Antipruritic agent

Abstract

To provide an antipruritic agent that can suppress occurrence of itching caused by a mediator other than histamine.SOLUTION: An antipruritic agent contains at least one kind of component selected from the group consisting of linalool, cineole, eucalyptus oil, lavender oil, rose oil, and peppermint oil. The antipruritic agent can be an agent that exerts antipruritic activity when a subject sniffs aroma. The antipruritic agent can be an agent for suppressing immediate itching, and / or persistent itching. The antipruritic agent can be used by being added to an external composition, an ophthalmic composition, an otolaryngologic composition, or a composition to be applied to an article or a space.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to an antipruritic agent and an antipruritic composition to be used by applying to the skin, etc. [Background technology]

[0002] Itching is caused by a variety of diseases. Skin diseases or disorders accompanied by itching include allergic symptoms to pollen, dust mites, house dust, etc., urticaria, atopic dermatitis, eczema / prurigo, contact dermatitis, seborrheic dermatitis, insect bites, eosinophilic pustular folliculitis, pemphigoid, mycosis fungoides, psoriasis, etc. In addition to skin diseases, itching can also be caused by liver disease, heart disease, blood disorders, collagen diseases, etc. Even people without skin diseases are prone to itching due to external stimuli such as dryness, cold, ultraviolet rays, friction from clothing, and a decrease in moisturizing ingredients due to excessive washing, as well as internal factors such as lack of sleep, nutrient deficiencies in the skin due to an unbalanced diet, aging, and stress. The number of people suffering from itching is increasing every year. Itching is a painful sensation that can disrupt sleep and cause stress from having to resist scratching, significantly impairing quality of life, concentration, judgment, and work efficiency.

[0003] Itching usually begins when itch-causing mediators are produced in the skin, which then bind to receptors on peripheral nerves distributed in the skin, activating the nerves. Histamine is a common mediator that causes itching, and antihistamines that act on histamine receptors (H1 receptors) are widely used to suppress itching. However, in recent years, knowledge has begun to emerge about histamine-independent itching caused by mediators other than histamine, and there is a need to develop itch suppression technologies that can address a variety of types of itching. Summary of the Invention [Problem to be solved by the invention]

[0004] Mediators that cause itch are broadly divided into histamine and other substances. Itching can be broadly divided into histamine-induced itch and itch caused by substances other than histamine. While antihistamines can provide an antipruritic effect against histamine-induced itch, as mentioned above, antihistamines are ineffective against histamine-independent itch (refractory itch). The mechanisms underlying histamine-independent refractory itch are diverse and incompletely understood, making it extremely difficult to develop antipruritic drugs for each mechanism. Therefore, there is a need for antipruritic drugs that suppress central itch transmission pathways rather than inhibiting the actions of each mediator individually, i.e., centrally acting antipruritic drugs that activate the endogenous antipruritic circuit. A main object of the present invention is to provide an antipruritic agent that is also effective against histamine-independent itching. [Means for solving the problem]

[0005] The present inventors have conducted extensive research to solve the above problems and have found that linalool, cineole, eucalyptus oil, lavender oil, rose oil, and peppermint oil effectively suppress the occurrence of itching caused by mediators other than histamine, and that in particular, smelling the scents of linalool, cineole, eucalyptus oil, lavender oil, rose oil, and peppermint oil effectively suppresses the occurrence of itching.

[0006] The present invention was completed based on the above findings, and provides the following [1] to [7]. [1] An antipruritic agent comprising at least one component selected from the group consisting of linalool, cineole, eucalyptus oil, lavender oil, rose oil, and peppermint oil. [2] The antipruritic agent according to [1], which exerts an antipruritic effect when a subject smells the fragrance. [3] The antipruritic agent according to [1] or [2], which suppresses histamine-independent itching. [4] The antipruritic agent according to any one of [1] to [3], which provides antipruritic effect lasting for 1 to 100 minutes. [5] An antipruritic composition comprising at least one component selected from the group consisting of linalool, cineole, eucalyptus oil, lavender oil, rose oil, and peppermint oil. [6] The composition according to [5], which is used once every 1 to 100 minutes. [7] The composition according to [5] or [6], wherein the amount of at least one component selected from the group consisting of linalool, cineole, eucalyptus oil, lavender oil, rose oil, and peppermint oil used per administration is 0.00001 to 5000 mg when the composition is an external composition, 0.00001 to 500 mg when the composition is an ophthalmic composition, or 0.00001 to 5000 mg when the composition is an otolaryngological composition. [Effects of the Invention]

[0007] The antipruritic agent of the present invention effectively suppresses itching caused by mediators other than histamine. Many skin diseases are accompanied by itching that is not mediated by histamine, but there are few preparations containing ingredients that suppress such itching. The antipruritic agent of the present invention is useful in that it can suppress histamine-independent itching. Furthermore, because anti-inflammatory agents, immunosuppressants, and the like suppress itching by suppressing inflammation of the disease that causes itching, they do not immediately suppress itching. They are also selective for itch mediators. In contrast, the antipruritic agent of the present invention suppresses the occurrence of histamine-independent itching at the central nervous system by activating the endogenous antipruritic circuit via olfactory stimulation, and therefore has an immediate effect on histamine-independent itching.

[0008] Furthermore, the antipruritic agent of the present invention suppresses itching not by percutaneous absorption but by the subject's inhalation of the fragrance. Therefore, the antipruritic agent of the present invention can be used in a wide range of applications, such as suppressing itching by adding it to preparations to be applied to the body, such as topical compositions, ophthalmic compositions, and otolaryngological compositions, but also to preparations to be attached to wearable articles, such as clothing, masks, and glasses, or to preparations to be attached to the walls of a house or the inside of a car, or to be dispersed into the air inside a house or car. [Brief explanation of the drawings]

[0009] [Figure 1] This figure shows that scratching behavior in mice induced by intradermal administration of chloroquine was reduced in response to airborne linalool, cineole, or eucalyptus oil. (A) is a graph plotting the number of scratching behaviors over a 5-minute period against the elapsed time, and (B) is a graph showing the cumulative number of scratching behaviors over 6, 15, and 30 minutes. [Figure 2] This figure shows that scratching behavior in mice induced by intradermal administration of chloroquine was reduced in response to airborne lavender oil, rose oil, or peppermint oil. (A) is a graph plotting the number of scratching behaviors over a 5-minute period against the elapsed time, and (B) is a graph showing the cumulative number of scratching behaviors over 5, 15, and 30 minutes. [Figure 3] This figure shows that in olfactory-blocked mice, scratching behavior induced by intradermal administration of chloroquine did not significantly change in response to airborne linalool. (A) is a graph plotting the number of scratching behaviors over a 5-minute period against the elapsed time. (B) The left graph shows the cumulative number of scratching behaviors over a 6-minute period, and the right graph shows the cumulative number of scratching behaviors over a 30-minute period. [Figure 4] This figure shows that in olfactory-deprived mice, scratching behavior induced by intradermal administration of chloroquine did not significantly change in response to airborne lavender oil. (A) is a graph plotting the number of scratching incidents over a 5-minute period against the elapsed time. (B) The left graph shows the cumulative number of scratching incidents over a 5-minute period, and the right graph shows the cumulative number of scratching incidents over a 30-minute period. [Figure 5]This figure shows that in olfactory-deprived mice, scratching behavior induced by intradermal administration of chloroquine did not significantly change in response to airborne eucalyptus oil. (A) is a graph plotting the number of scratching incidents over a 5-minute period against the elapsed time. (B) The left graph shows the cumulative number of scratching incidents over a 5-minute period, and the right graph shows the cumulative number of scratching incidents over a 30-minute period. DETAILED DESCRIPTION OF THE INVENTION

[0010] The present invention will be described in detail below. (1) Antipruritic The antipruritic agent of the present invention contains at least one component (hereinafter sometimes referred to as "component (A)") selected from the group consisting of linalool, cineole, eucalyptus oil (particularly eucalyptus essential oil), lavender oil (particularly lavender essential oil), rose oil, and mint oil. Linalool, cineole, eucalyptus oil, lavender oil, rose oil, and / or mint oil are active ingredients of the antipruritic agent and can be used as is or added to various compositions. Antipruritic agents are also called antipruritic agents. Linalool is contained in essential oils such as bergamot, rosewood, basil, thyme, neroli, lavandin, geranium, petitgrain, clary sage, ylang-ylang, alpinia speciosa, sage, jasmine, palmarosa, and calmodance, and can therefore also be used as these essential oils. Furthermore, since cineole is contained in essential oils such as bay leaf, mugwort, basil, wormwood, rosemary, and sage in addition to eucalyptus oil, it can also be used as these essential oils.

[0011] The antipruritic agent of the present invention can be an antipruritic agent that not only alleviates itchy symptoms but also suppresses the occurrence of itching. It can also be an agent for suppressing itching other than histamine-mediated itching, i.e., histamine-independent itching, and in particular, it can be an agent for suppressing the occurrence of histamine-independent itching. Histamine-induced itching is itchy with a rapid onset and short duration, and antihistamines suppress such immediate-type itching. In contrast, the antipruritic agent of the present invention can be used to suppress not only immediate-type itching but also delayed-type or persistent itching. The antipruritic agent of the present invention can be used to provide antipruritic relief for, for example, 1 minute or more, 3 minutes or more, 5 minutes or more, 7 minutes or more, 10 minutes or more, 15 minutes or more, 20 minutes or more, 30 minutes or more, 40 minutes or more, or 50 minutes or more, and can also be used to provide antipruritic relief for 100 minutes or less, 80 minutes or less, 60 minutes or less, 40 minutes or less, or 30 minutes or less.

[0012] The antipruritic agent of the present invention can be an antipruritic agent that suppresses itching when a subject smells the aroma, i.e., an antipruritic agent that suppresses itching via the sense of smell. Because the antipruritic agent of the present invention can be an antipruritic agent that suppresses itching via the sense of smell, it can be an agent that suppresses itching by activating an endogenous antipruritic circuit or a central antipruritic agent. The antipruritic agent of the present invention can also be used to suppress itching caused by histamine-independent diseases or disorders. Examples of histamine-independent diseases or disorders include skin diseases such as urticaria, atopic dermatitis, eczema / prurigo, contact dermatitis, seborrheic dermatitis, insect bites, eosinophilic pustular folliculitis, pemphigoid, mycosis fungoides, and psoriasis; and non-skin diseases such as liver / gallbladder disease, heart disease, chronic kidney disease, diabetes, thyroid dysfunction, blood diseases, collagen diseases, cancer, neuropathic pruritus (such as multiple sclerosis), psychogenic pruritus caused by mental disorders, and drug-induced pruritus caused by morphine, contrast agents, and the like. The antipruritic agent of the present invention can also be used to suppress itching associated with dialysis.

[0013] (2) Antipruritic composition The present invention encompasses an antipruritic composition containing at least one component (component (A)) selected from the group consisting of linalool, cineole, eucalyptus oil, lavender oil, rose oil, and peppermint oil. The antipruritic composition of the present invention encompasses cases in which linalool, cineole, eucalyptus oil, lavender oil, rose oil, and / or peppermint oil are contained as active ingredients that exert an antipruritic effect. The antipruritic agent (component (A)) of the present invention can be incorporated into various compositions, or can be incorporated into articles by kneading it in before molding.

[0014] The concentration of component (A) in the antipruritic composition to be applied to the body (by application, spraying, etc.) can be 0.000001% by mass or more, 0.00001% by mass or more, 0.0001% by mass or more, 0.0001% by mass or more, 0.001% by mass or more, 0.01% by mass or more, 0.1% by mass or more, 0.5% by mass or more, or 1% by mass or more, or 50% by mass or less, 40% by mass or less, 30% by mass or less, 25% by mass or less, 20% by mass or less, 12% by mass or less, 10% by mass or less, 8% by mass or less, 5% by mass or less, 4% by mass or less, 2.5% by mass or less, 1% by mass or less, 0.5% by mass or less, 0.2% by mass or less, 0.1% by mass or less, or 0.05% by mass or less, based on the total amount of the composition. Within this range, the antipruritic effect can be sufficiently exerted.

[0015] The concentration of component (A) in the antipruritic composition to be applied (sprayed, sprayed, etc.) to an item or space other than the body can be 0.000001% by mass or more, 0.00001% by mass or more, 0.0001% by mass or more, 0.0001% by mass or more, 0.01% by mass or more, 0.1% by mass or more, 1% by mass or more, 3% by mass or more, or 5% by mass or more, relative to the total amount of the composition, and can be 40% by mass or less, 30% by mass or less, 20% by mass or less, 10% by mass or less, 5% by mass or less, 2.5% by mass or less, or 1% by mass or less. Within this range, the antipruritic effect can be sufficiently exerted.

[0016] Because the antipruritic effect of component (A) is long-lasting, the antipruritic composition of the present invention can continuously suppress itching even when the application interval is extended. Whether the antipruritic composition of the present invention is applied to the body or to an item or space other than the body, the application interval can be 1 minute or more, 3 minutes or more, 5 minutes or more, 7 minutes or more, 10 minutes or more, 15 minutes or more, 20 minutes or more, 30 minutes or more, 40 minutes or more, or 50 minutes or more. Even with an interval within this range, itching can be continuously suppressed. Furthermore, the application interval can be 100 minutes or less, 80 minutes or less, 60 minutes or less, 40 minutes or less, or 30 minutes or less. Within this range, itching can be continuously suppressed.

[0017] External composition Examples of the formulation of the antipruritic composition for external use include solutions, suspensions, emulsions, creams, emulsion ointments, ointments, gels, liniments, lotions, foams, sprays, aerosols, pump foams, sticks, and sheets. Emulsion compositions such as emulsions, creams, and emulsion ointments may be either oil-in-water or water-in-oil. Of these, oil-in-water compositions are preferred. Furthermore, when the antipruritic external composition is a bath additive, the formulation may be in the form of a tablet, liquid, emulsion, suspension, powder, granules, etc., and can be used by adding it to hot or cold water. The antipruritic topical composition of the present invention may be a topical composition for skin, a topical composition for mucous membranes such as lips, a topical composition for hair or scalp, etc. It may also be a pharmaceutical composition or a quasi-drug composition.

[0018] The concentration of component (A) in the antipruritic composition for external use can be 0.000001% by mass or more, 0.00001% by mass or more, 0.0001% by mass or more, 0.001% by mass or more, 0.01% by mass or more, or 0.1% by mass or more, relative to the total amount of the composition, and can be 50% by mass or less, 25% by mass or less, 10% by mass or less, 5% by mass or less, 2.5% by mass or less, 1% by mass or less, 0.5% by mass or less, 0.2% by mass or less, 0.1% by mass or less, or 0.05% by mass or less. Within this range, the antipruritic effect can be sufficiently exerted. When the antipruritic topical composition is a bath additive, the concentration of component (A) in the composition (preparation) can be 0.000001% by mass or more, 0.00001% by mass or more, 0.0001% by mass or more, 0.001% by mass or more, 0.01% by mass or more, 0.1% by mass or more, 0.5% by mass or more, or 1% by mass or more, and can be 12% by mass or less, 8% by mass or less, 4% by mass or less, or 2% by mass or less. Within these ranges, a sufficient antipruritic effect can be exerted. When added to hot or cold bathwater, the amount of component (A) added can be 0.005g or more, 0.05g or more, 0.25g or more, or 0.5g or more, and 6g or less, 4g or less, 2g or less, or 1g or less.

[0019] The antipruritic topical composition can be applied to the skin by painting or spraying, depending on the dosage form. The frequency of application to the skin can be 1 to 5 times or 1 to 3 times a day, or it can be applied whenever itching is felt. For example, for persistent itching, it can be applied at intervals of once every 1 to 100 minutes as described above, thereby maintaining a state in which itching is suppressed. The amount of the antipruritic topical composition to be used may be such that the amount of component (A) used per application is 0.00001 mg or more, 0.0001 mg or more, 0.001 mg or more, 0.005 mg or more, 0.01 mg or more, 0.05 mg or more, 0.1 mg or more, or 0.5 mg or more, and is 5000 mg or less, 1000 mg or less, 500 mg or less, 100 mg or less, 70 mg or less, 50 mg or less, 20 mg or less, or 10 mg or less.

[0020] In addition to component (A), the antipruritic topical composition may contain additives that can be used in topical preparations, and one or more physiologically or pharmacologically active ingredients other than component (A), within a range that does not interfere with the effects of the present invention.

[0021] Examples of additives include bases, antioxidants, surfactants, thickeners, pH adjusters, stabilizers, chelating agents, irritation reducers, ultraviolet absorbers, ultraviolet scattering agents, colorants, and fragrances.

[0022] The base includes an oily base and an aqueous base. Oily bases include hydrocarbons such as petrolatum (white petrolatum, yellow petrolatum), gelling hydrocarbons (such as Plastibase), ozokerite, ceresin, microcrystalline wax, squalene, squalane, α-olefin oligomers, paraffin, liquid paraffin, and light liquid paraffin; higher alcohols such as cetyl alcohol, cetostearyl alcohol, stearyl alcohol, and behenyl alcohol; sterols such as cholesterol, phytosterol, and phytosteryl hydroxystearate; shea butter, Vegetable fats such as carnauba wax, cocoa butter, and candelilla wax; vegetable oils such as avocado oil, olive oil, camellia oil, macadamia nut oil, evening primrose oil, jojoba oil, rapeseed oil, egg yolk oil, sesame oil, castor oil, safflower oil, cottonseed oil, soybean oil, tea seed oil, rice bran oil, rice germ oil, wheat germ oil, peanut oil, sunflower oil, almond oil, corn oil, coconut oil, orange oil, sage oil, palm oil, mink oil, meadowfoam oil, lavender oil, rosemary oil, and rosehip oil; lanolin, orange roughy oil, squalane, horse oil, spermaceti, and and animal fats and oils such as beeswax; hydrogenated oils; silicone oils such as methylpolysiloxane, crosslinked methylpolysiloxane, highly polymerized methylpolysiloxane, cyclic silicone, alkyl-modified silicone, crosslinked alkyl-modified silicone, amino-modified silicone, polyether-modified silicone, polyglycerin-modified silicone, crosslinked polyether-modified silicone, crosslinked alkylpolyether-modified silicone, silicone-alkyl chain co-modified polyether-modified silicone, silicone-alkyl chain co-modified polyglycerin-modified silicone, polyether-modified branched silicone, polyglycerin-modified branched silicone, acrylic silicone, phenyl-modified silicone, and silicone resin; natural polymer derivatives such as ethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethylcellulose, and cationized guar gum; synthetic polymers such as polyvinylpyrrolidone, carboxyvinyl polymer, and alkyl acrylate methacrylate copolymer; natural polymers such as carrageenan, alginic acid, cellulose, guar gum, quince seed, dextran, and gellan gum;Esters such as diethylhexyl succinate, isopropyl myristate, octyldodecyl myristate, isopropyl palmitate, cetyl palmitate, isononyl isononanoate, pentaerythrityl tetra-2-ethylhexanoate, and caprylic / capric triglyceride; polysaccharides such as dextrin and maltodextrin; glycol ethers such as ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monopropyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monopropyl ether, diethylene glycol monobutyl ether, propylene glycol monoethyl ether, propylene glycol monopropyl ether, dipropylene glycol monoethyl ether, and dipropylene glycol monopropyl ether; Examples of aqueous bases include water; lower alcohols such as ethanol and isopropanol; and polyhydric alcohols such as polyethylene glycol, propylene glycol, dipropylene glycol, 1,3-butylene glycol, glycerin, diglycerin, and isoprene glycol.

[0023] Examples of antioxidants include dibutylhydroxytoluene, butylhydroxyanisole, p-hydroxyanisole, sorbic acid, sodium sulfite, ascorbic acid, ascorbic acid derivatives (ascorbic acid stearate, ascorbic acid palmitate, ascorbyl dipalmitate, ascorbic acid monophosphate, ascorbic acid diphosphate, ascorbic acid triphosphate, ascorbic acid sulfate, etc.), tocopherol, tocopherol derivatives (tocopherol acetate, tocopherol succinate, tocopherol calcium succinate, etc.), erythorbic acid, L-cysteine ​​hydrochloride, lycopene, glutathione, propyl gallate, tannic acid, epigallocatechin, anthocyanin, hydroxytyrosol, nordihydroguaiaretic acid, caffeic acid, and enzymes (catalase, superoxide dismutase, glutathione peroxidase, elastase, etc.).

[0024] Surfactants include POE-2-decyltetradecyl alcohol, POE-alkyl ethers such as polyoxyethylene oleyl ether and polyoxyethylene cetyl ether; sorbitan monostearate, sorbitan sesquistearate, sorbitan tristearate, sorbitan monooleate, and other sorbitan fatty acid esters; POE (20) sorbitan monoisostearate, POE (20) sorbitan monooleate, POE (20) sorbitan monostearate, POE (20) sorbitan monococonut oil fatty acid POE (20) sorbitan, and la POE-sorbitan fatty acid esters such as POE(80) sorbitan urate; glycerin fatty acid esters such as glyceryl monostearate and glyceryl oleate; POE-glycerin fatty acid esters such as polyoxyethylene glyceryl stearate and polyoxyethylene glyceryl trioleate; POE-dihydrocholesterol ester, POE-hydrogenated castor oil (e.g., polyoxyethylene hydrogenated castor oil 40 (HCO-40), polyoxyethylene hydrogenated castor oil 50 (HCO-50), polyoxyethylene hydrogenated castor oil POE-hydrogenated castor oils such as POE-60 (HCO-60), polyoxyethylene hydrogenated castor oil 80, etc.; POE-castor oils such as POE(3) castor oil, POE(20) castor oil, etc.; POE-hydrogenated castor oil fatty acid esters such as POE-hydrogenated castor oil isostearate; POE-alkylaryl ethers; glycerin alkyl ethers such as cumyl alcohol, batyl alcohol, and selachyl alcohol; POE-glycerin alkyl ethers such as POE-monostearyl glyceryl ether; poly stearate POE fatty acid esters such as lyoxyl; POE sterols and hydrogenated sterols such as POE(20) phytosterol, POE(30) phytosterol, POE(25) phytostanol, and POE(30) cholestanol; sucrose fatty acid esters such as sucrose palmitate, sucrose stearate, sucrose oleate, sucrose isostearate, sucrose linoleate, and sucrose linolenate; polyethylene glycol fatty acid esters such as polyethylene glycol dioleate;Examples of surfactants include polyglycerin fatty acid esters such as alkyl polyglycosides, diglyceryl monostearate, diglyceryl monoisostearate, decaglyceryl monostearate, decaglyceryl monooleate, decaglyceryl pentaoleate, and hexaglyceryl polyricinoleate; and nonionic surfactants such as alkyl-modified silicones and emulsifying silicone elastomers. Also, higher alkyl sulfates (e.g., sodium lauryl sulfate, potassium lauryl sulfate, etc.); alkyl ether sulfates (e.g., POE-lauryl triethanolamine sulfate, POE-lauryl sodium sulfate, etc.); N-acyl sarcosinates (e.g., sodium lauroyl sarcosinate, etc.); higher fatty acid amide sulfonates (e.g., sodium stearoyl methyl taurate, sodium myristoyl methyl taurate, sodium cocoyl methyl taurate, sodium cocoyl methyl taurate, etc.); phosphate esters and their salts (sodium POE-oleyl ether phosphate, POE-stearyl ether phosphate, potassium cetyl phosphate, cetyl phosphate, etc.); sulfosuccinates (e.g., sodium di-2-ethylhexyl sulfosuccinate, etc.); alkyl benzene sulfonates (e.g., sodium linear dodecyl benzene sulfonate, etc.); Other examples of anionic surfactants include: sodium lauroyl glutamate, higher fatty acid ester sulfate salts (e.g., hydrogenated coconut oil fatty acid glycerin sodium sulfate, etc.); N-acyl glutamates (e.g., monosodium lauroyl glutamate, sodium stearoyl glutamate, sodium myristoyl glutamate, etc.); N-acyl alanine salts (e.g., sodium lauroyl methyl alanine, cocoyl alanine triethanolamine salt, etc.); sulfated oils (e.g., turmeric oil, etc.); POE-alkyl ether carboxylic acids; POE-alkyl allyl ether carboxylic acid salts; α-olefin sulfonates; higher fatty acid ester sulfonates; secondary alcohol sulfate salts; higher fatty acid alkylolamide sulfate salts; sodium lauroyl monoethanolamide succinate; N-palmitoyl aspartic acid ditriethanolamine; and sodium caseinate. Further examples include cationic surfactants such as mono- or di-long-chain alkyl tertiary or quaternary ammonium salts having a linear or branched long-chain alkyl group, to which alkylene oxide may be added. Also included are amphoteric surfactants such as carbobetaines, sulfobetaines, imidazolinium betaines, and amidobetaines. Other examples include naturally occurring surfactants such as lecithin, hydrogenated lecithin, saponin, sodium surfactin, and bile acid.

[0025] Examples of thickeners include guar gum, locust bean gum, carrageenan, xanthan gum, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, acrylic acid alkyl methacrylate copolymer, polyethylene glycol, bentonite, alginic acid, macrogol, and cellulose-based thickeners (methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, carboxymethyl cellulose, carboxyethyl cellulose, etc.).

[0026] Examples of pH adjusters include inorganic acids (such as hydrochloric acid and sulfuric acid), organic acids (such as lactic acid, sodium lactate, citric acid, sodium citrate, succinic acid, and sodium succinate), inorganic bases (such as potassium hydroxide and sodium hydroxide), and organic bases (such as triethanolamine, diisopropanolamine, and triisopropanolamine).

[0027] The stabilizer may include sodium polyacrylate, dibutylhydroxytoluene, butylhydroxyanisole, and the like.

[0028] Chelating agents include EDTA disodium salt and EDTA calcium disodium salt.

[0029] Irritation reducers include licorice extract and sodium alginate.

[0030] UV absorbers include 2-ethylhexyl paramethoxycinnamate, 2-[4-(diethylamino)-2-hydroxybenzoyl]benzoic acid hexyl ester, methylenebisbenzotriazolyltetramethylbutylphenol, bisethylhexyloxyphenol methoxyphenyl triazine, ethylhexyl triazone, 2,4,6-tris[4-(2-ethylhexyloxycarbonyl)anilino]-1,3,5-triazine, and dimethoxybenzylidene oxoimidazolidine propionate. Examples include 2-ethylhexyl pionate, 2,4-bis-[{4-(2-ethylhexyloxy)-2-hydroxy}-phenyl]-6-(4-methoxyphenyl)-1,3,5-triazine, t-butylmethoxydibenzoylmethane, dibenzylidene dioxoimidazolidine ethylhexyl propylonate, ethoxyhexyl triazoline, para-aminobenzoic acid and its derivatives, octyl paradimethylaminobenzoate, ethylene glycol salicylate, and dihydroxybenzophenone.

[0031] Examples of ultraviolet scattering agents include inorganic compounds such as zinc oxide, titanium oxide, iron oxide, cerium oxide, zirconium oxide, titanium silicate, zinc silicate, anhydrous silicic acid, cerium silicate, and hydrous silicic acid; these inorganic compounds coated with inorganic powder such as hydrous silicic acid, aluminum hydroxide, mica, and talc; these inorganic compounds composited with resin powder such as polyamide, polyethylene, polyester, polystyrene, and nylon; and these inorganic compounds treated with silicone oil, fatty acid aluminum salt, or the like.

[0032] Examples of colorants include those listed in the Legal Dyes Handbook (edited by the Japan Cosmetic Industry Association (2004)).

[0033] Examples of physiologically or pharmacologically active ingredients other than component (A) include anti-inflammatory agents, local anesthetics, antibacterial ingredients, antihistamines, antipruritics other than component (A) and antihistamines, moisturizing ingredients, vitamins, terpenoids other than component (A), peptides or derivatives thereof, blood circulation promoting ingredients, cell activating ingredients, anti-aging ingredients, keratin softening ingredients, astringent ingredients, mucopolysaccharides, amino acids, proteins, plant extracts, seaweed extracts, and antifungal agents.

[0034] The anti-inflammatory agent may be either a non-steroidal or a steroidal agent. Non-steroidal anti-inflammatory agents include allantoin, glycyrrhizinic acid, glycyrrhetinic acid, acetaminophen, epsilon-aminocaproic acid, berberine, azulene, bromelain, and zinc; plant extracts such as licorice extract, sage extract, and rosemary extract; enzyme-based anti-inflammatory agents such as lysozyme, serrapeptase, and semi-alkaline proteinase; fenamic acid-based anti-inflammatory agents such as mefenamic acid, tolfenamic acid, and flufenamic acid; acemetacin, indomethacin, indomethacin farnesyl, etodolac, diclofenac, sulindac, and nabumetamol. arylacetic acid anti-inflammatory agents such as thiamin, fenbufen, proglumetacin, and mofezolac; propionic acid anti-inflammatory agents such as aminoprofen, ibuprofen, oxaprozin, ketoprofen, zaltoprofen, tiaprofenic acid, naproxen, flurbiprofen, zaltoprofen, ibuprofen piconol, flurbiprofen axetil, fenoprofen, pranoprofen, and loxoprofen; and oxicam anti-inflammatory agents such as ampiroxicam, tenoxicam, piroxicam, meloxicam, and lornoxicam. These may be salts, such as dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, stearyl glycyrrhizinate, stearyl glycyrrhetinate, indomethacin hydrochloride, diclofenac sodium salt, bromfenac sodium salt, berberine sulfate, berberine hydrochloride, berberine tannate, azulene sulfonate sodium salt, zinc sulfate, zinc lactate, lysozyme hydrochloride, ufenamate (butyl flufenamate), proglumetacin maleate, fenoprofen calcium salt, and loxoprofen sodium salt.

[0035] Steroidal anti-inflammatory agents include prednisolone, hydrocortisone, cortisone, dexamethasone, triamcinolone, triamcinolone acetonide, difluprednate, mometasone, diflucortolone, fluocinside, beclomethasone, deprodone, alclometasone, flumethasone, amcinonide, clobetasone, diflorasone, and derivatives thereof. Derivatives include prednisolone esters such as prednisolone valerate acetate, prednisolone succinate, prednisolone acetate, and prednisolone phosphate; dexamethasone esters such as dexamethasone valerate, dexamethasone propionate, dexamethasone acetate, dexamethasone phosphate, dexamethasone metasulfobenzoate, dexamethasone cipesilate, and dexamethasone palmitate; hydrocortisone butyrate (especially hydrocortisone-17-butyrate); and hydrocortisone. Examples of hydrocortisone esters include acetate, hydrocortisone succinate, hydrocortisone butyrate propionate, and hydrocortisone phosphate, mometasone furoate, diflucortolone valerate, beclomethasone propionate, beclomethasone dipropionate, clobetasone butyrate, deprodone propionate, alclometasone propionate, flumethasone pivalate, clobetasone propionate, clobetasone butyrate, and diflorasone acetate.

[0036] Examples of local anesthetics include local anesthetics having an amine structure or an amide structure such as lidocaine, dibucaine, mepivacaine, bupivacaine, ropivacaine, levobupivacaine, oxethazaine, and salts thereof; local anesthetics having an amine structure or an ester structure such as cocaine, procaine, chloroprocaine, tetracaine, and salts thereof; and local anesthetics having an ester structure such as ethyl aminobenzoate and oxypolyethoxydodecane. Examples of salts include lidocaine hydrochloride, dibucaine hydrochloride, mepivacaine hydrochloride, bupivacaine hydrochloride, ropivacaine hydrochloride, levobupivacaine hydrochloride, oxethazaine hydrochloride, cocaine hydrochloride, procaine hydrochloride, chloroprocaine hydrochloride, and tetracaine hydrochloride.

[0037] Examples of antibacterial ingredients include isopropylmethylphenol, quaternary ammonium salts such as benzethonium chloride and benzalkonium chloride, salicylic acid, benzoic acid, amorolfine, chlorhexidine, acrinol, ethanol, cresol, gluconic acid and its derivatives, povidone-iodine, potassium iodide, iodine, triclocarban, triclosan, photosensitizer No. 101, photosensitizer No. 201, phenoxyethanol, alkyldiaminoglycine hydrochloride, and salts thereof.

[0038] Antihistamines include ethanolamine antihistamines such as diphenhydramine, bromodiphenhydramine, clemastine, chlorphenoxamine, diphenylpyraline, doxylamine, orphenadrine, and phenyltoloxamine; propylamine antihistamines such as chlorpheniramine, dimethindene, and talastine; ethylenediamine antihistamines such as mepyramine, methapyrilene, and tripelennamine; phenothiazine antihistamines such as alimemazine, hydroxyethylpromethazine, isothipendyl, mequitazine, oxomemazine, and promethazine; piperazine antihistamines such as benzodiazepine, cetirizine, homochlorcyclizine, cyclizine, hydroxyzine, levocetirizine, meclizine, and oxatomide, ketotifen, olopatadine, fexofenadine, loratadine, terfenadine, antazoline, azatadine, bamipine, cyproheptadine, deptropine, ebastine, emedastine, epinastine, mebhydroline, mizolastine, pimethixene, pyrobutamine, quifenadine, rupatadine, triprolidine, acrivastine, astemizole, azelastine, bilastine, desloratadine, and salts thereof. Salts include diphenhydramine hydrochloride, bromodiphenhydramine hydrochloride, clemastine fumarate, chlorphenoxamine hydrochloride, diphenylpyraline hydrochloride, doxylamine succinate, orphenadrine hydrochloride, phenyltoloxamine citrate, chlorpheniramine maleate, chlorpheniramine fumarate, dimethindene maleate, mepyramine maleate, methapyrilene hydrochloride, tripelennamine hydrochloride, alimemazine tartrate, isothipendyl hydrochloride, oxomemazine hydrochloride, and promethazine hydrochloride. salt, cetirizine hydrochloride, homochlorcyclizine hydrochloride, cyclizine hydrochloride, hydroxyzine hydrochloride, levocetirizine hydrochloride, meclizine hydrochloride, ketotifen fumarate, olopatadine hydrochloride, fexofenadine hydrochloride, antazoline hydrochloride, azatadine dimaleate, bamipine hydrochloride, cyproheptadine hydrochloride, deptropinc citrate, emedastine fumarate, epinastine hydrochloride, mebhydroline napadisilate, rupatadine fumarate, triprolidine hydrochloride, azelastine hydrochloride and the like.

[0039] Antipruritic agents other than component (A) and antihistamines include crotamiton, ichthammol, moctal, thymol, etc.

[0040] Examples of moisturizing ingredients include polyhydric alcohols such as glycerin, dipropylene glycol, 1,3-butylene glycol, propylene glycol, polyethylene glycol, diglycerin, pentanediol, hexanediol, and octanediol; sugars such as trehalose, xylitol, and sorbitol; polymeric compounds such as keratin, chitin, and chitosan; lipids such as ceramide, cholesterol, and phospholipids; and plant extracts such as chamomile extract, witch hazel extract, tea extract, and aloe extract.

[0041] Vitamins include retinol derivatives such as retinol, retinol acetate, and retinol palmitate, retinal, retinoic acid, methyl retinoate, ethyl retinoate, retinol retinoate, vitamin A such as d-δ-tocopheryl retinoate, α-tocopheryl retinoate, and β-tocopheryl retinoate; β-carotene, α-carotene, γ-carotene, δ-carotene, lycopene, zeaxanthin, and cryptoxanthin. Provitamins A such as dl-α-tocopherol, echinenone, etc.; Vitamin E such as δ-tocopherol, dl-α-tocopherol, dl-α-tocopherol acetate, dl-α-tocopherol succinate, dl-α-tocopherol calcium succinate, and tocopherol nicotinate; Riboflavin, flavin mononucleotide, flavin adenine dinucleotide, riboflavin butyrate, riboflavin tetrabutyrate, and riboflavin 5'-phosphate ester. Vitamin B2 compounds such as sodium nicotinate and riboflavin tetranicotinate; nicotinic acids such as dl-α-tocopherol nicotinate, benzyl nicotinate, methyl nicotinate, β-butoxyethyl nicotinate, and 1-(4-methylphenyl)ethyl nicotinate; vitamin C compounds such as ascorbyl stearate, L-ascorbyl dipalmitate, ascorbyl tetraisopalmitate (ascorbyl tetra-2-hexyldecanoate), ascorbic acid, sodium ascorbate, dehydroascorbic acid, sodium ascorbyl phosphate, magnesium ascorbyl phosphate, ascorbyl glucoside, ascorbigen-A, ascorbyl stearate, and ascorbyl palmitate; vitamin D compounds such as methylhesperidin, ergocalciferol, and cholecalciferol; vitamin K compounds such as phylloquinone and farnoquinone;Vitamin B1 compounds such as dibenzoyl thiamine, dibenzoyl thiamine hydrochloride, thiamine hydrochloride, thiamine cetyl hydrochloride, thiamine thiocyanate, thiamine lauryl hydrochloride, thiamine nitrate, thiamine monophosphate, thiamine lysine salt, thiamine triphosphate, thiamine monophosphate ester, thiamine diphosphate ester, thiamine diphosphate ester hydrochloride, thiamine triphosphate, thiamine triphosphate monophosphate; pyridoxine hydrochloride, pyridoxine acetate, pyridoxal hydrochloride, pyridoxal 5'-phosphate, pyridoxal hydrochloride Vitamin B6 compounds such as cyanocobalamin, hydroxocobalamin, and deoxyadenosylcobalamin; folic acids such as folic acid and pteroylglutamic acid; nicotinic acids such as nicotinic acid and nicotinamide; pantothenic acids such as pantothenic acid, calcium pantothenate, pantothenyl alcohol (panthenol), D-pantethine, D-pantethine, coenzyme A, and pantothenyl ethyl ether; biotins such as bioticin; vitamin-like factors such as gamma-oryzanol, carnitine, ferulic acid, alpha-lipoic acid, and orotic acid;

[0042] Examples of terpenoids other than component (A) include menthol, camphor, borneol, geraniol, citronellol, anethole, limonene, eugenol, etc. The terpenoid may be in any of the d-, l-, or dl-form.

[0043] Examples of peptides or derivatives thereof include keratin-decomposed peptides, hydrolyzed keratin, collagen, gelatin, elastin, elastin-decomposed peptides, collagen-decomposed peptides, hydrolyzed collagen, and hydrolyzed silk.

[0044] Preferred examples of blood circulation-promoting ingredients include plant-derived ingredients, such as ingredients derived from ginseng, angelica tree, arnica, ginkgo, emmeisou, Dutch oak, gentian, burdock, rice, hawthorn, shiitake mushroom, European hawthorn, European juniper, cnidium rhizome, Swertia japonica, thyme, clove, tangerine peel, angelica acutiloba, peach kernel, spruce, carrot, garlic, butcher's broom, grape, peony, horse chestnut, melissa, yuzu, coix seed, rosemary, rosehip, peach, apricot, walnut, corn, etc. (e.g., extracts of these plants), and glucosyl hesperidin.

[0045] Cell-activating ingredients include amino acids such as gamma-aminobutyric acid, gamma-amino-beta-hydroxybutyric acid, and epsilon-aminocaproic acid, vitamins such as retinol, thiamine, riboflavin, pyridoxine hydrochloride, pantothenic acids, and biotin, alpha-hydroxy acids such as glycolic acid and lactic acid, tannins, flavonoids, saponin, allantoin, photosensitizer No. 301, placenta extract, hinokitiol, cepharanthine, and kiwi seed extract.

[0046] Anti-aging ingredients include pangamic acid, kinetin, ursolic acid, turmeric extract, sphingosine derivatives, silicon, silicic acid, N-methyl-L-serine, and mevalonolactone.

[0047] Examples of keratin softening ingredients include salicylic acid, salicylic acid derivatives, glycolic acid, fruit acids, phytic acid, sulfur, ethyl alcohol, isopropyl alcohol, propanol, butanol, 1,3-butylene glycol, propylene glycol, polyethylene glycol (macrogol), glycerin, benzyl alcohol, phenylethyl alcohol, propylene carbonate, hexyldodecanol, allantoin, dimethyl sulfoxide, dimethylacetamide, dimethylformamide, triethanolamine, diisopropyl adipate, ethyl laurate, lanolin, fatty acid dialkylolamide, urea, sulfur, resorcinol, glycolic acid, phytic acid, lactic acid, lactate, sodium hydroxide, and potassium hydroxide.

[0048] Astringent ingredients include zinc paraphenolsulfonate, zinc oxide, and ethanol.

[0049] Examples of mucopolysaccharides include heparin-like substances; chondroitin sulfates or salts thereof such as chondroitin sulfate and sodium chondroitin sulfate; dermatan sulfates or salts thereof such as dermatan sulfate and sodium dermatan sulfate; hyaluronic acid or salts thereof such as hyaluronic acid, sodium hyaluronate, potassium hyaluronate, magnesium hyaluronate, and calcium hyaluronate; hyaluronic acid derivatives or salts thereof such as acetylated hyaluronic acid, sodium acetylated hyaluronate, potassium acetylated hyaluronate, magnesium acetylated hyaluronate, and calcium acetylated hyaluronate; heparan sulfate; heparin; keratan sulfate I and II.

[0050] Plant extracts include mulberry bark, saxifrage, perilla, rice bran, sake lees, white mustard, peony, barley bark, lotus seed, Job's tears seed, Pandanus amaryllifolius Roxb., Arcangelicia flava Merrilli, chamomile, coral grass, rice leaf, apricot fruit, Euonymus chinensis, rose flower, bamboo shoot skin, gentian, carrot, ginseng, red ginseng, loofah, peach, peach kernel, kiwi, sunflower, and Zizyphus Examples of plant extracts include joazeiro, pau d'arco, daylily, hibiscus flower, silverleaf wormwood, cherimoya, mango, Benifuki, Bletilla serrata, Japanese pepper peel or seed coat, safflower flower, Casablanca lily, guava leaf, Houttuynia cordata, Banpeiyu, aloe, fig flower, apple, white asparagus, yerba mate tea, cherry blossom leaf, and ylang ylang leaves.

[0051] Seaweed extracts include green algae such as Chlorella vulgaris, Chlorella pyrenoidosa, Chlorella ellipsoidea, green laver, sea lettuce, and sea lettuce; brown algae such as kelp (Kagome kelp, Laminaria japonica, Lisilis kelp, Narrow Laminaria japonica, Mitsuishi kelp, etc.), giant kelp, wakame or blue wakame, mozuku, unripe seaweed, hijiki, fucus, sea fan, thin-leaved sea fan, red-leaved sea fan, Kona sea fan, Okinawa fan, thin-leaved snow fan, and Etsuki sea fan; and brown algae such as Hijirimen and Maku. and red algae such as Aster or Aster, Hirakusa, Onikusa, Obakusa, Kataobakusa, Yatabegusa, Yukikiri, Shimatengusa, Tosakanori, Togekirinsai, Amakusa Gingerbread Cypress, Eucheuma, Byakushin Gingerbread Cypress, Tsunomata, Oobatsumata, Tochaka or Yahazutsunomata, Ezotsunomata, Togetsunomata, Hirakotoji, Kotojitsunomata, Ibotsunomata, Marubatsumata, Suginori, Shikinori, Kainori, Yareusubanori, Kagiusubanori, Sujiusubanori, Haiusubanori, and Akamomijinanori.

[0052] Antifungal agents include terbinafine, naftifine, butenafine, tolnaftate, liranaftate, miconazole, lanoconazole, luliconazole, isoconazole, ketoconazole, clotrimazole, neticonazole, sulconazole, bifonazole, oxiconazole, econazole, fluconazole, itraconazole, fosfluconazole, voriconazole, efinaconazole, butoconazole, fenticonazole, and sertaconazole.

[0053] The antipruritic composition for external use may be contained in a container. The container may be made of, in whole or in part, an olefin-based resin such as ethylene-based resin [e.g., polyethylene (including high-density polyethylene, low-density polyethylene, very-low-density polyethylene, linear low-density polyethylene, ultra-high-molecular-weight polyethylene, etc.), ethylene-propylene copolymer, etc.], propylene-based resin [e.g., polypropylene (PP) (including isotactic polypropylene, syndiotactic polypropylene, atactic polypropylene, etc.), propylene-ethylene copolymer, etc.], or methylpentene-based resin (e.g., polymethylpentene, etc.); styrene-based resin such as polystyrene, acrylonitrile-containing styrene-based resin (e.g., acrylonitrile-styrene copolymer (AS resin), acrylonitrile-butadiene-styrene copolymer (ABS resin)), etc.); acrylic resin containing, as a polymerization component, an acrylic acid ester such as methyl acrylate, or a methacrylic acid ester such as methyl methacrylate, cyclohexyl methacrylate, or t-butylcyclohexyl methacrylate; aromatic polyester-based resin [e.g., alkylene terephthalate, polyester-based resins such as resins having alkylene naphthalate units (alkylene terephthalate-based resins: for example, polyethylene terephthalate (PET), polytrimethylene terephthalate, polybutylene terephthalate (PBT)), and resins having alkylene naphthalate units (for example, polyethylene naphthalate (PEN), polybutylene naphthalate); polycarbonate-based resins; fluororesins such as fluorine-substituted polyethylene (polytetrafluoroethylene, polychlorotrifluoroethylene, etc.), polyvinylidene fluoride, polyvinyl fluoride, perfluoroalkoxy fluororesin, tetrafluoroethylene-hexafluoropropylene copolymer, ethylene-tetrafluoroethylene copolymer, and ethylene-chlorotrifluoroethylene copolymer; chlorine-based resins such as polyvinyl chloride; polyamide-based resins; polyacetal-based resins that contain only oxymethylene units as well as polyphenylene ether-based resins that contain modified polyphenylene ethers such as polystyrene-modified polyphenylene ether; polyarylates such as amorphous polyarylates; polysulfones;Examples of the resin include polyimide resins such as aromatic polyimides, such as polymers of pyromellitic dianhydride and 4,4'-diaminodiphenyl ether; cellulose resins such as cellulose acetates, such as cellulose diacetate and cellulose triacetate; hydrocarbon resins that may be substituted with halogen atoms; resins containing cyclic olefin polymers (COP-containing resins) (including polymers obtained by copolymerizing cyclic olefins and acyclic olefins, or resins containing hydrogenated products thereof (COC-containing resins)), and other plastics, aluminum, glass, and the like;

[0054] Examples of container forms include bottle containers, tube containers, spray containers (pump containers, aerosol containers, etc.), jar containers, dropper containers, dispenser containers, pouch bags, cheer packs, sponge head containers, roll-on containers, and stick containers.

[0055] Ophthalmic composition The antipruritic ophthalmic composition can be in the form of a liquid (including a viscous one), a gel, a semi-solid (ointment, etc.), or the like. Ophthalmic compositions include eye drops (also called eye drops or eye drops; eye drops include eye drops that can be applied while wearing contact lenses), artificial tears, eyewashes (also called eyewashes or eyewashes; eyewashes include eyewashes that can be applied while wearing contact lenses), and contact lens compositions (contact lens wetting solutions; contact lens care compositions such as contact lens disinfectants, contact lens preservatives, contact lens cleaners, and contact lens cleaning and preservatives). "Contact lenses" includes hard contact lenses and soft contact lenses (including both ionic and non-ionic, and both silicone hydrogel contact lenses and non-silicone hydrogel contact lenses).

[0056] The antipruritic ophthalmic composition may be a pharmaceutical composition or a quasi-drug composition.

[0057] The concentration of component (A) in the antipruritic ophthalmic composition can be 0.000001% by mass or more, 0.00001% by mass or more, 0.0001% by mass or more, 0.001% by mass or more, or 0.01% by mass or more, relative to the total amount of the composition, and can be 1% by mass or less, 0.5% by mass or less, 0.1% by mass or less, or 0.05% by mass or less. Within this range, the antipruritic effect can be sufficiently exerted.

[0058] Among the antipruritic ophthalmic compositions, eye drops and artificial tears can be applied 1 to 6 times a day, 1 to 2 drops per application (e.g., eye drops), or can be applied whenever an itch is felt. Eye washes can be used 1 to 6 times a day, or whenever an itch is felt. Compositions for contact lenses can be used in the usual manner depending on the type. For example, for persistent itching, it can be applied at intervals of once every 1 to 100 minutes as described above, thereby maintaining a state in which itching is suppressed. The amount of the antipruritic ophthalmic composition used per administration may be an amount such that the amount of component (A) used per administration is 0.00001 mg or more, 0.0001 mg or more, 0.001 mg or more, 0.005 mg or more, 0.01 mg or more, 0.05 mg or more, 0.1 mg or more, or 0.5 mg or more, and is 500 mg or less, 100 mg or less, 70 mg or less, 50 mg or less, 20 mg or less, or 10 mg or less.

[0059] In addition to component (A), the antipruritic ophthalmic composition may contain one or more pharmacologically or physiologically active ingredients that can be incorporated into ophthalmic compositions, as long as the effects of the present invention are not impaired. Examples of pharmacologically or physiologically active ingredients include decongestants (vasoconstrictors), ocular muscle regulating agents, anti-inflammatory agents, antihistamines, vitamins, amino acids, antibacterial ingredients, antiallergic agents, antioxidants, local anesthetics, and soothing agents.

[0060] Decongestants include epinephrine or a salt thereof (e.g., epinephrine hydrochloride, epinephrine bitartrate), ephedrine or a salt thereof (e.g., ephedrine hydrochloride), methylephedrine or a salt thereof (e.g., methylephedrine hydrochloride, particularly dl-methylephedrine hydrochloride), tetrahydrozoline or a salt thereof (e.g., tetrahydrozoline hydrochloride), naphazoline or a salt thereof (e.g., naphazoline hydrochloride, naphazoline nitrate), phenylephrine or a salt thereof (e.g., phenylephrine hydrochloride), oxymetazoline or a salt thereof (e.g., oxymetazoline hydrochloride), and the like.

[0061] Examples of ocular muscle adjusters include neostigmine or a salt thereof (particularly, neostigmine methylsulfate), physostigmine or a salt thereof (e.g., physostigmine salicylate, physostigmine sulfate), distigmine or a salt thereof (e.g., distigmine bromide), tropicamide, atropine or a salt thereof (particularly, atropine heleniensulfate), and pilocarpine or a salt thereof (e.g., pilocarpine hydrochloride).

[0062] Anti-inflammatory agents include epsilon-aminocaproic acid, pranoprofen, allantoin, berberine or a salt thereof (e.g., berberine chloride, berberine sulfate), azulene sulfonic acid or a salt thereof (e.g., sodium azulene sulfonate, potassium azulene sulfonate, calcium azulene sulfonate, magnesium azulene sulfonate), glycyrrhizic acid or a salt thereof (e.g., dipotassium glycyrrhizinate, monoammonium glycyrrhizinate), zinc salts (e.g., zinc sulfate, zinc lactate), lysozyme or a salt thereof (e.g., lysozyme chloride), indomethacin, silver salts (e.g., silver nitrate), diclofenac acid or a salt thereof (e.g., diclofenac sodium), bromfenac acid or a salt thereof (e.g., bromfenac sodium), and the like.

[0063] Antihistamines include diphenhydramine or a salt thereof (e.g., diphenhydramine hydrochloride), chlorpheniramine or a salt thereof (e.g., chlorpheniramine maleate, chlorpheniramine fumarate), ketotifen or a salt thereof (e.g., ketotifen fumarate), olopatadine or a salt thereof (e.g., olopatadine hydrochloride), and the like.

[0064] Examples of vitamins include flavin adenine dinucleotide or a salt thereof (e.g., flavin adenine dinucleotide sodium), cobalamin or a salt thereof (e.g., cyanocobalamin, methylcobalamin, hydroxocobalamin, adenosylcobalamin), retinol or a salt thereof (e.g., retinol acetate, retinol palmitate), pyridoxine or a salt thereof (e.g., pyridoxine hydrochloride), panthenol, pantothenic acid or a salt thereof (e.g., sodium pantothenate, potassium pantothenate, calcium pantothenate, magnesium pantothenate), tocopherol or a salt thereof (e.g., tocopherol acetate, tocopherol succinate, tocopherol nicotinate), pyridoxal or a salt thereof (e.g., pyridoxal phosphate), and ascorbic acid or a salt thereof (e.g., sodium ascorbate, calcium ascorbate).

[0065] Examples of amino acids include chondroitin sulfate or a salt thereof (e.g., sodium chondroitin sulfate), L-aspartic acid or a salt thereof (e.g., potassium L-aspartate, sodium L-aspartate, magnesium L-aspartate, calcium L-aspartate, magnesium potassium L-aspartate (a mixture of equal parts of magnesium L-aspartate and potassium L-aspartate)), aminoethylsulfonic acid (taurine), glutamic acid or a salt thereof (e.g., sodium glutamate, magnesium glutamate), creatinine, glycine, alanine, arginine, lysine, γ-aminobutyric acid, and γ-aminovaleric acid.

[0066] Examples of antibacterial components include sulfa-based antibacterial agents such as sulfamethoxazole or a salt thereof (e.g., sulfamethoxazole sodium, sulfamethoxazole potassium, sulfamethoxazole calcium, sulfamethoxazole magnesium), sulfisoxazole, sulfisomidine or a salt thereof (e.g., sulfisomidine sodium, sulfisomidine potassium, sulfisomidine calcium, sulfisomidine magnesium), alkylpolyaminoethylglycine, chloramphenicol, ofloxacin, norfloxacin, levofloxacin, lomefloxacin hydrochloride, and acyclovir.

[0067] Antiallergic drugs include cromoglycic acid or a salt thereof (for example, sodium cromoglycate, potassium cromoglycate, calcium cromoglycate, magnesium cromoglycate), ashitazanolast, amlexanox, ibudilast, tranilast, pemirolast potassium, ketotifen, etc.

[0068] Lipid-soluble antioxidants include butyl-containing phenols such as dibutylhydroxytoluene (BHT) and butylhydroxyanisole (BHA); nordihydroguaiaretic acid (NDGA); ascorbic acid esters such as ascorbyl palmitate, ascorbyl stearate, aminopropyl ascorbyl phosphate, tocopheryl ascorbyl phosphate, ascorbyl triphosphate, and ascorbyl palmitate; tocopherols such as α-tocopherol, β-tocopherol, γ-tocopherol, and δ-tocopherol; tocopherol derivatives such as tocopherol acetate, tocopherol nicotinate, and tocopherol succinate; gallic acid esters such as ethyl gallate, propyl gallate, octyl gallate, and dodecyl gallate; and propyl gallate. 3-Butyl-4-hydroxyquinolin-2-one; carotenoids such as lutein and astaxanthin; anthocyanins, catechins, tannins, polyphenols such as curcumin; retinol, retinol esters (retinol acetate, retinol propionate, retinol butyrate, retinol octoate, retinol laurate, retinol stearate, retinol myristate, retinol oleate, retinol linoleate, retinol linoleate, retinol palmitate, etc.), retinal, retinal esters Vitamin A compounds such as vitamin A (retinal acetate, retinal propionate, retinal palmitate, etc.), retinoic acid, retinoic acid esters (methyl retinoate, ethyl retinoate, retinol retinoate, tocopherol retinoate, etc.), dehydroretinol, dehydroretinol, dehydroretinol, provitamin A (α-carotene, β-carotene, γ-carotene, δ-carotene, lycopene, zeaxanthin, β-cryptoxanthin, echinenone, etc.), vitamin A; CoQ10, etc. Examples of water-soluble antioxidants include ascorbic acid, ascorbic acid derivatives (such as disodium ascorbic acid 2-sulfate, sodium ascorbate, magnesium ascorbyl 2-phosphate, and sodium ascorbyl 2-phosphate), sodium bisulfite, sodium sulfite, sodium pyrosulfite, sodium thiosulfate, and edetic acid or its salts (sodium edetate, disodium edetate, and tetrasodium edetate).

[0069] Examples of local anesthetics or analgesics include chlorobutanol, oxybuprocaine hydrochloride, cocaine hydrochloride, cornecaine hydrochloride, dibucaine hydrochloride, tetracaine hydrochloride, diethylaminoethyl parabutylaminobenzoate hydrochloride, piperocaine hydrochloride, procaine hydrochloride, proparacaine hydrochloride, hexothiocaine hydrochloride, and lidocaine hydrochloride.

[0070] The antipruritic ophthalmic composition of the present invention may contain one or more additives that can be incorporated into ophthalmic compositions, provided that the effects of the present invention are not impaired. Examples of additives include bases, refreshing agents, inorganic salts, thickening agents, preservatives, surfactants, buffers, pH adjusters, isotonicity agents, stabilizers, oils, sugars, and polyhydric alcohols.

[0071] The base may include water, ethanol, and the like.

[0072] Examples of cooling agents include terpenoids such as menthol, anethole, eugenol, camphor, geraniol, borneol, limonene, and rhubarb, which may be in the d-, l-, or dl-isomer. Other examples include essential oils such as cool mint oil, spearmint oil, peppermint oil, fennel oil, cinnamon oil, and bergamot oil.

[0073] Examples of inorganic salts include chloride salts such as sodium chloride, potassium chloride, zinc chloride, calcium chloride, and magnesium chloride; carbonates such as sodium bicarbonate, sodium carbonate (including dry sodium carbonate), potassium bicarbonate, and potassium carbonate; phosphates such as sodium hydrogen phosphate, potassium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate, and dipotassium hydrogen phosphate; sulfates such as magnesium sulfate and zinc sulfate; sulfites such as sodium hydrogen sulfite and sodium sulfite; thiosulfates such as sodium thiosulfate; borates such as sodium tetraborate and potassium tetraborate; and acetates such as potassium acetate and sodium acetate.

[0074] Examples of thickening agents include polysaccharides containing sulfated amino sugars such as chondroitin sulfate or its salts, dermatan sulfate or its salts, keratan sulfate or its salts, heparan sulfate or its salts, and heparin, and their salts (sodium salts, potassium salts, etc.); cellulose compounds such as hydroxypropylmethylcellulose, hydroxyethylcellulose, methylcellulose, ethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, and potassium carboxymethylcellulose; polyvinyl alcohol (including fully or partially saponified products), and polyvinylpyrrolide. vinyl polymers such as carboxyvinyl polymers; polyethylene glycol, dextran, alginic acid, guar gum, gum arabic, karaya gum, xanthan gum, agar, starch, chitin and its derivatives, chitosan and its derivatives, carrageenan, gelatin, collagen, pectin, elastin, macrogol, polyethyleneimine alginate (e.g., sodium alginate), alginate esters (e.g., propylene glycol alginate), powdered tragacanth, α-cyclodextrin, dextrin, glucose, sorbitol, liquid paraffin, and glycerin.

[0075] Examples of preservatives include alkylpolyaminoethylglycine, boric acid, alkyldiaminoethylglycine and / or its salts (e.g., alkyldiaminoethylglycine hydrochloride), benzoic acid and / or its salts (e.g., sodium benzoate, potassium benzoate), ethanol, quaternary ammonium salts (e.g., benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride), chlorhexidine and / or its salts (e.g., chlorhexidine gluconate), chlorobutanol, sorbic acid and / or its salts (e.g., potassium sorbate), sodium dehydroacetate, parahydroxybenzoic acid esters (e.g., methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, butyl parahydroxybenzoate), oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, biguamides such as polyhexamethylene biguanide, Gloquil (trade name, Rhodia), and polydronium chloride.

[0076] The surfactant is preferably a nonionic surfactant. Nonionic surfactants include POE (20) sorbitan monolaurate (polysorbate 20), POE (20) sorbitan monopalmitate (polysorbate 40), POE (20) sorbitan monostearate (polysorbate 60), POE (20) sorbitan tristearate (polysorbate 65), and POE (20) sorbitan monooleate (polysorbate 80) fatty acid esters; poloxamer 407, poloxamer 235, poloxamer 188, poloxamer 403, and poloxamer 188. POE-POP block copolymers such as Poloxamer 237 and Poloxamer 124; POE hydrogenated castor oils such as POE hydrogenated castor oil 40, POE hydrogenated castor oil 50, POE hydrogenated castor oil 60, and POE hydrogenated castor oil 80; POE castor oils such as POE castor oil 3, POE castor oil 4, POE castor oil 6, POE castor oil 7, POE castor oil 10, POE castor oil 13.5, POE castor oil 17, POE castor oil 20, POE castor oil 25, POE castor oil 30, POE castor oil 35, and POE castor oil 50; polyethylene monostearate Polyethylene glycol (2 E.O.), polyethylene glycol monostearate (4 E.O.), polyethylene glycol monostearate (9 E.O.), polyethylene glycol monostearate (10 E.O.), polyethylene glycol monostearate (23 E.O.), polyethylene glycol monostearate (25 E.O.), polyethylene glycol monostearate (32 E.O.), polyethylene glycol monostearate (40 E.O., Polyoxyl 40 stearate), polyethylene monostearate polyethylene glycol monostearate such as polyethylene glycol (45 E.O.), polyethylene glycol monostearate (55 E.O.), polyethylene glycol monostearate (75 E.O.), polyethylene glycol monostearate (140 E.O.); 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. In the compounds exemplified above, POE stands for polyoxyethylene, POP stands for polyoxypropylene, and the numbers in parentheses indicate the number of moles added.

[0077] Other usable surfactants include amphoteric surfactants such as glycine-type amphoteric surfactants (e.g., alkyldiaminoethylglycine, alkylpolyaminoethylglycine) and betaine-type amphoteric surfactants (e.g., lauryldimethylaminoacetic acid betaine, imidazolinium betaine); and cationic surfactants such as alkyl quaternary ammonium salts (e.g., benzalkonium chloride, benzethonium chloride).

[0078] Examples of buffers include borate buffers, phosphate buffers, carbonate buffers, citrate buffers, acetate buffers, epsilon-aminocaproic acid buffers, and aspartate buffers. Examples of borate buffer components include boric acid and borate salts (sodium borate, potassium tetraborate, potassium metaborate, ammonium borate, borax, etc.). Borates may be hydrates. Examples of phosphate buffer components include phosphoric acid and phosphate salts (disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, trisodium phosphate, dipotassium phosphate, calcium monohydrogen phosphate, calcium dihydrogen phosphate, etc.). Phosphates may be hydrates. Examples of carbonate buffer components include carbonic acid and carbonate salts (potassium carbonate, sodium carbonate, calcium carbonate, potassium bicarbonate, sodium bicarbonate, magnesium carbonate, etc.). Components of citrate buffers include citric acid and citrate salts (sodium citrate, potassium citrate, calcium citrate, sodium dihydrogen citrate, disodium citrate, etc.). Components of acetate buffers include acetic acid and acetate salts (ammonium acetate, potassium acetate, calcium acetate, sodium acetate, etc.). Components of aspartic acid buffers include aspartic acid and salts of aspartic acid (sodium aspartate, magnesium aspartate, potassium aspartate, etc.).

[0079] Examples of pH adjusters include hydrochloric acid, sulfuric acid, polyphosphoric acid, organic acids (propionic acid, oxalic acid, gluconic acid, fumaric acid, lactic acid, tartaric acid, malic acid, succinic acid, etc.), sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, triethanolamine, monoethanolamine, and diisopropanolamine.

[0080] Examples of isotonicity agents include sodium chloride, potassium chloride, calcium chloride, magnesium chloride, potassium acetate, sodium acetate, magnesium sulfate, glycerin, propylene glycol, etc. Some isotonicity agents are formulated as inorganic salts.

[0081] Stabilizers include trometamol, sodium formaldehyde sulfoxylate (Rongalit), monoethanolamine, aluminum monostearate, and glyceryl monostearate.

[0082] Examples of oils include animal oils such as squalane; mineral oils such as liquid paraffin and vaseline; and vegetable oils such as castor oil and sesame oil.

[0083] Examples of sugars include monosaccharides and disaccharides, specifically glucose, maltose, trehalose, sucrose, cyclodextrin, xylitol, sorbitol, mannitol, etc. Some sugars are also used as thickening agents.

[0084] Examples of polyhydric alcohols include polyethylene glycol, glycerin, propylene glycol, xylitol, diethylene glycol, mannitol, sorbitol, etc. Some polyhydric alcohols are also used as thickening agents.

[0085] The viscosity of the antipruritic ophthalmic composition can be 1.1 mPa·s or more, 2 mPa·s or more, or 3 mPa·s or more, and can be 100 mPa·s or less, 50 mPa·s or less, or 20 mPa·s or less. Within this range, the contact time with the eyeball or contact lens is sufficiently long, allowing the composition to exert a sufficient antipruritic effect. The viscosity of the antipruritic ophthalmic composition was measured at 25°C using a B-type rotational viscometer (RB-80L; Toki Sangyo Co., Ltd.) according to the method described in the 18th Edition of the Japanese Pharmacopoeia, under the heading "Single Cylindrical Rotational Viscometer (Brookfield Viscometer)" in the "Viscosity Measurement Methods" section of the "Method 2: Rotational Viscometer Method." The rotor, rotation speed, and other conditions were selected according to the instruction manual for the machine.

[0086] The pH of the antipruritic ophthalmic composition can be 3 or more, 4 or more, 5 or more, 5.5 or more, or 6 or more, and can be 10 or less, 9 or less, 8.5 or less, or 8 or less. If the pH is within the above range, eye irritation is suppressed and a sufficient antipruritic effect is obtained.

[0087] The antipruritic ophthalmic composition can be contained in a container. Examples of the container material include those exemplified as the container for the antipruritic topical composition. Examples of the container form include a bottle container, a tube container, a jar container, a dropper container, a roll-on container, and a stick container.

[0088] Otolaryngological composition The antipruritic otorhinological composition can be in the form of a liquid (including a viscous one), a gel, a semi-solid (e.g., an ointment), a stick, etc. Examples of the otorhinological composition include nasal drops (including nasal drops and nasal solutions), nasal washes (including nasal washes and nasal solutions), inhalants, and ear drops (including ear drops and ear drops). The composition can also be a pharmaceutical composition, a quasi-drug composition, or a general medical device.

[0089] The concentration of component (A) in the antipruritic otorhinological composition can be 0.000001% by mass or more, 0.00001% by mass or more, 0.0001% by mass or more, 0.001% by mass or more, or 0.01% by mass or more, relative to the total amount of the composition, and can be 40% by mass or less, 30% by mass or less, 20% by mass or less, 10% by mass or less, 5% by mass or less, 2.5% by mass or less, 1% by mass or less, or 0.1% by mass or less. Within this range, the antipruritic effect can be sufficiently exerted.

[0090] The antipruritic otorhinological composition can be applied to the nasal cavity by spraying, dropping, painting, inhalation, etc. The number of times of application to the nasal cavity can be 1 to 8 times, particularly 1 to 6 times, per day, or it can be applied whenever an itch is felt. For persistent itching, it can be applied at intervals of once every 1 to 100 minutes as described above, thereby maintaining a state in which itching is suppressed. The amount of the antipruritic otorhinologic composition to be used may be such that the amount of component (A) used per dose is 0.00001 mg or more, 0.0001 mg or more, 0.0005 mg or more, 0.001 mg or more, 0.005 mg or more, or 0.01 mg or more, and 5000 mg or less, 1000 mg or less, 500 mg or less, 100 mg or less, 10 mg or less, 1 mg or less, 0.8 mg or less, 0.5 mg or less, 0.3 mg or less, 0.1 mg or less, or 0.05 mg or less.

[0091] In addition to component (A), the antipruritic otorhinological composition may contain one or more pharmacologically or physiologically active ingredients that can be incorporated into otorhinological agents, as long as the effects of the present invention are not impaired. Pharmacologically or physiologically active ingredients include antiallergic drugs such as olopatadine, montelukast, and pranlukast; vasoconstrictors such as oxymetazoline, epinephrine, ephedrine, tetrahydrozoline, naphazoline, phenylephrine, methylephedrine, and pseudoephedrine; antihistamines such as iproheptine, diphenhydramine, and chlorpheniramine; astringents such as zinc oxide, zinc lactate, and zinc sulfate; disinfectants such as acrinol, cetylpyridinium, benzalkonium, benzethonium, and chlorhexidine;Non-steroidal anti-inflammatory agents (glycyrrhetinic acid, glycyrrhizinic acid, methyl salicylate, glycol salicylate, allantoin, azulene, azulene sulfonic acid, guaiazulene, tranexamic acid, ε-aminocaproic acid, berberine, lysozyme, licorice, indomethacin, ibuprofen, ibuprofen piconol, bufexamac, butyl flufenamate, bendazac, piroxicam, ketoprofen, felbinac, etc.), steroidal anti-inflammatory agents (prednisolone esters such as beclomethasone propionate, fluticasone furoate, prednisolone valerate acetate (PVA), prednisolone succinate, prednisolone acetate, prednisolone phosphate, dexamethasone valerate, dexamethasone propionate, dexamethasone acetate, dexamethasone phosphate, Anti-inflammatory agents include dexamethasone esters such as dexamethasone metasulfobenzoate, dexamethasone cipecilate, and dexamethasone palmitate; hydrocortisone esters such as hydrocortisone butyrate (particularly hydrocortisone-17-butyrate), hydrocortisone acetate, hydrocortisone succinate, hydrocortisone butyrate propionate, and hydrocortisone phosphate; mometasone furoate, diflucortolone valerate, beclomethasone propionate, beclomethasone dipropionate, clobetasone butyrate, deprodone propionate, alclometasone propionate, flumethasone pivalate, clobetasone propionate, clobetasone butyrate, and diflorasone acetate;

[0092] The antipruritic otolaryngological composition may contain one or more additives that can be incorporated into otolaryngological agents, provided that the effects of the present invention are not impaired. Examples of additives include those exemplified for the antipruritic ophthalmic composition.

[0093] The pH of the antipruritic otorhinological composition can be 4 or more, or 4.5 or more, and 9 or less, 7.5 or less, 7 or less, or 6.5 or less. If the pH is within this range, unpleasant irritation is unlikely to be felt when applied to the nasal mucosa, and a sufficient antipruritic effect can be obtained.

[0094] The antipruritic otorhinological composition can be contained in a container. Examples of the container material include those exemplified as containers for the antipruritic topical composition. Examples of the container form include a bottle container, a tube container, a spray container (e.g., a pump container, an aerosol container), a jar container, a dropper container, a dispenser container, a sponge head container, a roll-on container, and a stick container.

[0095] Antipruritic composition for application to an object or space The antipruritic composition of the present invention can be applied to an article or space (atmosphere such as air). For example, it can be sprayed, applied, placed, or attached to walls, floors, ceilings, curtains, furniture such as sofas and beds, bedding, clothing, masks, glasses, indoor spaces (air), car interior spaces (air), etc., and can exert an antipruritic effect due to the components in the space or the components volatilized in the space where the article is placed. Alternatively, the composition can be impregnated into a porous carrier to produce a composition that exerts an antipruritic effect by volatilizing the components. Examples of the carrier include carriers made of natural fibers such as cotton, plant fibers, and pulp, synthetic fibers such as rayon, polyester, and polyethylene terephthalate, or mixtures thereof; wood carriers such as wood chips, rattan, and bamboo; and sponge carriers such as urethane foam resin.

[0096] The antipruritic composition for application to an object or space can be a liquid, semi-solid (such as a gel), or solid formulation. The antipruritic composition to be applied to an article or space may contain one or more additives to the extent that the effects of the present invention are not impaired. Examples of additives include water, surfactants, lower alcohols such as methanol, ethanol, propyl alcohol, isopropyl alcohol, and butanol, polyhydric alcohols such as ethylene glycol, propylene glycol, dipropylene glycol, glycerin, and sorbitol, gelling agents such as carrageenan, gelatin, pectin, agar, pectin, and gellan gum, paraffin hydrocarbons (such as plasmonic isoparaffin and plasmonic normal paraffin), 3-methoxy-3-methyl-1-butanol, glycol ethers such as propylene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol monopropyl ether, dipropylene glycol monomethyl ether, tripropylene glycol monomethyl ether, and propylene glycol propyl ether, polyoxyethylene alkylphenyl ethers, pH adjusters, antioxidants, preservatives, fragrances, dyes, pigments, and ultraviolet absorbers.

[0097] When spraying, applying, or adhering to an article, the amount used and the number of applications can be determined appropriately depending on the space in which the article is placed and the size of that space. When spraying into a space, the amount used can also be determined appropriately depending on the size of the space. The number of applications to the article or space can be once every 0.01 to 5 hours, 0.1 to 3 hours, or 0.25 to 1 hour. Because the antipruritic effect of the antipruritic composition of the present invention is sustained, itching can generally be suppressed even when the spray interval is extended. For example, for persistent itching, it can be applied at intervals of once every 1 to 100 minutes as described above, thereby maintaining a state in which itching is suppressed. The amount of the antipruritic composition used when sprayed, applied, or attached to an article or space may be such that the amount of component (A) used per application is 0.0001 mg or more, 0.001 mg or more, 0.01 mg or more, 0.1 mg or more, 1 mg or more, 10 mg or more, or 50 mg or more, and 100 mg or less, 150 mg or less, 250 mg or less, 350 mg or less, 500 mg or less, or 1000 mg or less. When the antipruritic composition is placed in a space (such as a room or a car), an excess amount of the composition may be placed so that component (A) is continuously released into the space.

[0098] The antipruritic composition to be applied to an object or space may be contained in a container. Examples of the container include those exemplified for the antipruritic external composition. [Example]

[0099] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

[0100] Test 1 (Histamine-independent itching suppression test 1) Male ICR mice weighing 30–43 g were acclimated for 5 days and then intradermally administered 50 μL of chloroquine solution (4 μg / μL) to the dorsal neck. The chloroquine dose was 200 μg. The mice were then placed in a 1-L observation chamber filled with the test sample (100%: 1 mL of 100% test sample was placed in a 20-mL glass vial, and allowed to evaporate at room temperature in a 0.32-L odor chamber. Odorless air was introduced into the chamber at a flow rate of 1 L / min, and the resulting odor was then introduced into a 1-L observation chamber. See Tashiro et al. Sci Rep 6:37129 (2016)). The mice were exposed to the odor for 30 minutes. Their scratching behavior was monitored by video and the number of scratching bouts was visually counted. Mice that had been similarly administered with chloroquine were placed in an observation chamber filled with only odorless air (control group), and the number of scratching behaviors was similarly counted visually. Each group consisted of 8 to 12 mice, and each mouse was placed in an observation chamber.

[0101] Linalool, cineole, or eucalyptus oil was used as the test sample. A Dunnett multiple comparison test was used to test for significance. The results are shown in Figure 1. (A) shows the change in the number of scratching behaviors over a 30-minute period, and (B) shows the total number of scratching behaviors over 6, 15, and 30 minutes. In Figure 1, * indicates a significant difference (p<0.05), and ** indicates a significant difference (p<0.01). As shown in Figure 1, mice administered chloroquine, a representative nonhistamine pruritus-inducing drug, showed a significant decrease in scratching behavior when exposed to the airborne scents of linalool, cineole, or eucalyptus oil. Thus, linalool, cineole, and eucalyptus oil suppressed histamine-independent itch. Furthermore, it was clear that linalool, cineole, and eucalyptus oil suppressed itch not through percutaneous absorption but through the scent.

[0102] Furthermore, no differences were observed in the distance traveled by mice in the observation chamber or rearing (the behavior of rearing up on their hind legs and exploring the chamber) between the presence and absence of fragrance exposure to linalool, cineole, and eucalyptus oil (visual observation) (Tashiro et al. 2016). In other words, no changes in activity, an important indicator of sedative effects, were observed, and no sedative effects were observed under these experimental conditions. This indicates that the antipruritic effects observed in this study are not due to decreased activity caused by sedation.

[0103] Test 2 (Histamine-independent itching suppression test 2) The inhibitory effect on histamine-independent itching was evaluated in the same manner as in Test 1, except that lavender oil, peppermint oil, or rose oil was used as the test sample.

[0104] A Dunnett's multiple comparison test was used to test for significance. The results are shown in Figure 2. (A) shows the change in the number of scratching behaviors over 30 minutes, and (B) shows the total number of scratching behaviors over 5, 15, and 30 minutes. In Figure 2, * indicates a significant difference (p<0.05, ** indicates a significant difference (p<0.01), and *** indicates a significant difference (p<0.001). As shown in Figure 2, similar to Test Example 1, mice administered chloroquine, a representative non-histamine pruritus-inducing drug, showed a significant decrease in scratching behavior when exposed to the scent of lavender oil, peppermint oil, or rose oil in the air. Thus, lavender oil, peppermint oil, and rose oil suppressed histamine-independent itching.

[0105] Furthermore, no differences were observed in the distance traveled by mice in the observation chamber or in rearing (the behavior of rearing up on their hind legs and exploring the chamber) between lavender, peppermint, and rose oils (visual observation) (Tashiro et al. 2016). In other words, no changes in activity, an important indicator of sedative effects, were observed, and no sedative effects were observed under these experimental conditions. This indicates that the antipruritic effects observed in this study are not due to decreased activity caused by sedation.

[0106] Test 3 (Confirmation of antipruritic effect via olfactory sensation 1) A blunt-ended catheter was inserted into the olfactory bulbs of deeply anesthetized C57 / Bl6 male mice weighing 25–32 g. Both olfactory bulbs were crushed and aspirated. The mice were then allowed to rest for 2 weeks for recovery, followed by 5 days of acclimation. Subsequently, 50 μL of chloroquine solution (4 μg / μL) was administered intradermally to the neck of the mice. The chloroquine dose was 200 μg. Next, mice were placed in a 1-L observation chamber filled with linalool (100%; 1.0 mL of 100% test sample was placed in a 20-mL glass vial and allowed to evaporate at room temperature in a 0.32-L odor chamber. Odorless air was introduced into the odor chamber at a flow rate of 1 L / min, and the resulting odor was then introduced into a 1-L observation chamber. See Tashiro et al. Sci Rep 6:37129 (2016)). The mice were exposed to the odor for 30 minutes. The scratching behavior of the mice during the 30 minutes was observed by video, and the number of scratching bouts was visually counted. The number of scratching behaviors was also visually counted for a control group of olfactory bulbectomized mice administered chloroquine in the same manner, placed in an observation chamber filled with only odorless air. Each group consisted of 7 to 9 mice, and each mouse was placed in an observation chamber.

[0107] A significance test was performed using an unpaired t-test. The results are shown in Figure 3. (A) shows the change in the number of scratching behaviors over 30 minutes, (B) shows the total number of scratching behaviors over 6 minutes, and (B) shows the total number of scratching behaviors over 30 minutes. No difference was observed in the number of scratching behaviors in olfactory bulbectomized mice that had chloroquine administered to the skin between those with and without linalool vaporized in the air.

[0108] Test 4 (Confirmation of antipruritic effect via olfactory sensation 2) The inhibitory effect of histamine-independent itching when the sense of smell was blocked was evaluated in the same manner as in Test 3, except that ICR male mice weighing 29 to 39 g were used as test animals and lavender essential oil was used as the test sample. The results are shown in Figure 4. (A) shows the change in the number of scratching behaviors over 30 minutes, (B) the left graph shows the total number of scratching behaviors over 5 minutes, and (B) the right graph shows the total number of scratching behaviors over 30 minutes. No difference was observed in the number of scratching behaviors in olfactory bulbectomized mice that had chloroquine administered to their skin, whether or not lavender oil was vaporized into the air.

[0109] Test 5 (Confirmation of antipruritic effect via olfactory sensation 3) The inhibitory effect on histamine-independent itching when the sense of smell was blocked was evaluated in the same manner as in Test 4, except that eucalyptus oil was used as the test sample. The results are shown in Figure 5. (A) shows the change in the number of scratching behaviors over 30 minutes, (B) the left graph shows the total number of scratching behaviors over 5 minutes, and (B) the right graph shows the total number of scratching behaviors over 30 minutes. No difference was observed in the number of scratching behaviors in olfactory bulbectomized mice that had chloroquine administered to their skin, whether or not eucalyptus oil was vaporized into the air.

[0110] Thus, the antipruritic effects of linalool, lavender oil, and eucalyptus oil were not observed in mice in which the sense of smell was blocked by removing the olfactory bulb. This indicates that the antipruritic effects of linalool and eucalyptus oil in Test 1 and lavender oil in Test 2 are central antipruritic effects caused by olfactory input evoked by the linalool, eucalyptus, or lavender scents, i.e., antipruritic effects due to activation of the endogenous antipruritic circuit. Furthermore, because they suppress itch centrally rather than inhibiting the action of each mediator, they are thought to suppress not only chloroquine-induced itch but also various itches caused by various mediators such as serotonin, especially various histamine-independent itches. Furthermore, cineole, mint oil, and rose oil, like linalool, lavender oil, and eucalyptus oil, are essential oils or essential oil components, and an antipruritic effect can be obtained by smelling their scent. Therefore, it is thought that they exerted a central antipruritic effect in Tests 1 and 2. [Industrial Applicability]

[0111] The antipruritic agent of the present invention is one of the few antipruritic agents that can suppress histamine-independent itching. Furthermore, since the antipruritic effect is exerted by inhaling the scent, the antipruritic effect can be obtained not only by applying it to the skin but also by using it on personal items, personal belongings, and even the air around us. Furthermore, the antipruritic effect is immediate and sustained. These points make the antipruritic agent of the present invention extremely useful.

Claims

1. An antipruritic agent comprising at least one component selected from the group consisting of linalool, cineole, eucalyptus oil, lavender oil, rose oil, and peppermint oil.

2. The antipruritic agent according to claim 1, which exerts an antipruritic effect when a subject smells the fragrance.

3. The antipruritic agent according to claim 1 or 2, which suppresses histamine-independent itching.

4. An antipruritic composition comprising at least one component selected from the group consisting of linalool, cineole, eucalyptus oil, lavender oil, rose oil, and peppermint oil.

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