Ophthalmic composition

Abstract

To provide an ophthalmic composition capable of reducing ocular friction.SOLUTION: The present invention pertains to an ophthalmic composition that contains (A) at least one selected from the group consisting of chondroitin sulfate and salts thereof, wherein the content of component (A) is 0.7 w / v% or more with respect to the total amount of the ophthalmic composition.SELECTED DRAWING: None

Description

[Technical Field]

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

[0002] In the eye, friction occurs between the eyelids, cornea, and conjunctiva when movements such as blinking are applied, and this friction is said to be one of the causes of abnormalities in the cornea and conjunctiva, tear film, or eyelids. In particular, when wearing contact lenses, friction also occurs between the contact lenses and these tissues, and this friction is thought to lead to a deterioration in the comfort of wearing the contact lenses.

[0003] Methods for reducing friction in the eye have not yet been thoroughly investigated. Summary of the Invention [Problem to be solved by the invention]

[0004] An object of the present invention is to provide an ophthalmic composition that can reduce friction in the eye. [Means for solving the problem]

[0005] The present inventors have found that by incorporating a specific amount or more of at least one selected from the group consisting of chondroitin sulfate and its salts into an ophthalmic composition, friction in the eye can be reduced. The present invention is based on this finding and provides the following inventions.

[0006] [1] An ophthalmic composition comprising (A) at least one selected from the group consisting of chondroitin sulfate and its salts, wherein the content of component (A) is 0.7 w / v% or more based on the total amount of the ophthalmic composition. [2] An ophthalmic composition comprising (A) at least one component selected from the group consisting of chondroitin sulfate and salts thereof, wherein the content of component (A) is 1 to 3 w / v% based on the total amount of the ophthalmic composition. [3] The ophthalmic composition according to [1] or [2], further comprising at least one member selected from the group consisting of (B) (B-1) amino acids other than component (A), (B-2) oily components, (B-3) nonionic surfactants, (B-4) biguanide bactericides, (B-5) fat-soluble vitamins, and (B-6) vinyl polymer compounds. [4] The ophthalmic composition according to [3], wherein the component (B-1) is at least one selected from the group consisting of aspartic acid, aminoethylsulfonic acid, hyaluronic acid, and salts thereof; the component (B-2) is at least one selected from the group consisting of sesame oil, castor oil, and liquid paraffin; the component (B-3) is at least one selected from the group consisting of polyoxyethylene-polyoxypropylene glycol, polyoxyethylene hydrogenated castor oil, and polyoxyethylene sorbitan fatty acid esters; the component (B-4) is at least one selected from the group consisting of chlorhexidine, polyhexanide, and salts thereof; the component (B-5) is at least one selected from the group consisting of vitamins A and E; and the component (B-6) is at least one selected from the group consisting of polyvinylpyrrolidone and polyvinyl alcohol. [5] The ophthalmic composition according to [3] or [4], wherein the content of component (B) is 0.0000001 w / v% or more based on the total amount of the ophthalmic composition. [6] (C) The ophthalmic composition according to any one of [1] to [5], further comprising a terpenoid. [7] A method for imparting to an ophthalmic composition the effect of reducing friction in the eye, comprising blending (A) at least one selected from the group consisting of chondroitin sulfate and salts thereof in an amount of 0.7 w / v% or more, based on the total amount of the ophthalmic composition, with the ophthalmic composition. [Effects of the Invention]

[0007] According to the present invention, an ophthalmic composition capable of reducing friction in the eye can be provided. [Brief explanation of the drawings]

[0008] [Figure 1] 1 is a graph showing the friction coefficient reduction rate of each of the ophthalmic compositions of Comparative Example 1-2, Example 1-1, Example 1-2, and Example 1-3. DETAILED DESCRIPTION OF THE INVENTION

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

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

[0011] [1. Ophthalmic composition] The ophthalmic composition according to this embodiment contains at least one selected from the group consisting of chondroitin sulfate and salts thereof (also simply referred to as "component (A)").

[0012] [Component (A)] The ophthalmic composition according to this embodiment contains (A) at least one selected from the group consisting of chondroitin sulfate and salts thereof (also simply referred to as "component (A)").

[0013] Chondroitin sulfate and its salts, which are component (A), are not particularly limited as long as they are pharmaceutically, pharmacologically (pharmaceutical), or physiologically acceptable. The molecular weight of chondroitin sulfate and its salts is not particularly limited as long as they are pharmaceutically, pharmacologically (pharmaceutical), or physiologically acceptable, but typically, those with a weight-average molecular weight of about 1,000 to 100,000, preferably about 5,000 to 50,000, and more preferably about 10,000 to 40,000 can be used.

[0014] Examples of salts of chondroitin sulfate include alkali metal salts and alkaline earth metal salts. Examples of alkali metal salts include sodium salt and potassium salt. Examples of alkaline earth metal salts include magnesium salt and calcium salt.

[0015] As chondroitin sulfate and salts thereof, chondroitin sulfate and alkali metal salts of chondroitin sulfate are preferred, chondroitin sulfate and sodium chondroitin sulfate are more preferred, and sodium chondroitin sulfate is even more preferred.

[0016] Chondroitin sulfate and salts thereof may be commercially available. One type of chondroitin sulfate and salts thereof may be used alone, or two or more types may be used in combination.

[0017] The content of component (A) in the ophthalmic composition according to this embodiment is 0.7 w / v% or more, based on the total amount of the ophthalmic composition. The lower limit of the content of component (A) is not particularly limited as long as it is 0.7 w / v% or more, and is set appropriately depending on the type of component (A), the types and amounts of other components added, the intended use and formulation of the ophthalmic composition, etc. From the viewpoint of more significantly achieving the effects of the present invention, the lower limit of the content of component (A) is, for example, preferably 0.8 w / v% or more, more preferably 0.9 w / v% or more, even more preferably 1 w / v% or more, even more preferably 2 w / v% or more, and particularly preferably 2.5 w / v% or more. The upper limit of the content of component (A) is not particularly limited, and is set appropriately depending on the type of component (A), the types and amounts of other components added, the intended use and formulation of the ophthalmic composition, etc. The upper limit of the content of component (A) is, for example, preferably 5 w / v% or less, more preferably 4 w / v% or less, even more preferably 3.5 w / v% or less, and even more preferably 3 w / v% or less, from the viewpoint of more significantly exhibiting the effects of the present invention and from the viewpoint of usability. The content of component (A) in the ophthalmic composition according to this embodiment may be, for example, 0.7 to 5 w / v%, 0.7 to 4 w / v%, 0.7 to 3 w / v%, 0.8 to 5 w / v%, 0.8 to 4 w / v%, 0.8 to 3 w / v%, 0.9 to 5 w / v%, 0.9 to 4 w / v%, 0.9 to 3 w / v%, 1 to 5 w / v%, 1 to 4 w / v%, or 1 to 3 w / v%, based on the total amount of the ophthalmic composition. In another aspect, the content of component (A) in the ophthalmic composition of this embodiment may be, for example, 2 to 4 w / v%, 2.5 to 3.5 w / v%, or 3 w / v%, based on the total amount of the ophthalmic composition.

[0018] [(B) component] The ophthalmic composition according to this embodiment may further contain at least one selected from the group consisting of amino acids other than components (B), (B-1), and (A) (also referred to simply as "component (B-1)"), (B-2) oily components (also referred to simply as "component (B-2)"), (B-3) nonionic surfactants (also referred to simply as "component (B-3)"), (B-4) biguanide bactericides (also referred to simply as "component (B-4)"), (B-5) fat-soluble vitamins (also referred to simply as "component (B-5)"), and (B-6) vinyl polymers (also referred to simply as "component (B-6)"). (Hereinafter, components (B-1) to (B-6) will be collectively referred to simply as "component (B)"). When the ophthalmic composition contains component (B), the effects of the present invention are more pronounced.

[0019] The component (B) may be used alone or in combination of two or more.

[0020] The content of component (B) in the ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the type of component (B), the types and contents of other components, the intended use and formulation of the ophthalmic composition, etc. From the viewpoint of more significantly achieving the effects of the present invention, the lower limit of the content of component (B) is, for example, preferably 0.0000001 w / v% or more, more preferably 0.000001 w / v% or more, and even more preferably 0.00001 w / v% or more. The upper limit of the content of component (B) is not particularly limited and is set appropriately depending on the type of component (B), the types and contents of other components, the intended use and formulation of the ophthalmic composition, etc. From the viewpoint of more significantly achieving the effects of the present invention and the feel when used, the upper limit of the content of component (B) is, for example, preferably 5 w / v% or less, more preferably 4 w / v% or less, and even more preferably 3 w / v% or less.

[0021] [(B-1) component] The amino acids other than component (A) that are component (B-1) are not particularly limited as long as they are medicamentarily, pharmacologically (pharmaceutical), or physiologically acceptable. Amino acids include compounds having an amino group and a carboxyl group and / or a sulfo group in the molecule, as well as derivatives thereof and salts thereof.

[0022] Examples of amino acids other than component (A) include glutamic acid, aspartic acid, aminoethylsulfonic acid (taurine), hyaluronic acid, and salts thereof. The amino acids may be in the D-, L-, or DL-form.

[0023] Examples of salts that can be taken by amino acids other than component (A) include alkali metal salts and alkaline earth metal salts. Examples of alkali metal salts include sodium salts and potassium salts. Examples of alkaline earth metal salts include magnesium salts and calcium salts.

[0024] As the amino acids other than component (A), aspartic acid, aminoethylsulfonic acid, hyaluronic acid and salts thereof are preferred, aminoethylsulfonic acid and sodium hyaluronate are more preferred, and sodium hyaluronate is even more preferred.

[0025] The amino acids other than component (A) may be commercially available. The amino acids other than component (A) may be used singly or in combination of two or more.

[0026] The content of component (B-1) in the ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the type of component (B-1), the types and contents of other blended components, the intended use and formulation of the ophthalmic composition, etc. From the viewpoint of more significantly exhibiting the effects of the present invention, the content of component (B-1) is, for example, preferably 0.0001 to 5 w / v%, more preferably 0.001 to 4 w / v%, even more preferably 0.01 to 3 w / v%, and even more preferably 0.1 to 2 w / v%, based on the total amount of the ophthalmic composition.

[0027] The ratio of component (B-1) to component (A) in the ophthalmic composition according to this embodiment is not particularly limited and is appropriately determined depending on the types of components (A) and (B-1), the types and amounts of other components, the intended use of the ophthalmic composition, and the formulation form. From the viewpoint of further enhancing the effects of the present invention, the ratio of component (B-1) to component (A) is preferably 0.00001 to 10 parts by weight, more preferably 0.0001 to 5 parts by weight, even more preferably 0.0003 to 2 parts by weight, and particularly preferably 0.0003 to 1 part by weight, per part by weight of the total content of component (A) in the ophthalmic composition according to this embodiment. Also preferred is an embodiment in which the total content of component (B-1) is 0.001 part by weight or more, or 0.01 part by weight or more, per part by weight of the total content of component (A).

[0028] When the component (B-1) is hyaluronic acid or a salt thereof, the content of the component (B-1) is, for example, preferably 0.001 to 1 w / v%, more preferably 0.01 to 0.5 w / v%, and even more preferably 0.1 to 0.3 w / v%, based on the total amount of the ophthalmic composition.

[0029] When the (B-1) component is hyaluronic acid or a salt thereof, the content ratio of the (B-1) component to the (A) component is, for example, preferably 0.0001 to 2 parts by mass, more preferably 0.001 to 1 part by mass, more preferably 0.01 to 0.3 parts by mass, and even more preferably 0.03 to 0.1 parts by mass, of the total content of the (B-1) component per 1 part by mass of the total content of the (A) component contained in the ophthalmic composition of this embodiment.

[0030] [(B-2) component] The oily component (B-2) is not particularly limited as long as it is medicamentally, pharmacologically (pharmaceutical), or physiologically acceptable. Oily components include plant-derived vegetable oils, animal-derived animal oils, and natural or synthetic mineral oils.

[0031] Examples of oily components include vegetable oils such as soybean oil, rice oil, rapeseed oil, cottonseed oil, sesame oil, safflower oil, almond oil, castor oil, olive oil, cacao oil, camellia oil, sunflower oil, palm oil, linseed oil, perilla oil, shea oil, coconut oil, jojoba oil, grapeseed oil, and avocado oil; animal oils such as beeswax, lanolin (refined lanolin, etc.), orange roughy oil, squalane, and horse oil; and mineral oils such as petrolatum (white petrolatum, yellow petrolatum, etc.) and liquid paraffin.

[0032] As the oily component, an oily component other than petrolatum is preferred, vegetable oil and mineral oil are more preferred, sesame oil, castor oil and liquid paraffin are even more preferred, and sesame oil is even more preferred.

[0033] The oil component may be a commercially available product. One oil component may be used alone, or two or more oil components may be used in combination.

[0034] The content of component (B-2) in the ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the type of component (B-2), the types and contents of other blended components, the intended use and formulation of the ophthalmic composition, etc. From the viewpoint of more significantly exhibiting the effects of the present invention, the content of component (B-2) is, for example, preferably 0.0001 to 5 w / v%, more preferably 0.001 to 1 w / v%, even more preferably 0.003 to 0.5 w / v%, and even more preferably 0.005 to 0.1 w / v%, based on the total amount of the ophthalmic composition.

[0035] The content ratio of component (B-2) relative to component (A) in the ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the types of components (A) and (B-2), the types and contents of other blended components, the intended use and formulation of the ophthalmic composition, etc. From the viewpoint of further enhancing the effects of the present invention, the content ratio of component (B-2) relative to component (A) is, for example, preferably 0.0001 to 5 parts by mass, more preferably 0.0005 to 2.5 parts by mass, even more preferably 0.001 to 1 part by mass, even more preferably 0.005 to 0.5 parts by mass, particularly preferably 0.01 to 0.1 parts by mass, and particularly more preferably 0.01 to 0.05 parts by mass, relative to 1 part by mass of the total content of component (A) contained in the ophthalmic composition according to this embodiment.

[0036] [(B-3) component] The nonionic surfactant serving as component (B-3) is not particularly limited as long as it is medicamentarily, pharmacologically (pharmaceutical) or physiologically acceptable.

[0037] Examples of nonionic surfactants include polyoxyethylene (20) sorbitan monolaurate (polysorbate 20), polyoxyethylene (20) sorbitan monopalmitate (polysorbate 40), polyoxyethylene (20) sorbitan monostearate (polysorbate 60), polyoxyethylene (20) sorbitan tristearate (polysorbate 65), and polyoxyethylene (20) sorbitan monooleate (polysorbate 80). ), polyoxyethylene sorbitan fatty acid esters such as 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 Polyoxyethylene hydrogenated castor oils such as 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); polyoxyethylene castor oils such as 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); polyoxyethylene alkyl ethers such as polyoxyethylene (9) lauryl ether; polyoxyethylene-polyoxypropylene alkyl ethers such as polyoxyethylene (20) polyoxypropylene (4) cetyl ether;Polyoxyethylene (20) polyoxypropylene (20) glycol (Pluronic L44), polyoxyethylene (42) polyoxypropylene (67) glycol (Poloxamer 403, Pluronic P123), polyoxyethylene (54) polyoxypropylene (39) glycol (Poloxamer 235, Pluronic P85), polyoxyethylene (120) polyoxypropylene (40) glycol (Pluronic F87), polyoxyethylene (160) poly Examples include polyoxyethylene-polyoxypropylene glycols such as oxypropylene (30) glycol (Poloxamer 188, Pluronic F68), polyoxyethylene (196) polyoxypropylene (67) glycol (Poloxamer 407, Pluronic F127), and polyoxyethylene (200) polyoxypropylene (70) glycol; and polyethylene glycol monostearates such as polyoxyl 10 stearate and polyoxyl 40 stearate. In the compounds exemplified above, the numbers in parentheses indicate the number of moles added.

[0038] Preferred nonionic surfactants are polyoxyethylene sorbitan fatty acid esters, polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil, polyoxyethylene-polyoxypropylene glycol, and polyethylene glycol monostearate, more preferred are polyoxyethylene hydrogenated castor oil and polyoxyethylene-polyoxypropylene glycol, and even more preferred are polyoxyethylene hydrogenated castor oil 60 and polyoxyethylene (196) polyoxypropylene (67) glycol.

[0039] The nonionic surfactant may be a commercially available one. The nonionic surfactant may be used alone or in combination of two or more.

[0040] The content of component (B-3) in the ophthalmic composition according to this embodiment is not particularly limited and is appropriately determined depending on the type of component (B-3), the types and contents of other components, the intended use of the ophthalmic composition, and the formulation form. To more significantly exhibit the effects of the present invention, the content of component (B-3) is, for example, preferably 0.0001 to 5 w / v%, more preferably 0.001 to 3 w / v%, and even more preferably 0.005 to 2 w / v%, based on the total amount of the ophthalmic composition. Also preferred are embodiments in which the total content of component (B-3) is 0.01 to 1 w / v%, or 0.05 to 0.5 w / v%.

[0041] The content ratio of component (B-3) relative to component (A) in the ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the types of components (A) and (B-3), the types and contents of other blended components, the intended use and formulation of the ophthalmic composition, etc. From the viewpoint of further enhancing the effects of the present invention, the content ratio of component (B-3) relative to component (A) is, for example, preferably 0.0001 to 10 parts by mass, more preferably 0.0005 to 5 parts by mass, even more preferably 0.001 to 3 parts by mass, even more preferably 0.003 to 1 part by mass, particularly preferably 0.01 to 0.5 parts by mass, and particularly more preferably 0.01 to 0.25 parts by mass, relative to 1 part by mass of the total content of component (A) contained in the ophthalmic composition according to this embodiment.

[0042] [(B-4) component] The biguanide fungicide as component (B-4) is not particularly limited as long as it is medicamentarily, pharmacologically (pharmaceutical) or physiologically acceptable.

[0043] Examples of biguanide antiseptics include chlorhexidine, polyhexanide (polyhexamethylene biguanide), alexidine, and salts thereof. Examples of chlorhexidine salts include hydrochloride, acetate, and gluconate. Examples of polyhexanide salts include hydrochloride. Examples of alexidine salts include hydrochloride (dihydrochloride).

[0044] As the biguanide antiseptic, chlorhexidine, polyhexanide and salts thereof are preferred, chlorhexidine hydrochloride, chlorhexidine acetate, chlorhexidine gluconate and polyhexanide hydrochloride are more preferred, and chlorhexidine gluconate is even more preferred.

[0045] As the biguanide fungicide, commercially available products may be used. The biguanide fungicides may be used alone or in combination of two or more.

[0046] The content of component (B-4) in the ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the type of component (B-4), the types and contents of other blended components, the intended use and formulation of the ophthalmic composition, etc. From the viewpoint of more significantly exhibiting the effects of the present invention, the content of component (B-4) is, for example, preferably 0.0000005 to 0.5 w / v%, more preferably 0.000001 to 0.2 w / v%, even more preferably 0.000005 to 0.1 w / v%, even more preferably 0.00001 to 0.01 w / v%, and particularly preferably 0.00005 to 0.01 w / v%, based on the total amount of the ophthalmic composition.

[0047] The content ratio of component (B-4) relative to component (A) in the ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the types of components (A) and (B-4), the types and contents of other blended components, the intended use and formulation of the ophthalmic composition, etc. From the viewpoint of further enhancing the effects of the present invention, the content ratio of component (B-4) relative to component (A) is, for example, preferably 0.000001 to 0.5 parts by mass, more preferably 0.000005 to 0.1 parts by mass, even more preferably 0.00001 to 0.05 parts by mass, even more preferably 0.00002 to 0.02 parts by mass, and particularly preferably 0.00002 to 0.01 parts by mass, relative to 1 part by mass of the total content of component (A) contained in the ophthalmic composition according to this embodiment.

[0048] [(B-5) component] The fat-soluble vitamin that is the component (B-5) is not particularly limited as long as it is medicamentarily, pharmacologically (pharmaceutical) or physiologically acceptable.

[0049] Examples of fat-soluble vitamins include vitamin A (retinal, retinol, retinoic acid, carotene, dehydroretinal, lycopene, etc.), vitamin D (ergocalciferol, cholecalciferol, etc.), vitamin E (d-α-tocopherol, dl-α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, etc.), and vitamin K (phylloquinone, menaquinone, etc.).

[0050] As the fat-soluble vitamin, vitamins A and E are preferred, vitamins A are more preferred, retinol and its derivatives are even more preferred, retinol acetate and retinol palmitate are even more preferred, and retinol palmitate is particularly preferred.

[0051] The fat-soluble vitamins may be commercially available ones. The fat-soluble vitamins may be used alone or in combination of two or more kinds.

[0052] The content of component (B-5) in the ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the type of component (B-5), the types and contents of other blended components, the intended use and formulation of the ophthalmic composition, etc. From the viewpoint of more significantly exhibiting the effects of the present invention, the content of component (B-5) is, for example, preferably 0.00001 to 1 w / v%, more preferably 0.0001 to 0.5 w / v%, even more preferably 0.001 to 0.1 w / v%, and even more preferably 0.01 to 0.05 w / v%, based on the total amount of the ophthalmic composition.

[0053] The content ratio of component (B-5) relative to component (A) in the ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the types of components (A) and (B-5), the types and contents of other blended components, the intended use and formulation of the ophthalmic composition, etc. From the viewpoint of further enhancing the effects of the present invention, the content ratio of component (B-5) relative to component (A) is, for example, preferably 0.0001 to 0.5 parts by mass, more preferably 0.0005 to 0.1 parts by mass, even more preferably 0.001 to 0.05 parts by mass, and even more preferably 0.001 to 0.025 parts by mass, of the total content of component (B-5) relative to 1 part by mass of the total content of component (A) contained in the ophthalmic composition according to this embodiment.

[0054] When the (B-5) component is a vitamin A, the content of the (B-5) component in the ophthalmic composition according to this embodiment is not particularly limited and is appropriately determined depending on the type of the (B-5) component, the type and content of other ingredients, the intended use of the ophthalmic composition, and the formulation. To more significantly achieve the effects of the present invention, the content of the (B-5) component is preferably 0.1 to 100,000 IU / 100 mL, more preferably 0.5 to 70,000 IU / 100 mL, and even more preferably 10,000 to 50,000 IU / 100 mL, based on the total volume of the ophthalmic composition. The term "IU" refers to the international unit determined by the method described in the Vitamin A Quantitation Method in the Japanese Pharmacopoeia, Seventeenth Edition. For example, the monographs of the Japanese Pharmacopoeia, Seventeenth Edition, state that retinol acetate contains at least 2.5 million units of vitamin A per gram, and retinol palmitate contains at least 1.5 million units of vitamin A per gram.

[0055] When component (B-5) is a vitamin A, the content ratio of component (B-5) relative to component (A) in the ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the types of components (A) and (B-5), the types and contents of other blended components, the intended use and formulation of the ophthalmic composition, etc. From the viewpoint of further enhancing the effects of the present invention, the content ratio of component (B-5) relative to component (A) is, for example, preferably 5,000 to 150,000 IU, more preferably 1,000 to 100,000 IU, and even more preferably 3,000 to 50,000 IU per gram of the total content of component (A) contained in the ophthalmic composition according to this embodiment.

[0056] [(B-6) component] The vinyl polymer compound serving as component (B-6) is not particularly limited as long as it is medicamentarily, pharmacologically (pharmaceutical) or physiologically acceptable.

[0057] Examples of vinyl polymer compounds include polyvinylpyrrolidone, polyvinyl alcohol, and carboxyvinyl polymers.

[0058] As the vinyl polymer compound, polyvinylpyrrolidone and polyvinyl alcohol are preferred, polyvinylpyrrolidone is more preferred, polyvinylpyrrolidone K17, polyvinylpyrrolidone K25, polyvinylpyrrolidone K30, polyvinylpyrrolidone K90 are even more preferred, and polyvinylpyrrolidone K90 is even more preferred.

[0059] The vinyl polymer compound may be a commercially available product. The vinyl polymer compound may be used alone or in combination of two or more.

[0060] The content of component (B-6) in the ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the type of component (B-6), the types and contents of other blended components, the intended use and formulation of the ophthalmic composition, etc. From the viewpoint of more significantly exhibiting the effects of the present invention, the content of component (B-6) is, for example, preferably 0.00005 to 5 w / v%, more preferably 0.0001 to 3 w / v%, even more preferably 0.0005 to 3 w / v%, and even more preferably 0.001 to 1 w / v%, based on the total amount of the ophthalmic composition.

[0061] The content ratio of component (B-6) relative to component (A) in the ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the types of components (A) and (B-6), the types and contents of other blended components, the intended use and formulation of the ophthalmic composition, etc. From the viewpoint of further enhancing the effects of the present invention, the content ratio of component (B-6) relative to component (A) is, for example, preferably 0.00001 to 5 parts by mass, more preferably 0.00005 to 3 parts by mass, even more preferably 0.0001 to 1 part by mass, still more preferably 0.0003 to 0.5 parts by mass, and particularly preferably 0.0003 to 0.25 parts by mass, relative to 1 part by mass of the total content of component (A) contained in the ophthalmic composition according to this embodiment.

[0062] [(C) component] The ophthalmic composition according to this embodiment may further contain a terpenoid (C) (also simply referred to as "component (C)"). When the ophthalmic composition contains component (C), the effects of the present invention are more pronounced.

[0063] The terpenoid serving as component (C) is not particularly limited as long as it is medicamentarily, pharmacologically (pharmaceutical), or physiologically acceptable.

[0064] Terpenoids include, for example, cyclic and acyclic terpenes.

[0065] Cyclic terpenes are terpenoids that contain at least one ring structure within the molecule. Examples of cyclic terpenes include menthol, camphor, borneol (also known as "ryunou"), menthone, cineole, carvone, anethole, eugenol, limonene, pinene, and derivatives thereof.

[0066] Acyclic terpenes are terpenoids that do not have a ring structure within the molecule. Examples of acyclic terpenes include geraniol, citronellol, linalool, linalyl acetate, and derivatives thereof.

[0067] In the present invention, essential oils containing the above-mentioned compounds may be used as terpenoids, such as eucalyptus oil, bergamot oil, peppermint oil, cool mint oil, spearmint oil, peppermint oil, fennel oil, cinnamon oil, and rose oil.

[0068] Terpenoids may be any of the d-, l-, and dl-isomers, and examples thereof include dl-menthol, d-menthol, l-menthol, dl-camphor, d-camphor, l-camphor, dl-borneol, d-borneol, l-borneol, dl-menthone, d-menthone, and l-menthone. However, some terpenoids, such as geraniol and cineole, do not have optical isomers.

[0069] As the terpenoid, menthol, camphor, borneol, menthone, geraniol, eucalyptus oil and bergamot oil are preferred, menthol, camphor and borneol are more preferred, l-menthol, d-camphor, dl-camphor and d-borneol are even more preferred, and l-menthol is even more preferred.

[0070] The terpenoids used may be commercially available products. One type of terpenoid may be used alone, or two or more types may be used in combination.

[0071] The content of component (C) in the ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the type of component (C), the types and contents of other blended components, the intended use and formulation 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 0.00001 to 1 w / v%, more preferably 0.00005 to 0.5 w / v%, even more preferably 0.0001 to 0.1 w / v%, even more preferably 0.0005 to 0.05 w / v%, and particularly preferably 0.001 to 0.05 w / v%, based on the total amount of the ophthalmic composition.

[0072] The content ratio of component (C) relative to component (A) in the ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the types of components (A) and (C), the types and contents of other blended components, the intended use and formulation of the ophthalmic composition, etc. From the viewpoint of further enhancing the effects of the present invention, the content ratio of component (C) relative to component (A) is, for example, preferably 0.00005 to 0.5 parts by mass, more preferably 0.0001 to 0.1 parts by mass, even more preferably 0.0003 to 0.05 parts by mass, and even more preferably 0.0003 to 0.03 parts by mass, of the total content of component (C) relative to 1 part by mass of the total content of component (A) in the ophthalmic composition according to this embodiment.

[0073] [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 effects of the present invention are more pronounced. The inorganic salt is not particularly limited as long as it is medicamentarily, pharmacologically (pharmaceutical), or physiologically acceptable.

[0074] Examples of inorganic salts include metal chlorides such as calcium chloride, magnesium chloride, sodium chloride, and potassium chloride; ammonium chloride; and metal sulfates such as calcium sulfate, magnesium sulfate, sodium sulfate, potassium sulfate, and ammonium sulfate.

[0075] As the inorganic salts, metal chlorides are preferred, calcium chloride, magnesium chloride, sodium chloride and potassium chloride are more preferred, and sodium chloride and potassium chloride are even more preferred.

[0076] The inorganic salts may be commercially available. One type of inorganic salt may be used alone, or two or more types may be used in combination.

[0077] The content of inorganic salts in the ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the type of inorganic salts, the types and contents of other blended ingredients, the intended use and formulation 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 0.01 to 10 w / v%, more preferably 0.05 to 5 w / v%, and even more preferably 0.1 to 1 w / v%, based on the total amount of the ophthalmic composition.

[0078] The content ratio of inorganic salts relative to component (A) in the ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the types of component (A) and inorganic salts, the types and contents of other blended components, the intended use and formulation of the ophthalmic composition, etc. From the viewpoint of further enhancing the effects of the present invention, the content ratio of inorganic salts relative to component (A) is, for example, preferably 0.001 to 5 parts by mass, more preferably 0.005 to 1 part by mass, and even more preferably 0.01 to 0.3 parts by mass, of the total content of inorganic salts relative to 1 part by mass of the total content of component (A) contained in the ophthalmic composition according to this embodiment. [Buffer] The ophthalmic composition according to this embodiment preferably further contains a buffer. When the ophthalmic composition further contains a buffer, the effects of the present invention are more pronounced. The buffer is not particularly limited as long as it is medicamentarily, pharmacologically (pharmaceutical), or physiologically acceptable.

[0079] Examples of the buffer include inorganic buffers, which are buffers derived from inorganic acids, and organic buffers, which are buffers derived from organic acids or organic bases.

[0080] Examples of inorganic buffers include borate buffers, phosphate buffers, and carbonate buffers. Examples of borate buffers include boric acid or its salts (alkali metal borates, alkaline earth metal borates, etc.). Examples of phosphate buffers include phosphoric acid or its salts (alkali metal phosphates, alkaline earth metal phosphates, etc.). Examples of carbonate buffers include carbonic acid or its salts (alkali metal carbonates, alkaline earth metal carbonates, etc.). Furthermore, hydrates of borate, phosphate, or carbonate may be used as borate buffers, phosphate buffers, or carbonate buffers. More specific examples of borate buffers include boric acid or salts thereof (sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, borax, etc.); phosphate buffers include phosphoric acid or salts thereof (disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, trisodium phosphate, tripotassium phosphate, calcium monohydrogen phosphate, calcium dihydrogen phosphate, etc.); and carbonate buffers include carbonic acid or salts thereof (sodium bicarbonate, sodium carbonate, ammonium carbonate, potassium carbonate, calcium carbonate, potassium bicarbonate, magnesium carbonate, etc.).

[0081] Examples of organic buffers include citrate buffers, acetate buffers, lactate buffers, succinate buffers, Tris buffers, and AMPD buffers. Examples of citrate buffers include citric acid or salts thereof (such as alkali metal citrates and alkaline earth metal citrates). Examples of acetate buffers include acetic acid or salts thereof (such as alkali metal acetates and alkaline earth metal acetates). Examples of lactate buffers include lactic acid or salts thereof (such as alkali metal lactates and alkaline earth metal lactates). Examples of succinate buffers include succinic acid or salts thereof (such as alkali metal succinates). Furthermore, hydrates of citrate, acetate, lactate, or succinate may be used as citrate buffers, acetate buffers, lactate buffers, or succinate buffers. More specific examples of citrate buffers include citric acid or its salts (sodium citrate, potassium citrate, calcium citrate, sodium dihydrogen citrate, disodium citrate, etc.); acetate buffers include acetic acid or its salts (ammonium acetate, sodium acetate, potassium acetate, calcium acetate, etc.); lactate buffers include lactic acid or its salts (sodium lactate, potassium lactate, calcium lactate, etc.); and succinate buffers include succinic acid or its salts (monosodium succinate, disodium succinate, etc.). Examples of Tris buffers include trometamol or its salts (trometamol hydrochloride, etc.). Examples of AMPD buffers include 2-amino-2-methyl-1,3-propanediol or its salts.

[0082] As the buffer, boric acid buffer (e.g., a combination of boric acid and borax), phosphate buffer (e.g., a combination of disodium hydrogen phosphate and sodium dihydrogen phosphate), and Tris buffer (e.g., trometamol) are preferred, with boric acid buffer being more preferred, boric acid and its salts being even more preferred, and a combination of boric acid and borax being even more preferred.

[0083] The buffering agent may be a commercially available product. One type of buffering agent may be used alone, or two or more types may be used in combination.

[0084] The content of the buffering agent in the ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the type of buffering agent, the types and contents of other blended ingredients, the intended use and formulation 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 even more preferably 0.1 to 3 w / v%, based on the total amount of the ophthalmic composition.

[0085] The content ratio of the buffering agent relative to the component (A) in the ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the types of component (A) and buffering agent, the types and contents of other blended components, the intended use and formulation of the ophthalmic composition, etc. From the viewpoint of further enhancing the effects of the present invention, the content ratio of the buffering agent relative to the component (A) is, for example, preferably 0.01 to 10 parts by mass, more preferably 0.1 to 5 parts by mass, and even more preferably 0.5 to 3 parts by mass, of the total content of the buffering agent relative to 1 part by mass of the total content of the component (A) contained in the ophthalmic composition according to this embodiment.

[0086] The pH of the ophthalmic composition according to this embodiment is not particularly limited as long as it is within a medicamentarily, pharmacologically (pharmaceutical), or physiologically acceptable range. The pH of the ophthalmic composition according to this embodiment may be, for example, 4.0 to 9.5, preferably 4.0 to 9.0, more preferably 4.5 to 9.0, even more preferably 4.5 to 8.5, even more preferably 5.0 to 8.5, particularly preferably 5.5 to 8.0, and particularly more preferably 6.0 to 7.8.

[0087] The ophthalmic composition according to this embodiment can be adjusted to an osmotic pressure ratio within a biologically acceptable range, as needed. The appropriate osmotic pressure ratio varies depending on the application site, dosage form, etc.; however, from the viewpoint of more significantly achieving the effects of the present invention, it is preferably 0.05 to 6, more preferably 0.4 to 5, even more preferably 0.6 to 3, and even more preferably 0.8 to 2. The osmotic pressure can be adjusted using inorganic salts, polyhydric alcohols, etc., by methods known in the art. The osmotic pressure ratio is defined as the ratio of the osmotic pressure of the sample to 286 mOsm (the osmotic pressure of a 0.9 w / v% sodium chloride aqueous solution) according to the 17th Edition of the Japanese Pharmacopoeia. The osmotic pressure is measured using the osmotic pressure measurement method (freezing-point depression method) described in the Japanese Pharmacopoeia. The standard solution for measuring osmolality ratios (0.9 w / v% sodium chloride aqueous solution) can be prepared by drying sodium chloride (Japanese Pharmacopoeia standard reagent) at 500-650°C for 40-50 minutes, allowing it to cool in a desiccator (silica gel), accurately weighing 0.900 g of the solution, and dissolving it in purified water to make exactly 100 mL; alternatively, a commercially available standard solution for measuring osmolality ratios (0.9 w / v% sodium chloride aqueous solution) can be used.

[0088] The viscosity of the ophthalmic composition according to this embodiment is not particularly limited as long as it is within a medicamentarily, pharmacologically (pharmaceutical), or physiologically acceptable range. The viscosity of the ophthalmic composition according to this embodiment, as measured at 20°C using a rotational viscometer (TV-20 type viscometer, manufactured by Toki Sangyo Co., Ltd., rotor: 1°34' x R24), is preferably 0.1 to 10,000 mPa·s, more preferably 1 to 3,000 mPa·s, even more preferably 1 to 1,000 mPa·s, even more preferably 1 to 100 mPa·s, particularly preferably 1 to 50 mPa·s, even more preferably 1 to 10 mPa·s, and even more preferably 1.3 to 5 mPa·s.

[0089] The ophthalmic composition according to this embodiment may contain, in addition to the above-mentioned components, a combination of various pharmacologically active components and physiologically active components in appropriate amounts, as long as the effects of the present invention are not impaired. The components are not particularly limited, and examples thereof include active ingredients in ophthalmic drugs listed in the 2012 edition of the OTC Drug Manufacturing and Marketing Approval Standards (supervised by the Japan Society of Regulatory Science). Specific examples of components used in ophthalmic drugs include the following: Antiallergic agents: for example, sodium cromoglycate, tranilast, pemirolast potassium, etc. Antihistamines: for example, diphenhydramine hydrochloride, iproheptine, chlorpheniramine maleate, levocabastine hydrochloride, ketotifen fumarate, pemirolast potassium, olopatadine hydrochloride, etc. Anti-inflammatory agents: 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, sodium azulene sulfonate, etc. Steroids: for example, fluticasone propionate, fluticasone furoate, mometasone furoate, beclomethasone propionate, flunisolide, etc. Decongestants: for example, tetrahydrozoline hydrochloride, tetrahydrozoline nitrate, naphazoline hydrochloride, naphazoline nitrate, epinephrine, epinephrine hydrochloride, ephedrine hydrochloride, phenylephrine hydrochloride, dl-methylephedrine hydrochloride, etc. Ocular muscle regulating agents: For example, cholinesterase inhibitors having an active center similar to that of acetylcholine, specifically neostigmine methylsulfate, tropicamide, helenien, atropine sulfate, etc. Vitamins other than (B-5) ingredient: For example, flavin adenine dinucleotide sodium, cyanocobalamin, pyridoxine hydrochloride, panthenol, calcium pantothenate, ascorbic acid, sodium ascorbate, etc. Others: For example, sulfamethoxazole, sulfisoxazole, sulfisomidine and their salts.

[0090] The ophthalmic composition according to this embodiment may contain one or more additives selected appropriately in a conventional manner depending on the intended use and formulation, as long as the effects of the present invention are not impaired. Examples of such additives include those listed in the Pharmaceutical Additives Dictionary 2007 (edited by the Japan Pharmaceutical Additives Association). Representative additives include the following: Carrier: For example, an aqueous solvent such as water or aqueous ethanol. Chelating agents: for example, ethylenediaminediacetic acid (EDDA), ethylenediaminetriacetic acid, ethylenediaminetetraacetic acid (EDTA), N-(2-hydroxyethyl)ethylenediaminetriacetic acid (HEDTA), diethylenetriaminepentaacetic acid (DTPA), etc. Bases: for example, octyldodecanol, titanium oxide, potassium bromide, plastibase, etc. pH adjusters: for example, hydrochloric acid, acetic acid, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, triethanolamine, diisopropanolamine, etc. Stabilizers: for example, sodium formaldehyde sulfoxylate (Rongalit), sodium hydrogen sulfite, sodium pyrosulfite, aluminum monostearate, glycerin monostearate, cyclodextrin, monoethanolamine, dibutylhydroxytoluene, etc. Isotonic agents: for example, sodium hydrogen sulfite, sodium sulfite, potassium chloride, calcium chloride, sodium chloride, magnesium chloride, potassium acetate, sodium acetate, sodium hydrogen carbonate, sodium carbonate, sodium thiosulfate, magnesium sulfate, glycerin, propylene glycol, etc. Thickeners other than component (A), component (B-1), and component (B-6): for example, cellulose-based polymer compounds (e.g., methyl cellulose, ethyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, sodium carboxymethyl cellulose, etc.), guar gum, hydroxypropyl guar gum, gum arabic, karaya gum, xanthan gum, agar, alginic acid and its salts (sodium salt, etc.), starch, chitin and its derivatives, chitosan and its derivatives, carrageenan, etc. Sugars: for example, glucose, cyclodextrin, etc. Sugar alcohols: for example, xylitol, sorbitol, mannitol, glycerin, etc. These may be in the d-, l- or dl-form. Anionic surfactants: for example, polyoxyethylene alkyl ether phosphates, polyoxyethylene alkyl ether sulfates, alkylbenzenesulfonates, alkyl sulfates, N-acyltaurine salts, etc. Amphoteric surfactants: for example, lauryl dimethylaminoacetic acid betaine. Preservatives other than component (B-4): for example, alkyldiaminoethylglycine hydrochloride, sodium benzoate, ethanol, sodium edetate, zinc chloride, chlorobutanol, sorbic acid, potassium sorbate, sodium dehydroacetate, methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, butyl parahydroxybenzoate, oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, benzalkonium chloride, Gloquil (trade name, manufactured by Rhodia), etc.

[0091] From the viewpoint of significantly achieving the effects of the present invention, the ophthalmic composition of this embodiment preferably does not contain at least one selected from the group consisting of petrolatum, benzalkonium chloride, potassium sorbate, sodium cromoglycate, phenylephrine hydrochloride, pranoprofen, diphenhydramine and its salts, ketotifen and its salts, and parahydroxybenzoic acid esters (parabens). Furthermore, from the viewpoint of significantly achieving the effects of the present invention, the ophthalmic composition of this embodiment preferably does not contain epsilon-aminocaproic acid in an amount of 3 w / v% or more, based on the total amount of the ophthalmic composition, and more preferably does not contain epsilon-aminocaproic acid. Furthermore, from the viewpoint of significantly achieving the effects of the present invention, the ophthalmic composition of this embodiment preferably does not contain hydroxypropyl methylcellulose in an amount of 5 w / v% or more, based on the total amount of the ophthalmic composition. Furthermore, from the viewpoint of significantly achieving the effects of the present invention, the ophthalmic composition of this embodiment preferably does not contain glycerin in an amount of 0.2 w / v% or more, based on the total amount of the ophthalmic composition.

[0092] When the ophthalmic composition according to the present embodiment contains component (B-1), from the viewpoint of significantly achieving the effects of the present invention, it is preferable that the ophthalmic composition does not contain at least one selected from the group consisting of petrolatum, benzalkonium chloride, and potassium sorbate. When the ophthalmic composition according to the present embodiment contains component (B-1), from the viewpoint of significantly achieving the effects of the present invention, it is preferable that the ophthalmic composition does not contain 3 w / v% or more of epsilon-aminocaproic acid, based on the total amount of the ophthalmic composition, and more preferably does not contain epsilon-aminocaproic acid. When the ophthalmic composition according to the present embodiment contains component (B-1), from the viewpoint of significantly achieving the effects of the present invention, it is preferable that the ophthalmic composition does not contain 5 w / v% or more of hydroxypropyl methylcellulose, based on the total amount of the ophthalmic composition.

[0093] When the ophthalmic composition according to this embodiment contains the component (B-2), from the viewpoint of significantly achieving the effects of the present invention, it is preferable that the ophthalmic composition does not contain petrolatum. Furthermore, when the ophthalmic composition according to this embodiment contains the component (B-2), from the viewpoint of significantly achieving the effects of the present invention, it is preferable that the ophthalmic composition does not contain 5 w / v% or more (preferably 3 w / v% or more) of epsilon-aminocaproic acid based on the total amount of the ophthalmic composition, and more preferably does not contain epsilon-aminocaproic acid.

[0094] When the ophthalmic composition according to this embodiment contains the component (B-3), from the viewpoint of significantly achieving the effects of the present invention, it is preferable that the ophthalmic composition does not contain at least one selected from the group consisting of sodium cromogrochate and phenylephrine hydrochloride. When the ophthalmic composition according to this embodiment contains the component (B-3), from the viewpoint of significantly achieving the effects of the present invention, it is preferable that the ophthalmic composition does not contain 5 w / v% or more (preferably 3 w / v% or more) of epsilon-aminocaproic acid based on the total amount of the ophthalmic composition, and more preferably does not contain epsilon-aminocaproic acid.

[0095] When the ophthalmic composition according to this embodiment contains the component (B-4), from the viewpoint of significantly achieving the effects of the present invention, it is preferable that the ophthalmic composition does not contain at least one selected from the group consisting of sodium cromogrochate, benzalkonium chloride, and potassium sorbate. When the ophthalmic composition according to this embodiment contains the component (B-4), from the viewpoint of significantly achieving the effects of the present invention, it is preferable that the ophthalmic composition does not contain 3 w / v % or more of epsilon-aminocaproic acid, based on the total amount of the ophthalmic composition, and more preferably does not contain epsilon-aminocaproic acid.

[0096] When the ophthalmic composition according to this embodiment contains the component (B-5), it is preferable that it does not contain at least one selected from the group consisting of petrolatum and potassium sorbate, from the viewpoint of being able to significantly exhibit the effects of the present invention. When the ophthalmic composition according to this embodiment contains the component (B-5), it is preferable that it does not contain 3 w / v % or more of epsilon-aminocaproic acid, based on the total amount of the ophthalmic composition, from the viewpoint of being able to significantly exhibit the effects of the present invention, and it is more preferable that it does not contain epsilon-aminocaproic acid.

[0097] When the ophthalmic composition according to this embodiment contains the component (B-6), it is preferable that it does not contain benzalkonium chloride, from the viewpoint of being able to significantly exhibit the effects of the present invention.

[0098] The ophthalmic composition according to this embodiment may be an aqueous composition (mainly containing an aqueous or hydrophilic base or carrier) or an oil-based composition (mainly containing an oil-based or hydrophobic base or carrier). When the ophthalmic composition is an aqueous composition, the water content is, for example, preferably 50% by weight or more, more preferably 75% by weight or more, even more preferably 80% by weight or more, even more preferably 85% by weight or more, and particularly preferably 90% by weight or more, based on the total weight of the ophthalmic composition. When the ophthalmic composition is an aqueous composition, the water content is, for example, preferably less than 100% by weight, more preferably 99.5% by weight or less, even more preferably 99.2% by weight or less, even more preferably 99.0% by weight or less, particularly preferably 97.0% by weight or less, and most preferably 96.5% by weight or less, based on the total weight of the ophthalmic composition. When the ophthalmic composition is an oily composition, the water content is, for example, preferably less than 50% by weight, more preferably 30% by weight or less, and even more preferably 20% by weight or less, based on the total weight of the ophthalmic composition. The ophthalmic composition according to this embodiment is preferably an aqueous composition.

[0099] The water used in the ophthalmic composition according to this embodiment may be any water that is medicamentally, pharmacologically (pharmaceutical), or physiologically acceptable. Examples of such water include distilled water, tap water, purified water, sterile purified water, water for injection, and distilled water for injection. These definitions are based on the Japanese Pharmacopoeia, 17th Edition.

[0100] The ophthalmic composition according to the present embodiment can be prepared, for example, by adding and mixing component (A) and, if necessary, other components to obtain a desired content. Specifically, the composition can be prepared, for example, by dissolving or suspending the components in purified water, adjusting the pH and osmotic pressure to a predetermined value, and sterilizing the mixture by filtration or the like.

[0101] The ophthalmic composition according to the present embodiment can be in various dosage forms depending on the purpose, such as a liquid, a gel, a semi-solid (ointment, etc.), etc. Among these, a liquid is preferred, and an aqueous liquid is more preferred.

[0102] The ophthalmic composition according to this embodiment can be used, for example, as eye drops (also referred to as eye drops or eye drops; eye drops include artificial tears and eye drops that can be applied to the eyes while wearing contact lenses), eyewash (also referred to as eyewash or eyewash; eyewashes include eyewashes that can be applied to the eyes while wearing contact lenses), or a contact lens composition (contact lens wetting solution, contact lens care composition (contact lens disinfectant, contact lens preservative, contact lens cleaner, contact lens cleaning and preservative), contact lens wetting solution that can be used both as a contact lens wetting solution and as an eye drop while wearing contact lenses, etc.). Suitable examples of the ophthalmic composition according to this embodiment include eye drops, eyewash, and contact lens compositions, more suitable examples include eye drops that can be applied to the eyes while wearing contact lenses, eyewashes that can be applied to the eyes while wearing contact lenses, contact lens wetting solution, and contact lens wetting solution, and even more suitable examples include eye drops that can be applied to the eyes while wearing contact lenses. The term "contact lenses" includes hard contact lenses and soft contact lenses (including both ionic and non-ionic contact lenses, and both silicone hydrogel contact lenses and non-silicone hydrogel contact lenses).

[0103] When the ophthalmic composition according to this embodiment is in the form of eye drops, the effects of the present invention can be more significantly exhibited, and therefore the ophthalmic composition is preferably an eye drop that can be instilled while wearing contact lenses, and more preferably an eye drop that can be instilled while wearing soft contact lenses (eye drops for soft contact lenses). When the ophthalmic composition according to this embodiment is in the form of eye drops, the dosage and administration method are not particularly limited as long as they are effective and have few side effects. For example, for adults (15 years of age or older) and children aged 7 years of age or older, 1 to 2 drops at a time are instilled 2 to 4 times a day, or 4 times a day, or 1 to 2 drops, 1 to 3 drops, or 2 to 3 drops at a time are instilled 5 to 6 times a day.

[0104] The ophthalmic composition according to this embodiment is preferably an artificial tear, since this allows the effects of the present invention to be more pronounced. When the ophthalmic composition according to this embodiment is an artificial tear, it is preferable that the ophthalmic composition does not contain any of an anti-inflammatory agent, an antiallergic agent, an antihistamine, a steroid, a decongestant, an eye muscle regulating agent, a vitamin, an astringent, sulfamethoxazole, sulfisoxazole, or sulfisomidine.

[0105] The ophthalmic composition according to this embodiment is provided in any container. The container for containing the ophthalmic composition according to this embodiment is not particularly limited and may be made of, for example, glass or plastic. Plastic is preferred. Examples of plastic include polyethylene terephthalate, polyarylate, polyethylene naphthalate, polycarbonate, polyethylene, polypropylene, polyimide, copolymers of monomers constituting these, and mixtures of two or more of these. Polypropylene, polyethylene, and polyethylene terephthalate are preferred, and polyethylene terephthalate is more preferred. Furthermore, the container for containing the ophthalmic composition according to this embodiment may be a transparent container that allows the interior of the container to be seen, or an opaque container that makes it difficult to see the interior of the container. A transparent container is preferred. Here, the term "transparent container" includes both colorless transparent containers and colored transparent containers.

[0106] 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, for example, glass or plastic. Plastic is preferred. Examples of plastic include polybutylene terephthalate, polyethylene, polypropylene, polyethylene naphthalate, copolymers of monomers constituting these, and mixtures of two or more of these. From the viewpoint of further enhancing the effects of the present invention, polypropylene, polyethylene, polyethylene terephthalate, and polyethylene naphthalate are preferred as the material of the nozzle, with polyethylene being more preferred.

[0107] The container for holding the ophthalmic composition of this embodiment may be a multi-dose type that holds an amount for multiple uses, or a unit-dose type that holds an amount for a single use, but it is preferable that it be a multi-dose type as this allows the effects of the present invention to be more pronounced.

[0108] 2. Method for imparting an effect of reducing friction in the eye to an ophthalmic composition The ophthalmic composition according to this embodiment can reduce friction in the eye by incorporating at least one selected from the group consisting of chondroitin sulfate and its salts at 0.7 w / v% or more, based on the total amount of the ophthalmic composition. Accordingly, one embodiment of the present invention provides a method for imparting an ophthalmic composition with the effect of reducing friction in the eye, comprising incorporating at least one selected from the group consisting of (A) chondroitin sulfate and its salts at 0.7 w / v% or more, based on the total amount of the ophthalmic composition. Another embodiment of the present invention provides an ophthalmic friction-reducing agent comprising an ophthalmic composition containing at least one selected from the group consisting of (A) chondroitin sulfate and its salts, the ophthalmic composition comprising at least 0.7 w / v% of the component (A) based on the total amount of the ophthalmic composition. Another embodiment of the present invention provides a method for reducing friction in the eye, using an ophthalmic composition containing at least one selected from the group consisting of (A) chondroitin sulfate and its salts, the ophthalmic composition comprising at least 0.7 w / v% of the component (A) based on the total amount of the ophthalmic composition. Furthermore, as one embodiment of the present invention, there is provided the use of one or more members selected from the group consisting of (A) chondroitin sulfate and salts thereof in an amount of 0.7 w / v% or more, based on the total amount of the ophthalmic composition, for the manufacture of an ophthalmic composition for reducing friction in the eye.

[0109] In this embodiment, the type and content of component (A), the type and content of other components, the formulation and use of the ophthalmic composition, etc. are as described in [1. Ophthalmic Composition]. [Example]

[0110] The present invention will be specifically explained below based on test examples, but the present invention is not limited to these.

[0111] [Test Example 1: Friction Evaluation (1)] Ophthalmic compositions (eye drops; 100 mL) of each of the Examples and Comparative Examples shown in Table 1 were prepared by a conventional method. The units of each component in Table 1 are w / v %. A soft contact lens (product name: Proclear 1day (omafilcon A), soft contact lens classification according to the U.S. Food and Drug Administration (FDA): Group II, manufactured by CooperVision) was rinsed with saline (Otsuka saline), excess liquid on the surface was wiped off, and then the lens was immersed in each of the prepared ophthalmic compositions for approximately 16 hours. The soft contact lens was then attached to the contact of a friction tester (Tribomaster TL201Ts, manufactured by Trinity Labs). Meanwhile, artificial leather was attached to the moving table of the friction tester to cover the entire surface of the moving table, and 4 mL of the test formulation was spread on the artificial leather so that it covered the entire surface where the contacts could move. Next, a 20 g weight was attached to the measurement unit. The contacts to which the soft contact lenses had been attached were attached to the measurement unit, and measurements were performed 1,000 times per second for 50 seconds. The average value of the friction coefficients obtained from the measurement results 25 to 35 seconds after the start of measurement was calculated and used as the friction coefficient (μk) of each ophthalmic composition. The friction coefficient reduction rates of the other formulation examples, that is, Comparative Example 1-2 and Examples 1-1 to 1-3, relative to the corresponding comparative example (Comparative Example 1-1) were calculated according to the following formula 1. The results are shown in Table 1 and FIG. [Equation 1] Friction coefficient reduction rate (%) = {(friction coefficient of corresponding comparative example - friction coefficient of each formulation example) / friction coefficient of corresponding comparative example} × 100 The sodium chondroitin sulfate used was non-prescription sodium chondroitin sulfate for eye drops and injections (manufactured by Maruha Nichiro Foods Co., Ltd.).

[0112] [Table 1]

[0113] Compared with Comparative Example 1-2 containing 0.5 w / v% sodium chondroitin sulfate, Examples 1-1 and 1-2 containing 1 w / v% or 3 w / v% sodium chondroitin sulfate unexpectedly showed a higher friction coefficient reduction rate, and it was confirmed that the friction-reducing effect was significantly improved.Furthermore, Example 1-3 containing 0.1 w / v% sodium hyaluronate in addition to 3 w / v% sodium chondroitin sulfate showed a further higher friction coefficient reduction rate, and it was confirmed that the friction-reducing effect was also improved.

[0114] [Test Example 2: Friction Evaluation (2)] Ophthalmic compositions (eye drops; 100 mL) of each Example and Comparative Example shown in Table 2 were prepared by a conventional method. The units of each component in Table 2 are w / v %. For each prepared ophthalmic composition, friction evaluation was performed in the same manner as in Test Example 1, except that Comparative Example 2-1 was used as the corresponding comparative example. The results are shown in Table 2. The sodium chondroitin sulfate used was non-prescription sodium chondroitin sulfate for eye drops and injections (manufactured by Maruha Nichiro Foods Co., Ltd.).

[0115] [Table 2]

[0116] Compared to Comparative Example 2-1, which did not contain sodium chondroitin sulfate, Example 2-1, which contained 3 w / v% sodium chondroitin sulfate and 0.1 w / v% sesame oil, was confirmed to have a significantly increased friction coefficient reduction rate.

[0117] [Test Example 3: Usability Evaluation (1)] Ophthalmic compositions (eye drops; 100 mL) of each of the Examples and Comparative Examples shown in Table 3 were prepared by a conventional method. The units of each component in Table 3 are w / v %. Each prepared ophthalmic composition was aseptically filled into a polyethylene terephthalate eye dropper container (internal volume 14.2 mL) at 13 mL. After filling, a polyethylene nozzle was attached to the eye dropper container, and each ophthalmic composition was instilled into both eyes of 12 subjects (9 with no eye contact and 3 with soft contact lenses). Immediately after instillation, 1) ease of blinking and 2) moisturizing sensation were evaluated to determine which ophthalmic composition was more noticeable when instilled. The sodium chondroitin sulfate used was non-prescription sodium chondroitin sulfate for eye drops and injections (manufactured by Maruha Nichiro Foods Co., Ltd.).

[0118] [Table 3]

[0119] [Table 4]

[0120] Among all subjects, the majority of subjects felt that blinking was easier and that their eyes felt more moisturized when Example 3-1 containing 3 w / v% sodium chondroitin sulfate was instilled.Furthermore, among soft contact lens wearers only, the percentage of subjects who felt that blinking was easier and that their eyes felt more moisturized when Example 3-1 was instilled was significantly higher (Table 4).

[0121] [Test Example 4: Friction Evaluation (3)] Ophthalmic compositions (eye drops; 100 mL) of each Example and Comparative Example shown in Table 5 were prepared by a conventional method. The units of each component in Table 5 are w / v %. The unit of retinol palmitate is IU / 100 mL. For each prepared ophthalmic composition, friction was evaluated in the same manner as in Test Example 1, except that Comparative Example 4-1 was used as the corresponding comparative example. The results are shown in Table 5. The sodium chondroitin sulfate used was non-prescription sodium chondroitin sulfate for eye drops and injections (manufactured by Maruha Nichiro Foods Co., Ltd.).

[0122] [Table 5]

[0123] It was confirmed that the friction coefficient reduction rate significantly increased by including sodium chondroitin sulfate, chlorhexidine gluconate, polyoxyethylene (196) polyoxypropylene (67) glycol, retinol palmitate, or polyvinylpyrrolidone K90.

[0124] [Test Example 5: Friction Evaluation (4)] Ophthalmic compositions (eye drops; 100 mL) of each Example and Comparative Example shown in Table 6 were prepared by a conventional method. The unit of each component in Table 6 is w / v %. For each prepared ophthalmic composition, friction evaluation was performed in the same manner as in Test Example 1, except that Comparative Example 5-1 was used as the corresponding comparative example. The results are shown in Table 6. The sodium chondroitin sulfate used was non-standard sodium chondroitin sulfate (Seikagaku Corporation, weight-average molecular weight approximately 20,000), and the sodium hyaluronate used was one that conformed to the standards for purified sodium hyaluronate in the 17th edition of the Japanese Pharmacopoeia.

[0125] [Table 6]

[0126] It was confirmed that the inclusion of 0.001 w / v% and 0.01 w / v% sodium hyaluronate or poloxamer 407 in addition to 3 w / v% sodium chondroitin sulfate increased the friction coefficient reduction rate and improved the friction reduction effect.

[0127] [Test Example 6: Friction Evaluation (5)] Ophthalmic compositions (eye drops; 100 mL) of each Example and Comparative Example shown in Table 7 were prepared by a conventional method. The units of each component in Table 7 are w / v % unless otherwise specified in the table. For each prepared ophthalmic composition, friction evaluation was performed in the same manner as in Test Example 1, except that Example 6-1 was used as the corresponding Comparative Example. The results are shown in Table 7. The sodium chondroitin sulfate used was non-standard sodium chondroitin sulfate (manufactured by Seikagaku Corporation, weight-average molecular weight: approximately 20,000).

[0128] [Table 7]

[0129] It was confirmed that the inclusion of sesame oil, retinol palmitate, or tocopherol acetate in addition to 3 w / v% sodium chondroitin sulfate increased the friction coefficient reduction rate and improved the friction reduction effect.

[0130] [Test Example 7: Evaluation of Usability (2)] The ophthalmic compositions (eye drops; 100 mL) of each of the Examples and Comparative Examples shown in Table 8 were prepared by a conventional method. The units of each component in Table 8 are w / v % unless otherwise specified in the table. Each prepared ophthalmic composition was aseptically filled into a polyethylene terephthalate eye dropper container (internal volume: 14.2 mL) at 13 mL. After filling, a polyethylene nozzle was attached to the eye dropper container, and each ophthalmic composition was instilled into both eyes of four soft contact lens wearers. Immediately after instillation, the subjects were evaluated to determine which ophthalmic composition provided the greatest moisturizing sensation. The sodium chondroitin sulfate used was non-standard sodium chondroitin sulfate (manufactured by Seikagaku Corporation, weight-average molecular weight: approximately 20,000).

[0131] [Table 8]

[0132] No person felt that Comparative Example 7-1 was more moisturizing, 3 people felt that Example 7-1 was more moisturizing, and 1 person felt that they were equally moisturizing.

[0133] [Test Example 8: Usability Evaluation (3)] Ophthalmic compositions (eye drops; 100 mL) of each of the Examples and Comparative Examples shown in Table 9 were prepared by a conventional method. The unit of each component in Table 9 is w / v %. Each prepared ophthalmic composition was aseptically filled into a polyethylene terephthalate eye dropper container (internal volume: 14.2 mL) at 13 mL. After filling, a polyethylene nozzle was attached to the eye dropper container, and four soft contact lens wearers instilled each ophthalmic composition into both eyes. Immediately after instillation, each ophthalmic composition was evaluated for ease of blinking and moisturizing sensation using the visual analog scale (VAS). Specifically, subjects were asked to mark the area of ​​a subjective symptom survey sheet with a 100 mm line drawn on it, with 0 mm representing "very difficult" and 100 mm representing "very easy," and 0 mm representing "none" and 100 mm representing "very present" for moisturizing sensation. The length (mm) of each line was measured as a subjective symptom score. The scores of the four subjects were then averaged. Using this VAS value, the VAS improvement rate (%) of each Example relative to the comparative example was calculated using the following formula 2: The results are shown in Table 9. Here, the comparative example serving as the reference is comparative example 8-1. [Formula 2] VAS improvement rate (%) = {(VAS value of Example - VAS value of Reference Comparative Example) / VAS value of Reference Comparative Example} × 100 The sodium chondroitin sulfate used was non-standard sodium chondroitin sulfate (Seikagaku Corporation, weight-average molecular weight approximately 20,000), and the sodium hyaluronate used was one that conformed to the standards for purified sodium hyaluronate in the 17th edition of the Japanese Pharmacopoeia.

[0134] [Table 9]

[0135] The results in Table 9 confirm that when Example 8-1 was applied to the eyes, blinking became easier and the feeling of moisturization was stronger than when Comparative Example 8-1 was applied to the eyes.

[0136] [Formulation example] Formulation examples are shown in Tables 10 to 12 below. The units of each ingredient in Tables 10 to 12 are all w / v % unless otherwise specified in the tables. Formulation Examples 1 to 17 are all eye drops. 10 mL of each formulation example was filled into a polyethylene terephthalate container and a polyethylene nozzle was attached, resulting in Formulation Examples 1' to 17'. 10 mL of each formulation example was filled into a polyethylene terephthalate container and a polybutylene terephthalate nozzle was attached, resulting in Formulation Examples 1" to 17". The eye drops of Formulation Examples 1 to 17 can be used as eye drops that can be applied while wearing hard contact lenses, while wearing soft contact lenses, or while not wearing contact lenses.

[0137] [Table 10]

[0138] [Table 11]

[0139] [Table 12]

Claims

1. (A) at least one selected from the group consisting of chondroitin sulfate and salts thereof; (B) An ophthalmic composition comprising (B-1) at least one selected from the group consisting of hyaluronic acid, aspartic acid, aminoethylsulfonic acid, and salts thereof, (B-2) at least one selected from the group consisting of sesame oil and castor oil, (B-4) at least one selected from the group consisting of chlorhexidine, polyhexanide, and salts thereof, and (B-5) at least one selected from the group consisting of vitamin E, wherein the content of component (A) is 0.7 to 3 w / v % based on the total amount of the ophthalmic composition.

2. 2. The ophthalmic composition according to claim 1, further comprising (B) at least one selected from the group consisting of (B-3) a nonionic surfactant and (B-6) a vinyl polymer compound.

3. 3. The ophthalmic composition according to claim 2, wherein the component (B-3) is at least one selected from the group consisting of polyoxyethylene-polyoxypropylene glycol, polyoxyethylene hydrogenated castor oil, and polyoxyethylene sorbitan fatty acid esters, and the component (B-6) is at least one selected from the group consisting of polyvinylpyrrolidone and polyvinyl alcohol.

4. The ophthalmic composition according to any one of claims 1 to 3, wherein the content of component (B) is 0.0000001 w / v % or more based on the total amount of the ophthalmic composition.

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

6. The ophthalmic composition comprises: (A) 0.7 to 3 w / v % of at least one selected from the group consisting of chondroitin sulfate and salts thereof based on the total amount of the ophthalmic composition; (B) A method for imparting an effect of reducing friction in the eye to the ophthalmic composition, the method comprising blending (B-1) at least one selected from the group consisting of hyaluronic acid, aspartic acid, aminoethylsulfonic acid, and salts thereof, (B-2) at least one selected from the group consisting of sesame oil and castor oil, (B-4) at least one selected from the group consisting of chlorhexidine, polyhexanide, and salts thereof, and (B-5) at least one selected from the group consisting of vitamin E.

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