JP2009184951A - External skin care preparation composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an external skin care preparation that ameliorates atopic dermatitis and rough skin caused by sensitive skin and dry dermopathy and is effective as a therapeutic agent for atopic dermatitis by using both components (A) and (B). <P>SOLUTION: The external skin care preparation includes (A) clobetasone butyrate and (B) one or more kinds of physiologically active components selected from tocopherol acetate, vitamin A oil, urea, crotamiton, isopropylmethylphenol, ethyl aminobenzoate, lidocaine hydrochloride, lidocaine, dibucaine hydrochloride, dibucaine, camphor, diphenhydramine, diphenhydramine hydrochloride, chlorpheniramine maleate, menthol, benzethonium chloride, glycol salicylate, methyl salicylate, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, glycyrrhetic acid, chlorhexidine hydrochloride, allantoin, zinc oxide, eucalyptus oil, soft essence of Angelica acutiloba, heparin analog and soft essence of lithospermum root. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to an external preparation for skin and an eczema drug, and is particularly used for prevention and improvement of rough skin accompanied by atopic dermatitis, sensitive skin, dry dermatosis and the like.

  The number of people with various skin diseases, especially atopic dermatitis, sensitive skin, and dry dermatosis, continues to increase with the westernization of eating habits, changes in the living environment, aging and increased stress. . These diseases are accompanied by strong pruritus and rough skin, and for the treatment thereof, dermatological drugs containing antipruritic ingredients such as crotamiton and antihistamines as active ingredients are widely used.

  However, the effect of the dermatological agent containing an antipruritic component such as crotamiton or an antihistamine as an active ingredient has not been sufficient for the improvement of strong pruritus and rough skin. In other words, skin drugs containing crotamiton and antihistamines can be expected to have some effect of suppressing itching, but their onset time is slow and their action time is short, so frequent application is required and rough skin is required. Had the problem of poor improvement.

  In addition, quasi-drugs and cosmetics that mainly contain moisturizing agents are effective to some extent for rough skin caused by low sebum amount and moisture, but for rough skin where the amount of sebum is high and desquamation is observed. Has almost no effect, and has a problem that it cannot be expected to be effective enough to improve a wide range of types of rough skin.

JP-A-9-157161 JP 2000-229884 A JP 2000-229852 A

  The present invention has been made in view of the above circumstances, and is an external preparation for skin that is effective not only for rough skin but also for improving and preventing rough skin caused by skin diseases such as atopic dermatitis, sensitive skin, and dry dermatosis. The purpose is to provide.

  As a result of intensive studies to achieve the above object, the present inventor has found that atopic dermatitis and sensitive skin can be obtained by using an ester-based steroid and a specific physiologically active component (component (B)) such as tocopherol acetate in combination. In addition, the present inventors have found that the present invention provides an excellent preventive and ameliorating effect on a wide range of rough skin including dry skin associated with dry dermatosis.

Therefore, the present invention
(A) Ester steroid (B) Tocopherol acetate, vitamin A oil, urea, crotamiton, isopropylmethylphenol, ethyl aminobenzoate, lidocaine hydrochloride, lidocaine, dibucaine hydrochloride, dibucaine, camphor, diphenhydramine, diphenhydramine hydrochloride, chlorfeni maleate Lamin, menthol, benzethonium chloride, glycol salicylate, methyl salicylate, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, glycyrrhetinic acid, chlorhexidine hydrochloride, allantoin, zinc oxide, eucalyptus oil, eucalyptus soft extract, heparin-like substance, shikon soft extract A skin external preparation characterized by containing one or two or more physiologically active ingredients.
I will provide a.

According to the present invention, the combined use of (A) and (B) can improve rough skin associated with atopic dermatitis, sensitive skin and dry dermatosis.

Hereinafter, the present invention will be described in more detail. In the external preparation for skin of the present invention, as the ester steroid as component (A), clobetasone butyrate, dexamethasone acetate, prednisolone acetate valerate, prednisolone acetate, hydrocortisone acetate, hydrocortisone butyrate, Betamethasone valerate, cortisone acetate Etc. The amount of the ester steroid compounded in the external preparation for skin of the present invention is 0.01 to 1.0% by mass, preferably 0.02 to 0.5% by mass, more preferably 0.025 to 0% in the preparation. .2% by mass. If the amount is less than 0.01% by mass, the effect is not exhibited, and if the amount exceeds 1.0% by mass, there may be inconveniences such as worsening the usability of the preparation.

Component (B) used in the present invention is tocopherol acetate, vitamin A oil, urea, crotamiton, isopropylmethylphenol, ethyl aminobenzoate, lidocaine hydrochloride, lidocaine, dibucaine hydrochloride, dibucaine, camphor, diphenhydramine, diphenhydramine hydrochloride, chlor maleate Select from phenylamine, menthol, benzethonium chloride, glycol salicylate, methyl salicylate, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, glycyrrhetinic acid, chlorhexidine hydrochloride, allantoin, zinc oxide, eucalyptus oil, toki soft extract, heparin-like substance, and shikon soft extract Or one or more compounds. The vitamin A oil written in the component (B) indicates any one of three types of retinol, retinol acetate, and retinol palmitate.
(B) It is preferable that the compounding quantity of a component shall be the effective dose (following) of each component.
Tocopherol acetate (0.1-2.0 mass%), vitamin A oil (0.005-5.0 mass%), urea (3.0-20.0 mass%), crotamiton (1.0-0.0 mass%), isopropylmethylphenol (0.01-2.0 mass%), Ethyl aminobenzoate (0.3-5.0 mass%), lidocaine hydrochloride (1.0-3.0 mass%), lidocaine (0.2-2.5 mass%), dibucaine hydrochloride (0.05-0.5 mass%), dibucaine (0.1-0.3 mass%), Camphor (0.1-12.0 mass%), diphenhydramine hydrochloride (0.5-2.0 mass%), diphenhydramine (0.1-1.0 mass%), chlorpheniramine maleate (0.05-1.0 mass%), menthol (0.1-5.0 mass%), Benzethonium chloride (0.01-0.1 mass%), glycol salicylate (0.4-2.0 mass%), methyl salicylate (0.04-5.0 mass%), dipotassium glycyrrhizinate (0.3-1.0 mass%), glycyrrhizin Monoammonium stannate (0.3-1.0 mass%), glycyrrhetinic acid (0.1-1.0 mass%), chlorhexidine hydrochloride (0.1-0.3 mass%), allantoin (0.2-1.0 mass%), zinc oxide (0.5-50.0 mass%) , Eucalyptus oil (0.1-2.0 mass%), Toki soft extract (0.002-8.0 mass%), heparin-like substance (0.1-0.5 mass%), Sikon soft extract (0.002-8.0 mass%)

In the external preparation for skin of the present invention, in addition to the above essential components, oily components, water-soluble components, preservatives, pH adjusters, thickeners, antioxidants, surfactants, coloring, which are usually used in external preparations for skin A fragrance, a flavoring agent, and the like can be blended as necessary.
Examples of oil components include liquid paraffin, petrolatum, squalane, microcrystalline wax, almond oil, olive oil, hydrogenated oil, jojoba oil, coconut oil, castor oil, palm oil, beeswax, lanolin, lauryl alcohol, cetanol, stearyl alcohol, Oleyl alcohol, octyldodecanol, behenyl alcohol, lauric acid, myristic acid, palmitic acid, stearic acid, isostearic acid, oleic acid, isopropyl myristate, myristyl myristate, isopropyl palmitate, isopropyl adipate and the like can be blended. (Preferred blending amount 3.0-25.0% by mass)
As an aqueous component, for example, glycerin, propylene glycol, sorbitol, polyethylene glycol, 1,3-butylene glycol, ethanol, isopropanol and the like can be blended.
(Preferred blending amount 0.5-20.0 mass%)
Examples of preservatives include parabens, benzoic acids, benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, alkyltrimethylammonium chloride, alkyldiaminoethylglycine hydrochloride, chlorhexidine hydrochloride, chlorobutanol, salicylic acids, domifene bromide, sorbine An acid, phenoxyethanol, etc. can be mix | blended. (Preferred blending amount 0.01-1.0 mass%)
As the pH adjuster, for example, acids such as citric acid, tartaric acid and lactic acid, and alkalis such as sodium hydroxide, potassium hydroxide and triethanolamine can be blended. (Preferable pH 2.5-6.5)
As the thickener, for example, sodium carboxymethylcellulose, sodium alginate, carboxyvinyl polymer, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, polyvinyl alcohol and the like can be blended. (Preferred blending amount 0.05 to 1.0 mass%)
As the antioxidant, tocopherol, erythorbic acid, propyl gallate, BHT (butylhydroxytoluene), BHA (butylhydroxyanisole), NDGA (nordihydroguaiaretic acid) and the like can be blended. (Preferred blending amount 0.01-1.0 mass%)
Surfactants include fatty acid glycerin ester, sorbitan fatty acid ester, sucrose fatty acid ester, polyglycerin fatty acid ester, polyhydric alcohol fatty acid ester, polyoxyethylene alkyl ether, polyoxyethylene alkyl allyl ether, polyoxyethylene fatty acid ester, poly Oxyethylene sorbitan ester, polyoxyethylene glycerin fatty acid ester, polyoxyethylene hydrogenated castor oil and the like can be blended. (Preferred blending amount 0.2-7.0% by mass)

  The dosage form of the external preparation for skin of the present invention is arbitrary, and examples include lotions, emulsions, creams, gels, ointments, packs, aerosols, body shampoos and the like. However, it is not limited to the above dosage form.

EXAMPLES Hereinafter, although an Example and a comparative example are shown and this invention is demonstrated concretely, this invention is not restrict | limited to the following Example.

About formulation shown in Tables 1-4, the oil phase component containing the clobetasone butyrate (A) heated to 70 degreeC and the oil-soluble (B) component contains the water-soluble (B) component similarly heated at 70 degreeC In addition to the aqueous phase component to be emulsified, a cream was prepared and subjected to the following tests. In addition, the unit of the compounding quantity in a table | surface is all the mass%.
<Skin amelioration test associated with atopic dermatitis, sensitive skin and dry dermatosis>
Using an atopy model animal, the rough skin improvement effect was evaluated. NC / Nga mice widely used for research were used as the atopy model animals. Commercially available male NC / Nga mice (CLEA Japan, Inc.) were purchased at the age of 6 weeks, and the temperature was 23 ± 1 ° C., the humidity was 60 ± 10%, and the light / dark cycle was (7: 0 to 19:00 (bright) → 19: Under normal SPF (Specific Patobogen Free: aseptic special environment) set to 00 to 7:00 (dark)), normal bait (trade name “CE2” manufactured by Nippon Agricultural Industry Co., Ltd.) and water can be freely ingested and shaved. External application of 1 mg / mL extracted mite antigen (manufactured by LSL Co., Ltd.) was performed twice a week for a total of 4 weeks on the hair dorsal skin to induce skin symptoms and used for experiments.
Using the mouse having developed the rough skin symptoms as a sample, 0.2 mL of each sample (composition for external use of skin) of Examples 1-28 and Comparative Examples 1-2 was applied to a part of the onset site using a paint brush. After applying twice a day for 3 consecutive days, the recovery state of rough skin at the application site was determined by comparison with the non-application site.
As a result, the composition of the present invention (Examples 1 to 28) containing (A) clobetasone butyrate and (B) drug was compared with Comparative Example 2 in which only (A) was blended, and only in (B). Compared to Example 1, good results were obtained.

[Formulation 1] Lotion preparation clobetasone butyrate 0.05
Dipotassium glycyrrhizinate 0.3
Allantoin 0.2
Trimethylglycine 3.0
Glycerin 3.0
Hydroxypropyl methylcellulose 0.1
Phenoxyethanol 0.3
Total remaining amount of purified water 100.0 (mass%)
Dissolve each component in purified water to prepare a lotion preparation. The product of the present invention is used as a daily care agent for patients with atopic dermatitis.

[Formulation 2] Gelatin clobetasone butyrate 0.05
Dipotassium glycyrrhizinate 0.5
Water-soluble placenta extract 0.1
Trimethylglycine 5.0
1,3-butylene glycol 3.0
Carboxyvinyl polymer 0.6
Phenoxyethanol 0.3
Ethanol 5.0
Sodium hydroxide 0.1
Total remaining amount of purified water 100.0 (mass%)
Each component is dissolved in purified water and neutralized with an aqueous sodium hydroxide solution to prepare a transparent gel. The product of the present invention is used as a sensitive skin care agent.

[Formulation 3] Latex oil phase clobetasone butyrate 0.05
Glycyrrhetinic acid 0.3
Cetanol 5.0
Squalane 2.0
Soy lecithin 1.0
POE (20) lauryl ether 3.5
Glycerol monostearate 1.5
l-Menthol 1.0
Aqueous betaine (trimethylglycine) 5.0
Glycerin 1.0
Propylene glycol 2.0
Smectite 0.5
Dibucaine hydrochloride 0.5
Sodium carboxymethylcellulose 0.2
Total remaining amount of purified water 100.0 (mass%)
Heat to 70 ° C., add the dissolved oil phase to the aqueous phase heated to 70 ° C., and emulsify with an emulsifier to prepare an emulsion. The product of the present invention is used for the treatment and care of dry dermatosis.

Claims (1)

(A) Ester steroid (B) Tocopherol acetate, vitamin A oil, urea, crotamiton, isopropylmethylphenol, ethyl aminobenzoate, lidocaine hydrochloride, lidocaine, dibucaine hydrochloride, dibucaine, camphor, diphenhydramine, diphenhydramine hydrochloride, chlorfeni maleate Lamin, menthol, benzethonium chloride, glycol salicylate, methyl salicylate, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, glycyrrhetinic acid, chlorhexidine hydrochloride, allantoin, zinc oxide, eucalyptus oil, eucalyptus soft extract, heparin-like substance, shikon soft extract A skin external preparation composition comprising one or more types of physiologically active ingredients.