JP4771675B2 - Contact lens composition - Google Patents

Description

  The present invention relates to an ophthalmic composition. More specifically, the present invention relates to a composition for contact lenses in which the medicinal effect of ketotifen or a salt thereof is enhanced. The present invention also relates to a method for suppressing adsorption of ketotifen or a salt thereof to a contact lens.

  Ketotifen and its salts are widely used as antiallergic drugs because they have excellent antiallergic effects and high safety. However, in the past, there are concerns about the adsorption of ketotifen to contact lenses, and it is unclear whether the intended antiallergic effect can be appropriately obtained by instilling while wearing contact lenses. However, application of a composition containing ketotifen has been avoided (see Non-Patent Document 1).

  In recent years, contact lenses have rapidly spread, and accordingly, antiallergic drugs that can be used even while wearing contact lenses have been desired, and ketotifen-containing preparations that can be applied while wearing contact lenses have been developed (for example, patents). Reference 1). Patent Document 1 discloses a composition containing ketotifen, a nonionic tonicity agent and a preservative. However, the anti-allergic action exerted during contact lens wearing is not satisfactory with the composition of this document. On the other hand, for antiallergic drugs for contact lenses, a method of using a polymer compound and a nonionic surfactant in combination with an antiallergic drug has been proposed from the viewpoint of improving durability (see Patent Document 2). However, the method of Patent Document 2 is not satisfactory in terms of the antiallergic action to be exerted and the suppression of adsorption of antiallergic drugs to contact lenses.

  As described above, anti-allergic drug-containing preparations that can be used while wearing contact lenses have both an allergic symptom-improving effect and an anti-allergic drug adsorption suppression on contact lenses, despite the awaited appearance. Currently, satisfactory formulations have not been developed yet.

On the other hand, terpenes and polyhydric alcohols are components generally blended in ophthalmic compositions, but what effects can be obtained by blending these components with ketotifen or a salt thereof in a specific combination mode. Is not known.
Special Table 2003-518498 Japanese Patent Laid-Open No. 2001-158750 Yoko Uebayashi et al., “About patient guidance when wearing contact lenses”, JJSH, 1994, Vol. 30, No. 1, pp. 77-81

  The object of the present invention is to solve the above-mentioned problems of the prior art. Specifically, an object of the present invention is to provide a composition for a contact lens that can exhibit an excellent antiallergic action even when used at the time of wearing a contact lens and in which adsorption of ketotifen to the contact lens is suppressed. To do. Another object of the present invention is to provide a method for suppressing adsorption of ketotifen or a salt thereof to a contact lens.

  As a result of intensive studies to solve the above-mentioned problems, the inventors of the present invention contain a composition containing ketotifen or a salt thereof, a polyhydric alcohol and menthols at a specific ratio, and ketotifen or a salt thereof, glycerin and a terpene. It has been found that the composition exhibits a remarkably excellent antiallergic effect even when applied to an eye wearing a contact lens, and can suppress the adsorption of ketotifen to the contact lens. The present invention has been completed by further studies based on this finding.

That is, the present invention is the following contact lens composition:
Item 1. 0.001 to 0.1% by weight of ketotifen or a salt thereof, 0.1 to 10% by weight of polyhydric alcohol, and 0.001 to 0.1% by weight of menthols based on the total weight of the composition A composition for contact lenses.
Item 2. Item 2. The contact lens composition according to Item 1, having a pH of 3 to 6.2.
Item 3. Item 3. The contact lens according to Item 1 or 2, wherein the polyhydric alcohol is at least one selected from the group consisting of propylene glycol, ethylene glycol, glucose, lactose, maltose, fructose, sorbitol, trehalose, maltose, mannitol, and xylitol. Composition.
Item 4. Item 1 to 3 further comprising at least one terpene selected from the group consisting of camphor, borneol, geraniol, cineol, anethole, limonene, eugenol, pinene, ferrandrene, linalool, citronellol, citronellal, menthone and carvone. The contact lens composition according to any one of the above.
Item 5. A contact lens composition comprising ketotifen or a salt thereof, glycerin and a terpene.
Item 6. Item 6. The terpene is at least one selected from the group consisting of menthol, camphor, borneol, geraniol, cineol, anethole, limonene, eugenol, pinene, ferrandolene, linalool, citronellol, citronellal, menthone and carvone. Contact lens composition.
Item 7. Item 5 containing ketotifen or a salt thereof in an amount of 0.001 to 0.1% by weight, glycerin 0.1 to 5% by weight, and terpene 0.001 to 0.5% by weight based on the total weight of the composition. Or the composition for contact lenses of 6.

Furthermore, the present invention is a method for suppressing adsorption of ketotifen or a salt thereof to a contact lens described below:
Item 8. Item 8. A method for suppressing adsorption of ketotifen or a salt thereof to a contact lens, comprising contacting the contact lens composition according to any one of Items 1 to 7 with the contact lens.

  Hereinafter, the present invention will be described in detail. In the present specification, the term “contact lens” is used to include all types of contact lenses such as hard, oxygen-permeable hard, and soft unless otherwise specified.

(I) Contact lens composition-1
The composition for contact lenses of the present invention comprises ketotifen or a salt thereof in an amount of 0.001 to 0.1% by weight, a polyhydric alcohol in an amount of 0.1 to 10% by weight, and menthols in an amount of 0.001 to 0.1% by weight. It is characterized by containing.

  Ketotifen used in the contact lens composition of the present invention, that is, 4,9-dihydro-4- (1-methyl-4-piperidylidene) -10H-benzo [4,5] cyclohepta [1,2-b] thiophene- 10-one is a known compound, and those synthesized by a known method can be used. Moreover, a commercial item can also be used simply.

  In the present invention, a salt of ketotifen may be used instead of ketotifen or in combination with ketotifen. The ketotifen salt is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Examples of such salts include organic acid salts [for example, monocarboxylates (acetate, trifluoroacetate, butyrate, palmitate, stearate, etc.), polyvalent carboxylates (fumarate, Maleate), oxycarboxylate (lactate, tartrate, citrate, succinate, malonate, etc.), organic sulfonate (methanesulfonate, toluenesulfonate, tosylate, etc.) )], Inorganic acid salts (eg, hydrochloride, sulfate, nitrate, hydrobromide, phosphate, etc.), salts with organic bases (eg, methylamine, triethylamine, triethanolamine, morpholine, piperazine) , Salts with organic amines such as pyrrolidine, tripyridine, picoline, etc.), salts with inorganic bases [eg ammonium salts; alkali metals (sodium, potassium, etc.) ), Alkaline earth metal (calcium, magnesium etc.) and salts with metals such as aluminum or the like]. Of these, fumarate is particularly preferable. Ketotifen or a salt thereof can also be used in the form of a hydrate. These ketotifen or its salt may be used individually by 1 type, and may be used in arbitrary combination of 2 or more types.

  The polyhydric alcohol used in the present invention is not particularly limited as long as it can be used in the ophthalmic field. Examples include linear alcohols (having 5 or less carbon atoms), sugars (monosaccharides or disaccharides), sugar alcohols, polyvinyl alcohols, and the like. More specifically, linear alcohols such as glycerin, propylene glycol and ethylene glycol; sugars such as glucose, lactose, maltose, fructose, sorbitol and trehalose; sugar alcohols such as maltitol, mannitol and xylitol; and a molecular weight of 500 or more Polyvinyl alcohol etc. can be illustrated. The saponification degree of the polyvinyl alcohol may be complete or partial. Among these, linear alcohols, particularly preferably glycerin, are preferable, and the effects of the present invention can be further enhanced by using these. These polyhydric alcohols can be used alone or in combination of two or more.

  In the present invention, menthol means l-menthol, d-menthol and dl-menthol. As the menthol used in the present invention, preferably, 1-menthol can be mentioned. These menthols may be used alone or in any combination of two or more. In the present invention, the composition for contact lenses contains menthols by blending essential oils containing the menthols (for example, peppermint oil, cool mint oil, peppermint oil, and mixtures thereof). Also good.

  The content ratio of the above three components in the composition for contact lenses of the present invention varies depending on the form, use, type of components used, etc., but ketotifen or its salt is 0 with respect to the total weight of the composition. 0.001 to 0.1% by weight, polyhydric alcohol 0.1 to 10% by weight, and menthols 0.001 to 0.1% by weight. Preferably, the ratio which becomes 0.005-0.07 weight% of ketotifen or its salt, 0.2-5 weight% of polyhydric alcohol, and 0.002-0.07 weight% of menthols can be mentioned.

  In the composition for contact lenses of the present invention, the blending ratio (weight ratio) of the three components is, for example, 1 to 10,000 parts by weight of a polyhydric alcohol and 0.1% by weight of menthols relative to 1 part by weight of ketotifen or a salt thereof. 01-100 weight part; Preferably, the ratio used as polyhydric alcohol 3-1000 weight part and menthol 0.03-14 weight part can be mentioned. If the ratio deviates significantly from this ratio, the effect of the present invention cannot be obtained sufficiently, or an unpleasant irritation tends to occur.

By further blending a terpene other than menthols with the contact lens composition of the present invention, the anti-allergic effect and the effect of suppressing the adsorption of ketotifen or a salt thereof to the contact lens can be further enhanced.
Such a terpene is not particularly limited as long as it can be used in the ophthalmic field. For example, camphor, borneol, geraniol, cineol, anethole, limonene, eugenol, pinene, ferrandlene, linalool, citronellol, citronellal, menthone And carvone. These do not ask the distinction between d-form, l-form, or dl-form. Of these, d-camphor, dl-camphor, d-borneol and dl-borneol can be preferably used. Moreover, the essential oil containing the said terpene can also be used as the said terpene. Examples of the essential oil containing the terpene include eucalyptus oil, bergamot oil, fennel oil, cinnamon oil, rose oil, spearmint oil, peppermint oil, cool mint oil and peppermint oil. These terpenes may be used alone or in any combination of two or more.

  When blending these terpenes, the blending ratio of the terpenes varies depending on the type of terpene used and cannot be uniformly defined. In the case of using terpenes), 0.001 to 0.5% by weight, preferably 0.002 to 0.2% by weight.

  Moreover, you may mix | blend a buffering agent with the composition for contact lenses of this invention further. By blending a buffering agent, it is possible to more effectively suppress the adsorption of ketotifen or a salt thereof to the contact lens. The buffer that can be incorporated into the composition for contact lenses of the present invention is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Examples of such buffers include borate buffer, 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. Preferred buffering agents are borate buffer, phosphate buffer, carbonate buffer and citrate buffer. Particularly preferred buffering agents are borate buffer, citrate buffer or phosphate buffer. Examples of the borate buffer include borates such as alkali metal borate and alkaline earth metal borate. Examples of the phosphate buffer include phosphates such as alkali metal phosphates and alkaline earth metal phosphates. Examples of the citrate buffer include alkali metal citrate. Moreover, you may use the borate or the hydrate of a phosphate as a borate buffer or a phosphate buffer. As more specific examples, boric acid or a salt thereof (sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, borax, etc.), phosphoric acid or a salt thereof (disodium hydrogen phosphate, dihydrogen phosphate) Sodium, potassium dihydrogen phosphate, trisodium phosphate, dipotassium phosphate, calcium monohydrogen phosphate, calcium dihydrogen phosphate, etc., carbonic acid or a salt thereof (sodium bicarbonate, sodium carbonate, ammonium carbonate, potassium carbonate, Calcium carbonate, potassium hydrogen carbonate, magnesium carbonate, etc.), 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, calcium acetate, sodium acetate ), Aspartic acid or a salt thereof (sodium aspartate, magnesium aspartate, and potassium aspartate) and the like. These buffering agents may be used alone or in any combination of two or more.

  When a buffering agent is blended in the contact lens composition of the present invention, the blending ratio of the buffering agent varies depending on the type of buffering agent used and the expected effect, and cannot be defined uniformly. For example, the proportion of the buffering agent is 0.001 to 10% by weight, preferably about 0.1 to 5% by weight, based on the total weight of the composition. More specifically, when the ratio of the buffer in the composition is a borate buffer or a phosphate buffer, for example, 0.0001 to 10% by weight, preferably 0.01 to 5% by weight. When using a carbonate buffer, for example, 0.001 to 5% by weight, preferably about 0.005 to 3% by weight; When using a citrate buffer, for example, 0.001 to 5%. %, Preferably about 0.005 to 3% by weight; if an acetate buffer is used, for example, about 0.001 to 5% by weight, preferably 0.005 to 3% by weight; if epsilon-aminocaproic acid is used For example, 0.005 to 10% by weight, preferably about 0.01 to 5% by weight; if aspartic acid or a salt thereof is used, for example, 0.005 to 10% by weight, preferably 0.01 ~ 5 weight Proportions such that the degree is exemplified.

  The contact lens composition of the present invention is liquid or gel, preferably liquid, and ophthalmically acceptable water, preferably purified water or ultrapure water is used as the base material of the composition. The

  The pH of the contact lens composition of the present invention is not particularly limited as long as it is within a pharmaceutically acceptable range. As an example of pH of the composition for contact lenses of this invention, the range used as 3-6.2, Preferably 3.3-5.8, More preferably, it is 3.5-5.4 can be mentioned. If the composition for contact lenses of the present invention is adjusted to be in such a pH range, an excellent antiallergic effect can be realized, and adsorption of ketotifen or a salt thereof to the contact lens can be suppressed. Moreover, if it is in the said pH range, it is safe even if it applies to eyes, and it is practical as an ophthalmic formulation.

  In order to adjust the pH so as to be in the above range, a pharmacologically, pharmacologically (pharmaceutically) or physiologically acceptable pH adjusting agent may be used by a method known in the art. it can.

  Examples of pH adjusters that can be used include inorganic acids (hydrochloric acid, sulfuric acid, phosphoric acid, polyphosphoric acid, boric acid, etc.), organic acids (lactic acid, acetic acid, citric acid, tartaric acid, malic acid, succinic acid, oxalic acid, glucone). Acid, fumaric acid, propionic acid, acetic acid, aspartic acid, epsilon-aminocaproic acid, glutamic acid, aminoethylsulfonic acid, etc.), gluconolactone, ammonium acetate, inorganic base (sodium bicarbonate, sodium carbonate, potassium hydroxide, hydroxide) Sodium, calcium hydroxide, magnesium hydroxide, etc.), organic bases (monoethanolamine, triethanolamine, diisopropanolamine, triisopropanolamine, lysine, etc.), borax, and pharmacologically acceptable salts thereof. Can be mentioned. These pH adjusting agents may be used alone or in any combination of two or more.

  The osmotic pressure of the composition for contact lenses of the present invention is not particularly limited as long as it is within a range acceptable for a living body. For example, the osmotic pressure ratio at the time of using the contact lens composition is usually 0.3 to 4.2, preferably 0.3 to 2.1, more preferably 0.7 to 1.8, and particularly preferably 1. About 1 to 1.5 can be mentioned. The osmotic pressure can be adjusted using an inorganic salt, a polyhydric alcohol, or the like. The osmotic pressure can be adjusted according to a method known in the art using the components described above or below.

  In the present invention, the osmotic pressure ratio is the ratio of the osmotic pressure of the sample to the osmotic pressure of a 0.9 g / 100 mL sodium chloride aqueous solution based on the 14th revised Japanese pharmacopoeia. Measure using the measurement method (freezing point depression method). In addition, the osmotic pressure of the standard solution for osmotic pressure ratio measurement is measured before and after the measurement of the test sample, and the osmotic pressure ratio is calculated using the actual measurement value obtained at this time. The standard solution for measuring the osmotic pressure ratio was sodium chloride (Japanese Pharmacopoeia standard reagent) dried at 500 to 650 ° C. for 40 to 50 minutes, then allowed to cool in a desiccator (silica gel), and 0.900 g was accurately weighed. Dissolve in purified water to make exactly 100 mL, or use a commercially available standard solution for osmotic pressure ratio measurement (0.9 g / 100 mL sodium chloride aqueous solution).

  The composition for contact lenses of the present invention contains various components (including pharmacologically active ingredients and physiologically active ingredients) in addition to ketotifen or a salt thereof, as long as the effects of the present invention are not hindered. Can do. The type of such components is not particularly limited, and examples thereof include, for example, a decongestant component, an eye regulator component, an anti-inflammatory component or an astringent component, an antihistamine component or an antiallergic component, vitamins, amino acids, and antibacterial agents. Examples include components, bactericidal components, oligosaccharides, polysaccharides or derivatives thereof, cellulose or derivatives thereof or salts thereof, water-soluble polymers other than those described above, local anesthetic components, steroid components, glaucoma treatment components, cataract treatment components, etc. it can. Examples of suitable components include the following components.

  Decongestant: α-adrenergic drugs such as imidazoline derivatives (naphazoline, tetrahydrozoline, etc.), β-phenylethylamine derivatives (phenylephrine, epinephrine, ephedrine, methylephedrine, etc.), and their pharmaceutically or physiologically acceptable Salts (eg, inorganic acid salts such as naphazoline hydrochloride, naphazoline nitrate, tetrahydrozoline hydrochloride, tetrahydrozoline nitrate, phenylephrine hydrochloride, epinephrine hydrochloride, ephedrine hydrochloride, and methylephedrine hydrochloride; organic acid salts such as epinephrine hydrogen tartrate).

  Eye muscle modulator component: Cholinesterase inhibitor having an active center similar to acetylcholine, for example, quaternary ammonium compounds such as neostigmine methyl sulfate and salts thereof.

  Anti-inflammatory or astringent ingredients: pranoprofen, celecoxib, rofecoxib, indomethacin, diclofenac, diclofenac sodium, piroxicam, meloxicam, aspirin, mefenamic acid, indomethacin farnesyl, acemetacin, ibuprofen, thiaprofenic acid, loxoprofen sodium, cyronamide hydrochloride Aminocaproic acid, berberine and pharmacologically acceptable salts (eg berberine chloride, berberine sulfate), azulene sulfonic acid and pharmacologically acceptable salts (eg sodium azulene sulfonate, etc.), zinc salts ( For example, zinc sulfate, zinc lactate, etc.), lysozyme, lysozyme chloride, methyl salicylate, allantoin, glycyrrhizic acid and pharmacologically acceptable salts ( In example, dipotassium glycyrrhizin acid, ammonium glycyrrhizin acid, etc.).

  Antihistamine component or antiallergic component: for example, acitazanolast, bepotastine, chlorpheniramine, diphenhydramine, iproheptin, emedastine, clemastine, azelastine, levocabastine, olopatadine, cromoglycic acid, tranilast, amlexazine, mequitazine, mequitazine, , Cetirizine, ibudilast, suplatast, pemirolast, repirinast, tazanolast, oxatomide, terfenadine, epinastine, astemizole, ebastine or a salt thereof (e.g., chlorpheniramine maleate, diphenhydramine hydrochloride, iproheptine hydrochloride, emedastine fumarate, fumarate cremasastine hydrochloride, , Levocabastine hydrochloride, olopatadine hydrochloride, sodium cromoglycate Potassium, etc.).

  Vitamins: For example, vitamins A [eg, retinal, retinol, retinoic acid, carotene, dehydroretinal, lycopene and pharmacologically acceptable salts thereof (eg, retinol acetate, retinol palmitate, etc.), vitamin B [Thiamine, dicetiamine, thiamine hydrochloride, thiamine nitrate, bisthiamine nitrate, thiamine disulfide, thiamine dicetyl nitrate ester salt, dicetiamine hydrochloride, fursultiamine hydrochloride, octothiamine, chicotiamine, bisibtiamine, bisbenchamine, fursultiamine, Prosultiamine, benfotiamine, flavin adenine dinucleotide, flavin adenine dinucleotide sodium, riboflavin, riboflavin sodium phosphate, riboflavin butyrate, pyridoxine, pyri hydrochloride Doxin, pyridoxal, pyridoxal phosphate, pyridoxal calcium phosphate, hydroxocobalamin hydrochloride, hydroxocobalamin acetate, cyanocobalamin, hydroxocobalamin, methylcobalamin, deoxyadenocobalamin, folate, tetrahydrofolate, dihydrofolate, nicotinic acid, nicotinamide, nicotinic Alcohol, panthenol, pantothenic acid, calcium pantothenate, sodium pantothenate, biotin, choline, inositol, etc.], vitamin C [ascorbic acid and derivatives thereof, erythorbic acid and derivatives thereof and pharmacologically acceptable salts thereof ( For example, sodium ascorbate, sodium erythorbate, etc.)], vitamin Ds [eg ergocalciferol, cholecalciferol, Hydroxycholecalciferol, dihydroxycholecalciferol, dihydrotaxosterol and pharmacologically acceptable salts thereof, etc.]], vitamin E [for example, tocopherol and its derivatives, ubiquinone derivatives and their pharmacologically acceptable Salts (such as tocopherol acetate, tocopherol nicotinate, tocopherol succinate, calcium tocopherol succinate, etc.)], other vitamins [eg carnitine, ferulic acid, γ-oryzanol, orotic acid, cyanocobalamin, rutin, eriocitrin, hesperidin and Pharmacologically acceptable salts thereof (such as carnitine chloride)].

  Amino acids: for example, leucine, isoleucine, valine, methionine, threonine, alanine, phenylalanine, tryptophan, lysine, glycine, asparagine, aspartic acid, serine, glutamine, glutamic acid, proline, tyrosine, cysteine, histidine, ornithine, hydroxyproline, hydroxy Lysine, glycylglycine, aminoethylsulfonic acid (taurine) or a salt thereof (for example, potassium aspartate, magnesium aspartate, cysteine hydrochloride, etc.) and the like.

  Antibacterial component or bactericidal component: Sulfonamides (for example, sulfamethoxazole, sulfisoxazole, sulfisomidine and pharmacologically acceptable salts (sulfamethoxazole sodium, sulfisomidine sodium, etc.) ), Acrinol, quaternary ammonium compounds (eg, benzalkonium, benzethonium, cetylpyridinium, and pharmacologically acceptable salts (benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, cetylpyridinium bromide, etc.), Alkylpolyaminoethylglycine, new quinolone (lomefloxacin, levofloxacin, ciprofloxacin, ofloxacin, norfloxacin, ciprofloxacin hydrochloride, etc.), berberine or a salt thereof (eg, berberine sulfate), β-lac Antibiotics (such as sulbenicillin, cefmenoxime), aminoglycoside antibiotics (such as kanamycin, gentamicin, tobramycin, sisomycin, micronomycin), tetracycline antibiotics (such as oxytetracycline), macrolide antibiotics (such as erythromycin), Chloramphenicol antibiotics (such as chloramphenicol), polypeptide antibiotics (such as colistin), etc. Antiviral drugs (doxuridine, acyclovir, adenine arabinoside, ganciclovir, foscarnet, valacyclovir, avian Such as fluorothymidine, cidophobia, carbocyclic oxetanocin G), antifungal drugs (pimaricin, fluconazole, itraconazole, miconazole, flucytosine, amphotericin B) ), And the like.

  Oligosaccharides: for example, lactulose, raffinose, pullulan, cyclodextrin, etc.).

  Polysaccharides or derivatives thereof: gum arabic, karaya gum, xanthan gum, carob gum, guar gum, guaiac gum, quince seed, dalman gum, tragacanth, benzoin gum, locust bean gum, casein, agar, alginic acid, dextrin, dextran, carrageenan, gelatin, collagen, Pectin, starch, polygalacturonic acid (alginate), chitin and derivatives thereof, chitosan and derivatives thereof, elastin, heparin, heparinoid, heparin sulfate, heparan sulfate, hyaluronic acid, chondroitin sulfate or a salt thereof (sodium alginate, sodium hyaluronate, chondroitin) Such as sodium sulfate).

  Cellulose or a derivative thereof or a salt thereof: cellulose, methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, carboxyethyl cellulose, nitrocellulose, and the like.

  Water-soluble polymers other than those described above: polyvinylpyrrolidone, polyvinyl alcohol having a molecular weight of less than 500 (completely or partially saponified product), and the like.

  Local anesthetic ingredients: lidocaine, oxybuprocaine, dipcaine, procaine, ethyl aminobenzoate, meprilucaine, mepivacaine, bupivacaine, cocaine and their salts (such as lidocaine hydrochloride, oxybuprocaine hydrochloride).

  Steroid component: hydrocortisone, prednisolone, cortisol, methylprednisolone, triamcinolone, parameterzone, betamethasone and their salts.

  Glaucoma treatment ingredients: timolol maleate, carteolol hydrochloride, betaxolol hydrochloride, latanoprost, unoprostone, dipivefrine hydrochloride, epinephrine, apraclonidine hydrochloride, pilocarpine hydrochloride, carbachol, dorzolamide hydrochloride, acetazolamide, metazolamide and their salts.

  Cataract treatment ingredients: pirenoxine, glutathione, salivary gland hormone, thiopronin, dihydro azapentacene disulfonate and salts thereof (for example, Sodium 5,12-dihydro azapentacene disulfonate).

The blending ratio of these components can be selected according to the form of the composition, the type of the active ingredient, etc., and the blending ratio of various components is known in the art. For example, these components can be contained in a proportion of about 0.0001 to 30% by weight, preferably about 0.001 to 10% by weight, based on the total weight of the composition. More specifically, at the time of use, each component can be contained in the proportions exemplified below with respect to the total weight of the composition.
Decongestant component (vasoconstrictor or sympathomimetic drug): for example, 0.0001 to 0.5 wt%, preferably 0.0005 to 0.3 wt%, more preferably 0.001 to 0.1 wt% %.
Ocular muscle modulator component: For example, 0.0001 to 0.5% by weight, preferably 0.0005 to 0.1% by weight, and more preferably 0.0005 to 0.01% by weight.
Anti-inflammatory component or astringent component: for example 0.0001 to 10% by weight, preferably 0.0001 to 5% by weight.
Antihistamine component or antiallergic agent component: for example, 0.0001 to 10% by weight, preferably 0.001 to 5% by weight.
Vitamins: For example, 0.0001 to 1% by weight, preferably 0.0001 to 0.5% by weight.
Amino acids: For example, 0.0001 to 10% by weight, preferably 0.001 to 3% by weight.
Antibacterial component or bactericidal component: for example, 0.00001 to 10% by weight, preferably 0.0001 to 10% by weight.
Oligosaccharides: For example, 0.0001 to 5% by weight, preferably 0.001 to 5% by weight, more preferably 0.01 to 2% by weight.
Polysaccharide or derivative thereof: for example, 0.0001 to 2% by weight, preferably 0.01 to 2% by weight, more preferably 0.01 to 1% by weight.
Cellulose or a derivative thereof or a salt thereof: For example, 0.001 to 5% by weight, preferably 0.01 to 1% by weight.
Water-soluble polymers other than those described above: for example, 0.001 to 10% by weight, preferably 0.001 to 5% by weight, and more preferably 0.01 to 3% by weight.
Local anesthetic component: For example, 0.001-1% by weight, preferably 0.01-1% by weight.
Steroid component: For example, 0.001-1% by weight, preferably 0.01-1% by weight.
Glaucoma treatment component: for example, 0.001 to 5% by weight, preferably 0.01 to 1% by weight.
Cataract treatment component: for example, 0.0001 to 10% by weight, preferably 0.001 to 5% by weight.

  In order to prepare the contact lens composition of the present invention in various desired forms, various components and additives are appropriately selected according to conventional methods within a range not impairing the effects of the present invention, and one or more are used in combination. Can be blended. As these components or additives, for example, carriers (aqueous solvents, aqueous or oily bases, etc.) commonly used for the preparation of ophthalmic topical preparations, liquids, thickeners, sugars, surfactants, Various additives such as antiseptics, bactericides or antibacterial agents, isotonic agents, fragrances or refreshing agents, chelating agents, buffering agents and the like can be mentioned. Although the typical component which can be used is illustrated below, it is not limited to these.

  Thickeners: for example, polysaccharides or derivatives thereof (gum arabic, karaya gum, xanthan gum, carob gum, guar gum, guayac fat, quince seed, dammar gum, tragacanth gum, benzoin gum, locust bean gum, casein, agar, alginic acid, dextrin, dextran, Carrageenan, gelatin, collagen, pectin, starch, polygalacturonic acid, chitin and its derivatives, chitosan and its derivatives, elastin, heparin, heparinoid, heparin sulfate, heparan sulfate, hyaluronic acid, chondroitin sulfate, etc., ceramide, cellulose derivative (methylcellulose) , Ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose , Carboxyethyl cellulose, cellulose, nitrocellulose, etc.), polyvinyl alcohol (completely or partially saponified product), polyvinylpyrrolidone, macrogol, polyvinyl methacrylate, polyacrylic acid, carboxyvinyl polymer, polyethyleneimine, polyethylene oxide, polyethylene glycol, ribo Nucleic acids, deoxyribonucleic acid, methyl vinyl ether / maleic anhydride copolymer, and pharmacologically acceptable salts thereof (for example, sodium alginate).

  Surfactant: For example, polyoxyethylene (POE) -polyoxypropylene (POP) block copolymer (eg, poloxamer 407, poloxamer 235, poloxamer 188, etc.), polyoxyethylene-polyoxypropylene block copolymer adduct of ethylenediamine (eg, , Poloxamine), POE sorbitan fatty acid esters such as POE (20) sorbitan monolaurate (polysorbate 20), POE (20) sorbitan monooleate (polysorbate 80), polysorbate 60, POE such as POE (60) hydrogenated castor oil Hardened castor oil, POE alkyl ethers such as POE (9) lauryl ether, POE / POP alkyl ethers such as POE (20) POP (4) cetyl ether, POE alkyl phenyl ethers such as POE (10) nonylphenyl ether Nonionic surfactants such as tellurium and POE alkylphenyl ethers such as POE (10) nonylphenyl ether; glycine type such as alkyldiaminoethylglycine, betaine acetate type such as lauryldimethylaminoacetic acid betaine, imidazoline type Amphoteric surfactants; POE alkyl ether phosphates such as POE (10) sodium lauryl ether phosphate and salts thereof, N-acyl amino acid salts such as sodium lauroylmethylalanine, alkyl ether carboxylates, N-cocoyl methyl taurate sodium, etc. N-acyl taurine salt of sodium, sulfonate such as sodium tetradecene sulfonate, alkyl sulfate such as sodium lauryl sulfate, POE alkyl ether sulfate such as POE (3) sodium lauryl ether sulfate, α-ole Anionic surfactants such as sulfonic acid salts; cationic interfaces such as alkylamine salts, alkyl quaternary ammonium salts (eg benzalkonium chloride, benzethonium chloride), alkylpyridinium salts (eg cetylpyridinium chloride, cetylpyridinium bromide) Activators etc. The numbers in parentheses indicate the number of added moles.

  Preservatives, bactericides or antibacterial agents: for example, sorbic acid or a salt thereof (such as sorbic acid, potassium sorbate, sodium sorbate, triclocarban sorbate), paraoxybenzoic acid ester (methyl paraoxybenzoate, ethyl paraoxybenzoate, Propyl paraoxybenzoate, butyl paraoxybenzoate, etc.), acrinol, methylrosaniline chloride, benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, cetylpyridinium bromide, chlorhexidine or its salts, polyhexamethylene biguanide, alkylpolyaminoethylglycine, benzyl Alcohol, phenethyl alcohol, chlorobutanol, isopropanol, propanol, ethanol, phenoxyethanol, zirconium phosphate silver, Mercury , Popidone iodine, thimerosal, dehydroacetic acid, chlorxylenol, chlorophene, resorcin, orthophenylphenol, isopropylmethylphenol, thymol, hinokitiol, sulfamine, lysozyme, lactoferrin, triclosan, 8-hydroxyquinoline, undecylenic acid, capryl Acid, propionic acid, benzoic acid, propionic acid, halocarban, thiabendazole, polymyxin B, 5-chloro-2-methyl-4-isothiazolin-3-one, 2-methyl-4-isothiazolin-3-one, polylysine, peroxy Hydrogen oxide, polydronium chloride, Glokill (trade name such as Glokill PQ, manufactured by Rhodia), polydiallyldimethylammonium chloride, poly [oxyethylene (dimethyliminio) ethylene- (di Tyriminio) etylene dichloride], polyethylene polyamine / dimethylamine epichlorohydrin polycondensate (trade name, eg Busan 1157, manufactured by Bachman), biguanide compound (cosmosyl CQ (trade name, polyhexamethylene biguanide hydrochloride containing about 20% by weight, apicia) Etc.) and pharmacologically acceptable salts thereof.

  Isotonizing agents: for example, inorganic salts (eg, sodium chloride, potassium chloride, sodium carbonate, sodium bicarbonate, calcium chloride, magnesium sulfate, sodium hydrogen phosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, thiosulfuric acid Sodium, sodium acetate, etc.).

  Chelating agents: for example, edetic acid, citric acid, polyphosphoric acid, hexametaphosphoric acid, metaphosphoric acid, ascorbic acid, succinic acid, trihydroxymethylaminomethane, nitrilotriacetic acid, 1-hydroxyethane-1,1-diphosphonic acid, and the like Pharmacologically acceptable salts and the like.

  Buffer: borate buffer, phosphate buffer, carbonate buffer, citrate buffer, acetate buffer, epsilon-aminocaproic acid, aspartate and the like. For example, boric acid or a salt thereof (sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, borax, etc.), phosphoric acid or a salt thereof (sodium hydrogen phosphate, sodium dihydrogen phosphate, dihydrogen phosphate) Potassium, trisodium phosphate, dipotassium phosphate, calcium monohydrogen phosphate, calcium dihydrogen phosphate), carbonic acid or a salt thereof (sodium hydrogen carbonate, sodium carbonate, ammonium carbonate, potassium carbonate, calcium carbonate, potassium hydrogen carbonate) , Magnesium carbonate, etc.), 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, calcium acetate, Sodium acetate), aspartic acid or Is its salt (sodium aspartate, magnesium aspartate, potassium aspartate, etc.).

  What is necessary is just to set the mixture ratio of these various components and additives suitably according to the form, kind, etc. of a composition.

  The contact lens composition according to the present invention is, for example, ketotifen or a salt thereof, a polyhydric alcohol and menthol, optionally added to an aqueous solvent such as purified water, physiological saline, or a contact lens care solution. Agents and components are added to a desired concentration and prepared according to conventional methods.

  If the composition for contact lenses of this invention is used so that it may contact a contact lens, the form and application will not be restrict | limited. For example, eye drops (agent) for contact lenses (eye drops that can be used while wearing contact lenses), eye wash solutions for contact lenses (eye wash solutions that can be used while wearing contact lenses), contact lens wearing liquids, contact lenses Examples include care solutions (contact lens disinfectant, contact lens storage solution, contact lens cleaning solution, and contact lens cleaning storage solution). From the viewpoint of ease of use and the obtained antiallergic effect, eye drops for contact lenses and eyewashes for contact lenses are preferred.

  The contact lens composition of the present invention may be stored in any container, but a container having a low water permeability is preferable, and a container that does not easily adsorb each component is preferably used. In particular, as the container, it is preferable to use a hard plastic container. For example, the hard plastic container may be two or more selected from polycarbonate, polyethylene terephthalate, polyethylene naphthalate, polyarylate, polypropylene, polyethylene, or a group thereof. It is preferable to be formed including a plastic having

  The composition for contact lenses of the present invention can be used for all contact lenses including hard contact lenses and soft contact lenses. Among them, soft contact lenses are suitable for oxygen-permeable hard contact lenses and soft contact lenses, particularly soft contact lenses, because adsorption of ketotifen can be effectively suppressed.

  The method for using the contact lens composition is not particularly limited as long as it is a known method having a step of bringing the contact lens composition into contact with the contact lens. For example, in the case of eye drops (eye drops, eye drops), the contact lens composition of the present invention can be used for eye drops before, during, or during wearing of the contact lens. In the case of eyewash (eye drops, eye drops), the contact lens composition of the present invention can be used for eye washing while wearing the contact lens. In addition, when the composition for contact lenses of the present invention is eye drops (eye drops, eye drops) or eye wash (eye drops, eye drops), when wearing a contact lens, of course, when not wearing But it can be used for eye drop and eye wash. In the case of a contact lens care solution, the contact lens is used by immersing the contact lens in the solution.

  When the contact lens composition of the present invention is eye drops (eye drops, eye drops), the dose of the eye drops (eye drops, eye drops) to the eye is not particularly limited, It is desirable that ketotifen or a salt thereof is 1 to 5000 μg, preferably 5 to 1000 μg, more preferably 10 to 300 μg in one administration. In addition, the dose to each eye per day for adults is such that ketotifen or a salt thereof is, for example, about 0.01 to 15 mg, preferably about 0.01 to 10 mg, more preferably about 0.01 to 5 mg. It can be mentioned, but is not limited to these.

  Since the composition for contact lenses of the present invention can exhibit excellent antiallergic action even when applied to eyes wearing contact lenses, it can be used as an allergy symptom improving agent used during contact lens wear. Useful.

(II) Contact lens composition-2
From another viewpoint, the present invention provides a composition for contact lenses containing ketotifen or a salt thereof, glycerin and terpene.

  In the contact lens composition, ketotifen or a salt thereof used is the same as the composition (I).

  Moreover, the terpene used for the said composition for contact lenses will not be specifically limited if it can be used for an ophthalmology field. Examples of terpenes include menthol, camphor, borneol, geraniol, cineole, anethole, limonene, eugenol, pinene, ferrandolene, linalool, citronellol, citronellal, menthone and carvone. These do not ask the distinction between d-form, l-form, or dl-form. Among these, preferably 1-menthol, d-menthol, dl-menthol, d-camphor, dl-camphor, d-borneol and dl-borneol, more preferably l-menthol, d-menthol and dl-menthol, Particularly preferred is l-menthol. These terpenes may be used alone or in any combination of two or more. In the present invention, a terpene may be contained in the contact lens composition by blending the essential oil containing the terpene. The terpene-containing essential oil includes, for example, essential oils containing menthols such as peppermint oil, cool mint oil and mint oil, as well as eucalyptus oil, bergamot oil, fennel oil, cinnamon oil, rose oil, spearmint oil and the like. Essential oils can be exemplified.

  In the present invention, menthols described in the above (I) can be preferably used as terpenes.

  The content ratio of the three components in the composition for contact lenses varies depending on the form, use, type of components used, etc., but as an example, ketotifen or a salt thereof relative to the total weight of the composition 0.001 to 0.1 wt%, glycerin 0.1 to 5 wt%, and terpene 0.001 to 0.5 wt%; preferably ketotifen or a salt thereof 0.005 to 0.07 wt%, glycerin 0 The ratio which becomes 0.1 to 3.5 weight% and terpene 0.002 to 0.2 weight% can be mentioned.

  In the contact lens composition of the present invention, the mixing ratio (weight ratio) of the three components is, for example, 1 to 5000 parts by weight of glycerin and 0.01 to 500 parts of terpene with respect to 1 part by weight of ketotifen or a salt thereof. Weight part; Preferably, the ratio which becomes 1.5-700 weight part of glycerol and 0.03-40 weight part of terpenes can be mentioned. If the ratio deviates significantly from this ratio, the effect of the present invention cannot be obtained sufficiently, or an unpleasant irritation tends to occur.

  The contact lens composition is in the form of a liquid or a gel, preferably a liquid, like the composition of (I), and an ophthalmically acceptable water as a base material of the composition, preferably Purified water or ultrapure water is used. The composition for contact lenses may optionally contain a polyhydric alcohol other than glycerin (specifically, a polyhydric alcohol that can be blended in the composition (I)). In addition, other components and additives that can be blended in the contact lens composition and the blending ratio thereof are the same as those in the composition (I).

  In addition, the pH, osmotic pressure, preparation method, form, application, container to be used, contact lens to be used, usage method, and the like of the composition for contact lenses are the same as those in the composition (I).

  Since the contact lens composition can exhibit an excellent antiallergic effect even when applied to an eye wearing a contact lens, like the composition of (I), It is useful as an allergy symptom improving agent to be used.

(III) Method for suppressing adsorption of ketotifen or a salt thereof to a contact lens The method for suppressing adsorption of ketotifen to a contact lens of the present invention comprises the contact lens composition according to (I) or (II) above and a contact lens. It is characterized by contacting.

  In the method of the present invention, the specific form of the contact lens composition (I) or (II) is not particularly limited. For example, contact lens ophthalmic solution, contact lens eye wash solution, contact lens mounting solution, contact lens care solution (contact lens disinfectant solution, contact lens storage solution, contact lens cleaning solution, contact lens cleaning solution) I just need it. A contact lens mounting liquid and a contact lens care liquid are preferable, and a contact lens care liquid is more preferable.

  In the adsorption suppression method of the present invention, the contact lens composition (I) or (II) may be brought into contact with the contact lens in accordance with a normal use method according to the form and use of the composition to be used. Specifically, according to the method for using the contact lens composition described in the above (I) or (II), the contact lens composition can be used by using the contact lens composition.

  According to the contact lens composition of the present invention, an excellent antiallergic action can be exhibited even when used while wearing a contact lens, and adsorption of ketotifen to the contact lens can be suppressed. Therefore, by using the composition for contact lenses of the present invention, allergy symptoms can be alleviated easily and effectively for the contact lens user.

  Moreover, according to the method for suppressing adsorption of ketotifen or a salt thereof of the present invention, it is possible to suppress the adsorption of ketotifen or a salt thereof to a contact lens by a simple method. Therefore, this method is useful, for example, for eye drops, eye washing, or contact lens care of a contact lens user.

  Hereinafter, the present invention will be described in detail based on test examples, examples, and the like, but the present invention is not limited thereto.

Test Example 1 Allergy Symptom Improvement Effect Confirmation Test In order to evaluate the allergic symptom improvement effect exhibited by the composition for contact lenses of the present invention, the following test was conducted.

Ophthalmic solutions for contact lenses (Example 1 and Comparative Example 1) having the formulations shown in Table 1 below were prepared. 6 men and women with a history of allergies who have soft contact lens wearers as panelists, and when they feel allergic symptoms (itch) while wearing soft contact lenses, the eye drops of Example 1 and Comparative Example 1 remain worn. The degree of improvement of itching was evaluated by self-scoring based on the following evaluation criteria. Further, the same test was performed even when the lens was not worn.
<< Evaluation criteria for itching improvement effect >>
5 points: 4 points that were greatly improved: 3 points that were considerably improved: 2 points that were slightly improved: 1 point that was hardly improved: 1 point that was not improved at all The results obtained are shown in Table 1. Table 1 shows the average score (average evaluation value) of the evaluation values of the itch improvement effect determined by each panel. As can be seen from Table 1, in the case where the ophthalmic solution of Example 1 was applied, itching significantly improved compared to the case where the ophthalmic solution of Comparative Example 1 was applied both when wearing the contact lens and when not wearing it. The effect was recognized. In addition, in the ophthalmic solution of Comparative Example 1, the application to the eye wearing the contact lens significantly reduced the itching improvement effect compared to the application to the naked eye. On the other hand, in the ophthalmic solution of Example 1, the application to the eye wearing the contact lens had a higher itching improvement effect than the application to the naked eye.

  From the above results, it is clear that the composition for contact lenses of the present invention is useful as an eye drop or eye wash when wearing contact lenses.

Test Example 2 Adsorption Suppression Test In order to examine the influence of the composition for contact lenses of the present invention on the adsorption of ketotifen to contact lenses, the following tests were conducted.

  The contact lens compositions (Example 2-3 and Comparative Example 2) shown in Table 2 below were prepared according to a conventional method. In this test, the trade name “Sophina DX” (manufactured by Ciba Vision, non-water-containing, main material: butyl acrylate / butyl methacrylate polymer) was used as the soft contact lens.

<Test method>
(1) One contact lens is immersed in 5 mL of ISO10344 “Optical and optical machine-contact lens-saline solution for contact lens inspection” (hereinafter abbreviated as “saline solution for ISO contact lens”) at room temperature overnight. (About 25 ° C.). Subsequently, the contact lens was extracted from the physiological saline for ISO contact lenses, and the moisture was gently wiped off.
(2) 5 mL each of the contact lens compositions of Example 1-2 and Comparative Example 1 were dispensed into clear glass vials with high sealing performance, and each contact lens composition was obtained in (1). The contact lens was immersed and shaken at 34 ° C. at 20 times / minute for about 24 hours, and then the contact lens was extracted. Next, the amount of ketotifen fumarate remaining in each contact lens composition after the contact lens immersion treatment was measured using high performance liquid chromatography (HPLC).
(3) Again, dispense 5 mL each of the contact lens compositions of Example 1-2 and Comparative Example 1 into transparent glass vials with high sealing properties, and obtain each of the contact lens compositions in the above step. The obtained contact lens was immersed and shaken at 34 ° C. at 20 times / minute for about 24 hours, and then the contact lens was extracted. Next, the amount of ketotifen fumarate remaining in each contact lens composition after the contact lens immersion treatment was measured using high performance liquid chromatography (HPLC).
(4) The same immersion treatment as in (3) was repeated twice.
(5) The same steps as (2) to (4) above were performed except that the contact lens was not immersed, and the amount of ketotifen fumarate remaining in the contact lens composition when the contact lens was not immersed was measured ( blank).
(5) Sum of the amount of ketotifen fumarate (total of 4 times) in each contact lens composition after contact lens immersion treatment measured in steps (2) to (4) and each blank contact in (5) The amount of ketotifen fumarate adsorbed on the contact lens was calculated from the difference from the sum of the amount of ketotifen fumarate in the lens composition (a total of four times).

  The obtained results are also shown in Table 2. As can be seen from Table 2, in the contact lens compositions of Examples 2 and 3, the adsorption of ketotifen fumarate to the contact lens was significantly suppressed as compared to the contact lens composition of Comparative Example 2. In particular, in the contact lens composition of Example 3, it was confirmed that the adsorption suppression of ketotifen fumarate was more remarkably exhibited.

  From the above results, it was revealed that the composition for contact lenses of the present invention can effectively suppress the adsorption of ketotifen or a salt thereof to the contact lenses.

Example 4-24
According to conventional methods, eye drops, eyewashes, contact lens mounting liquids (in the table, referred to as CL mounting liquids) and contact lens disinfectants (in the table, referred to as CL disinfectants) having the formulations shown in Table 3-5 below. Prepared.

Claims (10)

A contact lens composition comprising ketotifen or a salt thereof, glycerin and menthol . The composition for contact lenses according to claim 1, which is contained in a proportion of 1 to 5000 parts by weight of glycerin and 0.01 to 500 parts by weight of menthol with respect to 1 part by weight of ketotifen or a salt thereof . It is contained at a ratio of 0.001 to 0.1% by weight of ketotifen or a salt thereof, 0.1 to 5% by weight of glycerin, and 0.001 to 0.5% by weight of menthol , based on the total weight of the composition. Item 3. The contact lens composition according to Item 1 or 2. Furthermore, it contains at least one terpene selected from the group consisting of camphor, borneol, geraniol, cineol, anethole, limonene, eugenol, pinene, ferrandlene, linalool, citronellol, citronellal, menthone and carvone. The composition for contact lenses of description. The composition for contact lenses according to any one of claims 1 to 4, wherein the pH is 3 to 6.2. Furthermore, the composition for contact lenses in any one of the Claims 1 thru | or 5 characterized by containing a buffering agent . Furthermore, surfactant is contained, The composition for contact lenses in any one of the Claims 1 thru | or 6 characterized by the above-mentioned . The composition for contact lenses according to any one of claims 1 to 7, which is used to improve itchiness when wearing contact lenses . The contact lens composition according to claim 1, wherein the contact lens is a soft contact lens . A method for imparting a contact lens adsorption inhibiting action to a contact lens composition, comprising blending glycerin and menthol with a composition for contact lens containing ketotifen or a salt thereof .