JP2019199468A - Aqueous ophthalmic composition - Google Patents

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

  The present invention relates to an aqueous ophthalmic composition.

  In general, an aqueous ophthalmic composition is filled in a container having an opening, and is repeatedly used by taking out the aqueous ophthalmic composition from the opening at the time of use. At that time, it is known that the aqueous ophthalmic composition adhering to the opening may dry and generate precipitates, causing various problems.

  For example, the accumulation of deposits in the opening not only attaches to the periphery of the opening, but also to the inside of the lid or cap, which not only gives an unpleasant impression to the user, but also when used repeatedly. May make it difficult to open and close the opening. Further, in the case of eye drops, the diameter of the spout, which is an opening, is often very small, and even a slight amount of deposits can block the passage of the aqueous ophthalmic composition and accurately. There is a possibility that the liquid amount may not be dropped. Furthermore, when deposits accumulate at the eye drop outlet, there is also a concern that the precipitates may enter the eye together when instilled.

  On the other hand, in the case of an aqueous ophthalmic composition that is applied directly to the ocular mucosa, when the liquid leaking out of the eye after application is dried and precipitation occurs, a white solid is present around the eye such as the eyelids, eyelashes, and under the eyes. Since it adheres, generation | occurrence | production of the precipitate by drying of an aqueous ophthalmic composition is a problem also from an external appearance or a cosmetic viewpoint.

  As a method for suppressing the generation of precipitates after drying in an aqueous composition, for example, Patent Document 1 reports a method of blending chlorpheniramines and amino acids into an aqueous composition blended with a new quinolone agent. .

JP 2012-250918 A

  However, regarding the aqueous ophthalmic composition containing allantoin and epsilon-aminocaproic acid, the generation of precipitates after drying has not been reported so far. As a result of various studies on aqueous ophthalmic compositions containing allantoin and epsilon-aminocaproic acid, the present inventors have a problem that when the aqueous ophthalmic composition is dried, a white solid called white residue is precipitated. It was confirmed.

  An object of the present invention is to provide an aqueous ophthalmic composition in which the generation of precipitates after drying is suppressed while containing allantoin and at least one selected from the group consisting of epsilon-aminocaproic acid and salts thereof. And

  The present inventors surprisingly added at least one selected from the group consisting of chondroitin sulfate and a salt thereof to an aqueous ophthalmic composition containing allantoin and epsilon-aminocaproic acid and a salt thereof. It was also found that the generation of precipitates in the aqueous ophthalmic composition was suppressed. The present invention is based on this finding, and provides the following inventions.

[1]
(A) Allantoin, and at least one selected from the group consisting of epsilon-aminocaproic acid and its salt, and (B) at least one selected from the group consisting of chondroitin sulfate and its salt An aqueous ophthalmic composition, wherein the content of the 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 the 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 the 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]
(D) The aqueous ophthalmic composition according to any one of [1] to [4], further containing a terpenoid.
[6]
In the aqueous ophthalmic composition, (A) at least one selected from the group consisting of allantoin and epsilon-aminocaproic acid and a salt thereof, and (B) 0.7 w / v% based on the total amount of the aqueous ophthalmic composition The method to suppress generation | occurrence | production of the precipitate in this aqueous ophthalmic composition including mix | blending at least 1 sort (s) selected from the group which consists of the above chondroitin sulfate and its salt.

  According to the present invention, there is provided an aqueous ophthalmic composition in which the generation of precipitates after drying is suppressed while containing allantoin and at least one selected from the group consisting of epsilon-aminocaproic acid and salts thereof. Can do.

  Hereinafter, embodiments for carrying out the present invention will be described in detail. However, the present invention is not limited to the following embodiments.

  In the present specification, unless otherwise specified, the unit of content “%” means “w / v%” and is synonymous with “g / 100 mL”.

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

[Component (A)]
Allantoin, which is the component (A), and epsilon-aminocaproic acid and salts thereof are not particularly limited as long as they are pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Epsilon-aminocaproic acid may be a free form or a pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable salt.

  Allantoin is a known compound also called 2-ureidohydantoin.

  Examples of the epsilon-aminocaproic acid salt include a salt with an inorganic base. Examples of the salt with an inorganic base include alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as magnesium salt and calcium salt. As epsilon-aminocaproic acid and its salt, epsilon-aminocaproic acid is preferable.

  Commercially available allantoin, epsilon-aminocaproic acid, and salts thereof can also be used. Allantoin, epsilon-aminocaproic acid and salts thereof may be used alone or in combination of two or more.

  The content of the component (A) in the eye drop according to this embodiment is preferably 0.001 to 5 w / v% based on the total amount of the aqueous ophthalmic composition. 0.005 to 4 w / v%, more preferably 0.01 to 3 w / v%, still more preferably 0.06 to 2.5 w / v%, 0 0.1-2 w / v% is particularly preferable, and 0.2-2 w / v% is particularly preferable.

  In the case of using allantoin as the component (A), the allantoin content is preferably 0.01 to 1 w / v%, for example, based on the total amount of the aqueous ophthalmic composition. 0.03-0.5 w / v% is more preferable, 0.05-0.4 w / v% is still more preferable, and 0.06-0.3 w / v% is more preferable. More preferably, it is 0.2 to 0.3 w / v%.

  In the case of using epsilon-aminocaproic acid and its salt as the component (A), the content of epsilon-aminocaproic acid and its salt is, for example, based on the total amount of the aqueous ophthalmic composition, epsilon-aminocaproic acid and its salt. The total content is preferably 0.01 to 5 w / v%, more preferably 0.05 to 4 w / v%, still more preferably 0.1 to 3 w / v%, Still more preferably, it is 5 to 2 w / v%. The content of epsilon-aminocaproic acid and its salt is preferably less than 3 w / v% based on the total amount of the aqueous ophthalmic composition, from the viewpoint that the effects of the present invention can be remarkably exhibited.

[(B) component]
In addition to the component (A), the aqueous ophthalmic composition according to this embodiment is at least one selected from the group consisting of (B) chondroitin sulfate and a salt thereof (also simply referred to as “component (B)”). Containing.

  The chondroitin sulfate and salt thereof as the component (B) are not particularly limited as long as they are pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. The molecular weight of chondroitin sulfate and its salt is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutical) or physiologically acceptable, but it usually has a weight average molecular weight of 10,000 to 100,000. About, preferably about 50,000 to 50,000, more preferably about 10,000 to 40,000 can be used.

  Examples of the chondroitin sulfate salt include alkali metal salts and alkaline earth metal salts. Examples of the alkali metal salt include sodium salt and potassium salt. Examples of the alkaline earth metal salt include a magnesium salt and a calcium salt.

  As chondroitin sulfate and a salt thereof, chondroitin sulfate and an alkali metal salt of chondroitin sulfate are preferable, chondroitin sulfate and sodium chondroitin sulfate are more preferable, and sodium chondroitin sulfate is more preferable.

  A commercially available thing can also be used for chondroitin sulfate and its salt. Chondroitin sulfate and its salt may be used individually by 1 type, or may be used in combination of 2 or more type.

  The content of the 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 the component (B) is not particularly limited as long as it is 0.7 w / v% or more, and the type of the component (B), the type and content of other compounding components, the use of the aqueous ophthalmic composition, and It is appropriately set according to the formulation form. As a lower limit of content of (B) component, it is preferable that it is 0.8 w / v% or more from a viewpoint of exhibiting the effect by this invention more notably, for example, it is 0.9 w / v% or more. Is more preferably 1 w / v% or more, still 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 appropriately set according to the type of component (B), the type and content of other compounding components, the use and formulation form of the aqueous ophthalmic composition, and the like. . (B) As an upper limit of content of a component, it is preferable that it is 5 w / v% or less from a viewpoint which show | plays the effect by this invention more notably, and a viewpoint of usability, for example, 4 w / v% or less It is more preferable that it is 3.5 w / v% or less, and it is still more preferable that it is 3 w / v% or less. In addition, the content of the component (B) in the aqueous ophthalmic composition according to this embodiment is, for example, 0.7 to 5 w / v%, 0.7 to 4 w / v% based on the total amount of the aqueous ophthalmic composition. 0.7-3 w / v%, 0.8-5 w / v%, 0.8-4 w / v%, 0.8-3 w / v%, 0.9-5 w / v%, 0.9- It may be 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%. As another aspect, the content of the component (B) in the aqueous ophthalmic composition according to this embodiment is, for example, 2 to 4 w / v%, 2.5 to 3.5 w based on the total amount of the aqueous ophthalmic composition. / V%, or 3w / v% may be sufficient.

  In the aqueous ophthalmic composition according to the present embodiment, the content ratio of the component (B) to the component (A) is not particularly limited, and the types of the components (A) and (B), the types and contents of the other compounding components. It is appropriately set according to the use and formulation form of the aqueous ophthalmic composition. The content ratio of the component (B) relative to the component (A) is, for example, from the viewpoint of further enhancing the effect of the present invention, for example, the total content of the component (A) contained in the aqueous ophthalmic composition according to this embodiment is 1 mass. The total content of component (B) is preferably 0.05 to 50 parts by mass, more preferably 0.1 to 30 parts by mass, and 0.5 to 15 parts by mass with respect to parts. More preferably it is. Moreover, 1-40 mass parts and 1.5-30 mass parts are illustrated as a preferable range.

  When allantoin is used as the component (A), the content ratio of the component (B) relative to the component (A) is 1 part by mass of the total content of the component (A) included in the aqueous ophthalmic composition according to this embodiment. On the other hand, the total content of the component (B) is preferably 0.3 to 100 parts by mass, more preferably 1 to 50 parts by mass, and further preferably 3 to 15 parts by mass. Moreover, 5-40 mass parts and 10-30 mass parts are illustrated as a preferable range.

  When using epsilon-aminocaproic acid and a salt thereof as the component (A), the content ratio of the component (B) to the component (A) is the total of the components (A) included in the aqueous ophthalmic composition according to the present embodiment. The total content of the component (B) is preferably 0.05 to 20 parts by mass, more preferably 0.1 to 10 parts by mass with respect to 1 part by mass of content, and 0.5 to More preferably, it is 6 parts by mass. Moreover, 1-40 mass parts and 1.5-30 mass parts are illustrated as a preferable range.

[Component (C)]
The aqueous ophthalmic composition according to this embodiment may further contain (C) neostigmine methylsulfate (also simply referred to as “(C) component”). The effect by this invention is show | played more notably because an aqueous ophthalmic composition contains (C) component.

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

  Methyl sulfate neostigmine is a known compound also called methyl sulfate (3-dimethylcarbamoyloxyphenyl) trimethylammonium.

  The content of the component (C) in the aqueous ophthalmic composition according to this embodiment is not particularly limited, and is appropriately set according to the type and content of other compounding components, the use and formulation form of the aqueous ophthalmic composition, and the like. . The content of the component (C) is, for example, from the viewpoint of more prominently achieving the effects of the present invention, for example, based on the total amount of the aqueous ophthalmic composition, the total content of the component (C) is 0.00005 to 0.005. 1 w / v% is preferable, 0.0001 to 0.05 w / v% is more preferable, 0.0005 to 0.01 w / v% is further more preferable, and 0.001 to 0.001. Even more preferably, it is 005 w / v%.

  In the aqueous ophthalmic composition according to this embodiment, the content ratio of the component (C) to the component (A) is not particularly limited, and the types of the components (A) and (C), the types and contents of the other compounding components. It is appropriately set according to the use and formulation form of the aqueous ophthalmic composition. As a content ratio of the component (C) with respect to the component (A), for example, from the viewpoint of further enhancing the effect of the present invention, the total content of the component (A) contained in the aqueous ophthalmic composition according to the present embodiment is 1 mass. The total content of component (C) is preferably 0.00005 to 0.5 parts by mass, more preferably 0.0001 to 0.1 parts by mass, and 0.0005 to parts by mass. More preferably, it is 0.05 mass part.

  In the aqueous ophthalmic composition according to the present embodiment, the content ratio of the (C) component to the (B) component is not particularly limited, and the types of the (B) component and (C) component, the types and contents of other compounding components. It is appropriately set according to the use and formulation form of the aqueous ophthalmic composition. As a content ratio of the component (C) with respect to the component (B), from the viewpoint of further enhancing the effect of the present invention, for example, the total content of the component (B) contained in the aqueous ophthalmic composition according to the present embodiment is 1 mass. The total content of the component (C) is preferably 0.00005 to 0.05 parts by mass, more preferably 0.0001 to 0.01 parts by mass, and 0.0003 to More preferably, it is 0.005 parts by mass. Moreover, 0.0005-0.003 mass part and 0.001-0.002 mass part are also illustrated as a preferable range.

[Component (D)]
The aqueous ophthalmic composition according to the present embodiment may further contain (D) a terpenoid (also simply referred to as “(D) component”). The effect by this invention is show | played more notably because an aqueous ophthalmic composition contains (D) component.

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

  Examples of terpenoids include cyclic terpenes and acyclic terpenes.

  Cyclic terpenes are terpenoids having at least one ring structure in the molecule. Examples of the cyclic terpene include menthol, camphor, borneol (also referred to as “ryuunou”), menthone, cineol, carvone, anethole, eugenol, limonene, pinene, and derivatives thereof.

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

  In the present invention, an essential oil containing the above compound may be used as the terpenoid. Examples of such essential oils include eucalyptus oil, bergamot oil, peppermint oil, cool mint oil, spearmint oil, peppermint oil, fennel oil, cinnamon oil, and rose oil.

  Terpenoids may be any of d-form, l-form, and dl-form, and include dl-menthol, d-menthol, l-menthol, dl-camphor, d-camphor, l-camphor, dl-borneol, d-borneol, and l-borneol. , Dl-menton, d-menton, and l-menton. However, optical isomers may not exist depending on terpenoids such as geraniol and cineol.

  As terpenoids, 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 more preferred, Even more preferred is l-menthol.

  A commercially available terpenoid may be used. A terpenoid may be used individually by 1 type, or may be used in combination of 2 or more type.

  Content of (D) component in the aqueous ophthalmic composition which concerns on this embodiment is not specifically limited, The kind of (D) component, the kind and content of another compounding component, the use and formulation form of an aqueous ophthalmic composition, etc. It is set appropriately according to As the content of the component (D), from the viewpoint of more prominently achieving the effects of the present invention, for example, the total content of the component (D) is 0.00001 to 1 w / w based on the total amount of the aqueous ophthalmic composition. It is preferably v%, more preferably 0.00005 to 0.5 w / v%, still more preferably 0.0001 to 0.1 w / v%, and 0.0005 to 0.05 w / v. It is still more preferable that it is v%, and it is especially preferable that it is 0.001-0.05 w / v%.

  In the aqueous ophthalmic composition according to this embodiment, the content ratio of the component (D) to the component (A) is not particularly limited, and the types of the components (A) and (D), the types and contents of the other compounding components. It is appropriately set according to the use and formulation form of the aqueous ophthalmic composition. The content ratio of the component (D) relative to the component (A) is, for example, from the viewpoint of further enhancing the effects of the present invention, for example, the total content of the component (A) contained in the aqueous ophthalmic composition according to this embodiment is 1 mass. The total content of component (D) is preferably 0.00001 to 5 parts by mass, more preferably 0.00005 to 2 parts by mass, and 0.0001 to 1 part by mass relative to parts by mass. It is still more preferable, and it is still more preferable that it is 0.0005-0.5 mass part.

  In the aqueous ophthalmic composition according to the present embodiment, the content ratio of the component (D) to the component (B) is not particularly limited, and the types of the component (B) and the component (D) and the types and contents of the other compounding components. It is appropriately set according to the use and formulation form of the aqueous ophthalmic composition. The content ratio of the component (D) relative to the component (B) is, for example, from the viewpoint of further enhancing the effect of the present invention, for example, the total content of the component (B) contained in the aqueous ophthalmic composition according to this embodiment is 1 mass. The total content of the component (D) is preferably 0.00005 to 0.5 parts by mass, more preferably 0.0001 to 0.1 parts by mass, and 0.0003 to It is still more preferable that it is 0.05 mass part, and it is still more preferable that it is 0.0003-0.03 mass part.

[Surfactant]
The aqueous ophthalmic composition according to the present embodiment may further contain a surfactant. When the aqueous ophthalmic composition further contains a surfactant, the effect of the present invention is more remarkably exhibited. The surfactant is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable.

  Examples of the surfactant include a nonionic surfactant and an ionic (anionic, amphoteric, cationic) surfactant.

  Examples of the nonionic surfactant include monolauric acid POE (20) sorbitan (polysorbate 20), monopalmitic acid POE (20) sorbitan (polysorbate 40), monostearic acid POE (20) sorbitan (polysorbate 60), and tristearin. POE sorbitan fatty acid esters such as acid POE (20) sorbitan (polysorbate 65) and monooleic acid POE (20) sorbitan (polysorbate 80); POE / POP glycols; POE hydrogenated castor oil 40, POE hydrogenated castor oil 50, POE hydrogenated castor oil 60, POE hydrogenated castor oil 80, etc .; POE hydrogenated castor oil; 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 such as POE castor oil 35 and POE castor oil 50; polyethylene glycol monostearate (2E.O.), polyethylene glycol monostearate (4E.O.), polyethylene glycol monostearate (9E.O.) , Polyethylene glycol monostearate (10E.O.), polyethylene glycol monostearate (23E.O.), polyethylene glycol monostearate (25E.O.), polyethylene glycol monostearate (32E.O.), mono Polyethylene glycol stearate (40 EO, polyoxyl 40 stearate), polyethylene glycol monostearate (45 EO), polyethylene glycol monostearate (55 EO), polyethylene glycol monostearate (75 EO), monostearin Polyethylene glycol monostearate such as polyethylene glycol acid (140E.O.); POE alkyl ethers such as POE (9) lauryl ether; POE-POP alkyl ethers such as POE (20) POP (4) cetyl ether; POE (10) POE alkylphenyl ethers such as nonylphenyl ether. In the compounds exemplified above, POE is polyoxyethylene, POP is polyoxypropylene, and the numbers in parentheses indicate the number of moles added.

  Examples of the anionic surfactant include polyoxyethylene alkyl ether phosphate, polyoxyethylene alkyl ether sulfate, alkylbenzene sulfonate, alkyl sulfate, and N-acyl taurate.

  Examples of the amphoteric surfactant include lauryldimethylaminoacetic acid betaine and alkyldiaminoethylglycine hydrochloride.

  Examples of the cationic surfactant include benzalkonium chloride, benzalkonium bromide, benzethonium chloride, chlorhexidine gluconate, polydronium hydrochloride, and cetylpyridinium chloride.

  As the surfactant, a nonionic surfactant is preferable. As the nonionic surfactant, POE sorbitan fatty acid esters; POE / POP glycols; POE hydrogenated castor oil; POE castor oil; polyethylene glycol monostearate is preferable, and polysorbate 80, poloxamer 407, POE hydrogenated castor oil 40, POE Hardened castor oil 60, POE castor oil 3, POE castor oil 10, POE castor oil 35, and stearic acid polyoxyl 40 are more preferable, and polysorbate 80, POE hardened castor oil 40, POE hardened castor oil 60, and stearic acid polyoxyl 40 are more preferable. Polysorbate 80 and POE hydrogenated castor oil 60 are particularly preferred.

  A commercially available surfactant may be used. Surfactant may be used individually by 1 type, or may be used in combination of 2 or more type.

  The content of the surfactant in the aqueous ophthalmic composition according to this embodiment is not particularly limited, depending on the type of surfactant, the type and content of other compounding components, the use and formulation form of the aqueous ophthalmic composition, etc. Is set as appropriate. As the content of the surfactant, from the viewpoint of more prominently achieving the effects of the present invention, for example, the total content of the surfactant is 0.00001 to 5 w / v% on the basis of the total amount of the aqueous ophthalmic composition. It is preferably 0.00005 to 1 w / v%, more preferably 0.0001 to 0.5 w / v%, and 0.001 to 0.3 w / v%. Even more preferred.

  When the surfactant is a nonionic surfactant, the surfactant content is, for example, based on the total amount of the aqueous ophthalmic composition, and the total surfactant content is 0.001 to 5 w / v. %, More preferably 0.005 to 1 w / v%, still more preferably 0.01 to 0.5 w / v%.

  When the surfactant is a cationic surfactant, the surfactant content is, for example, based on the total amount of the aqueous ophthalmic composition, and the total surfactant content is 0.00001 to 1 w / v. %, More preferably 0.00005 to 0.1 w / v%, still more preferably 0.0001 to 0.05 w / v%, and 0.001 to 0.01 w / v. % Is even more preferred.

  In the aqueous ophthalmic composition according to the present embodiment, the content ratio of the surfactant to the component (A) is not particularly limited, and the type of the component (A) and the surfactant, the type and content of other compounding components, and the aqueous It is appropriately set according to the use and formulation form of the ophthalmic composition. As the content ratio of the surfactant to the component (A), from the viewpoint of further enhancing the effect of the present invention, for example, the total content of the component (A) contained in the aqueous ophthalmic composition according to the present embodiment is 1 part by mass. The total surfactant content is preferably 0.0005 to 100 parts by mass, more preferably 0.001 to 50 parts by mass, and 0.005 to 10 parts by mass. Is more preferable.

  In the aqueous ophthalmic composition according to the present embodiment, the content ratio of the surfactant to the component (B) is not particularly limited, and the types of the component (B) and the surfactant, the types and contents of other compounding components, and the aqueous It is appropriately set according to the use and formulation form of the ophthalmic composition. As the content ratio of the surfactant to the component (B), from the viewpoint of further enhancing the effect of the present invention, for example, the total content of the component (B) contained in the aqueous ophthalmic composition according to the present embodiment is 1 part by mass. The total surfactant content is preferably 0.00001 to 5 parts by mass, more preferably 0.0005 to 3 parts by mass, and 0.0001 to 3 parts by mass. Is more preferably 0.001 to 1 part by mass, particularly preferably 0.005 to 0.5 part by mass, and particularly preferably 0.01 to 0.5 part by mass. preferable.

[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 remarkably exhibited. The buffer is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable.

  Examples of the buffer include inorganic buffers that are buffers derived from inorganic acids, and organic buffers that are buffers derived from organic acids or organic bases.

  Examples of the inorganic buffer include borate buffer, phosphate buffer, and carbonate buffer. Examples of the boric acid buffer include boric acid or a salt thereof (alkali metal borate, alkaline earth metal borate, etc.). Examples of the phosphate buffer include phosphoric acid or a salt thereof (such as an alkali metal phosphate or an alkaline earth metal phosphate). Examples of the carbonate buffer include carbonic acid or a salt thereof (an alkali metal carbonate, an alkaline earth metal carbonate, etc.). Further, borate, phosphate or carbonate hydrates may be used as borate buffer, phosphate buffer or carbonate buffer. As a more specific example, boric acid or a salt thereof (sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, borax, etc.); as a phosphate buffer, phosphoric acid or a salt thereof Salt (disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, trisodium phosphate, tripotassium phosphate, calcium monohydrogen phosphate, calcium dihydrogen phosphate, etc.); Or the salt (Sodium hydrogencarbonate, sodium carbonate, ammonium carbonate, potassium carbonate, calcium carbonate, potassium hydrogencarbonate, magnesium carbonate etc.) etc. can be illustrated.

  Examples of the organic buffer include citrate buffer, acetate buffer, lactic acid buffer, succinate buffer, Tris buffer, and AMPD buffer. Examples of the citrate buffer include citric acid or salts thereof (alkali metal citrate, alkaline earth metal citrate, etc.). Examples of the acetate buffer include acetic acid or a salt thereof (alkali metal acetate, alkaline earth metal acetate, etc.). Examples of the lactic acid buffer include lactic acid or a salt thereof (such as an alkali metal lactate or alkaline earth metal lactate). Examples of the succinic acid buffer include succinic acid or a salt thereof (such as an alkali metal succinate). Moreover, you may use the hydrate of a citrate, acetate, lactate, or a succinate as a citrate buffer, an acetate buffer, a lactic acid buffer, or a succinate buffer. As a more specific example, citric acid or a salt thereof (sodium citrate, potassium citrate, calcium citrate, sodium dihydrogen citrate, disodium citrate, etc.); Or salts thereof (ammonium acetate, sodium acetate, potassium acetate, calcium acetate, etc.); lactic acid or salts thereof (sodium lactate, potassium lactate, calcium lactate, etc.) as lactic acid buffers; succinic acid or salts thereof as succinic acid buffers ( Examples thereof include monosodium succinate and disodium succinate. As a tris buffer, trometamol or its salt (trometamol hydrochloride etc.) is mentioned, for example. Examples of the AMPD buffer include 2-amino-2-methyl-1,3-propanediol or a salt thereof.

  Examples of the buffer include a borate buffer (for example, a combination of boric acid and borax), a phosphate buffer (for example, a combination of disodium hydrogen phosphate and sodium dihydrogen phosphate), a Tris buffer (for example, , Trometamol), boric acid buffers are more preferred, boric acid and its salts are more preferred, and a combination of boric acid and borax is even more preferred.

  A commercially available buffer may be used. A buffering agent may be used individually by 1 type, or may be used in combination of 2 or more type.

  The content of the buffering agent in the aqueous ophthalmic composition according to this embodiment is not particularly limited, and is appropriately determined according to the type of buffering agent, the type and content of other compounding components, the use and formulation form of the aqueous ophthalmic composition, and the like. Is set. The content of the buffering agent is, for example, from the viewpoint of more prominently achieving the effects of the present invention, for example, the total content of the buffering agent is 0.01 to 10 w / v% based on the total amount of the aqueous ophthalmic composition. It is preferably 0.05 to 5 w / v%, more preferably 0.1 to 3 w / v%.

  In the aqueous ophthalmic composition according to the present embodiment, the content ratio of the buffer to the component (A) is not particularly limited, and the type of the component (A) and the buffer, the type and content of other compounding components, and the aqueous ophthalmic composition. It is set as appropriate according to the use of the product and the formulation form. As a content ratio of the buffering agent with respect to the component (A), from the viewpoint of further enhancing the effect of the present invention, for example, the total content of the component (A) contained in the aqueous ophthalmic composition according to the present embodiment is 1 part by mass. On the other hand, the total content of the buffer is preferably 0.01 to 10 parts by mass, more preferably 0.1 to 5 parts by mass, and further preferably 0.5 to 3 parts by mass. preferable.

  In the aqueous ophthalmic composition according to the present embodiment, the content ratio of the buffer to the component (B) is not particularly limited, and the type of the component (B) and the buffer, the type and content of other compounding components, and the aqueous ophthalmic composition. It is set as appropriate according to the use of the product and the formulation form. As a content ratio of the buffer to the component (B), from the viewpoint of further enhancing the effect of the present invention, for example, the total content of the component (B) contained in the aqueous ophthalmic composition according to the present embodiment is 1 part by mass. On the other hand, the total content of the buffer is preferably 0.01 to 10 parts by mass, more preferably 0.1 to 5 parts by mass, and further preferably 0.5 to 3 parts by mass. Preferably, it is still more preferable that it is 0.5-1 mass part.

  The pH of the aqueous ophthalmic composition according to the present embodiment is not particularly limited as long as it is within a pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable range. As pH of the aqueous ophthalmic composition which concerns on this embodiment, it may be 4.0-9.5, for example, it is preferable that it is 4.0-9.0, and it is 4.5-9.0. Is more preferably 4.5 to 8.5, even more preferably 5.0 to 8.5, particularly preferably 5.5 to 8.0, and 6. It is especially more preferable that it is 0-7.0.

  The aqueous ophthalmic composition which concerns on this embodiment can be adjusted to the osmotic pressure ratio in the range accept | permitted by a biological body as needed. The appropriate osmotic pressure ratio varies depending on the application site, dosage form, and the like, but is preferably 0.05 to 6, and more preferably 0.4 to 5, from the viewpoint of more prominently achieving the effects of the present invention. Preferably, it is set as 0.6-3, and it is still more preferable to set it as 0.8-2. The osmotic pressure can be adjusted by a method known in the art using inorganic salts, polyhydric alcohols, and the like. The osmotic pressure ratio is the ratio of the osmotic pressure of the sample to 286 mOsm (0.9 w / v% sodium chloride aqueous solution) based on the 17th revised Japanese Pharmacopoeia. Measure with reference to (freezing point depression method). The standard solution for measuring the osmotic pressure ratio (0.9 w / v% sodium chloride aqueous solution) was dried in sodium chloride (Japanese Pharmacopoeia standard reagent) at 500 to 650 ° C. for 40 to 50 minutes, and then in a desiccator (silica gel). The solution is allowed to cool and 0.900 g is accurately weighed and dissolved in purified water to prepare exactly 100 mL, or a commercially available standard solution for osmotic pressure ratio measurement (0.9 w / v% sodium chloride aqueous solution) can be used.

  The viscosity of the aqueous ophthalmic composition according to the present embodiment is not particularly limited as long as it is within a pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable range. As the viscosity of the aqueous ophthalmic composition according to the present embodiment, for example, the viscosity at 20 ° C. measured with a rotational viscometer (TV-20 viscometer, manufactured by Toki Sangyo Co., Ltd., rotor: 1 ° 34 ′ × R24). It is preferably 0.1 to 10000 mPa · s, more preferably 1 to 3000 mPa · s, still more preferably 1 to 1000 mPa · s, still more preferably 1 to 100 mPa · s, It is particularly preferably 1 to 50 mPa · s, particularly preferably 1 to 10 mPa · s, still more preferably 1.3 to 5 mPa · s, and further preferably 1.5 to 3 mPa · s. Is most preferred.

The aqueous ophthalmic composition according to the present embodiment contains an appropriate amount of a combination of components selected from various pharmacologically active components and physiologically active components in addition to the above components, as long as the effects of the present invention are not impaired. May be. The said component is not specifically limited, For example, the active ingredient in the ophthalmic medicine described in the over-the-counter medicine manufacture sale approval standard 2012 version (supervised by General Society of Regulatory Science) can be illustrated. Specific examples of components used in ophthalmic drugs include the following components.
Antiallergic agents: for example, sodium cromoglycate, tranilast, pemirolast potassium and the like.
Antihistamine: for example, diphenhydramine hydrochloride, iproheptin, chlorpheniramine maleate, levocabastine hydrochloride, ketotifen fumarate, pemirolast potassium, olopatadine hydrochloride, etc. The aqueous ophthalmic composition according to this embodiment preferably does not contain diphenhydramine or a salt thereof from the viewpoint of further enhancing the effects of the present invention.
Anti-inflammatory agents other than component (A): for example, methyl salicylate, glycol salicylate, dipotassium glycyrrhizinate, tranexamic acid, berberine, berberine sulfate, berberine sulfate, lysozyme, lysozyme chloride, azulene sulfonic acid, sodium azulene sulfonate, indomethacin, plano Profen, ibuprofen, ibuprofen piconol, ketoprofen, felbinac, bendazac, piroxicam, bufexamac, butyl flufenamate, zinc sulfate and the like.
Steroid agents: For example, fluticasone propionate, fluticasone furancarboxylate, mometasone furancarboxylate, beclomethasone propionate, flunisolide and the like.
Decongestant: for example, tetrahydrozoline hydrochloride, tetrahydrozoline nitrate, naphazoline hydrochloride, naphazoline nitrate, epinephrine, epinephrine hydrochloride, ephedrine hydrochloride, phenylephrine hydrochloride, dl-methylephedrine hydrochloride. The aqueous ophthalmic composition according to this embodiment preferably does not contain phenylephrine hydrochloride from the viewpoint of further enhancing the effects of the present invention.
(C) Ocular muscle modulating agent other than component: for example, cholinesterase inhibitor having an active center similar to acetylcholine, specifically tropicamide, helenien, atropine sulfate and the like.
Vitamins: for example, retinol acetate, retinol palmitate, tocopherol acetate, sodium flavin adenine dinucleotide, cyanocobalamin, pyridoxine hydrochloride, panthenol, calcium pantothenate, ascorbic acid, sodium ascorbate and the like.
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 and potassium chloride; ammonium chloride; metal sulfates such as calcium sulfate, magnesium sulfate, sodium sulfate, potassium sulfate and ammonium sulfate.
Astringent: For example, zinc white, zinc lactate, zinc sulfate and the like.
Others: For example, sulfamethoxazole, sulfisoxazole, sulfisomidine, and salts thereof.

In the aqueous ophthalmic composition according to the present embodiment, various additives are appropriately selected according to a conventional method depending on the use and the formulation form, as long as the effects of the present invention are not impaired. The above may be used in combination to contain an appropriate amount. Examples of such additives include various additives described in Pharmaceutical Additives Encyclopedia 2007 (edited by Japan Pharmaceutical Additives Association). Typical additives include the following additives.
Carrier: An aqueous solvent such as water or hydrous ethanol.
Chelating agent: for example, ethylenediaminediacetic acid (EDDA), ethylenediaminetriacetic acid, ethylenediaminetetraacetic acid (EDTA), N- (2-hydroxyethyl) ethylenediaminetriacetic acid (HEDTA), diethylenetriaminepentaacetic acid (DTPA) and the like.
Base: for example, octyldodecanol, titanium oxide, potassium bromide, plastibase and the like.
pH adjuster: For example, hydrochloric acid, acetic acid, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, triethanolamine, diisopropanolamine and the like.
Stabilizers: For example, sodium formaldehyde sulfoxylate (Longalite), sodium bisulfite, sodium pyrosulfite, aluminum monostearate, glyceryl monostearate, cyclodextrin, monoethanolamine, dibutylhydroxytoluene and the like.
Preservatives, bactericides or antibacterials: for example, zinc chloride, sodium benzoate, ethanol, chlorobutanol, sorbic acid, potassium sorbate, sodium dehydroacetate, methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, paraoxy Butyl benzoate, oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, biguanide compounds (specifically, polyhexanide hydrochloride (polyhexamethylene biguanide), etc.), glow kill (trade name, manufactured by Rhodia), etc. It is preferable that the aqueous ophthalmic composition which concerns on this embodiment does not contain paraoxybenzoic acid ester (paraben) from a viewpoint which raises the effect by this invention more.
Isotonizing agents: for example, sodium bisulfite, sodium sulfite, potassium chloride, calcium chloride, sodium chloride, magnesium chloride, potassium acetate, sodium acetate, sodium bicarbonate, sodium carbonate, sodium thiosulfate, magnesium sulfate, glycerin, propylene glycol etc. When the aqueous ophthalmic composition according to this embodiment contains propylene glycol, if the content of propylene glycol exceeds 3 w / v% based on the total amount of the aqueous ophthalmic composition, the osmotic pressure becomes too high. Therefore, it is preferably 3 w / v% or less.
Thickener: For example, cellulose polymer compound (for example, methylcellulose, ethylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, sodium carboxymethylcellulose), polyvinyl polymer compound (polyvinylpyrrolidone, polyvinyl alcohol, etc.), carboxyvinyl polymer, guar gum , Hydroxypropyl guar gum, gum arabic, karaya gum, xanthan gum, agar, alginic acid and its salts (sodium salt, etc.), mucopolysaccharides (eg heparin analogues, heparin, heparin sulfate, heparan sulfate, heparinoid, hyaluronic acid and its salts ( Sodium salt, etc.), starch, chitin and derivatives thereof, chitosan and derivatives thereof, carrageenan and the like.
Sugars: for example, glucose, cyclodextrin and the like.
Sugar alcohols: For example, xylitol, sorbitol, mannitol, glycerin and the like. These may be d-form, l-form 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 petrolatum.

  In the case where the aqueous ophthalmic composition according to this embodiment contains water, the content of water is, for example, from the viewpoint of more prominently achieving the effects of the present invention, for example, based on the total amount of the aqueous ophthalmic composition. The amount is preferably 80 w / v% or more and less than 100 w / v%, more preferably 85 w / v% or more and 99.5 w / v% or less, and 90 w / v% or more and 99.2 w / v% or less. More preferably.

  The water used in the aqueous ophthalmic composition according to the present embodiment may be anything that is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Examples of such water include distilled water, normal water, purified water, sterilized purified water, water for injection, and distilled water for injection. These definitions are based on the 17th revised Japanese Pharmacopoeia.

  The aqueous ophthalmic composition according to the present embodiment is prepared, for example, by adding and mixing the component (A), the component (B), and other components as necessary so as to obtain a desired content. Can do. Specifically, for example, the components can be dissolved or suspended in purified water, adjusted to a predetermined pH and osmotic pressure, and sterilized by filtration sterilization or the like.

  The aqueous ophthalmic composition according to this embodiment can take various dosage forms according to the purpose, and examples thereof include a liquid agent, a gel agent, and a semi-solid agent (ointment, etc.). Among these, a liquid agent is preferable and an aqueous liquid agent is more preferable.

  The aqueous ophthalmic composition according to the present embodiment includes, for example, 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), eyewashes. (Also referred to as eyewash or eyewash. In addition, eyewash contains eyewash that can be washed while wearing contact lenses), contact lens compositions [contact lens mounting liquids, contact lens care compositions (contact Lens disinfectant, contact lens preservative, contact lens cleaner, contact lens cleaner preservative, etc.]. The “contact lens” includes hard contact lenses and soft contact lenses (including both ionic and non-ionic, including both silicone hydrogel contact lenses and non-silicone hydrogel contact lenses).

  The aqueous ophthalmic composition according to the present embodiment is preferably an eye drop (including an eye drop that can be applied while wearing a contact lens) because the effects of the present invention can be exhibited more remarkably. When the aqueous ophthalmic composition according to this embodiment is an ophthalmic solution, its usage / dose is not particularly limited as long as it is effective and has few side effects. For example, adults (15 years and older) and 7 For children over the age of 1 to 2 drops per day, or 4 drops per day, 1 to 2 drops, 1 to 3 drops, or 2 to 3 drops per day The method of instilling 5-6 times and using can be illustrated.

  The aqueous ophthalmic composition according to the present embodiment is provided by being housed in an arbitrary container. The container for housing the aqueous ophthalmic composition according to the present embodiment is not particularly limited, and may be made of glass or plastic, for example. Preferably it is made of plastic. Examples of the plastic include polyethylene terephthalate, polyarylate, polyethylene naphthalate, polycarbonate, polyethylene, polypropylene, polyimide, a copolymer of monomers constituting these, and a mixture of these two or more. Preferred are polypropylene, polyethylene, and polyethylene terephthalate, and more preferred is polyethylene terephthalate. Moreover, the container which accommodates the aqueous ophthalmic composition which concerns on this embodiment may be a transparent container which can visually recognize the inside of a container, and may be an opaque container where it is difficult to visually recognize the inside of a container. A transparent container is preferable. Here, the “transparent container” includes both a colorless transparent container and a colored transparent container.

  A nozzle may be attached to the container that stores the aqueous ophthalmic composition according to the present embodiment. The material of the nozzle is not particularly limited, and may be made of glass or plastic, for example. Preferably it is made of plastic. Examples of the plastic include polybutylene terephthalate, polyethylene, polypropylene, polyethylene naphthalate, a copolymer of monomers constituting these, and a mixture of two or more of these. As a material of the nozzle, polypropylene, polyethylene, polyethylene terephthalate, and polyethylene naphthalate are preferable, and polyethylene is more preferable from the viewpoint of further enhancing the effects of the present invention.

  The container for storing the aqueous ophthalmic composition according to the present embodiment may be a multi-dose type in which a plurality of usage amounts are stored, or a unit dose type in which a single usage amount is stored. However, since the effects of the present invention can be exhibited more remarkably, a multi-dose type is preferable.

[2. Method for suppressing generation of precipitate in aqueous ophthalmic composition]
The aqueous ophthalmic composition according to the present embodiment is at least one selected from the group consisting of allantoin and epsilon-aminocaproic acid and salts thereof, and 0.7 w / v% or more based on the total amount of the aqueous ophthalmic composition By adding at least one selected from the group consisting of chondroitin sulfate and salts thereof, the generation of precipitates in the aqueous ophthalmic composition is remarkably suppressed. Therefore, as one embodiment of the present invention, the aqueous ophthalmic composition includes (A) allantoin and at least one selected from the group consisting of epsilon-aminocaproic acid and a salt thereof, and (B) the total amount of the aqueous ophthalmic composition. A method for suppressing the generation of precipitates in the aqueous ophthalmic composition, comprising blending at least one selected from the group consisting of chondroitin sulfate and its salt at 0.7 w / v% or more based on The

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

[3. Method for improving unpleasant taste after administration in aqueous ophthalmic composition]
The aqueous ophthalmic composition according to this embodiment includes at least one selected from the group consisting of epsilon-aminocaproic acid and a salt thereof, and chondroitin sulfate of 0.7 w / v% or more based on the total amount of the aqueous ophthalmic composition. And at least one selected from the group consisting of the salts thereof, the unpleasant taste after administration in the aqueous ophthalmic composition (bitter taste) is improved. Therefore, as one embodiment of the present invention, the aqueous ophthalmic composition includes (A1) at least one selected from the group consisting of epsilon-aminocaproic acid and a salt thereof, and (B) based on the total amount of the aqueous ophthalmic composition. There is provided a method for improving an unpleasant taste after administration in the aqueous ophthalmic composition, comprising blending one or more selected from the group consisting of 0.7 w / v% or more of chondroitin sulfate and a salt thereof . Moreover, as one embodiment of the present invention, the aqueous ophthalmic composition is based on (A1) at least one selected from the group consisting of epsilon-aminocaproic acid and a salt thereof, and (B) the total amount of the aqueous ophthalmic composition. Provided is a method for improving an unpleasant bitter taste after administration in the aqueous ophthalmic composition, comprising blending at least one selected from the group consisting of 0.7 w / v% or more of chondroitin sulfate and a salt thereof Is done.

  In addition, in this embodiment, the type and content of the component (A1), the type and content of the component (B), the type and content of other components, the formulation form and use of the aqueous ophthalmic composition, etc. [1. As described in [Aqueous ophthalmic composition].

  Hereinafter, the present invention will be specifically described based on test examples, but the present invention is not limited thereto.

[Test Example 1: Evaluation of precipitate generation (1)]
The aqueous ophthalmic compositions (100 mL) of each Example and Comparative Example shown in Table 1 were prepared by a conventional method. The unit of each component in Table 1 is 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 stand still overnight at 60 ° C. in a laboratory-use drier (LabWareDryingOven, DG82; manufactured by Yamato Scientific Co., Ltd.). And dried. 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 generation>
There is a clearly visible deposit on the entire bottom of the well: +++
There is a deposit that can be clearly seen in a part of the well: ++
Some of the wells have obscure precipitates: +
No precipitate:-
In addition, as the chondroitin sulfate sodium, external standard chondroitin sulfate sodium eye drops / injection (manufactured by Maruha Nichiro Foods Co., Ltd.) was used.

  In the aqueous ophthalmic composition of Comparative Example 1-1 containing only allantoin, generation of precipitates was observed. Moreover, generation | occurrence | production of the deposit was recognized also in the aqueous ophthalmic composition of the comparative example 1-2 which mix | blended 0.5 w / v% sodium chondroitin sulfate with allantoin. On the other hand, it was confirmed that no precipitate was generated in the aqueous ophthalmic compositions of Examples 1-1 and 1-2 in which 1 w / v% or 3 w / v% sodium chondroitin sulfate was added to allantoin.

[Test Example 2: Evaluation of occurrence of precipitates (2)]
Aqueous ophthalmic compositions (100 mL) of Examples and Comparative Examples shown in Tables 2 and 3 were prepared by a conventional method. The unit of each component in Tables 2 and 3 is w / v%. Next, each aqueous ophthalmic composition was dried in the same manner as in Test Example 1, and the generation of precipitates after drying was evaluated. The results are shown in Tables 2 and 3.
In addition, as the chondroitin sulfate sodium, external standard chondroitin sulfate sodium eye drops / injection (manufactured by Maruha Nichiro Foods Co., Ltd.) was used.

  In the aqueous ophthalmic compositions of Comparative Examples 2-1 and 2-3 containing only epsilon-aminocaproic acid, generation of precipitates (white residue) was observed. Moreover, generation | occurrence | production of the deposit (white residue) was recognized also in the aqueous ophthalmic composition of Comparative Example 2-2 and 2-4 which mix | blended 0.5 w / v% sodium chondroitin sulfate with the epsilon-aminocaproic acid. In contrast, in the aqueous ophthalmic compositions of Examples 2-1, 2-2, and 2-3 in which 1 w / v% or 3 w / v% sodium chondroitin sulfate was blended with epsilon-aminocaproic acid, precipitates were generated. It was confirmed not to.

[Test Example 3: Taste evaluation]
The aqueous ophthalmic compositions (100 mL) of each Example and Comparative Example shown in Table 4 were prepared by a conventional method. The unit of each component in Table 4 is w / v%. Next, the bitter taste index of each aqueous ophthalmic composition was measured using a taste recognition device (SA402B; manufactured by Intelligent Sensor Technology Co., Ltd.). The measurement method was according to the instruction manual of SA402B, and the potential difference between the reference solution and each aqueous ophthalmic composition was measured as an index of bitter taste. Using the obtained measured value, the difference from Comparative Example 3-1 was calculated for the bitter taste of Example 3-1 by the following formula. The results are shown in Table 4.
[Formula 1] Index difference from Comparative Example 3-1 = Measured value of Comparative Example 3-1−Measured value of Example 3-1 In addition, as chondroitin sulfate sodium, external standard sodium chondroitin sulfate for eye drops / injection (Manufactured by Maruha Nichiro Foods, Inc.) was used.

  In 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, Comparative Example 3-1 containing only epsilon-aminocaproic acid It was confirmed that the index of bitter taste was significantly reduced as compared with the aqueous ophthalmic composition.

[Test Example 4: Evaluation of occurrence of precipitates (3)]
The aqueous ophthalmic compositions (100 mL) of each Example and Comparative Example shown in Table 5 were prepared by a conventional method. The unit of each component in Table 5 is w / v%. Next, each aqueous ophthalmic composition was dried in the same manner as in Test Example 1, and the generation of precipitates after drying was evaluated. The results are shown in Table 5.
As sodium chondroitin sulfate, extraordinary sodium chondroitin sulfate (manufactured by Seikagaku Corporation, weight average molecular weight of about 20000) was used.

  In the aqueous ophthalmic compositions of Comparative Examples 4-1 and 4-3 containing only allantoin, and the aqueous ophthalmic composition of Comparative Example 4-2 in which a boric acid buffer was added to allantoin, generation of precipitates was observed. . On the other hand, the aqueous ophthalmic compositions of Examples 4-1 to 4-4, 4-6 and 4-7, in which 1 w / v% or 3 w / v% sodium chondroitin sulfate was added to allantoin, and 3 w to allantoin In the aqueous ophthalmic composition of Example 4-5 containing / v% sodium chondroitin sulfate and neostigmine methyl sulfate, it was confirmed that no precipitate was generated.

[Formulation example]
Tables 6 and 7 below show formulation examples. The units of each component in Tables 6 and 7 are all w / v% except those specified in the tables. Formulation Examples 1 to 13 are all eye drops. Preparation examples 1 ′ to 13 ′ are prepared by filling 10 mL of each preparation example into a polyethylene terephthalate container and mounting a polyethylene nozzle. Each formulation example is filled with 10 mL of a polyethylene terephthalate container and equipped with a polybutylene terephthalate nozzle. The eye drops of Formulation Examples 1 to 13 can be used as eye drops that can be instilled when wearing hard contact lenses, eye drops that can be instilled when wearing soft contact lenses, or eye drops that can be instilled when not wearing contact lenses. .

Claims (6)

  Aqueous ophthalmology containing (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 An aqueous ophthalmic composition, wherein the content of the component (B) is 0.7 w / v% or more based on the total amount of the aqueous ophthalmic composition.   The aqueous ophthalmic composition according to claim 1, wherein the content of the component (A) is 0.001 w / v% to 5 w / v% based on the total amount of the aqueous ophthalmic composition.   The aqueous ophthalmic composition according to claim 1 or 2, wherein the content of the component (B) is 1 w / v% to 5 w / v% based on the total amount of the aqueous ophthalmic composition.   (C) The aqueous ophthalmic composition as described in any one of Claims 1-3 which further contains methylsulfate neostigmine.   (D) The aqueous ophthalmic composition according to any one of claims 1 to 4, further comprising a terpenoid. In the aqueous ophthalmic composition, (A) at least one selected from the group consisting of allantoin and epsilon-aminocaproic acid and a salt thereof, and (B) 0.7 w / v% based on the total amount of the aqueous ophthalmic composition The method to suppress generation | occurrence | production of the precipitate in this aqueous ophthalmic composition including mix | blending at least 1 sort (s) selected from the group which consists of the above chondroitin sulfate and its salt.