Ophthalmologic composition

Abstract

To provide a novel ophthalmologic composition that can reduce the elastic modulus of a soft contact lens.SOLUTION: An ophthalmologic composition contains (A) at least one selected from the group consisting of retinol and derivatives thereof, tocopherol and derivatives thereof, azulene sulfonate and salts thereof, chlorpheniramine and salts thereof, and terpenoids and (B) polyoxyethylene polyoxypropylene glycol, while being free of dibutylhydroxytoluene and butylhydroxyanisol.SELECTED DRAWING: None

Description

[Technical field]

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

[0002] Soft contact lenses contain a lot of water, and are softer and more comfortable to wear than hard contact lenses, and therefore are widely used. Here, as a preparation for use with soft contact lenses, for example, an ophthalmic composition containing a zinc compound and citric acid or a salt thereof has been reported (for example, Patent Document 1). [Prior art documents] [Patent documents]

[0003] [Patent Document 1] JP 2021-155414 A Summary of the Invention [Problem to be solved by the invention]

[0004] However, when a soft contact lens comes into contact with an ophthalmic composition, the shape and physical properties of the soft contact lens may change depending on the composition of the ophthalmic composition, and the use of an ophthalmic composition that increases the elastic modulus of a soft contact lens causes problems such as discomfort when wearing and / or mounting the soft contact lens due to a rough feeling, stiff feeling, poor wearing comfort, etc. Therefore, it is desired to create an ophthalmic composition that can reduce the elastic modulus of a soft contact lens.

[0005] The present invention has been made in view of the above circumstances, and an object of the present invention is to provide a new ophthalmic composition capable of reducing the elastic modulus of a soft contact lens. [Means for solving the problem]

[0006] The present inventors have unexpectedly found that an ophthalmic composition containing at least one selected from the group consisting of retinol and derivatives thereof, tocopherol and derivatives thereof, azulene sulfonic acid and salts thereof, chlorpheniramine and salts thereof, and terpenoids, and polyoxyethylene polyoxypropylene glycol, but not containing dibutylhydroxytoluene or butylhydroxyanisole, can reduce the elastic modulus of a soft contact lens.

[0007] The present invention provides, for example, the following inventions. [1] An ophthalmic composition comprising: (A) at least one selected from the group consisting of retinol and derivatives thereof, tocopherol and derivatives thereof, azulene sulfonic acid and salts thereof, chlorpheniramine and salts thereof, and terpenoids; and (B) polyoxyethylene polyoxypropylene glycol, and not containing dibutylhydroxytoluene or butylhydroxyanisole. [2] The ophthalmic composition according to [1], wherein component (B) contains polyoxyethylene polyoxypropylene glycol having a ratio (EO / PO) of the average degree of polymerization of ethylene oxide (EO) to the average degree of polymerization of propylene oxide (PO) of 1.0 to 5.0. [3] The ophthalmic composition according to [1] or [2], wherein the content of component (B) is 0.01 to 0.9 w / v % based on the total amount of the ophthalmic composition. [4] The ophthalmic composition according to any one of [1] to [3], further comprising (C) polyoxyethylene hydrogenated castor oil and / or polyoxyethylene castor oil. [5] The ophthalmic composition according to any one of [1] to [4], further comprising (D) polyvinylpyrrolidone. [6] The ophthalmic composition according to any one of [1] to [5], which has a pH of 5 to 9. [7] The ophthalmic composition according to any one of [1] to [6], which is for use in soft contact lenses. [8] The ophthalmic composition according to any one of [1] to [7], which does not further contain benzalkonium and / or a salt thereof. [9] The ophthalmic composition according to any one of [1] to [8], which does not further contain sorbic acid and / or a salt thereof.

[10] The ophthalmic composition according to any one of [1] to [9], which does not further contain at least one selected from the group consisting of chlorhexidine, alexidine, polyhexamethylene biguanide, polyaminopropyl biguanide, and salts thereof.

[11] An agent for reducing the elastic modulus of a soft contact lens, comprising (A) at least one member selected from the group consisting of retinol and derivatives thereof, tocopherol and derivatives thereof, azulene sulfonic acid and salts thereof, chlorpheniramine and salts thereof, and terpenoids, and (B) polyoxyethylene polyoxypropylene glycol, and not containing dibutylhydroxytoluene or butylhydroxyanisole.

[12] An agent for reducing discomfort when wearing and / or inserting soft contact lenses, comprising (A) at least one selected from the group consisting of retinol and derivatives thereof, tocopherol and derivatives thereof, azulene sulfonic acid and salts thereof, chlorpheniramine and salts thereof, and terpenoids, and (B) polyoxyethylene polyoxypropylene glycol, and not containing dibutylhydroxytoluene or butylhydroxyanisole.

[13] An agent for facilitating the wearing of soft contact lenses on the eye, comprising (A) at least one member selected from the group consisting of retinol and derivatives thereof, tocopherol and derivatives thereof, azulene sulfonic acid and salts thereof, chlorpheniramine and salts thereof, and terpenoids, and (B) polyoxyethylene polyoxypropylene glycol, and not containing dibutylhydroxytoluene or butylhydroxyanisole.

[14] An agent for reducing eye fatigue when wearing and / or inserting soft contact lenses, comprising (A) at least one selected from the group consisting of retinol and derivatives thereof, tocopherol and derivatives thereof, azulene sulfonic acid and salts thereof, chlorpheniramine and salts thereof, and terpenoids, and (B) polyoxyethylene polyoxypropylene glycol, and not containing dibutylhydroxytoluene or butylhydroxyanisole. Effect of the Invention

[0008] According to the present invention, it is possible to provide an ophthalmic composition capable of reducing the elastic modulus of a soft contact lens while containing at least one selected from the group consisting of retinol and its derivatives, tocopherol and its derivatives, azulene sulfonic acid and its salts, chlorpheniramine and its salts, and terpenoids. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0009] Hereinafter, the embodiment for carrying out the present invention will be described in detail. However, the present invention is not limited to the following embodiment. In this specification, unless otherwise specified, the unit of content "%" means "w / v%" and is synonymous with "g / 100 mL".

[0010] The ophthalmic composition according to this embodiment contains (A) at least one selected from the group consisting of retinol and derivatives thereof, tocopherol and derivatives thereof, azulene sulfonic acid and salts thereof, chlorpheniramine and salts thereof, and terpenoids (also referred to simply as "component (A)") and (B) polyoxyethylene polyoxypropylene glycol (also referred to simply as "component (B)"), and does not contain dibutylhydroxytoluene (also referred to as "BHT", also known as 2,6-di-tert-butyl-p-cresol) and butylhydroxyanisole (also referred to as "BHA", also known as 3-tert-butyl-4-hydroxyanisole).

[0011] [Component (A)] The component (A) may be used alone or in combination of two or more types.

[0012] The content of component (A) in the ophthalmic composition according to this embodiment is not particularly limited, and is appropriately set depending on the type of component (A), the types and contents of other blended components, the formulation form of the ophthalmic composition, etc. From the viewpoint of more significantly exhibiting the effects of the present invention, the content of component (A) is, for example, preferably 0.00001 to 1 w / v%, more preferably 0.00005 to 0.5 w / v%, even more preferably 0.00008 to 0.3 w / v%, particularly preferably 0.0001 to 0.2 w / v%, and particularly more preferably 0.0005 to 0.15 w / v%, based on the total amount of the ophthalmic composition.

[0013] [Component (A): Retinol and its derivatives] Retinol and its derivatives are not particularly limited as long as they are medicamentally, pharmacologically (pharmaceutical) or physiologically acceptable. Examples of retinol derivatives include retinol palmitate (also known as retinol palmitate), retinol acetate, retinal, and retinoic acid.

[0014] As retinol and its derivatives, retinol palmitate is preferred from the viewpoint of further enhancing the effects of the present invention.

[0015] Retinol or its derivatives may be commercially available. Retinol and its derivatives may be used alone or in combination of two or more.

[0016] The content of retinol and its derivatives in the ophthalmic composition according to the present embodiment is not particularly limited, and is appropriately set depending on the type of retinol and its derivatives, the type and content of other blended components, the formulation form of the ophthalmic composition, etc. From the viewpoint of more significantly exhibiting the effects of the present invention, for example, the content of retinol and its derivatives is preferably 0.0005 to 0.06 w / v%, more preferably 0.001 to 0.055 w / v%, even more preferably 0.002 to 0.05 w / v%, even more preferably 0.003 to 0.045 w / v%, particularly preferably 0.004 to 0.04 w / v%, and particularly more preferably 0.005 to 0.03 w / v%, based on the total amount of the ophthalmic composition. In addition, the content of retinol and its derivatives is preferably 1000 to 100000 IU / 100 ml, more preferably 3000 to 80000 IU / 100 ml, more preferably 5000 to 70000 IU / 100 ml, particularly preferably 8000 to 60000 IU / 100 ml, and particularly preferably 10000 to 55000 IU / 100 ml, based on the total amount of the ophthalmic composition, from the viewpoint of more clearly demonstrating the effects of the present invention. Note that "IU" refers to an international unit determined by a method described in the Vitamin A Quantitative Method of the Japanese Pharmacopoeia, 17th Edition. For example, the pharmaceutical articles of the Japanese Pharmacopoeia, 17th Edition, state that retinol acetate contains 2.5 million units of vitamin A or more per gram, and retinol palmitate contains 1.5 million units of vitamin A or more per gram.

[0017] [Component (A): Tocopherol and its derivatives] Tocopherol and its derivatives are not particularly limited as long as they are medicamentally, pharmacologically (pharmaceutical) or physiologically acceptable. Examples of tocopherol derivatives include tocopherol acetate (also known as tocopherol acetate), tocopherol succinate, tocopherol nicotinate, etc.

[0018] As tocopherol and its derivatives, tocopherol acetate is preferred from the viewpoint of further enhancing the effects of the present invention.

[0019] The tocopherol and its derivatives may be commercially available. The tocopherol and its derivatives may be used alone or in combination of two or more.

[0020] The content of tocopherol and its derivatives in the ophthalmic composition according to the present embodiment is not particularly limited, and is appropriately set depending on the type of tocopherol and its derivatives, the type and content of other blended components, the formulation form of the ophthalmic composition, etc. From the viewpoint of more significantly exhibiting the effects of the present invention, the content of tocopherol and its derivatives is, for example, preferably 0.001 to 0.5 w / v%, more preferably 0.003 to 0.3 w / v%, further preferably 0.005 to 0.1 w / v%, particularly preferably 0.008 to 0.08 w / v%, and particularly more preferably 0.01 to 0.05 w / v%, based on the total amount of the ophthalmic composition.

[0021] [Component (A): Azulene sulfonic acid and its salts] There is no particular limitation on the azulene sulfonic acid and its salts, so long as they are medicamentally, pharmacologically (pharmaceutical) or physiologically acceptable. Examples of the salts of azulene sulfonic acid include alkali metal salts such as sodium salts and potassium salts.

[0022] As the azulene sulfonic acid and its salts, from the viewpoint of further enhancing the effects of the present invention, an alkali metal salt of azulene sulfonic acid is preferred, and sodium azulene sulfonate is more preferred.

[0023] The azulene sulfonic acid and its salt may be commercially available. The azulene sulfonic acid and its salt may be used alone or in combination of two or more.

[0024] The content of azulene sulfonic acid and its salt in the ophthalmic composition according to this embodiment is not particularly limited, and is appropriately set according to the type of azulene sulfonic acid and its salt, the type and content of other blended components, the formulation form of the ophthalmic composition, etc. As for the content of azulene sulfonic acid and its salt, from the viewpoint of more significantly exhibiting the effects of the present invention, for example, based on the total amount of the ophthalmic composition, the total content of azulene sulfonic acid and its salt is preferably 0.001 to 0.05 w / v%, more preferably 0.002 to 0.04 w / v%, further preferably 0.003 to 0.03 w / v%, particularly preferably 0.0035 to 0.025 w / v%, and particularly preferably 0.004 to 0.02 w / v%.

[0025] [Component (A): Chlorpheniramine and its salts] Chlorpheniramine and its salts are not particularly limited as long as they are medicamentally, pharmacologically (pharmaceutical) or physiologically acceptable. Examples of chlorpheniramine salts include chlorpheniramine maleate.

[0026] As chlorpheniramine and its salts, chlorpheniramine maleate is preferred from the viewpoint of further enhancing the effects of the present invention.

[0027] Chlorpheniramine and its salts may be commercially available. Chlorpheniramine and its salts may be used alone or in combination of two or more.

[0028] The content of chlorpheniramine and its salt in the ophthalmic composition according to the present embodiment is not particularly limited, and is appropriately set depending on the type of chlorpheniramine and its salt, the type and content of other blended components, the formulation form of the ophthalmic composition, etc. From the viewpoint of more significantly exhibiting the effects of the present invention, for example, the content of chlorpheniramine and its salt is preferably 0.001 to 0.05 w / v%, more preferably 0.003 to 0.045 w / v%, further preferably 0.004 to 0.04 w / v%, particularly preferably 0.005 to 0.035 w / v%, and particularly more preferably 0.006 to 0.03 w / v%, based on the total amount of the ophthalmic composition.

[0029] [Component (A): Terpenoid] Terpenoids are not particularly limited as long as they are medicamentally, pharmacologically (pharmaceutical) or physiologically acceptable. Examples of terpenoids include menthol, menthone, camphor (also called "camphor" or "camphor"), borneol (also called "ryunou" or "borneol"), geraniol, nerol, cineol, citronellol, carvone, anethole, eugenol, limonene, linalool and linalyl acetate. Terpenoids may be in the d-, l- or dl-form, and examples include l-menthol, d-menthol, dl-menthol, dl-camphor, d-camphor, dl-borneol and d-borneol. However, some terpenoids, such as geraniol, nerol and cineol, may not have optical isomers.

[0030] Terpenoids may also be used as essential oils containing terpenoids, such as eucalyptus oil, bergamot oil, peppermint oil, fennel oil, rose oil, cinnamon oil, spearmint oil, camphor oil, cool mint, and peppermint oil.

[0031] As the terpenoid, from the viewpoint of further enhancing the effects of the present invention, menthol, peppermint oil, cool mint, and peppermint oil are preferred, menthol is more preferred, and l-menthol is even more preferred.

[0032] The terpenoids used may be commercially available ones. The terpenoids may be used alone or in combination of two or more kinds.

[0033] The content of the terpenoid in the ophthalmic composition according to the present embodiment is not particularly limited, and is appropriately set depending on the type of terpenoid, the types and contents of other blended components, the formulation form of the ophthalmic composition, etc. From the viewpoint of more significantly exhibiting the effects of the present invention, the content of the terpenoid is, for example, preferably 0.0001 to 0.5 w / v%, more preferably 0.0005 to 0.4 w / v%, further preferably 0.0008 to 0.3 w / v%, particularly preferably 0.001 to 0.2 w / v%, and particularly more preferably 0.005 to 0.1 w / v%, based on the total amount of the ophthalmic composition.

[0034] [Component (B): Polyoxyethylene polyoxypropylene glycol] There are no particular limitations on the polyoxyethylene polyoxypropylene glycol, so long as it is medicamentally, pharmacologically (pharmaceutical) or physiologically acceptable.

[0035] Examples of polyoxyethylene polyoxypropylene glycols include POE(196)POP(67) glycol (Poloxamer 407, Pluronic F-127), POE(200)POP(70) glycol, POE(120)POP(40) glycol (Pluronic F-87), POE(160)POP(30) glycol (Pluronic F-68, Poloxamer 188), polyoxyethylene(54)polyoxypropylene(39) glycol (Pluronic P-85, Poloxamer 235), polyoxyethylene(20)polyoxypropylene(20) glycol (Pluronic L-44, Poloxamer 124), polyoxyethylene(42)polyoxypropylene(67) glycol (Pluronic P123, Poloxamer 403), and the like.

[0036] From the viewpoint of further enhancing the effects of the present invention, the polyoxyethylene polyoxypropylene glycol is preferably one in which the ratio (EO / PO) of the average degree of polymerization of ethylene oxide (EO) to the average degree of polymerization of propylene oxide (PO) is 1.0 to 5.0, more preferably 1.5 to 4.5, even more preferably 2.0 to 4.0, particularly preferably 2.5 to 3.5, and particularly more preferably 2.8 to 3.0.

[0037] As the polyoxyethylene polyoxypropylene glycol, from the viewpoint of further enhancing the effects of the present invention, POE(196)POP(67) glycol (poloxamer 407, Pluronic F-127), POE(200)POP(70) glycol, POE(120)POP(40) glycol (Pluronic F-87), polyoxyethylene(54)polyoxypropylene(39) glycol (Pluronic P-85, Poloxamer 235), polyoxyethylene(20)polyoxypropylene(20) glycol (Pluronic L-44, Poloxamer 124) are preferred, and POE(196)POP(67) glycol (Poloxamer 407, Pluronic F-127) is more preferred.

[0038] The polyoxyethylene polyoxypropylene glycol may be a commercially available product. The polyoxyethylene polyoxypropylene glycol may be used alone or in combination of two or more kinds.

[0039] The content of polyoxyethylene polyoxypropylene glycol in the ophthalmic composition of this embodiment is not particularly limited, and is set appropriately depending on the type of polyoxyethylene polyoxypropylene glycol, the types and contents of other blended components, the formulation form of the ophthalmic composition, etc.

[0040] From the viewpoint of more prominently exhibiting the effects of the present invention, the content of polyoxyethylene polyoxypropylene glycol in the ophthalmic composition according to this embodiment is, for example, based on the total amount of the ophthalmic composition, preferably a total content of polyoxyethylene polyoxypropylene glycol of 0.001 to 3 w / v%, more preferably 0.005 to 2 w / v%, even more preferably 0.008 to 1 w / v%, particularly preferably 0.01 to 0.9 w / v%, and particularly more preferably 0.01 to 0.5 w / v%.

[0041] When component (A) is retinol or a derivative thereof, the content ratio of polyoxyethylene polyoxypropylene glycol relative to component (A) in the ophthalmic composition according to this embodiment is not particularly limited, but from the viewpoint of more significantly exhibiting the effects of the present invention, for example, the total content of polyoxyethylene polyoxypropylene glycol is preferably 0.0001 to 30 g, more preferably 0.0006 to 6.7 g, even more preferably 0.0011 to 2 g, particularly preferably 0.0016 to 1.125 g, and particularly more preferably 0.0018 to 0.5 g, per 10,000 IU of total content of component (A) contained in the ophthalmic composition.

[0042] When component (A) is tocopherol and its derivatives, the content ratio of polyoxyethylene polyoxypropylene glycol relative to component (A) in the ophthalmic composition of this embodiment is not particularly limited, but from the viewpoint of more significantly achieving the effects of the present invention, for example, the total content of polyoxyethylene polyoxypropylene glycol per 1 part by mass of the total content of component (A) contained in the ophthalmic composition is preferably 0.002 to 3,000 parts by mass, more preferably 0.016 to 667 parts by mass, even more preferably 0.08 to 200 parts by mass, particularly preferably 0.12 to 113 parts by mass, and particularly more preferably 0.2 to 50 parts by mass.

[0043] When component (A) is azulene sulfonic acid and a salt thereof, the content ratio of polyoxyethylene polyoxypropylene glycol relative to component (A) in the ophthalmic composition of this embodiment is not particularly limited, but from the viewpoint of more significantly achieving the effects of the present invention, for example, the total content of polyoxyethylene polyoxypropylene glycol per 1 part by mass of the total content of component (A) contained in the ophthalmic composition is preferably 0.02 to 3000 parts by mass, more preferably 0.12 to 1000 parts by mass, even more preferably 0.26 to 334 parts by mass, particularly preferably 0.4 to 258 parts by mass, and particularly more preferably 0.5 to 125 parts by mass.

[0044] When component (A) is chlorpheniramine and a salt thereof, the content ratio of polyoxyethylene polyoxypropylene glycol relative to component (A) in the ophthalmic composition of this embodiment is not particularly limited, but from the viewpoint of more significantly achieving the effects of the present invention, for example, the total content of polyoxyethylene polyoxypropylene glycol per 1 part by mass of the total content of component (A) contained in the ophthalmic composition is preferably 0.02 to 3,000 parts by mass, more preferably 0.1 to 667 parts by mass, even more preferably 0.2 to 250 parts by mass, particularly preferably 0.28 to 180 parts by mass, and particularly more preferably 0.3 to 84 parts by mass.

[0045] When the component (A) is a terpenoid, the content ratio of polyoxyethylene polyoxypropylene glycol relative to the component (A) in the ophthalmic composition of this embodiment is not particularly limited, but from the viewpoint of more significantly achieving the effects of the present invention, for example, the total content of polyoxyethylene polyoxypropylene glycol relative to 1 part by mass of the total content of the component (A) contained in the ophthalmic composition is preferably 0.002 to 30,000 parts by mass, more preferably 0.012 to 4,000 parts by mass, even more preferably 0.026 to 1,250 parts by mass, particularly preferably 0.05 to 900 parts by mass, and particularly more preferably 0.1 to 100 parts by mass.

[0046] [Component (C): Polyoxyethylene hydrogenated castor oil and / or polyoxyethylene castor oil] The ophthalmic composition according to the present embodiment preferably further contains (C) polyoxyethylene hydrogenated castor oil and / or polyoxyethylene castor oil (also simply referred to as "component (C)"). When the ophthalmic composition contains component (C), the effects of the present invention are more significantly exhibited.

[0047] There are no particular limitations on the polyoxyethylene polyoxypropylene glycol, so long as it is medicamentally, pharmacologically (pharmaceutical) or physiologically acceptable. Examples of polyoxyethylene hydrogenated castor oil include polyoxyethylene (5) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 5), polyoxyethylene (10) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 10), polyoxyethylene (20) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 20), polyoxyethylene (30) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 30), polyoxyethylene (40) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 40), polyoxyethylene (60) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 60), polyoxyethylene (80) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 80), and polyoxyethylene (100) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 100). Examples of polyoxyethylene castor oils include polyoxyethylene (3) castor oil (polyoxyethylene castor oil 3), polyoxyethylene (10) castor oil (polyoxyethylene castor oil 10), polyoxyethylene (35) castor oil (polyoxyethylene castor oil 35), and polyoxyethylene (70) castor oil (polyoxyethylene castor oil 70).

[0048] As the polyoxyethylene hydrogenated castor oil, from the viewpoint of further enhancing the effects of the present invention, polyoxyethylene hydrogenated castor oil 60 is preferred. As the polyoxyethylene castor oil, from the viewpoint of further enhancing the effects of the present invention, polyoxyethylene castor oil 10 is preferred.

[0049] The component (C) may be a commercially available product. The component (C) may be used alone or in combination of two or more. From the viewpoint of further enhancing the effects of the present invention, it is preferable to use polyoxyethylene hydrogenated castor oil and polyoxyethylene castor oil in combination, and it is more preferable to use polyoxyethylene hydrogenated castor oil 60 and polyoxyethylene castor oil 10 in combination.

[0050] The content of component (C) in the ophthalmic composition according to this embodiment is not particularly limited, and is appropriately set depending on the type of component (C), the types and contents of other blended components, the formulation form of the 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 0.0001 to 10 w / v%, more preferably 0.0008 to 8 w / v%, even more preferably 0.001 to 5 w / v%, particularly preferably 0.005 to 3 w / v%, and particularly more preferably 0.01 to 1 w / v%, based on the total amount of the ophthalmic composition.

[0051] When the component (A) is retinol or a derivative thereof, the content ratio of the component (C) to the component (A) in the ophthalmic composition of this embodiment is not particularly limited; however, from the viewpoint of more significantly exhibiting the effects of the present invention, for example, the total content of the component (C) per 10,000 IU of the component (A) contained in the ophthalmic composition is preferably 0.001 to 5 g, more preferably 0.005 to 3 g, even more preferably 0.008 to 2 g, particularly preferably 0.01 to 1 g, and particularly more preferably 0.03 to 0.5 g.

[0052] When component (A) is tocopherol and its derivatives, the content ratio of component (C) relative to component (A) in the ophthalmic composition of this embodiment is not particularly limited; however, from the viewpoint of more significantly achieving the effects of the present invention, for example, the total content of component (C) per 1 part by mass of the total content of component (A) contained in the ophthalmic composition is preferably 0.001 to 50 parts by mass, more preferably 0.005 to 30 parts by mass, even more preferably 0.01 to 20 parts by mass, particularly preferably 0.05 to 10 parts by mass, and particularly more preferably 0.1 to 5 parts by mass.

[0053] When the (A) component is azulene sulfonic acid and its salts, the content ratio of the (C) component to the (A) component in the ophthalmic composition of this embodiment is not particularly limited; however, from the viewpoint of more prominently exhibiting the effects of the present invention, for example, the total content of the (C) component per 1 part by mass of the total content of the (A) component contained in the ophthalmic composition is preferably 0.001 to 50 parts by mass, more preferably 0.005 to 40 parts by mass, even more preferably 0.01 to 30 parts by mass, particularly preferably 0.05 to 20 parts by mass, and particularly more preferably 0.1 to 15 parts by mass.

[0054] When component (A) is chlorpheniramine and its salts, the content ratio of component (C) relative to component (A) in the ophthalmic composition of this embodiment is not particularly limited; however, from the viewpoint of more significantly achieving the effects of the present invention, for example, the total content of component (C) per 1 part by mass of the total content of component (A) contained in the ophthalmic composition is preferably 0.001 to 50 parts by mass, more preferably 0.005 to 40 parts by mass, even more preferably 0.01 to 30 parts by mass, particularly preferably 0.05 to 20 parts by mass, and particularly more preferably 0.1 to 10 parts by mass.

[0055] When the (A) component is a terpenoid, the content ratio of the (C) component to the (A) component in the ophthalmic composition of this embodiment is not particularly limited; however, from the viewpoint of more significantly achieving the effects of the present invention, for example, the total content of the (C) component per 1 part by mass of the total content of the (A) component contained in the ophthalmic composition is preferably 0.001 to 50 parts by mass, more preferably 0.008 to 40 parts by mass, even more preferably 0.01 to 35 parts by mass, particularly preferably 0.05 to 30 parts by mass, and particularly more preferably 0.1 to 25 parts by mass.

[0056] [Component (D): Polyvinylpyrrolidone] The ophthalmic composition according to this embodiment preferably further contains (D) polyvinylpyrrolidone (also simply referred to as "component (D)"). When the ophthalmic composition contains component (D), the effects of the present invention are more pronounced. There are no particular limitations on the polyvinylpyrrolidone, so long as it is medicamentally, pharmacologically (pharmaceutical), or physiologically acceptable.

[0057] The K value of polyvinylpyrrolidone is not particularly limited, but from the viewpoint of achieving the effects of the present invention remarkably, it is preferably 10 to 200, more preferably 30 to 150, and even more preferably 60 to 120. Among them, polyvinylpyrrolidone K25, polyvinylpyrrolidone K30, polyvinylpyrrolidone K60, and polyvinylpyrrolidone K90 are preferable, polyvinylpyrrolidone K25, polyvinylpyrrolidone K30, and polyvinylpyrrolidone K90 are more preferable, and polyvinylpyrrolidone K90 is even more preferable. The K value (viscosity characteristic value) of polyvinylpyrrolidone is calculated according to the method described in the 17th revised Japanese Pharmacopoeia "Povidone". Since the K value is 90 to 108% of the indicated K value, for example, "K90" refers to a K value (viscosity characteristic value) in the range of 81.0 to 97.2.

[0058] The content of polyvinylpyrrolidone in the ophthalmic composition according to the present embodiment is not particularly limited, and is appropriately set depending on the type of polyvinylpyrrolidone, the types and contents of other blended components, the formulation form of the ophthalmic composition, etc. From the viewpoint of more significantly exhibiting the effects of the present invention, the content of polyvinylpyrrolidone is, for example, preferably 0.0001 to 10 w / v%, more preferably 0.005 to 8 w / v%, further preferably 0.001 to 5 w / v%, particularly preferably 0.005 to 4 w / v%, and particularly more preferably 0.01 to 3 w / v%, based on the total amount of the ophthalmic composition.

[0059] When the component (A) is retinol or a derivative thereof, the content ratio of the component (D) to the component (A) in the ophthalmic composition of this embodiment is not particularly limited; however, from the viewpoint of more significantly achieving the effects of the present invention, for example, the total content of the component (D) per 10,000 IU of the component (A) contained in the ophthalmic composition is preferably 0.0001 to 10 g, more preferably 0.005 to 8 g, even more preferably 0.001 to 5 g, particularly preferably 0.003 to 4 g, and particularly more preferably 0.005 to 3 g.

[0060] When the component (A) is tocopherol and its derivatives, the content ratio of the component (D) relative to the component (A) in the ophthalmic composition of this embodiment is not particularly limited; however, from the viewpoint of more significantly achieving the effects of the present invention, for example, the total content of the component (D) per 1 part by mass of the total content of the component (A) contained in the ophthalmic composition is preferably 0.002 to 200 parts by mass, more preferably 0.001 to 100 parts by mass, even more preferably 0.05 to 80 parts by mass, particularly preferably 0.1 to 70 parts by mass, and particularly more preferably 0.2 to 60 parts by mass.

[0061] When the (A) component is azulene sulfonic acid and its salts, the content ratio of the (D) component to the (A) component in the ophthalmic composition of this embodiment is not particularly limited; however, from the viewpoint of more significantly achieving the effects of the present invention, for example, the total content of the (D) component per 1 part by mass of the total content of the (A) component contained in the ophthalmic composition is preferably 0.002 to 200 parts by mass, more preferably 0.001 to 100 parts by mass, even more preferably 0.05 to 80 parts by mass, particularly preferably 0.1 to 70 parts by mass, and particularly more preferably 0.2 to 60 parts by mass.

[0062] When the component (A) is chlorpheniramine and its salts, the content ratio of the component (D) relative to the component (A) in the ophthalmic composition of this embodiment is not particularly limited; however, from the viewpoint of more significantly achieving the effects of the present invention, for example, the total content of the component (D) per 1 part by mass of the total content of the component (A) contained in the ophthalmic composition is preferably 0.003 to 350 parts by mass, more preferably 0.005 to 300 parts by mass, even more preferably 0.01 to 200 parts by mass, particularly preferably 0.05 to 150 parts by mass, and particularly more preferably 0.1 to 100 parts by mass.

[0063] When the (A) component is a terpenoid, the content ratio of the (D) component to the (A) component in the ophthalmic composition of this embodiment is not particularly limited; however, from the viewpoint of more significantly achieving the effects of the present invention, for example, the total content of the (D) component per 1 part by mass of the total content of the (A) component contained in the ophthalmic composition is preferably 0.1 to 10,000 parts by mass, more preferably 0.3 to 8,000 parts by mass, even more preferably 0.5 to 6,000 parts by mass, particularly preferably 0.8 to 7,000 parts by mass, and particularly more preferably 1 to 3,000 parts by mass.

[0064] [Inorganic salts] The ophthalmic composition according to the present embodiment preferably further contains an inorganic salt. When the ophthalmic composition further contains an inorganic salt, the effect of the present invention is more pronounced. The inorganic salt is not particularly limited as long as it is medicamentarily, pharmacologically (pharmaceutical) or physiologically acceptable.

[0065] Examples of inorganic salts include 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; sodium hydrogen sulfite; and sodium sulfite.

[0066] As the inorganic salt, from the viewpoint of further enhancing the effect of the present invention, a metal chloride is preferable, and sodium chloride is more preferable.

[0067] The inorganic salts may be commercially available. The inorganic salts may be used alone or in combination of two or more.

[0068] The content of inorganic salts in the ophthalmic composition according to the present embodiment is not particularly limited, and is appropriately set depending on the type of inorganic salts, the types and contents of other blended components, the formulation form of the ophthalmic composition, etc. From the viewpoint of more significantly exhibiting the effects of the present invention, the content of inorganic salts is, for example, preferably 0.0001 to 10 w / v%, more preferably 0.001 to 5 w / v%, and even more preferably 0.01 to 1 w / v%, based on the total amount of the ophthalmic composition.

[0069] [Buffer] The ophthalmic composition according to the present embodiment preferably further contains a buffering agent. When the ophthalmic composition further contains a buffering agent, the effect of the present invention is more pronounced. The buffering agent is not particularly limited as long as it is medicamentarily, pharmacologically (pharmaceutical) or physiologically acceptable.

[0070] Examples of the buffer include inorganic buffers derived from inorganic acids, and organic buffers derived from organic acids or organic bases.

[0071] Examples of inorganic buffers include boric acid buffers, phosphate buffers, and carbonate buffers. Examples of boric acid 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.). In addition, hydrates of borates, phosphates, or carbonates may be used as boric acid buffers, phosphate buffers, or carbonate buffers. More specific examples include borate buffers such as boric acid or salts thereof (sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, borax, etc.); phosphate buffers such as 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 such as carbonic acid or salts thereof (sodium bicarbonate, sodium carbonate, ammonium carbonate, potassium carbonate, calcium carbonate, potassium bicarbonate, magnesium carbonate, etc.).

[0072] 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 its salts (alkali metal citrate, alkaline earth metal citrate, etc.). Examples of acetate buffers include acetic acid or its salts (alkali metal acetate, alkaline earth metal acetate, etc.). Examples of lactate buffers include lactic acid or its salts (alkali metal lactate, alkaline earth metal lactate, etc.). Examples of succinate buffers include succinic acid or its salts (alkali metal succinate, etc.). In addition, hydrates of citrate, acetate, lactate, or succinate may be used as citrate buffers, acetate buffers, lactate buffers, or succinate buffers. More specific examples of the citrate buffer include citric acid or its salts (sodium citrate, potassium citrate, calcium citrate, sodium dihydrogen citrate, disodium citrate, etc.); acetic acid buffer includes acetic acid or its salts (ammonium acetate, sodium acetate, potassium acetate, calcium acetate, etc.); lactic acid buffer includes lactic acid or its salts (sodium lactate, potassium lactate, calcium lactate, etc.); succinic acid buffer includes succinic acid or its salts (monosodium succinate, disodium succinate, etc.). Examples of the tris buffer include trometamol or its salts (trometamol hydrochloride, etc.). Examples of the AMPD buffer include 2-amino-2-methyl-1,3-propanediol or its salts.

[0073] As the buffer, from the viewpoint of further enhancing the effect of the present invention, an inorganic buffer is preferable, a borate buffer (for example, a combination of boric acid and borax, etc.) is more preferable, and a combination of boric acid and borax is even more preferable.

[0074] The buffering agent may be a commercially available one. The buffering agent may be used alone or in combination of two or more kinds.

[0075] The content of the buffering agent in the ophthalmic composition according to the present embodiment is not particularly limited, and is appropriately set depending on the type of the buffering agent, the types and contents of other blended components, the formulation form of the 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 further preferably 0.1 to 3 w / v%, based on the total amount of the ophthalmic composition.

[0076] The pH of the ophthalmic composition according to the present embodiment is not particularly limited as long as it is within a medicamentously, pharmacologically (pharmaceutical) or physiologically acceptable range. The pH of the ophthalmic composition according to the present embodiment is, for example, preferably 5 to 9, more preferably 5.5 to 8.5, and even more preferably 6 to 8.

[0077] The ophthalmic composition according to the present embodiment can be adjusted to an osmotic pressure ratio within a range acceptable to the living body, if necessary. The appropriate osmotic pressure ratio can be appropriately set depending on the formulation form, method of use, etc. of the ophthalmic composition, and can be, for example, 0.4 to 2.0, preferably 0.6 to 1.8, and more preferably 0.8 to 1.6. The osmotic pressure ratio is 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) based on the 17th revised Japanese Pharmacopoeia, and the osmotic pressure is measured with reference to the osmometric 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 measuring 0.900 g of it, 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.

[0078] The viscosity of the ophthalmic composition according to the present embodiment is not particularly limited as long as it is within a medicamentously, pharmacologically (pharmaceutical) or physiologically acceptable range. The viscosity of the ophthalmic composition according to the present embodiment is preferably 1 to 100 mPa·s, more preferably 1 to 20 mPa·s, and even more preferably 1 to 10 mPa·s, as measured at 20°C using a rotational viscometer (TV-20 type viscometer, manufactured by Toki Sangyo Co., Ltd., rotor: 1°34'×R24).

[0079] The ophthalmic composition according to the present embodiment may contain an appropriate amount of a combination of various pharmacologically active ingredients and physiologically active ingredients in addition to the above-mentioned ingredients, as long as the effects of the present invention are not impaired. The ingredients are not particularly limited, and examples thereof include active ingredients in ophthalmic drugs listed in the 2017 edition of the General Drug Manufacturing and Sales Approval Standards (supervised by the Japan Society of Regulatory Science). Specific examples of ingredients used in ophthalmic drugs include the following ingredients. Antiallergic agents: for example, cromoglycic acid or a salt thereof (for example, sodium cromoglycate), tranilast, pemirolast potassium, ashitazanolast, amlexanox, ibudilast, etc. Antihistamines other than chlorpheniramine and its salts: for example, diphenhydramine or a salt thereof (e.g., diphenhydramine hydrochloride), iproheptine or a salt thereof (e.g., iproheptine hydrochloride), levocabastine or a salt thereof (e.g., levocabastine hydrochloride), ketotifen or a salt thereof (e.g., ketotifen fumarate), pemirolast potassium, olopatadine or a salt thereof (e.g., olopatadine hydrochloride), epinastine or a salt thereof (e.g., epinastine hydrochloride), etc. Steroids: for example, fluticasone propionate, fluticasone furoate, mometasone furoate, beclomethasone propionate, flunisolide, etc. Decongestants: for example, tetrahydrozoline hydrochloride, naphazoline hydrochloride, epinephrine, epinephrine hydrochloride, ephedrine hydrochloride, phenylephrine hydrochloride, dl-methylephedrine hydrochloride, and the like. Ocular muscle regulating drugs: For example, cholinesterase inhibitors having an active center similar to that of acetylcholine, specifically, neostigmine methylsulfate, tropicamide, helenien, atropine sulfate, pilocarpine hydrochloride, etc. Anti-inflammatory agents other than azulene sulfonic acid and its salts: 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, glycyrrhizic acid or its salts (for example, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate), zinc sulfate, zinc lactate, etc. Retinol and its derivatives, and vitamins other than tocopherol and its derivatives: for example, flavin adenine dinucleotide sodium, pyridoxine hydrochloride, panthenol, calcium pantothenate, cyanocobalamin, ascorbic acid, sodium ascorbate, etc. Amino acids: for example, L-arginine, glutamic acid, glycine, alanine, lysine, γ-aminobutyric acid, γ-aminovaleric acid, trimethylglycine, taurine, aspartic acid, and salts thereof. Astringents: For example, zinc oxide. Others: For example, sulfamethoxazole, sulfisoxazole, sulfisomidine and their salts.

[0080] In the ophthalmic composition according to this embodiment, various additives may be appropriately selected according to the formulation form, and one or more types may be used in combination in an appropriate amount, as long as the effect of the present invention is not impaired. Examples of such additives include, for example, various additives listed in the Pharmaceutical Additives Encyclopedia 2021 (edited by the Japan Pharmaceutical Additives Association). Representative components include the following additives. Carrier: For example, an aqueous solvent such as water or aqueous ethanol. Chelating agents: for example, ethylenediaminetetraacetic acid (EDTA, edetic acid), ethylenediaminetriacetic acid, ethylenediaminediacetic acid (EDDA), 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, monoethanolamine, diisopropanolamine, etc. Polyoxyethylene polyoxypropylene glycol, and surfactants other than polyoxyethylene hydrogenated castor oil and polyoxyethylene castor oil: for example, nonionic surfactants such as tyloxapol, polyoxyethylene sorbitan fatty acid esters, polyoxyl stearic acid, etc.; anionic surfactants such as polyoxyethylene alkyl ether phosphates, polyoxyethylene alkyl ether sulfates, alkylbenzene sulfonates, alkyl sulfates, N-acyltaurine salts, etc.; zwitterionic surfactants such as lauryl dimethylaminoacetate betaine, etc. Thickeners: for example, cellulose-based polymer compounds such as methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, and sodium carboxymethylcellulose; guar gum; hydroxypropyl guar gum; gum arabic; karaya gum; xanthan gum; agar; alginic acid and its salts (sodium salt, etc.); mucopolysaccharides such as heparin-like substances, heparin, heparin sulfate, heparan sulfate, heparinoids, hyaluronic acid and its salts (sodium salt, etc.), and chondroitin sulfate and its salts (sodium salt, etc.); starch; chitin and its derivatives; chitosan and its derivatives; carrageenan; monosaccharides such as glucose, etc. Stabilizers other than dibutylhydroxytoluene and butylhydroxyanisole: for example, sodium formaldehyde sulfoxylate (Rongalit), aluminum monostearate, glycerin monostearate, cyclodextrin, monoethanolamine, sodium pyrosulfite, sodium sulfite, sodium hydrogensulfite, sodium thiosulfate, potassium iodide, etc. Preservatives: for example, alkyl polyaminoethyl glycines, benzethonium chloride, polydonium chloride, sodium benzoate, ethanol, chlorobutanol, sodium dehydroacetate, methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, butyl parahydroxybenzoate, oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, Glokil (trade name, manufactured by Rhodia), and the like. Sugar alcohols: for example, xylitol, sorbitol, mannitol, glycerin, etc. Glycols: for example, propylene glycol, ethylene glycol, etc. Oils: For example, vegetable oils such as sesame oil, castor oil, soybean oil, olive oil, etc.; animal oils such as squalane, etc.; mineral oils such as liquid paraffin, Vaseline, etc.

[0081] From the viewpoint of further enhancing the effect of the present invention, the ophthalmic composition according to the present embodiment preferably does not contain benzalkonium and / or a salt thereof. Examples of benzalkonium salts include benzalkonium chloride.

[0082] From the viewpoint of further enhancing the effects of the present invention, the ophthalmic composition according to the present embodiment preferably does not contain sorbic acid and / or a salt thereof. Examples of sorbic acid salts include potassium sorbate.

[0083] From the viewpoint of further enhancing the effects of the present invention, the ophthalmic composition according to the present embodiment preferably does not contain at least one selected from the group consisting of chlorhexidine and its salts (chlorhexidine hydrochloride, chlorhexidine acetate, chlorhexidine gluconate, etc.), alexidine and its salts (alexidine dihydrochloride, etc.), polyhexamethylene biguanide and its salts (polyhexamethylene biguanide hydrochloride, etc.), and polyaminopropyl biguanide and its salts (polyaminopropyl biguanide hydrochloride, etc.), and more preferably does not contain chlorhexidine and its salts (chlorhexidine hydrochloride, chlorhexidine acetate, chlorhexidine gluconate, etc.), alexidine and its salts (alexidine dihydrochloride, etc.), polyhexamethylene biguanide and its salts (polyhexamethylene biguanide hydrochloride, etc.), and polyaminopropyl biguanide and its salts (polyaminopropyl biguanide hydrochloride, etc.).

[0084] When the ophthalmic composition of this embodiment contains water, from the viewpoint of more significantly achieving the effects of the present invention, the water content 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 ophthalmic composition.

[0085] The water used in the ophthalmic composition according to the present 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, distilled water for injection, etc. The definitions of these are based on the 17th edition of the Japanese Pharmacopoeia.

[0086] The ophthalmic composition according to the present embodiment can be prepared by adding and mixing desired amounts of component (A), component (B), and other components as necessary to obtain desired concentrations. For example, the composition can be prepared by dissolving or dispersing those components in purified water, adjusting the pH and osmotic pressure ratio to a predetermined value, and sterilizing the composition by filtration sterilization or the like.

[0087] The ophthalmic composition according to the present embodiment may be in various formulation forms depending on the purpose, such as liquid, gel, semi-solid (ointment, etc.), etc.

[0088] The ophthalmic composition according to the present embodiment can be used, for example, as eye drops (also called eye drops or eye drops. Eye drops include artificial tears and eye drops that can be applied while wearing contact lenses), eyewash (also called eyewash or eyewash. Eyewash includes eyewash that can be applied while wearing contact lenses), and a composition for contact lenses [contact lens wetting solution, contact lens care composition (contact lens disinfectant, contact lens preservative, contact lens cleaner, contact lens cleaning preservative), contact lens wetting solution used for both contact lens wetting solution and eye drops while wearing contact lenses, etc.]. The term "contact lenses" includes hard contact lenses and soft contact lenses (including both ionic and non-ionic, and including both silicone hydrogel contact lenses and non-silicone hydrogel contact lenses). Suitable examples of the ophthalmic composition according to this embodiment include eye drops, eye washes, and contact lens compositions, more suitable examples include eye drops that can be applied while wearing contact lenses, eye washes that can be applied while wearing contact lenses, contact lens wetting solution, and contact lens wetting eye drops, and even more suitable examples include eye drops that can be applied while wearing contact lenses. Another suitable example of the ophthalmic composition according to this embodiment includes an ophthalmic composition for soft contact lenses (eye drops that can be applied while wearing soft contact lenses, eye washes that can be applied while wearing soft contact lenses, soft contact lens wetting solution, and soft contact lens wetting eye drops), and more suitable examples include eye drops that can be applied while wearing soft contact lenses.

[0089] Here, "ionic" soft contact lenses refer to those in which the molar percentage of monomers containing anions is 0.5% or more among the constituent monomers of the raw material polymer, in accordance with PSEHB / PED Notification No. 0330-6 by the Director of the Drug Evaluation and Licensing Division, Pharmaceutical and Food Safety Bureau, Ministry of Health, Labour and Welfare and PSEHB / MDEL Notification No. 0330-4 by the Director of the Medical Device Evaluation and Licensing Division, Pharmaceutical and Food Safety Bureau, Ministry of Health, Labour and Welfare "Regarding the handling of documents to be attached when applying for approval to manufacture (import) soft contact lenses and soft contact lens disinfectants" (March 30, 2021).

[0090] According to PSEHB / PED Notification No. 0330-6 from the Director of the Pharmaceutical Evaluation and Licensing Division, Pharmaceutical and Food Safety Bureau, Ministry of Health, Labour and Welfare and PSEHB / MDEL Notification No. 0330-4 from the Director of the Medical Device Evaluation and Licensing Division, Pharmaceutical and Food Safety Bureau, Ministry of Health, Labour and Welfare, "Regarding the handling of documents to be attached when applying for approval to manufacture (import) soft contact lenses and soft contact lens disinfectants" (March 30, 2021), soft contact lenses classified as Group 1 are non-ionic and have a water content of less than 50%, soft contact lenses classified as Group 2 are non-ionic and have a water content of 50% or more, soft contact lenses classified as Group 3 are ionic and have a water content of less than 50%, and soft contact lenses classified as Group 4 are ionic and have a water content of 50% or more.

[0091] The "water content" of a soft contact lens refers to the proportion of water in the soft contact lens, and is specifically calculated by the following formula. Water content (%) = (weight of water / weight of soft contact lens in hydrated state) x 100 The moisture content can be measured by gravimetric methods as described in ISO 18369-4:2017.

[0092] In order to more significantly exhibit the effects of the present invention, the ophthalmic composition according to this embodiment is preferably used for soft contact lenses, and more preferably for Group 2 silicone hydrogel contact lenses.

[0093] In addition, since the ophthalmic composition according to this embodiment can reduce the deterioration of the wearing comfort of soft contact lenses, the soft contact lenses are preferably of a two-week continuous wear type or a conventional type, and more preferably of a two-week continuous wear type.

[0094] The ophthalmic composition according to the present embodiment is preferably used as eye drops (including eye drops that can be applied while wearing contact lenses) because it can more significantly exhibit the effects of the present invention, more preferably as eye drops that can be applied while wearing soft contact lenses, and even more preferably as eye drops that can be applied while wearing silicone hydrogel contact lenses of group 2. When the ophthalmic composition according to the present embodiment is an eye drop, its dosage and administration are not particularly limited as long as it is effective and has few side effects, but for example, in the case of adults (15 years or older) and children aged 7 years or older, 1 to 3 drops, 1 to 2 drops, or 2 to 3 drops at a time, 2 to 4 times a day, or 5 to 6 times a day can be exemplified, and a method of applying 1 to 2 drops or 1 to 3 drops at a time, 4 times a day, or 5 to 6 times a day is preferred, with 1 to 3 drops at a time and 5 to 6 times a day being more preferred.

[0095] When the ophthalmic composition according to the present embodiment is an eye drop, it may be an artificial tear. Note that the artificial tear preferably does not contain any active ingredient such as an antiallergic agent, an antihistamine, a steroid, a congestion remover, an eye muscle regulating agent, an anti-inflammatory agent, or a vitamin.

[0096] The ophthalmic composition according to the present embodiment is provided in an arbitrary container. The container for containing the ophthalmic composition according to the present embodiment may be a multi-dose type container for containing an amount for multiple uses, or a unit-dose type container for containing an amount for single use.

[0097] The material of the container for containing the ophthalmic composition according to the present embodiment is not particularly limited, and may be made of glass or plastic, for example. It is preferably made of plastic. Examples of plastic include polyesters such as polyethylene terephthalate, polybutylene terephthalate, and polyethylene naphthalate; polyolefins such as low-density polyethylene, high-density polyethylene, low-density polypropylene, high-density polypropylene, ethylene-propylene copolymer, ethylene-vinyl acetate copolymer, polymethylpentene, cyclic olefin polymer, and cyclic olefin copolymer; polyarylate, polycarbonate, polyimide, and copolymers of monomers constituting these, and mixtures of two or more of these. When the container for containing the ophthalmic composition according to the present embodiment is a multi-dose type, the plastic is preferably polyethylene terephthalate. When the container for containing the ophthalmic composition according to the present embodiment is a unit-dose type, the plastic is preferably low-density polyethylene, high-density polyethylene, cyclic olefin polymer, cyclic olefin copolymer, and copolymers of monomers constituting these, and mixtures of two or more of these. In addition, when the plastic contains a cyclic olefin copolymer and polyethylene, the content ratio of the cyclic olefin copolymer to the polyethylene may be, for example, 50:50 to 95:5, 55:45 to 90:10, or 60:40 to 85:15. In addition, the container for storing the ophthalmic composition according to the present embodiment may be a transparent container that allows the inside of the container to be visually confirmed, or may be an opaque container that makes it difficult to visually confirm the inside of the container. A transparent container is preferable. Here, the "transparent container" includes both a colorless transparent container and a colored transparent container.

[0098] A nozzle may be attached to the container that contains the ophthalmic composition according to this embodiment. The material of the nozzle is not particularly limited, and may be made of glass or plastic, for example. It is preferably made of plastic. Examples of plastic include polyesters such as polyethylene terephthalate, polybutylene terephthalate, and polyethylene naphthalate; polyolefins such as low-density polyethylene, high-density polyethylene, low-density polypropylene, high-density polypropylene, cyclic olefin polymers, and cyclic olefin copolymers; polyarylate, polycarbonate, polyimide, and copolymers of monomers that constitute these, and mixtures of two or more of these. As the material of the nozzle, polyethylene terephthalate, polybutylene terephthalate, and polyethylene naphthalate are preferred, and polyethylene terephthalate is more preferred.

[0099] The shape and capacity of the container for containing the ophthalmic composition according to the present embodiment are not particularly limited, and may be appropriately set according to the application. For example, when the container for containing the ophthalmic composition according to the present embodiment is a multi-dose type container and contains an eye drop, an eyewash used by dropping, or a contact lens wearing solution, the capacity may be, for example, 1 mL or more and 50 mL or less, preferably 2 mL or more and 40 mL or less, and more preferably 4 mL or more and 25 mL or less. In addition, when the container for containing the ophthalmic composition according to the present embodiment is a unit dose type, the capacity may be, for example, 0.01 mL or more and 1 mL or less, preferably 0.05 mL or more and 0.8 mL or less, and more preferably 0.1 mL or more and 0.5 mL or less. Furthermore, if the container is a container for containing an eyewash or contact lens care solution using an eyewash cup, the capacity may be, for example, 40 mL or more and 600 mL or less.

[0100] The container containing the ophthalmic composition according to the present embodiment may be sealed in a housing. The housing is not particularly limited, and examples thereof include Ageless Omac (manufactured by Mitsubishi Gas Chemical Company, Inc.), Oxyguard (manufactured by Toyo Seikan Co., Ltd.), Oxydec (manufactured by Toyo Seikan Co., Ltd.), Oxycatch (manufactured by Kyodo Printing Co., Ltd.), Diamiron (manufactured by Mitsubishi Chemical Corporation), Hyster O2 (manufactured by Star Plastics Industry Co., Ltd.), and Cryovac (manufactured by Sealed Air Co., Ltd.).

[0101] When the container containing the ophthalmic composition according to the present embodiment is sealed in an enclosure, an oxygen absorber may be enclosed in the enclosure.The oxygen absorber is not particularly limited, and examples thereof include Ageless (manufactured by Mitsubishi Gas Chemical Co., Ltd.), StabilOx (manufactured by Multisorb Co., Ltd.), Wellpack (manufactured by Taisei Co., Ltd.), Everfresh (manufactured by Toriyoshi Sangyo Co., Ltd.), Oxyter (manufactured by Ueno Pharmaceutical Co., Ltd.), Keepit (manufactured by Dorancy Co., Ltd.), Kepron (manufactured by Kepron Co., Ltd.), Sansocut (manufactured by Iris Fine Products Co., Ltd.), Sansoles (manufactured by Hakuyo Co., Ltd.), Secur (manufactured by Nisso Resin Co., Ltd.), Tamotsu (manufactured by Oe Chemical Industry Co., Ltd.), Vitalon (manufactured by Tokiwa Sangyo Co., Ltd.), Modulan (manufactured by Nippon Kayaku Food Techno Co., Ltd.), Wonder Keep (manufactured by Powder Tech Co., Ltd.), and Freshness Preservation Agent C (manufactured by Toppan Printing Co., Ltd.) as is or appropriately packaged.

[0102] An ophthalmic composition containing the (A) component and the (B) component and not containing dibutylhydroxytoluene and butylhydroxyanisole has the effect of significantly reducing the elastic modulus of a soft contact lens. Therefore, as one embodiment of the present invention, an agent for reducing the elastic modulus of a soft contact lens is provided, which contains the (A) component and the (B) component and does not contain dibutylhydroxytoluene and butylhydroxyanisole. Also, as one embodiment of the present invention, a method for imparting an effect of reducing the elastic modulus of a soft contact lens to an ophthalmic composition is provided, which includes blending the (A) component and the (B) component into the ophthalmic composition and not blending dibutylhydroxytoluene and butylhydroxyanisole. Also, as one embodiment of the present invention, a method for reducing the elastic modulus of a soft contact lens is provided, which includes blending the (A) component and the (B) component into the ophthalmic composition and not blending dibutylhydroxytoluene and butylhydroxyanisole. Note that the types and amounts of the (A) component and the (B) component used, the content ratio, the types and amounts of other components blended, the formulation form of the ophthalmic composition, etc. are the same as those of the ophthalmic composition according to the above embodiment.

[0103] Here, the reduction rate of the elastic modulus of a soft contact lens by the ophthalmic composition in this embodiment (hereinafter also referred to as the "elastic modulus reduction rate") is calculated by the following formula. [Formula] Elastic modulus decrease rate (%) = (elastic modulus (Pa) of a soft contact lens immersed in a composition (comparative composition) that does not contain component (A) and has the same composition as the ophthalmic composition except for the content of component (B) - elastic modulus (Pa) of a soft contact lens immersed in an ophthalmic composition) / elastic modulus (Pa) of a soft contact lens immersed in a comparative composition × 100 The elastic modulus reduction rate is not particularly limited, but is preferably 10 to 50%.

[0104] When the elastic modulus of the soft contact lens is decreased, the soft contact lens becomes soft, and thus discomfort caused by the roughness, stiffness, and poor wearing comfort when wearing and / or attaching the soft contact lens can be reduced. Therefore, as one embodiment of the present invention, an agent for reducing discomfort when wearing and / or attaching a soft contact lens is provided, which contains component (A) and component (B) and does not contain dibutylhydroxytoluene and butylhydroxyanisole. As one embodiment of the present invention, a method for imparting an effect of reducing discomfort when wearing and / or attaching a soft contact lens to an ophthalmic composition is provided, which comprises blending component (A) and component (B) into the ophthalmic composition, and not blending dibutylhydroxytoluene and butylhydroxyanisole. As one embodiment of the present invention, a method for reducing discomfort when wearing and / or attaching a soft contact lens is provided, which comprises blending component (A) and component (B) into the ophthalmic composition, and not blending dibutylhydroxytoluene and butylhydroxyanisole. The types of the (A) component and the (B) component used, their blend amounts, content ratios, the types and amounts of other components blended, and the formulation form of the ophthalmic composition are the same as those of the ophthalmic composition of the present embodiment described above.

[0105] When the elastic modulus of a soft contact lens is high, it is easy to cause a gritty feeling or discomfort when worn, and the soft contact lens does not fit well on the eye, but by reducing the elastic modulus of the soft contact lens, it becomes easier to wear the soft contact lens on the eye. Therefore, as one embodiment of the present invention, an agent that makes it easier to wear a soft contact lens on the eye is provided, which contains components (A) and (B) and does not contain dibutylhydroxytoluene and butylhydroxyanisole. Also, as one embodiment of the present invention, a method is provided for imparting an effect of making it easier to wear a soft contact lens on the eye to an ophthalmic composition, which includes blending components (A) and (B) into the ophthalmic composition and not blending dibutylhydroxytoluene and butylhydroxyanisole. Also, as one embodiment of the present invention, a method is provided for making it easier to wear a soft contact lens on the eye, which includes blending components (A) and (B) into the ophthalmic composition and not blending dibutylhydroxytoluene and butylhydroxyanisole. The types of the (A) component and the (B) component used, their blend amounts, content ratios, the types and amounts of other components blended, and the formulation form of the ophthalmic composition are the same as those of the ophthalmic composition of the present embodiment described above.

[0106] When the elastic modulus of a soft contact lens is high, it is difficult for the lens to fit properly on the cornea and conjunctiva, which causes irritation due to the soft contact lens and discomfort and strange feeling due to wearing the soft contact lens, which makes the eye more likely to feel tired. When the elastic modulus of a soft contact lens is decreased, the lens is less irritated when worn and attached, and the lens is less uncomfortable and strange feeling, which makes the eye less likely to feel tired. Therefore, as one embodiment of the present invention, an agent for reducing eye fatigue when wearing and / or attaching a soft contact lens is provided, which contains component (A) and component (B) and does not contain dibutylhydroxytoluene and butylhydroxyanisole. In addition, as one embodiment of the present invention, a method for imparting an effect of reducing eye fatigue when wearing and / or attaching a soft contact lens to an ophthalmic composition is provided, which comprises blending component (A) and component (B) into the ophthalmic composition, and not blending dibutylhydroxytoluene and butylhydroxyanisole. In addition, as one embodiment of the present invention, there is provided a method for reducing eye fatigue during wearing and / or placement of soft contact lenses, which comprises blending component (A) and component (B) into an ophthalmic composition and not blending dibutylhydroxytoluene and butylhydroxyanisole. Note that the types and blending amounts of component (A) and component (B) used, the content ratio, the types and blending amounts of other components blended, the formulation form of the ophthalmic composition, etc. are the same as those of the ophthalmic composition according to the above embodiment. EXAMPLES

[0107] The present invention will be specifically described below based on test examples, but the present invention is not limited to these.

[0108] [Evaluation of the elastic modulus of contact lenses] <Preparation of test solution and soft contact lens (SCL)> The ophthalmic compositions shown in Table 1 were prepared according to a conventional method. The units of each component in Table 1 are w / v%. As the soft contact lens (SCL), "Clarity 1day" (a silicone hydrogel contact lens of group 2, manufactured by CooperVision) was used. 4 mL of physiological saline (manufactured by Otsuka Pharmaceutical Factory) was dispensed into a 12-well plate (BD Falcon, No. 35-3043), and one soft contact lens was immersed in each well and left to stand at room temperature for 4 hours or more. After lightly wiping off the moisture from the soft contact lens with lint-free paper, each ophthalmic composition shown in Table 1 was dispensed into a 12-well plate (BD Falcon, No. 35-3043) in 4 mL portions, and one soft contact lens was placed in each well, followed by standing at 34°C for 18 hours.

[0109] <Calculation of elastic modulus> Using an MCR302 rheometer (manufactured by AntonPaar), the parallel plate PP12 / P12 (diameter 12 mm, grid pattern; 1×0.5, product number: 23935), the cap plate P-PTD200 / 80-77 / SS / P2 (grid pattern, product number: 7894), the measurement temperature was set to 34°C, the frequency was set to 1Hz, and the measurement time was set to "no time setting" mode, and the shear stress (Pa) was measured for strains of 0.01 to 1%. Specifically, 0.5 mL of physiological saline was dropped onto the cap plate, and the convex surface of a soft contact lens (SCL) that had been wiped dry was placed on top of it (the convex surface of the lens was placed facing the cap plate), and 0.5 mL of physiological saline was dropped onto the SCL. The parallel plate was lowered to approach the cap plate, and the position was set so that the SCL was sandwiched between the two plates at a distance of 0.1 mm, and the measurement of shear stress (Pa) was started. The measurement intervals were 5 equal points for strain amounts of 0.01 to 0.1% and 5 equal points for strain amounts of 0.1 to 1%. The elastic modulus (Pa) was then calculated using formula 1, taking 0.0325% as the second measurement interval for strain amounts of 0.01 to 0.1% and 1% as the measurement interval for strain amounts of 0.1 to 1%. The measurement was performed three times, and the average value was taken as the average elastic modulus. [Formula 1] Elastic modulus (Pa) = shear stress / strain = (shear stress at 1% strain) - (shear stress at 0.0325% strain) / (1-0.0325)

[0110] <Calculation of elastic modulus decrease rate> Next, the reduction rate of the average elastic modulus of the soft contact lens (SCL) immersed in the ophthalmic composition of the Example relative to the average elastic modulus of the SCL immersed in the control ophthalmic composition (elastic modulus reduction rate) was determined. Specifically, the elastic modulus reduction rate was calculated using Equation 2. In the following Equation 2, Comparative Example 1 was used as the control for Examples 1 to 5 and Comparative Examples 2 to 3. The results are also shown in Table 1. [Formula 2] Elastic modulus reduction rate (%) relative to the comparative example of the control = (average elastic modulus (Pa) of the SCL immersed in the control ophthalmic composition - average elastic modulus (Pa) of the SCL immersed in the ophthalmic composition of the example) / average elastic modulus (Pa) of the SCL immersed in the control ophthalmic composition × 100

[0111] [Table 1]

Claims

1. An ophthalmic composition comprising (A) at least one selected from the group consisting of retinol and derivatives thereof, tocopherol and derivatives thereof, azulene sulfonic acid and salts thereof, chlorpheniramine and salts thereof, and terpenoids, and (B) polyoxyethylene polyoxypropylene glycol, and not containing dibutylhydroxytoluene or butylhydroxyanisole.

2. 2. The ophthalmic composition according to claim 1, wherein component (B) contains a polyoxyethylene polyoxypropylene glycol having a ratio (EO / PO) of the average degree of polymerization of ethylene oxide (EO) to the average degree of polymerization of propylene oxide (PO) of 1.0 to 5.

0.

3. The ophthalmic composition according to claim 1, wherein the content of component (B) is 0.01 to 0.9 w / v % based on the total amount of the ophthalmic composition.

4. The ophthalmic composition according to claim 1, further comprising (C) polyoxyethylene hydrogenated castor oil and / or polyoxyethylene castor oil.

5. The ophthalmic composition of claim 1 , further comprising (D) polyvinylpyrrolidone.

6. The ophthalmic composition of claim 1, having a pH of 5 to 9.

7. The ophthalmic composition according to claim 1 , which is for use in soft contact lenses.

8. The ophthalmic composition of claim 1 , further comprising no benzalkonium and / or a salt thereof.

9. The ophthalmic composition of claim 1 , further comprising no sorbic acid and / or a salt thereof.

10. 2. The ophthalmic composition of claim 1, further comprising no at least one selected from the group consisting of chlorhexidine, alexidine, polyhexamethylene biguanide, and polyaminopropyl biguanide, and salts thereof.

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