Aqueous ophthalmic composition

Abstract

To provide an aqueous ophthalmic composition that suppresses a discomfort taste associated with astringency.SOLUTION: An aqueous ophthalmic composition has (A) at least one selected from the group consisting of zinc salt, and glycyrrhizinic acid, azulene sulfonic 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 0.8 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] Once applied to the ocular mucosa, the formulation, either undiluted or diluted with tears, is aspirated through the lacrimal puncta, passes through the nasolacrimal duct into the nasal cavity, and then reaches the oral cavity. Therefore, even though the components contained in the formulation are not directly applied to the oral cavity, users may experience an unpleasant taste, such as bitterness or astringency, after application to the ocular mucosa. Such an unpleasant sensation can be one of the reasons for hesitation in using ophthalmic compositions such as eye drops, ultimately reducing user compliance. Therefore, it is important to improve the sensation of use by alleviating the unpleasant taste caused by the components incorporated into ophthalmic compositions (e.g., Patent Document 1). [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Patent Publication No. 2003-137781 Summary of the Invention [Problem to be solved by the invention]

[0004] The present inventors have conducted various studies on aqueous ophthalmic compositions containing zinc salts, glycyrrhizinic acid, or azulene sulfonic acid and have found that there is a problem in that unpleasant astringent taste or astringent irritation (hereinafter collectively referred to as "astringent-related taste") is felt after administration.

[0005] An object of the present invention is to provide an aqueous ophthalmic composition that contains a zinc salt and at least one selected from the group consisting of glycyrrhizinic acid, azulene sulfonic acid, and salts thereof, and that suppresses unpleasant astringent taste sensation after administration. [Means for solving the problem]

[0006] The present inventors have unexpectedly found that by incorporating a specific amount of at least one selected from the group consisting of chondroitin sulfate and its salts into an aqueous ophthalmic composition containing a zinc salt, glycyrrhizinic acid, azulene sulfonic acid, and their salts, the unpleasant astringent taste sensation after administration of the aqueous ophthalmic composition can be suppressed.The present invention is based on this finding and provides the following inventions.

[0007] [1] An aqueous ophthalmic composition comprising (A) at least one selected from the group consisting of a zinc salt, and glycyrrhizinic acid, azulene sulfonic 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 0.8 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 0.0001 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 suppressing unpleasant astringent taste after administration of an aqueous ophthalmic composition, comprising blending into the aqueous ophthalmic composition (A) at least one selected from the group consisting of a zinc salt, and glycyrrhizinic acid, azulene sulfonic acid, and salts thereof, and (B) at least one selected from the group consisting of chondroitin sulfate and salts thereof in an amount of 0.8 w / v% or more, based on the total amount of the aqueous ophthalmic composition. [Effects of the Invention]

[0008] According to the present invention, it is possible to provide an aqueous ophthalmic composition that contains a zinc salt and at least one selected from the group consisting of glycyrrhizinic acid, azulene sulfonic acid, and salts thereof, while suppressing unpleasant astringent taste after administration. DETAILED DESCRIPTION OF THE INVENTION

[0009] Hereinafter, embodiments of the present invention will be described in detail, but the present invention is not limited to the following embodiments.

[0010] In this specification, unless otherwise specified, the unit of content "%" means "w / v%" and is synonymous with "g / 100 mL".

[0011] [1. Aqueous ophthalmic composition] The aqueous ophthalmic composition according to this embodiment contains (A) a zinc salt and at least one selected from the group consisting of glycyrrhizinic acid, azulene sulfonic acid, and salts thereof (also referred to simply as "component (A)"). Hereinafter, at least one selected from the group consisting of glycyrrhizinic acid and salts thereof may be referred to as "component (A1)," the zinc salt as "component (A2)," and at least one selected from the group consisting of azulene sulfonic acid and salts thereof as "component (A3)."

[0012] [Component (A)] The zinc salt, glycyrrhizinic acid, azulene sulfonic acid, and salts thereof, which are component (A), are not particularly limited as long as they are medicamentally, pharmacologically (pharmaceutical), or physiologically acceptable. Glycyrrhizinic acid and azulene sulfonic acid may be in the free form or may be in the form of a medicamentally, pharmacologically (pharmaceutical), or physiologically acceptable salt.

[0013] The zinc salt may be any compound capable of forming zinc ions in the aqueous ophthalmic composition, and examples thereof include salts with inorganic acids, salts with organic acids, and chlorides. Examples of salts with inorganic acids include sulfates. Examples of salts with organic acids include lactates. Examples of chlorides include zinc chloride. Preferred zinc salts are zinc sulfate, zinc lactate, and zinc chloride, with zinc sulfate being more preferred. The zinc salt may also be a hydrate (e.g., zinc sulfate heptahydrate).

[0014] Examples of salts of glycyrrhizinic acid include alkali metal salts, alkaline earth metal salts, and ammonium salts. Examples of alkali metal salts include sodium salts and potassium salts. Examples of alkaline earth metal salts include magnesium salts and calcium salts.

[0015] As glycyrrhizinic acid and salts thereof, glycyrrhizinic acid, alkali metal salts of glycyrrhizinic acid and ammonium salts of glycyrrhizinic acid are preferred, dipotassium glycyrrhizinate and monoammonium glycyrrhizinate are more preferred, and dipotassium glycyrrhizinate is even more preferred.

[0016] Examples of the salts of azulene sulfonic acid include alkali metal salts, such as sodium salts and potassium salts.

[0017] As the azulene sulfonic acid and its salts, azulene sulfonic acid and alkali metal salts of azulene sulfonic acid are preferred, azulene sulfonic acid and sodium azulene sulfonate are more preferred, and sodium azulene sulfonate is even more preferred.

[0018] Commercially available zinc salts, glycyrrhizinic acid, azulene sulfonic acid, and salts thereof may be used. One type of zinc salt, glycyrrhizinic acid, azulene sulfonic acid, and salts thereof may be used alone, or two or more types may be used in combination.

[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 0.0001 to 5 w / v%, more preferably 0.0004 to 2 w / v%, even more preferably 0.001 to 1 w / v%, and even more preferably 0.004 to 0.25 w / v%.

[0020] When a zinc salt is used as component (A), the content of the zinc salt, for example, based on the total amount of the aqueous ophthalmic composition, is preferably 0.005 to 2 w / v%, more preferably 0.01 to 1.5 w / v%, more preferably 0.03 to 1 w / v%, even more preferably 0.05 to 0.75 w / v%, even more preferably 0.125 to 0.5 w / v%, and particularly preferably 0.15 to 0.25 w / v%.

[0021] When glycyrrhizinic acid and salts thereof are used as component (A), the content of glycyrrhizinic acid and salts thereof is, for example, preferably 0.005 to 2 w / v%, more preferably 0.05 to 1 w / v%, even more preferably 0.125 to 0.5 w / v%, and even more preferably 0.2 to 0.25 w / v%, based on the total amount of the aqueous ophthalmic composition.

[0022] When azulene sulfonic acid and its salts are used as component (A), the content of azulene sulfonic acid and its salts is, for example, based on the total amount of the aqueous ophthalmic composition, preferably 0.0004 to 0.5 w / v%, more preferably 0.001 to 0.1 w / v%, even more preferably 0.004 to 0.05 w / v%, and even more preferably 0.01 to 0.02 w / v%.

[0023] [(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)").

[0024] 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.

[0025] 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.

[0026] 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.

[0027] 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.

[0028] The content of component (B) in the aqueous ophthalmic composition according to this embodiment is 0.8 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 0.8 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 0.9 w / v% or more, 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. Furthermore, the content of component (B) in the aqueous ophthalmic composition according to this embodiment may be, for example, 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.

[0029] 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 0.1 to 5,000 parts by mass, more preferably 0.5 to 1,000 parts by mass, even more preferably 1 to 500 parts by mass, and even more preferably 4 to 300 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 5 to 300 parts by mass and 10 to 300 parts by mass.

[0030] When a zinc salt is used as component (A), the ratio of component (B) to component (A) is preferably 0.1 to 500 parts by mass, more preferably 0.5 to 100 parts by mass, even more preferably 1 to 60 parts by mass, and even more preferably 4 to 25 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 25 parts by mass and 10 to 20 parts by mass.

[0031] When glycyrrhizinic acid and its salts are used as component (A), the ratio of component (B) to component (A) is preferably 0.1 to 500 parts by mass, more preferably 0.5 to 100 parts by mass, even more preferably 1 to 60 parts by mass, and even more preferably 4 to 25 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 according to this embodiment. Preferred ranges also include 5 to 40 parts by mass and 10 to 25 parts by mass.

[0032] When azulene sulfonic acid and its salts are used as component (A), the ratio of component (B) to component (A) is preferably 1 to 5,000 parts by mass, more preferably 5 to 1,000 parts by mass, even more preferably 10 to 750 parts by mass, even more preferably 25 to 500 parts by mass, and particularly preferably 50 to 300 parts by mass, per part by mass of the total content of component (A) in the aqueous ophthalmic composition of this embodiment. Preferred ranges also include 100 to 300 parts by mass and 150 to 300 parts by mass.

[0033] [(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.

[0034] Neostigmine methylsulfate, which is component (C), is not particularly limited as long as it is medicamentarily, pharmacologically (pharmaceutical) or physiologically acceptable.

[0035] Neostigmine methylsulfate is a known compound also known as (3-dimethylcarbamoyloxyphenyl)trimethylammonium methylsulfate.

[0036] 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.

[0037] 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 0.0001 to 50 parts by mass, more preferably 0.0005 to 10 parts by mass, even more preferably 0.001 to 5 parts by mass, and even more preferably 0.004 to 1.25 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.

[0038] 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.

[0039] [(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.

[0040] The terpenoid serving as component (D) is not particularly limited as long as it is medicamentarily, pharmacologically (pharmaceutical), or physiologically acceptable.

[0041] Terpenoids include, for example, cyclic and acyclic terpenes.

[0042] 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.

[0043] 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.

[0044] 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.

[0045] 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.

[0046] 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.

[0047] 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.

[0048] 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.

[0049] 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.

[0050] 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.

[0051] [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.

[0052] Examples of surfactants include nonionic surfactants and ionic (anionic, amphoteric, cationic) surfactants.

[0053] 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.

[0054] Examples of anionic surfactants include polyoxyethylene alkyl ether phosphates, polyoxyethylene alkyl ether sulfates, alkyl benzene sulfonates, alkyl sulfates, and N-acyltaurine salts.

[0055] Examples of amphoteric surfactants include lauryl dimethylaminoacetic acid betaine and alkyldiaminoethylglycine hydrochloride.

[0056] Examples of cationic surfactants include benzalkonium chloride, benzalkonium bromide, benzethonium chloride, chlorhexidine gluconate, polidronium hydrochloride, and cetylpyridinium chloride.

[0057] 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.

[0058] The surfactant may be a commercially available product. One surfactant may be used alone, or two or more surfactants may be used in combination.

[0059] 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.

[0060] 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.

[0061] 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.

[0062] 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 0.00001 to 1,000 parts by mass, more preferably 0.00005 to 500 parts by mass, even more preferably 0.0001 to 100 parts by mass, and even more preferably 0.0004 to 75 parts by mass, relative to 1 part by mass of the total content of component (A) in the aqueous ophthalmic composition according to this embodiment.

[0063] 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.

[0064] [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.

[0065] 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.

[0066] 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.).

[0067] 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.

[0068] 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.

[0069] 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.

[0070] 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.

[0071] 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 0.05 to 5000 parts by mass, more preferably 0.1 to 1000 parts by mass, and even more preferably 0.4 to 750 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.

[0072] 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.

[0073] [Thickener] The aqueous ophthalmic composition according to this embodiment preferably further contains a thickener. When the aqueous ophthalmic composition further contains a thickener, the effects of the present invention are more pronounced. The thickener is not particularly limited, as long as it is medicamentally, pharmacologically (pharmaceutical), or physiologically acceptable.

[0074] Examples of thickeners include cellulose-based polymer compounds (e.g., methylcellulose, ethylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, sodium carboxymethylcellulose, 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 other than component (B) (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, and carrageenan.

[0075] As the thickener, mucopolysaccharides other than component (B) are preferred, hyaluronic acid and salts thereof are more preferred, and sodium hyaluronate is even more preferred.

[0076] The thickener may be a commercially available product. One type of thickener may be used alone, or two or more types may be used in combination.

[0077] The content of the thickener in the aqueous ophthalmic composition according to this embodiment is not particularly limited, and is set appropriately depending on the type of thickener, 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 thickener is, for example, preferably 0.0001 to 5 w / v%, more preferably 0.001 to 1 w / v%, even more preferably 0.01 to 0.5 w / v%, even more preferably 0.05 to 0.3 w / v%, and particularly preferably 0.1 to 0.15 w / v%, based on the total amount of the aqueous ophthalmic composition.

[0078] The content ratio of the thickener 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 thickener, 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 thickener relative to the component (A) is, for example, preferably 0.01 to 1000 parts by mass, more preferably 0.05 to 500 parts by mass, and even more preferably 0.1 to 100 parts by mass, per 1 part by mass of the total content of component (A) included in the aqueous ophthalmic composition according to this embodiment.

[0079] The content ratio of the thickener relative to 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 thickener, 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 thickener relative to component (B) is, for example, preferably 0.0001 to 5 parts by mass, more preferably 0.001 to 1 part by mass, even more preferably 0.01 to 0.5 parts by mass, even more preferably 0.05 to 0.3 parts by mass, and particularly preferably 0.1 to 0.12 parts by mass, per 1 part by mass of the total content of component (B) included in the aqueous ophthalmic composition according to this embodiment.

[0080] 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 5.5 to 7.0.

[0081] 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.

[0082] 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.

[0083] 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, allantoin, tranexamic acid, lysozyme, lysozyme chloride, indomethacin, pranoprofen, ibuprofen, ibuprofen piconol, ketoprofen, felbinac, bendazac, piroxicam, bufexamac, butyl flufenamate, epsilon-aminocaproic acid, berberine chloride, berberine sulfate, etc. When the aqueous ophthalmic composition according to this embodiment contains epsilon-aminocaproic acid, the content of epsilon-aminocaproic acid is preferably less than 3 w / v% based on the total amount of the aqueous ophthalmic composition, in order to further enhance the effects of the present invention. Furthermore, the aqueous ophthalmic composition according to this embodiment preferably does not contain epsilon-aminocaproic acid, in order to further enhance the effects of the present invention. 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. Others: For example, sulfamethoxazole, sulfisoxazole, sulfisomidine and their salts.

[0084] 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, 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). Isotonic 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. 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.

[0085] 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.

[0086] 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.

[0087] 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.

[0088] 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.

[0089] 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).

[0090] 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.

[0091] 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.

[0092] 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.

[0093] 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.

[0094] 2. Method for Improving Unpleasant Astringent Taste After Administration of an Aqueous Ophthalmic Composition The aqueous ophthalmic composition of this embodiment contains at least one selected from the group consisting of a zinc salt, glycyrrhizinic acid, azulene sulfonic acid, and salts thereof, and at least one selected from the group consisting of chondroitin sulfate and salts thereof in an amount of 0.8 w / v% or more, based on the total amount of the aqueous ophthalmic composition, thereby improving the unpleasant astringent taste experienced by the aqueous ophthalmic composition after administration. Accordingly, one embodiment of the present invention provides a method for improving the unpleasant astringent taste experienced by the aqueous ophthalmic composition after administration, comprising blending (A) at least one selected from the group consisting of a zinc salt, glycyrrhizinic acid, azulene sulfonic acid, and salts thereof, and (B) at least one selected from the group consisting of chondroitin sulfate and salts thereof in an amount of 0.8 w / v% or more, based on the total amount of the aqueous ophthalmic composition, into the aqueous ophthalmic composition.

[0095] 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].

[0096] 3. Method for Improving the Defoaming Rate in an Aqueous Ophthalmic Composition The aqueous ophthalmic composition of this embodiment contains at least one selected from the group consisting of glycyrrhizinic acid and its salts, and at least one selected from the group consisting of chondroitin sulfate and its salts in an amount of 0.8 w / v% or more, based on the total amount of the aqueous ophthalmic composition, thereby significantly improving the defoaming rate of the aqueous ophthalmic composition. Accordingly, one embodiment of the present invention provides a method for improving the defoaming rate of an aqueous ophthalmic composition, comprising incorporating into the aqueous ophthalmic composition (A1) at least one selected from the group consisting of glycyrrhizinic acid and its salts, and (B) at least one selected from the group consisting of chondroitin sulfate and its salts in an amount of 0.8 w / v% or more, based on the total amount of the aqueous ophthalmic composition.

[0097] 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 use etc. of the aqueous ophthalmic composition are as described in [1. Aqueous ophthalmic composition].

[0098] 4. Method for reducing the amount of foaming in an aqueous ophthalmic composition The aqueous ophthalmic composition of this embodiment contains at least one selected from the group consisting of glycyrrhizinic acid and its salts, and at least one selected from the group consisting of chondroitin sulfate and its salts in an amount of 0.8 w / v% or more, based on the total amount of the aqueous ophthalmic composition, thereby significantly reducing the amount of foaming in the aqueous ophthalmic composition. Accordingly, one embodiment of the present invention provides a method for reducing the amount of foaming in an aqueous ophthalmic composition, comprising incorporating into the aqueous ophthalmic composition (A1) at least one selected from the group consisting of glycyrrhizinic acid and its salts, and (B) at least one selected from the group consisting of chondroitin sulfate and its salts in an amount of 0.8 w / v% or more, based on the total amount of the aqueous ophthalmic composition.

[0099] 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 use etc. of the aqueous ophthalmic composition are as described in [1. Aqueous ophthalmic composition].

[0100] 5. Method for inhibiting the occurrence of cloudiness in aqueous ophthalmic compositions The aqueous ophthalmic composition of this embodiment significantly suppresses the occurrence of cloudiness by incorporating a zinc salt and at least one selected from the group consisting of chondroitin sulfate and salts thereof in an amount of 0.8 w / v% or more, based on the total amount of the aqueous ophthalmic composition. Accordingly, one embodiment of the present invention provides a method for suppressing the occurrence of cloudiness in an aqueous ophthalmic composition, comprising incorporating (A2) a zinc salt and (B) at least one selected from the group consisting of chondroitin sulfate and salts thereof in an amount of 0.8 w / v% or more, based on the total amount of the aqueous ophthalmic composition, into the aqueous ophthalmic composition.

[0101] In the present embodiment, the type and content etc. of the (A2) 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].

[0102] 6. Method for inhibiting the formation of precipitates in aqueous ophthalmic compositions The aqueous ophthalmic composition of this embodiment significantly suppresses the formation of precipitates by incorporating a zinc salt and at least one selected from the group consisting of chondroitin sulfate and salts thereof in an amount of 0.8 w / v% or more, based on the total amount of 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 (A2) a zinc salt and (B) at least one selected from the group consisting of chondroitin sulfate and salts thereof in an amount of 0.8 w / v% or more, based on the total amount of the aqueous ophthalmic composition, into the aqueous ophthalmic composition.

[0103] In the present embodiment, the type and content etc. of the (A2) 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].

[0104] 7. Method for stabilizing at least one member selected from the group consisting of azulene sulfonic acid and its salts in an aqueous ophthalmic composition The aqueous ophthalmic composition of this embodiment contains at least one selected from the group consisting of azulene sulfonic acid and its salts, and at least one selected from the group consisting of chondroitin sulfate and its salts in an amount of 0.8 w / v% or more, based on the total amount of the aqueous ophthalmic composition, thereby improving the stability of the azulene sulfonic acid and its salts in the aqueous ophthalmic composition and suppressing discoloration. Therefore, one embodiment of the present invention provides a method for stabilizing at least one selected from the group consisting of azulene sulfonic acid and its salts in an aqueous ophthalmic composition, comprising incorporating (A3) at least one selected from the group consisting of azulene sulfonic acid and its salts, and (B) at least one selected from the group consisting of chondroitin sulfate and its salts in an amount of 0.8 w / v% or more, based on the total amount of the aqueous ophthalmic composition. Furthermore, as one embodiment of the present invention, there is provided a method for suppressing discoloration in an aqueous ophthalmic composition, comprising blending into the aqueous ophthalmic composition (A3) at least one selected from the group consisting of azulene sulfonic acid and salts thereof, and (B) 0.8 w / v % or more of one or more selected from the group consisting of chondroitin sulfate and salts thereof, based on the total amount of the aqueous ophthalmic composition.

[0105] In the present embodiment, the type and content etc. of the component (A3), the type and content etc. of the component (B), the type and content etc. of other components, the formulation form and uses of the aqueous ophthalmic composition, etc. are as described in [1. Aqueous ophthalmic composition]. [Example]

[0106] The present invention will be specifically explained below based on test examples, but the present invention is not limited to these.

[0107] [Test Example 1: Taste Evaluation (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, the astringency and astringency irritation indices 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 SA402B instruction manual, and the potential difference between the reference solution and each aqueous ophthalmic composition was measured as an index of astringency and astringency irritation. Using the obtained measurements, the difference in astringency and astringency irritation of each Example compared to Comparative Example 1-1 was calculated using the following formula 1. The results are shown in Table 1. [Formula 1] Difference in index from Comparative Example 1-1 = Measured value of Comparative Example 1-1 - Measured value of Example The sodium chondroitin sulfate used was non-prescription sodium chondroitin sulfate for eye drops and injections (manufactured by Maruha Nichiro Foods Co., Ltd.).

[0108] [Table 1]

[0109] It was confirmed that the aqueous ophthalmic compositions of Examples 1-1 and 1-2, in which dipotassium glycyrrhizinate was blended with 1 w / v% or 3 w / v% sodium chondroitin sulfate, had lower indices of both astringency and astringency irritation compared to the aqueous ophthalmic composition of Comparative Example 1-1, which contained only dipotassium glycyrrhizinate.

[0110] [Test Example 2: Taste Evaluation (2)] Aqueous ophthalmic compositions (100 mL) of each Example and Comparative Example shown in Table 2 were prepared by a conventional method. The units for each component in Table 2 are w / v %. Next, measurements were performed in the same manner as in Test Example 1, except that the indices measured were astringency and sourness, and the differences in astringency and sourness between Example 2-1 and Comparative Example 2-1 were calculated. The results are shown in Table 2. The sodium chondroitin sulfate used was non-prescription sodium chondroitin sulfate for eye drops and injection (manufactured by Maruha Nichiro Foods Co., Ltd.), and the zinc sulfate used was zinc sulfate heptahydrate.

[0111] [Table 2]

[0112] It was confirmed that the aqueous ophthalmic composition of Example 2-1, in which 3 w / v% sodium chondroitin sulfate was blended with zinc sulfate, had lower indices for both astringency and sourness compared to the aqueous ophthalmic composition of Comparative Example 2-1, which contained only zinc sulfate.

[0113] [Test Example 3: Taste Evaluation (3)] Aqueous ophthalmic compositions (100 mL) of each Example and Comparative Example shown in Table 3 were prepared by a standard method. The units for each component in Table 3 are w / v %. Next, measurements were performed in the same manner as in Test Example 1, except that the indices measured were astringent irritation and bitter imperfection, and the differences in astringent irritation and bitter imperfection for each Example compared to Comparative Example 3-1 were calculated. The results are shown in Table 3. The sodium chondroitin sulfate used was non-prescription sodium chondroitin sulfate for eye drops and injections (manufactured by Maruha Nichiro Foods Co., Ltd.).

[0114] [Table 3]

[0115] It was confirmed that the aqueous ophthalmic compositions of Examples 3-1 and 3-2, which contained sodium azulene sulfonate at 1 w / v% or 3 w / v% sodium chondroitin sulfate, had lower indices for both astringency and bitterness compared to the aqueous ophthalmic composition of Comparative Example 3-1, which contained only sodium azulene sulfonate.

[0116] Test Example 4: Evaluation of Foaming and Antifoaming Properties (1) Aqueous ophthalmic compositions (100 mL) of each of the Examples and Comparative Examples shown in Table 4 were prepared by a conventional method. The units for each component in Table 4 are w / v %. Next, 30 mL of the prepared aqueous ophthalmic compositions were filled into polyethylene terephthalate (PET) containers (50 mL centrifuge tubes, Corning Incorporated No. 430304), and the defoaming rates were evaluated by the following method. Each aqueous ophthalmic composition filled in a container was shaken 1,500 times (300 rpm / min for 5 minutes) using a strong shaker SR-2DW (manufactured by TAITEC Co., Ltd.). Immediately after shaking, the foam and aqueous solution portions were visually confirmed, and the volume of the foam portion was measured (an index of foamability). Next, the compositions were allowed to stand, and the time until the amount of foam was reduced by half was measured (an index of defoamability). Foamability was evaluated by calculating the ratio of the volume of the foam portion in Example 4-1 to the volume of the foam portion in Comparative Example 4-1 immediately after shaking, which was set to 100. The results are shown in Table 4. The sodium chondroitin sulfate used was non-prescription sodium chondroitin sulfate for eye drops and injections (manufactured by Maruha Nichiro Foods Co., Ltd.).

[0117] [Table 4]

[0118] It was confirmed that the aqueous ophthalmic composition of Example 4-1 containing 3 w / v% sodium chondroitin sulfate was less prone to foaming and exhibited significantly better defoaming than the aqueous ophthalmic composition of Comparative Example 4-1 not containing sodium chondroitin sulfate.

[0119] Test Example 5: Evaluation of antifoaming properties 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, 30 mL of each prepared aqueous ophthalmic composition was filled into a polyethylene terephthalate (PET) container (a 50 mL centrifuge tube, Corning Incorporated No. 430304), and the defoaming rate was evaluated by the following method. Each aqueous ophthalmic composition filled in a container was shaken 1,500 times (300 rpm / min for 5 minutes) using a strong shaker SR-2DW (manufactured by TAITEC Co., Ltd.). Immediately after shaking, the foam and aqueous solution portions were visually confirmed, and the volume of the foam portion was measured. Next, they were left to stand, and the time until the volume of foam was reduced by half was measured. The sodium chondroitin sulfate used was non-prescription sodium chondroitin sulfate for eye drops and injections (manufactured by Maruha Nichiro Foods Co., Ltd.).

[0120] [Table 5]

[0121] The aqueous ophthalmic composition of Example 5-1 containing 1 w / v% sodium chondroitin sulfate was confirmed to have a significant defoaming effect compared to the aqueous ophthalmic composition of Comparative Example 5-1 containing no sodium chondroitin sulfate.Furthermore, when 0.1 w / v% sodium hyaluronate was contained, it was confirmed to have an even more significant defoaming effect (Example 5-2).

[0122] Test Example 6: Turbidity Evaluation Aqueous ophthalmic compositions (100 mL) of each of the Examples and Comparative Examples shown in Table 6 were prepared by a standard method. The units for each component in Table 6 are w / v %. After preparation, 20 mL of each aqueous ophthalmic composition was filled into a 20 mL transparent glass screw vial, and the composition was visually observed at a brightness of 5000 lux, and the turbidity was evaluated according to the following evaluation criteria. <Turbidity evaluation criteria> The background is not visible and it is clearly cloudy :+++ The background is visible, but it's clearly cloudy:++ White turbidity can be seen against a black background:+ No cloudiness is visible even against a black background: Each aqueous ophthalmic composition was placed in a 96-well plate (Tissue Culture Plate (FALCON)) at 200 μL, and the absorbance at 660 nm was measured using a plate reader (Versa Max (Molecular Devices)) to determine the turbidity. The absorbance at 660 nm of purified water was also measured as a control. The sodium chondroitin sulfate used was non-prescription sodium chondroitin sulfate for eye drops and injection (manufactured by Maruha Nichiro Foods Co., Ltd.), and the zinc sulfate used was zinc sulfate heptahydrate. The results are shown in Table 6.

[0123] [Table 6]

[0124] The aqueous ophthalmic composition of Comparative Example 6-1, which contained only zinc sulfate, exhibited obvious cloudiness. The aqueous ophthalmic composition of Comparative Example 6-2, which contained zinc sulfate and 0.5 w / v% sodium chondroitin sulfate, also exhibited cloudiness. In contrast, the aqueous ophthalmic composition of Example 6-1, which contained zinc sulfate and 1 w / v% sodium chondroitin sulfate, exhibited significantly less cloudiness. The absorbances at 660 nm of the aqueous ophthalmic composition of Example 6-1 and purified water were 0.047 and 0.046, respectively, demonstrating that Example 6-1 had clarity comparable to that of purified water.

[0125] [Test Example 7: Evaluation of Precipitate Generation (1)] Aqueous ophthalmic compositions (100 mL) of each Example and Comparative Example shown in Table 7 were prepared by a conventional method. The units of each component in Table 7 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 7. <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 injection (manufactured by Maruha Nichiro Foods Co., Ltd.), and the zinc sulfate used was zinc sulfate heptahydrate.

[0126] [Table 7]

[0127] The formation of precipitates was observed in the aqueous ophthalmic composition of Comparative Example 7-1, which contained only zinc sulfate.In contrast, it was confirmed that no precipitates were formed in the aqueous ophthalmic compositions of Examples 7-1 and 7-2, which contained zinc sulfate and 1 w / v % or 3 w / v % sodium chondroitin sulfate.

[0128] Test Example 8: Evaluation of stability Aqueous ophthalmic compositions (100 mL) of each Example and Comparative Example shown in Table 8 were prepared by a conventional method. The units of each component in Table 8 are w / v %. Next, 5 mL of each aqueous ophthalmic composition was filled into a glass ampoule (volume: 10 mL), sealed, and stored in a thermostatic chamber at 60°C in the dark for 7 days. Before and after storage, 200 μL of each aqueous ophthalmic composition was placed in a 96-well plate (Tissue Culture Plate (FALCON)), and the absorbance at 568 nm was measured using a plate reader (Versa Max (Molecular Devices)). The discoloration rate of each aqueous ophthalmic composition was calculated as an index of stability evaluation using the measured absorbance according to the following formula 2. The results are shown in Table 8. [Formula 2] Discoloration rate (%) = {(absorbance before storage - absorbance after storage) / absorbance before storage} x 100 The sodium chondroitin sulfate used was non-prescription sodium chondroitin sulfate for eye drops and injections (manufactured by Maruha Nichiro Foods Co., Ltd.).

[0129] [Table 8]

[0130] Compared to the aqueous ophthalmic composition of Comparative Example 8-1 containing only sodium azulene sulfonate, the aqueous ophthalmic composition of Example 8-1, in which sodium azulene sulfonate was blended with 1 w / v% sodium chondroitin sulfate, was confirmed to have improved stability of sodium azulene sulfonate and to significantly suppress discoloration.

[0131] Test Example 9: Evaluation of Foaming and Antifoaming Properties (2) Aqueous ophthalmic compositions (100 mL) of each of the Examples and Comparative Examples shown in Table 9 were prepared by a conventional method. The unit of each component in Table 9 is w / v %. Next, 30 mL of the prepared aqueous ophthalmic composition was filled into a polyethylene terephthalate (PET) container (a 50 mL centrifuge tube, Corning Incorporated No. 430304), and the defoaming rate was evaluated by the following method. Each aqueous ophthalmic composition filled in a container was shaken 1,500 times (300 rpm / min for 5 minutes) using a strong shaker SR-2DW (manufactured by TAITEC Co., Ltd.). Immediately after shaking, the foam portion and the aqueous solution portion were visually confirmed, and the volume of the foam portion was measured (an index of foamability). Next, they were left to stand, and the time until the amount of foam was reduced by half was measured, which was taken as the foam half-life (an index of defoaming property). The measured foam half-life was used to calculate the foam half-life reduction rate (%) using the following formula 3. The results are shown in Table 9. [Formula 3] Foam half-life reduction rate (%) = {(Foam half-life of comparative example - Foam half-life of example) / Foam half-life of comparative example} × 100 The comparative example in question is Comparative Example 9-1 for Examples 9-1 and 9-2, and Comparative Example 9-2 for Examples 9-3 and 9-4. The foaming property was evaluated by calculating the ratio of the volume of the foam in the corresponding Example to the volume of the foam in the Comparative Example immediately after shaking, which was set to 100. The results are shown in Table 9. The sodium chondroitin sulfate used was non-standard sodium chondroitin sulfate (manufactured by Seikagaku Corporation, weight-average molecular weight: approximately 20,000).

[0132] [Table 9]

[0133] It was confirmed that the aqueous ophthalmic compositions of the Examples containing sodium chondroitin sulfate were less prone to foaming and exhibited significantly better defoaming than the aqueous ophthalmic compositions of the Comparative Examples which did not contain sodium chondroitin sulfate.

[0134] Test Example 10: Evaluation of Foaming and Antifoaming Properties (3) Aqueous ophthalmic compositions (100 mL) of each of the Examples and Comparative Examples shown in Table 10 were prepared by a conventional method. The units for each component in Table 10 are w / v %. Next, 30 mL of the prepared aqueous ophthalmic compositions were filled into polyethylene terephthalate (PET) containers (50 mL centrifuge tubes, Corning Incorporated No. 430304), and the defoaming rates were evaluated by the following method. Each aqueous ophthalmic composition filled in a container was shaken 1,500 times (300 rpm / min for 5 minutes) using a strong shaker SR-2DW (manufactured by TAITEC Co., Ltd.). Immediately after shaking, the foam and aqueous solution portions were visually confirmed, and the volume of the foam portion was measured (an index of foamability). Next, they were left to stand, and the time until the amount of foam was reduced by half was measured, which was used as the foam half-life (an index of defoaming property). The sodium chondroitin sulfate used was non-standard sodium chondroitin sulfate (manufactured by Seikagaku Corporation, weight-average molecular weight: approximately 20,000).

[0135] [Table 10]

[0136] The foam half-life of Example 10-1 containing sodium chondroitin sulfate was 5 minutes, which was significantly shorter than the foam half-life of Comparative Example 10-1 not containing sodium chondroitin sulfate.In addition, the volume of the foam portion of Example 10-1 immediately after shaking was also significantly reduced compared to the volume of the foam portion of Comparative Example 10-1 immediately after shaking.

[0137] [Test Example 11: Evaluation of Precipitate Generation (2)] Aqueous ophthalmic compositions (100 mL) of each Example and Comparative Example shown in Table 11 were prepared by a conventional method. The units of each component in Table 11 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 11. <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:+ There is a small, unclear precipitate in part of the well: ± No deposits:- The sodium chondroitin sulfate used was non-standard sodium chondroitin sulfate (manufactured by Seikagaku Corporation, weight-average molecular weight: approximately 20,000).

[0138] [Table 11]

[0139] The formation of precipitates was observed in the aqueous ophthalmic compositions of Comparative Examples 11-1 and 11-2, which contained only zinc sulfate hydrate. In contrast, the formation of precipitates was confirmed in the aqueous ophthalmic compositions of Examples 11-1, 11-2, 11-4, and 11-5, in which 1 w / v% or 3 w / v% sodium chondroitin sulfate was blended with zinc sulfate hydrate, and the aqueous ophthalmic composition of Example 11-3, in which 3 w / v% sodium chondroitin sulfate and neostigmine methyl sulfate were blended with zinc sulfate hydrate.

[0140] [Formulation example] Formulation examples are shown in Tables 12 and 13 below. The units of each ingredient in Tables 12 and 13 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.

[0141] [Table 12]

[0142]

Table 13

Claims

1. An aqueous ophthalmic composition comprising (A) at least one selected from the group consisting of zinc sulfate, zinc lactate, and zinc chloride, and (B) at least one selected from the group consisting of chondroitin sulfate and its salts, wherein the content of component (B) is 0.8 w / v% or more based on the total amount of the aqueous ophthalmic composition (however, excluding eye drops containing sodium chondroitin sulfate, hydroxypropyl methylcellulose, phenylephrine hydrochloride, neostigmine methylsulfate, epsilon-aminocaproic acid, allantoin, sodium azulene sulfonate, zinc sulfate, sodium cromoglycate, sodium flavin adenine dinucleotide, cyanocobalamin, hydroxyethylcellulose, boric acid, chlorhexidine gluconate, sodium edetate, polysorbate 80, propylene glycol, l-menthol, dl-camphor, and borneol).

2. The aqueous ophthalmic composition according to Claim 1, wherein the content of component (A) is 0.0001 w / v% to 5 w / v% based on the total amount of the aqueous ophthalmic composition.

3. The aqueous ophthalmic composition according to claim 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. The aqueous ophthalmic composition according to any one of claims 1 to 3, further comprising (C) neostigmine methylsulfate.

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

6. A method for suppressing unpleasant astringent taste after administration of an aqueous ophthalmic composition (excluding eye drops containing sodium chondroitin sulfate, hydroxypropyl methylcellulose, phenylephrine hydrochloride, neostigmine methylsulfate, epsilon-aminocaproic acid, allantoin, sodium azulene sulfonate, zinc sulfate, sodium cromoglycate, sodium flavin adenine dinucleotide, cyanocobalamin, hydroxyethylcellulose, boric acid, chlorhexidine gluconate, sodium edetate, polysorbate 80, propylene glycol, l-menthol, dl-camphor, and borneol), comprising: (A) at least one selected from the group consisting of zinc sulfate, zinc lactate, and zinc chloride; and (B) at least one selected from the group consisting of chondroitin sulfate and salts thereof in an amount of 0.8 w / v% or more based on the total amount of the aqueous ophthalmic composition.