JP2011219446A - Ophthalmic composition for contact lens - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an ophthalmic composition for contact lenses which can inhibit the adhesion of corneal epithelial cells to contact lenses.SOLUTION: The ophthalmic composition which can inhibit the adhesion of corneal epithelial cells to contact lenses can be prepared by combined use of (A) glutathione and (B) at least one kind selected from the group consisting of boric acid and a salt thereof.

Description

  The present invention relates to an ophthalmic composition for contact lenses that can suppress adhesion of corneal epithelial cells to contact lenses. The present invention also relates to a method for suppressing adhesion of corneal epithelial cells to contact lenses. Furthermore, the present invention relates to a method for suppressing contact lens size change caused by boric acid and / or a salt thereof, and a method for suppressing adhesion of Acanthamoeba to the contact lens.

  In recent years, contact lenses have spread rapidly, and in particular, the number of wearers of soft contact lenses (SCL) has increased, and contact lenses that can be worn continuously over a long period of time have also been developed. On the other hand, since the cornea is vulnerable to physical stimulation and easily damaged, contact lenses that are in direct contact with the cornea are required to have high safety. However, friction is inevitably generated between the contact lens and the cornea when the contact lens is detached or when the lens moves on the cornea while wearing the contact lens. Such friction between the contact lens and the cornea may cause the corneal epithelial cells to peel from the cornea. Further, the detachment of the corneal epithelial cells may cause damage to the corneal surface and pain associated therewith, and as a result, the quality of life (QOL) of the contact lens user is significantly reduced. Therefore, in order to reduce the detachment of the corneal epithelial cells due to the friction between the contact lens and the cornea, it is required to reduce the adhesion of the corneal epithelial cells to the contact lens as much as possible. However, at present, a technique for suppressing adhesion of corneal epithelial cells to a contact lens using an ophthalmic composition has not been sufficiently studied.

  On the other hand, oxidized glutathione (GSSG) is a peptide in which two molecules of glutathione in which glutamic acid, cysteine and glycine are peptide-bonded from the N-terminal side (hereinafter sometimes referred to as reduced glutathione or GSH) are linked by a disulfide bond. It is. Oxidized glutathione is used in the ophthalmic field for intraocular and extraocular cleaning and ocular perfusion during ophthalmic surgery such as cataracts, vitreous, and glaucoma. In addition, boric acid and / or a salt thereof has a buffering action, and thus has been used in ophthalmic compositions as a buffering agent for pharmaceutical preparations.

  However, so far, neither the effect of oxidized glutathione nor boric acid and / or its salt on the adhesion of corneal epithelial cells to contact lenses has been clarified. In addition, when the oxidized glutathione and boric acid and / or a salt thereof are used in combination, the influence on the adhesion of the corneal epithelial cells to the contact lens cannot be estimated at present.

Japanese Patent Publication No. 6-507503

  An object of this invention is to provide the ophthalmic composition for contact lenses which can suppress adhesion | attachment of the corneal epithelial cell to a contact lens.

  As a result of intensive studies to solve the above problems, the present inventors have surprisingly found that an ophthalmic composition for contact lenses containing oxidized glutathione and boric acid and / or a salt thereof is a contact lens. It was found that the adhesion of corneal epithelial cells to can be effectively suppressed. In addition, as a result of investigations, the present inventors have surprisingly found that the size change of the contact lens caused by boric acid and / or a salt thereof can be suppressed by blending oxidized glutathione. Furthermore, the present inventors have also found that adhesion of Acanthamoeba to contact lenses can be suppressed by using oxidized glutathione together with boric acid and / or a salt thereof. The present invention has been completed by further studies based on this finding.

That is, this invention provides the ophthalmic composition for contact lenses of the aspect hung up below.
Item 1-1. An ophthalmic composition for contact lenses, comprising (A) oxidized glutathione and (B) at least one selected from the group consisting of boric acid and salts thereof.
Item 1-2. The ophthalmic composition for contact lenses according to Item 1-1, wherein the content of component (A) is 0.0001 to 2 w / v%.
Item 1-3. The ophthalmic composition for contact lenses according to Item 1-1 or 1-2, which contains boric acid as component (B).
Item 1-4. Item 4. The ophthalmic composition for contact lens according to any one of Items 1-1 to 1-3, wherein the content of component (B) is 0.001 to 3 w / v%.
Item 1-5. Item 5. The ophthalmic composition for contact lens according to any one of Items 1-1 to 1-4, wherein 0.001 to 2000 parts by weight of Component (B) is contained per part by weight of component (A).
Item 1-6. The ophthalmic composition for contact lens according to any one of Items 1-1 to 1-5, which is a contact lens care agent.
Item 1-7. Item 7. The ophthalmic composition for contact lens according to any one of Items 1-1 to 1-6, which is a contact lens disinfecting / cleaning / preserving solution.
Item 1-8. Item 9. The ophthalmic composition for contact lens according to any one of Items 1-1 to 1-7, which is used for a soft contact lens.
Item 1-9. Item 9. The ophthalmic composition for contact lens according to any one of Items 1-1 to 1-8, which is used for a silicone hydrogel contact lens.

Moreover, this invention provides the method of suppressing the adhesion | attachment of the corneal epithelial cell to the contact lens hung up below.
Item 2. Contacting an ophthalmic composition for contact lenses containing (A) oxidized glutathione, and (B) at least one selected from the group consisting of boric acid and salts thereof, and contact lenses, A method for suppressing adhesion of corneal epithelial cells to contact lenses.

In addition, the present invention provides a method for imparting to the ophthalmic composition for contact lens the action of suppressing the adhesion of corneal epithelial cells to the contact lens described below.
Item 3. A contact lens ophthalmic composition comprising (A) oxidized glutathione and (B) at least one selected from the group consisting of boric acid and a salt thereof in the contact lens ophthalmic composition. A method for imparting an inhibitory effect on adhesion of corneal epithelial cells to contact lenses.

Moreover, this invention provides the method of suppressing the size change of the contact lens by the boric acid and / or its salt which are hung up below.
Item 4. In the ophthalmic composition for contact lenses, (A) oxidized glutathione and (B) at least one selected from the group consisting of boric acid and salts thereof are used in combination. A method of suppressing the induced contact lens size change.

Moreover, this invention provides the method of providing the effect | action which suppresses the size change of the contact lens by the boric acid and / or its salt which are hung up to the following to the ophthalmic composition for contact lenses.
Item 5. (A) Component (B), characterized in that (B) at least one selected from the group consisting of boric acid and salts thereof is blended with an ophthalmic composition for contact lenses containing oxidized glutathione. A method of imparting an effect to the ophthalmic composition for contact lens to suppress the size change of the contact lens caused by.

Moreover, this invention provides the method of suppressing adhesion of an acanthamoeba to the contact lens hung up below.
Item 6. A contact lens, comprising: (A) an oxidized glutathione; and (B) at least one selected from the group consisting of boric acid and a salt thereof. To suppress adhesion of Acanthamoeba.

The present invention provides a method for imparting an acanthamoeba adhesion-suppressing action to contact lenses listed below to an ophthalmic composition for contact lenses.
Item 7. An Acanthamoeba for contact lenses, characterized in that (A) oxidized glutathione and (B) at least one selected from the group consisting of boric acid and salts thereof are blended in an ophthalmic composition for contact lenses. A method of imparting an action of suppressing adhesion to the ophthalmic composition for contact lenses.

  According to the ophthalmic composition for contact lens of the present invention, the adhesion of corneal epithelial cells to the contact lens can be effectively suppressed, so that the damage of the corneal surface due to the use of the contact lens and the pain associated therewith can be improved. In addition, it is known that it is difficult to recognize even when a cornea is damaged when a contact lens is worn, and if a contact lens is worn continuously over a long period of time, it may not be noticed until it becomes severe. However, according to the ophthalmic composition for contact lenses of the present invention, even if continuous wear of contact lenses is repeated for a long period of time, damage to the corneal surface is unlikely to occur. It is possible to wear the contact lens for a long period of time with high safety.

  In addition, in the ophthalmic composition for contact lenses, deformation (size change) of the contact lens caused by boric acid and / or salt thereof is effectively achieved by using oxidized glutathione together with boric acid and / or salt thereof. Therefore, the contact lens can be used without impairing the wearing feeling. In addition, the change in the size of the contact lens may cause unexpected physical stress to the eye, but the ophthalmic composition for contact lens of the present invention can suppress the change in the size of the contact lens, and thus has high safety. It is also effective for using contact lenses. In addition, an excessive change in the size of the contact lens may impair the original vision correction power of the lens, but the ophthalmic composition for contact lens of the present invention can effectively suppress the deformation of the contact lens. It is also effective for maintaining vision correction.

Furthermore, according to the ophthalmic composition for contact lenses of the present invention, adhesion of Acanthamoeba (for example, Acanthamoeba castellanii , Acanthamoeba polyphaga, etc.) to the contact lens can be suppressed, thereby preventing Acanthamoeba corneal infection via the contact lens. be able to. Although contact lenses are said to be a source of infection for Acanthamoeba corneal infection, by using the ophthalmic composition for contact lenses of the present invention, the use of contact lenses for Acanthamoeba corneal infections. Risk can be reduced.

  Thus, the ophthalmic composition for contact lenses of the present invention suppresses the adhesion of corneal epithelial cells to contact lenses, suppresses the change in size of contact lenses caused by boric acid and / or its salts, and accounts for contact lenses. Since it has an advantageous effect of suppressing the adhesion of amoeba, it is versatile and can be suitably used for various contact lenses, and its practical value is extremely high.

In Test Example 2, it is a figure which shows the result of having evaluated the influence which acts on the size change of a soft contact lens about a test liquid (Example 2 and Comparative Example 4). In Test Example 2, it is a figure which shows the result of having evaluated the influence which acts on the size change of a soft contact lens about a test liquid (Example 3 and Comparative Example 5).

1. Ophthalmic Composition for Contact Lens The ophthalmic composition for contact lens of the present invention contains oxidized glutathione (hereinafter sometimes simply referred to as “component (A)”).

  Oxidized glutathione is a compound known as a peptide in which two tripeptides (reduced glutathione; GSH) in which glutamic acid, cysteine and glycine are bound by a peptide bond are linked by a disulfide bond. The oxidized glutathione used in the present invention may be synthesized by a known method or obtained as a commercial product.

  In the ophthalmic composition for contact lenses of the present invention, the content ratio of the component (A) depends on the type of the component (A), the type of the component (B) to be used together, the formulation form of the ophthalmic composition for contact lenses, etc. As an example, the total amount of component (A) is 0.0001 to 2 w / v%, preferably 0.0005 to 1 w / v%, more preferably, based on the total amount of the ophthalmic composition for contact lenses. Is exemplified by 0.001 to 0.3 w / v%.

  The content ratio of the component (A) is suitable from the viewpoint of further enhancing the adhesion suppressing action of corneal epithelial cells to the contact lens, and the action of suppressing the size change of the contact lens caused by boric acid and / or a salt thereof, Or it is suitable also from a viewpoint of raising the adhesion inhibitory action of the acanthamoeba to a contact lens further.

  The ophthalmic composition for contact lenses of the present invention is at least one selected from the group consisting of boric acid and salts thereof in addition to the above component (A) (hereinafter sometimes simply referred to as component (B)). Containing. Thus, by using the components (A) and (B) together, it becomes possible to remarkably suppress the adhesion of corneal epithelial cells to the contact lens. In addition, the combined use of the components (A) and (B) can suppress the size change of the contact lens caused by boric acid and / or a salt thereof, and can also suppress the adhesion of the acanthamoeba to the contact lens. .

  Boric acid is a general term for boron oxo acids, and includes orthoboric acid, metaboric acid, tetraboric acid, and the like. Boric acid is a known compound, and may be synthesized by a known method or obtained as a commercial product.

  The salt of boric acid is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. For example, a salt with an organic base (for example, Salts with organic amines such as methylamine, triethylamine, triethanolamine, morpholine, piperazine, pyrrolidine, amino acids, tripyridine, picoline, etc.); salts with inorganic bases [alkali metal salts (for example, sodium salts, potassium salts, etc.); Alkaline earth metal salts (such as calcium salts and magnesium salts); other metal salts (such as aluminum salts)] and the like. Among these boric acid salts, preferred are salts with inorganic bases, more preferred are alkali metal salts, alkaline earth metal salts and ammonium salts, still more preferred are alkali metal salts, and particularly preferred is sodium. Salt. These boric acid salts may be used alone or in any combination of two or more.

  Moreover, boric acid and / or its salt can also be used with the form of a hydrate.

  In the ophthalmic composition for contact lenses of the present invention, the component (B) may be used alone or in combination of two or more of boric acid and its salts. Specific examples of the component (B) used in the present invention include boric acid such as orthoboric acid, metaboric acid, and tetraboric acid; sodium orthoborate, sodium metaborate, sodium tetraborate, sodium pentaborate, and hexaboron. Examples thereof include salts of boric acid such as sodium acid, sodium octaborate, sodium diborate, potassium orthoborate, potassium metaborate, potassium tetraborate, ammonium orthoborate, ammonium metaborate, ammonium tetraborate, borax and the like. Among these, boric acid (especially orthoboric acid) is particularly suitable as the component (B) of the present invention because it can further improve the contact lens size change suppressing effect or the acanthamoeba adhesion suppressing effect on the contact lens. It is. In the present invention, as a preferred embodiment of the component (B), boric acid alone or a combination of boric acid and borax can be mentioned. In addition, as for boric acid and borax, Japanese Pharmacopoeia conformity goods are used suitably and these can use a commercially available thing. When used in combination, these ratios are not particularly limited, but the total amount of borax per 1 part by weight of boric acid is usually 0.001 to 10 parts by weight, preferably 0.005. To 1 part by weight, more preferably 0.01 to 0.8 part by weight.

  In the ophthalmic composition for contact lenses of the present invention, the blending ratio of the component (B) depends on the type of the component (A) used in combination, the type of the component (B) used, the formulation form of the ophthalmic composition for contact lenses, etc. Depending on the total amount of the ophthalmic composition for contact lenses, as an example, the total amount of the component (B) is 0.001 to 5 w / v%, preferably 0.01 to 2 w / v%, More preferably 0.05 to 1 w / v%, particularly preferably 0.1 to 0.5 w / v% is exemplified. The content ratio of the component (B) is suitable from the viewpoint of further enhancing the adhesion suppressing action of corneal epithelial cells to the contact lens, and the action of suppressing the size change of the contact lens caused by boric acid and / or a salt thereof, Or it is suitable also from a viewpoint of raising the adhesion inhibitory action of the acanthamoeba to a contact lens further.

  Regarding the ratio of the component (A) and the component (B) in the ophthalmic composition for contact lenses of the present invention, the total amount of the component (A) is 1 part by weight from the viewpoint of further enhancing the action of suppressing the adhesion of corneal epithelial cells to the contact lens. On the other hand, the ratio by which (B) component becomes 0.001-2000 weight part in total amount, Preferably it is 0.01-500 weight part, More preferably, it is 0.2-100 weight part. The ratios exemplified here are also preferable from the viewpoint of further increasing the suppression of contact lens size change caused by boric acid and / or its salt, or further increasing the action of suppressing the adhesion of Acanthamoeba to the contact lens.

  The ophthalmic composition for contact lenses of the present invention may further contain a surfactant. The surfactant that can be blended in the ophthalmic composition of the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable, and is a nonionic surfactant, Any of an amphoteric surfactant, an anionic surfactant, and a cationic surfactant may be used.

  Specific examples of the nonionic surfactant that can be incorporated into the ophthalmic composition for contact lenses of the present invention include monolauric acid POE (20) sorbitan (polysorbate 20), monopalmitic acid POE (20) sorbitan (polysorbate 40). POE sorbitan fatty acid esters such as monostearic acid POE (20) sorbitan (polysorbate 60), tristearic acid POE (20) sorbitan (polysorbate 65), monooleic acid POE (20) sorbitan (polysorbate 80); POE / POP block copolymers such as poloxamer 235, poloxamer 188, poloxamer 403, poloxamer 237, poloxamer 124, etc .; POE cured castor oil such as POE (60) hydrogenated castor oil (polyoxyethylene hydrogenated castor oil 60); POE ( 9) POE alkyl ethers such as lauryl ether; POE-POP alkyl such as POE (20) POP (4) cetyl ether And ethers such as POE alkylphenyl ethers such as POE (10) nonylphenyl ether. In the compounds exemplified above, POE is polyoxyethylene, POP is polyoxypropylene, and the numbers in parentheses indicate the number of moles added. Specific examples of the amphoteric surfactant that can be incorporated into the ophthalmic composition for contact lenses of the present invention include alkyldiaminoethylglycine or a salt thereof (for example, hydrochloride). Specific examples of the cationic surfactant that can be incorporated into the ophthalmic composition for contact lenses of the present invention include benzalkonium chloride and benzethonium chloride. Specific examples of the anionic surfactant that can be incorporated into the ophthalmic composition for contact lenses of the present invention include alkylbenzene sulfonate, alkyl sulfate, polyoxyethylene alkyl sulfate, and aliphatic α-sulfo. Examples include methyl ester and α-olefin sulfonic acid.

  In the ophthalmic composition for contact lenses of the present invention, the surfactant may be used alone or in combination of two or more.

  Among the above surfactants, preferably nonionic surfactants; more preferably POE sorbitan fatty acid esters, POE hydrogenated castor oil, or POE / POP block copolymers; more preferably polysorbate 80, polyoxyethylene cured Castor oil 60 and Poloxamer 407 are used.

  When a surfactant is added to the ophthalmic composition for contact lenses of the present invention, the content of the surfactant is the type of the surfactant, the type and content of other components, and the ophthalmic composition. It can set suitably according to a formulation form etc. As an example of the content ratio of the surfactant, the total amount of the surfactant is 0.001 to 1.0 w / v%, preferably 0.005 to 0.00% with respect to the total amount of the ophthalmic composition for contact lens. Examples are 7 w / v%, more preferably 0.01 to 0.5 w / v%.

  The ophthalmic composition for contact lenses of the present invention may further contain an isotonic agent. The isotonic agent that can be incorporated into the ophthalmic composition for contact lenses of the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Specific examples of such isotonic agents include, for example, disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, sodium hydrogen sulfite, sodium sulfite, potassium chloride, calcium chloride, sodium chloride, magnesium chloride, acetic acid Examples include potassium, sodium acetate, sodium hydrogen carbonate, sodium carbonate, sodium thiosulfate, magnesium sulfate, glycerin, propylene glycol and the like. Among these isotonic agents, preferably, glycerin, propylene glycol, sodium chloride, potassium chloride, calcium chloride, and magnesium chloride are mentioned, more preferably sodium chloride or glycerin is mentioned, and sodium chloride is particularly preferred. Can be mentioned. These isotonic agents may be used alone or in any combination of two or more.

  When an isotonic agent is blended in the ophthalmic composition for contact lenses of the present invention, the content of the tonicity agent varies depending on the type of tonicity agent used, etc. However, for example, the total amount of the tonicity agent is 0.01 to 10 w / v%, preferably 0.05 to 5 w / v%, more preferably 0.8%, based on the total amount of the ophthalmic composition for contact lenses. A ratio of 1 to 3 w / v% is exemplified.

  The ophthalmic composition for contact lenses of the present invention may further contain a buffering agent other than boric acid and / or a salt thereof. The buffering agent other than boric acid and / or its salt is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Examples of such buffers include phosphate buffer, carbonate buffer, citrate buffer, acetate buffer, epsilon-aminocaproic acid, aspartic acid, aspartate and the like. These buffering agents may be used in combination. As a buffering agent other than boric acid and / or a salt thereof, a phosphate buffer, a carbonate buffer, and a citrate buffer are preferable, and a phosphate buffer is more preferable. Examples of the phosphate buffer include phosphoric acid or phosphates such as alkali metal phosphates and alkaline earth metal phosphates. Examples of the carbonate buffer include carbonates or carbonates such as alkali metal carbonates and alkaline earth metal carbonates. Examples of the citrate buffer include citric acid, alkali metal citrate, and alkaline earth metal citrate. Moreover, you may use the hydrate of a phosphate as a phosphate buffer. As a more specific example, as a phosphate buffer, phosphoric acid or a salt thereof (disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, trisodium phosphate, dipotassium phosphate, monophosphate Calcium hydrogen, calcium dihydrogen phosphate, etc.) Carbonic acid or a salt thereof (sodium hydrogen carbonate, sodium carbonate, ammonium carbonate, potassium carbonate, calcium carbonate, potassium hydrogen carbonate, magnesium carbonate, etc.); citrate buffer Citric acid or a salt thereof (sodium citrate, potassium citrate, calcium citrate, sodium dihydrogen citrate, disodium citrate, etc.); acetic acid or a salt thereof (ammonium acetate, potassium acetate, acetic acid) Calcium, sodium acetate, etc.); aspartic acid or a salt thereof (asparagine) Sodium, magnesium aspartate, potassium aspartate, etc.) and the like. These buffering agents other than boric acid and / or a salt thereof may be used alone or in any combination of two or more.

  When a buffering agent other than boric acid and / or a salt thereof is blended in the ophthalmic composition for contact lenses of the present invention, the content of the buffering agent is the type of buffering agent used, the type and content of other ingredients. The amount varies depending on the ratio, the dosage form of the ophthalmic composition for contact lenses, and the like, and cannot be uniformly defined. For example, the total amount of the buffer is about 0. 0 to the total amount of the ophthalmic composition for contact lenses. Examples include a ratio of 01 to 10 w / v%, preferably 0.1 to 5 w / v%, and more preferably 0.2 to 2 w / v%.

  The pH of the ophthalmic composition for contact lenses of the present invention is not particularly limited as long as it is within a pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable range. As an example of the pH of the ophthalmic composition for contact lenses of the present invention, 4.0 to 9.5, preferably 5.0 to 9.0, more preferably 6.2 to 8.5, and particularly preferably 6.5. The range which becomes -8 is mentioned.

  In addition, the osmotic pressure of the ophthalmic composition for contact lens of the present invention is not particularly limited as long as it is within a range acceptable for a living body. As an example of the osmotic pressure ratio of the ophthalmic composition for contact lenses of the present invention, a range of preferably 0.5 to 5.0, more preferably 0.6 to 3.0, and particularly preferably 0.7 to 2.0. Is mentioned. The osmotic pressure can be adjusted by a method known in the art using inorganic salts, polyhydric alcohols, sugar alcohols, saccharides and the like. The osmotic pressure ratio is the ratio of the osmotic pressure of the sample to 286 mOsm (0.9 w / v% sodium chloride aqueous solution) based on the 15th revised Japanese pharmacopoeia. Measure with reference to the descent method. The standard solution for measuring the osmotic pressure ratio (0.9 w / v% sodium chloride aqueous solution) was dried in sodium chloride (Japanese Pharmacopoeia standard reagent) at 500 to 650 ° C. for 40 to 50 minutes and then released in a desiccator (silica gel). Cool and accurately measure 0.900 g and dissolve in purified water to make exactly 100 mL, or use a commercially available standard solution for osmotic pressure ratio measurement (0.9 w / v% sodium chloride aqueous solution).

The ophthalmic composition for contact lenses of the present invention may contain an appropriate amount of various pharmacologically active ingredients and physiologically active ingredients in addition to the above-mentioned ingredients as long as the effects of the present invention are not hindered. Such an ingredient is not particularly limited, and examples thereof include an active ingredient in an ophthalmic drug described in the over-the-counter drug manufacturing (import) approval standard 2000 edition (supervised by the Pharmaceutical Affairs Research Committee). Specifically, the following components are listed as components used in ophthalmic drugs.
Antihistamines: for example, iproheptin, diphenhydramine hydrochloride, chlorpheniramine maleate, ketotifen fumarate, pemirolast potassium and the like.
Decongestant: For example, tetrahydrozoline hydrochloride, naphazoline hydrochloride, naphazoline sulfate, epinephrine hydrochloride, ephedrine hydrochloride, methylephedrine hydrochloride, and the like.
Bactericides: for example, cetylpyridinium, benzalkonium chloride, benzethonium chloride, chlorhexidine hydrochloride, chlorhexidine gluconate, polyhexanide hydrochloride, etc.
Vitamins: For example, flavin adenine dinucleotide sodium, cyanocobalamin, retinol acetate, retinol palmitate, pyridoxine hydrochloride, panthenol, calcium pantothenate, tocopherol acetate and the like.
Amino acids: For example, potassium aspartate, magnesium aspartate and the like.
Anti-inflammatory agents: for example, dipotassium glycyrrhizinate, pranoprofen, allantoin, azulene, sodium azulenesulfonate, guaiazulene, ε-aminocaproic acid, berberine chloride, berberine sulfate, lysozyme chloride, licorice, etc.
Other: For example, sodium cromoglycate, sodium chondroitin sulfate, sodium hyaluronate, sulfamethoxazole, sodium sulfamethoxazole and the like.

In addition, in the ophthalmic composition for contact lenses of the present invention, various additives are appropriately selected according to a conventional method according to the use and formulation form, as long as the effects of the invention are not impaired. An appropriate amount may be added in combination. Examples of these additives include various additives described in Pharmaceutical Additives Encyclopedia 2007 (edited by Japan Pharmaceutical Additives Association). Typical additives include the following additives.
Carrier: An aqueous carrier such as water or hydrous ethanol.
Sugars: For example, cyclodextrins and the like.
Sugar alcohols: For example, xylitol, sorbitol, mannitol and the like. These may be d-form, l-form or dl-form.
Preservatives, bactericides or antibacterial agents: for example, alkyldiaminoethylglycine hydrochloride, sodium benzoate, ethanol, benzalkonium chloride, benzethonium chloride, chlorhexidine gluconate, chlorobutanol, sorbic acid, potassium sorbate, sodium dehydroacetate, paraoxy Methyl benzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate, oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, Glow Kill (trade name, manufactured by Rhodia) and the like.
pH adjuster: for example, hydrochloric acid, epsilon-aminocaproic acid, citric acid, acetic acid, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, sodium bicarbonate, sodium carbonate, borax, triethanolamine, monoethanol Amine, diisopropanolamine, 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 and the like.
Stabilizers: for example, dibutylhydroxytoluene, trometamol, sodium formaldehyde sulfoxylate (Longalite), tocopherol, sodium pyrosulfite, monoethanolamine, aluminum monostearate, glyceryl monostearate and the like.

  The ophthalmic composition for contact lenses of the present invention is prepared by adding a desired amount of the above components (A) and (B) and, if necessary, other blending components so as to have a desired content ratio.

  If the ophthalmic composition for contact lenses of this invention is used in the ophthalmic field | area, it will not restrict | limit about the formulation form. For example, eye drops for contact lenses (eye drops that can be used while wearing contact lenses), eye wash for contact lenses (eye drops that can be used while wearing contact lenses), contact lens mounting solutions, and contact lens care agents (Contact lens disinfecting solution, contact lens preserving solution, contact lens cleaning solution, contact lens cleaning / preserving solution, contact lens disinfecting / cleaning / preserving solution (multipurpose solution), etc.). Among them, the contact lens care agent comes in contact with the cornea in a state where the preparation is attached to the front and back of the contact lens, etc., so that the corneal epithelial cell adhesion inhibitory action to the contact lens, the contact lens size change inhibitory action, and the contact lens Since it is a pharmaceutical form that is strongly required to impart an inhibitory action on the adhesion to Acanthamoeba, it is particularly suitable as a pharmaceutical form of the ophthalmic composition for contact lenses of the present invention. Further, a contact lens disinfecting / cleaning / preserving solution (multipurpose solution) is a preparation that directly contacts the cornea via a contact lens in order to disinfect, clean and store the contact lens in one solution. Therefore, the contact lens disinfecting / cleaning / preserving solution has a formulation form that is particularly required to have a corneal epithelial cell adhesion inhibitory effect on contact lenses, a contact lens size change inhibitory action, and an acanthamoeba adhesion inhibitory action on contact lenses. And is particularly suitable as a preparation form of the ophthalmic composition for contact lenses of the present invention.

  In the present invention, the contact lens includes any of a soft contact lens, a hard contact lens, and an oxygen permeable hard contact lens. Soft contact lenses include both ionic and non-ionic, silicone hydrogel contact lenses (hereinafter sometimes abbreviated as SHCL) and non-silicone hydrogel contact lenses (not silicone hydrogel lenses). Including both soft contact lenses).

  Corneal epithelial cell adhesion to contact lenses and contact lens size changes tend to be strongly observed in soft contact lenses. Acanthamoeba corneal infections often affect soft contact lens wearers among contact lens wearers, and there is a strong demand for soft contact lens wearers to suppress the adhesion of Acanthamoeba to the cornea. Yes. Therefore, the ophthalmic composition for soft contact lenses (that is, the ophthalmic composition for contact lenses in which the application target lens is a soft contact lens) is preferable as the formulation form of the ophthalmic composition of the present invention.

  In addition, soft contact lenses (ionic high water content contact lenses) whose SCL classification belongs to Group IV tend to cause size changes due to boric acid and / or salts thereof, and there is a strong demand for suppression of the size changes. It has been. From this point of view, an example of a suitable application target of the ophthalmic composition for contact lenses of the present invention is a soft contact lens having an SCL classification of Group IV.

  In addition, SHCL is expected to be used for a long period of time because of its high oxygen permeability, and may be worn continuously for a maximum of one month or throughout the day. The cornea may be worn during wearing compared to other soft contact lenses. There is a tendency to facilitate the adhesion of epithelial cells. Furthermore, SHCL tends to attach Acanthamoeba more easily than other soft contact lenses. Therefore, among soft contact lenses, an ophthalmic composition (ie, an ophthalmic composition for SHCL) applied particularly to SHCL has a stronger inhibitory effect on the adhesion of corneal epithelial cells and an inhibitory effect on acanthamoeba adhesion to contact lenses. It is a required formulation form. From this point of view, the ophthalmic composition for contact lenses of the present invention is preferably prepared as an ophthalmic composition for SHCL, more preferably an eye drop for SHCL and an SHCL care agent, particularly preferably an SHCL disinfecting / cleaning / preserving solution ( Multipurpose solution). In addition, in this specification, when it displays only as SHCL, both ionic SHCL and nonionic SHCL are included. Here, ionic SHCL refers to SHCL with an ionic component content of 1 mol% or more in the SHCL material in accordance with US FDA (US Food and Drug Administration) standards, and nonionic SHCL refers to US FDA (US According to Food and Drug Administration), this refers to SHCL whose ionic component content in contact lens materials is less than 1 mol%.

  Further, among SHCLs, nonionic SHCLs tend to have remarkable adhesion to corneal epithelial cells, and are ophthalmic compositions that are applied to nonionic SHCLs (that is, ophthalmic compositions for nonionic SHCLs). ) Is strongly required to suppress adhesion to corneal epithelial cells. From such a viewpoint, the ophthalmic composition for contact lenses of the present invention is preferably formulated as a nonionic SHCL ophthalmic composition, more preferably a nonionic SHCL eye drop and a nonionic SHCL care agent, particularly preferably. Non-ionic SHCL disinfection / cleaning / preservation solution (multipurpose solution).

  Among SHCLs, ionic SHCLs tend to be markedly attached to acanthamoeba. Ophthalmic compositions applied to ionic SHCLs (that is, ophthalmic compositions for ionic SHCLs) include There is a strong demand for suppression of amoeba adhesion. From this point of view, the ophthalmic composition for contact lenses of the present invention is preferably prepared as an ophthalmic composition for ionic SHCL, more preferably eye drops for ionic SHCL and ionic SHCL care solutions, particularly preferably ions. Basic SHCL disinfection / cleaning / preservation solution (multipurpose solution).

  According to the ophthalmic composition for contact lens of the present invention, the adhesion of corneal epithelial cells to the contact lens can be effectively suppressed, so that the corneal epithelial disorder caused by wearing the contact lens can be prevented. Therefore, the ophthalmic composition for contact lenses of the present invention can be used as a preventive agent for corneal epithelial disorder caused by wearing of contact lenses.

  In addition, since corneal epithelial cells also have a barrier function against allergens and the like, a corneal epithelial disorder caused by wearing contact lenses may decrease the barrier function and easily cause allergic symptoms of the eye. On the other hand, according to the ophthalmic composition for contact lenses of the present invention, the corneal epithelial cells are maintained in a normal state by suppressing the adhesion of the corneal epithelial cells to the contact lenses, and the barrier function of the corneal epithelial cells Can be maintained. Therefore, the ophthalmic composition for contact lenses of the present invention provides an eye disease preventive agent (for example, allergic symptoms) for a person wearing a contact lens to enhance and prevent various eye diseases including allergic symptoms. It is preferably used as a prophylactic agent).

  Moreover, since the ophthalmic composition for contact lenses of the present invention can exhibit an adhesion inhibitory action of Acanthamoeba to contact lenses, it can be used for the prevention of Acanthamoeba corneal infection.

2. Method for inhibiting adhesion of corneal epithelial cells to contact lens, and method for imparting an action for inhibiting adhesion of corneal epithelial cells to contact lens to an ophthalmic composition for contact lens As described above, oxidized glutathione, boric acid and By using together with / or a salt thereof, adhesion of corneal epithelial cells to the contact lens can be suppressed.

  Therefore, the present invention, from yet another point of view, (A) oxidized glutathione and (B) at least one selected from the group consisting of boric acid and salts thereof, and an ophthalmic composition for contact lenses, Provided is a method for suppressing adhesion of corneal epithelial cells to a contact lens, which comprises contacting the contact lens. The contact lens ophthalmic composition further comprises (A) oxidized glutathione and (B) at least one selected from the group consisting of boric acid and salts thereof. A method for imparting an ophthalmic composition with an inhibitory effect on adhesion of corneal epithelial cells to a contact lens is provided.

  In these methods, the types of the components (A) and (B) to be used, the content ratios thereof, the ratios thereof, the types and content ratios of the other components, the formulation form of the ophthalmic composition for contact lenses, the contact The type of lens and the like are the same as in “1. Ophthalmic composition for contact lens”.

3. Method for suppressing change in size of contact lens by boric acid and / or salt thereof, and method for imparting an action to suppress size change of contact lens by boric acid and / or salt thereof to ophthalmic composition
As described above, the size of a contact lens caused by contact with boric acid and / or a salt thereof by coexisting oxidized glutathione and boric acid and / or a salt thereof in an ophthalmic composition for contact lenses. Change can be suppressed.

  Therefore, from another viewpoint, the present invention uses (A) oxidized glutathione in combination with at least one selected from the group consisting of (B) boric acid and salts thereof in an ophthalmic composition for contact lenses. There is provided a method for suppressing a size change of a contact lens caused by the component (B). Further, the present invention is characterized in that (A) at least one selected from the group consisting of boric acid and salts thereof is blended with the ophthalmic composition for contact lenses containing oxidized glutathione. Provided is a method for imparting to the ophthalmic composition for a contact lens an effect of suppressing the size change of the contact lens caused by the component (B).

  In these methods, the types of the components (A) and (B) to be used, the content ratios thereof, the ratios thereof, the types and content ratios of the other components, the formulation form of the ophthalmic composition for contact lenses, the contact The type of lens and the like are the same as in “1. Ophthalmic composition for contact lens”.

4). A method for inhibiting the adhesion of Acanthamoeba to contact lenses, and a method for imparting an Acanthamoeba adhesion inhibiting action to contact lenses to an ophthalmic composition for contact lenses. Also, as described above, combined use of components (A) and (B) By this, adhesion of an acanthamoeba to a contact lens can be suppressed.

  Therefore, the present invention provides a contact lens ophthalmic composition comprising (A) oxidized glutathione and (B) at least one selected from the group consisting of boric acid and a salt thereof, from another viewpoint. A method for suppressing adhesion of an acanthamoeba to a contact lens is provided. Further, the present invention is characterized in that the ophthalmic composition for contact lenses is blended with (A) oxidized glutathione and (B) at least one selected from the group consisting of boric acid and salts thereof. There is also provided a method for imparting an action to suppress contact of Acanthamoeba to a contact lens to the ophthalmic composition for contact lens.

  In these methods, the types of the components (A) and (B) to be used, the content ratios thereof, the ratios thereof, the types and content ratios of the other components, the formulation form of the ophthalmic composition for contact lenses, the contact The type of lens and the like are the same as in “1. Ophthalmic composition for contact lens”.

  EXAMPLES The present invention will be described in detail below based on examples, but the present invention is not limited to these examples.

Test Example 1: Test for suppressing adhesion of corneal epithelial cells to contact lens Using the test solutions shown in Table 1 (Example 1 and Comparative Example 1-2), the effect of suppressing the adhesion of corneal epithelial cells to SCL was evaluated.

SCL (non-ionic SHCL, main material Lotrafilcon B, water content 33.0%, base curve (BC) 8.6, lens diameter (DIA) 14.2 mm) was quickly immersed in physiological saline (about 1 second) and adhered to the lens. Excess contact lens packaging solution was rinsed (lens pre-treatment).
The pretreated lenses were immersed one by one in 1 ml of each test solution (Example 1 and Comparative Example 1-2) shown in Table 1 and allowed to stand at 34 ° C. for 2 hours. SCL taken out from each test solution was immersed one by one in a 24-well plate (for bacterial test) containing 900 μL of a growth medium (DMEM medium containing 10% fetal bovine serum) with the convex surface facing upward. In each well, 100 μL of a cell suspension (1 × 10 ⁵ cell / ml) of a rabbit corneal epithelial cell line SIRC (ATCC number: CCL-60) prepared using a growth medium was seeded at 37 ° C., 5 ° C. After culturing for 48 hours under% CO ₂ conditions, the number of viable cells adhered to the lens was counted (sample group). In addition, as a control, using SCL, which was subjected to the same operation with the control test solution shown in Table 1, a cell suspension of a rabbit corneal epithelial cell line was seeded and cultured under the same conditions as described above, and adhered to SCL. The number of surviving cells was counted (control group). Furthermore, as a blank, a well containing only 1000 μL of growth medium (DMEM medium containing 10% fetal bovine serum) without seeding rabbit corneal epithelial cells was prepared, and the well was allowed to stand still at 37 ° C. and 5% CO ₂ for 48 hours. (Blank group). In addition, the cell adhesion suppression rate (%) was computed according to the following formula using Cell Counting Kit (Dojindo Laboratories) for the measurement of the number of living cells.

  The obtained results are also shown in Table 1. As a result, the cell adhesion inhibitory effect was slightly improved when treated with oxidized glutathione alone (Comparative Example 1) as compared to when treated with the control test solution. On the other hand, when treated with boric acids alone (Comparative Example 2), the cell adhesion inhibitory effect was rather deteriorated. In contrast, SCL treated with a test solution (Example 1) containing oxidized glutathione and boric acids at the same time was found to have a significantly high epithelial cell adhesion inhibitory effect. The cell adhesion inhibitory effect observed with the test solution of Example 1 is remarkably superior to the case of being treated with the test solution of Comparative Example 1 or 2.

Test Example 2: Contact Lens Size Change Suppression Test Using the test solutions described in Table 2 (Example 2-3 and Comparative Example 3-5), SCL (Soft Contact Lens Classification: Group IV, Main Material: etafilconA, The effect on the size change of water content (58%) was evaluated.

  Specifically, the evaluation was performed by the following method. First, SCLs were immersed one by one in 5 mL of physiological saline and allowed to stand for 24 hours to stabilize the lens size (lens pretreatment). After pretreatment, the lens was transferred to a cell filled with physiological saline, and the cell was set on a universal projector (product name: PROFILE PROJECTOR V-12B, manufactured by Nikon) to measure the size of the lens (start value) . Next, SCL was immersed in 20 mL of each test solution described in Table 2, and stored at room temperature for 4 hours. After 4 hours, the cells were co-washed with each test solution, and each cell was filled with each formulation solution to immerse the lens. Next, the cell was set on a universal projector, and the size of the lens was measured (value after storage). Then, the change in size of each lens was calculated by subtracting the start value from the stored value of the lens size. Subsequently, the relative value of the lens size change when each test solution was used was calculated with the change in size of the lens when the test solution of Comparative Example 3 was used as 100.

  In this test, the state in which the soft contact lens is immersed in physiological saline models the state in which the soft contact lens is in contact with only tear fluid, and the state in which the soft contact lens is immersed in the test solution is a soft contact lens. Has modeled a state in which an eye drop is instilled in a liquid for contact lens care or a soft contact lens is worn. If the size of the contact lens, that is, the physical properties of the lens changes greatly, various problems may occur, such as applying unexpected physical stress to the eye and causing eye damage. Therefore, it is desirable that the size of the contact lens be small when the contact lens is in contact with only tear fluid, and when the contact lens is worn or after instillation of eye drops.

  The results of this test are shown in FIGS. In the case of a test solution containing oxidized glutathione alone (Comparative Example 3), the soft contact lens was swollen. The soft contact lens was also swollen with a test solution containing boric acid and borax. On the other hand, when the oxidized glutathione was used in combination with boric acid and borax (Example 2-3), the swelling of the soft contact lens was unexpectedly suppressed.

Test Example 3: Acanthamoeba Adhesion Inhibition Test on Contact Lenses Using the test solutions shown in Table 3 (Example 4-5 and Comparative Example 6), SCL (ionic SHCL, SCL classification: Group III, main material: The adhesion of Acanthamoeba castellanii (ATCC30868) to BalafilconA, moisture content 36.0%, BC 8.6, DIA 14.0 mm) was evaluated.

SCL was immersed in approximately 3 mL overnight (lens pretreatment) in 1/4 Ringer solution (Japanese Pharmacopoeia Ringer solution diluted 1/4 with purified water; hereinafter 1 / 4RS). 500 μL of each test solution (Example 4-5 and Comparative Example 6) was prepared in a 48-well multiplate. The pre-treated lens was quickly immersed (about 1 second) in each test solution prepared in a separate container for rinsing to rinse off excess 1/4 Ringer solution. Thereafter, one SCL cut into a circle having a diameter of 6 mm with a biopsy trepan was placed in 500 μL of each test solution prepared in a 48-well multiplate. 1 / 4RS was used as a blank (n = 3). Further, 50 μL of Acanthamoeba castellanii bacterial solution (suspended in 1 / 4RS) adjusted to about 5 × 10 ⁵ cells / mL was placed in each well and stored for 4 hours under light shielding at room temperature. Next, quickly immerse each SCL in 1 / 4RS100mL with tweezers (about 1 second) to rinse the excess test solution, transfer to a 1.5mL capacity microtube containing 1 / 4RS1mL, and test tube mixer for 1 minute. , The amoeba adhering to each SCL was peeled off to obtain an adhering amoeba liquid.

The obtained adherent amoeba solution was diluted 10-fold with PYG medium, and further 10-fold dilution was repeated until it was diluted to 10 ^-4 (10 ^-1 , 10 ^-2 , 10 ^-3 , 10 ^-4 ). 180 μL each was put into a well plate and cultured at 32 ° C. for 7 days. The presence or absence of amoeba growth at each dilution stage was evaluated, and the number of adherent amoeba to SCL was determined by the Spearman-karber method. For details on the Spearman-karber method, in detail, the presence or absence of formed colonies was observed with a microscope (n = 4 per lens), and the number of samples in which the amoeba grew (0-4) at each dilution stage was counted. By applying this to the Spearman-karber equation, the number of bacteria (Ameba number) of Acanthamoeba castellanii in the original adherent amoeba solution was determined (sample group). In addition, as a control, the same operation was performed using the control test solution shown in Table 3, the test was performed under the same conditions as above, and the number of amoeba in the attached amoeba solution was measured (control group). From the number of obtained amoeba, the amoeba adhesion inhibition rate was calculated according to the following formula.

  The obtained results are also shown in Table 3. From this result, boric acid alone (Comparative Example 6) did not show the inhibitory effect of Acanthamoeba on SCL, but when oxidized glutathione and boric acid were used in combination (Example 4-5), Remarkably superior anti-adhesive effect of Acanthamoeba on SCL was observed.

Formulation Example A contact lens disinfecting / cleaning / preserving solution (multipurpose solution) (Example 6-11) is prepared according to the formulation described in Table 4.

Claims (6)

An ophthalmic composition for contact lenses, comprising (A) oxidized glutathione and (B) at least one selected from the group consisting of boric acid and salts thereof. The ophthalmic composition for contact lenses according to claim 1, comprising boric acid as component (B). The ophthalmic composition for contact lenses according to claim 1 or 2, comprising 0.001 to 2000 parts by weight of the total amount of component (B) per 1 part by weight of the total amount of component (A). The ophthalmic composition for contact lenses according to any one of claims 1 to 3, which is a contact lens disinfecting / cleaning / preserving solution. The ophthalmic composition for contact lenses according to any one of claims 1 to 4, which is used for soft contact lenses. The ophthalmic composition for contact lenses according to any one of claims 1 to 5, which is used for silicone hydrogel contact lenses.

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