JP3022541B1 - External preparation - Google Patents

Abstract

Abstract: PROBLEM TO BE SOLVED: To provide an excellent antipruritic effect even when a low concentration of an antipruritic agent is contained, to have less side effects, to be less greasy and to have a non-greasy feeling of use. And an external preparation which can be used for whole body skin. SOLUTION: A base is prepared by containing a polyhydric alcohol fatty acid ester, an oil component, a lower alcohol and water. An antipruritic agent is added to the base.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to external preparations such as pharmaceuticals and quasi-drugs.

[0002]

2. Description of the Related Art The mechanism of pruritus in the skin involves complicated factors, and there are still many unclear points. However, it has a function of reducing itching.
Antihistamines, steroids, anti-inflammatory analgesics, local anesthetics, antiallergic drugs and many other drugs have been reported. In general, external preparations are prepared by incorporating these drugs into an emulsion cream base, an emulsion lotion base, etc., mainly based on emulsification technology. More recently, in addition to these anti-pruritic agents, topical preparations containing capsaicin and nonylate vanillyl amide, which are alkaloid components of peppers and peppers, have been used for target diseases with itching and pain .

[0003]

However, an external preparation containing a high concentration of an antipruritic agent such as capsaicin or nonyl vanillyl amide (a so-called antipruritic preparation) is not suitable for atopic dermatitis as a disease accompanied by itch. A certain effect has been observed for psoriasis, pruritus cutis and the like.
On the other hand, there are many cases that complain of symptoms such as red hot sensation (burning sensation), irritation, pain, etc. of the skin for several hours at the time of use unique to capsaicin and nonyl vanillyl amide. The solution was urgently needed. In addition, itching is often felt on the whole body, and it has been pointed out that conventional bases have a problem of feeling of use such as stickiness and oiliness when applied to the whole body and are difficult to use.

[0004] The present invention has been made in view of the above points, and it is possible to maintain an excellent antipruritic effect even when an antipruritic agent is contained at a low concentration, to have few side effects, and to provide an oil. It is an object of the present invention to provide an external preparation which is less sticky, has a non-greasy feel, and has a dry feel and can be used on the whole body skin.

[0005]

An external preparation according to claim 1 of the present invention comprises a base prepared by adding a polyhydric alcohol fatty acid ester, an oil, a lower alcohol, and water,
It is characterized by comprising an antipruritic agent added to a base.

[0006] An external preparation according to a second aspect of the present invention is characterized by containing a polyhydric alcohol in addition to the constitution of the first aspect.

The external preparation according to claim 3 of the present invention, in addition to the constitution of claim 1 or 2, is selected from the group consisting of capsaicin, nonylate vanillylamide, and pepper extract as an antipruritic agent. It is characterized by comprising one or two or more kinds.

An external preparation according to a fourth aspect of the present invention, in addition to any one of the first to third aspects, further comprises an antipruritic agent in an amount of 0.0001 to 0.10 per 100 parts by weight of the base. It is characterized by being blended by weight.

An external preparation according to a fifth aspect of the present invention is characterized by comprising hinokitiol in addition to any one of the first to fourth aspects.

[0010]

Embodiments of the present invention will be described below.

The polyhydric alcohol fatty acid ester used in the present invention is an ester of a polyhydric alcohol and a fatty acid, such as sucrose fatty acid ester, polyglycerin fatty acid ester, glycerin fatty acid ester, sorbitan fatty acid ester, polyethylene glycol fatty acid ester and the like. Can be used alone or in combination of two or more.

As the sucrose fatty acid ester, those having a monoester content of 20 mol% or more are preferable, and those having a fatty acid ester substitution degree of 2.2 or less per sucrose molecule can be suitably used. . Further, those having a degree of ester substitution of 1.8 or less are more preferable. As the fatty acid, a saturated or unsaturated single fatty acid having 8 to 22 carbon atoms or a mixed fatty acid can be used. In particular,
Sucrose monomyristate, sucrose monostearate, sucrose monooleate, sucrose distearate, sucrose dioleate, and the like can be used alone or in combination of two or more.

The polyglycerin fatty acid ester includes
Monoester can be suitably used. As polyglycerin, those having a glycerin polymerization degree of 2 to 12,
As the fatty acid, a saturated or unsaturated single or mixed fatty acid having 8 to 22 carbon atoms can be used. Specifically, diglyceryl monostearate, diglyceryl monooleate, diglyceryl dioleate,
Diglyceryl monoisostearate, tetraglyceryl monostearate, tetraglyceryl monooleate,
Tetraglyceryl tristearate, tetraglyceryl pentastearate, tetraglyceryl pentaoleate, hexaglyceryl monolaurate, hexaglyceryl monomyristate, hexaglyceryl monostearate, hexaglyceryl monooleate, hexaglyceryl tristearate, pentastearic acid Hexaglyceryl, hexaglyceryl pentaoleate, hexaglyceryl polyricinoleate, decaglyceryl monolaurate, decaglyceryl monomyristate, decaglyceryl monostearate, decaglyceryl monooleate, decaglyceryl monolinoleate, decaglyceryl monoisostearate, Decaglyceryl distearate, decaglyceryl diisostearate, decaglyceryl tristearate, trio Decaglyceryl decanoate, decaglyceryl pentastearate, decaglyceryl pentaoleate, decaglyceryl pentaisostearate, decaglyceryl heptastearate, tetraglyceryl heptaoleate, decaglyceryl decastestearate, decaglyceryl decaoleate, decaisostearate decaglyceryl Glyceryl and the like can be used alone or in combination of two or more.

As the glycerin fatty acid ester, a monoester can be suitably used. As the fatty acid, a saturated or unsaturated single fatty acid having 8 to 22 carbon atoms or a mixed fatty acid can be used. Specifically, glyceryl monomyristate, glyceryl monostearate, glyceryl monooleate, glyceryl monoisostearate, or the like can be used alone or in combination of two or more.

As the sorbitan fatty acid ester, a monoester can be suitably used. As the fatty acid, a saturated or unsaturated single fatty acid having 8 to 22 carbon atoms or a mixed fatty acid can be used. Specifically, sorbitan monolaurate, sorbitan monopalmitate,
Sorbitan monostearate, sorbitan sesquistearate, sorbitan tristearate, sorbitan monooleate, sorbitan sesquioleate, sorbitan trioleate, sorbitan monoisostearate, sorbitan sesquiisostearate, etc. can be used alone or in combination of two or more. Or you can.

As the polyethylene glycol fatty acid ester, a monoester can be suitably used. As the polyethylene glycol, those having a degree of polymerization of ethylene oxide of 20 or less are used. As the fatty acids, those having 8 to 2 carbon atoms are used.
Two saturated and unsaturated single fatty acids or mixed fatty acids can be used. Specifically, polyethylene glycol monolaurate, polyethylene glycol monostearate, polyethylene glycol monooleate, ethylene glycol monostearate, ethylene glycol distearate, diethylene glycol stearate, polyethylene glycol distearate, polyethylene glycol diisostearate, etc. are used alone. They can be used alone or in combination of two or more.

The trehalose fatty acid ester preferably has a monoester content of 20 mol% or more.
Trehalose having a fatty acid ester substitution degree of 2.2 per molecule can be suitably used. Further, those having a degree of ester substitution of 1.8 or less are more preferable. As the fatty acid, a saturated or unsaturated single fatty acid having 8 to 22 carbon atoms or a mixed fatty acid can be used. Specifically, trehalose monomyristate, trehalose monostearate, trehalose monooleate, trehalose distearate, trehalose dioleate, and the like can be used alone or in combination of two or more.

As the oil component used in the present invention, animal and vegetable oils, ester oils, hydrocarbons, higher alcohols, silicones and the like can be used alone or in combination. Animal and vegetable oils include peanut oil, sesame oil, soybean oil, evening primrose oil, safflower oil, olive oil, avocado oil, jojoba oil, sunflower oil, corn oil, camellia oil, cocoa oil, coconut oil, castor oil, rapeseed oil, mentha oil Oils and oils such as poppy oil, lard, wool oil, and tallow, and those obtained by subjecting these oils and fats to chemical changes such as hydrogenation, and waxes such as salami beeswax, gay wax, wood wax, lanolin, carnauba wax, and shellac wax. Can be exemplified.

As the ester oils, normal fatty acid esters, sucrose fatty acid esters having a degree of ester substitution of more than 2.2, trehalose fatty acid esters, di- or triglycerin fatty acid esters, etc. may be used alone or in combination of two or more. Or you can.

Specifically, acetic acid (cetyl lanolyl) ester, triacetyl glyceryl, eicosanyl propionate, dilauryl thiodipropionate, lauryl lactate, myristyl lactate, cetyl lactate, octyl dodecyl lactate, diisostearyl malate, succinic acid Acid polypropylene glycol oligoester, 2-ethylhexyl succinate, stearyl heptanoate, diisopropyl adipate, diisobutyl adipate, dioctyl adipate,
Di-2-hexydecyl adipate, di (2-adipate)
Heptylundecyl), cetyl caprylate, cetyl 2-ethylhexanoate, cetostearyl 2-ethylhexanoate, glyceryl tri-2-ethylhexanoate, tetra-2-
Pentaerythritol ethylhexanoate, hexadecyl 2-ethylhexanoate, stearyl 2-ethylhexanoate, isostearyl 2-ethylhexanoate, ethylene glycol di-2-ethylhexanoate, di (2-ethylhexanoic acid)- 2,2-dimetal-1,3-propynediol, trimethylolpropane tri-2-ethylhexanoate, hexyldecyl dimethyloctanoate, octyldodecyl dimethyloctanoate, isononyl isononanoate,
Isodecyl isononanoate, isotridecyl isononanoate, propylene glycol dinonanoate, octyl pelargonate, octyl isoperargonate, tri (capryl ・
Glycerin, neopentyl glycol dicaprate, diisopropyl sebacate, hexyl laurate, isostearyl laurate, glyceryl trilaurate, glyceryl tricocoate, isopropyl myristate, butyl myristate, decyl myristate, isotridecyl myristate, myristine Myristic acid, cetyl myristate, isocetyl myristate,
Isostearyl myristate, octyldodecyl myristate, glyceryl trimyristate, pentaerythrit tetramyristate, isopropyl palmitate,
Octyl palmitate, cetyl palmitate, isocetyl palmitate, isostearyl palmitate, octyl isopalmitate, glyceryl tripalmitate, ethyl stearate, butyl stearate, octyl stearate, isocetyl stearate, stearyl stearate, curing stearate Castor oil, glyceryl tristearate, Balti stearate, ethyl isostearate, isopropyl isostearate, butyl isostearate, hexyl isostearate, isosetyl stearate, isostearyl isostearate, hydrogenated castor oil isostearate, octyldodecyl isostearate, isostearate Balch, polyglyceryl monoisostearate, glyceryl triisostearate, triisostearate Diglyceryl phosphate, trimethylolpropane triisostearate, polyglyceryl tetraisostearate, pentaerythrit tetraisostearate, 2-ethylhexyl hydroxystearate, ethyl oleate, decyl oleate, isodecyl oleate, oleyl oleate, octyl oleate Dodecyl, ethylene glycol dioleate, glyceryl trioleate, octyldodecyl ricinoleate, isodecyl pivalate, isostearyl pivalate, glyceryl tribehenate, octyldodecyl erucate, isopropyl lanolin fatty acid, octyldodecyl lanolin fatty acid, ethyl avocado fatty acid, mink Oil fatty acid ethyl,
Dipentaerythritol fatty acid ester, dipentaerythritol hexaoxystearate, diisopropyl dimer, ethyl linoleate, isopropyl linoleate,
Ethyl olive oleate, cetyl isooctanoate, cholesteryl stearate, phytosteryl isostearate, diethyl sebacate, diisopropyl sebacate, 12-stearoyl isocetyl stearate, 12
-Isostearyl stearoyl stearate, stearyl 12-stearoyl stearate, propylene glycol monocaprylate, propylene glycol dicaprylate, propylene glycol didecanoate, pentaerythritol tetra-2-ethylhexanoate, decaglyceryl decasterate, glyceryl decaoleate, deca Decaglyceryl isostearate and the like can be exemplified.

Examples of hydrocarbons include petrolatum, liquid paraffin, and squalane. Examples of higher alcohols include cetyl alcohol, stearyl alcohol, isostearyl alcohol, behenyl alcohol, and the like. Examples of higher fatty acids include palmitic acid, stearic acid, behenic acid and the like. Examples of the silicones include methylpolysiloxane, methylphenylpolysiloxane, and cyclic dimethylpolysiloxane. In addition, silicone derivatives generally used in pharmaceuticals, cosmetics, foods, and the like can be appropriately used.

As the lower alcohol used in the present invention, an alcohol consisting of a linear or branched alkyl group having 1 to 6 carbon atoms can be used.
Methyl alcohol, ethyl alcohol, propyl alcohol, isopropyl alcohol, butyl alcohol, isobutyl alcohol, tert-butyl alcohol, pentyl alcohol, hexyl alcohol and amyl alcohol can be used alone or in combination.

In the present invention, a water-soluble polyhydric alcohol having two or more hydroxyl groups in the molecule can be used, if necessary. Specifically, propylene glycol, 1,
3-butylene glycol, an alkylene glycol such as ethylene glycol or a higher polyalkylene glycol, and glycerin, diglycerin, a higher polyglycerin, and trimethylolethane, erythritol, pentaerythritol, sorbitan, glucose,
Sorbitol, maltitol, sucrose, raffinose, trihalose and the like can be used alone or in combination.

The base of the present invention can be prepared by a conventional method. For example, a polyhydric alcohol fatty acid ester and an oil component, and if necessary, a lower alcohol, and if necessary, a polyhydric alcohol are mixed, and 60 to 10 are mixed on a water bath.
Dissolve with heating to 0, preferably 75-90 ° C and stir to prepare a mixture. Separately, a preservative component and other additives are added to purified water, and if necessary, heated and dissolved to prepare an aqueous solution. The base of the present invention can be prepared by adding an aqueous solution to the mixture, stirring the mixture uniformly, and further adding a lower alcohol after cooling. The addition of medicinal ingredients, preservatives, etc.
Depending on its physicochemical properties, it is appropriately selected, for example, by mixing it with a polyhydric alcohol-based fatty acid ester or oil at the early stage of formulation into an external preparation, or by dissolving it in a lower alcohol at the final step of formulation and adding it. be able to.

In the present invention, the content of the polyhydric alcohol fatty acid ester is preferably set to 1.0 to 20.0% by weight based on the total amount. If the content of the polyhydric alcohol-based fatty acid ester is less than 1.0% by weight, there may be a problem that a stable base or an external preparation cannot be obtained, such as separation of some components. If the content of the polyhydric alcohol fatty acid ester is more than 20.0% by weight, the viscosity may be increased, and the problem that the elongation of the base or the external preparation may be reduced at the time of application to the skin or the like may occur. . In the present invention, the oil content is preferably set to 0.1 to 30.0% by weight based on the total amount. If the oil content is less than 0.1% by weight, the components may be separated and a problem that a gel or cream base cannot be stably prepared may occur. If the amount exceeds 30.0% by weight, a problem that components are separated may occur. Further, in the present invention, the content of the lower alcohol is 0.5 to the total amount.
It is preferably set to 10.0% by weight. When the content of the lower alcohol is less than 0.5% by weight, there is a possibility that a problem that a desired stable external preparation cannot be obtained depending on a component to be added (a medicinal component, a preservative, or the like) may occur. When the content of the alcohol exceeds 10.0% by weight, there is a possibility that a problem occurs that separation of some components occurs and a stable base or external preparation cannot be obtained. In the present invention, the content of the polyhydric alcohol is preferably set to 0.1 to 30.0% by weight based on the total amount. If the content of the polyhydric alcohol is less than 0.1% by weight, there is a possibility that some components may be separated depending on the composition, and a problem that a stable base or external preparation cannot be obtained may occur. Yes, polyhydric alcohol content is 3
If the content exceeds 0.0% by weight, stickiness due to a polyhydric alcohol (particularly, glycerin) may occur, and a problem that the functional surface (feel of use) is poor may occur. Particularly, from the viewpoint of the preparation, the external preparation is preferably in the form of a gel, and in order to obtain a stable gel preparation (external preparation), it is preferable to add 0.5% by weight or more of a polyhydric alcohol.

Further, the present invention can be prepared in the form of cream, gel, lotion (liquid) or the like, and these appearance properties are determined by the type and amount of polyhydric alcohol fatty acid ester and the type of oil component. The amount can be changed by appropriately changing the combination of the blending amount, the type and blending amount of the lower alcohol, and the type and blending amount of the polyhydric alcohol. For example, when the polyhydric alcohol fatty acid ester used is sucrose fatty acid ester, the concentration is kept constant with lower alcohol,
Oil: By changing the concentration of glyceryl tri-2-ethylhexanoate, the appearance properties can be changed from cream to gel or lotion.

The topical preparation of the present invention, which is an antipruritic preparation, can be prepared by adding an antipruritic agent as a drug to the above-mentioned base. As the antipruritic agent, for example, capsaicin, nonylyl vanillylamide, capsicum extract and the like can be used, and by using these, it is possible to impart an effect of promoting blood circulation in addition to anti-itch.

The amount of the antipruritic agent varies depending on the type of the base and the antipruritic agent, or the purpose of the compounding and the medicinal effect.
When capsaicin is used as an antipruritic agent, the amount is preferably set to 0.0001 to 0.10 parts by weight based on 100 parts by weight of the base. 0.00% of antipruritic agent
If the amount is less than 01 parts by weight, the drug efficacy and sustainability of the antipruritic agent cannot be sufficiently exerted. Side effects may occur. More preferably, 10
The amount of the antipruritic agent is set to 0.05 part by weight or less based on 0 part by weight.

In the present invention, vitamins, hormones, amino acids, plant extracts, whitening agents, bactericides, moisturizers, sequestering agents, antioxidants, anti-irritants, astringents and the like are required for the present invention. Can be contained in an appropriate amount according to

Examples of the vitamins include oil-soluble vitamins such as vitamin A oil (retinol), retinol acetate, retinol palmitate, retinol A, vitamin D derivatives, vitamin E (tocopherol), and dl acetate.
-Α-tocopherol, dl-α-tocopherol, tocopherol butyrate, tocopherol nicotinate, benzyl nicotinate, natural vitamin E, etc., and vitamin B1 and vitamin B2 as water-soluble vitamins.
(Riboflavin butyrate), vitamin B6 (fatty acid esters such as pyridoxine dicaprylate and pyridoxine dipalmitate), pantothenyl alcohol, pantothenyl ethyl ether, vitamin C (ascorbic acid), ascorbyl stearate, ascorbyl pantothenate, ascorbyl dipalmitate , Ascorbic acid phosphate magnesium salt, vitamin H (biotin) and the like can be used.

As hormones, female hormones (such as ethinyl estradiol) and corticosteroids can be used. Amino acids include arginine, cystine, leucine, histidine, isoleucine glutamate, lysine, methionine, phenylalanine, threonine, tryptophan, valine, serine,
Alanine, hydroxyproline, asparagine and the like can be used. As plant extracts, liquorice extract, lycopodium, horse chestnut, eucalyptus extract, yarrow, western horse chestnut extract, aloe extract, chamomile extract, sicon extract, carrot extract, lily bulb extract, safflower extract, hamamelis extract , Birch extract, loofah extract, cucumber extract, garlic extract, sugarcane extract, rosemary extract and the like can be used. Arbutin, kojic acid and the like can be used as a whitening agent. As a disinfectant, Irgasan DP300, isopropylmethylphenol, phenoxyethanol, chlorhexidine hydrochloride, chlorhexidine gluconate, benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, and the like can be used. As the humectant, pyrrolidone carboxylic acid, urea, hyaluronic acid, collagen, elastin hydrolyzate and the like can be used. As the metal sequestering agent, ethylenediaminetetraacetic acid, succinic acid, citric acid, polyphosphoric acid, and the like can be used. As the antioxidant, tocopherol, dibutylhydroxytoluene, butylhydroxyanisole, gallic esters and the like can be used. Glycyrrhetinic acid, glycyrrhizic acid, allantoin, azulene, epsilon aminocaproic acid, γ-oryzanol, and the like can be used as the skin roughness preventing agent. Astringents include zinc oxide, zinc sulfate, allantoin hydroxyaluminum, aluminum chloride,
Aluminum sulfate, zinc sulfocarbonate, tannic acid,
Citric acid, lactic acid and the like can be used.

Examples of the drug include antihistamines (diphenhydramine and derivatives thereof), ethyl aminobenzoate, methyl salicylate, dibucaine hydrochloride, allantoin, lidocaine hydrochloride, crotamine, glycol salicylate, aminoethyl sulfonate, acrinol, hydrogen peroxide And naphazoline hydrochloride, chlorpheniramine maleate, sulfisomidine, indomethacin and the like. Further, azulene as an anti-inflammatory agent and salicylic acid and sulfur as keratolytic agents can be used as agents.

In the present invention, if necessary, components for maintaining the antiseptic properties of the external preparation, for example, paraoxybenzoate, benzoic acid and its salts, salicylic acid and its salts, phenoxyethanol, hinokitiol, photosensitizer 201 It is also possible to use symbols as appropriate. When hinokitiol is used as a preservative, the amount is preferably set to 0.001 to 0.1% by weight based on the total amount of the external preparation in order to obtain a sufficient preservative effect.

Further, in the present invention, other conventional additives such as metal soaps, pigments, dyes, fragrances, ultraviolet absorbers, humectants, thickeners, antioxidants, metal sequestering agents, pH adjusters and the like are required. And a cooling agent such as l-menthol, dl-camphor, and borneol can be used as needed.

In the present invention, since the medicinal components are distributed in a well-balanced manner between the polyhydric alcohol fatty acid ester, the oil component and the lower alcohol, the effect of the antipruritic agent can be exerted at a high level, and Sex is longer.

[0036]

The present invention will be described below in detail with reference to examples.

Example 1 5.0 parts by weight of a sucrose fatty acid ester (a mixture of sucrose palmitate and sucrose stearate) and 2.0 parts by weight of glyceryl tri-2-ethylhexanoate as an oil component 5.0 parts by weight of polyhydric alcohol, concentrated glycerin, 2.0 parts by weight of 99.5% ethyl alcohol, 0.03 parts by weight of hinokitiol as a preservative, nonylic acid as an antipruritic An external preparation having a total amount of 100 parts by weight was prepared using 0.005 parts by weight of vanillylamide and the rest as purified water.

The preparation procedure is as follows.

(1) Sucrose fatty acid ester, glyceryl tri-2-ethylhexanoate, concentrated glycerin and vanillyl nonylate were weighed and mixed, and heated to about 80 ° C.

(2) The purified water was heated to about 80 ° C. and added to the mixture prepared in (1) with stirring.

(3) The mixture prepared in (2) is cooled,
At about 40 ° C., 99.5% concentration of ethyl alcohol and hinokitiol were added, and the mixture was further cooled to 30 ° C. or lower.

Example 2 5.0 parts by weight of a sucrose fatty acid ester (a mixture of sucrose palmitate and sucrose stearate) and 2.0 parts by weight of glyceryl tri-2-ethylhexanoate as an oil component 5.0 parts by weight of concentrated glycerin, a polyhydric alcohol, 5.0 parts by weight of ethyl alcohol at a concentration of 99.5%, 0.03 parts by weight of hinokitiol, a preservative, nonylic acid, an antipruritic agent 0.005 parts by weight of vanillylamide, 1-
The total amount of menthol was 0.05 parts by weight, dl-camphor as a cooling agent was 0.05 parts by weight, and the remainder was purified water.
An external preparation of 00 parts by weight was prepared.

The preparation procedure is as follows.

(1) A sucrose fatty acid ester, glyceryl tri-2-ethylhexanoate, concentrated glycerin, vanillyl amide nonylate, l-menthol and dl-camphor were weighed and mixed, and heated to about 80 ° C.

(2) The purified water was heated to about 80 ° C. and added to the mixture prepared in (1) with stirring.

(3) The mixture prepared in (2) is cooled,
At about 40 ° C, add ethyl alcohol and hinokitiol,
Thereafter, it was further cooled to 30 ° C. or lower.

Comparative Example 1 Nonyl acid vanillylamide was added to water-absorbing ointment (Nikko Pharmaceutical Co., Ltd., Nikko Pharmaceutical Co., Ltd.) in an amount of 0.005.
% By weight and mixed by a conventional method.

Comparative Example 2 Nonylate vanillylamide was added to a hydrophilic ointment (Nikko Pharmaceutical Co., Ltd., Nikko Pharmaceutical Co., Ltd.) in an amount of 0.005.
% By weight and mixed by a conventional method.

Comparative Example 3 An ethanol preparation containing 0.005% by weight of nonylate vanillylamide (ethanol 60
% Aqueous solution).

With respect to Examples 1 and 2 and Comparative Examples 1 to 3, the antipruritic effect and its persistence were evaluated.

(A) Antipruritic effect test The antipruritic effect was determined by randomly assigning Examples 1 and 2 and Comparative Examples 1 to 3 to five left and right itch panels except for the face, fist and soles. Apply once a day to each part of the body, once a day, in an appropriate amount, and then stop itching (improvement)
Was evaluated in the following five steps. The results are shown in Table 1, where the numerical values in the table are the sum of the evaluations of five people.

Remarkably improved: 5 Improved: 4 Slightly improved: 3 Unchanged: 2 Deteriorated: 1 (B) Persistence test The durability was determined by simply applying Examples 1 and 2 and Comparative Examples 1 to 3, respectively. The time during which the itch stopped was measured, and the time was evaluated on the following five scales. Table 1 shows the results
The numerical values in the table are the total of the evaluations of the five persons.

10 hours or more: 55 to 10 hours: 43 to 5 hours: 31 to 3 hours: 21 Within 1 hour: 1

[0054]

[Table 1]

As is clear from Table 1, Examples 1 and 2 had a high antipruritic effect, whereas Comparative Examples 1 to 3 had a low antipruritic effect. Further, Examples 1 and 2 had high persistence, while Comparative Example 3 had low persistence. In addition, since the antipruritic effect of Comparative Examples 1 and 2 was too low, the persistence could not be measured.

Example 3 5.0 parts by weight of a sucrose fatty acid ester (a mixture of sucrose palmitate and sucrose stearate) and 0.3 part by weight of glyceryl tri-2-ethylhexanoate as an oil component 5.0 parts by weight of polyhydric alcohol, concentrated glycerin, 2.0 parts by weight of 99.5% ethyl alcohol, 0.03 parts by weight of hinokitiol as a preservative, nonylic acid as an antipruritic 0.005 parts by weight of vanillylamide, 1-
The total amount of menthol was 0.05 parts by weight, dl-camphor as a cooling agent was 0.05 parts by weight, and the remainder was purified water.
An external preparation of 00 parts by weight was prepared.

The preparation procedure was the same as in Example 1.

(Comparative Example 4) An external preparation was prepared in the same manner as in Example 3 except that vanylyl nonylate was not used.

For Example 3 and Comparative Example 4, the pruritus-preventing effect was evaluated.

(C) Comparative test of pruritus-preventing effect The method of comparative test of pruritic-preventing effect was as follows: Example 3 and Comparative Example 4 were given to 30 men and women aged 20 to 71 with itching for one day. The appropriate amount was applied to the affected area and used. Then, as shown in Table 2, the subjective symptoms of itch were expressed stepwise from a non-itch state to the most itch state, and the degree of reduction of itch before and after use of Example 3 and Comparative Example 4 was described. I was asked to. Table 2 shows the results.

[0061]

[Table 2]

As is clear from Table 2, most of the persons who used Example 3 had the pruritus rank in the direction of reduction, whereas those of Comparative Example 4 had the pruritus rank in the direction of reduction. It was difficult to go.

The 30 males and females were examined for side effects, that is, increased skin eruption, irritation, and fever (burning sensation). Table 3 shows the results.

[0064]

[Table 3]

As is clear from Table 3, in both Example 3 and Comparative Example 4, 29 persons (96.7%) could use the compound without causing any side effects.

The above 30 men and women were asked to evaluate the feeling of use of Example 3 and Comparative Example 4. Table 4 shows the results.

[0067]

[Table 4]

As shown in Table 4, in Example 3, 27 persons evaluated that the feeling of use was very good to moderately good, and 90% of the persons evaluated that it was effective. The number of people who evaluated that the usability was very good was a little better, with only 21 people.

(D) Safety Test The safety of Examples 1 to 3 and Comparative Examples 1 and 2 was evaluated. The test method is as follows.

The filter paper impregnated with each of Examples 1 to 3 and Comparative Examples 1 and 2 was filtered using a Finn chamber and Scanpor tape.
The occlusion patch was applied to seven subjects for 48 hours, and the skin reaction was evaluated 1 hour and 24 hours after the removal of the patch. The evaluation results were rated according to the following criteria.

No response 0 Slight erythema 0.5 Obvious erythema 1.0 Erythema with papules or edema 2.0 After removal of the patch, the one with the highest score was selected from the evaluation results of 1 hour and 24 hours. The total score was divided by the number of subjects, and the quotient percentage was defined as the skin irritation index. Table 5 shows the results.

[0072]

[Table 5]

As apparent from Table 5, Examples 1 to 3
Was less irritating than Comparative Example 2.

[0074]

As described above, according to the first aspect of the present invention, a base is prepared by containing a polyhydric alcohol fatty acid ester, an oil component, a lower alcohol and water, and the base is prepared. Because it contains an antipruritic agent, it can maintain an excellent antipruritic effect even if it contains an antipruritic agent at a low concentration, and has few side effects, and is less oily and non-greasy. It has a feeling of use and can be used on whole body skin.

In the invention according to claim 2 of the present invention, the polyhydric alcohol is contained, so that the moisturizing effect can be enhanced.

The invention according to claim 3 of the present invention uses one or more selected from the group consisting of capsaicin, nonylate vanillylamide, and pepper extract as an antipruritic agent. In addition to the stopping action, it can provide an effect of promoting blood circulation.

In the invention according to claim 4 of the present invention, the antipruritic agent is used in an amount of 0.0001-0.
By blending 10 parts by weight, it is possible to surely obtain an anti-itch effect and to achieve low irritation.

In the invention according to claim 5 of the present invention, since hinokitiol is added, the preservative effect can be improved.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification code FI A61K 47/10 A61K 47/10 47/14 47/14 47/44 47/44 A61P 17/04 A61P 17/04 (58) Survey Field (Int.Cl. ⁷ , DB name) A61K 45/00 A61K 9/08 A61K 31/165 A61K 35/78 A61K 47/02 A61K 47/10 A61K 47/14 A61K 47/44 CAPLUS (STN)

Claims (5)

(57) [Claims] 1. An external preparation comprising a polyhydric alcohol fatty acid ester, an oil, a lower alcohol, and water to prepare a base, and an antipruritic agent mixed with the base. . 2. The external preparation according to claim 1, wherein the base contains a polyhydric alcohol. 3. The method according to claim 1, wherein the antipruritic comprises one or more selected from the group consisting of capsaicin, nonylate vanillylamide, and pepper extract. External preparation according to the description. 4. The external preparation according to claim 1, wherein the antipruritic agent is added in an amount of 0.0001 to 0.10 parts by weight based on 100 parts by weight of the base. 5. The external preparation according to claim 1, wherein hinokitiol is blended.