JP2023025297A - Contact lens eye drop for friction reduction, method of using the same, and method of reducing friction of contact lens when worn - Google Patents

Abstract

PROBLEM TO BE SOLVED: 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

COPYRIGHT: (C)2023,JPO&INPIT

Description

TECHNICAL FIELD The present invention relates to a friction-reducing contact lens eye drop that reduces friction, in particular that maintains friction reduction.

In the eye, friction occurs between the eyelid, cornea, and conjunctiva when motion such as blinking is applied, and this is said to cause abnormalities in the keratoconjunctiva, the tear film, and the eyelid. In particular, when a contact lens is worn, friction is generated between the contact lens and these tissues, and this friction is thought to lead to deterioration in wearing comfort of the contact lens.

Conventionally, as a method for reducing the friction of contact lenses, hypromellose with a viscosity of 2 w / w% aqueous solution at 20 ° C. of 5.1 mPa s or less has a concentration of 0.5 to 1.5 w / v%, 4 w at 20 ° C. /w% aqueous solution with a viscosity of 10 to 35 mPa·s is contained at a concentration of 0.8 to 2 w/v%, and the kinematic viscosity at 20 ° C. is 3.0 to 8.0 mm ² /s (Patent Document 1).

JP 2012-198538 A

There is a need for a method of reducing friction that is more effective and convenient for contact lens wearers. The present invention provides a contact lens eye drop for friction reduction of a contact lens used to reduce friction, particularly to sustain friction reduction, a method of using the same, and a method of reducing friction of a contact lens during wear. Its purpose is to

As a result of intensive studies to solve the above problems, the present inventors selected (A) polyvinylpyrrolidone having a K value of 70 or more among polyvinylpyrrolidones as a component of eye drops for contact lenses. The inventors have unexpectedly found that the resulting contact lens eye drop can significantly reduce the friction of the contact lens during wear by incorporating (B) a buffering agent into (B), and have completed the present invention.

That is, the present invention provides the following [1] to [9].
[1] An eye drop for contact lenses for reducing friction, containing (A) polyvinylpyrrolidone having a K value of 70 or more and (B) a buffering agent.
[2] The contact lens ophthalmic solution of [1], wherein the component (A) is polyvinylpyrrolidone K90.
[3] The eye drop for contact lenses according to [1] or [2], wherein the content of component (A) is 0.001 to 5 w/v% based on the total weight of the eye drop.
[4] The contact lens of 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. Eye drops for.
[5] The eye drop for contact lenses according to any one of [1] to [4], wherein the content of component (B) is 0.001 to 10 w/v% based on the total weight of the eye drop. .
[6] The contact lens ophthalmic solution according to any one of [1] to [5], further comprising (C) a salt.
[7] The eye drop for contact lenses according to [6], wherein the content of component (C) is 0.001 to 5 w/v% based on the total weight of the eye drop.
[8] A method of using the contact lens ophthalmic solution according to any one of [1] to [7], wherein the dose of the contact lens ophthalmic solution is 10 to 200 μL per eye drop. .
[9] A method of reducing friction by instilling a contact lens eye drop containing (A) polyvinylpyrrolidone having a K value of 70 or more and (B) a buffer while wearing a contact lens.

The contact lens eye drop of the present invention contains (A) polyvinylpyrrolidone having a K value of 70 or more and (B) a buffering agent, thereby providing an eye drop capable of effectively suppressing friction. It becomes possible.

Next, an embodiment of the present invention will be described in detail. However, the present invention is not limited to the following embodiments.

As used herein, the content unit "w/v %" indicates the ratio of mass to volume, and is synonymous with "g/100 mL".
As used herein, unless otherwise specified, the abbreviation "POE" means polyoxyethylene.
As used herein, unless otherwise specified, the abbreviation "POP" means polyoxypropylene.

The eye drops for contact lenses according to the present embodiment (hereinafter sometimes abbreviated as "eye drops") are for reducing the friction of contact lenses during wear, and include (A) polyvinylpyrrolidone having a K value of 70 or more; , and (B) a buffer. Each component will be described below.

<(A) Component>
The (A) polyvinylpyrrolidone having a K value of 70 or more is a nonionic water-soluble polymer, and the K value is calculated according to the method described in the Japanese Pharmacopoeia 17th Edition "Povidone". be.

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

Among these, polyvinylpyrrolidone with a K value of 80 or more is preferable, polyvinylpyrrolidone with a K value of 90 or more is more preferable, and polyvinylpyrrolidone with a K value of 90 to 120 is preferable from the viewpoint of exhibiting the effects of the present invention more remarkably. is more preferred. Among them, polyvinylpyrrolidone K90 is particularly preferably used. Here, the K value is 90 to 108% of the displayed K value in accordance with the description of the K value in the Japanese Pharmacopoeia 17th Edition "Povidone". Viscosity characteristic value) is in the range of 81.0 to 97.2.

The above-mentioned polyvinylpyrrolidone K90 may be synthesized by a known method. ), Povidone K90 (manufactured by DSP Gokyo Food & Chemical Co., Ltd.) and other commercially available products may be used. And these may be used individually by 1 type, or may be used in combination of 2 or more type.

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

<(B) Component>
(B) The buffering agent is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutical) or physiologically acceptable.

Such buffers (B) include, for example, borate buffers, phosphate buffers, carbonate buffers, citric acid buffers, acetate buffers, epsilon-aminocaproic acid, and sodium L-glutamate. etc. These (B) buffering agents can be used alone or in combination of two or more.
Boric acid-based buffers include boric acid or salts thereof (alkali metal borates, alkaline earth metal borates, etc.). Phosphate-based buffers include phosphoric acid and salts thereof (alkali metal phosphate, alkaline earth metal phosphate, etc.). Carbonic acid-based buffering agents include carbonic acid and salts thereof (alkali metal carbonates, alkaline earth metal carbonates, etc.). The citric acid-based buffer includes citric acid or salts thereof (alkali metal citrate, alkaline earth metal citrate, etc.). Examples of acetic acid-based buffers include acetic acid and salts thereof (alkali metal acetate, alkaline earth metal acetate, etc.).
In addition, borate, phosphate, carbonate, citrate, acetate, or A hydrate of sodium L-glutamate may also be used. More specific examples include boric acid or a salt thereof (sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, borax, etc.) as a boric acid-based buffer; phosphoric acid as a phosphate-based buffer; or a salt thereof (disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, trisodium phosphate, tripotassium phosphate, calcium monohydrogen phosphate, calcium dihydrogen phosphate, etc.); carbonate-based buffering agent as carbonic acid or its salts (sodium hydrogen carbonate, sodium carbonate, ammonium carbonate, potassium carbonate, calcium carbonate, potassium hydrogen carbonate, magnesium carbonate, etc.); potassium acetate, calcium citrate, sodium dihydrogen citrate, disodium citrate, etc.); acetic acid 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), phosphate buffers (for example, a combination of disodium hydrogen phosphate and sodium dihydrogen phosphate), Citric acid-based buffers, epsilon-aminocaproic acid, sodium L-glutamate are preferred, boric acid-based buffers, phosphate-based buffers and citric acid-based buffers are more preferred, and boric acid-based buffers (boric acid and its salts at least one of) is more preferable.

The content of the buffering agent (B) is appropriately set according to the type of the buffering agent (B), the type and content of other components, and the like. (B) The content of the buffering agent is preferably 0.001 to 10 w/v%, more preferably 0.005 to 5 w/v%, more preferably 0.005 to 5 w/v%, based on the total amount of the eye drop. 01 to 2.5 w/v% is more preferred, and 0.04 to 2 w/v% is even more preferred.

The content ratio of component (B) to component (A) in the eye drops according to the present embodiment is not particularly limited. It is appropriately set according to the use of the agent, the formulation form, and the like. As for the content ratio of component (B) to component (A), from the viewpoint of exhibiting the effects of the present invention more remarkably, for example, the content of component (A) contained in the eyedrops according to the present embodiment is On the other hand, the content of component (B) is preferably 0.0001 to 500 parts by mass, more preferably 0.001 to 300 parts by mass, and 0.01 to 100 parts by mass. It is more preferably 0.1 to 50 parts by mass, and particularly preferably 0.4 to 25 parts by mass.

<(C) Component>
Moreover, it is preferable that the eyedrops according to the present embodiment further contain (C) salts from the viewpoint of exhibiting the effects of the present invention more remarkably.

As the salt (C), both inorganic salts and organic salts can be used (except for the component (B)). 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 (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.

When the above-mentioned (C) salt is contained, the content thereof is appropriately set according to the type of (C) salt, the type and content of other ingredients, and the like. (C) The content of salts is, for example, preferably 0.001 to 5 w/v%, more preferably 0.01 to 3 w/v%, based on the total amount of the ophthalmic solution according to the present embodiment. is more preferably 0.05 to 2 w/v%, even more preferably 0.1 to 1 w/v%, particularly 0.4 to 0.8 w/v% preferable.

The content ratio of component (C) to component (A) in the ophthalmic solution according to the present embodiment is not particularly limited. It is appropriately set according to the use of the agent, the formulation form, and the like. As for the content ratio of component (C) to component (A), from the viewpoint of exhibiting the effects of the present invention more remarkably, for example, the content of component (A) contained in the eye drops according to the present embodiment is On the other hand, the content of component (C) is preferably 0.001 to 500 parts by mass, more preferably 0.01 to 100 parts by mass, and 0.05 to 50 parts by mass. More preferably, it is still more preferably 0.1 to 20 parts by mass.

<Other optional ingredients>
The eyedrops according to the present embodiment can 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. Amino acids mean compounds or derivatives thereof having an amino group and a carboxy group or a sulfo group in the molecule. Specifically, amino acids, mucopolysaccharides, and salts thereof are exemplified. Among amino acids, amino acids and salts thereof include, for example, monoaminomonocarboxylic acids such as glycine, alanine, γ-aminobutyric acid, and γ-aminovaleric acid; monoaminodicarboxylic acids such as aspartic acid and glutamic acid; and salts thereof. diaminomonocarboxylic acids such as arginine and lysine and salts thereof; derivatives such as aminoethylsulfonic acid (taurine) and salts thereof. The amino acids and salts thereof may be L-, D-, or DL-forms, and examples thereof include potassium L-aspartate, magnesium L-aspartate, and a mixture of equal amounts of magnesium and potassium L-aspartate. . Among amino acids, mucopolysaccharides, derivatives thereof, and salts thereof include, for example, acidic mucopolysaccharides such as chondroitin sulfate, hyaluronic acid, alginic acid, and salts thereof. Amino acid salts or mucopolysaccharide salts include pharmaceutically, pharmacologically or physiologically acceptable salts. Such salts include salts with organic acids [e.g., monocarboxylic acid salts (acetate, trifluoroacetate, butyric acid salt, palmitate, stearate, etc.), polycarboxylic acid salts (fumarate , maleate, etc.), oxycarboxylate (lactate, tartrate, citrate, succinate, malonate, etc.), organic sulfonate (methanesulfonate, toluenesulfonate, etc.), etc.] , salts with inorganic acids (e.g., hydrochlorides, sulfates, nitrates, hydrobromides, phosphates, etc.), salts with organic bases (e.g., methylamine, triethylamine, triethanolamine, morpholine, piperazine, salts with organic amines such as pyrrolidine, tripyridine and picoline), salts with inorganic bases [e.g., ammonium salts; alkali metals (sodium, potassium, etc.), alkaline earth metals (calcium, magnesium, etc.), metals such as aluminum and the like] can be exemplified, and can be 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.

Among such amino acids, potassium aspartate, magnesium aspartate, an equivalent mixture of magnesium and potassium L-aspartate, aminoethylsulfonic acid, and mucopolysaccharides are particularly preferable, and mucopolysaccharides are more preferable, sodium chondroitin sulfate, Sodium hyaluronate is more preferred, and sodium chondroitin sulfate is particularly preferred.
These amino acids can be used alone or in combination of two or more.

The content of the above amino acids is not particularly limited, and is appropriately set according to the type of amino acid, the type and content of components (A) and (B) used in combination, and the like. The amino acid content is preferably 0.01 to 8 w/v%, preferably 0.02 to 5 w/v%, based on the total amount of the ophthalmic solution according to the present embodiment. v % is more preferred, 0.05 to 3 w/v % is more preferred, and 0.1 to 2 w/v % is particularly preferred.

Moreover, the eyedrops according to the present embodiment can further contain a thickening agent in addition to the components (A) and (B) within a range that does not impair the effects of the present invention. Examples of such thickening agents include polyvinyl alcohol (fully or partially saponified), polyvinylpyrrolidone (K25, K30), carboxyvinyl polymer, cellulose derivatives [methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, (hypromellose) (2208, 2906, 2910, etc.), carboxymethylcellulose, carboxyethylcellulose, nitrocellulose or salts thereof], gum arabic, tragacanth, dextran (40, 70, etc.), etc., preferably polyvinyl alcohol (complete or partially saponified products), polyvinylpyrrolidone (K25, K30), carboxyvinyl polymer, cellulose derivatives, dextran (70), more preferably cellulose derivatives, still more preferably hydroxyethyl cellulose, hydroxypropylmethyl cellulose, Hydroxypropylmethylcellulose 2208, Hydroxypropylmethylcellulose 2906 and Hydroxypropylmethylcellulose 2910 are even more preferred.
These thickeners can be used alone or in combination of two or more.

When the above-mentioned thickening agent is contained, its content is appropriately set according to the type of thickening agent, the type and content of other ingredients, and the like. As for the content of the thickening agent, for example, the content of the thickening agent is preferably 0.0001 to 5 w/v%, preferably 0.001 to 5 w/v%, based on the total amount of the eye drops according to the present embodiment. It is more preferably 3 w/v %, still more preferably 0.01 to 2 w/v %, and particularly preferably 0.1 to 1 w/v %.

The eye drops according to the present embodiment can 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. Nonionic surfactants are not particularly limited as long as they are pharmaceutically, pharmacologically (pharmaceutical) or physiologically acceptable.

Specific examples of nonionic surfactants that can be used in the eye drops according to the present embodiment include POE (20) sorbitan monourarate (polysorbate 20), POE (20) sorbitan monopalmitate (polysorbate 40), mono POE sorbitan fatty acid esters such as POE (20) sorbitan stearate (polysorbate 60), POE (20) sorbitan tristearate (polysorbate 65), POE (20) sorbitan monooleate (polysorbate 80); POE (40) hardened castor POE hydrogenated castor oil such as oil (polyoxyethylene hydrogenated castor oil 40), POE (60) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 60); POE (3) castor oil (polyoxyethylene hydrogenated castor oil 3), POE (10) POE castor oil such as castor oil (polyoxyethylene castor oil 10), POE (35) castor oil (polyoxyethylene castor oil 35); POE (9) POE alkyl ether such as lauryl ether; POE (20) POE-POP alkyl ethers such as POP(4) cetyl ether; 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), polyoxyethylene/polyoxypropylene glycol such as POE (200) POP (70) glycol; and polyethylene glycol monostearate such as polyoxyl 40 stearate. In the compounds exemplified above, the numbers in parentheses indicate the number of moles of alkylene oxide added.

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

When the above nonionic surfactant is contained, its content is appropriately determined according to the type of nonionic surfactant used, the type and content of other compounding ingredients, the application of eye drops, the formulation form, the method of use, etc. For example, the content of the nonionic surfactant is preferably 0.001 to 3 w/v%, more preferably 0.005 to 2 w/v%, based on the total amount of the eye drops according to the present embodiment. v % is more preferred, 0.01 to 1 w/v % is more preferred, and 0.05 to 0.5 w/v % is particularly preferred.

Moreover, the eye drops according to the present embodiment can further contain a cooling agent in addition to the components (A) and (B) within a range that does not impair the effects of the present invention. The cooling agent is not particularly limited as long as it is a substance that imparts a refreshing feeling to the eye drops. For example, terpenoids, terpenoid-containing essential oils (eg, eucalyptus oil, bergamot oil, peppermint oil, fennel oil, rose oil, cinnamon oil, spearmint oil, camphor oil, cool mint, mint oil, etc.). Terpenoids include, for example, menthol, menthone, camphor (also referred to as “camphor” or “camphor”), borneol (also referred to as “ryunou” or “borne”), geraniol, nerol, cineol, citronellol, carvone, anethole, eugenol, Limonene, linalool and linalyl acetate are mentioned. Terpenoids may be d-, l- or dl-forms, exemplified by l-menthol, d-menthol, dl-menthol, dl-camphor, d-camphor, dl-borneol and d-borneol. From the viewpoint of exhibiting the effects of the present invention more remarkably, menthol, camphor, borneol, geraniol or mint oil are preferred, l-menthol, d-camphor, dl-camphor or d-borneol are more preferred, l- Menthol is particularly preferred.
These cooling agents can be used alone or in combination of two or more.

The content of the cooling agent is not particularly limited, and is appropriately set according to the type of the cooling agent, the type and content of the components (A) and (B) used in combination, and the like. The content of the cooling agent can be measured as a terpenoid. For example, the content of the cooling agent (as a terpenoid) is 0.00001 to 1 w/w based on the total amount of the eye drops according to the present embodiment. v%, more preferably 0.00005 to 0.5 w/v%, even more preferably 0.0001 to 0.2 w/v%, 0.0005 to 0.1 w/v% % is particularly preferred, and 0.001 to 0.05 w/v % is particularly preferred. The above content of the cooling agent is suitable from the viewpoint of exhibiting the effects of the present invention more remarkably.

The eye drops according to the present embodiment can 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. Polyhydric alcohols include, for example, polyethylene glycol (400, 4000, 6000, etc.), propylene glycol, glycerin and the like. As the polyhydric alcohol, propylene glycol, glycerin, and polyethylene glycol are preferred, and polyethylene glycol is more preferred, from the viewpoint of exhibiting the effects of the present invention more remarkably. A commercially available polyhydric alcohol can also be used.
These polyhydric alcohols may be used alone or in combination of two or more.

The content of the polyhydric alcohol that can be used in the eye drops according to the present embodiment is not particularly limited, and the type of polyhydric alcohol, the type and content of other compounding ingredients, the application and formulation form of the eye drops, etc. is set as appropriate. The content of the polyhydric alcohol is, for example, 0.01 to 5 w/v% based on the total amount of the eye drop, from the viewpoint of exhibiting the effect of the present invention more remarkably. is preferred, 0.05 to 2 w/v% is more preferred, 0.1 to 1 w/v% is even more preferred, and 0.1 to 0.75 w/v% is particularly preferred.

The pH of the eye drops according to the present embodiment is not particularly limited as long as it is within a pharmaceutically, 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, and even more preferably 5.5 to 8.5. Even more preferably 6.5 to 8.0.

Moreover, the osmotic pressure ratio of the eye drops according to the present embodiment is not particularly limited as long as it is within a range acceptable to living organisms. 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. , 0.8 to 1.55. Adjustment of osmotic pressure can be performed by methods known in the art using inorganic salts, polyhydric alcohols, sugar alcohols or sugars. The osmotic pressure ratio is the ratio of the osmotic pressure of the sample to 286 mOsm (osmotic pressure of 0.9 w/v% sodium chloride aqueous solution) based on the 17th revision of the Japanese Pharmacopoeia, and the osmotic pressure is the osmotic pressure measurement method described in the Japanese Pharmacopoeia. (freezing point depression method). In addition, for the standard solution for osmotic pressure ratio measurement (0.9 w/v% sodium chloride aqueous solution), after drying sodium chloride (Japanese Pharmacopoeia standard reagent) at 500 to 650 ° C. for 40 to 50 minutes, in a desiccator (silica gel) Allow to cool, accurately weigh 0.900 g, dissolve in purified water to prepare exactly 100 mL, or use a commercially available standard solution for osmotic pressure ratio measurement (0.9 w / v% sodium chloride aqueous solution). .

The viscosity of the eyedrops according to the present embodiment is not particularly limited as long as it is within a range acceptable to living organisms. 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, 1 to 100 mPa s. s, more preferably 1 to 50 mPa·s.

Further, in the eye drops according to the present embodiment, in addition to the above ingredients, various pharmacologically active ingredients or physiologically active ingredients are appropriately selected and used alone or in combination of two or more, as long as the effects of the present invention are not hindered. may be contained in an appropriate amount. Such ingredients are not particularly limited, and can be exemplified by, for example, active ingredients in various drugs described in the 2012 version of the Standards for Approval of Manufacturing and Marketing of OTC Drugs (supervised by the Japanese Society of Regulatory Science). Specifically, the components used in ophthalmic drugs include the following components.

Antihistamines: for example, iproheptine, diphenhydramine hydrochloride, chlorpheniramine maleate, ketotifen fumarate, olopatadine hydrochloride, levocabastine hydrochloride and the like.
- Anti-allergic agents: for example, cromoglycate sodium, tranilast, pemirolast potassium, acitazanolast and the like.
- Steroid agents: for example, fluticasone propionate, fluticasone furoate, mometasone furoate, beclomethasone propionate, flunisolide and the like.
• Decongestants: for example, tetrahydrozoline hydrochloride, tetrahydrozoline nitrate, naphazoline hydrochloride, naphazoline nitrate, epinephrine, epinephrine hydrochloride, ephedrine hydrochloride, phenylephrine hydrochloride, dl-methylephedrine hydrochloride and the like.
Ocular muscle modulating drug: For example, cholinesterase inhibitors having an active center similar to that of acetylcholine, specifically neostigmine methyl sulfate, tropicamide, helenien, atropine sulfate, and the like.
Antiphlogistic agent: 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, and the like.
- Astringents: for example, zinc white, zinc lactate, zinc sulfate and the like.
Vitamins: for example, flavin adenine dinucleotide sodium, cyanocobalamin, pyridoxine hydrochloride, panthenol, calcium pantothenate, sodium pantothenate, retinol acetate, retinol palmitate, tocopherol acetate and the like.
• Local anesthetics: eg, lidocaine and the like.
- Others: For example, sulfamethoxazole, sulfamethoxazole sodium and the like.

In addition, in the eye drops according to the present embodiment, various additives are appropriately selected according to a conventional method according to the application or formulation form, as long as the effects of the invention are not impaired, and one or two additives are added. More than seeds may be used in combination to contain an appropriate amount. Examples of such additives include various additives described in Pharmaceutical Excipients Encyclopedia 2016 (edited by Japan Pharmaceutical Excipients Association). Typical ingredients include the following additives.

• Carrier: For example, an aqueous carrier such as water or hydrous ethanol.
- Sugars: For example, glucose, cyclodextrin, and the like.
- Sugar alcohols: for example, xylitol, sorbitol, mannitol, and the like. These may be d-, l- or dl-forms.
Stabilizers: e.g. trometamol, sodium formaldehyde sulfoxylate (Rongalit), tocopherol, edetic acid and its salts (sodium edetate), sodium pyrosulfite, monoethanolamine, aluminum monostearate, glyceryl monostearate, dibutyl hydroxytoluene and the like.
Anionic surfactants: for example, alkylbenzenesulfonates, alkylsulfates, polyoxyethylene alkylsulfates, α-sulfo fatty acid ester salts, α-olefinsulfonic acids and the like.
Antiseptics, fungicides or antibacterial agents: for example zinc chloride, alkyldiaminoethylglycine hydrochloride, sodium benzoate, ethanol, benzalkonium chloride, benzethonium chloride, chlorobutanol, sorbic acid, potassium sorbate, sodium dehydroacetate, paraoxy Methyl benzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, butyl parahydroxybenzoate, oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, biguanide compounds (specifically, polyhexanide or its hydrochloride, etc.), polydronium chloride, glochil ( product name manufactured by Rhodia), etc.
- pH adjuster: 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, apple acid, succinic acid, gluconolactone, ammonium acetate and the like.
Oils: For example, vegetable oils such as sesame oil, castor oil, soybean oil, and olive oil, animal oils such as squalane, liquid paraffin, and mineral oils such as petrolatum.

The eye drops according to the present embodiment are prepared by incorporating the components (A) and (B) and, if necessary, other optional components into a carrier in desired amounts. As the carrier, pharmaceutically, pharmacologically (pharmaceutical) or physiologically acceptable water may be used, and examples of such water include distilled water, ordinary water, purified water, and sterilized water. Purified water, water for injection, distilled water for injection and the like are exemplified.

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 drops according to the present embodiment. can.

The eye drop according to the present embodiment has a water content of 85 w/v% or more, preferably 90 w/v% or more, and preferably 92 w/v% or more, based on the total amount of the eye drop. More preferably, it is 94 w/v% or more, and particularly preferably 95 w/v% or more.

The eye drops according to this embodiment can take various formulation forms depending on the purpose. Examples of formulation forms include liquids and gels. The eye drops according to the present embodiment are preferably liquid formulations.

The ophthalmic solution according to this embodiment is provided in an arbitrary container. The container for containing 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 plastics include polyethylene terephthalate, polyarylate, polyethylene naphthalate, polycarbonate, polyethylene, polypropylene, polyimide, copolymers of these monomers, and mixtures of two or more of these. Preferred is polyethylene terephthalate. Moreover, the container containing the eye drops according to the present embodiment may be a transparent container in which the inside of the container can be visually recognized, or an opaque container in which the inside of the container is difficult to visually recognize. A transparent container is preferred. Here, the "transparent container" includes both a colorless transparent container and a colored transparent container. The ophthalmic solution according to the present embodiment can be used, for example, in a multi-dose form that can be used repeatedly, in a colored and transparent plastic container or the like. Moreover, as another aspect, it can also be used by housing in the form of a unit dose.

In addition, the usage and dosage of the eye drops according to the present embodiment are not particularly limited as long as they are effective and have few side effects. From the viewpoint of the effects of the present invention, it is preferable that the volume is 20 to 150 μL. A single eye drop dosage is, for example, for adults (15 years old or older) and children aged 7 years or older, when an interval of about 15 minutes or more (replacement time of tear fluid) is opened, at the time of single use Refers to the eye drop administration amount (drip amount), and usually refers to an amount equivalent to 1 to 3 drops.
In addition, the frequency of instillation is preferably 3 to 6 times a day (for example, morning, noon, evening, and before bedtime), and more preferably 5 to 6 times.

The eye drops according to the present embodiment are eye drops for contact lenses that can be used as pharmaceuticals or quasi-drug formulations and can be applied to the eye while wearing contact lenses. The eye drops for contact lenses of the present invention can be used for the purpose of instillation even when not wearing contact lenses, including before and after wearing contact lenses, in addition to when wearing contact lenses. In addition, the eye drop for contact lenses of the present invention only needs to include an embodiment in which it is used by instillation into the eye, and therefore, for example, in addition to the above embodiment, it also has an embodiment in which it is used by directly dropping it onto a contact lens before wearing. Eye drops for contact lenses may also be used.

In addition, the eye drops according to the present embodiment are preferably used for soft contact lenses among contact lenses. Among them, it can be applied to any soft contact lens classified into Groups I to IV in the soft contact lens classification according to the standards of the US Food and Drug Administration (FDA). , ionic) is particularly preferred. Here, ionic means that the content of the ionic component in the contact lens is 1 mol % or more.

Soft contact lenses classified into Group IV include, for example, etafilcon A, metafilcon A, metafilcon B, occufilcon A, occufilcon B, occufilcon C, and occufilcon in the United States Approved Names. D, occufilcon E, femfilcon A, bifilcon A, etc., and the effects of the present invention are more remarkably exhibited during wearing of these, so the eye drops according to the present embodiment can be preferably used. . Etafilcon A is particularly preferred.

In addition, among soft contact lenses, colored contact lenses that have colors or patterns printed on the surface by a method such as printing have greater friction on the contact lens surface than non-colored contact lenses. It is also preferred that it is an eye drop for contact lenses.

The eye drops according to the present embodiment reduce friction on all surfaces of the 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) when the contact lens is worn. Therefore, the friction between the contact lens and the cornea and between the contact lens and the conjunctiva can be effectively reduced. Therefore, it is possible to reduce foreign body sensation while wearing contact lenses, and to improve ease of blinking and comfort.
At the same time, the eye drops in the present embodiment are used in ocular tissues (conjunctiva [conjunctiva at the eyelid margin: including lid wiper], between the conjunctiva and the cornea, etc.) in contact with the eye drop, during blinking, etc. Since the frictional resistance is reduced and smoothed, there is an effect that the discomfort in the eyes is more significantly reduced.

Furthermore, since the eye drops in the present embodiment reduce the frictional contact of the contact lens, the contact lens itself can be prevented from being scratched due to the friction of the contact lens (contact friction with the cornea, conjunctiva, and dust). can. If there is a scratch on the contact lens, not only will it cause a decrease in corrected vision, but also dirt and bacteria may easily adhere to the contact lens, causing damage to the cornea and conjunctiva. These problems can also be prevented by preventing the occurrence of scratches.

In addition, the replacement time of the aqueous tear layer is usually about 15 minutes. The reduction effect decreases sharply. However, the eye drops according to the present embodiment can maintain the friction-reducing effect even when the lacrimal liquid is replaced after the eye drop.

Therefore, as one embodiment of the present invention, an ophthalmic solution containing (A) polyvinylpyrrolidone having a K value of 70 or more and (B) a buffer to reduce friction, particularly to sustain friction reduction. Provided are contact lens drops for reducing friction of the eye.

Further, as one embodiment of the present invention, there is provided a method for reducing contact lens friction during wearing of a contact lens, comprising (A) polyvinylpyrrolidone having a K value of 70 or more, and (B) a buffering agent. A method is provided that includes instilling an agent into the eye. "While wearing a contact lens" may be a state in which the contact lens is worn, and may be immediately after wearing the contact lens or after a certain period of time has elapsed while wearing the contact lens.

As a method for reducing the friction of contact lenses, in addition to eye drops, a method of blending a substance having a friction-reducing effect into the packaging liquid of the contact lens or kneading it into the contact lens itself can be considered. In the case of contact lenses, there is a problem that the handling performance when removing the contact lens from the case may be deteriorated, the friction reduction effect is reduced by continuous wear, and it is not possible to immediately deal with the friction when it is detected. . On the other hand, the eye drops and the method for reducing friction in the present embodiment can be applied universally regardless of the type of contact lens to be targeted, and can be applied when a feeling of friction is felt to detect symptoms. You can get rid of the symptoms immediately. In addition, by applying the eye drops to the contact lenses to which stains such as lipids and proteins have adhered due to wearing, a significant effect of reducing friction can be exhibited.

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

EXAMPLES 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 each component amount in the table below is all "w/v %". In addition, "appropriate amount" in the table indicates an amount to obtain a predetermined pH.

<Test Example 1: Evaluation of friction reduction>
Soft contact lens [product name: 1day Acuvue (etafilcon A), soft contact lens classification according to US Food and Drug Administration (FDA) standards: Group IV, manufactured by Johnson & Johnson], phosphate buffered saline Rinse with water (sodium chloride: 0.8 w / v%, sodium hydrogen phosphate dodecahydrate: 0.6 w / v%, sodium dihydrogen phosphate dihydrate: 0.053 w / v%), After wiping off the excess liquid that adhered, 2 mL each of the lipid-protein stain liquid shown in Table 1 below was filled in a 12-well plate (made of polystyrene), immersed one by one, and shaken at 34 ° C. for 72 hours. stored for minutes (lipid-protein stain solution treatment).

After that, 12-well plates (made of polystyrene) were filled with 2 mL of each prescription solution shown in Table 2 below, and the contact lenses after the lipid-protein staining solution treatment were immersed for 15 minutes.
After that, the contact lens was taken out, and the soft contact lens was adhered to the contactor of a friction tester (Tribomaster TL201Ts, manufactured by Trinity Lab). On the other hand, an artificial leather immersed in physiological saline for 1 hour was attached to a moving table of a friction tester, and 4 mL of physiological saline was spread over the artificial leather so as to sufficiently cover the entire surface on which the contactor could move. Next, a weight of 20 g was attached to the measuring unit. The contact to which the soft contact lens was adhered was attached to the measurement unit, and measurement was performed 100 times per second for 20 seconds. The average value of the friction coefficients obtained from the measurement results for 5 to 20 seconds after the start of measurement was calculated and used as the friction coefficient (μk) of the formulation.
For the obtained coefficient of friction values, the following formula 1 was used to calculate the friction reduction rate (%) with respect to the corresponding comparative example. 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, and Comparative Example 1-3 for Example 1-3. Comparative Example 1-3 and Example 1-4 correspond to Comparative Example 1-4, and Example 1-5 corresponds to Comparative Example 1-5.

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

In a test simulating the case where a composition containing polyvinylpyrrolidone K90 and a borate buffer was applied to the contact lens after being worn for a certain period of time, Example 1-1-1 in Table 2 above and Comparative Example 1 corresponding thereto As can be seen from the comparison with -1, it was confirmed that the composition of the example tends to significantly lower the coefficient of friction. Similarly, when the blending amount of polyvinylpyrrolidone K90 is changed, it was confirmed that the friction reduction effect can be obtained similarly when the conditions such as the type and concentration of the buffering agent and salts, and the pH are changed.

<Test Example 2: Evaluation of Friction Reduction Sustainability>
One piece of soft contact lens [product name: 1day Acuvue (etafilcon A), soft contact lens classification according to US Food and Drug Administration (FDA) standards: Group IV, manufactured by Johnson & Johnson), phosphate buffered saline Rinse with (sodium chloride: 0.8 w/v%, sodium hydrogen phosphate dodecahydrate: 0.6 w/v%, sodium dihydrogen phosphate dihydrate: 0.053 w/v%) and adhere to the surface After wiping off the excess liquid, immerse each plate in a 12-well plate (made of polystyrene) filled with 2 mL of the lipid-protein stain liquid shown in Table 1 above, and shake at 34 ° C. for 36 minutes. Stored (lipid-protein stain solution treatment).
After that, prepare 12-well plates (made of polystyrene) filled with 2 mL each of the formulation solutions shown in Table 3 below, and immerse the contact lenses after the lipid-protein staining solution treatment, and shake at 34 ° C. Stored under conditions for 15 minutes.
Then, after thoroughly rinsing the surface of the contact lens with physiological saline, each contact lens was immersed in a 12-well plate (made of polystyrene) filled with 2 mL each of the lipid-protein stain solution shown in Table 1 above. and stored under shaking conditions at 34° C. for 36 minutes (re-treatment with lipid-protein staining solution after immersion in 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 Equation 1 above.
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.

From Table 3 above, it was confirmed that the friction coefficient tends to be reduced even in the contact lenses that are treated again with the lipid-protein stain solution after being immersed in the prescription solution. From this result, it was confirmed that the contact lens during wear has a friction-reducing effect, that is, a friction-reducing sustained effect even after a certain period of time has passed since the application.

<Test Example 3: Usability Test (1)>
Each eye drop was prepared according to the prescription examples shown in Table 4 below, and 13 mL was aseptically filled into a polyethylene terephthalate eye drop container having an inner volume of 14.2 mL. After filling, the eye dropper was fitted with a polyethylene nozzle. In 10 subjects wearing soft contact lenses (product name: 1day Acuvue (etafilcon A), soft contact lens classification according to US Food and Drug Administration (FDA) standards: Group IV, manufactured by Johnson & Johnson), contact Eight hours after wearing the lenses, one drop (40 μL) of each eye drop was applied to each of the left and right eyes, and the feeling of use after the eye drop was evaluated on a VAS (Visual Analog Scale: Visual evaluation scale), and the amount of change in score before and after instillation (after instillation - before instillation) was determined.The results are also shown in Table 4 below.The test was conducted on the left and right eyes of the subject. It was implemented after confirming that there was no difference in the state.
[Evaluation of usability]
On the subjective symptom survey sheet with a line of 100 mm, immediately after instillation,
・100 mm when blinking is very easy, 0 mm when blinking is very difficult,
・100 mm when feeling a foreign object very much, 0 mm when there is no foreign object feeling,
- The level of the item felt by the subject was marked with 100 mm when the wearing feeling of the contact lens was very good and 0 mm when it was very bad. This length (mm) was taken as the VAS value.
That is, regarding the ease of blinking, the more positive the change in the VAS value, the more the ease of blinking due to eye drops is improved. With regard to the feeling of wearing contact lenses, the more positive the VAS value is, the more the feeling of wearing contact lenses with eye drops is improved.

In eye drops after 8 hours of contact lens wear, in Example 3-1 in Table 4 above, compared to Comparative Example 3-1, the amount of change in ease of blinking was high, and the amount of change in foreign body sensation was low. Since the amount of change in the feeling of wearing contact lenses was large, it was confirmed that the eye drops of the Examples made it easier to blink, eliminated the foreign body sensation, and improved the feeling of wearing contact lenses.
Further, the same test was performed using the same formulation example (Example 3-1′) as Example 3-1 except that polyvinylpyrrolidone K90 was 0.05 w/v%. It was confirmed that Example 3-1′ tended to feel easier to blink than Example 3-1′.

<Test Example 4: Usability Test (2)>
Each eye drop was prepared according to the prescription examples shown in Table 5 below, and the evaluation before and after the eye drop was performed 1 hour after wearing the contact lens. In the same manner as in Test Example 3, the amount of change in these items due to instillation was examined.

In the evaluation after 1 hour of contact lens wearing, in Example 4-1 in Table 5 above, compared to Comparative Example 4-1, the amount of change in the ease of blinking was high, and the amount of change in the feeling of wearing the contact lens. Therefore, it was confirmed that the eye drops of the Examples made it easier to blink and improved the feeling of wearing contact lenses.

It was confirmed that when the number of instillations per day was 5, the feeling of wearing contact lenses was improved, as in the above-described example group.

<Formulation example>
Eye drops for contact lenses (CL) (formulation examples 1 to 34) are prepared by a conventional method according to the formulations shown in Tables 6 to 9 below. The unit of each component amount in the table is "w/v %" except for those described in the table.

INDUSTRIAL APPLICABILITY The present invention can be widely used as contact lens eye drops for reducing contact lens friction during wear.

Claims (1)

An eye drop for contact lenses for reducing friction, containing (A) polyvinylpyrrolidone having a K value of 70 or more and (B) a buffering agent.