 ⁵ CFU / mL. Moreover, after leaving still for 1 day, the number of viable bacteria per mL was measured, and after leaving still at 25 degreeC for 2 days, the number of viable bacteria per mL was measured.

2. Test for 60 ° C storage product:
An aqueous ophthalmic composition was prepared according to the formulation described in Table 13 below, filtered through a 0.2 μm membrane filter, filled into sterile eye drop bottles, and used as eye drops (Examples 2-1 and 2). -2 and Comparative Examples 2-1 and 2-2), each composition was filled into a PET eye drop container and stored in a 60 ° C incubator for 5 days. Thereafter, in accordance with the method prescribed in the Japanese Pharmacopoeia (15th revision), the above 1. The number of viable bacteria was measured according to the same procedure as the test for the product immediately after preparation.

  Table 13 shows the results of evaluation for Escherichia coli. The smaller the number of viable bacteria, the higher the preservation effect. From these results, (c) ophthalmic solutions containing diphenhydramine hydrochloride tend to have reduced storage efficacy after storage at 60 ° C., but a specific ratio of (a) component to (c) component ( By blending with the component b), high storage efficacy was obtained even after storage at 60 ° C.

[Formulation example]
Ophthalmic aqueous compositions (formulation examples 1 to 20) are prepared according to the formulations described in Tables 14 to 16. In the formulations shown in Tables 14 to 16, sesame oil, castor oil, soybean oil, diphenhydramine hydrochloride, and polysorbate 80 are used in conformity with Japanese Pharmacopoeia, respectively, and polyoxyethylene hydrogenated castor oil 60 conforms to Pharmaceutical Additive Standard 2003. Goods are used. Hydrochloric acid and sodium hydroxide are used for pH adjustment, and the ophthalmic aqueous composition is added so as to have the pH described in Tables 14-16. Purified water is added so that the total amount of the ophthalmic aqueous composition is 100 ml.

Claims (5)

(A) one or more vegetable oils selected from the group consisting of sesame oil, castor oil and soybean oil;
(B) a nonionic surfactant;
(C) diphenhydramine hydrochloride,
Ophthalmic aqueous composition whose content of said (c) component is 0.1-50 mass parts with respect to 1 mass part of said (a) component.   The aqueous ophthalmic composition according to claim 1, further comprising at least one selected from the group consisting of boric acid and salts thereof, phosphoric acid and salts thereof, and citric acid and salts thereof.   The aqueous ophthalmic composition according to claim 1, which is an eye drop. The aqueous ophthalmic composition according to any one of claims 1 to 3, wherein the pH is 4.0 to 9.5. An aqueous ophthalmic composition comprising (a) one or more vegetable oils selected from the group consisting of sesame oil, castor oil and soybean oil; and (b) a nonionic surfactant.
(C) Discoloration and / or turbidity of an aqueous ophthalmic composition in which diphenhydramine hydrochloride is blended so that the component (c) is in the range of 0.1 to 50 parts by mass with respect to 1 part by mass of the component (a). how to suppress.