JP5731046B1 - Contact lens composition - Google Patents

Abstract

[PROBLEMS] To (1) further improve the wettability of a contact lens, (2) to suppress lipid adhesion to the contact lens and not to disturb the structure of tears, and (3) the shape stability of the contact lens. A novel contact lens composition that can advantageously achieve any of the above is provided. A contact lens composition contains hypromellose having a polydispersity of 8 or more. Preferably, the weight average molecular weight of hypromellose is 50,000 or more and 1,000,000 or less. Further, it is preferable that the substitution degree of methoxyl group in hypromellose is 27.0 to 30.0% and the substitution degree of hydroxypropoxyl group is 4.0 to 12.0%. Furthermore, it preferably further comprises taurine. [Selection figure] None

Description

  The present invention relates to a contact lens composition used as, for example, a contact lens mounting liquid.

  Conventionally, various contact lens compositions used for contact lenses have been devised, such as contact lens cleaning solutions, contact lens preserving solutions, contact lens mounting solutions, eye drops, and eye wash solutions.

  By the way, such a composition for contact lenses is required to suppress the feeling of foreign matter and discomfort that tend to occur when the contact lens is worn. For example, Japanese Patent Laid-Open No. 2001-125052 (Patent Document 1) describes a contact lens mounting liquid that improves the feeling of wearing when a contact lens is mounted by improving the wettability of the contact lens. In the contact lens composition described in Patent Document 1, the wettability of the contact lens surface is improved by blending hypromellose (hydroxymethylpropylcellulose) or the like as a thickener.

  However, even if such a contact lens composition is used, depending on the user, it may not be possible to obtain a sufficient improvement in wearing feeling, and a contact lens composition that can further improve the wettability of the contact lens. The demand is growing.

  In addition, even if the contact lens composition contains hypromellose to improve the wettability of the contact lens, the improvement in wearing feeling has not been obtained yet because continuous wettability has not been obtained. As the wettability decreases as the wearing time elapses, it is considered that dirt easily adheres to the contact lens. That is, the foreign object feeling and discomfort at the time of wearing the contact lens are not only caused by the contact lens itself, but may also be caused by dirt attached to the contact lens. In particular, in recent years, silicone hydrogel soft contact lenses are becoming more popular as lenses with better oxygen permeability. However, silicone hydrogel soft contact lenses have more lipid stains than conventional lenses. There is a tendency to be easy. Therefore, there is an increasing demand for a contact lens composition that can eliminate the feeling of foreign matter and discomfort caused by lipid contamination in the market.

  In contrast, JP 2012-198538 A (Patent Document 2) describes that lipid adhesion to contact lenses can be suppressed by appropriately blending hypromellose and the like. However, it is required to use a low-viscosity product of hypromellose at a certain concentration (0.5 w / v%) or more. The low-viscosity product has a function of enhancing the surface active ability of the preparation as compared with the high-viscosity product, and thereby has the effect of improving the wettability of the contact lens and the effect of solubilizing the lipid. However, as a contact lens composition, it is important not only to impart wettability and lipid solubilization effect, but also to maintain the stability of tears when administered to the anterior eye part. Is not mentioned. Therefore, in addition to imparting wettability to contact lenses and suppressing adhesion of lipid stains, it is desired as an effect required for the composition for contact lenses not to adversely affect the state of tears.

  On the other hand, expiration dates are set for most contact lenses, and they may be stored in the distribution package for several years after being manufactured until the user uses the lenses. When the contact lens is stored in the distribution package for a long time in this way, there is a concern about the change in the shape of the contact lens due to the storage liquid, particularly the influence on the desired lens power. Therefore, it is important how to suppress changes in the diameter of the contact lens and the curvature of the rear surface.

  On the other hand, in Japanese translations of PCT publication No. 2009-520219 (Patent Document 3), a soft contact lens made of silicone hydrogel is immersed in a storage solution containing 0.02-5.0% by mass of saccharides. There has been proposed a method of suppressing the change in the diameter of the soft contact lens by storing it. However, Patent Document 3 does not show specific component examples or formulation examples of saccharides, and further does not disclose the action of saccharides on the above method.

  Therefore, (1) further improvement of the wettability of the contact lens, (2) suppression of lipid adhesion to the contact lens and not disturbing the structure of tears, and (3) shape stability of the contact lens, The present situation is that the contact lens composition that can achieve any of the above and further improve the wearing feeling of the contact lens has not yet been provided.

JP 2001-125052 JP 2012-198538 A Special table 2009-520219 gazette

  The present invention has been made in the background of the above-mentioned circumstances, and the problem to be solved is (1) further improvement of the wettability of the contact lens, and (2) suppression of lipid adhesion to the contact lens and tears. It is an object of the present invention to provide a novel composition for contact lenses that can advantageously achieve both the liquid structure and (3) the shape stability of contact lenses.

  In the course of diligent studies to solve such problems, the present inventors pay attention to the polydispersity of hypromellose, and by controlling the polydispersity, the effects (1) to (3) described above are achieved. He newly found out that he could perform at the same time, and completed the present invention.

  That is, the first aspect of the present invention is characterized in that the contact lens composition contains hypromellose having a polydispersity of 8 or more.

  According to this aspect, (1) contact lenses can be obtained by a simple configuration in which the polydispersity of hypromellose (hydroxypropylmethylcellulose) that has been conventionally used in a composition for contact lenses as a thickener or the like is set to 8 or more. The improvement of the wettability of the contact lens, (2) the suppression of lipid adhesion to the contact lens and the disorder of the tear fluid structure, and (3) the shape stability of the contact lens can be achieved at the same time. Normal tears are composed of an oil layer, an aqueous layer, and a mucin layer, and the stable formation of these layers is considered to be greatly involved in tear stability. “Disrupting the tear film structure” in the present application means disordering of these layer structures, thinning / thinning of the layers, or reduction of tear film breakdown time caused by them.

  Here, the polydispersity of hypromellose can be calculated by the ratio (Mw / Mn) of the weight average molecular weight (Mw) and the number average molecular weight (Mn) of the whole hypromellose contained in the contact lens composition. The technical reason for achieving the above effect by adjusting the polydispersity of hypromellose is not yet clear. However, among hypromellose, relatively low molecular weight hypromellose penetrates into the lens and penetrates into the lens. It is thought that it plays a role in keeping the hypromellose, which cannot be polymerized, away from the lens periphery. Among them, if a medium molecular weight hypromellose is present, it is preferentially present around the lens as compared with the high molecular weight hypromellose, so that the high molecular weight hypromellose contributes greatly to the addition of wettability. Cannot stay around the lens, and it is assumed that sufficient improvement in lens wettability cannot be achieved.

  A second aspect of the present invention is the contact lens composition described in the first aspect, wherein the hypromellose has a weight average molecular weight of 50,000 or more and 1,000,000 or less.

  According to this embodiment, the weight average molecular weight of hypromellose is further specified in the range of 50,000 or more and 1,000,000 or less, so that the effect of the present invention can be further exerted, as well as the applied contact lens composition. It is also possible to make the product easier to manufacture.

  According to a third aspect of the present invention, in the contact lens composition described in the first or second aspect, the hypromellose has a methoxyl group substitution degree of 27.0 to 30.0% and a hydroxy group. The degree of substitution of the propoxyl group is 4.0 to 12.0%.

  According to this aspect, by using hypromellose having a substitution degree of methoxyl group of 27.0 to 30.0% and a substitution degree of hydroxypropoxyl group of 4.0 to 12.0%, A tear film can be stably formed and held on the surface of the contact lens. Thereby, it becomes possible to maintain a good wearing feeling over a long period of time.

  According to a fourth aspect of the present invention, the contact lens composition described in any one of the first to third aspects further includes taurine.

  According to this aspect, by including taurine in the contact lens composition, the shape stability of the ionic soft contact lens can be maintained even better.

  According to a fifth aspect of the present invention, in the contact lens composition described in any one of the first to fourth aspects, the polydispersity of the hypromellose is 10 or more and 20 or less. By adjusting the polydispersity of hypromellose to a range of 10 or more and 20 or less, the effects (1) to (3) can be achieved more reliably.

  The hypromellose having the above specific polydispersity and weight average molecular weight can be obtained by appropriately controlling the depolymerization reaction conditions and the like among known hypromellose production methods, as well as commercially available hypromellose (Shin-Etsu Chemical Co., Ltd.). It can be obtained by mixing multiple types of commercially available hypromellose such as Metrose (registered trademark).

  According to the composition for contact lenses according to the present invention, (1) improvement of the wettability of the contact lens and (1) improvement of the wettability of the contact lens by a simple configuration in which the polydispersity of the contained hypromellose (hydroxypropylmethylcellulose) is set to 8 or more. 2) Suppressing lipid adhesion to the contact lens and not disturbing the structure of the tears, and (3) shape stability of the contact lens can be achieved at the same time. A feeling can be improved. A method for obtaining the effects of (1) to (3) above by obtaining a composition for contact lenses containing hypromellose having a polydispersity of 8 or more, or contact by obtaining these effects. A method for improving the wearing feeling of the lens is also included in the present invention.

  Hereinafter, in order to clarify the present invention more specifically, embodiments of the present invention relating to a composition for contact lenses will be described in detail.

  The composition for contact lenses as one embodiment of the present invention contains hypromellose adjusted to have a polydispersity of 8 or more, thereby improving the wettability of the contact lens, the shape stability of the contact lens, Furthermore, it is possible to realize suppression of lipid adhesion to the contact lens and not disturbing the structure of tears. More specifically, the composition for contact lenses according to the present embodiment comprises various solutions used in direct or indirect contact with contact lenses, such as contact lens mounting liquid, contact lens cleaning liquid, contact lens preserving liquid, contact It is used as a lens rinse solution, protein treatment agent, contact lens multipurpose solution (MPS), contact lens disinfectant solution, eye drops, eye wash, contact lens packaging solution, contact lens mounting / eye drops, etc. It is not limited to these. More specifically, for example, the contact lens mounting solution described in “Pharmaceutical Manufacturing and Sales Guidelines Separate Occupational Drug Manufacturing and Sales Approval Criteria 2012 Edition (Jiho Co., Ltd.)”, Contact lens wear medicines described and regulated in “Yakuyoku Kaihatsu No. 0716006” “Safety Voluntary Safety Standards for Contact Lens Cleaning Agents, Preservatives, Cleaning Preservatives, etc., 6th Edition” (Edited by Contact Lens Association, General Incorporated Association, It is suitably used as a contact lens preserving solution, a contact lens rinsing solution, or a contact lens distribution preserving solution defined in November 2011). In addition, contact lens wearing / eye drops that can function as eye contact lenses while wearing contact lens mounting liquid, contact lens mounting / eye washing drugs that combine eye wash and contact lens mounting liquid, and contact lens mounting liquid and contact lenses It can also be used as a liquid agent in combination with a preservative liquid or a distribution preservative liquid (contact lens packaging liquid). In the present application, “contact lens mounting drug” and “contact lens mounting liquid” are collectively referred to as “contact lens mounting liquid” without being distinguished from each other. Among them, the composition for contact lenses according to the present embodiment is worn in a state where the composition is in contact with the contact lens or is in contact with the contact lens being worn (the composition remaining in the conjunctival sac and the contact lens). Contact lens mounting solution, contact lens preserving solution, contact lens rinsing solution, contact lens multipurpose solution (MPS), contact lens disinfecting solution, eye drops, eye wash, contact It is preferably at least one selected from lens packaging solutions.

The composition for contact lenses according to this embodiment can be used for various known contact lenses. Specifically, hard contact lenses and software that meet the contact lens approval standards described in “Amendments to the Contact Lens Approval Standards” issued on April 28, 2009, issued by the Ministry of Health, Labor and Welfare. Hydrogel) contact lenses and non-vision correction soft (hydrogel) contact lenses. Furthermore, ISO18369-1 (2006 and Amendement 1, 2009)
And hydrogel materials classified as groups I to V and non-hydrogel materials classified as groups I to IV. In addition, eye contact, anterior chamber sealing, drug delivery, corneal curvature changes (including orthokeratology contact lenses), retina treatment, and other therapeutic and examination contact lenses, visual field contrast It also includes sunglasses contact lenses that have functions such as amplification and reduction of incident light, reduction of incident light, polarization, and dimming. In particular, shape stability can be advantageously ensured by using it for silicone hydrogels and ionic soft contact lenses (groups III to IV).

  Concerning the shape of contact lenses, there are two or more types of materials, including corneal contact lenses, semi-scleral contact lenses, scleral contact lenses, and hybrid contact lenses (contact lenses that combine oxygen-permeable hard contact lenses and soft contact lenses). It may be a contact lens). Any contact lens design may be used, such as for astigmatism, for farsightedness, for astigmatism, for both near and near, and for shortsightedness. A contact lens may be a disposable contact lens that is used only for a short period of time within one day or from one week to several months, or a normal contact lens that is used for a longer period of time. Also good.

  The hypromellose (hydroxymethylpropylcellulose) blended in the contact lens composition is a mixture of multiple types of commercially available hypromellose that is easily available on the market that conforms to the 16th revision Japanese Pharmacopoeia. You can choose from hypromellose. For example, the substitution degree type is selected from 2208, 2906, and 2910. Among them, those having the substitution degree type of 2910 and 2906 are particularly preferably selected. Specifically, for example, TC-5E and TC-5M, TC-5R, TC-5S, Metrows 60SH-50, 60SH-1500, 60SH-4000, 65SH-15, 65SH-50, manufactured by Shin-Etsu Chemical Co., Ltd., 65SH-100, 65SH-1500, 65SH-4000, etc. can be employed.

  As the hypromellose contained in the contact lens composition of the present embodiment, those having a polydispersity of 8 or more, preferably 8 or more and 30 or less, more preferably 9 or more and 25 or less, and further preferably 10 or more and 20 or less are used. . As shown in the examples described later, when the polydispersity of hypromellose is less than 8, improvement in wettability of the contact lens, suppression of lipid adhesion to the contact lens, and not disturbing the structure of tears, However, the shape stability effect of the contact lens is not sufficiently exhibited. On the other hand, it is not realistic to adjust the polydispersity of hypromellose to more than 30 because the production difficulty from commercially available hypromellose becomes high. By adjusting the polydispersity to a limited range of 9 or more and 25 or less, and further 10 or more and 20 or less, the wearing feeling of the contact lens can be further improved. The polydispersity of hypromellose can be calculated by the ratio (Mw / Mn) of the weight average molecular weight (Mw) and the number average molecular weight (Mn) of the whole hypromellose contained in the contact lens composition.

  When adjusting hypromellose having a polydispersity of 8 or more, for example, by mixing commercially available hypromellose, for example, the value of the weight average molecular weight is greatly separated, that is, the difference in weight average molecular weight (the most of the hypromellose to be mixed). By mixing two hypromellose having a weight average molecular weight of a high molecular weight hypromellose and the lowest molecular weight hypromellose of 400,000 or more in a ratio of high molecular weight hypromellose: low molecular weight hypromellose = 3: 7 to 7: 3 Can be advantageously obtained.

  The hypromellose content in the contact lens composition is preferably from 0.0001 to 5.0 w / v%, more preferably from 0.001 to 3.0 w / v%, still more preferably from 0.001 to 5.0 w / v%. 005 to 1.5 w / v%. If the content of hypromellose is less than 0.0001 w / v%, contact lens wettability is improved, lipid adhesion to the contact lens is suppressed, and the tear structure is not disturbed. Stabilization is not fully expressed. Moreover, it is because the viscosity of a contact lens composition will become large too much when it exceeds 5.0 w / v%. Moreover, in order not to affect the stability of tears, the concentration of a low-viscosity product having a high surface active ability (the viscosity of a 2 w / w% aqueous solution at 20 ° C. is 7.0 mPa · s or less) is preferably 0.5 w. More preferably, it is blended at a concentration of / v% or less. In addition, about these viscosity measurements, it can carry out with reference to the 16th revision Japanese Pharmacopoeia general test method 2.53 viscosity measurement method 1st method or 2nd method.

  In addition, the weight average molecular weight of hypromellose is preferably 50,000 or more and 1,000,000 or less, more preferably 100,000 or more and 800,000 or less, and further preferably 200,000 or more and 600,000 or less. Is done. By specifying the weight-average molecular weight of hypromellose within such a range, the effects of the present invention can be further exerted, as well as the production of the applied contact lens composition can be facilitated.

  Furthermore, in the contact lens composition of the present embodiment, the effect of stably forming and maintaining a tear film on the surface of the contact lens after wearing the contact lens can be advantageously expressed as compared with the conventional contact lens composition. However, it is possible to further improve the feeling of wearing. In particular, it is desirable to use hypromellose having a substitution degree of methoxyl group of 27.0 to 30.0% and a substitution degree of hydroxypropoxyl group of 4.0 to 12.0%. Thereby, the tear film can be stably formed and held on the surface of the contact lens after the contact lens is mounted, and a good wearing feeling can be maintained over a long period of time.

  Moreover, it is preferable that the composition for contact lenses of this embodiment contains taurine. This is because the shape stability of the ionic soft contact lens can be particularly advantageously ensured.

  In the contact lens composition of the present embodiment, the remainder other than hypromellose improves the wettability of the contact lens by the present contact lens composition, suppresses lipid adhesion to the contact lens, and does not disturb the structure of tears. In addition, as long as the effects such as the shape stability of the contact lens are not impaired, additives and the like used in known contact lens compositions may be blended within an ophthalmologically acceptable range. Specifically, for example, known buffers, pH adjusters, surfactants, thickeners, tonicity agents, chelating agents, wetting agents, stabilizers, fragrances or cooling agents, drugs, antibacterial agents, preservatives -A disinfectant etc. may be mix | blended 1 type or in combination of 2 or more types.

  Examples of the buffer include boric acid, borax and borate buffer, carbonate buffer, citric acid and citrate buffer, carboxylic acids such as acetic acid, acids such as oxycarboxylic acid and salts thereof, taurine, Amino acids such as aspartic acid (salt), glycine, arginine, glutamic acid, ε-aminocaproic acid, 2-amino-2-methyl-1,3-propane (AMP) buffer, tris (hydroxymethyl) aminomethane (Tris) Buffers, bis (2-hydroxyethyl) iminotris (hydroxymethyl) methane (Bis-Tris), phosphoric acid and phosphate buffers, Good-Buffer, and the like.

  Examples of the pH adjuster include phosphates such as hydrochloric acid, citric acid, acetic acid, sodium hydroxide, potassium hydroxide, sodium carbonate, sodium hydrogen carbonate, boric acid, borax, sodium hydrogen phosphate, sodium dihydrogen phosphate and the like. And sulfuric acid. As known, the acidity and basicity, the pH before pH adjustment, and the desired pH are appropriately selected. They can be adjusted to a desired pH in the form of powder, liquid or aqueous solution.

  As the surfactant, any of conventionally known anionic surfactants, nonionic surfactants, and amphoteric surfactants can be appropriately employed. Examples of such surfactants include polyglycerin fatty acid esters, polyoxyethylene sorbitan fatty acid esters (polysorbates), polyoxyethylene alkylphenyl ether formaldehyde condensates, polyoxyethylene hydrogenated castor oil, polyoxyethylene alkylphenyl ether, Polyoxyethylene glycerin fatty acid ester, polyoxyethylene castor oil, polyoxyethylene sterol, polyoxyethylene hydrogenated sterol, polyoxyethylene fatty acid ester, polyoxyethylene polyoxypropylene alkyl ether, polyoxyethylene polyoxypropylene block copolymer (poloxamer) ), Polyoxyethylene polyoxypropylene substituted ethylenediamine (poloxamines), polyoxy Tylene lanolin alcohol, polyoxyethylene alkylamine, polyoxyethylene alkylamide, polyoxyethylene alkyl ether phosphate, polyoxyethylene alkyl ether carboxylate, polyoxyethylene alkyl ether sulfate, alkyl fatty acid salt, alkyl phosphate, N-acyl taurine salt, alkyl glutamate, alkyl glycine salt, alkyl alanine salt, cocoyl fatty acid arginine, alkyl sulfate, alkyl sulfonate, betaine acetate type double-sided activator, alkyloxyhydroxypropyl arginine salt, cocoyl arginine ethyl PCA, etc. Is mentioned.

  Examples of thickeners include synthetic organic polymers such as polyethylene glycol, polypropylene glycol, polyacrylamide, poly (meth) acrylic acid and salts, polyvinyl pyrrolidone, polyvinyl alcohol, and Polymer 845 (copolymer of polyvinyl pyrrolidone and dimethylaminoethyl methacrylate). Molecular compounds, etc., cellulose derivatives such as methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, carboxyethyl cellulose, starch derivatives, alginic acid (salt), pectin, chitosan and their salts, Dextrans, such as Dextran 70, and Chitosa, such as cationized chitosan Polysaccharide derivatives, and gellan gum heteropolysaccharide, hyaluronic acid (salt) may be added mucopolysaccharides such chondroitin sulfate, etc. (salt). In particular, when the contact lens composition of the present invention is applied to a contact lens mounting solution, contact lens mounting / ophthalmic solution, it is more preferable to add at least one selected from sodium chondroitin sulfate and sodium hyaluronate. .

  Examples of tonicity agents include sodium chloride, potassium chloride, calcium chloride, sodium bisulfite, sodium sulfite, magnesium chloride, potassium acetate, sodium acetate, sodium thiosulfate, magnesium sulfate, and other inorganic salts, propylene glycol, glycerin, D -Polyhydric alcohols such as mannitol, trehalose, glucose or ethers or esters thereof.

  Examples of chelating agents include ethylenediaminetetraacetic acid (EDTA) and salts thereof (ethylenediaminetetraacetic acid, disodium (EDTA, 2Na), ethylenediaminetetraacetic acid, trisodium (EDTA, 3Na), ethylenediaminetetraacetic acid, tetrasodium (EDTA, 4Na). Etc.), phytic acid, citric acid and the like.

  Examples of the wetting agent include glycerin, propylene glycol, polyethylene glycol, polypropylene glycol, xylitol, sorbitol, mannitol, erythritol, trehalose, glucose, sucrose, maltose, lactose and other polyhydric alcohols, sugars, sugar alcohols, glucosamines (salts), Amino sugars such as acetylglucosamine, galactosamine, acetylgalactosamine, sugar derivatives such as glucosyl trehalose, dextrans such as dextran 70, polyvinylpyrrolidone, poly (meth) acrylic acid and salts, copolymer 845 (copolymerization of polyvinylpyrrolidone and dimethylaminoethyl methacrylate) Polymer), polyvinyl compounds such as 2-methacryloyloxyethyl phosphorylcholine, and the like. Cellulose derivatives such as loin, hydroxyethyl cellulose and methyl cellulose, lower or higher alcohols such as ethanol, isopropanol, oleyl alcohol, lauryl alcohol, almond oil, lanolin, olive oil, oleic acid and / or salt thereof, liquid paraffin, triglyceride, squalane, Examples include fats and oils such as petroleum jelly, silicone oil, sesame oil, perilla oil, soybean oil, camellia oil, jojoba oil, corn oil, and castor oil. In addition, because it is safe for the eyes and reduces the influence on the contact lens, and further improves the usability of the contact lens composition, glycerin, propylene glycol, polyethylene glycol, polypropylene glycol, xylitol, Polyhydric alcohols such as sorbitol, mannitol, erythritol, trehalose, glucose, sucrose, maltose, lactose, sugar derivatives such as sugar, sugar alcohol, glucosyl trehalose, dextrans such as dextran 70, polyvinylpyrrolidone, poly (meth) acrylic acid and Salt, Copolymer 845 (copolymer of polyvinylpyrrolidone and dimethylaminoethyl methacrylate), 2-methacryloyloxyethyl phosphorylcholine, etc. Ribiniru compounds, cationic cellulose, that cellulose derivatives such as hydroxyethyl cellulose and methylcellulose are selected preferably.

  Stabilizers include ascorbic acid, ascorbic acid glucoside, sodium edetate, cyclodextrin, condensed phosphoric acid, sulfite, citric acid, dibutylhydroxytoluene, trometamol, sodium formaldehyde sulfoxylate (Longalite), tocopherol, sodium pyrosulfite, Examples include monoethanolamine and aluminum monostearate.

  Examples of the fragrance or refreshing agent include anethole, eugenol, camphor, chlorobutanol, geraniol, cineol, borneol, menthol, limonene, ryuuno, fennel oil, cool mint oil, cinnamon oil, spearmint oil, peppermint water, peppermint oil, peppermint Oil, bergamot oil, eucalyptus oil, rose oil and the like.

  Examples of the drug include antiallergic agents such as cromoglycic acid, chlorpheniramine maleate, diphenhydramine hydrochloride, amlexanox, ibudilast, pemirolast potassium, emedastine fumarate, ketotifen fumarate, olopatadine hydrochloride, ebastine, levocabastine, cetirizine hydrochloride, Glycyrrhizic acid and its salts, ε-aminocaproic acid, allantoin, sodium azulene sulfonate, berberine chloride, berberine sulfate, zinc sulfate, zinc lactate, lysozyme, fluorometholone and other steroidal or nonsteroidal anti-inflammatory agents, epinephrine, epinephrine hydrochloride , Ephedrine hydrochloride, naphazoline hydrochloride, naphazoline nitrate, phenylephrine hydrochloride, tetrahydrozoline hydrochloride, and other vasoconstrictors, methyl sulfate neostigmine, etc. Agents for improving the function of regulating insulin, betaxolol, timolol, dipivefrin, carteolol, latanoplast, tafluplast, travoplast, nipradilol, levobunol, etc., mucin secretion production promoters such as rebamipide, diquafosol sodium, sodium hyaluronate, etc. Corneal epithelial wound healing agent, flavin adenine dinucleotide sodium, cyanocobalamin, retinol acetate, retinol palmitate, pyridoxine hydrochloride, panthenol, calcium pantothenate, sodium pantothenate, tocopherol acetate, aspartic acid and its salts, taurine And amino acids such as chondroitin sulfate, arginine, alanine, lysine and glutamic acid.

  Antibacterial agents include, for example, sulfamethoxazole, sulfamethoxazole sodium, sulfisoxazole, sulfisomidine sodium and other sulfa drugs, ofloxacin, norfloxacin, levofloxacin, gatifloxacin, moxifloxacin, tosufloxacin New quinolone antibacterial agents such as lomefloxacin and ciprofloxacin, aminoglycoside antibacterial agents such as tobramycin, gentamicin, micronomycin, dibekacin and sisomycin, tetracycline antibacterial agents such as tetracycline and minocycline, and macrolide antibacterial agents such as erythromycin And chloramphenicol antibacterial agents such as chloramphenicol, and cephem antibacterial agents such as cefmenoxime.

  Examples of preservatives and bactericides include sorbic acid, potassium sorbate, benzoic acid or salts thereof, ethyl paraoxybenzoate, butyl paraoxybenzoate, propyl paraoxybenzoate, methyl paraoxybenzoate, chlorobutanol, benzalkonium chloride, Polyhexanide hydrochloride (polyhexamethylene biguanide; PHMB), alkyldiaminoethylglycine hydrochloride, cetylpyridinium chloride (CPC), chlorhexidine, alexidine, chlorpheniramine or a salt thereof, allantoin, chlorine dioxide, stabilized chlorine dioxide, sodium chlorite, And polyquaterniums such as sodium perborate and polydronium chloride.

  As described above, according to the contact lens composition according to the present embodiment, hypromellose having a polydispersity of less than 8 is obtained by including hypromellose adjusted to have a polydispersity of 8 or more as a blend. Compared with conventional contact lens compositions, it is advantageous to improve the wettability of contact lenses, suppress lipid adhesion to contact lenses and not disturb the structure of tears, and further improve the shape stability of contact lenses It can be realized. In addition, when a methoxyl group having a substitution degree of 27.0 to 30.0% and a hydroxypropoxyl group substitution degree of 4.0 to 12.0% is used, contact is performed after the contact lens is mounted. A tear film can be stably formed and held on the surface of the lens, and a good wearing feeling can be maintained over a long period of time. In addition, by further containing taurine, it is possible to ensure the shape stability of the ionic soft contact lens more advantageously.

  As mentioned above, although the preferred embodiment of the composition for contact lenses concerning this invention has been explained in detail, concretely, these are illustrations to the last and this invention is what by the above-mentioned concrete description. It should not be construed as limiting. For example, the contact lens composition of the present embodiment improves the wettability of the contact lens, suppresses adhesion of lipid to the contact lens and does not disturb the structure of tears, and further, effects of shape stability of the contact lens In addition to the above, it is natural that the present invention includes those that exhibit further functions by including specific components as required.

  Hereinafter, in order to further clarify the technical significance of the present invention, the present invention will be described more specifically with reference to examples and comparative examples. However, the present invention is not limited to the following examples.

[Examples 1 to 10, Comparative Examples 1 to 42]
First, according to the composition table of [Table 1] and [Table 2] below, each component in the table is dissolved in purified water according to a conventional method, pH is adjusted, and then each solution is aseptically filtered. The composition for contact lenses of 1-10 and Comparative Examples 1-42 was prepared.

  In general, hypromellose can be obtained by known methods described in JP-A-10-158302 and JP-A-08-301901. For example, a method of obtaining hypromellose by immersing purified wood pulp or linker pulp in a sodium hydroxide solution to obtain swollen alkali cellulose and then dehydrating it to simultaneously act on methyl chloride and propylene oxide. Hypromellose according to the present invention can be obtained by adjusting a desired polydispersity by mixing a high molecular weight hypromellose prepared by these methods and a low molecular weight hypromellose at a predetermined ratio. For example, the following [Table 3] ] Can be adjusted to a desired polydispersity by mixing a plurality of types of hypromellose according to the mixing ratio described in [Table 4] below (Examples 1 to 9 and Comparative Example 1). Hypromellose (HPMC) formulated in a contact lens composition of ~ 41). Furthermore, it is possible to obtain hypromellose having a desired polydispersity by appropriately selecting the reaction conditions in the method for producing hypromellose (hypromellose blended in the contact lens compositions of Example 10 and Comparative Example 42). (HPMC)).

In addition, the substitution degree of HPMC mix | blended with Example 10 and the comparative example 42 is as follows, respectively. The degree of substitution was measured by the method described in the 16th revised Japanese Pharmacopoeia Pharmaceuticals Articles Hypromellose Determination Method.
Hypromellose blended in Example 10:
Degree of substitution with methoxyl group (%): 29.2
Hydroxypropoxyl group (%): 10.6
Hypromellose blended in Comparative Example 42:
Degree of substitution with methoxyl group (%): 29.7
Hydroxypropoxyl group (%): 10.8

Moreover, the measurement of the polydispersity degree of each hypromellose mix | blended with Examples 1-10 and Comparative Examples 1-42 was performed in the following procedures. First, the total concentration of each hypromellose mixed at the ratio shown in [Table 4] was 0.1 w / w (%) (for HPMC blended in Example 10 and Comparative Example 42, the HPMC concentration was 0). 0.1 w / w (%)) was dissolved in a 0.1 mol / L aqueous solution of sodium nitrate (manufactured by Wako Pure Chemical Industries, Ltd.) to prepare each test solution. And gel filtration chromatography (GPC) was performed using each test solution, the molecular weight distribution curve of the hypromellose in each test solution was calculated | required, and the weight average molecular weight (Mw) and the number average molecular weight (Mn) were computed. This measurement was performed 3 times, and the average value was calculated to determine Mw and Mn of hypromellose. Thereafter, Mw / Mn was calculated to determine the polydispersity of each hypromellose. The results are also shown in [Table 4]. The weight average molecular weight (Mw), number average molecular weight (Mn) and polydispersity of hypromellose blended in Example 10 and Comparative Example 42 were as follows.
Hypromellose blended in Example 10:
Weight average molecular weight (Mw): 336000
Number average molecular weight (Mn): 32000
Polydispersity: 10.5
Hypromellose blended in Comparative Example 42:
Weight average molecular weight (Mw): 82000
Number average molecular weight (Mn): 28500
Polydispersity: 2.9

  In the above measurement, a differential refractive index detector (for 2410 Alliance HPLC system) manufactured by Waters Co., Ltd. is used as a chromatogram detector, and “OHpak SB-806mHQ” manufactured by Showa Denko KK is used as a column. “8 mm × 300 mm” was employed, and measurement was performed under the conditions of a flow rate of 1.0 mL / min, a temperature of 30 ° C., and an injection amount of 20 mL. In addition, as a compound having a known molecular weight, monodisperse polyethylene oxide SE-5, SE-8, SE-30, SE-150 (molecular weights in order 46,000, 95000, 250,000, 920000) manufactured by TOSO are used under the above conditions. And a calibration curve of elution time-molecular weight was prepared. And the molecular weight distribution of hypromellose was calculated | required from the elution time of each test solution using this calibration curve. At that time, the chromatogram obtained from each test solution was analyzed using data up to 11.0 minutes, which is the column exclusion limit, using analysis software “Empower2” manufactured by Waters Inc.

[Moisture retention effect evaluation test]
First, “2WEEK Menicon Premio” (trade name) manufactured by Menicon Co., Ltd., which is a contact lens made of silicone hydrogel, was prepared as a test lens. After immersing this test lens in 2 ml of cobalt chloride (II) hexahydrate aqueous solution (20 w / v%) for 4 hours or more, the test lens was taken out and excess water on the lens surface was made by Nippon Paper Crecia Co., Ltd. It was wiped lightly with “Kimwipe” (trade name), a paper waste. Thereafter, the test lens is immersed in 2 ml of each of the test solutions of Examples 1 to 10 and Comparative Examples 1 to 42, and the water on the surface of the test lens is absorbed by “Kimwipe”. It was allowed to stand in the room and dried. Each test lens was visually observed 20 minutes after the start of drying, and those that were completely blue were evaluated as x and those that remained red were evaluated as ◯. The results of this evaluation test are shown in [Table 5] described later.

[Surface tension evaluation test]
Using each test solution, the surface tension of each test solution was measured by “Drop Master 500” manufactured by Kyowa Interface Chemical Co., Ltd. About the result of this measurement, surface tension evaluated 50 mN / m or more as x, and less than 50 mN / m was evaluated as (circle). The results of this evaluation test are also shown in [Table 5] described later.

[Wettability improvement rate evaluation test]
First, a test lens (2WEEK Menicon Premio) was immersed in each of 2 ml of each test solution of Examples 1 to 10 and Comparative Examples 1 to 42 and 2 ml of physiological saline defined in ISO18369-3 for 4 hours or more. After each test lens was removed from the test solution, excess water on the surface of each test lens was gently wiped off with “Kimwipe”. Thereafter, physiological saline is dropped on the front curve surface of each test solution and each lens immersed in physiological saline, and the contact angle of the water droplet is measured by “Drop Master 500” manufactured by Kyowa Interface Chemical Co., Ltd. The improvement rate of the wettability of the test solution with respect to water was evaluated. The wettability improvement rate (%) was calculated by the contact angle (°) of the water droplet with respect to the lens immersed in physiological saline / the contact angle (°) of the water droplet with respect to the lens immersed in the test solution. The results of this evaluation test are also shown in [Table 5] described later.

  As is clear from [Table 5], in the contact lens compositions of Examples 1 to 10 in which the polydispersity of hypromellose was adjusted to 8 or more, good water retention and surface tension were exhibited. Yes. Moreover, the wettability improvement rate at the time of using a contact lens mounting liquid is 236-312, and the remarkable wettability improvement is aimed at. On the other hand, in the contact lens compositions of Comparative Examples 1 to 42 in which the polydispersity of hypromellose is less than 8, at least one of water retention and surface tension is poor, and the wettability improvement rate is 98 to 172. Therefore, it remains at a very low value as compared with Examples 1-10. From these test results, when the contact lens mounting solutions of Examples 1 to 10 in which the polydispersity of hypromellose was adjusted to 8 or more were used, the amount of hypromellose was increased even when hypromellose was contained as in the conventional composition. It has been confirmed that the wettability of the contact lens, and thus the wearing feeling of the contact lens, can be dramatically improved as compared with Comparative Examples 1 to 42 in which the degree of dispersion is less than 8.

[Lipid adhesion evaluation test]
First, the test lens was immersed in 2 mL of physiological saline defined by ISO18369-3 for 16 hours or more, and then immersed in each test solution of Examples 1-9 and Comparative Examples 1-11 for 16 hours or more. Next, “Sudan Black” (manufactured by Wako Pure Chemical Industries, Ltd.) was dissolved in 10 mL of 70% ethanol, and then the lens was immersed in 2 mL of Sudan Black solution prepared by adding 90 mL of distilled water for 2 hours. Then, the lens was taken out and rinsed with physiological saline, and then each test lens was photographed in physiological saline to confirm the degree of lipid adhesion. Then, the photograph was visually checked, and evaluation was made with ○ indicating that the lipid was hardly attached and × indicating that the lipid was confirmed to be attached. As a test lens, “Acuvue Oasis” (registered trademark), which is a silicone hydrogel contact lens manufactured by Johnson & Johnson, was used. The results of this evaluation test are shown in [Table 6] described later.

  As a result, in the contact lens compositions of Examples 1 to 9 in which the polydispersity of hypromellose is adjusted to 8 or more, the contact lens compositions of Comparative Examples 1 to 11 in which the polydispersity of hypromellose is less than 8 are used. It was found that lipid adhesion to the soft contact lens made of silicone hydrogel can be well suppressed as compared with the case where it was.

[Tear fluid stability test]
First, “Menicon 1DAY” (trade name) manufactured by Menicon Co., Ltd., which is a high water content soft contact lens, was prepared as a test lens. After wetting the test lens with each of the test solutions of Examples 1 to 9 and Comparative Examples 1 to 11, each lens was worn on the subject's eye, and the state of tears after 5 minutes and 15 minutes after wearing was observed. did. In addition, this observation was implemented about 4 eyes and the state of tears was observed with the dry eye observation apparatus "DR-1" by Kowa Co., Ltd. In addition, the tear film is sufficiently thick and the oil layer can be confirmed on the water layer (the most stable tear film) is score 1. The tear film is thin and the test lens surface is exposed. The state of tearing (the state in which the tear film is most unstable) was scored 5, and the state of tears at 5 minutes and 15 minutes after wearing was evaluated with scores 1 to 5. This evaluation test is performed three times, the average value of the scores is calculated to determine the score of the test solution for each subject, and the average value of the scores between the subjects is calculated to determine the score of each test solution did. When the score of this test solution is less than 2, the case of 2 or more and less than 3 is evaluated as ◯, the case of 3 or more and less than 4 is evaluated as △, and the case of 4 or more is evaluated as ×. It shows together with [Table 6]. On the other hand, for Example 1 and Comparative Example 1, in addition to the evaluations after 5 minutes and 15 minutes after wearing separately, wearing of contact lenses was continued after 15 minutes and contact of the subject 30 minutes after wearing. Two drops were instilled into the lens wearing eye, and evaluation was also performed 5 minutes and 30 minutes after the instillation. In addition, evaluation was performed 35 minutes after wearing and 60 minutes after wearing contact lenses without instillation. The evaluation results are shown in [Table 6].

  As is apparent from [Table 6], in the contact lens compositions of Examples 1 to 9 in which the polydispersity of hypromellose is adjusted to 8 or more, good tear stability is ensured. In particular, the substitution degree of methoxyl group within the range of substitution degree of methoxyl group and hydroxypropoxyl group of hypromellose according to the third aspect of the present invention is 28.0 to 30.0%, and hydroxypropoxyl group In Examples 1 to 8 where hypromellose having a substitution degree of 7.0 to 12.0% is used, good tear stability is maintained even 15 minutes after wearing, and good tears are obtained. It has been found that the wettability of the contact lens due to the liquid stability, and thus the improvement in wearing feeling, is maintained for a long time. On the other hand, in the composition for contact lenses of Comparative Examples 1 to 11 where the polydispersity of hypromellose is less than 8, sufficient tear fluid stability is often not maintained even after 5 minutes after wearing, It was confirmed that the tear film became unstable in 15 minutes after wearing. As a result, it has been achieved for the first time by adjusting the polydispersity of the hypromellose to 8 or more, that the lipid adhesion of the contact lens and the structure of the tears are not disturbed, both of which have been difficult to achieve in the past. Was confirmed. On the other hand, with respect to the case where Example 1 was used, it was confirmed that the tear stability was continued by performing further instillation. However, it was found that the effect of tear fluid stability was not obtained even when further instillation was performed on Comparative Example 1 which was different from Example 1 only in that the polydispersity of hypromellose was outside the scope of the present invention.

[Lens diameter change evaluation test (shape stability)]
First, each contact lens of the lenses 1 to 3 whose diameter (mm) was measured in advance was immersed in each test solution of Examples 1 to 10 and Comparative Examples 1 to 42 added in a glass vial for contact lenses. The package was sealed and then autoclaved at 121 ° C. for 30 minutes. Then, in accordance with FDA (US Food and Drug Administration) guidelines for accelerated shelf life test, the lens for each contact lens of lenses 1 to 3 was immersed in each test solution after being stored for 9 months at 45 ° C. and 45% humidity. The diameter was measured again, and the amount of change in lens diameter before and after the test was calculated. Then, the lens diameter change amount of less than 0.10 mm was evaluated as ◎, the change amount of 0.10 mm or more and less than 0.20 mm was evaluated as ◯, and the change amount of 0.20 mm or more was evaluated as ×. The lens 1 is a silicone hydrogel lens “Accuview Advance” (registered trademark) manufactured by Johnson & Johnson, and the lens 2 is a non-ionic water-containing soft contact lens “Medalist Plus” ( (Registered Trademark) is used as the lens 3 and "One Day Accuview" (Registered Trademark) manufactured by Johnson & Johnson Co. is used as the ionic water-containing soft contact lens, and the diameter before these tests is 14.0 mm. The lens power was -0.50D. The results of this evaluation test are shown in [Table 7] described later.

[Rear curvature radius change evaluation test (shape stability)]
First, as the test lens 4, “Menicon Z” (trade name) manufactured by Menicon Co., Ltd., which is an oxygen-permeable hard contact lens, was used, and test lenses whose rear curvature radius (mm) was measured in advance were used in Examples 1 to 10. The sample was immersed in 2 ml of each test solution of Comparative Examples 1-42. Then, following the FDA (US Food and Drug Administration) guidelines for accelerated shelf life tests, store for 9 months at 45 ° C and 45% humidity, then re-measure the radius of curvature of the rear surface of the lens immersed in each test solution. The amount of change in the radius of curvature of the rear surface of the lens before and after the test was calculated. The change amount of the radius of curvature of the rear surface of the lens is ◎ if the change amount is less than 0.05 mm, ○ if the change amount is 0.05 mm or more and less than 0.10 mm, and change amount is 0.10 mm or more Was evaluated as x. In addition, the measurement of the curvature radius was implemented according to "ISO10338: 1996 (E) Optics and optical instruments-Contact lengths-Determination of curvature". Moreover, the lens power of the test lens was −3D. The results of this evaluation test are also shown in [Table 7].

  As is apparent from [Table 7], in the contact lens compositions of Examples 1 to 10 in which the polydispersity of hypromellose is adjusted to 8 or more, both the lens diameter change amount and the rear curvature radius change amount are good. The shape stability of the contact lens is achieved more advantageously than the silicone hydrogel lens 1, the non-ionic water-containing soft contact lens 2, and the ionic water-containing soft contact lens 3. I found out that Particularly, in Examples 1, 3, 4, 6, 8, and 10 in which taurine is blended, it is easy to ensure good shape stability of the contact lens even with respect to the ionic water-containing soft contact lens. It was confirmed that there is. On the other hand, in the contact lens compositions of Comparative Examples 1 to 42 in which the polydispersity of hypromellose is less than 8, at least one of the lens diameter change amount and the rear surface curvature radius change amount is poor or has a sufficient suppressing effect. It was not obtained and it was found that stable shape stability of the contact lens could not be secured. In short, by adjusting the polydispersity of hypromellose contained in the contact lens preservation solution to 8 or more, it is possible to ensure better shape stability than before for many types of contact lenses.

[Marking visibility evaluation test (physical property stability)]
First, each test solution of Examples 1 to 9 and Comparative Examples 1 to 41 in which the contact lenses of the lenses 1 and 5 previously marked with the letter “123” were added to the glass vial for contact lenses. Soaked in. The package was sealed and then autoclaved at 121 ° C. for 30 minutes. After that, according to FDA (US Food and Drug Administration) guidelines for accelerated shelf life tests, marking for each contact lens of lenses 1 and 5 after storage for 9 months at 45 ° C and 45% humidity. The visibility of was evaluated. For the evaluation method, the character “123” in the marking portion is observed with an optical microscope at a magnification of 10 ×, and ◎ indicates that the character is clear, ○ indicates that the character is slightly inferior but can be confirmed. A case where the characters were not clear and could be confirmed was indicated by Δ, and a case where characters were hardly confirmed was indicated by ×. In this evaluation test, as the lens 1, “Accuview Advance” (registered trademark) manufactured by Johnson End Johnson Co., Ltd. is used as a lens made of silicone hydrogel, and as the lens 5, Johnson End Johnson Co., Ltd. is used as an ionic water-containing soft contact lens. “2 Week Accuview” (registered trademark) manufactured by the company was employed, and the diameters before these tests were all 14.0 mm and the lens powers were both −0.50 D. The results of this evaluation test are shown in [Table 8].

  As is clear from [Table 8], in the contact lens compositions of Examples 1 to 9 in which the polydispersity of hypromellose is adjusted to 8 or more, the marking visibility is the lens 1 made of silicone hydrogel and the ions. It was found that all of the lenses 5 of the water-containing soft contact lens were clear. In particular, in Examples 1, 3, 4, 6, and 8 in which taurine was blended, it was confirmed that the ionic water-containing soft contact lens was useful for ensuring the marking visibility. On the other hand, in the contact lens compositions of Comparative Examples 1 to 41 in which the polydispersity of hypromellose is less than 8, good marking visibility is not achieved. In short, by adjusting the polydispersity of hypromellose contained in the contact lens composition to 8 or more, the visibility of the marking can be stabilized better than before for many types of contact lenses.

[Precipitation reduction effect evaluation test]
First, 30 μL of each test solution of Examples 1 to 9 and Comparative Examples 1 to 11 was dropped near the discharge port of an LDPE (low density polyethylene) eye drop container, and an AS (acrylonitrile-styrene copolymer) cap was attached. Closed and dried at 60 ° C. This operation was repeated 10 times, and deposits adhered to the discharge port and the cap were visually observed. The case where no precipitate was confirmed was evaluated as ◎, the case where it did not affect the opening and closing of the cap was evaluated as ◯, and the case where the precipitate appeared so as to affect the opening and closing of the cap was evaluated as ×. The results of this evaluation test are shown in [Table 9].

  As is clear from [Table 9], in the contact lens compositions of Examples 1 to 9 in which the polydispersity of hypromellose is adjusted to 8 or more, the formation of precipitates is favorably reduced. In Comparative Examples 1 to 11 having a polydispersity of less than 8, precipitates were generated that had an effect on the opening and closing of the cap. By using the contact lens composition of the present invention as a storage solution or a mounting solution, the generation of precipitates can be suppressed, and the occurrence of a foreign object feeling after mounting due to the influence of the deposits can be prevented in advance. The wearing feeling of the lens can be improved.

[Prescription example]
Contact lens solutions (formulation examples 1 to 60) were prepared according to the formulations described in [Table 10] to [Table 16]. In [Table 10] to [Table 16], the unit of each blending component is g / 100 mL unless otherwise specified. Moreover, in the prescription examples 46-60 as described in [Table 15] and [Table 16], the hypromellose from which substitution degree differs is combined. Furthermore, in the prescription examples, prescriptions such as contact lens mounting liquid, eye drops, contact lens preserving liquid, contact lens rinsing liquid, MPS (multipurpose liquid for contact lenses) are shown for each application. It can be used for contact lenses.

Claims (5)

  A composition for contact lenses comprising hypromellose having a polydispersity of 8 or more.   The composition for contact lenses according to claim 1, wherein the hypromellose has a weight average molecular weight of 50,000 or more and 1,000,000 or less.   The contact according to claim 1 or 2, wherein the hypromellose has a methoxyl group substitution degree of 27.0 to 30.0% and a hydroxypropoxyl group substitution degree of 4.0 to 12.0%. Lens composition.   The composition for contact lenses according to any one of claims 1 to 3, further comprising taurine.   The contact lens composition according to claim 1, wherein the polydispersity of the hypromellose is 10 or more and 20 or less.