JP2011207874A - Ophthalmic composition for soft contact lens - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an ophthalmic composition for soft contact lens which controls absorption of an antihistamine selected from diphenhydramine and a salt of the same to the soft contact lens and performs excellent exchange of a lacrimal liquid in attaching the soft contact lens.SOLUTION: The ophthalmic composition for soft contact lens includes (A) diphenhydramine and/or the salt of the same, (B) cromoglycic acid and/or a salt of the same, (C) glycyrrhetinic acid and/or a salt of the same, and (D) chondroitin sulfuric acid and/or a salt of the same.

Description

  The present invention relates to an ophthalmic composition for a soft contact lens containing an antihistamine selected from diphenhydramine and a salt thereof, an adsorption inhibitor and a method for inhibiting adsorption of the antihistamine on a soft contact lens.

  When a soft contact lens (SCL) is mounted, the lens surface is dried and pollen and contaminants from the outside are likely to adhere, and allergic symptoms such as itching and inflammatory hyperemia are likely to occur. Therefore, a soft contact lens user composition containing an anti-inflammatory component, an antihistamine component or an anti-hyperemia component has been desired for some time.

  Among them, diphenhydramine, chlorpheniramine and salts thereof, which are antihistamine components, are excellent in the effect of suppressing itching and are widely used in eye drops for the purpose of suppressing itching. However, these antihistamine components have a high affinity with soft contact lenses, so when used as a composition for soft contact lens users, they can be adsorbed on the lens surface and accumulate in the lens over time. There is a possibility of adverse effects such as physical properties of the lens, feeling during use, and side effects. Therefore, in order to adapt to the soft contact lens user, it is necessary to suppress the adsorption of the antihistamine component to the lens.

  Conventionally, as a method of suppressing the adsorption of a drug to a soft contact lens, a method of suppressing the adsorption of a fat-soluble vitamin with a polymer compound and a nonionic surfactant (see Patent Document 1: JP 2001-158734 A), A method for suppressing adsorption of dipotassium glycyrrhizinate with an amino acid or the like (Patent Document 2: Japanese Patent Application Laid-Open No. 2001-002563), a method for suppressing protein adsorption with hydroxypropylmethylcellulose (Patent Document 3: Japanese Patent Application Laid-Open No. 2002-322048) Patent Literature 4), and a method for suppressing adsorption of a cooling agent with polyhydric alcohols (see Patent Literature 4: Japanese Patent Laid-Open No. 2001-122774). In addition, a method for suppressing adsorption of chlorpheniramine maleate to a container by adjusting the pH of the composition to 5 to 6 (see Patent Document 5: JP 2002-249445 A), a cyclodextrin, and a container There is known a method for suppressing the adsorption to the surface (see Patent Document 6: Japanese Patent Application Laid-Open No. 2004-359679). Moreover, as a method for suppressing the adsorption of the antihistamine component to the soft contact lens, the pH of the composition is adjusted to 3.5 to 4.8, whereby the basic drug containing the antihistamine component is applied to the soft contact lens. Methods of suppressing adsorption (Patent Document 7: JP 2009-161455 A, Patent Document 8: International Publication No. 2007/077783 pamphlet) are known, but adsorption to a soft contact lens in a neutral region is suppressed. The method is not known.

JP 2001-158734 A JP 2001-002563 A JP 2002-322048 A JP 2001-122774 A JP 2002-249445 A JP 2004-359679 A JP 2009-161455 A International Publication No. 2007/077783 Pamphlet

  The present invention has been made in view of the above circumstances, and suppresses the adsorption of an antihistamine selected from diphenhydramine and a salt thereof to a soft contact lens and improves ocular fluid exchange when the soft contact lens is worn. An object is to provide a composition. Another object of the present invention is to provide an adsorption inhibitor and a method for inhibiting adsorption of the antihistamine to the soft contact lens.

  As a result of intensive studies to achieve the above object, the inventors of the present invention have developed an ophthalmic composition for soft contact lenses containing an antihistamine selected from diphenhydramine and a salt thereof, cromoglycic acid and / or a salt thereof, glycyrrhizic acid and / or Or the salt thereof and chondroitin sulfate and / or a salt thereof are found to suppress the adsorption of the antihistamine to the soft contact lens, and promote tear exchange when the soft contact lens is worn. It came to make this invention.

Accordingly, the present invention provides the following ophthalmic compositions for contact lenses, antihistamine adsorption inhibitors and adsorption inhibition methods for soft contact lenses.
[1]. Containing (A) diphenhydramine and / or a salt thereof, (B) cromoglycic acid and / or a salt thereof, (C) glycyrrhizic acid and / or a salt thereof, and (D) chondroitin sulfate and / or a salt thereof. An ophthalmic composition for soft contact lenses.
[2]. The ophthalmic composition for soft contact lenses according to [1], further comprising (E) a nonionic surfactant.
[3]. The ophthalmic composition for soft contact lens according to [1] or [2], wherein the soft contact lens is a lens of FDA contact lens classification group IV.
[4]. The ophthalmic composition for soft contact lenses according to any one of [1] to [3], which does not contain a preservative.
[5]. The soft contact according to any one of [1] to [4], further comprising (F) one or more components selected from boric acid, borate, trometamol, sodium edetate, menthol, camphor, borneol and geraniol. Ophthalmic composition for lenses.
[6]. (A) Formulated in an ophthalmic composition for soft contact lenses containing diphenhydramine and / or a salt thereof, (B) cromoglycic acid and / or a salt thereof, (C) glycyrrhizic acid and / or a salt thereof, and (D) An adsorption inhibitor for the soft contact lens of the component (A), comprising chondroitin sulfate and / or a salt thereof.
[7]. (A) Ophthalmic composition for soft contact lens containing diphenhydramine and / or salt thereof, (B) cromoglycic acid and / or salt thereof, (C) glycyrrhizic acid and / or salt thereof, and (D) chondroitin sulfate And / or a salt thereof, and a method for suppressing adsorption of the component (A) to the soft contact lens.

  According to the present invention, there is provided an ophthalmic composition for a soft contact lens that suppresses the adsorption of an antihistamine selected from diphenhydramine and a salt thereof to a soft contact lens, and that improves the tear fluid exchange when the soft contact lens is worn. Can do. By promoting tear exchange, the supply of oxygen and nutrients is promoted, and an effect of improving symptoms such as dry eye can be expected. Moreover, according to this invention, the antihistamine adsorption inhibitor and the adsorption | suction suppression method to a soft contact lens can be provided.

<(A) Diphenhydramine and its salt>
Component (A), diphenhydramine and a salt thereof, are active ingredients of the present invention having an antihistamine action. More specifically, diphenhydramine hydrochloride is preferable as diphenhydramine and a salt thereof used in the present invention. These can be used individually by 1 type or in combination of 2 or more types.

  The blending amount of the component (A) is preferably 0.001 to 1.0 w / v% (mass / volume w / v% (g / 100 mL), the same applies hereinafter) in the ophthalmic composition for soft contact lenses, and more preferably. It is 0.005-0.5 w / v%, More preferably, it is the range of 0.01-0.05 w / v%. If it is less than 0.001 w / v%, the antihistamine action may be insufficient, and if it exceeds 1.0 w / v%, an improvement in the effect may not be expected. If it is the range of 0.001-1.0 w / v%, a favorable effect will be acquired from the point of effectiveness.

<(B) Cromoglycic acid and its salt>
Cromoglycic acid and its salt are antiallergic agents, and when added to an ophthalmic composition containing the component (A), the component (A) is suppressed from adsorbing to the soft contact lens. Examples of cromoglycic acid and salts thereof include cromoglycate such as sodium cromoglycate in addition to cromoglycic acid itself. Cromoglycic acid and a salt thereof can be usually blended in an ophthalmic composition in an amount of 0.01 to 10.0 w / v%, preferably 0.1 to 3.0 w / v%, more preferably 0.8. It is in the range of 5 to 2.0 w / v%. By setting it as the range of 0.01-10.0 w / v%, the antiallergic effect and the effect of this invention can be acquired more.

<(C) Glycyrrhizic acid and its salt>
Glycyrrhizic acid and its salts are anti-inflammatory agents and are added to ophthalmic compositions containing the component (A) to suppress the adsorption of the component (A) to the soft contact lens and promote tear exchange. To do. Examples of glycyrrhizic acid and salts thereof include glycyrrhizic acid salts such as dipotassium glycyrrhizinate in addition to glycyrrhizic acid itself. Glycyrrhizic acid and a salt thereof can be usually blended in an ophthalmic composition in an amount of 0.01 to 5.0 w / v%, preferably 0.01 to 3.0 w / v%, more preferably 0.8. It is the range of 05-1.0 w / v%. By making it the range of 0.01-5.0 w / v%, the anti-inflammatory effect and the effect of this invention can be acquired more.

<(D) Chondroitin sulfate and its salt>
Chondroitin sulfate and its salts are a kind of amino acid, and by further adding the component (D) to the components (B) and (C), the component (A) is further suppressed from adsorbing to the soft contact lens, and Improve tear exchange when wearing soft contact lenses. Chondroitin sulfate and salts thereof include chondroitin sulfate such as sodium chondroitin sulfate in addition to chondroitin sulfate itself. Chondroitin sulfate and salts thereof can be usually blended in the ophthalmic composition in an amount of 0.01 to 5.0 w / v%, preferably 0.01 to 3.0 w / v%, more preferably 0.8. It is the range of 05-1.0 w / v%. If it is the range of 0.01-5.0 w / v%, the effect favorable from the point of the effect of this invention and the usability | use_condition of an eyedrop composition will be acquired.

<(E) Nonionic surfactant>
In the present invention, the addition of (E) nonionic surfactant to the components (B) to (D) further suppresses the adsorption of the component (A) to the soft contact lens. In addition, the lacrimal fluid exchange is improved when the soft contact lens is worn. Examples of the nonionic surfactant include higher fatty acid esters such as water-soluble polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan higher fatty acid ester, sucrose fatty acid ester, polyoxyethylene polyoxypropylene glycol and the like. Specifically, for example, polyoxyethylene (p = 40, 50, 60) hydrogenated castor oil, polyoxyethylene (p = 20) sorbitan monooleate (polysorbate 80), polyoxyethylene (200) polyoxypropylene ( 70) Glycol and the like. More specifically, for example, polyoxyethylene hydrogenated castor oil such as HCO-40, HCO-50, HCO-60 (polyoxyethylene hydrogenated castor oil 60) manufactured by Nikko Chemicals Co., Ltd., polyoxyethylene sorbitan monoolee Examples of the polyoxyethylene polyoxypropylene glycol include TO-10MV manufactured by Nikko Chemicals Co., Ltd., Lutrol F127 manufactured by BASF Corporation, and Unilube 70DP-950B manufactured by NOF Corporation. These can be used individually by 1 type or in combination of 2 or more types. Among these, polyoxyethylene (p = 60) hydrogenated castor oil, polyoxyethylene (p = 20) sorbitan monooleate, polyoxyethylene (200) polyoxypropylene (70) glycol and the like are preferably used. (E) Although the compounding quantity of a component is not restrict | limited in particular, Usually, 0.001-10.0 w / v% is preferable with respect to the whole composition, More preferably, it is 0.01-5.0 w / v%, More preferably, it is the range of 0.05-3.0 w / v%. If it is the range of 0.001-10.0 w / v%, a preferable effect will be acquired from the point of the effect of this invention and the property of an eye drop composition.

<Other ingredients>
In the ophthalmic composition of the present invention, in addition to the above components, various components that can be blended in the ophthalmic composition can be blended within a range not impairing the effects of the present invention. These components include buffers, thickeners, pH adjusters, preservatives, isotonic agents, stabilizers, cooling agents, drugs, water and the like. These can be used individually by 1 type or in combination of 2 or more types, respectively, and can mix | blend suitable amount.

  Examples of the buffer include boric acid or a salt thereof (such as borax), citric acid or a salt thereof (such as sodium citrate), phosphoric acid or a salt thereof (such as sodium monohydrogen phosphate), tartaric acid or a salt thereof (tartaric acid) Sodium), gluconic acid or a salt thereof (sodium gluconate, etc.), acetic acid or a salt thereof (sodium acetate, etc.), various amino acids (ε-aminocaproic acid, potassium aspartate, aminoethylsulfonic acid, glutamic acid, sodium glutamate, etc.) And trometamol. Of these, trometamol is preferable from the viewpoint of low irritation and the antiseptic effect of the composition. Further, when boric acid and borax are used in combination, a particularly high antiseptic effect is obtained. The content of the buffer is preferably 0.001 to 10 w / v% in the ophthalmic composition, and more preferably 0.01 to 5 w / v%.

  Examples of the thickener include hydroxyethyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, polyvinyl alcohol, sodium hyaluronate, polyacrylic acid, carboxyvinyl polymer, and the like. The blending amount of the thickening agent is, for example, preferably 0.001 to 10 w / v% in the ophthalmic composition, more preferably 0.001 to 5 w / v%, still more preferably 0.01 to 3 w / v%. is there.

  As the pH adjuster, it is preferable to use an inorganic acid or an inorganic alkali agent. For example, (dilute) hydrochloric acid etc. are mentioned as an inorganic acid. Examples of the inorganic alkaline agent include sodium hydroxide, potassium hydroxide, sodium carbonate, sodium hydrogen carbonate and the like. Of these, hydrochloric acid and sodium hydroxide are preferable. The blending amount of the pH adjusting agent is, for example, preferably 0.00001 to 10 w / v% in the ophthalmic composition, more preferably 0.0001 to 5 w / v%, still more preferably 0.001 to 3 w / v%. .

  Examples of the preservative include quaternary ammonium salts such as benzalkonium chloride, benzethonium chloride, polydronium chloride, polyhexamethylene biguanide, sorbic acid or a salt thereof, paraoxybenzoic acid ester (methylparaben, ethylparaben, propylparaben, etc.) And phenylethyl alcohol. The preservative content is, for example, preferably 0.00001 to 5 w / v% in the ophthalmic composition, more preferably 0.0001 to 3 w / v%, and still more preferably 0.001 to 2 w / v%. In addition, it does not contain the above-mentioned preservative (compound), is filled into a container with a sterile filter, a unit dose type container or a single-use container, or is replaced with the above preservative compound or the following stabilizing agent. One or more selected from (F) boric acid, borate (borax), trometamol, sodium edetate, menthol, camphor, borneol and geraniol, preferably 2 An antiseptic effect can also be exhibited by a composition in which more than one species is appropriately combined. In particular, a composition (preservative composition) appropriately combining boric acid, trometamol, and sodium edetate is preferable, and this is combined with one or more selected from menthol, camphor, borneol, and geraniol. And more preferred. It is most preferable from the viewpoint of reducing eye irritation that an ophthalmic solution using the above preservative composition is filled in a multi-dose normal container.

  Examples of the isotonic agent include sodium chloride and potassium chloride. The blending amount of the isotonic agent is, for example, preferably 0.001 to 5 w / v% in the ophthalmic composition, more preferably 0.01 to 3 w / v%, still more preferably 0.1 to 2 w / v%. is there.

  Examples of the stabilizer include sodium edetate hydrate, cyclodextrin, sulfite, dibutylhydroxytoluene and the like. The blending amount of the stabilizer is, for example, preferably 0.001 to 5 w / v% in the ophthalmic composition, more preferably 0.01 to 3 w / v%, still more preferably 0.1 to 2 w / v%. . Among these, sodium edetate is preferable for enhancing the antiseptic power and enhancing the stability of the drug.

  Examples of the refreshing agent include menthol, camphor, borneol, geraniol, and the like. The content of the refreshing agent is preferably 0.0001 to 5 w / v%, more preferably 0.001 to 2 w / v%, and more preferably 0.005 to 1 w / v%, as the total amount of the compound in the ophthalmic composition. Further preferred is 0.007 to 0.8 w / v%.

  Examples of drugs (pharmaceutical active ingredients) include other antihistamines (for example, iproheptin hydrochloride, isothipentyl hydrochloride, etc.), vitamins (for example, retinol acetate, retinol palmitate, pyridoxine hydrochloride, pantenol, calcium pantothenate, pantothenic acid) Sodium, tocopherol acetate, flavin adenine dinucleotide, cyanocobalamin), decongestant (eg, naphazoline hydrochloride, tetrahydrozoline hydrochloride, phenylephrine hydrochloride, epinephrine, ephedrine hydrochloride, dl-methylephedrine hydrochloride, tetrahydrozoline nitrate, naphazoline nitrate), anti-inflammation / convergence Agents (for example, neostigmine methyl sulfate, ε-aminocaproic acid, allantoin, berberine chloride, zinc sulfate, zinc lactate, lysozyme chloride, methyl salicylate) Tranexamic acid, sodium azulene sulfonate, etc.), amino acids (eg, potassium L-aspartate, magnesium L-aspartate, aminoethyl sulfonic acid, etc.), sulfa drugs, fungicides (eg, sulfur, isopropylmethylphenol, hinokitiol, etc.), A local anesthetic (eg, lidocaine, lidocaine hydrochloride, procaine hydrochloride, dibucaine hydrochloride, etc.) and an antiallergic agent (eg, ketotifen fumarate, etc.) can be appropriately blended.

  The amount of these components in the ophthalmic composition is appropriately selected according to the type of preparation, the type of drug, etc., and the amounts of various components are known in the technical field to which the present invention belongs. For example, 0.0001-30 w / v% is preferable with respect to the whole ophthalmic composition, More preferably, it can select from the range of about 0.001-10 w / v%. More specifically, the content of each component is, for example, as follows for the ophthalmic composition.

  If it is an antihistamine, it is 0.0001-10 w / v%, for example, Preferably it is 0.001-5 w / v%. If it is a vitamin, it is 0.0001-1 w / v%, Preferably it is 0.0001-0.5 w / v%. If it is a decongestant, for example, it is 0.0001 to 0.5 w / v%, preferably 0.0005 to 0.3 w / v%, more preferably 0.001 to 0.1 w / v%. If it is a flame retardant / astringent, it is 0.0001-10 w / v%, for example, Preferably it is 0.0001-5 w / v%. If it is an amino acid, it is 0.0001-10 w / v%, Preferably it is 0.001-3 w / v%. If it is a sulfa agent and a disinfectant, it is 0.00001-10 w / v%, for example, Preferably it is 0.0001-10 w / v%. If it is a local anesthetic, it is 0.001-1 w / v%, for example, Preferably it is 0.01-1 w / v%. If it is an antiallergic agent, it is 0.001-5 w / v%, for example, Preferably it is 0.01-3 w / v%.

  The ophthalmic composition of the present invention is liquid, and the viscosity of the ophthalmic composition is preferably 1 to 50 mPa · s, more preferably 1 to 20 mPa · s, and still more preferably 1 to 10 mPa · s. In the present invention, the viscosity value is a value measured at 20 ° C. using an E-type viscometer (VISCONIC ELD-R, Tokyo Keiki Co., Ltd.).

  In addition, the pH (20 ° C.) of the ophthalmic composition of the present invention is preferably 4.0 to 9.0, more preferably 5.0 to 8.0, and still more preferably from the point of use as an eye drop. 5.5-8.0. If the pH is too low or too high, the irritation may be too strong. In the present invention, pH is a value measured at 20 ° C. using a pH osmometer (HOSM-1, Toa DKK Co., Ltd.).

  The preparation method of the ophthalmic composition of the present invention is not particularly limited. For example, the components (A) to (D) and, if necessary, the component (E) in an aqueous solvent such as purified water. And other components may be added at predetermined concentrations to adjust the pH. Thereafter, it can be aseptically filled into a suitable container such as a container made of polyethylene terephthalate.

  Specific examples of usage forms of the ophthalmic composition of the present invention include eye drops for soft contact lenses, soft contact lens mounting liquid, soft contact lens removal liquid, and the like. The type of soft contact lens to which the ophthalmic composition for soft contact lens of the present invention can be applied is not particularly limited, and is a one-day disposable soft contact lens, a one-week disposable soft contact lens, a two-week disposable soft contact lens. It can be used for either of these. In particular, among the soft contact lens classification groups I to IV according to the US Food and Drug Administration (FDA) standard, the soft contact lens of group IV (high water content (50% by mass or more) and ionic) in which (A) component is easily adsorbed The higher adsorption suppression effect and tear exchange effect of the component (A) can be obtained. The group IV soft contact lens has a negative charge due to containing methacrylic acid, and is considered to be adsorbed by the electrostatic interaction with the component (A) having a positive charge in the solution. It is done.

  The ophthalmic composition for soft contact lenses of the present invention has an effect of suppressing adsorption of the component (A) diphenhydramine and / or a salt thereof to the soft contact lens, and is therefore suitable as an adsorption inhibitor for the soft contact lens of the antihistamine. It is. Although the mechanism is not clear, each of the components (B) to (D) is an anionic component having a negative charge, and by interacting with the positive charge of the component (A), the adsorption suppressing effect is exerted. It is thought that it demonstrates. In addition, in the adsorption of the component (A) and the group IV soft contact lens, a hydrophobic interaction is also involved in addition to the electrostatic interaction, and the nonionic surfactant of the component (E) It is assumed that the action is weakened. In addition, the components (C) to (E) not only suppress the adsorption of the component (A), but also exhibit the effect of enhancing tear fluid exchange that has been lowered by wearing the soft contact lens, and are more suitable as an ophthalmic composition for soft contact lenses. It is. In particular, the components (C) and (E) have a surface active ability, making it easier for tears to enter the gap between the eye surface and the lens, and the component (D) is a water-soluble polymer compound. It is considered that tear fluid exchange is enhanced by increasing the slip between the surface and the lens.

The present invention provides an adsorption inhibitor and an adsorption inhibition method. Suitable components, blending amounts, and the like are the same as those for the ophthalmic composition.
(A) Formulated in an ophthalmic composition for soft contact lenses containing diphenhydramine and / or a salt thereof, (B) cromoglycic acid and / or a salt thereof, (C) glycyrrhizic acid and / or a salt thereof, and (D) An adsorption inhibitor for the soft contact lens of the component (A), comprising chondroitin sulfate and / or a salt thereof.
(A) Ophthalmic composition for soft contact lens containing diphenhydramine and / or salt thereof, (B) cromoglycic acid and / or salt thereof, (C) glycyrrhizic acid and / or salt thereof, and (D) chondroitin sulfate And / or a salt thereof, and a method for suppressing adsorption of the component (A) to the soft contact lens.

  EXAMPLES Hereinafter, although an Example and a comparative example are shown and this invention is demonstrated more concretely, this invention is not restrict | limited to the following Example.

[Examples 1 to 10, Comparative Examples 1 to 5]
After dissolving each compounding component in the table in sterilized purified water according to a conventional method so as to have the composition shown in Tables 1 to 3 (compounding unit: w / v%), each solution is aseptically filtered and soft contacted. A lens ophthalmic composition was prepared. The following test was implemented about each obtained composition. The results are shown in Tables 1-3.

[Test 1: Adhesion evaluation test of diphenhydramine (antihistamine) to soft contact lens]
(Adsorption evaluation test of diphenhydramine (antihistamine) on soft contact lens: n = 3)
5 mL of each ophthalmic composition for soft contact lenses was dispensed into 20 mL vials, and one soft contact lens was immersed in each vial. The vial in which the lens was immersed was shaken and stirred at 37 ° C. for 7 days, and then the amount of diphenhydramine in the solution was quantified by liquid chromatography according to a conventional method and by comparison with a standard sample. Based on the ratio to the amount of diphenhydramine in the control solution, the lens adsorption rate (%) of diphenhydramine to the soft contact lens was calculated from the ratio of the diphenhydramine in the control solution. Measurement was performed three times for one type of ophthalmic composition for soft contact lenses, and after calculating the average adsorption rate for the lens, evaluation was performed based on the following evaluation criteria.

(Lens adsorption rate calculation formula)
Lens adsorption rate (%) = [(control diphenhydramine amount−diphenhydramine amount of lens soaking solution) / control diphenhydramine amount] × 100
(Soft contact lens used)
The soft contact lens used was a group IV lens (high water content / ionic lens) in which diphenhydramine hydrochloride is most likely to be adsorbed from among four classifications (groups I to IV) by FDA (US Food and Drug Administration). Specifically, Accuview (manufactured by Johnson & Johnson Medical Co., Ltd.) was used.
(Evaluation criteria for adsorption suppression effect for soft contact lenses)
A: The average adsorption rate of diphenhydramine to the lens is less than 5%. O: The average adsorption rate of diphenhydramine to the lens is 5% or more and less than 8%. Δ: The average adsorption rate of diphenhydramine to the lens is 8% or more and less than 10%. Average adsorption rate of 10% or more

[Test 2: Evaluating effect on tear fluid exchange by eye drops]
Using each ophthalmic composition for soft contact lenses, 5 subjects wearing soft contact lenses were used as panelists, and the tear exchange rate under the soft contact lenses was evaluated by fluorophotometry.
Specifically, Accuview (manufactured by Johnson & Johnson Medical Co., Ltd.) was used as a soft contact lens, and 2 μL of a 10 mass% fluorescein dextran (dextran fluorescently labeled with fluorescein isothiocyanate) solution was used with a micropipette. The soft contact lens was put on as it was. After measuring the fluorescence intensity of the soft contact lens mounting part (corneal central part) immediately after mounting, 50 μL of the ophthalmic composition for soft contact lenses of Examples 1 to 10 and Comparative Examples 1 to 5 was instilled to measure the fluorescence intensity. Measurements were taken every minute until 10 minutes later. The decrease in fluorescence intensity over time was linearly regressed, and the tear exchange rate (% / min) was calculated from the slope. Furthermore, each panel was compared with the tear fluid exchange rate when the ophthalmic composition for soft contact lenses was not instilled and when it was instilled, and the increase rate of the tear fluid exchange rate during instillation with respect to non-instillation was calculated. The increase rate of tear exchange rate of 5 panelists was averaged and evaluated based on the following evaluation criteria.

(Evaluation criteria for rate of change in tear exchange rate)
◎: The increase rate of the tear fluid exchange rate during instillation relative to the tear fluid exchange rate during non-instillation is 20% or more ○: The increase rate of the tear fluid exchange rate during instillation relative to the tear fluid exchange rate during non-instillation is 10% or more Less than 20% Δ: The rate of increase in tear exchange rate at the time of instillation with respect to the rate of tear fluid exchange at the time of non-instillation is 5% or more and less than 10%. Less than 5% increase

ポリソルベート８０：商品名「ＮＩＫＫＯＬ ＴＯ−１０ＭＶ」、日光ケミカルズ（株）製
ポリオキシエチレン硬化ヒマシ油６０：商品名「ＮＩＫＫＯＬ ＨＣＯ−６０」、日光ケミカルズ（株）製
ポリオキシエチレン（２００）ポリオキシプロピレン（７０）グリコール：商品名「ユニルーブ７０ＤＰ−９５０Ｂ」、日油（株）製

Polysorbate 80: trade name “NIKKOL TO-10MV”, polyoxyethylene hydrogenated castor oil 60 manufactured by Nikko Chemicals Co., Ltd .: trade name “NIKKOL HCO-60”, polyoxyethylene (200) polyoxypropylene manufactured by Nikko Chemicals Co., Ltd. (70) Glycol: Trade name “Unilube 70DP-950B”, manufactured by NOF Corporation

  As shown in Tables 1 to 3, the tear fluid exchange rate was improved by instilling the ophthalmic composition for soft contact lenses of the present invention. Specifically, one panelist showed a tear fluid exchange rate of 18.1% / min when naked, but decreased to 10.2% / min when wearing a soft contact lens. When the composition shown in Example 5 was instilled there, the tear exchange rate improved to 13.7% / min, and the increase rate was 34.3%.

[Examples 11 and 12]
Further, after dissolving each compounding component in the table in sterilized purified water according to a conventional method so as to have the composition shown in Table 4 (compounding unit: w / v%), each solution is subjected to aseptic filtration and soft contact. A lens ophthalmic composition was prepared. About each obtained composition, in addition to the said test, the following test was implemented. The results are also shown in the table.

[Irritation]
10 expert panelists sensitive to irritability instilled 2 drops (80-100 μL) of an ophthalmic composition filled in a multi-dose type eye drop container, and the following evaluation criteria It was evaluated by. A result is shown based on the following irritation | stimulation evaluation from the average score of evaluation.
(Evaluation criteria)
5: Not at all 4: Slightly visible 3: Slightly visible 2: Stained 1: Slightly visible

(Irritation evaluation)
◎: Average score is 4.5 or more ○: Average score is 4.0 or more and less than 4.5 Δ: Average score is 3.0 or more and less than 4.0 ×: Average score is less than 3.0

[Preservation power]
When the test is conducted based on the preservative efficacy test described in the Japanese Pharmacopoeia Reference Information ("Fifteenth Amendment Japanese Pharmacopoeia Explanation Reference Information 28. Preservative Power Testing Method"), "If not satisfied," x ".

  As shown in Table 4, the ophthalmic composition for soft contact lens of the present invention had no eye irritation and had sufficient antiseptic power as an eye drop.

[Examples 13 to 24]
Each composition component in the table is dissolved in sterilized purified water according to a conventional method so that the composition shown in Tables 5 and 6 (composition unit: w / v%) is obtained. A lens ophthalmic composition was prepared.

Claims (7)

  Containing (A) diphenhydramine and / or a salt thereof, (B) cromoglycic acid and / or a salt thereof, (C) glycyrrhizic acid and / or a salt thereof, and (D) chondroitin sulfate and / or a salt thereof. An ophthalmic composition for soft contact lenses.   The ophthalmic composition for soft contact lenses according to claim 1, further comprising (E) a nonionic surfactant.   The ophthalmic composition for soft contact lens according to claim 1 or 2, wherein the soft contact lens is a lens of FDA contact lens classification group IV.   The ophthalmic composition for soft contact lenses according to any one of claims 1 to 3, wherein the composition does not contain a preservative.   The soft contact lens according to any one of claims 1 to 4, further comprising one or more components selected from (F) boric acid, borate, trometamol, sodium edetate, menthol, camphor, borneol and geraniol. Ophthalmic composition.   (A) Formulated in an ophthalmic composition for soft contact lenses containing diphenhydramine and / or a salt thereof, (B) cromoglycic acid and / or a salt thereof, (C) glycyrrhizic acid and / or a salt thereof, and (D) An adsorption inhibitor for the soft contact lens of the component (A), comprising chondroitin sulfate and / or a salt thereof.   (A) Ophthalmic composition for soft contact lens containing diphenhydramine and / or salt thereof, (B) cromoglycic acid and / or salt thereof, (C) glycyrrhizic acid and / or salt thereof, and (D) chondroitin sulfate And / or a salt thereof, and a method for suppressing adsorption of the component (A) to the soft contact lens.