Aqueous ophthalmic composition

Abstract

To provide an aqueous ophthalmic composition that prevents the occurrence of deposit.SOLUTION: An aqueous ophthalmic composition has (A) at least one selected from the group consisting of allantoin, and epsilon-aminocaproic acid and salt thereof, and (B) at least one selected from the group consisting of chondroitin sulfate and salt thereof, the content of the (B) component being 0.7 w / v% or more relative to the total amount of the aqueous ophthalmic composition.SELECTED DRAWING: None

Description

Technical Field

[0006] , , , , ,

[0001] The present invention relates to an aqueous ophthalmic composition.

Background Art

[0002] Generally, an aqueous ophthalmic composition is filled in a container having an opening, and is repeatedly used by discharging the aqueous ophthalmic composition from the opening during use. At that time, the aqueous ophthalmic composition adhering to the opening may dry and generate deposits, which are known to cause various problems.

[0003] For example, the accumulation of deposits at the opening adheres not only to the opening but also to its periphery and even to the inside of the lid or cap, giving the user an unpleasant impression. When repeatedly used, it may make it difficult to open and close the opening. In the case of eye drops, the diameter of the pouring outlet, which is the opening, is often very small, and even with the attachment of a small amount of deposits, there is a risk that the passage of the aqueous ophthalmic composition will be blocked and an accurate amount of liquid will not be dropped. Furthermore, when deposits accumulate at the pouring outlet of the eye drops, there is also concern that the deposits will enter the eye together when instilling the eye drops.

[0004] On the other hand, in the case of an aqueous ophthalmic composition directly applied to the eye mucosa, when the liquid leaking out of the eye after application dries and deposits are generated, white solids adhere to the peripheral parts of the eyes such as the eyelids, eyelashes, and under the eyes, so the generation of deposits due to the drying of the aqueous ophthalmic composition is also a problem from the viewpoints of appearance and beauty.

[0005] As a method for suppressing the generation of deposits after drying in an aqueous composition, for example, Patent Document 1 reports a method of blending chlorpheniramines and amino acids in an aqueous composition containing a new quinolone agent.

Prior Art Documents

Patent Documents

[0006]

Patent Document 1

[0007] However, there have been no previous reports of precipitate formation after drying in aqueous ophthalmic compositions containing allantoin or epsilon-aminocaproic acid. The present inventors conducted various studies on aqueous ophthalmic compositions containing allantoin or epsilon-aminocaproic acid and confirmed that when the aqueous ophthalmic compositions dry, a white solid substance called a white residue precipitates.

[0008] The present invention aims to provide an aqueous ophthalmic composition that contains allantoin and at least one selected from the group consisting of epsilon-aminocaproic acid and its salts, while suppressing the formation of precipitates after drying. [Means for solving the problem]

[0009] The present inventors have unexpectedly discovered that the formation of precipitates in an aqueous ophthalmic composition containing allantoin and epsilon-aminocaproic acid and its salts is suppressed by adding at least one substance selected from the group consisting of chondroitin sulfate and its salts in a specific amount or more. The present invention is based on this finding and provides the following inventions.

[0010] [1] An aqueous ophthalmic composition comprising (A) at least one selected from the group consisting of allantoin and epsilon-aminocaproic acid and its salts, and (B) at least one selected from the group consisting of chondroitin sulfate and its salts, wherein the content of component (B) is 0.7 w / v% or more based on the total amount of the aqueous ophthalmic composition. [2] (A) The aqueous ophthalmic composition according to [1], wherein the content of component (A) is 0.001 w / v% to 5 w / v% based on the total amount of the aqueous ophthalmic composition. [3] (B) The aqueous ophthalmic composition according to [1] or [2], wherein the content of component (B) is 1 w / v% to 5 w / v% based on the total amount of the aqueous ophthalmic composition. [4] (C) An aqueous ophthalmic composition according to any one of [1] to [3], further containing neostigmine methylsulfate. [5] (D) An aqueous ophthalmic composition according to any one of [1] to [4], further comprising a terpenoid. [6] A method for suppressing the formation of precipitates in an aqueous ophthalmic composition, comprising: (A) at least one selected from the group consisting of allantoin, epsilon-aminocaproic acid and its salts; and (B) at least one selected from the group consisting of chondroitin sulfate and its salts in an amount of 0.7 w / v% or more based on the total amount of the aqueous ophthalmic composition. [Effects of the Invention]

[0011] According to the present invention, it is possible to provide an aqueous ophthalmic composition that contains allantoin and at least one selected from the group consisting of epsilon-aminocaproic acid and its salts, while suppressing the formation of precipitates after drying. [Modes for carrying out the invention]

[0012] The embodiments for carrying out the present invention will be described in detail below. However, the present invention is not limited to the following embodiments.

[0013] In this specification, unless otherwise specified, the unit of content "%" means "w / v%" and is synonymous with "g / 100mL".

[0014] [1. Aqueous ophthalmic composition] The aqueous ophthalmic composition according to this embodiment contains (A) allantoin and at least one selected from the group consisting of epsilon-aminocaproic acid and its salts (also simply referred to as "component (A)"). In the following, at least one selected from the group consisting of epsilon-aminocaproic acid and its salts may be referred to as "component (A1)".

[0015] [Component (A)] (A) The components allantoin, epsilon-aminocaproic acid, and its salts are not particularly limited as long as they are pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Epsilon-aminocaproic acid may be in free form or as a pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable salt.

[0016] Allantoin is a well-known compound also known as 2-ureidohydantoin.

[0017] Examples of salts of epsilon-aminocaproic acid include salts with inorganic bases. Examples of salts with inorganic bases include alkali metal salts such as sodium salts and potassium salts; and alkaline earth metal salts such as magnesium salts and calcium salts. Epsilon-aminocaproic acid is preferred as epsilon-aminocaproic acid and its salts.

[0018] Allantoin, epsilon-aminocaproic acid, and their salts can also be commercially available. Allantoin, epsilon-aminocaproic acid, and their salts may be used individually or in combination of two or more.

[0019] In the eye drops according to the present embodiment, the content of the component (A) is preferably 0.001 to 5 w / v%, more preferably 0.005 to 4 w / v%, still more preferably 0.01 to 3 w / v%, still more preferably 0.06 to 2.5 w / v%, particularly preferably 0.1 to 2 w / v%, and particularly more preferably 0.2 to 2 w / v% based on the total amount of the aqueous ophthalmic composition.

[0020] When using allantoin as the component (A), the content of allantoin is, for example, preferably 0.01 to 1 w / v%, more preferably 0.03 to 0.5 w / v%, still more preferably 0.05 to 0.4 w / v%, still more preferably 0.06 to 0.3 w / v%, and particularly preferably 0.2 to 0.3 w / v% based on the total amount of the aqueous ophthalmic composition.

[0021] When using ε-aminocaproic acid and its salts as the component (A), the content of ε-aminocaproic acid and its salts is, for example, preferably 0.01 to 5 w / v%, more preferably from 0.05 to 4 w / v%, still more preferably 0.1 to 3 w / v%, and still more preferably 0.5 to 2 w / v% based on the total amount of the aqueous ophthalmic composition. Further, when the content of ε-aminocaproic acid and its salts is less than 3 w / v% based on the total amount of the aqueous ophthalmic composition, it is preferable from the viewpoint that the effects of the present invention can be significantly exhibited. [[ID=!0]]

[0022] n 〔Component (B)〕 The aqueous ophthalmic composition according to the present embodiment contains, in addition to the component (A), at least one selected from the group consisting of chondroitin sulfate and its salts (simply referred to as “component (B)”).

[0023] (B) The chondroitin sulfate and its salts, which are component (B), are not particularly limited as long as they are pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. The molecular weight of chondroitin sulfate and its salts is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable, but typically a weight-average molecular weight of about 0.1 million to 100,000, preferably about 0.5 million to 50,000, and more preferably about 10,000 to 40,000 can be used.

[0024] Examples of chondroitin sulfate salts include alkali metal salts and alkaline earth metal salts. Examples of alkali metal salts include sodium salts and potassium salts. Examples of alkaline earth metal salts include magnesium salts and calcium salts.

[0025] Chondroitin sulfate and its salts are preferably chondroitin sulfate and alkali metal salts of chondroitin sulfate, more preferably chondroitin sulfate and sodium chondroitin sulfate, and even more preferably sodium chondroitin sulfate.

[0026] Commercially available chondroitin sulfate and its salts may also be used. Chondroitin sulfate and its salts may be used individually or in combination of two or more types.

[0027] The content of component (B) in the aqueous ophthalmic composition according to this embodiment is 0.7 w / v% or more, based on the total amount of the aqueous ophthalmic composition. The lower limit of the content of component (B) is not particularly limited as long as it is 0.7 w / v% or more, and is set appropriately depending on the type of component (B), the types and amounts of other components, the use and formulation form of the aqueous ophthalmic composition, etc. As a lower limit of the content of component (B), it is preferably 0.8 w / v% or more, more preferably 0.9 w / v% or more, even more preferably 1 w / v% or more, even more preferably 2 w / v% or more, and particularly preferably 2.5 w / v% or more. The upper limit of the content of component (B) is not particularly limited, and is set appropriately depending on the type of component (B), the types and amounts of other components, the use and formulation form of the aqueous ophthalmic composition, etc. (B) The upper limit of the content of component (B) is preferably 5 w / v% or less, more preferably 4 w / v% or less, even more preferably 3.5 w / v% or less, and even more preferably 3 w / v% or less, from the viewpoint of more significantly demonstrating the effects of the present invention and from the viewpoint of usability. Furthermore, the content of component (B) in the aqueous ophthalmic composition according to this embodiment may be, for example, 0.7 to 5 w / v%, 0.7 to 4 w / v%, 0.7 to 3 w / v%, 0.8 to 5 w / v%, 0.8 to 4 w / v%, 0.8 to 3 w / v%, 0.9 to 5 w / v%, 0.9 to 4 w / v%, 0.9 to 3 w / v%, 1 to 5 w / v%, 1 to 4 w / v%, or 1 to 3 w / v%, based on the total amount of the aqueous ophthalmic composition. In another embodiment, the content of component (B) in the aqueous ophthalmic composition according to this embodiment may be, for example, 2 to 4 w / v%, 2.5 to 3.5 w / v%, or 3 w / v%, based on the total amount of the aqueous ophthalmic composition.

[0028] In the aqueous ophthalmic composition according to this embodiment, the content ratio of component (B) to component (A) is not particularly limited and is set appropriately depending on the types of components (A) and (B), the types and content of other components, the use and formulation form of the aqueous ophthalmic composition, etc. As for the content ratio of component (B) to component (A), from the viewpoint of further enhancing the effects of the present invention, for example, the total content of component (B) in the aqueous ophthalmic composition according to this embodiment is preferably 0.05 to 50 parts by mass, more preferably 0.1 to 30 parts by mass, and even more preferably 0.5 to 15 parts by mass, per 1 part by mass of the total content of component (A) contained in the aqueous ophthalmic composition according to this embodiment. Also, 1 to 40 parts by mass and 1.5 to 30 parts by mass are given as examples of preferred ranges.

[0029] When allantoin is used as component (A), the ratio of component (B) to component (A) is preferably 0.3 to 100 parts by mass, more preferably 1 to 50 parts by mass, and even more preferably 3 to 15 parts by mass, for every 1 part by mass of total component (A) contained in the aqueous ophthalmic composition according to this embodiment. 5 to 40 parts by mass and 10 to 30 parts by mass are also given as preferred ranges.

[0030] When using epsilon-aminocaproic acid and its salt as component (A), the content ratio of component (B) to component (A) is preferably 0.05 to 20 parts by mass, more preferably 0.1 to 10 parts by mass, and even more preferably 0.5 to 6 parts by mass, per 1 part by mass of the total content of component (A) in the aqueous ophthalmic composition according to this embodiment. Also, 1 to 40 parts by mass and 1.5 to 30 parts by mass are given as examples of preferred ranges.

[0031] [(C) component] The aqueous ophthalmic composition according to this embodiment may further contain (C) neostigmine methylsulfate (also simply referred to as "component (C)"). The effects of the present invention are more pronounced when the aqueous ophthalmic composition contains component (C).

[0032] (C) The component neostigmine methylsulfate is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable.

[0033] Neostigmine methylsulfate is a known compound also known as (3-dimethylcarbamoyloxyphenyl)trimethylammonium methylsulfate.

[0034] The content of component (C) in the aqueous ophthalmic composition according to this embodiment is not particularly limited and is set as appropriate depending on the type and content of other components, the use and formulation form of the aqueous ophthalmic composition, etc. As for the content of component (C), from the viewpoint of more significantly exhibiting the effects of the present invention, for example, based on the total amount of the aqueous ophthalmic composition, the total content of component (C) is preferably 0.00005 to 0.1 w / v%, more preferably 0.0001 to 0.05 w / v%, even more preferably 0.0005 to 0.01 w / v%, and even more preferably 0.001 to 0.005 w / v%.

[0035] In the aqueous ophthalmic composition according to this embodiment, the content ratio of component (C) to component (A) is not particularly limited and is set appropriately depending on the types of components (A) and (C), the types and content of other components, the use and formulation form of the aqueous ophthalmic composition, etc. As for the content ratio of component (C) to component (A), from the viewpoint of further enhancing the effects of the present invention, for example, the total content of component (C) in the aqueous ophthalmic composition according to this embodiment is preferably 0.00005 to 0.5 parts by mass, more preferably 0.0001 to 0.1 parts by mass, and even more preferably 0.0005 to 0.05 parts by mass, per 1 part by mass of the total content of component (A) contained in the aqueous ophthalmic composition according to this embodiment.

[0036] In the aqueous ophthalmic composition according to this embodiment, the content ratio of component (C) to component (B) is not particularly limited and is set appropriately depending on the types of components (B) and (C), the types and content of other components, the use and formulation form of the aqueous ophthalmic composition, etc. As for the content ratio of component (C) to component (B), from the viewpoint of further enhancing the effects of the present invention, for example, the total content of component (C) in the aqueous ophthalmic composition according to this embodiment is preferably 0.00005 to 0.05 parts by mass, more preferably 0.0001 to 0.01 parts by mass, and even more preferably 0.0003 to 0.005 parts by mass per 1 part by mass of the total content of component (B) contained in the aqueous ophthalmic composition according to this embodiment. Also, 0.0005 to 0.003 parts by mass and 0.001 to 0.002 parts by mass are also given as preferred ranges.

[0037] [(D) component] The aqueous ophthalmic composition according to this embodiment may further contain (D) terpenoid (also simply referred to as "component (D)"). The effects of the present invention are more pronounced when the aqueous ophthalmic composition contains component (D).

[0038] (D) The terpenoid component is not particularly limited, as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable.

[0039] Examples of terpenoids include cyclic terpenes and acyclic terpenes.

[0040] Cyclic terpenes are terpenoids that have at least one ring structure within their molecule. Examples of cyclic terpenes include menthol, camphor, borneol (also known as "limonol"), menthone, cineole, carvone, anethole, eugenol, limonene, pinene, and their derivatives.

[0041] Acyclic terpenes are terpenoids that do not have a ring structure within their molecule. Examples of acyclic terpenes include geraniol, citronellol, linalool, linalyl acetate, and their derivatives.

[0042] In the present invention, essential oils containing the above-mentioned compounds may be used as terpenoids. Examples of such essential oils include eucalyptus oil, bergamot oil, peppermint oil, cool mint oil, spearmint oil, peppermint oil, fennel oil, cinnamon oil, and rose oil.

[0043] Terpenoids can be d-, l-, or dl-isomers, with examples including dl-menthol, d-menthol, l-menthol, dl-camphor, d-camphor, l-camphor, dl-borneol, d-borneol, l-borneol, dl-menthone, d-menthone, and l-menthone. However, some terpenoids, such as geraniol and cineole, may not have optical isomers.

[0044] Preferred terpenoids include menthol, camphor, borneol, menthone, geraniol, eucalyptus oil, and bergamot oil; more preferably menthol, camphor, and borneol; even more preferably l-menthol, d-camphor, dl-camphor, and d-borneol; and even more preferably l-menthol.

[0045] Commercially available terpenoids may be used. Terpenoids may be used individually or in combination of two or more types.

[0046] The content of component (D) in the aqueous ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the type of component (D), the types and content of other components, the use and formulation form of the aqueous ophthalmic composition, etc. As for the content of component (D), from the viewpoint of more significantly exhibiting the effects of the present invention, for example, based on the total amount of the aqueous ophthalmic composition, the total content of component (D) is preferably 0.00001 to 1 w / v%, more preferably 0.00005 to 0.5 w / v%, even more preferably 0.0001 to 0.1 w / v%, even more preferably 0.0005 to 0.05 w / v%, and particularly preferably 0.001 to 0.05 w / v%.

[0047] In the aqueous ophthalmic composition according to this embodiment, the content ratio of component (D) to component (A) is not particularly limited and is set appropriately depending on the types of components (A) and (D), the types and content of other components, the use and formulation form of the aqueous ophthalmic composition, etc. As for the content ratio of component (D) to component (A), from the viewpoint of further enhancing the effects of the present invention, for example, the total content of component (D) in the aqueous ophthalmic composition according to this embodiment is preferably 0.00001 to 5 parts by mass, more preferably 0.00005 to 2 parts by mass, even more preferably 0.0001 to 1 part by mass, and even more preferably 0.0005 to 0.5 parts by mass, per 1 part by mass of the total content of component (A) contained in the aqueous ophthalmic composition according to this embodiment.

[0048] In the aqueous ophthalmic composition according to this embodiment, the content ratio of component (D) to component (B) is not particularly limited and is set appropriately depending on the types of components (B) and (D), the types and content of other components, the use and formulation form of the aqueous ophthalmic composition, etc. As for the content ratio of component (D) to component (B), from the viewpoint of further enhancing the effects of the present invention, for example, the total content of component (D) in the aqueous ophthalmic composition according to this embodiment is preferably 0.00005 to 0.5 parts by mass, more preferably 0.0001 to 0.1 parts by mass, even more preferably 0.0003 to 0.05 parts by mass, and even more preferably 0.0003 to 0.03 parts by mass, per 1 part by mass of the total content of component (B) contained in the aqueous ophthalmic composition according to this embodiment.

[0049] [Surfactants] The aqueous ophthalmic composition according to this embodiment may further contain a surfactant. The effects of the present invention are more pronounced when the aqueous ophthalmic composition further contains a surfactant. The surfactant is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable.

[0050] Examples of surfactants include nonionic surfactants and ionic (anionic, amphoteric, and cationic) surfactants.

[0051] Examples of nonionic surfactants include POE(20) 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); poloxamer 407, poloxamer 235, poloxamer 188, poloxamer 403, POE·POP glycols such as poloxamer 237 and poloxamer 124; POE hydrogenated castor oils such as POE hydrogenated castor oil 40, POE hydrogenated castor oil 50, POE hydrogenated castor oil 60, and POE hydrogenated castor oil 80; POE castor oils such as 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; polyethylene monostearate Polyethylene glycol (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), polyoxyl monostearate Examples include polyethylene glycol monostearate such as ethylene glycol (45 E.O.), polyethylene glycol monostearate (55 E.O.), polyethylene glycol monostearate (75 E.O.), and polyethylene glycol monostearate (140 E.O.); 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 number in parentheses indicates the number of moles added.

[0052] Examples of anionic surfactants include polyoxyethylene alkyl ether phosphates, polyoxyethylene alkyl ether sulfates, alkylbenzene sulfonates, alkyl sulfates, and N-acyl taurine salts.

[0053] Examples of amphoteric surfactants include lauryldimethylaminoacetic acid betaine and alkyldiaminoethylglycine hydrochloride.

[0054] Examples of cationic surfactants include benzalkonium chloride, benzalkonium bromide, benzethonium chloride, chlorhexidine gluconate, polydronium hydrochloride, and cetylpyridinium chloride.

[0055] As the surfactant, nonionic surfactants are preferred. Preferred nonionic surfactants include POE sorbitan fatty acid esters; POE-POP glycols; POE hydrogenated castor oil; POE castor oil; and polyethylene glycol monostearate. More preferably, polysorbate 80, poloxamer 407, 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 are preferred. Even more preferably, polysorbate 80, POE hydrogenated castor oil 40, POE hydrogenated castor oil 60, and polyoxyl stearate 40 are preferred, and polysorbate 80 and POE hydrogenated castor oil 60 are particularly preferred.

[0056] The surfactant may be a commercially available product. The surfactant may be used alone or in combination of two or more types.

[0057] The surfactant content in the aqueous ophthalmic composition according to this embodiment is not particularly limited and is appropriately set depending on the type of surfactant, the type and content of other components, the use and formulation form of the aqueous ophthalmic composition, etc. As for the surfactant content, from the viewpoint of more significantly exhibiting the effects of the present invention, for example, based on the total amount of the aqueous ophthalmic composition, the total surfactant content is preferably 0.00001 to 5 w / v%, more preferably 0.00005 to 1 w / v%, even more preferably 0.0001 to 0.5 w / v%, and even more preferably 0.001 to 0.3 w / v%.

[0058] When the surfactant is a nonionic surfactant, the total surfactant content is preferably 0.001 to 5 w / v%, more preferably 0.005 to 1 w / v%, and even more preferably 0.01 to 0.5 w / v%, based on the total amount of the aqueous ophthalmic composition.

[0059] When the surfactant is a cationic surfactant, the total surfactant content is preferably 0.00001 to 1 w / v%, more preferably 0.00005 to 0.1 w / v%, even more preferably 0.0001 to 0.05 w / v%, and even more preferably 0.001 to 0.01 w / v%, based on the total amount of the aqueous ophthalmic composition.

[0060] In the aqueous ophthalmic composition according to this embodiment, the content ratio of the surfactant to component (A) is not particularly limited and is set appropriately depending on the type of component (A) and the surfactant, the type and content of other components, the use and formulation form of the aqueous ophthalmic composition, etc. As for the content ratio of the surfactant to component (A), from the viewpoint of further enhancing the effects of the present invention, for example, the total content of the surfactant in the aqueous ophthalmic composition according to this embodiment is preferably 0.0005 to 100 parts by mass, more preferably 0.001 to 50 parts by mass, and even more preferably 0.005 to 10 parts by mass, per 1 part by mass of the total content of component (A) contained in the aqueous ophthalmic composition according to this embodiment.

[0061] In the aqueous ophthalmic composition according to this embodiment, the content ratio of the surfactant to component (B) is not particularly limited and is set appropriately depending on the type of component (B) and the surfactant, the type and content of other components, the use and formulation form of the aqueous ophthalmic composition, etc. As for the content ratio of the surfactant to component (B), from the viewpoint of further enhancing the effects of the present invention, for example, the total content of the surfactant in the aqueous ophthalmic composition according to this embodiment is preferably 0.00001 to 5 parts by mass, more preferably 0.0005 to 3 parts by mass, even more preferably 0.0001 to 3 parts by mass, even more preferably 0.001 to 1 part by mass, particularly preferably 0.005 to 0.5 parts by mass, and particularly most preferably 0.01 to 0.5 parts by mass, per 1 part by mass of the total content of component (B) contained in the aqueous ophthalmic composition according to this embodiment.

[0062] [Cushioning material] The aqueous ophthalmic composition according to this embodiment preferably further contains a buffering agent. The effects of the present invention are more pronounced when the aqueous ophthalmic composition further contains a buffering agent. The buffering agent is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable.

[0063] Examples of buffering agents include inorganic buffering agents derived from inorganic acids, and organic buffering agents derived from organic acids or organic bases.

[0064] Examples of inorganic buffers include borate buffers, phosphate buffers, and carbonate buffers. Examples of borate buffers include boric acid or its salts (alkali metal borate, alkaline earth metal borate, etc.). Examples of phosphate buffers include phosphoric acid or its salts (alkali metal phosphate, alkaline earth metal phosphate, etc.). Examples of carbonate buffers include carbonic acid or its salts (alkali metal carbonate, alkaline earth metal carbonate, etc.). In addition, hydrates of borates, phosphates, or carbonates may be used as borate buffers, phosphate buffers, or carbonate buffers. More specific examples include boric acid buffers such as boric acid or its salts (sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, borax, etc.); phosphoric acid buffers such as phosphoric acid or its salts (disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, trisodium phosphate, tripotassium phosphate, calcium monohydrogen phosphate, calcium dihydrogen phosphate, etc.); and carbonate buffers such as carbonate or its salts (sodium bicarbonate, sodium carbonate, ammonium carbonate, potassium carbonate, calcium carbonate, potassium bicarbonate, magnesium carbonate, etc.).

[0065] Examples of organic buffers include citrate buffers, acetate buffers, lactic acid buffers, succinate buffers, Tris buffers, and AMPD buffers. Examples of citrate buffers include citric acid or its salts (alkali metal citrate, alkaline earth metal citrate, etc.). Examples of acetate buffers include acetic acid or its salts (alkali metal acetate, alkaline earth metal acetate, etc.). Examples of lactic acid buffers include lactic acid or its salts (alkali metal lactate, alkaline earth metal lactate, etc.). Examples of succinate buffers include succinic acid or its salts (alkali metal succinate, etc.). In addition, citrate, acetate, lactate, or succinate hydrates may be used as citrate buffers, acetate buffers, lactic acid buffers, or succinate buffers. More specific examples include citric acid or its salts (sodium citrate, potassium citrate, calcium citrate, sodium dihydrogen citrate, disodium citrate, etc.) as citrate buffers; acetic acid or its salts (ammonium acetate, sodium acetate, potassium acetate, calcium acetate, etc.) as acetic acid buffers; lactic acid or its salts (sodium lactate, potassium lactate, calcium lactate, etc.) as lactic acid buffers; and succinic acid or its salts (monosodium succinate, disodium succinate, etc.) as succinic acid buffers. Examples of Tris buffers include trometamol or its salts (trometamol hydrochloride, etc.). Examples of AMPD buffers include 2-amino-2-methyl-1,3-propanediol or its salts.

[0066] Preferred buffering agents include boric acid buffers (e.g., a combination of boric acid and borax), phosphate buffers (e.g., a combination of disodium hydrogen phosphate and sodium dihydrogen phosphate), and Tris buffers (e.g., trometamol). Boric acid buffers are more preferred, boric acid and its salts are even more preferred, and a combination of boric acid and borax is even more preferred.

[0067] You may use commercially available cushioning material. You may use one type of cushioning material alone, or you may use two or more types in combination.

[0068] The buffering agent content in the aqueous ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the type of buffering agent, the types and amounts of other components, the use and formulation form of the aqueous ophthalmic composition, etc. As for the buffering agent content, from the viewpoint of more significantly exhibiting the effects of the present invention, for example, the total buffering agent content is preferably 0.01 to 10 w / v%, more preferably 0.05 to 5 w / v%, and even more preferably 0.1 to 3 w / v%, based on the total amount of the aqueous ophthalmic composition.

[0069] In the aqueous ophthalmic composition according to this embodiment, the content ratio of the buffering agent to component (A) is not particularly limited and is set appropriately depending on the type of component (A) and the buffering agent, the type and content of other components, the use of the aqueous ophthalmic composition and the formulation form, etc. As for the content ratio of the buffering agent to component (A), from the viewpoint of further enhancing the effects of the present invention, for example, the total content of the buffering agent in the aqueous ophthalmic composition according to this embodiment is preferably 0.01 to 10 parts by mass, more preferably 0.1 to 5 parts by mass, and even more preferably 0.5 to 3 parts by mass, per 1 part by mass of the total content of component (A) contained in the aqueous ophthalmic composition according to this embodiment.

[0070] In the aqueous ophthalmic composition according to this embodiment, the content ratio of the buffering agent to component (B) is not particularly limited and is set appropriately depending on the type of component (B) and the buffering agent, the type and content of other components, the use and formulation form of the aqueous ophthalmic composition, etc. As for the content ratio of the buffering agent to component (B), from the viewpoint of further enhancing the effects of the present invention, for example, the total content of the buffering agent is preferably 0.01 to 10 parts by mass, more preferably 0.1 to 5 parts by mass, even more preferably 0.5 to 3 parts by mass, and even more preferably 0.5 to 1 part by mass, per 1 part by mass of the total content of component (B) contained in the aqueous ophthalmic composition according to this embodiment.

[0071] The pH of the aqueous ophthalmic composition according to this embodiment is not particularly limited, as long as it is within a range that is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. The pH of the aqueous ophthalmic composition according to this embodiment may be, for example, 4.0 to 9.5, preferably 4.0 to 9.0, more preferably 4.5 to 9.0, even more preferably 4.5 to 8.5, even more preferably 5.0 to 8.5, particularly preferably 5.5 to 8.0, and particularly most preferably 6.0 to 7.0.

[0072] The aqueous ophthalmic composition according to this embodiment can be adjusted to an osmotic pressure ratio within a range acceptable to the body, as needed. The appropriate osmotic pressure ratio varies depending on the application site, dosage form, etc., but from the viewpoint of more significantly exhibiting the effects of the present invention, it is preferably 0.05 to 6, more preferably 0.4 to 5, even more preferably 0.6 to 3, and even more preferably 0.8 to 2. The osmotic pressure can be adjusted using inorganic salts, polyhydric alcohols, etc., by methods known in the art. The osmotic pressure ratio is the ratio of the osmotic pressure of the sample to 286 mOsm (osmotic pressure of 0.9 w / v% sodium chloride aqueous solution) based on the 17th edition of the Japanese Pharmacopoeia, and the osmotic pressure is measured by referring to the osmotic pressure measurement method (freezing point depression method) described in the Japanese Pharmacopoeia. The standard solution for osmotic pressure ratio measurement (0.9 w / v% sodium chloride aqueous solution) can be prepared by drying sodium chloride (Japanese Pharmacopoeia standard reagent) at 500-650°C for 40-50 minutes, then allowing it to cool in a desiccator (silica gel), accurately weighing 0.900 g of it, dissolving it in purified water to make exactly 100 mL, or by using a commercially available standard solution for osmotic pressure ratio measurement (0.9 w / v% sodium chloride aqueous solution).

[0073] The viscosity of the aqueous ophthalmic composition according to this embodiment is not particularly limited, as long as it is within a range that is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. The viscosity of the aqueous ophthalmic composition according to this embodiment is preferably 0.1 to 10000 mPa·s, more preferably 1 to 3000 mPa·s, even more preferably 1 to 1000 mPa·s, even more preferably 1 to 1000 mPa·s, even more preferably 1 to 100 mPa·s, particularly preferably 1 to 50 mPa·s, particularly more preferably 1 to 10 mPa·s, particularly still preferably 1.3 to 5 mPa·s, and most preferably 1.5 to 3 mPa·s.

[0074] The aqueous ophthalmic composition according to this embodiment may contain, in addition to the above-mentioned components, an appropriate amount of components selected from various pharmacologically active and physiologically active components, provided that the effects of the present invention are not impaired. The components are not particularly limited, and examples include the active ingredients in ophthalmic drugs described in the 2012 edition of the Standards for Approval of Manufacturing and Marketing of Over-the-Counter Drugs (supervised by the Japanese Society of Regulatory Science). Specifically, examples of components used in ophthalmic drugs include the following components. Antiallergic agents: For example, sodium cromoglycate, tranilast, pemirolast potassium, etc. Antihistamines: For example, diphenhydramine hydrochloride, iproheptine, chlorpheniramine maleate, levocabastine hydrochloride, ketotifen fumarate, pemirolast potassium, olopatadine hydrochloride, etc. From the viewpoint of further enhancing the effects of the present invention, it is preferable that the aqueous ophthalmic composition according to this embodiment does not contain diphenhydramine or a salt thereof. (A) Anti-inflammatory agents other than the component: for example, methyl salicylate, glycol salicylate, dipotassium glycyrrhizinate, tranexamic acid, berberine, berberine chloride, berberine sulfate, lysozyme, lysozyme chloride, azulene sulfonic acid, sodium azulene sulfonate, indomethacin, pranoprofen, ibuprofen, ibuprofen piconol, ketoprofen, felbinac, bendazac, piroxicam, bufexamac, butyl flufenamate, zinc sulfate, etc. Steroids: For example, fluticasone propionate, fluticasone furoate, mometasone furoate, beclomethasone propionate, flunisolide, etc. Decongestants: For example, tetrahydrozoline hydrochloride, tetrahydrozoline nitrate, naphazoline hydrochloride, naphazoline nitrate, epinephrine, epinephrine hydrochloride, ephedrine hydrochloride, phenylephrine hydrochloride, dl-methylephedrine hydrochloride, etc. From the viewpoint of further enhancing the effects of the present invention, the aqueous ophthalmic composition according to this embodiment preferably does not contain phenylephrine hydrochloride. (C) Extraocular muscle modulating agents other than the active ingredient: for example, cholinesterase inhibitors having an active site similar to acetylcholine, specifically tropicamide, helenien, atropine sulfate, etc. Vitamins: For example, retinol acetate, retinyl palmitate, tocopherol acetate, flavin adenine dinucleotide sodium, cyanocobalamin, pyridoxine hydrochloride, panthenol, calcium pantothenate, ascorbic acid, sodium ascorbate, etc. Amino acids: For example, glutamic acid, aspartic acid, arginine, aminoethylsulfonic acid (taurine), and their salts. Inorganic salts: For example, metal chlorides such as calcium chloride, magnesium chloride, sodium chloride, and potassium chloride; ammonium chloride; metal sulfates such as calcium sulfate, magnesium sulfate, sodium sulfate, potassium sulfate, and ammonium sulfate. Astringents: For example, zinc oxide, zinc lactate, zinc sulfate, etc. Others: For example, sulfamethoxazole, sulfisoxazole, sulfisomidine, and their salts.

[0075] The aqueous ophthalmic composition according to this embodiment may contain various additives in appropriate amounts, selected according to conventional methods, depending on its use and formulation, as long as the effects of the present invention are not impaired, and one or more additives may be used in combination. Examples of such additives include the various additives listed in the 2007 Dictionary of Pharmaceutical Additives (edited by the Japan Pharmaceutical Additives Association). The following are typical additives. Carrier: For example, an aqueous solvent such as water or aqueous ethanol. Chelating agents: For example, ethylenediaminediacetic acid (EDDA), ethylenediaminetriacetic acid, ethylenediaminetetraacetic acid (EDTA), N-(2-hydroxyethyl)ethylenediaminetriacetic acid (HEDTA), diethylenetriaminepentaacetic acid (DTPA), etc. Base: For example, octyldodecanol, titanium dioxide, potassium bromide, Plastibase, etc. pH adjusters: For example, hydrochloric acid, acetic acid, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, triethanolamine, diisopropanolamine, etc. Stabilizers: For example, sodium formaldehyde sulfoxylate (Longalit), sodium bisulfite, sodium pyrosulfite, aluminum monostearate, glyceryl monostearate, cyclodextrin, monoethanolamine, dibutylhydroxytoluene, etc. Preservatives, disinfectants, or antibacterial agents: For example, zinc chloride, sodium benzoate, ethanol, chlorobutanol, sorbic acid, potassium sorbate, sodium dehydroacetate, methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, butyl parahydroxybenzoate, oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, biguanide compounds (specifically, polyhexanide hydrochloride (polyhexamethylene biguanide), etc.), Glokill (a trade name of Rhodia Corporation), etc. From the viewpoint of further enhancing the effects of the present invention, it is preferable that the aqueous ophthalmic composition according to this embodiment does not contain parahydroxybenzoic acid esters (parabens). Isotonic agents: For example, sodium bisulfite, sodium sulfite, potassium chloride, calcium chloride, sodium chloride, magnesium chloride, potassium acetate, sodium acetate, sodium bicarbonate, sodium carbonate, sodium thiosulfate, magnesium sulfate, glycerin, propylene glycol, etc. When the aqueous ophthalmic composition according to this embodiment contains propylene glycol, the propylene glycol content is preferably 3 w / v% or less, based on the total amount of the aqueous ophthalmic composition, because if it exceeds 3 w / v%, the osmotic pressure becomes too high. Thickeners: For example, cellulosic polymers (e.g., methylcellulose, ethylcellulose, hydroxypropyl methylcellulose, hydroxyethylcellulose, sodium carboxymethylcellulose, etc.), polyvinyl polymers (e.g., polyvinylpyrrolidone, polyvinyl alcohol, etc.), carboxyvinyl polymers, guar gum, hydroxypropyl guar gum, acacia gum, karaya gum, xanthan gum, agar, alginic acid and its salts (sodium salts, etc.), mucopolysaccharides (e.g., heparinoids, heparin, heparin sulfate, heparan sulfate, heparinoids, hyaluronic acid and its salts (sodium salts, etc.)), starch, chitin and its derivatives, chitosan and its derivatives, carrageenan, etc. Sugars: For example, glucose, cyclodextrin, etc. Sugar alcohols: For example, xylitol, sorbitol, mannitol, glycerin, etc. These may be in d-isomer, l-isomer, or dl-isomer. Oils: For example, vegetable oils such as sesame oil, castor oil, soybean oil, and olive oil; animal oils such as squalane; and mineral oils such as liquid paraffin and petrolatum.

[0076] When the aqueous ophthalmic composition according to this embodiment contains water, from the viewpoint of more significantly exhibiting the effects of the present invention, for example, the water content is preferably 80 w / v% or more and less than 100 w / v%, more preferably 85 w / v% or more and 99.5 w / v%, and even more preferably 90 w / v% or more and 99.2 w / v%, based on the total amount of the aqueous ophthalmic composition.

[0077] The water used in the aqueous ophthalmic composition according to this embodiment may be any water that is pharmaceutically, pharmacologically (pharmaceutically), or physiologically acceptable. Examples of such water include distilled water, tap water, purified water, sterile purified water, water for injection, and distilled water for injection. These definitions are based on the 17th edition of the Japanese Pharmacopoeia.

[0078] The aqueous ophthalmic composition according to this embodiment can be prepared, for example, by adding and mixing component (A), component (B), and other components as needed, in desired amounts. Specifically, it can be prepared, for example, by dissolving or suspending the above components in purified water, adjusting to a predetermined pH and osmotic pressure, and sterilizing by filtration sterilization or the like.

[0079] The aqueous ophthalmic composition according to this embodiment can take various dosage forms depending on the purpose, such as liquid, gel, or semi-solid (ointment, etc.). Among these, liquid formulations are preferred, and aqueous liquid formulations are more preferred.

[0080] The aqueous ophthalmic composition according to this embodiment can be used, for example, as eye drops (also called eye solutions or eye medicines; eye drops include artificial tears and eye drops that can be used while wearing contact lenses), eye washes (also called eye wash solutions or eye medicines; eye washes include eye washes that can be used while wearing contact lenses), and contact lens compositions [contact lens insertion solutions, contact lens care compositions (contact lens disinfectants, contact lens preservatives, contact lens cleaning agents, contact lens cleaning and preservation agents), etc.]. Note that "contact lenses" include hard contact lenses and soft contact lenses (including both ionic and nonionic types, and including both silicone hydrogel contact lenses and non-silicone hydrogel contact lenses).

[0081] The aqueous ophthalmic composition according to this embodiment is preferably an eye drop (including eye drops that can be instilled while wearing contact lenses) because it can more clearly demonstrate the effects of the present invention. When the aqueous ophthalmic composition according to this embodiment is an eye drop, the method of use and dosage are not particularly limited as long as they are effective and have few side effects, but examples include using 1 to 2 drops 2 to 4 times a day, or 4 times a day, for adults (15 years of age or older) and children 7 years of age or older, or using 1 to 2 drops, 1 to 3 drops, or 2 to 3 drops 5 to 6 times a day.

[0082] The aqueous ophthalmic composition according to this embodiment is provided in any container. The container for containing the aqueous ophthalmic composition according to this embodiment is not particularly limited and may be made of glass or plastic, for example. Plastic is preferred. Examples of plastics include polyethylene terephthalate, polyarylate, polyethylene naphthalate, polycarbonate, polyethylene, polypropylene, polyimide and copolymers of monomers constituting these, and mixtures of two or more of these. Polypropylene, polyethylene, and polyethylene terephthalate are preferred, and polyethylene terephthalate is more preferred. The container for containing the aqueous ophthalmic composition according to this embodiment may be a transparent container that allows visibility of the inside of the container, or an opaque container that makes it difficult to see inside the container. A transparent container is preferred. Here, "transparent container" includes both colorless transparent containers and colored transparent containers.

[0083] A nozzle may be attached to the container for containing the aqueous ophthalmic composition according to this embodiment. The material of the nozzle is not particularly limited and may be made of glass or plastic, for example. Plastic is preferred. Examples of plastics include polybutylene terephthalate, polyethylene, polypropylene, polyethylene naphthalate and copolymers of monomers constituting these, and mixtures of two or more of these. From the viewpoint of further enhancing the effects of the present invention, polypropylene, polyethylene, polyethylene terephthalate, and polyethylene naphthalate are preferred as the material of the nozzle, and polyethylene is more preferred.

[0084] The container for containing the aqueous ophthalmic composition according to this embodiment may be a multi-dose type that contains multiple doses, or a unit-dose type that contains a single dose. However, a multi-dose type is preferred because it allows the effects of the present invention to be more pronounced.

[0085] [2. Method for suppressing the formation of precipitates in aqueous ophthalmic compositions] The aqueous ophthalmic composition according to this embodiment significantly suppresses the occurrence of precipitates in the aqueous ophthalmic composition by incorporating at least one selected from the group consisting of allantoin, epsilon-aminocaproic acid and its salts, and at least one selected from the group consisting of chondroitin sulfate and its salts in an amount of 0.7 w / v% or more based on the total amount of the aqueous ophthalmic composition. Therefore, as one embodiment of the present invention, a method is provided for suppressing the occurrence of precipitates in an aqueous ophthalmic composition, comprising incorporating (A) at least one selected from the group consisting of allantoin, epsilon-aminocaproic acid and its salts, and (B) one or more selected from the group consisting of chondroitin sulfate and its salts in an amount of 0.7 w / v% or more based on the total amount of the aqueous ophthalmic composition.

[0086] The types and content of component (A), component (B), other components, formulation form and use of the aqueous ophthalmic composition in this embodiment are as described in [1. Aqueous Ophthalmic Composition].

[0087] [3. Method for improving the unpleasant taste after administration of aqueous ophthalmic compositions] The aqueous ophthalmic composition according to this embodiment improves the unpleasant taste (bitter off-flavor) after administration of the aqueous ophthalmic composition by incorporating at least one selected from the group consisting of epsilon-aminocaproic acid and its salts, and at least one selected from the group consisting of chondroitin sulfate and its salts in an amount of 0.7 w / v% or more based on the total amount of the aqueous ophthalmic composition. Therefore, as one embodiment of the present invention, a method is provided to improve the unpleasant taste after administration of the aqueous ophthalmic composition, comprising incorporating (A1) at least one selected from the group consisting of epsilon-aminocaproic acid and its salts, and (B) one or more selected from the group consisting of chondroitin sulfate and its salts in an amount of 0.7 w / v% or more based on the total amount of the aqueous ophthalmic composition. Furthermore, as an embodiment of the present invention, a method is provided for improving the unpleasant bitter taste after administration of an aqueous ophthalmic composition, comprising blending the aqueous ophthalmic composition with (A1) at least one selected from the group consisting of epsilon-aminocaproic acid and its salts, and (B) one or more selected from the group consisting of chondroitin sulfate and its salts at a concentration of 0.7 w / v% or more based on the total amount of the aqueous ophthalmic composition.

[0088] The types and content of component (A1), component (B), other components, formulation form and uses of the aqueous ophthalmic composition in this embodiment are as described in [1. Aqueous Ophthalmic Composition]. [Examples]

[0089] The present invention will be described in detail below based on test examples, but the present invention is not limited to these.

[0090] [Test Example 1: Evaluation of Precipitate Formation (1)] Aqueous ophthalmic compositions (100 mL) for each example and comparative example shown in Table 1 were prepared by conventional methods. The units for each component in Table 1 are w / v%. Next, 0.5 mL of each aqueous ophthalmic composition was placed in a 24-well plate (IWAKI MICROPLATE: 3820-024) and dried overnight at 60°C in a laboratory equipment drying oven (LabWare Drying Oven, DG82; manufactured by Yamato Scientific Co., Ltd.). The state of each aqueous ophthalmic composition after drying was observed visually, and the occurrence of precipitates was evaluated according to the following evaluation criteria (N=2). The results are shown in Table 1. <Evaluation Criteria for Precipitation Formation> Clearly visible precipitates are present across the entire bottom surface of the well:+++ There are clearly visible precipitates in part of the well. There are some unclear precipitates in part of the well :+ No precipitates present. Furthermore, the chondroitin sulfate sodium used was the non-pharmacopoeial chondroitin sulfate sodium for eye drops and injection (manufactured by Maruha Nichiro Foods Co., Ltd.).

[0091] [Table 1]

[0092] In Comparative Example 1-1, an aqueous ophthalmic composition containing only allantoin, precipitate formation was observed. Similarly, precipitate formation was observed in Comparative Example 1-2, an aqueous ophthalmic composition containing allantoin and 0.5 w / v% chondroitin sulfate sodium. In contrast, in Examples 1-1 and 1-2, which contained allantoin and 1 w / v% or 3 w / v% chondroitin sulfate sodium, no precipitate formation was observed.

[0093] [Test Example 2: Evaluation of Precipitate Formation (2)] Aqueous ophthalmic compositions (100 mL) of each example and comparative example shown in Tables 2 and 3 were prepared by conventional methods. The units for each component in Tables 2 and 3 are w / v%. Next, each aqueous ophthalmic composition was dried in the same manner as in Test Example 1, and the formation of precipitates after drying was evaluated. The results are shown in Tables 2 and 3. Furthermore, the chondroitin sulfate sodium used was the non-pharmacopoeial chondroitin sulfate sodium for eye drops and injection (manufactured by Maruha Nichiro Foods Co., Ltd.).

[0094] [Table 2]

[0095] [Table 3]

[0096] In the aqueous ophthalmic compositions of Comparative Examples 2-1 and 2-3, which contained only epsilon-aminocaproic acid, the formation of precipitates (white residue) was observed. Similarly, in the aqueous ophthalmic compositions of Comparative Examples 2-2 and 2-4, which were formulated with 0.5 w / v% chondroitin sulfate sodium in addition to epsilon-aminocaproic acid, the formation of precipitates (white residue) was also observed. In contrast, in the aqueous ophthalmic compositions of Examples 2-1, 2-2, and 2-3, which were formulated with 1 w / v% or 3 w / v% chondroitin sulfate sodium in addition to epsilon-aminocaproic acid, it was confirmed that no precipitates formed.

[0097] [Test Example 3: Taste Evaluation] Aqueous ophthalmic compositions (100 mL) of each example and comparative example shown in Table 4 were prepared by conventional methods. The units for each component in Table 4 are w / v%. Next, the bitterness and off-flavor indicators of each aqueous ophthalmic composition were measured using a taste recognition device (SA402B; manufactured by Intelligent Sensor Technology Co., Ltd.). The measurement method followed the instruction manual for the SA402B, measuring the potential difference between the reference solution and each aqueous ophthalmic composition as an indicator of bitterness and off-flavor. Using the obtained measurement values, the difference in bitterness and off-flavor of Example 3-1 compared to Comparative Example 3-1 was calculated using the following formula. The results are shown in Table 4. [Equation 1] Difference in index from Comparative Example 3-1 = Measured value of Comparative Example 3-1 - Measured value of Example 3-1 Furthermore, the chondroitin sulfate sodium used was the non-pharmacopoeial chondroitin sulfate sodium for eye drops and injection (manufactured by Maruha Nichiro Foods Co., Ltd.).

[0098] [Table 4]

[0099] In the aqueous ophthalmic compositions of Examples 3-1 and 3-2, which contained epsilon-aminocaproic acid with 1 w / v% or 3 w / v% chondroitin sulfate sodium, it was confirmed that the bitterness and off-flavor indicators were significantly reduced compared to the aqueous ophthalmic composition of Comparative Example 3-1, which contained epsilon-aminocaproic acid alone.

[0100] [Test Example 4: Evaluation of Precipitate Formation (3)] Aqueous ophthalmic compositions (100 mL) for each example and comparative example shown in Table 5 were prepared by conventional methods. The units for each component in Table 5 are w / v%. Next, each aqueous ophthalmic composition was dried in the same manner as in Test Example 1, and the formation of precipitates after drying was evaluated. The results are shown in Table 5. Furthermore, the chondroitin sulfate sodium used was the non-pharmacopoeial chondroitin sulfate sodium (manufactured by Seikagaku Corporation, weight-average molecular weight approximately 20,000).

[0101] [Table 5]

[0102] In the aqueous ophthalmic compositions of Comparative Examples 4-1 and 4-3, which contained only allantoin, and in the aqueous ophthalmic composition of Comparative Example 4-2, which contained allantoin and a boric acid buffer, precipitate formation was observed. In contrast, in the aqueous ophthalmic compositions of Examples 4-1 to 4-4, 4-6 and 4-7, which contained allantoin with 1 w / v% or 3 w / v% chondroitin sulfate sodium, and in the aqueous ophthalmic composition of Example 4-5, which contained allantoin with 3 w / v% chondroitin sulfate sodium and methyl sulfate neostigmine, it was confirmed that no precipitate formation occurred.

[0103] [Examples of formulations] Tables 6 and 7 below show examples of formulations. Unless otherwise specified in the tables, all units for each component in Tables 6 and 7 are w / v%. Formulation examples 1 to 13 are all eye drops. Formulation examples 1' to 13' are obtained by filling 10 mL of each formulation into polyethylene terephthalate containers and attaching polyethylene nozzles. Formulation examples 1'' to 13'' are obtained by filling 10 mL of each formulation into polyethylene terephthalate containers and attaching polybutylene terephthalate nozzles. The eye drops of formulation examples 1 to 13 can be used as eye drops for use with hard contact lenses, soft contact lenses, or when not wearing contact lenses.

[0104] [Table 6]

[0105] [Table 7]

Claims

1. 1. An aqueous ophthalmic composition comprising: (A) 0.06 w / v % or more of allantoin, based on the total amount of the aqueous ophthalmic composition; and at least one selected from the group consisting of epsilon-aminocaproic acid and salts thereof, in an amount of 0.25 w / v % to 1.5 w / v % based on the total amount of the aqueous ophthalmic composition; and (B) 2 w / v % to 3.5 w / v % of at least one selected from the group consisting of chondroitin sulfate and salts thereof, based on the total amount of the aqueous ophthalmic composition; and 2 w / v % to 3.5 w / v % of at least one selected from the group consisting of chondroitin sulfate and salts thereof, in an amount of 5.0 or more, based on the total amount of the aqueous ophthalmic composition;

2. The aqueous ophthalmic composition of claim 1, further containing (C) neostigmine methylsulfate.

3. An aqueous ophthalmic composition described in claim 1 or 2, further containing (D) a terpenoid.

4. An aqueous ophthalmic composition described in any one of claims 1 to 3, further containing a buffering agent.

5. A composition containing allantoin and at least one selected from the group consisting of epsilon-aminocaproic acid and its salts, and at least one selected from the group consisting of chondroitin sulfate and its salts, A method for suppressing the formation of precipitates in an aqueous ophthalmic composition after drying, comprising preparing an aqueous ophthalmic composition that contains: (A) 0.06 w / v % or more of allantoin, based on the total amount of the aqueous ophthalmic composition, and at least one selected from the group consisting of epsilon-aminocaproic acid and salts thereof, in an amount of 0.25 w / v % to 1.5 w / v %, based on the total amount of the aqueous ophthalmic composition; and (B) 2 w / v % to 3.5 w / v % of at least one selected from the group consisting of chondroitin sulfate and salts thereof, based on the total amount of the aqueous ophthalmic composition; the aqueous ophthalmic composition having a pH of 5.0 or higher and in the form of a liquid.