JP5201795B2 - Pruritus inhibitor - Google Patents

Description

  The present invention relates to an itching inhibitor having an antipruritic effect that relieves or reduces eye itch caused by allergy.

  It is known that a typical allergy mechanism is caused by the following steps. That is, for a living body, an antigen that is a foreign substance enters the living body. When exposed to this antigen, the organism produces IgE antibodies against that antigen. The produced IgE adheres to the surface of mast cells and becomes IgE-binding mast cells. When an antigen invades into a living body where IgE-binding mast cells are formed again, an antigen-antibody reaction occurs on the surface of IgE-binding mast cells. As a result, degranulation of IgE-binding mast cells causes various chemical mediators such as histamine and leukotriene to be produced. Liberate. And allergic reaction arises by the effect | action of this chemical transmitter.

  By the way, itching occurs when the itching receptors present in the mucous membrane and skin are stimulated by the itching-inducing substance. A typical itch-inducing substance is histamine released as a result of the above-mentioned allergic reaction. Therefore, antihistamines such as chlorpheniramine maleate and antiallergic agents such as cromoglycate sodium that suppress mast cell degranulation are widely used for allergic itch.

  Causes of allergies include pollen, dust, mites, molds, animal hair and dandruff, contact lens stains, cosmetics and drugs. Allergic itching may be manifested as itching associated with diseases such as allergic conjunctivitis, hay fever, atopic keratoconjunctivitis, and infectious keratoconjunctivitis. The itching that occurs once in the eyes and in the immediate vicinity due to an allergic reaction is scratched excessively due to the intense itching, and the inflammation and edema of the easily damaged eye mucosa are often worsened.

  In order to suppress excessive pruritus with an antipruritic effect against such itching, eye drops containing both an antiallergic agent and an antihistamine, an antiallergic agent and an eyedrop containing an antihistamine and menthol Known (Patent Document 1: WO 98/13040).

  Then, this invention makes it a subject to provide the pruritus inhibitor which has a strong antipruritic effect with respect to the itching of the eye which arises due to allergic reaction.

  As a result of intensive studies to solve the problem, alginic acid or a salt thereof was found to have an antipruritic effect and an itching inhibitory effect. In addition, the present invention found that a preparation containing at least one selected from a) alginic acid or a salt thereof, and b) an antihistamine or an antiallergic agent has an excellent antipruritic effect and pruritus inhibitory effect. It came to be completed.

The present invention has been developed based on such knowledge.
That is, the present invention is the inventions listed in the following (1) to (12):
(1) a) an itching agent containing at least one selected from a) alginic acid or a salt thereof, and b) an antihistamine or an antiallergic agent,
(2) The itching inhibitor according to (1), containing alginic acid or a salt thereof at 0.001 to 5.0 w / v%,
(3) The pruritus suppressant according to (1), which contains at least one selected from antihistamines or antiallergic agents at 0.001 to 5.0 w / v%,
(4) The pruritus inhibitor according to any one of (1) to (3), further comprising one or more compounds selected from menthol, camphor or borneol,
(5) The pruritus suppressant according to (4), containing one or more compounds selected from menthol, camphor or borneol at a total amount of 0.0001 to 5 w / v%,
(6) The pruritus suppressant according to (1) to (5), further comprising at least one selected from vitamins, amino acids, and sugars,
(7) The pruritus suppressant according to (1) to (6), wherein the pruritus is eye itching,
(8) The pruritus is an itching caused by an allergic reaction, the pruritus inhibitor according to any one of (1) to (7),
(9) Further, one or more nonionic surfactants selected from a polyoxyethylene-polyoxypropylene block copolymer, a polyoxyethylene sorbitan fatty acid ester or a polyoxyethylene hydrogenated castor oil are added in an amount of 0.00. The itching inhibitor according to any one of claims 1 to 8, which is contained at 0001 to 5 w / v%,
(10) Eye drops, eye wash, contact lens mounting liquid (1) to (9) (11) Eye drops for contact lens, contact lens mounting liquid, eye wash for contact lens (1) to (10) An itching inhibitor according to any one of
(12) An itching inhibitor for allergic itching comprising at least one selected from a) alginic acid or a salt thereof, and b) an antihistamine or an antiallergic agent.
In the present specification, unless otherwise specified,% means w / v%. Further, in the present specification, the contact lens is meant to include all types of contact lenses such as hard, oxygen permeable hard, soft, and color.

The pruritus inhibitor of the present invention has an antipruritic effect on itching caused by an allergic reaction, and exhibits a significant pruritus inhibitory effect. In particular, it is highly effective in suppressing pruritus against itching caused by an allergic reaction. Therefore, the itching inhibitor of the present invention is suitable for use in eye drops, eye washes, nasal drops and the like applied to the eye, and can exhibit excellent effects on eye itchiness in contact lens wearers. Therefore, it is also suitable for use in eye drops for contact lenses, eye wash for contact lenses, and the like.
In the present invention, alginic acid or a salt thereof has been found to have an antipruritic effect and an itching inhibitory effect against allergic itching. Therefore, this invention also includes the antipruritic agent containing alginic acid or its salt.

The use of the pruritus suppressant of the present invention is not specified as long as the effect of the invention is utilized, and in various fields such as pharmaceuticals, quasi drugs, miscellaneous goods, etc. It can be used as an improving agent for conjunctivitis, hay fever, atopic keratoconjunctivitis, and the like. For example, eye drops (agents) (including eye drops that can be used while wearing contact lenses, also referred to as eye drops), eye wash (agents) (use contact lenses while wearing) It is also suitable for use as an eye ointment, contact lens mounting liquid, and the like. Alginic acid or a salt thereof has a high effect of retaining a drug in the mucosa, and alginic acid or a salt thereof has an advantage that there are no side effects when applied to the ocular mucosa because it is very safe.
Also, since contact lenses tend to increase allergic reactions, eyes wearing contact lenses are prone to itching. This tendency is particularly remarkable in soft contact lenses. The pruritus inhibitor of the present invention having a high antipruritic effect is a contact lens eye drop (artificial tear liquid type eye drop) that can be used while wearing a contact lens, a contact lens wearing liquid, and an eye wash that can be used while wearing a contact lens Useful for medicine. Alginic acid or a salt thereof has an advantage that it does not adversely affect the contact lens.

  As the alginic acid in the present invention, either a natural product or a synthetic product may be used. Typical natural products include Macrocystis on the west coast of the United States, Lessonia in Chile in South America, Ascophyllum in Scandinavia, etc. The extraction method includes an alkali extraction method, but is not particularly defined. Moreover, the mannuronic acid / guluronic acid ratio (M / G ratio) of alginic acid is not particularly specified, and a wide range of alginic acid from M rich to G rich can be used, but it is 4.0 or less. More preferably, it is 3.0 or less, More preferably, it is 2.5 or less, Most preferably, it is 2.0 or less. Commercially available alginic acid can also be used, and is commercially available from Kibun Food Chemifa Co., Ltd., Kimika Co., Ltd., Fuji Chemical Industry Co., Ltd. and the like.

  Examples of the alginic acid salt in the present invention include alginic acid salts such as sodium salt, potassium salt, triethanol salt, and ammonium salt of alginic acid, but are not limited thereto. Of these, sodium alginate and potassium alginate are preferable. Alginic acid or a salt thereof can be either a natural product or a synthetic product. Typical natural products include Macrocystis on the west coast of the United States, Lessonia in Chile in South America, Ascophyllum in Scandinavia, etc. The extraction method includes an alkali extraction method, but is not particularly defined. Moreover, the mannuronic acid / guluronic acid ratio (M / G ratio) of alginic acid is not particularly specified, and a wide range of alginic acid from M rich to G rich can be used, but it is 4.0 or less. More preferably, it is 3.0 or less, More preferably, it is 2.5 or less, Most preferably, it is 2.0 or less. Commercially available salts of alginic acid can be used, and are commercially available from Kibun Food Chemifa Co., Ltd., Kimika Co., Ltd., Fuji Chemical Industry Co., Ltd. and the like.

  The content of alginic acid or a salt thereof in the pruritus inhibitor of the present invention can be appropriately set according to the molecular weight, composition (M / G ratio) and other components coexisting in the preparation, but is usually 0.001. -10%, more preferably 0.005 to 5%, more preferably 0.005 to 3%, still more preferably 0.005 to 0.5%, and still more preferably 0.01 to 0.5%. .

  The pruritus inhibitor in the present invention contains at least one drug selected from antihistamines or antiallergic drugs or a combination of two or more drugs. Only an antihistamine or an antiallergic agent may be contained, or an antihistamine and an antiallergic agent may be contained in combination. Examples of antihistamines include diphenhydramine hydrochloride, chlorpheniramine maleate, clemastine fumarate, mequitazine, and antiallergic agents include, for example, acitazanolast, amlexanox, ibudilast, tranilast, levocabastine hydrochloride, fumaric acid. Ketotifen, sodium cromoglycate, pemirolast potassium and the like. Preferred are diphenhydramine hydrochloride, ketotifen fumarate, cromoglycate sodium, chlorpheniramine maleate, or combinations thereof.

  The content of the antihistamine or antiallergic agent in the pruritus suppressant of the present invention varies depending on the drug to be used and the application site, but is not particularly limited as long as the effect of the present invention is exhibited. Usually, the content of each drug is preferably 0.00001 to 5%, more preferably 0.00005 to 3%, and particularly preferably 0.00005 to 1%. More specifically, for example, 0.001 to 0.1% is particularly preferable for chlorpheniramine maleate, 0.001 to 0.2% is particularly preferable for diphenhydramine hydrochloride, and sodium cromoglycate If present, 0.05 to 5% is particularly preferable.

The pruritus inhibitor of the present invention preferably further contains at least one selected from vitamins, amino acids and saccharides. You may mix and mix these. Thereby, the antitussive effect becomes more prominent.
Examples of vitamins include retinol acetate, retinol palmitate, pyridoxine hydrochloride, sodium flavin adenine dinucleotide, pyridoxal phosphate, cyanocobalamin, panthenol, calcium pantothenate, sodium pantothenate, tocopherol acetate, among others. Preferred is pyridoxine hydrochloride.
Examples of amino acids include aminoethyl sulfonic acid (taurine), glutamic acid, potassium aspartate, magnesium aspartate, magnesium aspartate / potassium mixture, sodium glutamate, sodium chondroitin sulfate, and taurine is particularly preferred. It is.
Examples of the saccharide include glucose and trehalose. Among them, glucose is preferable.

  The content in the pruritus inhibitor is preferably 0.0001 to 1%, more preferably 0.0001 to 0.5%, particularly preferably 0.001 to 0.001 to 1%, as long as the total amount of each is a vitamin. 0.3%. If it is an amino acid, it is preferably 0.0001 to 10%, more preferably 0.001 to 3%. If it is a saccharide, it is preferably 0.0001 to 5%, more preferably 0.001 to 5%. Preferably it is 0.01 to 2%.

  The pruritus inhibitor of the present invention preferably further contains at least one selected from menthol, camphor or borneol. It is particularly preferable to blend two or more in combination. Thereby, the effect of suppressing pruritus becomes more remarkable. These may be d-form, l-form or dl-form. These compounds are all known compounds, and commercially available products can be used. In addition, essential oils containing menthol, camphor or borneol (for example, peppermint oil, eucalyptus oil, etc.) can also be used.

  In the present invention, the content of at least one selected from menthol, camphor or borneol in the pruritus inhibitor is usually 0.0001 to 5%, preferably 0.001 to 3%, as the total amount of these compounds. Preferably it is 0.005 to 2%, particularly preferably about 0.01 to 1%.

  The pruritus suppressant in the present invention further enhances the pruritus suppressive effect by containing a nonionic surfactant. Examples of such nonionic surfactants include polyoxyethylene (hereinafter also referred to as POE) -polyoxypropylene (hereinafter also referred to as POP) block copolymers (for example, poloxamer 407, poloxamer 235, poloxamer 188, etc.); poloxamine POE-POP block copolymer adduct of ethylenediamine such as: POE (20) sorbitan monolaurate (Polysorbate 20), POE (20) sorbitan monooleate (Polysorbate 80), POE sorbitan monostearate (Polysorbate 60), POE sorbitan POE sorbitan fatty acid esters such as tristearate (polysorbate 65); POE hydrogenated castor oil 5, POE hydrogenated castor oil 10, POE hydrogenated castor oil 20, POE hydrogenated castor oil 40, POE hydrogenated castor oil 50, POE hydrogenated castor oil 60POE hydrogenated castor oil such as POE hydrogenated castor oil 100; POE alkyl ethers such as POE (9) lauryl ether; POE (20) POP (4) POE and POP alkyl ethers such as cetyl ether; POE (10) nonyl POE alkyl phenyl ethers such as phenyl ether can be mentioned. The numbers in parentheses indicate the number of added moles.

  Among them, nonionic surfactants selected from polyoxyethylene-polyoxypropylene block copolymers, POE sorbitan fatty acid esters or POE hydrogenated castor oils are preferable, and polyoxyethylene-polyoxypropylene blocks are particularly preferable. Copolymer, polysorbate 80, polyoxyethylene hydrogenated castor oil 60.

  The content of the nonionic surfactant in the pruritus inhibitor varies depending on the type of the surfactant and the like, and thus cannot be defined unconditionally, but is usually 0.0001 to 5%, preferably 0.001 to 1%. Preferably it is used at 0.001 to 0.8%, particularly preferably about 0.005 to 0.5%.

  When setting the viscosity of the pruritus suppressant of the present invention, it is preferable to design the viscosity at 20 ° C. while maintaining the viscosity at 1.2 mPa · s or more, usually 1.2 to 1000 mPa · s, preferably 1.2 ˜500 mPa · s, particularly preferably 1.5 to 100 mPa · s, more preferably about 1.5 to 80 mPa · s. Since the viscosity of the preparation affects the effect of suppressing pruritus, it is preferable to adjust the viscosity within such a range.

Since the pH of the pruritus inhibitor of the present invention affects the effect of inhibiting pruritus, the pH is preferably 4.0 to 10.0, more preferably 4.5 to 9.5, and particularly preferably 5.0 to 9.0. It is desirable to adjust to. Such pH adjustment can be performed using a buffering agent, a pH adjusting agent described later, and the like.
Here, when using a buffering agent, a boric acid buffering agent, a phosphate buffering agent, a carbonate buffering agent, a citrate buffering agent, an acetic acid buffering agent etc. are mentioned. Preferred buffering agents are borate buffer, phosphate buffer, carbonate buffer and citrate buffer. Particularly preferred buffering agents are borate buffers or phosphate buffers. Examples of the boric acid buffer include borates such as boric acid, alkali metal borates, and alkaline earth metal borates, and combinations of boric acid and borates. Examples of the phosphate buffer include phosphates such as phosphoric acid, alkali metal phosphates, and alkaline earth metal phosphates, and combinations of phosphoric acid and phosphates. Moreover, you may use the borate or the hydrate of a phosphate as a borate buffer or a phosphate buffer. More specifically, boric acid or a salt thereof (sodium borate, potassium tetraborate, potassium metaborate, etc.), phosphoric acid or a salt thereof (sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, etc.) , Carbonic acid or a salt thereof (sodium bicarbonate, sodium carbonate, etc.), citric acid or a salt thereof (sodium citrate, potassium citrate, etc.). When a borate buffer or a phosphate buffer is used as the buffer, the concentration of these buffers in the pruritus suppressant of the present invention is, for example, preferably 0.0001 to 10.0%, more preferably 0. 0.001 to 5%, more preferably 0.005 to 5%, and particularly preferably 0.005 to 3%.

  In addition, since the osmotic pressure of the pruritus inhibitor of the present invention affects the pruritus suppressing effect, the osmotic pressure of the preparation is preferably 100 to 800 mOsm, more preferably 200 to 600 mOsm, still more preferably 250 to 550 mOsm, and particularly preferably. It is preferable to adjust to about 250-500 mOsm.

  The pruritus inhibitor in the present invention preferably further contains a cellulose derivative. Cellulose derivatives that can be used for pruritus inhibitors can be used, for example, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, carboxyethylcellulose or pharmacologically acceptable salts thereof. And so on. Among these, at least one selected from methyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, or a salt thereof is preferable. Here, examples of the pharmacologically acceptable salt include alkali metals such as sodium and potassium, alkaline earth metals such as calcium and magnesium, and salts with metals such as aluminum.

  The content of the cellulose derivative with respect to the pruritus inhibitor varies depending on the molecular weight and type, and thus cannot be defined unconditionally. Usually, the concentration of the cellulose derivative in the preparation is 0.001 to 10%, preferably 0.005 to 5%. More preferably, it can be used at 0.01 to 2%, particularly preferably about 0.1 to 2%.

The pruritus inhibitor of the present invention may contain various components (including pharmacologically active components and physiologically active components) in combination as long as the effects of the present invention are not hindered. The type of such component is not particularly limited, and examples thereof include a decongestant component, an eye regulator component, an anti-inflammatory component or an astringent component, an antibacterial component, a bactericidal component, a polysaccharide or a derivative thereof, Examples thereof include a functional polymer, a local anesthetic component, and a steroid component. Examples of suitable components in the present invention include the following components.
Decongestant: for example, naphazoline hydrochloride, tetrahydrozoline hydrochloride, naphazoline nitrate, epinephrine, epinephrine hydrochloride, ephedrine hydrochloride, oxymetazoline hydrochloride, phenylephrine hydrochloride, methylephedrine hydrochloride, epinephrine hydrogen tartrate, etc. 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, dipotassium glycyrrhizinate, diclofenac sodium, bromfena Sodium chloride, berberine chloride, berberine sulfate, etc.
Antibacterial component or bactericidal component: For example, alkylpolyaminoethylglycine, sulfamethoxazole, sulfisoxazole, sulfamethoxazole sodium, sulfisomidine sodium, berberine sulfate, berberine chloride, boro Acid, etc.
Polysaccharides or derivatives thereof: for example, sodium hyaluronate, sodium chondroitin sulfate, etc.
Water-soluble polymers other than those described above: polyvinyl alcohol (completely or partially saponified product), polyvinylpyrrolidone, and the like.
Local anesthetic components: for example, oxybuprocaine hydrochloride, cocaine hydrochloride, cornecaine hydrochloride, dibucaine hydrochloride, tetracaine hydrochloride, diethylaminoethyl parabutylaminobenzoate, piperocaine hydrochloride, procaine hydrochloride, proparacaine hydrochloride, hexothiocaine hydrochloride, lidocaine hydrochloride.
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.

  The amount of these components in the pruritus inhibitor is appropriately selected according to the type of preparation, the type of active ingredient, etc., and the amounts of various components are known in the art. For example, it can be selected from the range of about 0.0001 to 30%, preferably about 0.001 to 10% with respect to the whole preparation. More specifically, the content of each component is, for example, as follows for the ophthalmic composition.

Decongestant component (vasoconstrictor or sympathomimetic drug): For example, 0.0001 to 0.5%, preferably 0.0005 to 0.3%, more preferably 0.001 to 0.1%.
Eye muscle modulator component: For example, 0.0001 to 0.5%, preferably 0.0005 to 0.1%, more preferably 0.0005 to 0.01%.
Anti-inflammatory component or astringent component: for example, 0.0001-10%, preferably 0.0001-5%.
Polysaccharide or derivative thereof: for example, 0.0001 to 2%, preferably 0.01 to 2%, more preferably 0.01 to 1%.
Water-soluble polymers other than those described above: For example, 0.001 to 10%, preferably 0.001 to 5%, more preferably 0.01 to 3%.
Antibacterial component or bactericidal component: For example, 0.00001 to 10%, preferably 0.0001 to 10%.
Local anesthetic component: For example, 0.001-1%, preferably 0.01-1%.
Steroid component: For example, 0.001 to 1%, preferably 0.01 to 1%.

  In addition, the pruritus inhibitor of the present invention is appropriately selected from various components and additives according to conventional methods according to its use and form as long as the effects of the invention are not impaired. You may contain together. As those components or additives, for example, carriers (water, aqueous solvents, aqueous or oily bases, etc.) commonly used in the preparation of semi-solids and liquids, thickeners, sugars, surfactants, Various additives such as preservatives, bactericides or antibacterial agents, pH regulators, tonicity agents, fragrances or cooling agents can be mentioned.

Although the typical component used for the pruritus inhibitor of this invention is illustrated below, it is not limited to these.
Thickeners: for example, dextran, carboxyvinyl polymer, alginic acid or a salt thereof, polyvinyl alcohol (completely or partially saponified product), polyvinylpyrrolidone, macrogol, chondroitin sodium sulfate and the like.
Sugars: for example, glucose, cyclodextrin and the like.
Sugar alcohols: For example, xylitol, sorbitol, mannitol and the like.
These may be d-form, l-form or dl-form.
Surfactant: For example, glycine-type amphoteric surfactant such as alkyldiaminoethylglycine; alkyl quaternary ammonium salt (specifically, cationic surfactant such as benzalkonium chloride, benzethonium chloride, etc.) The number indicates the number of moles added.
Preservatives, bactericides or antibacterial agents: for example, alkyldiaminoethylglycine hydrochloride, sodium benzoate, ethanol, benzalkonium chloride, benzethonium chloride, chlorhexidine gluconate, chlorobutanol, sorbic acid, potassium sorbate, sodium dehydroacetate, paraoxy Methyl benzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate, oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, biguanide compounds (specifically, polyhexamethylene biguanide, etc.), Glow Kill (manufactured by Rhodia) Name) etc.
pH adjusting agent: for example, hydrochloric acid, boric acid, aminoethylsulfonic acid, epsilon-aminocaproic acid, acetic acid, sodium hydroxide, sodium hydrogen carbonate, sodium carbonate, borax, 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.
Stabilizer: Dibutylhydroxytoluene, trometamol, sodium formaldehyde sulfoxylate (Longalite), tocopherol, sodium pyrosulfite, monoethanolamine, aluminum monostearate, etc.
Solubilizer, base: octyldodecanol, titanium oxide, potassium bromide, paraffin, castor oil, sesame oil, plastibase, lanolin, petrolatum, etc.

Thickener: 0.0005 to 50%, for example, preferably 0.001 to 10%
Saccharides: for example 0.001 to 10%, preferably 0.01 to 5%
Surfactant: For example, 0.0001 to 10%, preferably 0.005 to 5%
Preservative, bactericidal agent or antibacterial agent: for example, 0.00001-5%, preferably 0.0001-2%
pH regulator: for example, 0.00001-5%, preferably 0.0001-2%
Isotonizing agent: for example 0.001 to 10%, preferably 0.01 to 5%
Perfume or refreshing agent: for example, 0.00001-5%, preferably 0.0001-2%

  The pruritus inhibitor of this invention can be manufactured by a well-known method. Semi-solid and liquid preparations can be prepared by mixing the base and each component. Furthermore, if necessary, a filtration sterilization treatment process, a container filling process, and the like can be added.

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

Test Example 1 Preparation method for pruritus suppression test test preparation:
Test preparation 1: 0.015 g chlorpheniramine maleate, 0.01 g l-menthol, 0.35 g borax, 1.8 g boric acid, 0.05 g polysorbate 80, appropriate amount of purified water / hydrochloric acid / sodium hydroxide In addition, the total amount was 100 ml (pH = 7.5).
Test preparation 2: 0.015 g chlorpheniramine maleate, 1.0 g sodium cromoglycate (trade name Intal), 0.01 g l-menthol 0.35 g borax, 1.8 g boric acid, 0.05 g polysorbate 80, an appropriate amount of purified water / hydrochloric acid / sodium hydroxide was added to prepare a test preparation having a total amount of 100 ml (pH = 7.5).
Test preparation 3: 0.1 g alginic acid, borax, 1.8 g boric acid, 0.05 g polysorbate 80, purified water / hydrochloric acid / sodium hydroxide are added in appropriate amounts, and the total amount is 100 ml (pH = 7.5). It was.
Test formulation 4: 0.015 g chlorpheniramine maleate, 0.1 g alginic acid, 0.01 g l-menthol, 0.1 g potassium chloride 0.35 g borax, 1.8 g boric acid, 0.05 g polysorbate 80 Then, an appropriate amount of purified water / hydrochloric acid / sodium hydroxide was added to prepare a test preparation having a total amount of 100 ml (pH = 7.5).
Test formulation 5: 0.015 g chlorpheniramine maleate, 1.0 g sodium cromoglycate, 0.1 g sodium alginate, 0.1 g pyridoxine hydrochloride, 0.01 g l-menthol, 0.1 g potassium chloride 0.35 g An appropriate amount of borax, 1.8 g boric acid, 0.05 g polysorbate 80, purified water / hydrochloric acid / sodium hydroxide was added to prepare a test preparation having a total amount of 100 ml (pH = 7.5).

Test method:
As test animals, 6-week-old male hairless mice (HOS: HR-1) were divided into 5 groups per group, and the following tests were conducted. Each test animal was acclimated for 1 week in the breeding room after purchase and used for the test.
A physiological saline solution or a test preparation was instilled into each eyelid 5 μl per eye into the eyelid conjunctival sac of both eyes. 30 minutes after the instillation, a physiological saline solution of histamine hydrochloride prepared so that the dosage of one eye was 0.2 mg was similarly instilled into both eyes, and the test was conducted for 30 minutes immediately after administration of histamine. The number of times the animal scratches the eye with its hind limbs was filmed and counted.
In addition, the scratching behavior is a series of behaviors from when the test animal starts scratching the administration site in the hind limb after administration of the pruritus-inducing drug until the hind limb is released, and the number of scratches measured for each test animal is measured. The average value of each test preparation group and physiological saline group was determined as the number of scratches of the individual, and the pruritus suppression rate was calculated from the following formula.
Pruritus suppression rate (%) = {1-(average value of the number of scratches in the test preparation group ÷ average value of the number of scratches in the physiological saline group)} × 1 0 0

  When the scratch inhibition rate is calculated for the number of scratches of the test animals in each test preparation group, test preparation 1 is 23.0%, test preparation 2 is 26.0%, test preparation 3 is 8.1%, and test preparation 4 is 34. 2% and test preparation 5 was 39.8%.

  A pruritus inhibition test using hairless mice as test animals showed that alginic acid or a salt thereof has an itching inhibitory effect against itch caused by histamine. Moreover, in the preparation containing alginic acid or sodium alginate together with chlorpheniramine maleate or sodium cromoglycate, the number of scratches was reduced, and an effect of suppressing pruritus was observed.

Claims (14)

An agent for suppressing eye itching caused by an allergic reaction, comprising only alginic acid or a salt thereof. Alginic acid or a salt thereof,
An eye itching inhibitor resulting from an allergic reaction , comprising at least one selected from chlorpheniramine maleate or sodium cromoglycate. The eye itching inhibitor according to claim 2, further comprising one or more compounds selected from menthol, camphor or borneol. The eye itching inhibitor according to claim 2 or 3, further comprising at least one selected from vitamins, amino acids, and sugars. The composition further comprises one or more nonionic surfactants selected from polyoxyethylene-polyoxypropylene block copolymers, polyoxyethylene sorbitan fatty acid esters or polyoxyethylene hydrogenated castor oils. The eye itching inhibitor as described in any one of 4. The eye itching inhibitor according to any one of claims 2 to 5, further comprising an isotonic agent. The eye itching inhibitor according to claim 6, wherein the tonicity agent is potassium chloride. The eye irritation inhibitor according to any one of claims 2 to 7, further comprising boric acid and borax. The eye itching inhibitor as described in any one of Claims 2-8 which contains alginic acid or its salt at 0.001-5.0 w / v%. The eye itching inhibitor as described in any one of Claims 2-9 which contains at least 1 sort (s) selected from chlorpheniramine maleate or cromoglycate sodium by 0.001-5.0 w / v%. Inhibition of eye irritation according to any one of claims 2 to 10, comprising one or more compounds selected from menthol, camphor or borneol at a total amount of 0.0001 to 5 w / v%. Agent. One or more nonionic surfactants selected from polyoxyethylene-polyoxypropylene block copolymers, polyoxyethylene sorbitan fatty acid esters or polyoxyethylene hydrogenated castor oil are added in an amount of 0.0001 to 5 w / v. The eye itching inhibitor as described in any one of Claims 2-11 contained in%. Eye drops, eye washes, contact lens wetting solution for contact lenses eye drops, a contact lens eyewash, eye antipruritic agent according to any one of claims 2-12. Is for itch elicited by histamine, ocular pruritus inhibitor according to any one of claims 1 to 13.