Contact lens eye drop for friction reduction, method of using the same, and method of reducing friction of contact lens when worn

Abstract

To provide a contact lens eye drop for friction reduction for reducing friction of a contact lens when worn.SOLUTION: A contact lens eye drop for reducing friction of an eye contains (A) a polyvinyl pyrrolidone with a K value of 70 or more and (B) a buffer agent.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to an eye drop for reducing friction for contact lenses, which reduces friction, and in particular, which provides sustained friction reduction. [Background technology]

[0002] In the eye, friction occurs between the eyelids, cornea, and conjunctiva when movements such as blinking are applied, and this is said to be the cause of abnormalities in the cornea and conjunctiva, tear film, and eyelids. In particular, when contact lenses are worn, friction 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] Conventional methods for reducing friction in contact lenses include a contact lens solution containing hypromellose at a concentration of 0.5 to 1.5 w / v%, which has a viscosity of 5.1 mPa·s or less in a 2 w / w% aqueous solution at 20°C, and polyvinyl alcohol at a concentration of 0.8 to 2 w / v%, which has a viscosity of 10 to 35 mPa·s in a 4 w / w% aqueous solution at 20°C, and which has a kinetic viscosity of 3.0 to 8.0 mm 2 A contact lens composition having the formula (I) and (II) is known (Patent Document 1). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] JP 2012-198538 A Summary of the Invention [Problem to be solved by the invention]

[0005] Contact lens wearers are in need of a more effective and convenient method for reducing friction. The present invention aims to provide an eye drop for contact lenses that reduces friction, particularly for reducing friction of contact lenses used to sustain the reduction in friction, a method for using the same, and a method for reducing friction of contact lenses while they are being worn. [Means for solving the problem]

[0006] As a result of intensive research to solve the above problems, the present inventors have unexpectedly found that by selecting, among polyvinylpyrrolidones, (A) polyvinylpyrrolidone having a K value of 70 or more as an ingredient of an eye drop for contact lenses and adding (B) a buffering agent thereto, the obtained eye drop for contact lenses can significantly reduce friction on the contact lenses while they are being worn, and have completed the present invention.

[0007] That is, the present invention provides the following [1] to [9]. [1] An eye drop for contact lenses for reducing friction, comprising (A) polyvinylpyrrolidone having a K value of 70 or more, and (B) a buffering agent. [2] The eye drops for contact lenses according to [1], wherein the component (A) is polyvinylpyrrolidone K90. [3] The eye drops for contact lenses according to [1] or [2], wherein the content of the component (A) is 0.001 to 5 w / v % based on the total amount of the eye drops. [4] The eye drops for contact lenses according to any one of [1] to [3], wherein the component (B) is at least one selected from the group consisting of boric acid, phosphoric acid, citric acid, and salts thereof. [5] The eye drops for contact lenses according to any one of [1] to [4], wherein the content of the component (B) is 0.001 to 10 w / v % based on the total amount of the eye drops. [6] The eye drops for contact lenses according to any one of [1] to [5], further comprising (C) a salt. [7] The eye drops for contact lenses according to [6], wherein the content of the component (C) is 0.001 to 5 w / v % based on the total amount of the eye drops. [8] A method for using the eye drops for contact lenses according to any one of [1] to [7], wherein the amount of the eye drops administered per time is 10 to 200 μL. [9] A method for reducing friction while wearing contact lenses by instilling an eye drop for contact lenses containing (A) polyvinylpyrrolidone having a K value of 70 or more, and (B) a buffering agent. Effect of the Invention

[0008] The eye drops for contact lenses of the present invention contain (A) polyvinylpyrrolidone having a K value of 70 or more and (B) a buffering agent, making it possible to provide an eye drop that can effectively suppress friction. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0009] Next, the embodiment of the present invention will be described in detail, however, 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 eye drops for contact lenses according to this embodiment (hereinafter sometimes abbreviated as "eye drops") are used to reduce friction of contact lenses while they are being worn, and contain (A) polyvinylpyrrolidone having a K value of 70 or more, and (B) a buffering agent. Each component will be described below.

[0012] <Component (A)> The above (A) polyvinylpyrrolidone having a K value of 70 or more is a non-ionic water-soluble polymer, and the K value is calculated in accordance with the method described in the Japanese Pharmacopoeia, 17th Edition, "Povidone."

[0013] Examples of the polyvinylpyrrolidone having a K value of 70 or more (A) include polyvinylpyrrolidone K80, polyvinylpyrrolidone K85, polyvinylpyrrolidone K90, polyvinylpyrrolidone K120, and the like.

[0014] Among these, from the viewpoint of more significantly exhibiting the effects of the present invention, polyvinylpyrrolidone having a K value of 80 or more is preferred, polyvinylpyrrolidone having a K value of 90 or more is more preferred, and polyvinylpyrrolidone having a K value of 90 to 120 is even more preferred. Among these, polyvinylpyrrolidone K90 is particularly preferably used. Here, the K value is 90 to 108% of the indicated K value in accordance with the description of the K value of "Povidone" in the 17th Edition of the Japanese Pharmacopoeia, so for example, "K90" refers to a K value (viscosity characteristic value) in the range of 81.0 to 97.2.

[0015] The polyvinylpyrrolidone K90 may be synthesized by a known method, or may be a commercially available product such as Eiftact K-90 (manufactured by Daiichi Kogyo Seiyaku Co., Ltd.), Kollidon K90 (manufactured by BASF Japan Ltd.), Plasdone K90 (manufactured by ISP Japan Ltd.), Povidone K90 (manufactured by DSP Gokyo Food & Chemical Co., Ltd.), etc. These may be used alone or in combination of two or more kinds.

[0016] The content of the (A) component is not particularly limited, but for example, based on the total amount of the eye drop according to the present embodiment, the content of the (A) component is preferably 0.001 to 5 w / v%, more preferably 0.005 to 3 w / v%, even more preferably 0.01 to 2.5 w / v%, even more preferably 0.02 to 2 w / v%, particularly preferably 0.03 to 1.5 w / v%, and most preferably 0.05 to 1 w / v%. The content of the (A) component is suitable from the viewpoint of more prominently exhibiting the effects of the present invention.

[0017] <(B) component> (B) The buffering agent is not particularly limited as long as it is medicamentously, pharmacologically (pharmaceutical) or physiologically acceptable.

[0018] Examples of such (B) buffers include boric acid buffers, phosphate buffers, carbonate buffers, citrate buffers, acetate buffers, epsilon-aminocaproic acid, sodium L-glutamate, etc. These (B) buffers may be used alone or in combination of two or more. Examples of boric acid buffers include boric acid or its salts (alkali metal borates, alkaline earth metal borates, etc.). Examples of phosphate buffers include phosphoric acid or its salts (alkali metal phosphates, alkaline earth metal phosphates, etc.). Examples of carbonate buffers include carbonic acid or its salts (alkali metal carbonates, alkaline earth metal carbonates, etc.). Examples of citric acid buffers include citric acid or its salts (alkali metal citrates, alkaline earth metal citrates, etc.). Examples of acetic acid buffers include acetic acid or its salts (alkali metal acetates, alkaline earth metal acetates, etc.). In addition, borate, phosphate, carbonate, citrate, acetate, or sodium L-glutamate hydrate may be used as the borate, phosphate, carbonate, citrate, acetate, or acetate buffer. More specific examples of borate-based buffers include boric acid or a salt thereof (sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, borax, etc.); phosphate-based buffers include phosphoric acid or a salt thereof (disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, trisodium phosphate, tripotassium phosphate, calcium hydrogen phosphate, calcium dihydrogen phosphate, etc.); carbonate-based buffers include carbonic acid or a salt thereof (sodium bicarbonate, sodium carbonate, ammonium carbonate, potassium carbonate, calcium carbonate, potassium bicarbonate, magnesium carbonate, etc.); citric acid-based buffers include citric acid or a salt thereof (sodium citrate, potassium citrate, calcium citrate, sodium dihydrogen citrate, disodium citrate, etc.); and acetic acid-based buffers include acetic acid or a salt thereof (ammonium acetate, potassium acetate, calcium acetate, sodium acetate, etc.). Among these buffers, boric acid buffers (e.g., a combination of boric acid and borax), phosphate buffers (e.g., a combination of disodium hydrogen phosphate and sodium dihydrogen phosphate), citrate buffers, epsilon-aminocaproic acid, and sodium L-glutamate are preferred, with boric acid buffers, phosphate buffers, and citrate buffers being more preferred, and boric acid buffers (at least one of boric acid and its salts) being even more preferred.

[0019] The content of the (B) buffering agent is appropriately set depending on the type of the (B) buffering agent, the types and contents of other components, etc. The content of the (B) buffering agent is preferably 0.001 to 10 w / v%, more preferably 0.005 to 5 w / v%, even more preferably 0.01 to 2.5 w / v%, and even more preferably 0.04 to 2 w / v%, based on the total amount of the ophthalmic solution.

[0020] In the eye drops according to the present embodiment, the content ratio of the (B) component to the (A) component is not particularly limited, and is appropriately set depending on the types of the (A) and (B) components, the types and contents of other blended components, the use of the eye drops, the formulation form, etc. From the viewpoint of more significantly exhibiting the effects of the present invention, for example, the content ratio of the (B) component to the (A) component is preferably 0.0001 to 500 parts by mass, more preferably 0.001 to 300 parts by mass, even more preferably 0.01 to 100 parts by mass, even more preferably 0.1 to 50 parts by mass, and particularly preferably 0.4 to 25 parts by mass, per part by mass of the (A) component contained in the eye drops according to the present embodiment.

[0021] <(C) component> In order to more significantly exhibit the effects of the present invention, the eye drop according to this embodiment preferably further contains (C) a salt.

[0022] As the (C) salts, either inorganic salts or organic salts can be used (however, excluding the (B) component). Examples of the inorganic salts include sodium hydrogen sulfite, sodium sulfite, potassium chloride, calcium chloride, sodium chloride, magnesium chloride, sodium thiosulfate, and magnesium sulfate. Examples of the organic salts include potassium acetate and sodium acetate. Among the (C) salts, inorganic salts are preferred, potassium chloride, calcium chloride, sodium chloride, and magnesium sulfate are more preferred, and potassium chloride and sodium chloride are even more preferred. These (C) salts can be used alone or in combination of two or more kinds.

[0023] When the above (C) salt is contained, its content is appropriately set depending on the type of (C) salt, the types and contents of other contained components, etc. The content of (C) salt is, for example, preferably 0.001 to 5 w / v%, more preferably 0.01 to 3 w / v%, even more preferably 0.05 to 2 w / v%, still more preferably 0.1 to 1 w / v%, and particularly preferably 0.4 to 0.8 w / v%, based on the total amount of the ophthalmic solution according to this embodiment.

[0024] The content ratio of the (C) component to the (A) component in the eye drops according to this embodiment is not particularly limited, and is appropriately set depending on the types of the (A) component and the (C) component, the types and contents of other blended components, the use of the eye drops, the formulation form, etc. From the viewpoint of more significantly exhibiting the effects of the present invention, for example, the content ratio of the (C) component to the (A) component is preferably 0.001 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, per part by mass of the (A) component contained in the eye drops according to this embodiment.

[0025] <Other optional ingredients> The eye drop according to the present embodiment may further contain amino acids other than the component (B) in addition to the components (A) and (B) within a range that does not impair the effects of the present invention. The amino acids refer to compounds having an amino group and a carboxyl group or a sulfo group in the molecule, or derivatives thereof. Specific examples include amino acids and mucopolysaccharides, as well as salts thereof. Among the amino acids, examples of amino acids and salts thereof include monoamino monocarboxylic acids such as glycine, alanine, γ-aminobutyric acid, and γ-aminovaleric acid; monoamino dicarboxylic acids such as aspartic acid and glutamic acid, and salts thereof; diamino monocarboxylic acids such as arginine and lysine, and salts thereof; and derivatives such as aminoethylsulfonic acid (taurine) and salts thereof. The amino acids and salts thereof may be in any of the L-, D-, and DL-forms, and examples thereof include potassium L-aspartate, magnesium L-aspartate, and an equal mixture of magnesium and potassium L-aspartate. Among amino acids, mucopolysaccharides and their derivatives and salts thereof include, for example, acidic mucopolysaccharides such as chondroitin sulfate, hyaluronic acid, alginic acid, etc., and their salts. The salts of amino acids or mucopolysaccharides include medicamentarily, pharmacologically, or physiologically acceptable salts. Examples of such salts include salts with organic acids [e.g., monocarboxylates (acetates, trifluoroacetates, butyrates, palmitates, stearates, etc.), polycarboxylates (fumarates, maleates, etc.), oxycarboxylates (lactates, tartrates, citrates, succinates, malonates, etc.), organic sulfonates (methanesulfonates, toluenesulfonates, etc.)], salts with inorganic acids (e.g., hydrochlorides, sulfates, nitrates, hydrobromides, phosphates, etc.), 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 metals such as alkali metals (sodium, potassium, etc.), alkaline earth metals (calcium, magnesium, etc.), and aluminum], and the like, and the salts are appropriately selected depending on the compound.For example, in the case of monoaminodicarboxylic acids, salts with inorganic bases are preferred, and alkali metal salts and alkaline earth metal salts are particularly preferred.

[0026] Among such amino acids, potassium aspartate, magnesium aspartate, an equal mixture of magnesium and potassium L-aspartate, aminoethylsulfonic acid, and mucopolysaccharides are particularly preferred, with mucopolysaccharides being more preferred, sodium chondroitin sulfate and sodium hyaluronate being even more preferred, and sodium chondroitin sulfate being particularly preferred. These amino acids can be used alone or in combination of two or more kinds.

[0027] The content of the amino acids is not particularly limited, and is appropriately set depending on the type of amino acid, the type and content of the (A) component and the (B) component used in combination, etc. The content of the amino acids is, for example, preferably 0.01 to 8 w / v%, more preferably 0.02 to 5 w / v%, even more preferably 0.05 to 3 w / v%, and particularly preferably 0.1 to 2 w / v%, based on the total amount of the ophthalmic solution according to this embodiment.

[0028] Moreover, the eye drop according to this embodiment may further contain a thickener in addition to the components (A) and (B) as long as the effects of the present invention are not impaired. Examples of such thickeners include polyvinyl alcohol (completely or partially saponified), polyvinylpyrrolidone (K25, K30), carboxyvinyl polymers, cellulose derivatives [methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose (hypromellose) (2208, 2906, 2910, etc.), carboxymethylcellulose, carboxyethylcellulose, nitrocellulose or salts thereof, etc.], gum arabic, tragacanth, dextran (40, 70, etc.), etc., and preferably polyvinyl alcohol (completely or partially saponified), polyvinylpyrrolidone (K25, K30), carboxyvinyl polymers, cellulose derivatives, dextran (70), more preferably cellulose derivatives, even more preferably hydroxyethylcellulose, hydroxypropylmethylcellulose, and even more preferably hydroxypropylmethylcellulose 2208, hydroxypropylmethylcellulose 2906, and hydroxypropylmethylcellulose 2910. These thickeners may be used alone or in combination of two or more kinds.

[0029] When the thickener is contained, the content is appropriately set depending on the type of the 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%, further preferably 0.01 to 2 w / v%, and particularly preferably 0.1 to 1 w / v%, based on the total amount of the ophthalmic solution according to this embodiment.

[0030] The eye drop according to the present embodiment may further contain a nonionic surfactant in addition to the components (A) and (B) within a range that does not impair the effects of the present invention. The nonionic surfactant is not particularly limited as long as it is medicamentally, pharmacologically (pharmaceutical) or physiologically acceptable.

[0031] Specific examples of nonionic surfactants that can be used in the eye drops according to this embodiment include POE(20) sorbitan monouranate (polysorbate 20), POE(20) sorbitan monopalmitate (polysorbate 40), POE(20) sorbitan monostearate (polysorbate 60), POE(20) sorbitan tristearate (polysorbate 65), POE(20) sorbitan monooleate (polysorbate 66), and POE(20) sorbitan monooleate (polysorbate 67). POE sorbitan fatty acid esters such as POE (40) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 40), POE (60) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 60), etc.; POE castor oils such as POE (3) castor oil (polyoxyethylene castor oil 3), POE (10) castor oil (polyoxyethylene castor oil 10), POE (35) castor oil (polyoxyethylene castor oil 35), etc.; POE alkyl ethers such as OE(9) lauryl ether; POE-POP alkyl ethers such as POE(20)POP(4) cetyl ether; polyoxyethylene / polyoxypropylene glycols such as POE(20)POP(20) glycol (Pluronic L44), POE(42)POP(67) glycol (Poloxamer 403, Pluronic P123), POE(54)POP(39) glycol (Poloxamer 235, Pluronic P85), POE(120)POP(40) glycol (Pluronic F87), POE(160)POP(30) glycol (Poloxamer 188, Pluronic F68), POE(196)POP(67) glycol (Poloxamer 407, Pluronic F127), and POE(200)POP(70) glycol; and polyethylene glycol monostearate such as polyoxyl 40 stearate. In the above-listed compounds, the numbers in parentheses indicate the number of moles of alkylene oxide added.

[0032] Among the above nonionic surfactants, POE sorbitan fatty acid ester, POE hydrogenated castor oil, POE castor oil, polyethylene glycol monostearate or POE·POP glycol is preferred, and polysorbate 80, POE hydrogenated castor oil 40, POE hydrogenated castor oil 60, POE castor oil 10, POE castor oil 35, polyoxyl 40 stearate, poloxamer 188 or poloxamer 407 is more preferred. These nonionic surfactants can be used alone or in combination of two or more kinds.

[0033] 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 application of the eye drop, the formulation form, the method of use, etc.; for example, based on the total amount of the eye drop according to this embodiment, the 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 0.5 w / v%.

[0034] In addition, the eye drops according to the present embodiment may further contain a refreshing agent in addition to the (A) and (B) components, so long as the effect of the present invention is not impaired. The refreshing agent is not particularly limited as long as it is a substance that imparts a refreshing feeling to the eye drops. For example, terpenoids and essential oils containing terpenoids (e.g., eucalyptus oil, bergamot oil, peppermint oil, fennel oil, rose oil, cinnamon oil, spearmint oil, camphor oil, cool mint, and peppermint oil, etc.) are included. Examples of terpenoids include menthol, menthone, camphor (also called "camphor" or "camphor"), borneol (also called "liu nou" or "borneol"), geraniol, nerol, cineole, citronellol, carvone, anethole, eugenol, limonene, linalool, and linalyl acetate. The terpenoid may be any of d-, l- and dl-isomers, and examples thereof include l-menthol, d-menthol, dl-menthol, dl-camphor, d-camphor, dl-borneol and d-borneol. From the viewpoint of more significantly exhibiting the effects of the present invention, menthol, camphor, borneol, geraniol or peppermint oil is preferred, l-menthol, d-camphor, dl-camphor or d-borneol is more preferred, and l-menthol is particularly preferred. These cooling agents may be used alone or in combination of two or more.

[0035] The content of the refreshing agent is not particularly limited, and is appropriately set according to the type of refreshing agent, the type and content of the (A) component and the (B) component used in combination, etc. The content of the refreshing agent can be measured as a terpenoid, and for example, based on the total amount of the eye drop according to this embodiment, the content of the refreshing agent (as a terpenoid) is preferably 0.00001 to 1 w / v%, more preferably 0.00005 to 0.5 w / v%, even more preferably 0.0001 to 0.2 w / v%, particularly preferably 0.0005 to 0.1 w / v%, and particularly more preferably 0.001 to 0.05 w / v%. The content of the refreshing agent is suitable from the viewpoint of more significantly exhibiting the effects of the present invention.

[0036] The eye drop according to the present embodiment may further contain a polyhydric alcohol in addition to the components (A) and (B) within a range that does not impair the effects of the present invention. Examples of the polyhydric alcohol include polyethylene glycol (400, 4000, 6000, etc.), propylene glycol, glycerin, etc. As the polyhydric alcohol, from the viewpoint of more significantly exhibiting the effects of the present invention, propylene glycol, glycerin, and polyethylene glycol are preferred, and polyethylene glycol is more preferred. In addition, commercially available polyhydric alcohols can also be used. These polyhydric alcohols can be used alone or in combination of two or more kinds.

[0037] The content of the polyhydric alcohol that can be used in the eye drops according to the present embodiment is not particularly limited, and is appropriately set depending on the type of polyhydric alcohol, the type and content of other blended ingredients, the use of the eye drops, the formulation form, 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 0.75 w / v%, based on the total amount of the eye drops.

[0038] The pH of the eye drops according to the present embodiment is not particularly limited as long as it is within a medicamentously, pharmacologically (pharmaceutical) or physiologically acceptable range. The pH of the eye drops is, for example, preferably 4.0 to 9.5, more preferably 5.0 to 9.0, even more preferably 5.5 to 8.5, and even more preferably 6.5 to 8.0.

[0039] The osmotic pressure ratio of the eye drops according to the present embodiment is not particularly limited as long as it is within the range acceptable to the living body. The osmotic pressure ratio of the eye drops 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 0.8 to 1.55. The osmotic pressure can be adjusted by a method known in the art using an inorganic salt, a polyhydric alcohol, a sugar alcohol, or a sugar. The osmotic pressure ratio is the ratio of the osmotic pressure of the sample to 286 mOsm (the osmotic pressure of a 0.9 w / v% sodium chloride aqueous solution) based on the 17th revised Japanese Pharmacopoeia, and the osmotic pressure is measured with reference to the osmotic pressure measurement method (freezing point depression method) described in the Japanese Pharmacopoeia. For the standard solution for measuring osmolality ratios (0.9 w / v% sodium chloride aqueous solution), sodium chloride (Japanese Pharmacopoeia standard reagent) is dried at 500-650°C for 40-50 minutes, then allowed to cool in a desiccator (silica gel), and 0.900 g of the solution is accurately weighed out and dissolved 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.

[0040] The viscosity of the eye drop according to the present embodiment is not particularly limited as long as it is within a range that is 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'×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.

[0041] In addition, the eye drops according to the present embodiment may contain various pharmacologically active or physiologically active ingredients in appropriate amounts, selected appropriately, in one or more combinations, in addition to the above-mentioned ingredients, so long as the effects of the present invention are not hindered. Such ingredients are not particularly limited, and examples thereof include the active ingredients in various medicines described in the 2012 edition of the General Drug Manufacturing and Sales Approval Standards (supervised by the Japan Society of Regulatory Science). Specifically, the following ingredients are used in ophthalmic drugs.

[0042] Antihistamines: For example, iproheptine, diphenhydramine hydrochloride, 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. - Eye muscle regulating drugs: For example, cholinesterase inhibitors that have an active center similar to 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, 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.

[0043] In addition, the eye drops according to the present embodiment may contain various additives selected appropriately according to the application or formulation form in a conventional manner, and may contain one or more additives in appropriate amounts, as long as the effects of the invention are not impaired. Examples of such additives include those listed in the Pharmaceutical Additives Encyclopedia 2016 (edited by the Japan Pharmaceutical Additives Association). Representative components include the following additives.

[0044] Carrier: For example, an aqueous carrier such as water or aqueous ethanol. · Sugars: e.g. glucose, cyclodextrin, etc. Sugar alcohols: for example, xylitol, sorbitol, mannitol, etc. These may be in the d-, l- or dl-form. Stabilizers: For example, trometamol, sodium formaldehyde sulfoxylate (Rongalit), tocopherol, edetic acid and its salts (sodium edetate), sodium pyrosulfite, monoethanolamine, aluminum monostearate, glyceryl monostearate, dibutylhydroxytoluene, etc. Anionic surfactants: For example, alkylbenzenesulfonates, alkyl sulfates, polyoxyethylene alkyl sulfates, α-sulfofatty acid ester salts, α-olefin sulfonates, etc. Preservatives, disinfectants or antibacterial agents: 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, biguanide compounds (specifically, polyhexanide or its hydrochloride, etc.), polydonium chloride, Gloquil (trade name manufactured by Rhodia), etc. pH adjusters: for example, hydrochloric acid, 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, and mineral oils such as liquid paraffin and Vaseline.

[0045] The eye drop according to the present embodiment is prepared by incorporating the above-mentioned components (A) and (B) and, if necessary, other optional components in a carrier at a desired content. As the carrier, medicamentarily, pharmacologically (pharmaceutical) or physiologically acceptable water may be used, and specific examples of such water include distilled water, tap water, purified water, sterilized purified water, water for injection, distilled water for injection, etc.

[0046] Then, for example, these components are dissolved or suspended in purified water, adjusted to a predetermined pH and osmotic pressure ratio, and sterilized by filtration sterilization or the like, to prepare the eye drop according to this embodiment.

[0047] The eye drops according to this embodiment have 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, based on the total volume of the eye drops.

[0048] The eye drop according to the present embodiment can be in various formulation forms depending on the purpose. Examples of the formulation form include a liquid agent, a gel agent, etc. The eye drop according to the present embodiment is preferably a liquid agent.

[0049] The eye drops according to the present embodiment are provided in any container. The container for storing the eye drops according to the present embodiment is not particularly limited, and may be made of glass or plastic, for example. It is preferably made of plastic. Examples of plastic include polyethylene terephthalate, polyarylate, polyethylene naphthalate, polycarbonate, polyethylene, polypropylene, polyimide, copolymers of monomers constituting these, and mixtures of two or more of these. It is preferably polyethylene terephthalate. In addition, the container for storing the eye drops according to the present embodiment may be a transparent container that allows the inside of the container to be visually confirmed, or may be an opaque container that makes it difficult to visually confirm the inside of the container. It is preferably a transparent container. Here, the "transparent container" includes both a colorless transparent container and a colored transparent container. The eye drops according to the present embodiment can be stored in, for example, a colored transparent plastic container in the form of a reusable multi-dose and used. In another embodiment, it can also be stored in the form of a unit dose and used.

[0050] The dosage and administration of the eye drops according to the present embodiment is not particularly limited as long as it is effective and has few side effects, but the dosage and administration is preferably 10 to 200 μL per administration from the viewpoint of the effect of the present invention, and more preferably 20 to 150 μL. The dosage and administration of the eye drops per administration refers to the dosage and administration (amount of drops) per administration when used at an interval of about 15 minutes or more (the time required for tears to be replaced) for adults (15 years or older) and children aged 7 years or older, and usually corresponds to 1 to 3 drops. The frequency of administration of eye drops is preferably 3 to 6 times a day (for example, in the morning, midday, evening, and before going to bed), and more preferably 5 to 6 times a day.

[0051] The eye drops according to this embodiment can be used as a pharmaceutical or quasi-drug preparation, and are eye drops for contact lenses that can be applied while wearing contact lenses. The eye drops for contact lenses of the present invention can be used for the purpose of application to the eyes not only when wearing contact lenses, but also before and after wearing contact lenses, and even when not wearing contact lenses. The eye drops for contact lenses of the present invention may include an embodiment in which they are applied to the eyes, and therefore may be, for example, an eye drop for contact lenses that has the above-mentioned embodiment and also an embodiment in which they are applied directly to contact lenses before wearing.

[0052] The eye drops according to the present embodiment are suitable for use in soft contact lenses, among contact lenses. In particular, the eye drops can be applied to any soft contact lenses classified into groups I to IV in the soft contact lens classification according to the U.S. Food and Drug Administration (FDA) standards, but are particularly preferably applied to soft contact lenses classified into group IV (water content of 50% or more, ionic). Here, ionic refers to a contact lens containing ionic components at a rate of 1 mol% or more.

[0053] Examples of soft contact lenses classified into the above Group IV include, in the United States Approved Names, etafilcon A, metafilcon A, metafilcon B, ocufilcon A, ocufilcon B, ocufilcon C, ocufilcon D, ocufilcon E, femfilcon A, and bifilcon A. During the wearing of these lenses, the effect of the present invention is more pronounced, and therefore the eye drops according to the present embodiment can be preferably used. Particularly preferred is etafilcon A.

[0054] Furthermore, among soft contact lenses, color contact lenses, which have colors or patterns printed on their surfaces, have higher friction on the contact lens surface than contact lenses other than color contact lenses, and therefore eye drops for color contact lenses are also preferred.

[0055] The eye drops according to the present embodiment can reduce friction on all surfaces of the contact lenses (including the front surface [surface that comes into contact with the outside world when worn], the back surface [surface that comes into contact with the eyeball when worn], and the edges) when the contact lenses are worn, and therefore effectively reduce friction between the contact lenses and the cornea, and between the contact lenses and the conjunctiva. This reduces the foreign body sensation while wearing the contact lenses, and also improves ease of blinking and comfort. At the same time, the eye drops of this embodiment reduce frictional resistance that occurs when blinking, etc., in eye tissues that come into contact with the eye drops (between the conjunctiva (including the lid wiper) and between the conjunctiva and cornea, etc.), making the tissues smooth, thereby achieving the effect of more significantly reducing discomfort in the eyes.

[0056] Furthermore, the eye drops of the present embodiment reduce frictional contact of the contact lens, and therefore can prevent the occurrence of scratches on the contact lens itself caused by friction of the contact lens (friction due to contact with the cornea, conjunctiva, and dirt). If a contact lens has scratches, not only will corrected vision decrease, but dirt, bacteria, and the like will easily adhere to the contact lens, and there is a risk of causing damage to the cornea and conjunctiva. Therefore, by preventing scratches on the contact lens, these problems can also be prevented.

[0057] In addition, the time required for the aqueous tear layer to be replaced is usually about 15 minutes, and if more time passes after application, the tear is completely replaced and the eye drops are also replaced, so that the friction reducing effect on the eye is usually greatly reduced. However, the eye drops according to the present embodiment can maintain the friction reducing effect even when the tear is replaced after application.

[0058] Therefore, as one embodiment of the present invention, there is provided an eye drop for contact lenses for reducing friction on the eye, which contains (A) polyvinylpyrrolidone having a K value of 70 or more and (B) a buffering agent, and is used to reduce friction, particularly to sustain the reduction in friction.

[0059] Furthermore, as one embodiment of the present invention, there is provided a method for reducing friction of contact lenses while the contact lenses are being worn, the method comprising the step of instilling an eye drop containing (A) polyvinylpyrrolidone having a K value of 70 or more and (B) a buffering agent. Note that "while wearing contact lenses" refers to the state in which the contact lenses are being worn, and does not matter whether it is immediately after putting on the contact lenses or after a certain period of time has passed while the contact lenses are being worn.

[0060] As a method for reducing friction of contact lenses, in addition to eye drops, a method of mixing a substance having a friction reducing effect into the packaging liquid of the contact lens or kneading it into the contact lens itself is conceivable, but these methods have the problem that the handling property of the contact lens may be reduced when the contact lens is taken out of the case, the friction reducing effect may be reduced by continuous wearing, and it is not possible to immediately deal with the friction when it is detected.In contrast, the eye drops and the friction reducing method in this embodiment can be generally applied regardless of the type of the target contact lens, and by applying them when a frictional sensation is felt, the symptoms can be immediately eliminated when the symptoms are detected.In addition, by applying the eye drops to the contact lens that has been stained with lipids, proteins, etc. due to wearing, the friction reducing effect can be significantly achieved.

[0061] At least one of the components (A) and (B) of the eye drop according to this embodiment may be contained as an active ingredient. EXAMPLES

[0062] 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 units of the amounts of each component in the tables below are all "w / v%." In addition, the "appropriate amount" in the tables indicates the amount required to obtain a desired pH.

[0063] <Test Example 1: Evaluation of Friction Reduction Property> A soft contact lens (product name: 1-DAY ACUVUE (etafilcon A), US Food and Drug Administration (FDA) soft contact lens classification: Group IV, Johnson & Johnson) was rinsed with phosphate buffered saline (sodium chloride: 0.8 w / v%, sodium hydrogen phosphate dodecahydrate: 0.6 w / v%, sodium dihydrogen phosphate dihydrate: 0.053 w / v%) and the excess liquid on the surface was wiped off. Then, the lens was immersed one by one in 2 mL of the lipid-protein soiling solution shown in Table 1, which was filled into a 12-well plate (made of polystyrene) and stored at 34°C under shaking conditions for 72 minutes (lipid-protein soiling solution treatment).

[0064] [Table 1]

[0065] Thereafter, 2 mL of each of the formulations shown in Table 2 below was filled into a 12-well plate (made of polystyrene) and the contact lenses that had been treated with the lipid-protein soil solution were immersed in the plates for 15 minutes. After that, the contact lens was removed, and the soft contact lens was attached to the contact of a friction tester (Tribomaster TL201Ts, manufactured by Trinity Labs). On the other hand, 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 on the artificial leather so that it was sufficiently distributed over the entire surface where the contact could move. Next, a 20 g weight was attached to the measurement unit. The contact to which the soft contact lens was attached was attached to the measurement unit, and measurements were performed 100 times per second for 20 seconds. The average value of the friction coefficient obtained from the measurement results for 5 to 20 seconds after the start of measurement was calculated, and this was taken as the friction coefficient (μk) of the formulation. For the obtained friction coefficient values, the friction reduction rate (%) relative to the corresponding comparative example was calculated using the following formula 1. The corresponding comparative examples are Comparative Example 1-1 for Examples 1-1-1 and 1-1-2, Comparative Example 1-2 for Example 1-2, Comparative Example 1-3 for Example 1-3, Comparative Example 1-4 for Example 1-4, and Comparative Example 1-5 for Example 1-5.

[0066] [Formula 1] Friction reduction rate (%) = (1 - friction coefficient of sample to be measured / friction coefficient of corresponding comparative example) x 100

[0067] [Table 2]

[0068] In a test simulating the case where a composition containing polyvinylpyrrolidone K90 and a boric acid buffer is instilled into contact lenses after wearing for a certain period of time, it was confirmed that the friction coefficient tends to be significantly reduced by using the composition of the example, as can be seen from a comparison between Example 1-1-1 and the corresponding Comparative Example 1-1 in Table 2 above. Similarly, it was confirmed that the friction reduction effect can be obtained when the amount of polyvinylpyrrolidone K90 is changed, and when the conditions such as the type, concentration, and pH of the buffer or salt are changed.

[0069] <Test Example 2: Evaluation of friction reduction durability> A soft contact lens (product name: 1-DAY ACUVUE (etafilcon A, soft contact lens classification according to the US Food and Drug Administration (FDA) standards: Group IV, manufactured by Johnson & Johnson) was rinsed with phosphate buffered saline (sodium chloride: 0.8 w / v%, sodium hydrogen phosphate dodecahydrate: 0.6 w / v%, sodium dihydrogen phosphate dihydrate: 0.053 w / v%), and after wiping off any excess liquid on the surface, the lens was immersed one by one in 2 mL of the lipid-protein soiling solution shown in Table 1, which was filled into a 12-well plate (made of polystyrene) and stored at 34°C under shaking conditions for 36 minutes (lipid-protein soiling solution treatment). Then, 2 mL of each of the formulations listed in Table 3 below was filled into a 12-well plate (made of polystyrene), and the contact lenses that had been treated with the lipid-protein soil solution were immersed in the plates and stored at 34°C under shaking conditions for 15 minutes. The surfaces of the contact lenses were then thoroughly rinsed with saline, and each lens was then immersed in 2 mL of the lipid-protein soil solution shown in Table 1, which was then filled into a 12-well plate (made of polystyrene), and stored at 34°C under shaking conditions for 36 minutes (re-treated with lipid-protein soil solution after immersion in the formulation solution). Thereafter, the friction coefficient of the treated contact lens was measured under the same conditions as in Test Example 1, and the friction reduction rate (%) was calculated using the above-mentioned formula 1. Here, the corresponding comparative examples are Comparative Example 2-1 for Example 2-1, Comparative Example 2-2 for Example 2-2, and Comparative Example 2-3 for Example 2-3.

[0070] [Table 3]

[0071] From Table 3 above, it was confirmed that the friction coefficient tended to be reduced even in contact lenses that were immersed in the prescription solution and then treated with the lipid-protein soiling solution. From this result, it was confirmed that the friction reducing effect, i.e., the friction reducing effect is sustained, even in contact lenses that are being worn and even after a certain period of time has passed since instillation.

[0072] <Test Example 3: Usability Test (1)> Each eye drop was prepared according to the formulation example shown in Table 4 below, and 13 mL was aseptically filled into a polyethylene terephthalate eye drop container with a capacity of 14.2 mL. After filling, a polyethylene nozzle was attached to the eye drop container. Ten subjects wearing soft contact lenses (product name: 1-DAY ACUVUE (etafilcon A, soft contact lens classification according to the U.S. Food and Drug Administration (FDA) standards: Group IV, manufactured by Johnson & Johnson) were administered one drop (40 μL) of each eye drop into each of the left and right eyes 8 hours after wearing the contact lenses. Then, according to the method described below, the feeling of use after administration was evaluated by VAS (visual analog scale) for each item, and the change in score before and after administration (after administration - before administration) was calculated. The results are also shown in Table 4 below. The test was conducted after confirming that there was no difference in the condition of the left and right eyes of the subjects. [Evaluation of Usability] Immediately after administering the medicine, the subjective symptoms survey sheet had a 100mm line drawn on it. - 100mm indicates very easy blinking, 0mm indicates very difficult blinking, 100mm indicates a strong foreign body sensation, 0mm indicates no foreign body sensation at all, The subject marked the degree of the item that they felt, with 100mm representing very good contact lens comfort and 0mm representing very bad comfort. This length (mm) was used as the VAS score. In other words, with regard to ease of blinking, the more positive the change in the VAS value, the more improved the ease of blinking due to the eye drops; with regard to foreign body sensation, the more negative the VAS value, the less the foreign body sensation due to the eye drops, i.e., the more improved; and with regard to comfort of wearing contact lenses, the more positive the VAS value, the more improved the comfort of wearing contact lenses due to the eye drops.

[0073] [Table 4]

[0074] When the eye drops were applied 8 hours after wearing the contact lenses, in Example 3-1 in Table 4 above, the change in ease of blinking was greater, the change in foreign body sensation was smaller, and the change in contact lens wearing comfort was greater than in Comparative Example 3-1. This confirms that the eye drops applied in the Example made blinking easier, eliminated foreign body sensation, and improved contact lens wearing comfort. In addition, a similar test was conducted using a formulation example (Example 3-1') similar to that of Example 3-1, except that the content of polyvinylpyrrolidone K90 was 0.05 w / v%, and it was confirmed that Example 3-1' tended to make the wearer feel that blinking was easier than Comparative Example 3-1.

[0075] <Test Example 4: Usability Test (2)> The same method as in Test Example 3 was used to examine the amount of change in the items due to instillation, except that each eye drop was prepared according to the formulation example shown in Table 5 below, that evaluation of instillation and the results before and after instillation was performed one hour after wearing the contact lenses, and that the test items were only ease of blinking and contact lens wearing comfort.

[0076] [Table 5]

[0077] In the evaluation one hour after wearing the contact lenses, Example 4-1 in Table 5 above showed a greater change in ease of blinking and a greater change in contact lens wearing comfort than Comparative Example 4-1, confirming that the Example made blinking easier and improved contact lens wearing comfort by instilling the eye drops.

[0078] When the eye drops were administered five times a day, it was confirmed that the contact lens wearing comfort was improved, as in the above Example group.

[0079] <Formulation examples> Eye drops for contact lenses (CL) (Preparation Examples 1 to 34) are prepared by a conventional method according to the formulations shown in the following Tables 6 to 9. The unit of each component amount in the tables is "w / v%" unless otherwise stated in the tables.

[0080] [Table 6]

[0081] [Table 7]

[0082] [Table 8]

[0083] [Table 9] [Industrial Applicability]

[0084] The present invention can be widely used as an eye drop for contact lenses for reducing friction of the contact lenses during wear.

Claims

[Claim 1] The invention described in the specification.

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