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]

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

[0002] In general, aqueous ophthalmic compositions are filled in a container with an opening, and are repeatedly used by dispensing the aqueous ophthalmic composition from the opening when in use. In this case, the aqueous ophthalmic composition adhering to the opening may dry out and form a precipitate, which is known to cause various problems.

[0003] For example, the accumulation of precipitates at the opening not only adheres to the opening but also to the surrounding area and even to the inside of the lid or cap, not only causing an unpleasant impression to the user but also making it difficult to open and close the opening when used repeatedly. Furthermore, in the case of eye drops, the diameter of the outlet, which is the opening, is often very small, and even a small amount of precipitate adhesion may clog the passage of the aqueous ophthalmic composition, preventing the accurate amount of liquid from being dripped. Furthermore, if precipitates accumulate at the outlet of the eye drop, there is a concern that the precipitates may get into the eye when the eye drop is administered.

[0004] On the other hand, in the case of aqueous ophthalmic compositions that are applied directly to the ocular mucosa, if the liquid that leaks out of the eye after application dries and precipitates, white solid matter will adhere to areas around the eye, such as the eyelids, eyelashes, and under the eye, and therefore the formation of precipitates due to drying of the aqueous ophthalmic composition is problematic from the standpoint of appearance and cosmetics.

[0005] As a method for suppressing the formation of precipitates in an aqueous composition after drying, for example, Patent Document 1 reports a method in which chlorpheniramines and amino acids are added to an aqueous composition containing a new quinolone agent. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Japanese Patent Application Laid-Open No. 2012-250918 Summary of the Invention [Problem to be solved by the invention]

[0007] However, there have been no reports to date of the occurrence of precipitates after drying in aqueous ophthalmic compositions containing allantoin or epsilon-aminocaproic acid. The present inventors have conducted various studies on aqueous ophthalmic compositions containing allantoin or epsilon-aminocaproic acid and have confirmed that there is a problem in that a white solid called white residue precipitates when the aqueous ophthalmic composition dries.

[0008] An object of the present invention is to provide an aqueous ophthalmic composition that contains allantoin and at least one selected from the group consisting of epsilon-aminocaproic acid and salts thereof, and that is inhibited from producing precipitates after drying. [Means for solving the problem]

[0009] The present inventors have unexpectedly found that the formation of precipitates in an aqueous ophthalmic composition containing allantoin and epsilon-aminocaproic acid and its salts can be suppressed by incorporating a specific amount or more of at least one member selected from the group consisting of chondroitin sulfate and its salts. 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 salts thereof, and (B) at least one selected from the group consisting of chondroitin sulfate and salts thereof, wherein the content of component (B) is 0.7 w / v% or more based on the total amount of the aqueous ophthalmic composition. [2] 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] 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) The aqueous ophthalmic composition according to any one of [1] to [3], further comprising neostigmine methylsulfate. [5] The aqueous ophthalmic composition according to any one of [1] to [4], further comprising (D) a terpenoid. [6] A method for inhibiting the formation of precipitates in an aqueous ophthalmic composition, comprising blending into the aqueous ophthalmic composition (A) at least one selected from the group consisting of allantoin, and epsilon-aminocaproic acid and salts thereof, and (B) at least one selected from the group consisting of chondroitin sulfate and salts thereof 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 salts thereof, while suppressing the formation of precipitates after drying. DETAILED DESCRIPTION OF THE INVENTION

[0012] Hereinafter, embodiments of the present invention will be described in detail, but 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 / 100 mL".

[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 salts thereof (also referred to simply as "component (A)"). Hereinafter, at least one selected from the group consisting of epsilon-aminocaproic acid and salts thereof may be referred to as "component (A1)."

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

[0016] Allantoin is a known compound that is also called 2-ureidohydantoin.

[0017] Salts of epsilon-aminocaproic acid include, for example, salts with inorganic bases. Examples of salts with inorganic bases include alkali metal salts such as sodium salt and potassium salt; and alkaline earth metal salts such as magnesium salt and calcium salt. Of epsilon-aminocaproic acid and salts thereof, epsilon-aminocaproic acid is preferred.

[0018] Allantoin, epsilon-aminocaproic acid, and salts thereof may be commercially available products. Allantoin, epsilon-aminocaproic acid, and salts thereof may be used alone or in combination of two or more.

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

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

[0021] When epsilon-aminocaproic acid and its salts are used as component (A), the total content of epsilon-aminocaproic acid and its salts is, for example, preferably 0.01 to 5 w / v%, more preferably 0.05 to 4 w / v%, even more preferably 0.1 to 3 w / v%, and even more preferably 0.5 to 2 w / v%, based on the total amount of the aqueous ophthalmic composition. Furthermore, it is preferable that the content of epsilon-aminocaproic acid and its salts is less than 3 w / v%, based on the total amount of the aqueous ophthalmic composition, from the viewpoint of significantly achieving the effects of the present invention.

[0022] [(B) component] The aqueous ophthalmic composition of this embodiment contains, in addition to component (A), at least one selected from the group consisting of (B) chondroitin sulfate and salts thereof (also simply referred to as "component (B)").

[0023] Chondroitin sulfate and its salts, which are component (B), are not particularly limited as long as they are pharmaceutically, pharmacologically (pharmaceutical), or physiologically acceptable. The molecular weight of chondroitin sulfate and its salts is not particularly limited as long as they are pharmaceutically, pharmacologically (pharmaceutical), or physiologically acceptable, but typically, those with a weight-average molecular weight of about 1,000 to 100,000, preferably about 5,000 to 50,000, and more preferably about 10,000 to 40,000 can be used.

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

[0025] As chondroitin sulfate and salts thereof, chondroitin sulfate and alkali metal salts of chondroitin sulfate are preferred, chondroitin sulfate and sodium chondroitin sulfate are more preferred, and sodium chondroitin sulfate is even more preferred.

[0026] Chondroitin sulfate and salts thereof may be commercially available. One type of chondroitin sulfate and salts thereof may be used alone, or two or more types may be used in combination.

[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 added, the intended use and formulation of the aqueous ophthalmic composition, etc. From the viewpoint of more significantly achieving the effects of the present invention, the lower limit of the content of component (B) is, for example, 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 added, the intended use and formulation of the aqueous ophthalmic composition, etc. The upper limit of the content of component (B) is, for example, 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 pronounced effects of the present invention and usability. 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 aspect, 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] The ratio of component (B) to component (A) in the aqueous ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the types of components (A) and (B), the types and amounts of other components blended, the intended use and formulation of the aqueous ophthalmic composition, and the like. From the viewpoint of further enhancing the effects of the present invention, the ratio of component (B) to component (A) is, for example, 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, of the total content of component (B) per 1 part by mass of the total content of component (A) in the aqueous ophthalmic composition according to this embodiment. Other preferred ranges include 1 to 40 parts by mass and 1.5 to 30 parts by mass.

[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 of the total content of component (B) per 1 part by mass of the total content of component (A) in the aqueous ophthalmic composition of this embodiment. Preferred ranges also include 5 to 40 parts by mass and 10 to 30 parts by mass.

[0030] When epsilon-aminocaproic acid and its salts are used as component (A), the 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 of the total content of component (B) per part by mass of the total content of component (A) in the aqueous ophthalmic composition of this embodiment. Preferred ranges also include 1 to 40 parts by mass and 1.5 to 30 parts by mass.

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

[0032] Neostigmine methylsulfate, which is component (C), is not particularly limited as long as it is medicamentarily, pharmacologically (pharmaceutical) 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 appropriately depending on the types and contents of other blended components, the intended use and formulation of the aqueous ophthalmic composition, etc. From the viewpoint of more significantly exhibiting the effects of the present invention, the content of component (C) is, for example, preferably 0.00005 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%, based on the total amount of the aqueous ophthalmic composition.

[0035] The content ratio of component (C) to component (A) in the aqueous ophthalmic composition according to the present embodiment is not particularly limited, and is set appropriately depending on the types of components (A) and (C), the types and contents of other blended components, the intended use and formulation of the aqueous ophthalmic composition, etc. From the viewpoint of further enhancing the effects of the present invention, the content ratio of component (C) to component (A) is, for example, preferably 0.00005 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, of the total content of component (C) per 1 part by mass of the total content of component (A) in the aqueous ophthalmic composition according to the present embodiment.

[0036] The ratio of component (C) to component (B) in the aqueous ophthalmic composition of this embodiment is not particularly limited and is set appropriately depending on the types of components (B) and (C), the types and amounts of other components blended, the intended use and formulation of the aqueous ophthalmic composition, and other factors. From the viewpoint of further enhancing the effects of the present invention, the ratio of component (C) to component (B) 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, of the total content of component (C) per 1 part by mass of the total content of component (B) in the aqueous ophthalmic composition of this embodiment. Other preferred ranges include 0.0005 to 0.003 parts by mass and 0.001 to 0.002 parts by mass.

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

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

[0039] Terpenoids include, for example, cyclic and acyclic terpenes.

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

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

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

[0043] Terpenoids may be any of the d-, l-, and dl-isomers, and examples thereof include 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, do not have optical isomers.

[0044] As the terpenoid, menthol, camphor, borneol, menthone, geraniol, eucalyptus oil and bergamot oil are preferred, menthol, camphor and borneol are more preferred, l-menthol, d-camphor, dl-camphor and d-borneol are even more preferred, and l-menthol is even more preferred.

[0045] The terpenoids used may be commercially available products. One type of terpenoid may be used alone, or two or more types may be used in combination.

[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 contents of other blended components, the intended use and formulation of the aqueous ophthalmic composition, etc. From the viewpoint of more significantly exhibiting the effects of the present invention, the content of component (D) is, for example, 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%, based on the total amount of the aqueous ophthalmic composition.

[0047] The content ratio of component (D) to component (A) in the aqueous ophthalmic composition according to the present embodiment is not particularly limited, and is set appropriately depending on the types of components (A) and (D), the types and contents of other blended components, the intended use and formulation of the aqueous ophthalmic composition, etc. From the viewpoint of further enhancing the effects of the present invention, the content ratio of component (D) to component (A) is, for example, 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, of the total content of component (D) per 1 part by mass of the total content of component (A) in the aqueous ophthalmic composition according to the present embodiment.

[0048] The content ratio of the component (D) to the component (B) in the aqueous ophthalmic composition according to this embodiment is not particularly limited, and is set appropriately depending on the types of the components (B) and (D), the types and contents of other blended components, the intended use and formulation of the aqueous ophthalmic composition, etc. From the viewpoint of further enhancing the effects of the present invention, the content ratio of the component (D) to the component (B) is, for example, 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, of the total content of the component (D) per 1 part by mass of the total content of the component (B) in the aqueous ophthalmic composition according to this embodiment.

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

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

[0051] Examples of nonionic surfactants include 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) fatty acid esters; 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), polyethylene monostearate polyethylene glycol monostearate such as polyethylene glycol (45 E.O.), polyethylene glycol monostearate (55 E.O.), polyethylene glycol monostearate (75 E.O.), 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; POE alkyl phenyl ethers such as POE (10) nonylphenyl ether. In the compounds exemplified above, POE stands for polyoxyethylene, POP stands for polyoxypropylene, and the numbers in parentheses indicate the number of moles added.

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

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

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

[0055] The surfactant is preferably a nonionic surfactant. Examples of the nonionic surfactant 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 40 stearate, and further preferably polysorbate 80, POE hydrogenated castor oil 40, POE hydrogenated castor oil 60, and polyoxyl 40 stearate, with polysorbate 80 and POE hydrogenated castor oil 60 being particularly preferred.

[0056] The surfactant may be a commercially available product. One surfactant may be used alone, or two or more surfactants may be used in combination.

[0057] The content of surfactant in the aqueous ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the type of surfactant, the types and contents of other blended components, the intended use and formulation of the aqueous ophthalmic composition, etc. From the viewpoint of more significantly exhibiting the effects of the present invention, the content of surfactant is, for example, 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%, based on the total amount of the aqueous ophthalmic composition.

[0058] When the surfactant is a nonionic surfactant, the content of the surfactant is, for example, 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 content of the surfactant is, for example, 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] The content ratio of the surfactant relative to the component (A) in the aqueous ophthalmic composition according to this embodiment is not particularly limited, and is set appropriately depending on the types of component (A) and surfactant, the types and contents of other blended components, the intended use and formulation of the aqueous ophthalmic composition, etc. From the viewpoint of further enhancing the effects of the present invention, the content ratio of the surfactant relative to the component (A) is, for example, 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, of the total content of the component (A) contained in the aqueous ophthalmic composition according to this embodiment, for example.

[0061] The content ratio of the surfactant relative to the component (B) in the aqueous ophthalmic composition according to this embodiment is not particularly limited, and is set appropriately depending on the types of component (B) and surfactant, the types and contents of other blended components, the intended use and formulation of the aqueous ophthalmic composition, etc. From the viewpoint of further enhancing the effects of the present invention, the content ratio of the surfactant relative to the component (B) is, for example, 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 more preferably 0.01 to 0.5 parts by mass, per 1 part by mass of the total content of component (B) in the aqueous ophthalmic composition according to this embodiment.

[0062] [Buffer] The aqueous ophthalmic composition according to this embodiment preferably further contains a buffer. When the aqueous ophthalmic composition further contains a buffer, the effects of the present invention are more pronounced. The buffer is not particularly limited, as long as it is medicamentarily, pharmacologically (pharmaceutical), or physiologically acceptable.

[0063] Examples of the buffer include inorganic buffers, which are buffers derived from inorganic acids, and organic buffers, which are buffers 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 borates, alkaline earth metal borates, etc.). Examples of phosphate buffers include phosphoric acid or its salts (alkali metal phosphates, alkaline earth metal phosphates, etc.). Examples of carbonate buffers include carbonic acid or its salts (alkali metal carbonates, alkaline earth metal carbonates, etc.). Furthermore, hydrates of borate, phosphate, or carbonate may be used as borate buffers, phosphate buffers, or carbonate buffers. More specific examples of borate buffers include boric acid or salts thereof (sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, borax, etc.); phosphate buffers include phosphoric acid or salts thereof (disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, trisodium phosphate, tripotassium phosphate, calcium monohydrogen phosphate, calcium dihydrogen phosphate, etc.); and carbonate buffers include carbonic acid or salts thereof (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, lactate buffers, succinate buffers, Tris buffers, and AMPD buffers. Examples of citrate buffers include citric acid or salts thereof (such as alkali metal citrates and alkaline earth metal citrates). Examples of acetate buffers include acetic acid or salts thereof (such as alkali metal acetates and alkaline earth metal acetates). Examples of lactate buffers include lactic acid or salts thereof (such as alkali metal lactates and alkaline earth metal lactates). Examples of succinate buffers include succinic acid or salts thereof (such as alkali metal succinates). Furthermore, hydrates of citrate, acetate, lactate, or succinate may be used as citrate buffers, acetate buffers, lactate buffers, or succinate buffers. More specific examples of citrate buffers include citric acid or its salts (sodium citrate, potassium citrate, calcium citrate, sodium dihydrogen citrate, disodium citrate, etc.); acetate buffers include acetic acid or its salts (ammonium acetate, sodium acetate, potassium acetate, calcium acetate, etc.); lactate buffers include lactic acid or its salts (sodium lactate, potassium lactate, calcium lactate, etc.); and succinate buffers include succinic acid or its salts (monosodium succinate, disodium succinate, etc.). 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] As the buffer, boric acid buffer (e.g., a combination of boric acid and borax), phosphate buffer (e.g., a combination of disodium hydrogen phosphate and sodium dihydrogen phosphate), and Tris buffer (e.g., trometamol) are preferred, with boric acid buffer being more preferred, boric acid and its salts being even more preferred, and a combination of boric acid and borax being even more preferred.

[0067] The buffering agent may be a commercially available product. One type of buffering agent may be used alone, or two or more types may be used in combination.

[0068] The content of the buffering agent 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 contents of other blended ingredients, the intended use and formulation of the aqueous ophthalmic composition, etc. From the viewpoint of more significantly exhibiting the effects of the present invention, the content of the buffering agent is, for example, 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] The content ratio of the buffering agent relative to the component (A) in the aqueous ophthalmic composition according to this embodiment is not particularly limited, and is set appropriately depending on the types of component (A) and buffering agent, the types and contents of other blended components, the intended use and formulation of the aqueous ophthalmic composition, etc. From the viewpoint of further enhancing the effects of the present invention, the content ratio of the buffering agent relative to the component (A) is, for example, 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, of the total content of the buffering agent relative to 1 part by mass of the total content of the component (A) in the aqueous ophthalmic composition according to this embodiment.

[0070] The content ratio of the buffering agent relative to the component (B) in the aqueous ophthalmic composition according to this embodiment is not particularly limited, and is set appropriately depending on the types of component (B) and buffering agent, the types and contents of other blended components, the intended use and formulation of the aqueous ophthalmic composition, etc. From the viewpoint of further enhancing the effects of the present invention, the content ratio of the buffering agent relative to the component (B) is, for example, 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, of the total content of the buffering agent relative to 1 part by mass of the total content of the component (B) 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 medicamentarily, pharmacologically (pharmaceutical), or physiologically acceptable range. 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 more 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 biologically acceptable range, as needed. The appropriate osmotic pressure ratio varies depending on the application site, dosage form, etc.; however, from the viewpoint of more significantly achieving 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 defined as the ratio of the osmotic pressure of the sample to 286 mOsm (the osmotic pressure of a 0.9 w / v% sodium chloride aqueous solution) according to the Japanese Pharmacopoeia, 17th Edition, and is measured using the osmotic pressure measurement method (freezing-point depression method) described in the Japanese Pharmacopoeia. The standard solution for measuring osmolality ratios (0.9 w / v% sodium chloride aqueous solution) can be prepared by drying sodium chloride (Japanese Pharmacopoeia standard reagent) at 500-650°C for 40-50 minutes, allowing it to cool in a desiccator (silica gel), accurately weighing 0.900 g of the solution, and dissolving it in purified water to make exactly 100 mL; alternatively, a commercially available standard solution for measuring osmolality ratios (0.9 w / v% sodium chloride aqueous solution) can be used.

[0073] The viscosity of the aqueous ophthalmic composition according to this embodiment is not particularly limited, as long as it is within a medicamentarily, pharmacologically (pharmaceutical), or physiologically acceptable range. The viscosity of the aqueous ophthalmic composition according to this embodiment, as measured at 20°C using a rotational viscometer (TV-20 viscometer, manufactured by Toki Sangyo Co., Ltd., rotor: 1°34' x R24), is preferably 0.1 to 10,000 mPa·s, more preferably 1 to 3,000 mPa·s, even more preferably 1 to 1,000 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, even more 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-described components, a combination of various pharmacologically active components and physiologically active components in appropriate amounts, as long as the effects of the present invention are not impaired. The components are not particularly limited, and examples thereof include active ingredients in ophthalmic drugs listed in the 2012 edition of the OTC Drug Manufacturing and Marketing Approval Standards (edited by the Japan Society of Regulatory Science). Specific examples of components used in ophthalmic drugs include the following: 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, the aqueous ophthalmic composition according to this embodiment preferably does not contain diphenhydramine or a salt thereof. Anti-inflammatory agents other than component (A): for example, methyl salicylate, glycol salicylate, dipotassium glycyrrhizinate, tranexamic acid, berberine, berberine chloride, berberine sulfate, lysozyme, lysozyme chloride, azulene sulfonic acid, azulene sulfonate sodium, 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) Ocular muscle regulating drugs other than the component: For example, cholinesterase inhibitors having an active center similar to that of acetylcholine, specifically tropicamide, helenien, atropine sulfate, etc. Vitamins: for example, retinol acetate, retinol 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 salts thereof. Inorganic salts: for example, metal chlorides such as calcium chloride, magnesium chloride, sodium chloride, potassium chloride, etc.; ammonium chloride; metal sulfates such as calcium sulfate, magnesium sulfate, sodium sulfate, potassium sulfate, ammonium sulfate, etc. Astringents: for example, zinc oxide, zinc lactate, zinc sulfate, etc. Others: For example, sulfamethoxazole, sulfisoxazole, sulfisomidine and their salts.

[0075] The aqueous ophthalmic composition of this embodiment may contain one or more additives selected appropriately in a conventional manner depending on the intended use and formulation, as long as the effects of the present invention are not impaired. Examples of such additives include those listed in the Pharmaceutical Additives Dictionary 2007 (edited by the Japan Pharmaceutical Additives Association). Representative additives include the following: Carrier: For example, an aqueous solvent such as water or aqueous ethanol. Chelating agents: for example, ethylenediaminediacetic acid (EDDA), ethylenediaminetriacetic acid, ethylenediaminetetraacetic acid (EDTA), N-(2-hydroxyethyl)ethylenediaminetriacetic acid (HEDTA), diethylenetriaminepentaacetic acid (DTPA), etc. Bases: for example, octyldodecanol, titanium oxide, potassium bromide, plastibase, etc. pH adjusters: for example, hydrochloric acid, acetic acid, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, triethanolamine, diisopropanolamine, etc. Stabilizers: for example, sodium formaldehyde sulfoxylate (Rongalit), sodium hydrogen sulfite, sodium pyrosulfite, aluminum monostearate, glycerin 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)), GLOQIL (trade name, manufactured by Rhodia), 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 parahydroxybenzoic acid esters (parabens). Isotonicity agents: for example, sodium hydrogen sulfite, sodium sulfite, potassium chloride, calcium chloride, sodium chloride, magnesium chloride, potassium acetate, sodium acetate, sodium hydrogen carbonate, sodium carbonate, sodium thiosulfate, magnesium sulfate, glycerin, propylene glycol, etc. When the aqueous ophthalmic composition according to this embodiment contains propylene glycol, the content of propylene glycol is preferably 3 w / v % or less, based on the total amount of the aqueous ophthalmic composition, because if the content exceeds 3 w / v %, the osmotic pressure becomes too high. Thickeners: for example, cellulose-based polymer compounds (e.g., methyl cellulose, ethyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, sodium carboxymethyl cellulose, etc.), polyvinyl-based polymer compounds (e.g., polyvinylpyrrolidone, polyvinyl alcohol, etc.), carboxyvinyl polymers, guar gum, hydroxypropyl guar gum, gum arabic, karaya gum, xanthan gum, agar, alginic acid and its salts (e.g., sodium salt), mucopolysaccharides (e.g., heparinoids, heparin, heparin, heparin sulfate, heparan sulfate, heparinoid, hyaluronic acid and its salts (e.g., sodium salt)), 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 the d-, l- or dl-form. Oils: For example, vegetable oils such as sesame oil, castor oil, soybean oil, and olive oil; animal oils such as squalane; mineral oils such as liquid paraffin and Vaseline; and the like.

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

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

[0078] The aqueous ophthalmic composition according to this embodiment can be prepared, for example, by adding and mixing the components (A), (B), and, if necessary, other components to obtain a desired content. Specifically, the composition can be prepared, for example, by dissolving or suspending the components in purified water, adjusting the pH and osmotic pressure to a predetermined value, and sterilizing the composition by filtration or the like.

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

[0080] The aqueous ophthalmic composition according to this embodiment can be used, for example, as eye drops (also referred to as eye drops or eye drops; eye drops include artificial tears and eye drops that can be applied while wearing contact lenses), eyewash (also referred to as eyewash or eyewash; eyewashes include eyewashes that can be used to wash the eyes while wearing contact lenses), and contact lens compositions [contact lens wetting solution, contact lens care compositions (contact lens disinfectants, contact lens preservatives, contact lens cleaners, contact lens cleaning and preservatives), etc.]. The term "contact lenses" includes hard contact lenses and soft contact lenses (including both ionic and non-ionic contact lenses, and both silicone hydrogel contact lenses and non-silicone hydrogel contact lenses).

[0081] The aqueous ophthalmic composition according to this embodiment is preferably an eye drop (including an eye drop that can be applied while wearing contact lenses), as this allows the effects of the present invention to be more pronounced. When the aqueous ophthalmic composition according to this embodiment is an eye drop, the dosage and administration method are not particularly limited as long as they are effective and cause few side effects. For example, for adults (15 years of age or older) and children aged 7 years of age or older, 1 to 2 drops can be applied 2 to 4 times a day, or 4 times a day, or 1 to 2 drops, 1 to 3 drops, or 2 to 3 drops can be applied 5 to 6 times a day.

[0082] The aqueous ophthalmic composition according to this embodiment is provided in any suitable 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 plastic include polyethylene terephthalate, polyarylate, polyethylene naphthalate, polycarbonate, polyethylene, polypropylene, polyimide, 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. Furthermore, the container for containing the aqueous ophthalmic composition according to this embodiment may be a transparent container that allows the interior of the container to be viewed, or an opaque container that makes it difficult to view the interior of the container. A transparent container is preferred. Here, the term "transparent container" includes both colorless transparent containers and colored transparent containers.

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

[0084] The container that holds the aqueous ophthalmic composition according to this embodiment may be a multi-dose type that holds an amount for multiple uses, or a unit-dose type that holds an amount for single use, but a multi-dose type is preferred because it allows the effects of the present invention to be more pronounced.

[0085] 2. Method for inhibiting the formation of precipitates in aqueous ophthalmic compositions The aqueous ophthalmic composition of this embodiment contains at least one selected from the group consisting of allantoin and epsilon-aminocaproic acid and salts thereof, and at least one selected from the group consisting of chondroitin sulfate and salts thereof in an amount of 0.7 w / v% or more, based on the total amount of the aqueous ophthalmic composition, thereby significantly suppressing the formation of precipitates in the aqueous ophthalmic composition. Accordingly, one embodiment of the present invention provides a method for suppressing the formation of precipitates in an aqueous ophthalmic composition, comprising incorporating into the aqueous ophthalmic composition (A) at least one selected from the group consisting of allantoin and epsilon-aminocaproic acid and salts thereof, and (B) at least one selected from the group consisting of chondroitin sulfate and salts thereof in an amount of 0.7 w / v% or more, based on the total amount of the aqueous ophthalmic composition.

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

[0087] 3. Method for Improving Unpleasant Taste After Administration of Aqueous Ophthalmic Composition The aqueous ophthalmic composition of this embodiment contains 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, thereby improving the unpleasant taste (bitterness or unpleasant taste) of the aqueous ophthalmic composition after administration. Thus, one embodiment of the present invention provides a method for improving the unpleasant taste of an aqueous ophthalmic composition after administration, comprising blending (A1) at least one selected from the group consisting of 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, into the aqueous ophthalmic composition. Furthermore, as one embodiment of the present invention, there is provided a method for improving an unpleasant bitter taste or off-flavor in an aqueous ophthalmic composition after administration, the method comprising blending into the aqueous ophthalmic composition (A1) at least one selected from the group consisting of epsilon-aminocaproic acid and salts thereof, and (B) one or more selected from the group consisting of chondroitin sulfate and salts thereof in an amount of 0.7 w / v% or more, based on the total amount of the aqueous ophthalmic composition.

[0088] In the present embodiment, the type and content etc. of the (A1) component, the type and content etc. of the (B) component, the type and content etc. of other components, the formulation form and uses etc. of the aqueous ophthalmic composition are as described in [1. Aqueous ophthalmic composition]. [Example]

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

[0090] [Test Example 1: Evaluation of Precipitate Occurrence (1)] Aqueous ophthalmic compositions (100 mL) of each Example and Comparative Example shown in Table 1 were prepared by a conventional method. The units of 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 allowed to dry overnight at 60°C in a laboratory utensil dryer (LabWare Drying Oven, DG82; Yamato Scientific Co., Ltd.). The state of each aqueous ophthalmic composition after drying was visually observed, 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 precipitate occurrence> There is clearly visible precipitate across the bottom of the well: +++ Some wells have clearly visible deposits:++ There is some unclear deposit in some parts of the well:+ No deposits:- The sodium chondroitin sulfate used was non-prescription sodium chondroitin sulfate for eye drops and injections (manufactured by Maruha Nichiro Foods Co., Ltd.).

[0091] [Table 1]

[0092] The aqueous ophthalmic composition of Comparative Example 1-1, which contained only allantoin, showed the formation of precipitates. The aqueous ophthalmic composition of Comparative Example 1-2, which contained 0.5 w / v% sodium chondroitin sulfate in addition to allantoin, also showed the formation of precipitates. In contrast, the aqueous ophthalmic compositions of Examples 1-1 and 1-2, which contained 1 w / v% or 3 w / v% sodium chondroitin sulfate in addition to allantoin, showed no formation of precipitates.

[0093] [Test Example 2: Evaluation of Precipitate Generation (2)] Aqueous ophthalmic compositions (100 mL) of each of the Examples and Comparative Examples shown in Tables 2 and 3 were prepared by a conventional method. The units of 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 occurrence of precipitates after drying was evaluated. The results are shown in Tables 2 and 3. The sodium chondroitin sulfate used was non-prescription sodium chondroitin sulfate for eye drops and injections (manufactured by Maruha Nichiro Foods Co., Ltd.).

[0094] [Table 2]

[0095] [Table 3]

[0096] The aqueous ophthalmic compositions of Comparative Examples 2-1 and 2-3, which contained only epsilon-aminocaproic acid, showed the formation of precipitates (white residue). The aqueous ophthalmic compositions of Comparative Examples 2-2 and 2-4, which contained epsilon-aminocaproic acid and 0.5 w / v% sodium chondroitin sulfate, also showed the formation of precipitates (white residue). In contrast, the aqueous ophthalmic compositions of Examples 2-1, 2-2, and 2-3, which contained epsilon-aminocaproic acid and 1 w / v% or 3 w / v% sodium chondroitin sulfate, showed no formation of precipitates.

[0097] [Test Example 3: Taste Evaluation] Aqueous ophthalmic compositions (100 mL) of each Example and Comparative Example shown in Table 4 were prepared by a standard method. The units of each component in Table 4 are w / v %. Next, the bitterness of each aqueous ophthalmic composition was measured using a taste recognition device (SA402B; manufactured by Intelligent Sensor Technology Co., Ltd.). The measurement method followed the SA402B instruction manual, and the potential difference between the reference solution and each aqueous ophthalmic composition was measured as an index of bitterness. The obtained measurement values ​​were used to calculate the difference in bitterness between Example 3-1 and Comparative Example 3-1 using the following formula. The results are shown in Table 4. [Formula 1] Difference in index from Comparative Example 3-1 = Measurement value of Comparative Example 3-1 - Measurement value of Example 3-1 The sodium chondroitin sulfate used was non-prescription sodium chondroitin sulfate for eye drops and injections (manufactured by Maruha Nichiro Foods Co., Ltd.).

[0098] [Table 4]

[0099] It was confirmed that the aqueous ophthalmic compositions of Examples 3-1 and 3-2, in which 1 w / v% or 3 w / v% sodium chondroitin sulfate was blended with epsilon-aminocaproic acid, had significantly lower bitterness and off-flavor indices than the aqueous ophthalmic composition of Comparative Example 3-1, which contained only epsilon-aminocaproic acid.

[0100] [Test Example 4: Evaluation of Precipitate Occurrence (3)] Aqueous ophthalmic compositions (100 mL) of each of the Examples and Comparative Examples shown in Table 5 were prepared by a conventional method. 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 occurrence of precipitates after drying was evaluated. The results are shown in Table 5. The sodium chondroitin sulfate used was non-standard sodium chondroitin sulfate (manufactured by Seikagaku Corporation, weight-average molecular weight: approximately 20,000).

[0101] [Table 5]

[0102] The formation of precipitates was observed 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 incorporated a borate buffer into allantoin. In contrast, the formation of precipitates was confirmed in the aqueous ophthalmic compositions of Examples 4-1 to 4-4, 4-6, and 4-7, which incorporated 1 w / v% or 3 w / v% sodium chondroitin sulfate into allantoin, and in the aqueous ophthalmic composition of Example 4-5, which incorporated 3 w / v% sodium chondroitin sulfate and neostigmine methylsulfate into allantoin.

[0103] [Formulation example] Formulation examples are shown in Tables 6 and 7 below. The units of each ingredient in Tables 6 and 7 are all w / v % unless otherwise specified in the tables. Formulation Examples 1 to 13 are all eye drops. 10 mL of each formulation example was filled into a polyethylene terephthalate container, and a polyethylene nozzle was attached, forming Formulation Examples 1' to 13'. 10 mL of each formulation example was filled into a polyethylene terephthalate container, and a polybutylene terephthalate nozzle was attached, forming Formulation Examples 1" to 13". The eye drops of Formulation Examples 1 to 13 can be used as eye drops that can be applied while wearing hard contact lenses, while wearing soft contact lenses, or while 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) 1 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; wherein the aqueous ophthalmic composition has a pH of 5.0 or more and is in the form of a liquid; provided that (i) the aqueous ophthalmic composition is made up of vitamin A, vitamin A oil, and vitamin A fatty acid ester. (ii) an aqueous eye drop containing at least one vitamin A selected from the group consisting of vitamin A, vitamin A oil, and vitamin A fatty acid esters, characterized by blending 250 to 1000% by weight of a nonionic surfactant with respect to the vitamin A, and 5 to 50% by weight of at least one flavoring component selected from the group consisting of l-menthol, dl-menthol, peppermint oil, and flavin adenine dinucleotide; or its salts, and (iii) an aqueous eye drop containing at least one vitamin A compound selected from the group consisting of vitamin A, vitamin A oil, and vitamin A fatty acid esters, wherein the aqueous eye drop contains at least one vitamin A compound selected from the group consisting of Tinuvin, anthraquinone yellow dyes, monoazo yellow dyes, cyanine blue, iron oxide, zinc oxide, and titanium oxide, and ... an aqueous eye drop characterized by being filled in a container made of an acrylonitrile resin that blocks the wavelengths of light below 1000 nm; (iv) an eye drop for soft contact lenses containing (a) vitamin E acetate and / or vitamin E succinate, (b) at least one selected from the group consisting of panthenol, pantothenic acid, pantethine, pantetheine, pantothenyl alcohol, pantothenyl ethyl ether, pantetheine pantothenyl alcohol, calcium pantothenate, and sodium pantothenate, and (c) hydroxypropyl methylcellulose;(v) An ophthalmic composition for soft contact lenses, which is substantially free of surfactants, and which comprises: (A) at least one selected from the group consisting of flavin adenine dinucleotide, flavin mononucleotide, riboflavin, riboflavin phosphate, riboflavin acetate, riboflavin butyrate, and sodium salts thereof, and / or at least one selected from the group consisting of cyanocobalamin, mecobalamin, hydroxocobalamin, their hydrochlorides, and their acetates; (B) chondroitin sulfate or a salt thereof; and (C) at least one selected from the group consisting of glycerin, propylene glycol, 1,3-butanediol, and polyethylene glycol. (vi) an ophthalmic composition comprising simultaneously blending sodium chondroitin sulfate, at least one selected from the group consisting of sodium azulene sulfonate, epsilon-aminocaproic acid, allantoin, berberine chloride, berberine sulfate, dipotassium glycyrrhizinate, zinc sulfate, zinc lactate, and lysozyme chloride, sodium cromoglycate, and at least one selected from the group consisting of chlorpheniramine maleate, d-chlorpheniramine maleate, diphenhydramine, diphenhydramine hydrochloride, clemastine fumarate, mequitazine, ketotifen fumarate, and levocabastine hydrochloride).

2. 2. The aqueous ophthalmic composition according to claim 1, wherein the content of allantoin is 0.06 w / v % to 1 w / v % based on the total amount of the aqueous ophthalmic composition.

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

4. The aqueous ophthalmic composition according to any one of claims 1 to 3, further comprising (D) a terpenoid.

5. By blending at least one selected from the group consisting of chondroitin sulfate and its salts with a composition containing allantoin and at least one selected from the group consisting of epsilon-aminocaproic acid and its salts, 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) 1 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; wherein the aqueous ophthalmic composition has a pH of 5.0 or more and is in the form of a liquid; provided that (i) allantoin is selected from the group consisting of vitamin A, vitamin A oil, and vitamin A fatty acid esters; (ii) an aqueous eye drop containing at least one vitamin A selected from the group consisting of vitamin A, vitamin A oil, and vitamin A fatty acid esters, characterized by blending 250 to 1000% by weight of a nonionic surfactant with respect to the vitamin A, and at least one flavoring component selected from the group consisting of l-menthol, dl-menthol, peppermint oil, and menthol-containing flavin adenine dinucleotide or menthol-containing flavin adenine dinucleotide .... or its salts, and (iii) an aqueous eye drop containing at least one vitamin A compound selected from the group consisting of vitamin A, vitamin A oil, and vitamin A fatty acid esters, wherein the aqueous eye drop contains at least one vitamin A compound selected from the group consisting of Tinuvin, anthraquinone yellow dyes, monoazo yellow dyes, cyanine blue, iron oxide, zinc oxide, and titanium oxide, and ... an aqueous eye drop characterized by being filled in a container made of an acrylonitrile resin that blocks the wavelengths of light below 1000 nm; (iv) an eye drop for soft contact lenses containing (a) vitamin E acetate and / or vitamin E succinate, (b) at least one selected from the group consisting of panthenol, pantothenic acid, pantethine, pantetheine, pantothenyl alcohol, pantothenyl ethyl ether, pantetheine pantothenyl alcohol, calcium pantothenate, and sodium pantothenate, and (c) hydroxypropyl methylcellulose;(v) An ophthalmic composition for soft contact lenses, which contains (A) at least one selected from the group consisting of flavin adenine dinucleotide, flavin mononucleotide, riboflavin, riboflavin phosphate, riboflavin acetate, riboflavin butyrate, and sodium salts thereof, and / or at least one selected from the group consisting of cyanocobalamin, mecobalamin, hydroxocobalamin, their hydrochlorides, and their acetates; (B) chondroitin sulfate or a salt thereof; and (C) at least one selected from the group consisting of glycerin, propylene glycol, 1,3-butanediol, and polyethylene glycol, and which is substantially free of surfactants; and (vi) a soft contact lens composition for soft contact lenses, which contains at least one selected from the group consisting of flavin adenine dinucleotide, flavin mononucleotide, riboflavin, riboflavin phosphate, riboflavin acetate, riboflavin butyrate, and sodium salts thereof, and / or at least one selected from the group consisting of cyanocobalamin, mecobalamin, hydroxocobalamin, their hydrochlorides, and their acetates; (B) chondroitin sulfate or a salt thereof; and (C) at least one selected from the group consisting of glycerin, propylene glycol, 1,3-butanediol, and polyethylene glycol, and which is substantially free of surfactants. a method for suppressing the formation of precipitates after drying in an aqueous ophthalmic composition by simultaneously blending sodium cromoglycate, at least one selected from the group consisting of sodium azulene sulfonate, epsilon-aminocaproic acid, allantoin, berberine chloride, berberine sulfate, dipotassium glycyrrhizinate, zinc sulfate, zinc lactate, and lysozyme chloride, sodium cromoglycate, and at least one selected from the group consisting of chlorpheniramine maleate, d-chlorpheniramine maleate, diphenhydramine, diphenhydramine hydrochloride, clemastine fumarate, mequitazine, ketotifen fumarate, and levocabastine hydrochloride;

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