Ophthalmic composition and method for imparting friction reduction action to the same

Abstract

To provide an ophthalmic composition for reducing friction in an eye part.SOLUTION: An ophthalmic composition for contact lenses contains polyvinyl pyrrolidone with a K value of 40 or more (A), trometamol (B), and at least one selected from the group consisting of chondroitin sulfate, hyaluronic acid and salts thereof (C), with the content of the component (A) of 0.003-0.3 w / v%, and a pH of 6.5-7.5, excluding the following compositions (i) and (ii): (i) an ophthalmologic composition for soft contact lenses comprising antihistamine, glycyrrhizinic acid and / or a salt thereof, chondroitin sulfate and / or a salt thereof, and 0.5 w / v% or more of polyvinyl pyrrolidone, with a pH of 5.5-6.8; and (ii) a composition for contact lens cleaning comprising (A) a polyvinyl water-soluble polymer compound and (B) a compound selected from mucopolysaccharide, mucopolysaccharide salt, polyphosphoric acid and polyphosphate).SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to ophthalmic compositions and methods for imparting friction-reducing properties thereto. [Background technology]

[0002] Polyvinylpyrrolidone is used in the field of ophthalmic compositions, for example, as a solubilizing agent (Patent Document 1).

[0003] In the eye, friction occurs between the eyelids, cornea, and conjunctiva when movements such as blinking are applied, and this is said to be one of the causes of abnormalities in the cornea and conjunctiva, tear film, and 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 contact lenses. Methods for reducing friction in the eye have not yet been thoroughly investigated. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Publication No. 1-294620 Summary of the Invention [Problem to be solved by the invention]

[0005] An object of the present invention is to provide an ophthalmic composition that reduces friction in the eye. [Means for solving the problem]

[0006] As a result of extensive research to achieve the above object, the present inventors have unexpectedly discovered that by selecting, as an ophthalmic composition component, polyvinylpyrrolidone (A) having a K value of 40 or more from among polyvinylpyrrolidones, and combining this with at least one member (B) selected from the group consisting of biguanide fungicides and trometamol, and at least one member (C) selected from the group consisting of amino acids and thickeners, the resulting ophthalmic composition can significantly reduce friction on the eye, leading to the completion of the present invention.

[0007] That is, the present invention provides the following [1] to [7]. [1] An ophthalmic composition comprising (A) polyvinylpyrrolidone having a K value of 40 or more, (B) at least one selected from the group consisting of biguanide fungicides and trometamol, and (C) at least one selected from the group consisting of amino acids and thickeners. [2] The ophthalmic composition according to [1], wherein the content of the component (A) is 0.001 to 10 w / v %. [3] The ophthalmic composition according to [1] or [2], wherein the component (A) is polyvinylpyrrolidone K90. [4] The ophthalmic composition according to any one of [1] to [3], wherein the component (B) is a biguanide fungicide. [5] The ophthalmic composition according to any one of [1] to [4], wherein the component (C) is at least one selected from the group consisting of aspartic acid, aminoethylsulfonic acid, mucopolysaccharides, cellulose derivatives, and salts thereof. [6] The ophthalmic composition according to any one of [1] to [5], further comprising at least one (D) selected from the group consisting of nonionic surfactants, edetic acid and its salts, inorganic salts, and terpenoids. [7] A method for imparting a friction-reducing effect to an ophthalmic composition, comprising incorporating into the ophthalmic composition (A) polyvinylpyrrolidone having a K value of 40 or more, (B) at least one selected from the group consisting of biguanide fungicides and trometamol, and (C) at least one selected from the group consisting of amino acids and thickeners. [Effects of the Invention]

[0008] The ophthalmic composition of the present invention contains polyvinylpyrrolidone (A) having a K value of 40 or more, at least one selected from the group consisting of biguanide fungicides and trometamol (B), and at least one selected from the group consisting of amino acids and thickeners (C), thereby reducing friction in the eye. DETAILED DESCRIPTION OF THE INVENTION

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

[0010] In this specification, the unit of content, "w / v%", indicates the ratio of mass to volume, and is synonymous with "g / 100 mL". In this specification, unless otherwise specified, the abbreviation "POE" means polyoxyethylene. In this specification, unless otherwise specified, the abbreviation "POP" means polyoxypropylene.

[0011] The ophthalmic composition according to this embodiment contains (A) polyvinylpyrrolidone having a K value of 40 or more, (B) at least one selected from the group consisting of biguanide fungicides and trometamol, and (C) at least one selected from the group consisting of amino acids and thickeners. Each of these components will be described below.

[0012] <Component (A)> The polyvinylpyrrolidone (A) having a K value of 40 or more refers to a nonionic water-soluble polymer having a viscosity characteristic value (K value) of 40 or more, calculated by applying the relative viscosity value (25°C) measured with a capillary viscometer to the following formula (1):

[0013] 〔formula〕 K=(1.5logη rel -1) / (0.15+0.003c)+[300clogη rel+(c+1.5clogη rel ) 2 ] 1 / 2 / (0.15c+0.003c 2 ) …(1) η rel : Relative viscosity of aqueous polyvinylpyrrolidone solutions to water c: Polyvinylpyrrolidone concentration (%) in the aqueous polyvinylpyrrolidone solution

[0014] Examples of polyvinylpyrrolidone (A) having a K value of 40 or more include polyvinylpyrrolidone K40, polyvinylpyrrolidone K50, polyvinylpyrrolidone K60, polyvinylpyrrolidone K80, polyvinylpyrrolidone K85, polyvinylpyrrolidone K90, and polyvinylpyrrolidone K120.

[0015] Among these, from the viewpoint of more significantly achieving the effects of the present invention, polyvinylpyrrolidone having a K value of 50 or more is preferred, polyvinylpyrrolidone having a K value of 70 or more is more preferred, polyvinylpyrrolidone having a K value of 90 or more is even more preferred, and polyvinylpyrrolidone having a K value of 90 to 120 is even more preferred. Of these, polyvinylpyrrolidone K90 is particularly preferably used. Here, the K value is 90 to 108% of the designated K value in accordance with the description of the K value in the Japanese Pharmacopoeia, Sixteenth Edition, for "Povidone." Therefore, for example, "K90" refers to a viscosity characteristic value (K value) calculated by applying the above formula (1) in the range of 81.0 to 97.2.

[0016] The polyvinylpyrrolidone K90 may be synthesized by a known method, or commercially available products such as Eiftact K-90 (manufactured by Dai-ichi Kogyo Seiyaku Co., Ltd.), Kollidon K90 (manufactured by BASF Japan Ltd.), Plasdone K90 (manufactured by ISP Japan Ltd.), and Povidone K90 (manufactured by DSP Gokyo Food & Chemical Co., Ltd.) may be used. These may be used alone or in combination of two or more.

[0017] The content of the component (A) is not particularly limited, but is preferably 0.001 to 10 w / v%, more preferably 0.005 to 5.0 w / v%, even more preferably 0.01 to 3.0 w / v%, and particularly preferably 0.03 to 1.0 w / v%, based on the total amount of the ophthalmic composition according to this embodiment. The content of the component (A) is suitable from the viewpoint of more significantly achieving the effects of the present invention. Also suitable is a content of 0.001 to 0.5 w / v%, preferably 0.002 to 0.4 w / v%, even more preferably 0.003 to 0.3 w / v%, and particularly preferably 0.005 to 0.1 w / v%.

[0018] <(B) component> The ophthalmic composition according to this embodiment contains, in addition to the component (A) and the component (C) described below, at least one kind (B) selected from the group consisting of biguanide fungicides and trometamol.

[0019] <Biguanide fungicides> The biguanide fungicides are compounds having at least one biguanide group represented by the formula -NH-C(=NH)-NH-C(=NH)-NH- in their structural formula. They are known fungicides as monomers having at least one biguanide group, polymers composed of such monomers, and salt-form compounds thereof. They can be produced by known methods or are commercially available.

[0020] The biguanide fungicide used in this embodiment is not particularly limited as long as it is medicamentarily, pharmacologically (pharmaceutical), or physiologically acceptable, and examples thereof include compounds represented by the following general formulae (2), (3), (4), and (5). These compounds may be in the form of salts.

[0021] [ka]

[0022] In the above general formulas (2) and (3), n is an integer of 1 or more, preferably an integer of 1 to 500, more preferably an integer of 1 to 100, even more preferably an integer of 1 to 40, and particularly preferably an integer of 10 to 13.

[0023] Specific examples of biguanide disinfectants used in this embodiment include hexamethylene biguanide and its polymers (i.e., polyhexamethylene biguanide (abbreviated as PHMB), polyhexanide), chlorhexidine, alexidine, hexetidine, etc., and from the viewpoint of more significantly exhibiting the effects of the present invention, preferred examples include hexamethylene biguanide and its polymers, and more preferably polymers of hexamethylene biguanide.

[0024] The biguanide fungicide salts used in this embodiment are not particularly limited as long as they are pharmaceutically, pharmacologically (pharmaceutical), or physiologically acceptable. Examples of biguanide fungicide salts used in this embodiment include inorganic acid salts such as hydrochloric acid, hydrobromic acid, sulfuric acid, boric acid, phosphoric acid, and nitric acid; organic acid salts such as acetic acid, gluconic acid, maleic acid, ascorbic acid, stearic acid, tartaric acid, and citric acid; and sulfonates such as methanesulfonate, isethionate, benzenesulfonate, and p-toluenesulfonate. Inorganic acid salts are preferred, and hydrochloride is more preferred. Specific examples of salts of biguanide disinfectants include polyhexanide hydrochloride (polyhexamethylene biguanide hydrochloride), alexidine hydrochloride, and chlorhexidine gluconate, with polyhexanide hydrochloride and chlorhexidine gluconate being preferred, and polyhexanide hydrochloride being more preferred.

[0025] The content of the biguanide bactericide is not particularly limited, but is appropriately set depending on the type, the components used in combination, and the content, etc. The content of the biguanide bactericide is, for example, typically 0.0000001 to 0.1 w / v%, preferably 0.000001 to 0.01 w / v%, more preferably 0.00001 to 0.001 w / v%, even more preferably 0.00001 to 0.00015 w / v%, and particularly preferably 0.00002 to 0.0001 w / v%, based on the total amount of the ophthalmic composition according to this embodiment.

[0026] The content ratio of the biguanide fungicide relative to component (A) in the ophthalmic composition according to the embodiment of the present invention is not particularly limited and is set appropriately depending on the types of component (A) and biguanide antibacterial agent, 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 ratio of the biguanide fungicide relative to component (A) is, for example, preferably 0.000001 to 1 part by mass, more preferably 0.000005 to 0.5 parts by mass, even more preferably 0.00001 to 0.1 parts by mass, and even more preferably 0.00005 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 the present embodiment.

[0027] <Trometamol> The above trometamol has the formula: CH 11 It is a known compound represented by NO3, and may be synthesized by a known method or may be commercially available.

[0028] The content of trometamol in the ophthalmic composition of this embodiment is not particularly limited, but is appropriately determined depending on the type, the amount, and other factors of the components used in combination. For example, the trometamol content is preferably 0.001 to 20 w / v%, more preferably 0.005 to 10 w / v%, even more preferably 0.01 to 5 w / v%, even more preferably 0.05 to 1 w / v%, and particularly preferably 0.05 to 0.5 w / v%, based on the total amount of the ophthalmic composition of this embodiment. A trometamol content of 0.2 w / v% or less is also preferred.

[0029] The content ratio of trometamol relative to component (A) in the ophthalmic composition according to the embodiment of the present invention is not particularly limited and is set appropriately depending on the type of component (A), 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 ratio of trometamol relative to component (A) is, for example, preferably 0.005 to 500 parts by mass, more preferably 0.01 to 100 parts by mass, even more preferably 0.05 to 50 parts by mass, and even more preferably 0.1 to 20 parts by mass, of the total content of trometamol relative to 1 part by mass of the total content of component (A) contained in the ophthalmic composition according to the present embodiment.

[0030] These biguanide fungicides and trometamol of component (B) may be used alone or in any combination of two or more. Among component (B), from the viewpoint of friction reduction rate, biguanide fungicides are preferred, chlorhexidine gluconate and polyhexanide hydrochloride are more preferred, and polyhexanide hydrochloride is even more preferred. From another viewpoint, polyhexanide hydrochloride, chlorhexidine gluconate, and trometamol may be preferred.

[0031] The content of component (B) is, for example, based on the total amount of the ophthalmic composition of this embodiment, typically 0.0000001 to 20 w / v%, preferably 0.000001 to 5 w / v%, more preferably 0.00001 to 1 w / v%, and even more preferably 0.00002 to 0.5 w / v%.

[0032] The content ratio of component (B) to component (A) in the ophthalmic composition according to the embodiment of the present invention is not particularly limited and is set appropriately depending on the types of components (A) and (B), 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 ratio of component (B) to component (A) is, for example, preferably 0.000001 to 500 parts by mass, more preferably 0.000005 to 100 parts by mass, even more preferably 0.00001 to 50 parts by mass, and even more preferably 0.00005 to 20 parts by mass, of the total content of component (B) per 1 part by mass of the total content of component (A) contained in the ophthalmic composition according to the present embodiment.

[0033] <(C) component> The ophthalmic composition according to this embodiment contains, in addition to the above-mentioned component (A) and component (B), at least one kind (C) selected from the group consisting of amino acids and thickeners.

[0034] <Amino acids> The amino acids refer to compounds or derivatives thereof having an amino group and a carboxyl group or a sulfo group in the molecule. Specific examples include amino acids, mucopolysaccharides, their derivatives, and salts thereof. Salts of amino acids, mucopolysaccharides, and their derivatives include pharmaceutically, pharmacologically, or physiologically acceptable salts. Examples of salts of amino acids, mucopolysaccharides, and derivatives thereof include salts with organic acids [e.g., monocarboxylates (acetate, trifluoroacetate, butyrate, palmitate, stearate, etc.), polycarboxylates (fumarate, maleate, etc.), oxycarboxylates (lactate, tartrate, citrate, succinate, malonate, etc.), organic sulfonates (methanesulfonate, toluenesulfonate, etc.)], salts with inorganic acids (e.g., hydrochloride, sulfate, nitrate, hydrobromide, phosphate), salts with organic bases (e.g., salts with organic amines such as methylamine, triethylamine, triethanolamine, morpholine, piperazine, pyrrolidine, tripyridine, picoline, etc.), salts with inorganic bases [e.g., ammonium salts; salts with alkali metals (sodium, potassium, etc.), alkaline earth metals (calcium, magnesium, etc.), aluminum, etc.], and the like, and the salts may be selected appropriately depending on the compound. Among these, salts with inorganic bases are preferred, with alkali metal salts and alkaline earth metal salts being more preferred. Among amino acids, examples of amino acids and their salts include monoaminomonocarboxylic acids such as glycine, alanine, γ-aminobutyric acid, and γ-aminovaleric acid; monoaminodicarboxylic acids such as aspartic acid and glutamic acid and their salts; diaminomonocarboxylic acids such as arginine and lysine and their salts; and derivatives such as aminoethylsulfonic acid (taurine) and their salts. Amino acids and their salts may be in the L-, D-, or DL-form, and examples include potassium L-aspartate, magnesium L-aspartate, and an equal-part mixture of magnesium and potassium L-aspartate. Furthermore, examples of mucopolysaccharides and their salts include chondroitin sulfate, hyaluronic acid, alginic acid, and their salts.

[0035] Among these amino acids, L-aspartic acid, aminoethylsulfonic acid, mucopolysaccharides, and their salts are particularly preferred, with potassium L-aspartate, magnesium L-aspartate, an equal parts mixture of magnesium and potassium L-aspartate, aminoethylsulfonic acid, and mucopolysaccharides being more preferred, with mucopolysaccharides being even more preferred, sodium chondroitin sulfate and sodium hyaluronate being even more preferred, and sodium chondroitin sulfate being particularly preferred.From another perspective, L-aspartic acid, aminoethylsulfonic acid, chondroitin sulfate, hyaluronic acid, and their salts are preferred, with potassium L-aspartate, magnesium L-aspartate, an equal parts mixture of magnesium and potassium L-aspartate, aminoethylsulfonic acid, sodium chondroitin sulfate, and sodium hyaluronate being even more preferred, with potassium L-aspartate, aminoethylsulfonic acid, sodium chondroitin sulfate, and sodium hyaluronate being even more preferred.

[0036] The content of the amino acids is not particularly limited and is appropriately determined depending on the type of amino acid, the type and content of the (A) and (B) components used in combination, and the like. For example, the total content of amino acids is preferably 0.0001 to 10 w / v%, more preferably 0.0005 to 5 w / v%, even more preferably 0.001 to 4 w / v%, even more preferably 0.01 to 3 w / v%, and particularly preferably 0.1 to 2.5 w / v%, based on the total amount of the ophthalmic composition according to this embodiment. Furthermore, a content of 2 w / v% or less is also preferred. The content of the amino acids is suitable from the viewpoint of more significantly exhibiting the effects of the present invention.

[0037] When the amino acids are chondroitin sulfate and its salts, for example, based on the total amount of the ophthalmic composition of this embodiment, the total content of chondroitin sulfate and its salts is preferably 0.01 to 5 w / v%, more preferably 0.05 to 3 w / v%, and even more preferably 0.1 to 1 w / v%. When the amino acids are hyaluronic acid and its salts, for example, the total content of hyaluronic acid and its salts is preferably 0.001 to 0.5 w / v%, more preferably 0.01 to 0.3 w / v%, and even more preferably 0.05 to 0.1 w / v%, based on the total amount of the ophthalmic composition of this embodiment.

[0038] The content ratio of amino acids relative to component (A) in the ophthalmic composition according to the embodiment of the present invention is not particularly limited, and is set appropriately depending on the types of component (A) and amino acids, 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 ratio of amino acids relative to component (A) is, for example, preferably 0.00005 to 500 parts by mass, more preferably 0.0001 to 100 parts by mass, even more preferably 0.0005 to 50 parts by mass, and even more preferably 0.001 to 10 parts by mass, of the total content of amino acids relative to 1 part by mass of the total content of component (A) contained in the ophthalmic composition according to the present embodiment.

[0039] When the amino acids are chondroitin sulfate and its salts, the content ratio of chondroitin sulfate and its salts relative to component (A) is, from the viewpoint of more significantly achieving the effects of the present invention, preferably 0.01 to 500 parts by mass, more preferably 0.05 to 100 parts by mass, and even more preferably 0.1 to 50 parts by mass, of the total content of chondroitin sulfate and its salts relative to 1 part by mass of the total content of component (A) contained in the ophthalmic composition of this embodiment, for example. When the amino acids are hyaluronic acid and its salts, the content ratio of hyaluronic acid and its salts relative to component (A) is, from the viewpoint of more significantly exhibiting the effects of the present invention, preferably 0.001 to 500 parts by mass, more preferably 0.01 to 100 parts by mass, and even more preferably 0.1 to 50 parts by mass, of the total content of hyaluronic acid and its salts relative to 1 part by mass of the total content of component (A) in the ophthalmic composition of this embodiment, for example.

[0040] <Thickener> Examples of the thickener include polyvinyl alcohol (fully or partially saponified), polyvinylpyrrolidone (K25, K30), carboxyvinyl polymer, cellulose derivatives [methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose (hypromellose) (2208, 2906, 2910, etc.), carboxymethyl cellulose, carboxyethyl cellulose, nitrocellulose, or salts thereof, gum arabic, tragacanth, dextran (40, 70, etc.), etc., preferably polyvinyl alcohol (fully or partially saponified), polyvinylpyrrolidone (K25, K30), carboxyvinyl polymer, cellulose derivative, dextran (70), more preferably cellulose derivative, even more preferably hydroxyethyl cellulose, hydroxypropyl methylcellulose, even more preferably hydroxypropyl methylcellulose 2208, hydroxypropyl methylcellulose 2906, hydroxypropyl methylcellulose 2910, and particularly preferably hydroxypropyl methylcellulose 2906. These thickeners may be used alone or in any combination of two or more.

[0041] When the thickener is contained, the content thereof is appropriately set depending on the type of thickener, the types and contents of other contained components, etc. The content of the thickener is, for example, preferably 0.0001 to 5 w / v%, more preferably 0.001 to 3 w / v%, even more preferably 0.005 to 1.5 w / v%, and particularly preferably 0.01 to 1 w / v%, based on the total amount of the ophthalmic composition according to this embodiment.

[0042] The content ratio of the thickener relative to the component (A) in the ophthalmic composition according to the embodiment of the present invention is not particularly limited and is set appropriately depending on the types of component (A) and thickener, the types and contents of other blended components, the intended use and formulation of the ophthalmic composition, etc. From the viewpoint of more significantly exhibiting the effects of the present invention, the content ratio of the thickener relative to the component (A) is, for example, preferably 0.001 to 500 parts by mass, more preferably 0.005 to 100 parts by mass, even more preferably 0.01 to 50 parts by mass, and even more preferably 0.05 to 10 parts by mass, of the total content of the thickener relative to 1 part by mass of the total content of the component (A) contained in the ophthalmic composition according to the present embodiment.

[0043] When the thickener is contained, its content is appropriately set depending on the type of component (C), the types and contents of other components contained, etc. The content of component (C), for example, based on the total amount of the ophthalmic composition according to this embodiment, is preferably 0.0001 to 10 w / v%, more preferably 0.0005 to 5 w / v%, even more preferably 0.001 to 3 w / v%, even more preferably 0.01 to 2 w / v%, and particularly preferably 0.1 to 1 w / v%.

[0044] In the ophthalmic composition according to the embodiment of the present invention, the content ratio of the thickener relative to the component (A) is not particularly limited and is set appropriately depending on the types of the 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 more significantly exhibiting the effects of the present invention, the content ratio of the component (C) relative to the component (A) is, for example, preferably 0.00005 to 500 parts by mass, more preferably 0.0001 to 100 parts by mass, even more preferably 0.0005 to 50 parts by mass, and even more preferably 0.001 to 10 parts by mass, of the total content of the thickener relative to 1 part by mass of the total content of the component (A) contained in the ophthalmic composition according to the present embodiment.

[0045] <(D) component> In addition, from the viewpoint of more significantly achieving the effects of the present invention, it is preferable that the ophthalmic composition of this embodiment further contains at least one member (D) selected from the group consisting of nonionic surfactants, edetic acid and its salts, inorganic salts, and terpenoids.

[0046] <Nonionic surfactants> The nonionic surfactant is not particularly limited as long as it is medicamentarily, pharmacologically (pharmaceutical) or physiologically acceptable. Specific examples of the nonionic surfactant include POE (20) sorbitan monolaurate (polysorbate 20), POE (20) sorbitan monooleate (polysorbate 80), POE sorbitan monostearate (polysorbate 60), POE sorbitan tristearate (polysorbate 65) and other POE sorbitan fatty acid esters, POE hydrogenated castor oil 5, POE hydrogenated castor oil 10, POE hydrogenated castor oils such as POE hydrogenated castor oil 20, POE hydrogenated castor oil 40, POE hydrogenated castor oil 50, POE hydrogenated castor oil 60, POE hydrogenated castor oil 100, POE castor oil 3, POE castor oil 4, POE castor oil 6, POE castor oil 7, POE castor oil 10, POE castor oil 13.5, POE castor oil 17, POE castor oil 20, POE castor oil 25, POE castor oil 30, POE castor oil 35, PO POE castor oil such as E castor oil 50, polyethylene glycol monostearate (2 E.O.), polyethylene glycol monostearate (4 E.O.), polyethylene glycol monostearate (9 E.O.), polyethylene glycol monostearate (10 E.O.), polyethylene glycol monostearate (23 E.O.), polyethylene glycol monostearate (25 E.O.), polyethylene glycol monostearate (32 E.O.), polyethylene glycol monostearate (40 E.O.), polyoxyl 40 stearate, polyethylene glycol monostearate (45 E.O.), polyethylene glycol monostearate (55 E.O.), polyethylene glycol monostearate (75 E.O.), polyethylene glycol monostearate (140 E.O.).POE-POP block copolymers such as POE(196)POP(67) glycol (Poloxamer 407, Pluronic F127), POE(54)POP(39) glycol (Poloxamer 235), POE(160)POP(30) glycol (Poloxamer 188), POE(42)POP(67) glycol (Poloxamer 403), POE(120)POP(40) glycol (Poloxamer 237), and POE(200)POP(70) glycol; POE-POP block copolymer adducts of ethylenediamine such as poloxamine; POE alkyl ethers such as POE(9) lauryl ether; POE·POP alkyl ethers such as POE(20)POP(4) cetyl ether; and POE alkyl phenyl ethers such as POE(10) nonylphenyl ether. The numbers in parentheses indicate the number of moles added. .

[0047] It is more preferable that the ophthalmic composition according to this embodiment contains one or more nonionic surfactants having an HLB value of less than 10 in combination.

[0048] Examples of nonionic surfactants having an HLB value of less than 10 include POE hydrogenated castor oils having an average number of moles of ethylene oxide added of less than 20, such as POE hydrogenated castor oil 5 and POE hydrogenated castor oil 10; POE castor oils having an average number of moles of ethylene oxide added of less than 23, such as POE castor oil 3, POE castor oil 4, POE castor oil 6, POE castor oil 7, POE castor oil 10, POE castor oil 13.5, POE castor oil 17, and POE castor oil 20; polyethylene glycol monostearate (2E.O.); Examples include polyethylene glycol monostearate having an average number of added moles of ethylene oxide of less than 7, such as polyethylene glycol (4E.O.), and among these, from the viewpoint of more significantly exhibiting the effects of the present invention, preferred are POE hydrogenated castor oil having an average number of added moles of ethylene oxide of less than 20 and POE castor oil having an average number of added moles of ethylene oxide of less than 23, more preferred are POE castor oil having an average number of added moles of ethylene oxide of less than 23, and POE castor oil 3 and POE castor oil 10 are even more preferred.

[0049] When the nonionic surfactant is contained, its content is appropriately set depending on the type of nonionic surfactant used, the types and contents of other blended ingredients, the intended use of the ophthalmic composition, the formulation, the method of use, etc. For example, based on the total amount of the ophthalmic composition of this embodiment, the total content of the nonionic surfactant is preferably 0.001 to 3 w / v%, more preferably 0.005 to 2 w / v%, even more preferably 0.01 to 1 w / v%, and particularly preferably 0.05 to 1 w / v%.

[0050] <Edetic acid and its salts> The edetic acid (ethylenediaminetetraacetic acid, EDTA) has the formula: C 10 H 16 It is a known compound represented by N2O8, and can be synthesized by known methods or obtained as a commercial product. Examples of salts of edetic acid include alkali metal salts such as sodium edetate, disodium edetate, and tetrasodium edetate, and examples of hydrates include sodium edetate hydrates such as disodium edetate dihydrate. Among these, edetate disodium dihydrate is preferably used.

[0051] When at least one of the edetic acid and its salts is contained, the content thereof is appropriately set depending on the type of edetic acid and its salt, the type and content of other components contained, etc. The content of at least one of edetic acid and its salt is, for example, preferably 0.001 to 1 w / v%, more preferably 0.005 to 0.5 w / v%, and even more preferably 0.01 to 0.1 w / v%, based on the total amount of the ophthalmic composition according to this embodiment.

[0052] <Inorganic salts> Examples of the inorganic salts include sodium hydrogen sulfite, sodium sulfite, potassium chloride, calcium chloride, sodium chloride, magnesium chloride, sodium hydrogen carbonate, sodium carbonate, sodium thiosulfate, magnesium sulfate, etc. Among these, potassium chloride, calcium chloride, sodium chloride, sodium hydrogen carbonate, sodium carbonate, and magnesium sulfate are preferred, and potassium chloride and sodium chloride are more preferred.

[0053] When the inorganic salts are contained, the content thereof is appropriately set depending on the type of inorganic salt, the type and content of other contained components, etc. The content of inorganic salts 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 1 w / v%, based on the total amount of the ophthalmic composition according to this embodiment.

[0054] <Terpenoids> Examples of terpenoids include menthol (l-menthol, dl-menthol, etc.), menthone, camphor (d-camphor, dl-camphor, etc.), borneol (d-borneol, dl-borneol, etc.), geraniol, cineole, citral, linalool, anethole, limonene, eugenol, etc. These may be in the d-, l-, or dl-isomer, but from the viewpoint of more significantly exhibiting the effects of the present invention, it is preferable to use l-menthol, d-camphor, dl-camphor, d-borneol, dl-borneol, or geraniol. Among these, l-menthol, d-camphor, dl-camphor, and geraniol are preferred, and l-menthol is more preferred. The terpenoids can also be used in the form of being contained in essential oils, and preferred essential oils are peppermint oil, eucalyptus oil, bergamot oil, fennel oil, cinnamon oil, rose oil, etc. These terpenoids can also be used alone or in combination of two or more.

[0055] The content of the terpenoid is not particularly limited and is set appropriately depending on the type of terpenoid, the types and contents of other ingredients, etc. For example, the total content of the terpenoid is preferably 0.00001 to 0.3 w / v%, 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 0.02 w / v%, based on the total amount of the ophthalmic composition according to this embodiment. The content of the terpenoid is suitable from the viewpoint of more significantly exhibiting the effects of the present invention.

[0056] <Other optional ingredients> The ophthalmic composition according to this embodiment preferably further contains a buffer to further enhance the effects of the present invention. This allows the effects of the present invention to be more significantly exhibited. The buffer is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutical), or physiologically acceptable. Examples of such buffers include borate buffers, phosphate buffers, carbonate buffers, citrate buffers, acetate buffers, etc. These buffers may be used alone or in combination of two or more. Examples of borate buffers include boric acid or salts thereof (such as alkali metal borates and alkaline earth metal borates). Examples of phosphate buffers include phosphoric acid or salts thereof (such as alkali metal phosphates and alkaline earth metal phosphates). Examples of carbonate buffers include carbonic acid or salts thereof (such as alkali metal carbonates and alkaline earth metal carbonates). 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 its salts (such as alkali metal acetates and alkaline earth metal acetates). Hydrates of borates, phosphates, carbonates, citrates, or acetates may also be used as borate buffers, phosphate buffers, carbonate buffers, citrate buffers, or acetate 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 hydrogen phosphate, calcium dihydrogen phosphate, etc.); carbonate buffers include carbonic acid or salts thereof (sodium bicarbonate, sodium carbonate, ammonium carbonate, potassium carbonate, calcium carbonate, potassium bicarbonate, magnesium carbonate, etc.); citrate buffers include citric acid or salts thereof (sodium citrate, potassium citrate, calcium citrate, sodium dihydrogen citrate, disodium citrate, etc.); and acetate buffers include acetic acid or salts thereof (ammonium acetate, potassium acetate, calcium acetate, sodium acetate, etc.).Among these buffers, boric acid buffers (for example, a combination of boric acid and borax) and phosphate buffers (for example, a combination of disodium hydrogen phosphate and sodium dihydrogen phosphate) are preferred, with boric acid buffers being more preferred.

[0057] When the buffering agent is contained, its content is appropriately set depending on the type of buffering agent, the types and contents of other contained components, etc. The content of the buffering agent is, for example, preferably 0.01 to 10 w / v%, more preferably 0.05 to 5 w / v%, even more preferably 0.1 to 3 w / v%, and particularly preferably 0.5 to 2 w / v%, based on the total amount of the ophthalmic composition according to this embodiment.

[0058] The ophthalmic composition according to this embodiment may further contain a polyhydric alcohol in order to further enhance the effects of the present invention. Examples of polyhydric alcohols include polyethylene glycol (400, 4000, 6000, etc.), propylene glycol, glycerin, etc. As the polyhydric alcohol, in order to more significantly exhibit the effects of the present invention, propylene glycol, glycerin, and polyethylene glycol are preferred, and polyethylene glycol is more preferred. Furthermore, commercially available polyhydric alcohols can also be used. The polyhydric alcohols may be used alone or in combination of two or more.

[0059] The content of the polyhydric alcohol that can be used in the ophthalmic composition according to this embodiment is not particularly limited and is set appropriately depending on the type of polyhydric alcohol, 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 the polyhydric alcohol is, for example, preferably 0.01 to 5 w / v%, more preferably 0.05 to 2 w / v%, even more preferably 0.1 to 1 w / v%, and particularly preferably 0.1 to 0.5 w / v%, based on the total amount of the ophthalmic composition.

[0060] 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 is, for example, preferably 4.0 to 9.5, more preferably 5.0 to 9.0, and even more preferably 5.5 to 8.5.

[0061] The osmotic pressure ratio of the ophthalmic composition according to this embodiment is not particularly limited as long as it is within a range acceptable to the body. The osmotic pressure ratio of the ophthalmic composition is, for example, preferably 0.5 to 5.0, more preferably 0.6 to 3.0, even more preferably 0.7 to 2.0, and particularly preferably 0.9 to 1.55. The osmotic pressure can be adjusted using inorganic salts, polyhydric alcohols, sugar alcohols, sugars, or the like, 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 16th Edition of the Japanese Pharmacopoeia, and 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.

[0062] The viscosity of the ophthalmic composition according to this embodiment is not particularly limited as long as it is within a range acceptable to the living body. The viscosity at 25°C measured with a rotational viscometer (RE550 type viscometer, manufactured by Toki Sangyo Co., Ltd., rotor: 1°34' x R24) is, for example, preferably 1 to 1000 mPa s, more preferably 1 to 100 mPa s, and even more preferably 1 to 50 mPa s.

[0063] In addition, the ophthalmic composition according to this embodiment may contain various pharmacologically active or physiologically active ingredients in appropriate amounts in addition to the above-mentioned ingredients, as long as the effects of the present invention are not impaired. Such ingredients are not particularly limited, and examples thereof include active ingredients in various pharmaceuticals listed in the 2012 edition of the OTC Drug Manufacturing and Marketing Approval Standards (supervised by the Japan Society of Regulatory Science). Specifically, the following ingredients can be used in ophthalmic drugs: Antihistamines: for example, iproheptine, diphenhydramine, chlorpheniramine maleate, ketotifen fumarate, olopatadine hydrochloride, levocabastine hydrochloride, etc. Antiallergic agents: for example, sodium cromoglycate, tranilast, pemirolast potassium, ashitazanolast, 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. Anti-inflammatory agents: for example, glycyrrhetinic acid, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, pranoprofen, methyl salicylate, glycol salicylate, allantoin, tranexamic acid, ε-aminocaproic acid, berberine chloride, berberine sulfate, sodium azulene sulfonate, lysozyme, licorice, etc. Astringents: for example, zinc oxide, zinc lactate, zinc sulfate, etc. Vitamins: for example, flavin adenine dinucleotide sodium, cyanocobalamin, pyridoxine hydrochloride, panthenol, calcium pantothenate, sodium pantothenate, retinol acetate, retinol palmitate, tocopherol acetate, etc. Local anesthetics: e.g., lidocaine. Others: for example, sulfamethoxazole, sulfamethoxazole sodium, etc.

[0064] The ophthalmic composition according to the present embodiment may contain one or more additives selected in a suitable amount in accordance with the intended use or formulation, as long as the effects of the invention are not impaired. Examples of such additives include those listed in the Pharmaceutical Additives Dictionary 2016 (edited by the Japan Pharmaceutical Additives Association). Representative additives include the following: Carrier: For example, an aqueous carrier such as water or aqueous ethanol. Sugars: for example, glucose, cyclodextrin, dextrose, etc. Sugar alcohols: for example, xylitol, sorbitol, mannitol, etc. These may be in the d-, l- or dl-form. Stabilizers: for example, sodium formaldehyde sulfoxylate (Rongalit), tocopherol, sodium pyrosulfite, monoethanolamine, aluminum monostearate, glycerin monostearate, dibutylhydroxytoluene, sodium hydrogensulfite, sodium sulfite, etc. Anionic surfactants: for example, alkylbenzenesulfonates, alkyl sulfates, polyoxyethylene alkyl sulfates, α-sulfofatty acid ester salts, α-olefin sulfonic acid, etc. (B) Preservatives, disinfectants or antibacterial agents other than the ingredients: for example, zinc chloride, alkyldiaminoethylglycine hydrochloride, sodium benzoate, ethanol, benzalkonium chloride, benzethonium chloride, chlorobutanol, sorbic acid, potassium sorbate, sodium dehydroacetate, methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, butyl parahydroxybenzoate, oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, etc. pH adjusters: for example, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, sulfuric acid, phosphoric acid, polyphosphoric acid, propionic acid, oxalic acid, gluconic acid, fumaric acid, lactic acid, tartaric acid, malic acid, succinic acid, gluconolactone, ammonium acetate, etc. Oils: For example, vegetable oils such as sesame oil, castor oil, soybean oil, and olive oil; animal oils such as squalane; mineral oils such as liquid paraffin and Vaseline; and the like.

[0065] The ophthalmic composition according to this embodiment is prepared by adding the above-mentioned components (A) to (C) and, if necessary, other optional components to a carrier so as to obtain a desired content. As the carrier, medicamentarily, pharmacologically (pharmaceutical), or physiologically acceptable water may be used. Specific examples of such water include distilled water, tap water, purified water, sterilized purified water, water for injection, and distilled water for injection.

[0066] The ophthalmic composition according to this embodiment can then be prepared, for example, by dissolving or suspending these components in purified water, adjusting the pH and osmotic pressure ratio to a predetermined value, and sterilizing the solution by filtration sterilization or the like.

[0067] The ophthalmic composition of this embodiment has a water content of 85 w / v% or more, preferably 90 w / v% or more, more preferably 92 w / v% or more, even more preferably 94 w / v% or more, and particularly preferably 95 w / v% or more, relative to the total amount of the ophthalmic composition.

[0068] The ophthalmic composition according to the present embodiment can be in various formulation forms depending on the purpose. Examples of the formulation form include a liquid, a gel, a semi-solid (e.g., ointment), etc. The ophthalmic composition according to the present embodiment is preferably a liquid.

[0069] The ophthalmic composition according to the present embodiment is provided in any suitable container. 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. Plastic is preferred. Examples of plastic include polyethylene terephthalate, polyarylate, polyethylene naphthalate, polycarbonate, polyethylene, polypropylene, polyimide, copolymers of these monomers, and mixtures of two or more of these. Polyethylene terephthalate is preferred. The container for containing the ophthalmic composition according to the present embodiment may be a transparent container that allows the interior of the container to be viewed, or an opaque container that makes it difficult to view the interior of the container. A transparent container is preferred. Here, the term "transparent container" includes both colorless and colored transparent containers. The ophthalmic composition according to the present embodiment can be contained in, for example, a colored and transparent plastic container in a reusable multi-dose form. Alternatively, the composition can be contained in a unit-dose form.

[0070] The ophthalmic composition according to this embodiment can be used as a pharmaceutical or quasi-drug formulation, and includes so-called eye drops (including eye drops that can be applied while wearing contact lenses), eyewash (including eyewashes that can be used to wash eyes while wearing contact lenses), contact lens compositions [contact lens wetting solution, contact lens care compositions (contact lens disinfectants, contact lens preservatives, contact lens cleaners, contact lens cleaning and preservatives, contact lens disinfecting, cleaning, and storage solutions (multi-purpose solutions)), etc.], contact lens wetting solutions that can be used both as contact lens wetting solutions and as eye drops while wearing contact lenses, etc. Preferred examples of the present invention include eye drops, eyewashes, contact lens wetting solutions, and contact lens wetting solutions, and particularly preferred examples include eye drops, contact lens wetting solutions, and contact lens wetting solutions. When used as a contact lens composition, it can be applied to any contact lens, including hard contact lenses and soft contact lenses (including both ionic and non-ionic contact lenses, and including both silicone hydrogel contact lenses and non-silicone hydrogel contact lenses).

[0071] Furthermore, in this embodiment, friction occurring in the eye, such as when blinking, can be reduced regardless of whether the eye is naked or wearing contact lenses. However, the friction-reducing effect is even more pronounced when wearing contact lenses, due to friction occurring between the contact lens and the conjunctiva, between the contact lens and the cornea, etc. Therefore, the ophthalmic composition is preferably for contact lenses, and particularly preferably for soft contact lenses. Among soft contact lenses, colored contact lenses, whose surfaces are printed with colors or patterns, for example, experience greater friction on the contact lens surface than contact lenses other than colored contact lenses, and therefore an ophthalmic composition for colored contact lenses is particularly preferred. Furthermore, silicone hydrogel contact lenses, which generally tend to be harder than other soft contact lenses, have a greater impact on the ocular surface due to friction, and therefore an ophthalmic composition for silicone hydrogel contact lenses is particularly preferred.

[0072] (I) Friction reduction effect Furthermore, by using the ophthalmic composition according to this embodiment, it is possible to expect an effect of reducing friction in the eye.

[0073] (II) Cell activation effect Generally, the eye is exposed to a state of malnutrition due to factors such as a decrease in tear fluidity caused by wearing contact lenses and a decrease in tear quality due to aging, which can result in a decrease in the survival rate of corneal cells. However, when the ophthalmic composition of this embodiment is used, the survival rate of corneal cells is significantly increased (corneal cells are activated).

[0074] (III) Resistance to oxidative stress after hypoxia exposure Generally, when contact lenses are worn and the eye is placed in a hypoxic state, and then the contact lenses are removed, or when waking up from sleep, excess oxygen tends to cause oxidative stress on the cornea and conjunctiva, resulting in inflammation, corneal damage, and the like. However, by using the ophthalmic composition according to this embodiment, it is possible to reduce inflammation and corneal damage caused by oxidative stress after exposure to hypoxia. When inflammation occurs, IL-6 is released, so by measuring the expression level of the IL-6 gene, it is possible to measure the degree of inflammation caused by oxidative stress after exposure to hypoxia. Furthermore, mucins are important for maintaining the homeostasis of tears and the ocular surface, and it has been reported that oxidative stress reduces mucin expression on the corneal surface. The expression level of MUC1, a gene involved in mucin expression, can be used as an indicator to evaluate corneal damage caused by oxidative stress after hypoxia exposure. On the other hand, as damage to the cornea occurs due to oxidative stress after hypoxia exposure, various antioxidant factors are secreted to reduce oxidative stress. Resistance to oxidative stress after hypoxia exposure can be measured by measuring genes related to antioxidant factors, such as GSTp-1 (one of the genes related to the expression of antioxidant factors) and HMOX-1 (one of the genes related to the expression of antioxidant factors).

[0075] (IV) In order to more effectively exert the above-mentioned effects, it is preferable to exclude from the ophthalmic composition of this embodiment any combination of pranoprofen or a salt thereof and at least one compound selected from the group consisting of antiallergic agents, anti-inflammatory agents, and water-soluble vitamins. It is also preferable that the ophthalmic composition does not contain pranoprofen or a salt thereof, and it is particularly preferable that the ophthalmic composition does not contain pranoprofen.

[0076] Furthermore, from the viewpoint of more preferably exerting the above-mentioned effect, when the ophthalmic composition according to this embodiment is used as an eye drop, it is preferable to exclude amphoteric surfactants, in particular, amphoteric surfactants represented by the following general formula (6), from the ophthalmic composition according to this embodiment.

[0077] [ka]

[0078] In the above general formula (6), R 1 is R or (CH2) n -NHC(O)R, where R is a C-C optionally substituted by hydroxyl 16 alkyl, n is 2, 3, or 4, and R 2 and R 3 are each independently selected from methyl, ethyl, propyl, or isopropyl, and R 4 is a C2-C8 alkylene optionally substituted with hydroxyl.

[0079] The ophthalmic composition of this embodiment reduces frictional resistance and makes smooth the target areas that come into contact with the ophthalmic composition when blinking or wearing contact lenses (the conjunctiva [including the conjunctiva at the eyelid margin: lid wiper]), cornea, contact lens (including the front surface [the surface that comes into contact with the outside world when worn], the back surface [the surface that comes into contact with the eyeball when worn], and the edge portion), etc., thereby reducing discomfort in the eye, the feeling of rubbing of the eye when blinking, the feeling of difficulty in blinking, the foreign body sensation in the eye (such as a gritty feeling), the feeling of the contact lens sticking, etc., and achieving the effect of providing a good wearing sensation for a long period of time even when wearing contact lenses. Furthermore, when wearing contact lenses, the friction generated between the contact lens and the conjunctiva and between the contact lens and the cornea is reduced, thereby reducing damage to the conjunctiva and cornea caused by the contact lens. Therefore, one embodiment of the present invention provides a friction reducer (preferably, a friction reducer for use during contact lens wear) comprising an ophthalmic composition containing polyvinylpyrrolidone (A) having a K value of 40 or more, at least one agent (B) selected from the group consisting of biguanide bactericides and trometamol, and at least one agent (C) selected from the group consisting of amino acids and thickeners.

[0080] Furthermore, as one embodiment of the present invention, there is provided a method for imparting a friction-reducing effect (preferably an effect of reducing friction during contact lens wear) to an ophthalmic composition by incorporating polyvinylpyrrolidone (A) having a K value of 40 or more, at least one agent (B) selected from the group consisting of biguanide fungicides and trometamol, and at least one agent (C) selected from the group consisting of amino acids and thickeners into the ophthalmic composition.

[0081] Furthermore, one embodiment of the present invention provides a method for reducing friction while wearing contact lenses, which comprises the step of applying to the contact lenses an ophthalmic composition containing polyvinylpyrrolidone (A) having a K value of 40 or more, at least one selected from the group consisting of biguanide bactericides and trometamol (B), and at least one selected from the group consisting of amino acids and thickeners (C). In this method, the ophthalmic composition may be applied to the contact lenses while the contact lenses are being worn, or while the contact lenses are still in place.

[0082] At least one of the components (A) to (C) of the present invention may be contained as an active ingredient. [Example]

[0083] The present invention will be described in detail below with reference to examples and test examples, but the present invention is not limited to these examples. The unit of the amount of each component in Tables 1 to 19 below is "w / v %." Additionally, the "appropriate amount" in Tables 1 to 7 and 15 to 19 indicates the amount that will give a predetermined pH.

[0084] [Test Example 1: Friction Evaluation (1)] A soft contact lens (product name: Proclear 1day (omafilcon A), soft contact lens classification according to the US Food and Drug Administration (FDA): Group II, manufactured by CooperVision) was rinsed with phosphate-buffered saline (sodium chloride: 0.83 w / v%, sodium hydrogen phosphate dodecahydrate: 0.5993 w / v%, sodium dihydrogen phosphate dihydrate: 0.0528 w / v%). After wiping off excess liquid from the surface, the lens was immersed in each formulation shown in Table 1 for 10 seconds. The soft contact lens was then attached to the contact points of a friction tester (Tribomaster TL201Ts, manufactured by Trinity Labs). Meanwhile, artificial leather soaked in saline for 1 hour was attached to the moving table of the friction tester, and 4 mL of saline was spread over the artificial leather so that it covered the entire surface where the contact points could move. A 20 g weight was then attached to the measurement unit. The contact lens was attached to the measurement unit, and measurements were taken 100 times per second for 20 seconds. The average value of the friction coefficient obtained from the measurement results 5 to 20 seconds after the start of measurement was calculated and used as the friction coefficient (μk) of the formulation. According to the following formula (7), the ratio of the friction coefficient of the other formulation examples, i.e., Comparative Examples 1-2 to 1-7 and Examples 1-1 and 1-2, was calculated when the friction coefficient of the corresponding comparative example (Comparative Example 1-1 (standard)) was set to 1. The results are shown in Tables 1 and 2 below.

[0085] 〔formula〕 Friction coefficient ratio = Friction coefficient in each formulation example / Friction coefficient in corresponding comparative example ... (7)

[0086] [Table 1]

[0087] [Table 2]

[0088] As can be seen from the results of above table 1 and 2, compared with the comparative example 1-1, 1-2, 1-3, 1-5 that contains polyvinylpyrrolidone K90, polyhexanide hydrochloride, sodium chondroitin sulfate or sodium hyaluronate alone, the example 1-1, 1-2 that contains polyvinylpyrrolidone K90, polyhexanide hydrochloride and sodium chondroitin sulfate or sodium hyaluronate is surprisingly greatly reduced in friction coefficient ratio, and confirmed that friction reducing effect is significantly improved.On the other hand, the comparative example 1-4, 1-7 that uses polyvinylpyrrolidone K25 instead of polyvinylpyrrolidone K90 does not show significant friction reducing effect.

[0089] [Test Example 2: Friction Evaluation (2)] The proportions of the coefficients of friction of other formulation examples were determined in the same manner as in Test Example 1, except that the formulations shown in Tables 3 to 5 below were used as formulation examples and that the corresponding comparative example was Comparative Example 2-1, with the coefficient of friction of the corresponding comparative example (Comparative Example 2-1 (reference)) being set to 1. The results are also shown in Tables 3 to 5 below.

[0090] [Table 3]

[0091] [Table 4]

[0092] [Table 5]

[0093] As can be seen from the results in Tables 3 to 5 above, in all cases, when polyvinylpyrrolidone K90, polyhexanide hydrochloride, and hydroxypropyl methylcellulose 2906 were contained (Example 2-1), when sodium chondroitin sulfate or sodium hyaluronate was contained instead of hydroxypropyl methylcellulose 2906 and the concentration of polyvinylpyrrolidone K90 was changed (Examples 2-2 to 2-5), when polyvinylpyrrolidone K90, polyhexanide hydrochloride, and aminoethylsulfonic acid were contained (Example 2-6), and when chlorhexidine gluconate or trometamol was contained instead of polyhexanide hydrochloride (Examples 2-7 to 2-10), the friction coefficient ratio was significantly reduced compared to Comparative Example 2-1, confirming a significant improvement in friction reduction effect.

[0094] [Test Example 3: Friction Evaluation (3)] The ratio of the coefficient of friction of other formulation examples was calculated in the same manner as in Test Example 1, except that the formulations shown in Table 6 below were used as formulation examples and the corresponding comparative example was Comparative Example 3-1, with the coefficient of friction of the corresponding comparative example (Comparative Example 3-1 (reference)) being set to 1. The results are also shown in Table 6 below.

[0095] [Table 6]

[0096] As can be seen from the results in Table 6 above, even when polyoxyethylene castor oil 10, polyoxyl 40 stearate, l-menthol, poloxamer 407, etc. were further contained in addition to polyvinylpyrrolidone K90, polyhexanide hydrochloride, and sodium chondroitin sulfate (Examples 3-1 to 3-3), the friction coefficient ratio was significantly reduced compared to Comparative Example 3-1, confirming that the friction-reducing effect was significantly improved.

[0097] [Test Example 4: Friction Evaluation (4)] The ratio of the coefficient of friction of other formulation examples was calculated in the same manner as in Test Example 1, except that the formulations shown in Table 7 below were used as formulation examples and the corresponding comparative example was Comparative Example 4-1, with the coefficient of friction of the corresponding comparative example (Comparative Example 4-1 (reference)) being set to 1. The results are also shown in Table 7 below.

[0098] [Table 7]

[0099] As can be seen from the results in Table 7 above, in both cases where polyvinylpyrrolidone K90, polyhexanide hydrochloride, and 0.1 w / v% sodium hyaluronate were contained (Example 4-1), and where chlorhexidine gluconate was contained instead of polyhexanide hydrochloride (Example 4-2), the friction coefficient ratio was significantly reduced compared to Comparative Example 4-1, confirming that a significant friction-reducing effect was achieved.

[0100] Test Example 5: Evaluation of cell activation effect (1) Each test solution (ophthalmic composition) was prepared according to the formulations shown in Tables 8 and 9 below. Immortalized human corneal epithelial cells (HCE-T) were cultured in a 96-well plate at 2 × 10 4 Cells were seeded at 100 μL / well and cultured until confluent. After removing the medium, 100 μL of each test solution was added and incubated at 37°C for 24 hours. At the same time, buffer alone was prepared as a control instead of each test solution. Then, using Cell-Counting Kit-8, the cell viability (%) of each test solution relative to the control was calculated. Next, using the following formula (8), the cell viability of the corresponding comparative example (Comparative Example 5-1 (reference)) was set to 1, and the cell viability of each test solution of the other formulation examples, i.e., Comparative Examples 5-2, 5-3, Examples 5-1, and 5-2, was calculated. The results are shown in Tables 8 and 9 below.

[0101] 〔formula〕 Cell viability = cell viability of each test solution / cell viability of corresponding comparative example (8)

[0102] [Table 8]

[0103] [Table 9]

[0104] As can be seen from the results of above-mentioned table 8 and 9, in the test solution of comparative example 5-2, 5-3, which contains only polyhexanide hydrochloride and sodium hyaluronate, compared with the test solution of comparative example 5-1, hardly any increase in cell survival rate is observed.On the other hand, in the test solution of example 5-1, 5-2, which contains polyvinylpyrrolidone K90 and further contains polyhexanide hydrochloride, sodium hyaluronate or aminoethylsulfonic acid, it is confirmed that cell survival rate is significantly increased. From the above results, it was confirmed that the use of the ophthalmic composition of the present invention significantly increases the cell survival rate, and therefore reduces the decrease in cell survival rate even when exposed to poor nutritional conditions, i.e., activates corneal cells.

[0105] Test Example 6: Evaluation of cell activation effect (2) The cell survival rate for each formulation was calculated in the same manner as in Test Example 5, except that the test liquid was changed to that shown in Tables 10 and 11 below, and Comparative Example 6-1 (standard) was used as the corresponding comparative example.

[0106] [Table 10]

[0107] [Table 11]

[0108] As can be seen from the results of above table 10 and 11, in the test solution of comparative example 6-2, which contains only sodium hyaluronate, compared with the test solution of comparative example 6-1, there is almost no increase in cell survival rate.On the other hand, in the test solution of example 6-1, which contains polyvinylpyrrolidone K90, further contains polyhexanide hydrochloride and sodium hyaluronate, it is confirmed that cell survival rate increases significantly.In addition, in the test solution of example 6-2, which contains polyvinylpyrrolidone K90, further contains polyhexanide hydrochloride and aminoethylsulfonic acid, it is confirmed that cell survival rate increases significantly.

[0109] Test Example 7: Evaluation of resistance to oxidative stress after hypoxia exposure (1) Each test solution (ophthalmic composition) was prepared according to the formulations shown in Tables 12 and 13 below. Immortalized human corneal epithelial cells (HCE-T) were seeded in 6-well plates and cultured in DMEM / F12 medium (470 mL of DMEM / F12 medium supplemented with 5 mL of 100x antibiotic, 2.5 mL of DMSO, 0.5 mL of EGF, 0.6 mL of insulin, and 25 mL of FBS) until confluent. Two mL of each test solution was added to each well and incubated at 37°C for 6 hours under hypoxic conditions using an Anaeropack™ (Mitsubishi Gas Chemical Company). RNA was extracted from the cells using a QIAshredder & RNase Mini Kit (QIAGEN). cRNA was reverse transcribed using SuperScript II (Life Technologies). q-PCR was performed using an ABI QuantStudio RealTime PCR (Thermo Fisher Scientific). The initial cycle (Ct) values ​​were measured. The relative expression ratio of the IL-6 gene to the corresponding comparative example was calculated using the following formula (9). The 18S gene (housekeeping gene) was used as an internal standard. The IL-6 gene expression level of a control example (blank) not containing the following ingredients (A) to (C) was set to 1, and the IL-6 gene expression ratios of the other formulation examples were calculated. The results are also shown in Tables 12 and 13 below. Comparative Example 7-1 and the corresponding comparative example in Example 7-1 are control examples.

[0110]

number

[0111] [Table 12]

[0112] [Table 13]

[0113] As can be seen from the results of Tables 12 and 13 above, it was confirmed that the test solution of Comparative Example 7-1, which contains only polyvinylpyrrolidone K90, increases the expression ratio of IL-6 gene, and may cause a high inflammatory reaction.Furthermore, in Example 7-1, which contains polyhexanide hydrochloride and sodium chondroitin sulfate, and Example 7-2, which contains polyhexanide hydrochloride and sodium hyaluronate, the expression ratio of IL-6 gene is reduced compared to the test solution of Comparative Example 7-1, and it was confirmed that there is a tendency for inflammatory reaction to be suppressed. Furthermore, the test solution of Example 7-2 was confirmed to show a tendency for the MUC1 equivalent value and GSTp-1 equivalent value to increase significantly (the conversion values ​​for MUC1 and GSTp-1, when the control example was set to 1, were 1.23 and 1.13, respectively). MUC1 is a gene involved in the expression of mucin, and GSTp-1 is a gene involved in the expression of antioxidant factors. An increase in these conversion values ​​is thought to reduce damage to the cornea during hypoxia and promote the production of genes that protect the cornea during oxidative stress.

[0114] From the above results, it was confirmed that even when exposed to hypoxic conditions, the use of the ophthalmic composition according to this embodiment has the effect of reducing inflammation caused by oxidative stress due to hypoxia exposure and the effect of promoting the production of genes that act to protect the cornea. Therefore, it was confirmed that the ophthalmic composition according to this embodiment is useful for treating or preventing corneal disorders caused by hypoxia exposure.

[0115] Test Example 8: Evaluation of resistance to oxidative stress after hypoxia (2) The same procedure as in Test Example 7 was carried out, except that a 12-well plate was used instead of a 6-well plate and the formulation example shown in Table 14 below was used. The corresponding comparative example was Comparative Example 8-1 (reference). The results are also shown in Table 14 below.

[0116] [Table 14]

[0117] As can be seen from the results in Table 14 above, it was confirmed that Example 8-1, which contained polyvinylpyrrolidone K90, polyhexanide hydrochloride, and potassium aspartate, had a reduced IL-6 gene expression ratio compared to the test solution of Comparative Example 8-1, and tended to suppress inflammatory responses. Furthermore, the test solution of Example 8-1 showed a tendency for the MUC1 equivalent value and HMOX-1 equivalent value to be significantly improved (when Comparative Example 8-1 was taken as 1, the equivalent values ​​were MUC1: 3.22 and HMOX-1: 2.74).

[0118] From the above results, it was confirmed that even when the formulation example was changed, the use of the ophthalmic composition according to this embodiment has the effect of reducing inflammation and corneal damage caused by oxidative stress due to hypoxia exposure, and the effect of promoting the production of genes that act to protect the cornea. Therefore, it was confirmed that the ophthalmic composition according to this embodiment is useful for treating or preventing corneal damage caused by hypoxia exposure.

[0119] [Test Example 9: Usability Test] Each aqueous composition (eye drops for contact lens wetting) was prepared according to the formulation shown in Table 15 below and used as a test solution. 13 mL of each test solution was filled into a 13 mL polyethylene terephthalate eye dropper container. After filling, a polyethylene nozzle was attached to the container. Four healthy subjects who normally wear soft contact lenses were used as subjects. Example 9-1 was applied to the right eye and Comparative Example 9-1 to the left eye, one drop per lens directly onto the concave surface (inner surface, the surface that comes into contact with the cornea) of the contact lens, and then the contact lens was worn. Eight hours after wearing the contact lenses, the effectiveness of the lenses in improving various eye symptoms (rubbing sensation when blinking, difficulty blinking, foreign body sensation in the eye, contact lens sticking sensation, dry eyes, eye fatigue, and blurred vision) was evaluated using the VAS (Visual Analog Scale) method, which uses a 10cm line with a scale ranging from 0 to 100. The lower the score, the less symptoms were felt and the more favorable the eye condition. On another day, the same subject applied Comparative Example 9-1 to the right eye and Example 9-1 to the left eye, and the same evaluation was carried out in the same manner as above. All scores obtained when each test solution was used were averaged to obtain the average VAS score for each test solution. Using the scores of each test solution, the symptom improvement rate (%) was calculated as the score reduction rate (%) for each item in Example 9-1 relative to Comparative Example 9-1 using the following formula (10). The results are also shown in Table 15 below.

[0120] 〔formula〕 Symptom improvement rate (score reduction rate) (%) = {(average VAS score value of the test solution of Comparative Example 9-1 - average VAS score value of the test solution of Example 9-1) / average VAS score value of the test solution of Comparative Example 1} × 100 ... (10)

[0121] [Table 15]

[0122] As can be seen from the results in Table 15 above, it was confirmed that by incorporating polyvinylpyrrolidone K90, polyhexanide hydrochloride, and hydroxypropyl methylcellulose, friction on the eye area was reduced, and the feeling of rubbing when blinking, difficulty in blinking, foreign body sensation in the eye, and feeling of contact lenses sticking to the eye were improved. In addition, it has been confirmed that the inclusion of polyvinylpyrrolidone K90, polyhexanide hydrochloride, and hydroxypropyl methylcellulose improves dry eyes, eye fatigue, and blurred vision.

[0123] <Formulation example> According to the formulations shown in Tables 16 to 19 below, eye drops (Formulation Examples 1 to 9), eye drops for contact lenses (CL) (Formulation Examples 10 to 23), and eye drops for contact lens wetting (Formulation Examples 24 to 26) are prepared by conventional methods. The unit of each component amount in Tables 16 to 19 is "w / v%."

[0124] [Table 16]

[0125] [Table 17]

[0126] [Table 18]

[0127] [Table 19]

[0128] Furthermore, the above-mentioned Formulation Examples 1 to 26 were placed in polyethylene terephthalate (PET) containers, and polyethylene (PE) nozzles were attached (Formulation Examples 1' to 26'). Similarly, each of the formulations having the exact same composition in Formulation Examples 1 to 26 was placed in a polyethylene terephthalate (PET) container, and a polybutylene terephthalate (PBT) nozzle was attached (Formulation Examples 1" to 26"). [Industrial Applicability]

[0129] The present invention can be widely used as an ophthalmic composition for reducing friction on the eye when blinking or wearing contact lenses.

Claims

[Claim 1] The composition contains polyvinylpyrrolidone (A) having a K value of 40 or more, trometamol (B), and at least one substance (C) selected from the group consisting of chondroitin sulfate, hyaluronic acid, and salts thereof, An ophthalmic composition for contact lenses, having a content of the component (A) of 0.003 to 0.3 w / v % and a pH of 6.5 to 7.5 (excluding the compositions (i) and (ii) below: (i) an ophthalmic composition for soft contact lenses, comprising an antihistamine, glycyrrhizinic acid and / or a salt thereof, chondroitin sulfate and / or a salt thereof, and 0.5 w / v % or more of polyvinylpyrrolidone, and having a pH of 5.5 to 6.8; (ii) a contact lens cleaning composition containing (A) a polyvinyl-based water-soluble polymer compound and (B) a compound selected from mucopolysaccharides, mucopolysaccharide salts, polyphosphoric acid, and polyphosphate salts).

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