JP2007070350A - Preparation for ocular-mucous membrane application - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a safe preparation for ocular-mucous membrane application, which can effectively control the itching of eyes, when soft contact lenses are applied to the eyes. <P>SOLUTION: This preparation for ocular-mucous membrane application is characterized by containing glycyrrhizic acid or its salt, pyridoxine hydrochloride, and a specific amount of one or more selected from the group consisting of menthol, camphor, borneol, geraniol, linalyl acetate, and menthone. Thereby, eye drops, eye washes and the like which can control an itching feeling at the time of soft contact lens application can be provided. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a preparation for ocular mucosa. The present invention relates to an ophthalmic mucosa-applied preparation for antipruritics that can effectively suppress peculiar eye itching that occurs when wearing soft contact lenses.

One of the indefinite complaints of soft contact lens wearers is resentment. Soft contact lenses are easy to adsorb components that become antigens of allergic reactions and continue to stimulate the keratoconjunctiva. When a wearer wearing a soft contact lens has a subjective symptom of itch of the keratoconjunctiva, the main cause is an allergic reaction involving allergic reactions such as atopic keratoconjunctivitis, allergic conjunctivitis, giant papillary conjunctivitis, etc. It is said.
However, there are many itchings not caused by so-called allergic reactions. Allergic itching does not immediately relieve even if CL wearing is stopped (as long as allergic reaction continues), non-allergic itching may be relieved if CL wearing is stopped It is a feature. Thus, there is no known ocular mucosa-applied preparation that safely and effectively suppresses special itch caused during soft contact lens wearing.

  The unique non-allergic itch that occurs during the wearing of soft contact lenses is due to mechanical irritation to the keratoconjunctiva due to inadequate lens edges and inadequate base curves, and oxygen produced by contact lenses preventing tear exchange. It is also presumed to be caused by chemical stimulation such as nutritional deficiencies, but there are many unknowns, and the cause has not yet been investigated. For allergic itching, many drugs including antihistamines have been provided and the effect has been demonstrated, whereas for non-allergic itching not caused by such immune reactions, it is clear There was no therapeutic agent that had a positive effect. Therefore, the best treatment for this non-allergic itching was to stop wearing soft contact lenses.

  However, there are many consumers who are not in an environment that can always use eyeglasses at the same time, so that the population of soft contact lens wearers will exceed 16 million, and the discontinuation of wearing soft contact lenses significantly damages QOV (= Quality Of Vision). It is. A method of suppressing non-allergic itch while wearing a soft contact lens is strongly desired.

  By the way, it is known that eye drops with menthol or camphor can improve eye itching while wearing contact lenses (Patent Document 1).

  In addition, it is known that an eye drop containing glycyrrhizinate and menthol having an anti-inflammatory action has an improving effect on itching of a subject having an allergic symptom of the eye (Patent Document 2). However, there is no known effect on the unique non-allergic itching that occurs during soft contact lens wear.

Japanese Patent Laid-Open No. 11-180858 JP 2005-162747 A

  An object of the present invention is to provide an ophthalmic mucosa-applied preparation that can be safely instilled even with an eye wearing a soft contact lens and can effectively suppress itch.

The inventor comprises (A) one or more selected from the group consisting of pyridoxine hydrochloride, glycyrrhizic acid and a salt of glycyrrhizic acid, and (B) menthol, camphor, borneol, geraniol, linalyl acetate, and menthone. An ophthalmic mucosa-applied preparation comprising one or more selected from the group in an amount of 0.005 (w / v)% or more based on the whole preparation is a remarkable antipruritic agent when a soft contact lens is used. It was found to be a safe preparation that has an effect but does not adversely affect the contact lens or ocular mucosa.
That is, this invention is the invention hung up below.
(1) (A) One or more selected from the group consisting of pyridoxine hydrochloride, glycyrrhizic acid and a salt of glycyrrhizic acid, and (B) from the group consisting of menthol, camphor, borneol, geraniol, linalyl acetate and menthone Ophthalmic mucosa-applied preparation for antipruritics at the time of wearing a soft contact lens, characterized by containing one or two or more selected at 0.005 (w / v)% or more with respect to the whole preparation,
(2) (A) One or more selected from the group consisting of pyridoxine hydrochloride, glycyrrhizic acid and a salt of glycyrrhizic acid, and (B) a group consisting of menthol, camphor, borneol, geraniol, linalyl acetate and menthone One or more selected from the group consisting of 0.005 (w / v)% or more based on the whole preparation, ophthalmic mucosa-applied preparation for antipruritics when wearing soft contact lenses ,
(3) The ocular mucosa-applied preparation according to (1) or (2), which is substantially free of chlorpheniramine maleate or diphenhydramine hydrochloride,
(4) The ocular mucosa-applied preparation according to any one of (1) to (3), which is an eye drop or an eye wash;
(5) The preparation for application to the ocular mucosa according to any one of (1) to (4), containing pyridoxine hydrochloride in an amount of 0.005 (w / v)% or more,
(6) The ocular mucosa-applied preparation according to any one of (1) to (5), which contains glycyrrhizic acid or a salt thereof in a total amount of 0.025 (w / v)% or more.
In the present specification, “%” means w / v% (g / 100 mL) unless otherwise specified. Further, the term “soft contact lens” is used to include all types of soft contact lenses such as disposable, high / low water content, and color unless otherwise specified.

  The ophthalmic mucosa preparation of the present invention comprises (A) one or more selected from the group consisting of pyridoxine hydrochloride, glycyrrhizic acid and a salt of glycyrrhizic acid, and (B) menthol, camphor, borneol, geraniol, linalyl acetate. And 0.005 (w / v)% or more of one or more selected from the group consisting of menthone in the entire preparation, and an eye for antipruritics when wearing a soft contact lens It is a preparation for mucosal application. Such an ophthalmic mucosa-applied preparation exhibits an effective antipruritic effect against itching during wearing of a soft contact lens. The ocular mucosa-applied preparation of the present invention can be safely instilled with a soft contact lens attached. It is useful for eye drops, eye wash and the like for improving eye itchiness peculiar to a wearer of a soft contact lens.

  The ophthalmic mucosa-applied preparation of the present invention comprises (A) one or more compounds selected from the group consisting of pyridoxine hydrochloride, glycyrrhizic acid and a salt of glycyrrhizic acid as essential components. Pyridoxine hydrochloride and glycyrrhizic acid are known compounds, and the glycyrrhizic acid salt is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include dipotassium glycyrrhizinate. In particular, when two types of pyridoxine hydrochloride and dipotassium glycyrrhizinate are used in combination, the effect of improving itchiness is excellent.

  In the ocular mucosa-applied preparation of the present invention, the content of the component (A) in the preparation is not particularly limited, but as a proportion of the ocular mucosa-applied preparation, for example, pyridoxine hydrochloride is 0.001 to 0.5%, preferably 0. 0.005 to 0.5%, more preferably 0.005 to 0.2%, and still more preferably 0.01 to 0.1%. Glycyrrhizic acid or a salt thereof is 0.001 to 1%, preferably 0.01 to 0.5%, more preferably 0.025 to 0.5%, particularly preferably 0.025 to 0.25%. A percentage is mentioned.

  When pyridoxine hydrochloride and glycyrrhizic acid or a salt thereof are used in combination, glycyrrhizic acid or a salt thereof is preferably 0.1 to 100 parts by weight, more preferably 0.1 parts by weight with respect to 1 part by weight of pyridoxine hydrochloride. -50 parts by weight, more preferably 1 part by weight to 50 parts by weight, particularly preferably 5 parts by weight to 25 parts by weight.

  The ophthalmic mucosa-applied preparation of the present invention is effective against peculiar itch produced when wearing soft contact lenses, and contains (A) component and (B) component as essential components, but is non-allergic during soft contact lens wearing. Since itching can sometimes occur with allergic itching, chlorpheniramine maleate, diphenhydramine hydrochloride, acitazanolast, amlexanox, ibudilast, tranilast, levocabastine hydrochloride, sodium cromoglycate, ketotifen fumarate, pemiro You may contain antiallergic drugs, such as last potassium, as needed.

  However, some antihistamines and antiallergic drugs, such as chlorpheniramine maleate and diphenhydramine hydrochloride, can adversely affect soft contact lenses, so they are compatible with such soft contact lenses. It is preferable to limit the content of the component having a problem to a small amount, and it is more preferable that the content is not substantially contained.

  The ocular mucosa-applied preparation of the present invention comprises (B) one or more selected from the group consisting of menthol, camphor, borneol, geraniol, linalyl acetate, and menthone, and the total amount of these is 0 for the entire preparation. 0.005 (w / v)% or more. These may be d-form, l-form or dl-form. Among them, the antipruritic effect is further enhanced by using menthol together with one or more selected from the group consisting of camphor, borneol, geraniol, linalyl acetate, and menthone. The ophthalmic mucosa-applied preparation of the present invention may contain menthol, camphor, borneol, geraniol, linalyl acetate, and menthone alone, or may contain an essential oil containing these compounds. For example, as essential oil containing menthol, mint oil and peppermint oil are exemplified; as essential oil containing linalyl acetate, bergamot oil and the like, and as essential oil containing menthol, peppermint oil and the like are exemplified.

  The effect of this invention is show | played when (B) component in an ocular mucosa application formulation contains 0.005% or more with respect to the whole formulation with a total amount. A higher effect can be obtained by 0.007% or more, and a higher effect can be obtained by 0.01% or more.

  The ophthalmic mucosa-applied preparation of the present invention is prepared by appropriately adjusting the pH normally used for an ophthalmic mucosa-applied preparation, and the pH is preferably 5.5 to 8.0 from the viewpoint of safety. More preferably, it is 6.0-7.5.

  The ocular mucosa-applied preparation of the present invention is not particularly limited. Examples of ophthalmic mucosa preparations include eye drops (agents) used while wearing soft contact lenses, eyewashes (agents) used when wearing soft contact lenses, and contact lens mounting solutions used when wearing soft contact lenses. Etc. Among these, eye drops (agent) and eye wash (agent) are preferable. Moreover, the ocular mucosa-applied preparation of the present invention can be applied to non-allergic itch that occurs immediately after removing a soft contact lens that has been worn continuously for a long time.

  The form of the preparation for application to the ocular mucosa of the present invention is not particularly limited, and examples thereof include a liquid preparation, a suspension preparation, and a liposome preparation.

  Since glycyrrhizic acid or a salt thereof, which is an essential component of the preparation for ocular mucosa of the present invention, also acts as an anti-inflammatory component, the preparation for ocular mucosa of the present invention can exhibit an anti-inflammatory action. Furthermore, other medicinal ingredients can be contained. For example, decongestant component, ocular muscle modulator component, anti-inflammatory component or astringent component, antihistamine component or antiallergic component, vitamins, amino acids, sulfa drugs, saccharides, polysaccharides or salts thereof, cellulose derivatives Or the salt, water-soluble polymers other than the above, a local anesthetic component, a steroid component, a glaucoma therapeutic agent etc. can be illustrated. Examples of suitable components in the present invention include the following components. However, it is preferable not to substantially contain a component that adversely affects the soft contact lens. However, if it is necessary to add a compound from the viewpoint of medicinal properties, the content is limited to a small amount or a soft contact lens. It is more preferable to contain after prescribing the formulation so that the component does not adsorb.

  Decongestant: For example, α-adrenergic agonists, specifically epinephrine, epinephrine hydrochloride, ephedrine hydrochloride, oxymetazoline hydrochloride, tetrahydrozoline hydrochloride, naphazoline hydrochloride, phenylephrine hydrochloride, methylephedrine hydrochloride, epinephrine hydrogen tartrate, naphazoline nitrate. These may be d-form, l-form or dl-form.

  Eye muscle modulator component: For example, cholinesterase inhibitor having an active center similar to acetylcholine, specifically, neostigmine methyl sulfate, tropicamide, atropine sulfate helenien, and the like.

  Anti-inflammatory component or astringent component: for example, zinc sulfate, zinc lactate, allantoin, epsilon-aminocaproic acid, indomethacin, lysozyme chloride, silver nitrate, pranoprofen, sodium azulenesulfonate, diclofenac sodium, bromfenac sodium, berberine chloride , Berberine sulfate and so on.

  Vitamins: for example, retinol acetate, retinol palmitate, sodium flavin adenine dinucleotide, pyridoxal phosphate, cyanocobalamin, panthenol, calcium pantothenate, sodium pantothenate, ascorbic acid, tocopherol acetate.

  Amino acids: For example, aminoethylsulfonic acid, magnesium aspartate, potassium aspartate, glutamic acid, creatinine, sodium glutamate and the like. These may be d-form, l-form or dl-form.

  Sulfa drugs: For example, sulfamethoxazole, sulfisoxazole, sulfamethoxazole sodium and the like.

  Sugars: for example, monosaccharides, disaccharides, specifically glucose, trehalose and the like.

  Polysaccharides or salts thereof: for example, sodium hyaluronate, sodium chondroitin sulfate, etc.

  Cellulose derivatives or salts thereof: For example, hydroxyethylcellulose, hydroxypropylmethylcellulose, methylcellulose, sodium carboxymethylcellulose and the like.

  Water-soluble polymers other than those described above: polyvinyl alcohol (completely or partially saponified product), polyvinylpyrrolidone, dextran and the like.

  Local anesthetic ingredients: for example, oxybuprocaine hydrochloride, cocaine hydrochloride, cornecaine hydrochloride, dibucaine hydrochloride, tetracaine hydrochloride, diethylaminoethyl parabutylaminobenzoate, piperocaine hydrochloride, procaine hydrochloride, proparacaine hydrochloride, hexothokine hydrochloride, lidocaine hydrochloride, chloro Butanol and so on.

  Steroid component: for example, dexamethasone, hydrocortisone, fluorometholone, prednisolone, methylprednisolone, hydroxymesterone, hydrocortisone caproate, prednisolone caproate, cortisone acetate, hydrocortisone acetate, prednisolone acetate, sodium dexamethasone metasulfobenzoate, sodium dexamethasone sulfate Dexamethasone sodium phosphate, triamcinolone acetonide, betamethasone sodium phosphate, dexamethasone sodium metasulfobenzoate, methylprednisolone and the like.

  Glaucoma treatment components: for example, isopropyl unoprostone, epinephrine, apraclonidine hydrochloride, carteolol hydrochloride, dipivefrin hydrochloride, dorzolamide hydrochloride, pilocarpine hydrochloride, bunazosin hydrochloride, bupranolol hydrochloride, betaxolol hydrochloride, benololol hydrochloride, carbachol, levobunolol hydrochloride, epinephrine hydrochloride , Distigmine bromide, nipradilol, timolol maleate, latanoprost and the like.

  The blending amount of these components in the preparation for application to the ocular mucosa is appropriately selected according to the kind of the preparation, the kind of the active ingredient, etc., for example, 0.0001-30%, preferably 0.001- The range can be selected from about 10%.

  In addition, in the ophthalmic mucosa-applied preparation of the present invention, various components and additives are appropriately selected according to conventional methods according to the use and form as long as the effects of the invention are not impaired. May be contained in combination. What is necessary is just to set suitably about the mixture ratio of this component or additive based on the range normally employ | adopted in this industry. Examples of the component or additive include a carrier (water, aqueous solvent, aqueous or oily base, etc.), a thickener, a pH adjuster, a tonicity agent, a fragrance Various additives, such as a refreshing agent, a chelating agent, a buffering agent, and surfactant, can be mentioned. Although the typical component used for the ocular mucosa application formulation of this invention is illustrated below, it is not limited to these. However, it is preferable not to substantially contain a component that adversely affects the soft contact lens. However, if it is necessary to add a compound from the viewpoint of medicinal properties, the content is limited to a small amount or a soft contact lens. It is more preferable to contain after prescribing the formulation so that the component does not adsorb.

  Nonionic surfactant: polyoxyethylene (hereinafter abbreviated as POE) -polyoxypropylene (hereinafter abbreviated as POP) block copolymer (specifically, poloxamer 407, etc.), ethylenediamine POE-POP block copolymer adduct (Specifically, poloxamine, etc.), POE sorbitan monooleate (specifically, polysorbate 80, etc.), POE hydrogenated castor oil (specifically, POE (60) hydrogenated castor oil, etc.), polyoxyl stearate, etc. .

  Preservatives: sorbic acid or its salt, polyhexamethylene biguanide or its salt, polymeric quaternary ammonium compound or its salt, sodium chlorite, hydrogen peroxide, etc.

  Aqueous carrier: for example, water, methanol, hydrous methanol, ethanol, hydrous ethanol and the like.

  Thickeners: for example, carboxyvinyl polymer, hydroxyethylcellulose, hydroxypropylmethylcellulose, methylcellulose, alginic acid or a salt thereof, polyvinyl alcohol (completely or partially saponified product), polyvinylpyrrolidone, macrogol, sodium carboxymethylcellulose, dextran, glycerin and the like.

  pH adjusting agent: for example, hydrochloric acid, epsilon-aminocaproic acid, acetic acid, sodium hydroxide, sodium bicarbonate, sodium carbonate, triethanolamine, monoethanolamine and the like.

  Isotonizing agents: for example, sodium bisulfite, sodium sulfite, potassium chloride, calcium chloride, sodium chloride, magnesium chloride, potassium acetate, sodium acetate, sodium bicarbonate, sodium carbonate, sodium thiosulfate, magnesium sulfate, dihydrogen phosphate Sodium, sodium dihydrogen phosphate, potassium dihydrogen phosphate, glycerin, propylene glycol and the like.

  Chelating agent: for example, ascorbic acid or its salt, edetic acid or its salt, citric acid or its salt, etc.

  Buffer: borate buffer, citrate buffer, acetate buffer, carbonate buffer, phosphate buffer, etc. Specifically, citric acid, sodium citrate, acetic acid, potassium acetate, sodium acetate, sodium hydrogen carbonate, sodium carbonate, disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate and the like.

  Stabilizer: Dibutylhydroxytoluene, trometamol, sodium formaldehyde sulfoxylate (Longalite), tocopherol, sodium pyrosulfite, monoethanolamine, aluminum monostearate, glycerin, propylene glycol, cyclodextrin, dextran, etc.

  Solubilizer, base: octyldodecanol, olive oil, sesame oil, titanium oxide, potassium bromide, soybean oil, camellia oil, corn oil, rapeseed oil, paraffin, castor oil, plastibase, peanut oil, lanolin, petrolatum, glycerin, propylene Glycol, cyclodextrin, macrogol, etc.

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

Test Example 1 Itching Feeling Inhibition Evaluation Test An eye drop (Example 1-23 and Comparative Example 1-3) prepared by filtering and aseptically filling a liquid preparation prepared according to the formulation described in Table 1-3 into a plastic eye drop container Manufactured. The following soft contact lens users were set as 10 subjects. The subjects were subjects with no objective findings such as allergies or keratoconjunctivitis.
Each subject was asked to wear a soft contact lens for 12 hours or more per day, and when the patient felt itching during the test period, the test eye drop was instilled.

  The degree of suppression of pruritus immediately after instillation and 10 minutes after instillation when each eye drop was applied was self-evaluated according to the following evaluation criteria, and the average score for 5 times per test eye drop for each prescription was determined for each subject. Scored. Furthermore, the average value of the scores of all subjects was calculated for each test eye drop to evaluate the degree of suppression of pruritus. The results are shown in Table 1-3.

Evaluation criteria: pruritus compared to before instillation (score)
Does not feel itching (5 points)
Itching sensation was significantly improved (4 points)
Pruritus was improved (3 points)
Itching was slightly improved (2 points)
Itching sensation does not change (1 point)

By containing 0.005 (w / v)% or more of menthol, camphor, borneol, geraniol, linalyl acetate or menthone together with pyridoxine hydrochloride or dipotassium glycyrrhizinate, it is possible to suppress stagnation during wearing of a soft contact lens. Was confirmed. This effect was observed not only immediately after instillation but also 10 minutes after instillation. Moreover, it was shown that it was more remarkable in the ophthalmic mucosa-applied preparation containing menthol and camphor or menthol and geraniol in combination.
Separately, a test eyewash (Example 24) was produced and tested in the same manner as described above. As in the results shown in the test eyedrops, the stagnation in wearing soft contact lenses was suppressed. It was confirmed that it was possible. In addition, about the eye wash, when the pruritus was felt immediately after removing the soft contact lens during the test period, the eye was washed with the test eye wash.

Test Example 2 Eye Drop Number Evaluation Test An eye drop was prepared by filtering a solution prepared according to the formulation shown in Table 4 and aseptically filling a plastic eye drop container. The following tests were conducted using three soft contact lens users who had no objective findings such as allergies and keratoconjunctivitis.
Each subject was asked to wear a soft contact lens for 12 hours or more per day, and was instilled with a test eye drop when they felt itching for 1 day per prescription.

  The average number of instillations per day for three subjects was calculated, and the results are shown in Table 4.

  By containing 0.005 (w / v)% or more of menthol and camphor, or menthol and geraniol, together with pyridoxine hydrochloride and dipotassium glycyrrhizinate, itching is suppressed during the wearing of soft contact lenses and the occurrence of itching is prevented. It was confirmed that the number of instillations due to itchiness per day was reduced.

Claims (6)

(A) One or more selected from the group consisting of pyridoxine hydrochloride, glycyrrhizic acid and a salt of glycyrrhizic acid, and (B) selected from the group consisting of menthol, camphor, borneol, geraniol, linalyl acetate and menthone An ophthalmic mucosa-applied preparation for antipruritics at the time of wearing a soft contact lens, characterized by containing one or more kinds in an amount of 0.005 (w / v)% or more based on the whole preparation. (A) One or more selected from the group consisting of pyridoxine hydrochloride, glycyrrhizic acid and a salt of glycyrrhizic acid, and (B) selected from the group consisting of menthol, camphor, borneol, geraniol, linalyl acetate and menthone 1 type or 2 types or more are contained in 0.005 (w / v)% or more with respect to the whole formulation, and the ocular mucosa application formulation for the antipruritic at the time of wearing a soft contact lens characterized by the above-mentioned. The ophthalmic mucosa-applied preparation according to claim 1 or 2, substantially free of chlorpheniramine maleate or diphenhydramine hydrochloride. The ophthalmic mucosa-applied preparation according to any one of claims 1 to 3, which is an eye drop or an eye wash. The preparation for ocular mucosa according to any one of claims 1 to 4, comprising pyridoxine hydrochloride in an amount of 0.005 (w / v)% or more. The ophthalmic mucosa-applied preparation according to any one of claims 1 to 5, comprising glycyrrhizic acid or a salt thereof in a total amount of 0.025 (w / v)% or more.