JP2000229884A - Skin lotion - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a skin lotion, having excellent improving and preventive effects on itching accompanied by dry dermatosis and inflammatory dermatosis or the like, such as atopic dermatosis by adding a specific amount of a heparin analogue to a preparation containing an antihistamic agent. SOLUTION: This skin lotion is obtained by adding (B) 0.01-2.0 wt.%, preferably 0.05-1.0 wt.% heparin analogue based on the whole preparation and in the proportion regulated so that the weight ratio of an antihistamic agent (e.g. diphenhydramine) to the component B may be (1:20)-(250:1), preferably (1:2)-(50:1) to (A) antihistamic agent-containing preparation. The component B is preferably polysulfate of mucopolysaccharides, prescribed in the standard of non-official drugs in the Pharmacopoeia of Japan. If necessary, an antiinflammatory agent, a local anesthetic, an antimicrobial agent, vitamins, a refrigerant or the like can be formulated with the preparation.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an external preparation for skin having an excellent effect of improving and preventing itch accompanying dry skin disease and inflammatory skin disease represented by atopic dermatitis and housewife eczema. About.

[0002]

2. Description of the Related Art With the westernization of dietary habits, changes in living environment, aging and increased stress, various skin diseases, especially dry skin diseases and inflammatory diseases represented by atopic dermatitis and housewife eczema, etc. The number of people suffering from skin diseases is increasing. These diseases are accompanied by strong pruritus, and dermatological drugs containing an antipruritic component such as crotamiton or an antihistamine as an active ingredient are widely used for the treatment.

[0003] However, the effect of a dermatological agent containing an antipruritic component such as crotamiton or an antihistamine as an active ingredient has not been sufficient for strong pruritus. In other words, in the dermatological drug containing crotamiton and an antihistamine, the effect of suppressing itch can be expected to some extent, but its action onset time is slow and its action time is short,
There is a problem that frequent application is required.

[0004] The present invention has been made in view of the above circumstances, and by using a heparin-like substance in combination with an antihistamine, the antipruritic effect of the antihistamine is enhanced, and dry skin typified by atopic dermatitis, housewife eczema, etc. It is an object of the present invention to provide an external preparation for skin having an excellent effect of improving and preventing intense itch accompanying diseases and inflammatory skin diseases.

[0005]

Means for Solving the Problems and Embodiments of the Invention The present inventors have conducted intensive studies in order to achieve the above object, and as a result, have found that dry skin represented by atopic dermatitis, housewife eczema, etc. Focusing on antihistamines for strong pruritus associated with diseases and inflammatory skin diseases, etc.
The present inventors have found that the combined use of a heparin-like substance having a blood circulation promoting action, a keratin water retention enhancing action, an anti-inflammatory action and the like enhances the antipruritic effect of an antihistamine, and has accomplished the present invention.

That is, the present invention provides an external preparation for skin characterized in that a preparation containing an antihistamine agent contains 0.01 to 2.0% by weight of a heparin-like substance. Here, it is particularly effective in a preparation containing 0.1 to 5.0% by weight of an antihistamine.

The external preparation for skin according to the present invention is a combination of an antihistamine and a specific amount of a heparin-like substance. Examples of the antihistamine used in the external preparation for skin of the present invention include diphenhydramine, diphenhydramine hydrochloride, lauryl. Examples include diphenhydramine sulfate, chlorpheniramine maleate, and isotipezil hydrochloride. These antihistamines can be used alone or in an appropriate combination of two or more.

The amount of the above-mentioned antihistamine in the external preparation for skin of the present invention can be appropriately selected, and the amount is not particularly limited. 0% by weight (hereinafter simply abbreviated as%), particularly preferably 0.5 to 3.0%.
If the amount is too large, no further effect can be obtained, so that it is not economical. If the amount is too small, a sufficient antipruritic effect cannot be obtained even if a large amount of a heparin-like substance is used in combination.

The heparin-like substance used in the external preparation for skin of the present invention is a polysulfate ester of mucopolysaccharide, and those listed in the Japanese Pharmacopoeia Non-Pharmaceutical Standard are preferably used.

The amount of the above-mentioned heparin-like substance in the external preparation for skin of the present invention can be appropriately selected, and the amount is not particularly limited. 2.0%, especially 0.05-1.0%
It is desirable that If the amount is too large, the effect of the further compounding cannot be obtained and it is not economical. If the amount is too small, a synergistic effect may not be obtained in combination with the antihistamine.

As described above, the heparin-like substance is used together with the above-mentioned antihistamine to enhance the antipruritic effect of the antihistamine, and to cause dry skin diseases and inflammatory skin diseases represented by atopic skin and housewife eczema. And the like, which synergistically improve the excellent and preventive effects against strong itch associated with the above. The mixing ratio of the heparin-like substance to the above-mentioned antihistamine is not particularly limited, but is usually an antihistamine: heparin-like substance. (Weight ratio) = 1: 20 to 250: 1, preferably 1: 2 to 50: 1. Outside the above range, the effects of the present invention due to the combined use thereof may not be sufficiently obtained.

The external preparation for skin of the present invention may further contain, if necessary, an anti-inflammatory agent, a topical agent, in addition to the above essential components, in order to further enhance the effects on various skin diseases and symptoms, as long as the effects of the present invention are not impaired. Various agents such as anesthetics, bactericides, vitamins, and cooling agents can be added.

Specific examples of these drugs include anti-inflammatory agents such as glycyrrhetinic acid, stearyl glycyrrhetinate, glyceryl glycerin, glycyrrhetinic acid pyridoxine and other glycyrrhetinic compounds, glycyrrhizic acid, trisodium glycyrrhizinate, dipotassium glycyrrhizinate Glycyrrhizic acid compounds such as monoammonium glycyrrhizinate, methyl glycyrrhizinate, hydrocortisone, hydrocortisone acetate, hydrocortisone butyrate, prednisolone, prednisolone valerate acetate, dexamethasone, dexamethasone valerate,
Steroidal anti-inflammatory drugs such as dexamethasone propionate, clobetasone butyrate, alclomethasone propionate, flumethasone pivalate, triamcinolone acetonide, fluocinolone acetonide, dexamethasone valerate, beclomethasone propionate, betamethasone valerate, halcinonide, amcinonide, and difluprednate Agents, non-steroidal anti-inflammatory agents such as bufexamac, ibuprofen, ibuprofen piconol, indomethacin, ufenamate, ketoprofen, suprofen, piroxicam, felbinac, flurbiprofen, bendazac, lysozyme chloride, bromelain, serrapeptase, semi-alkaline proteinase And the like, and these may be used alone or in appropriate combination of two or more. Can, as the amount thereof, it is preferable 0.01% to 5% of the total formulation.

Examples of the local anesthetic include lidocaine, dibucaine or a hydrochloride thereof, ethyl aminobenzoate and the like. These can be used alone or in combination of two or more as appropriate. as,
0.1 to 2% is suitable for the whole preparation.

Examples of the bactericide include chlorhexidine hydrochloride, benzalkonium chloride, benzethonium chloride, depotassium chloride, biosol, and phenol. These can be used alone or in combination of two or more. The compounding amount is preferably 0.05 to 1% based on the whole preparation.

The vitamins include, for example, tocopherol, tocopherol acetate, cholecalciferol, pyridoxine hydrochloride, retinol palmitate, vitamin A oil and the like. These may be used alone or in combination of two or more. It is possible that the compounding amount is 0.05 to 3% based on the whole preparation.

Examples of the cooling agent include menthol, camphor, borneol, cauliflower oil and the like.
These can be used alone or in appropriate combination of two or more kinds.
~ 5% is preferred.

Further, the skin external preparation of the present invention may contain, in addition to the above-mentioned components, surfactants, oils, alcohols, humectants, thickeners, etc., as long as the effects of the present invention are not impaired. Agents, organic and inorganic powders, preservatives, antioxidants,
Chelating agents, pH adjusters, fragrances, dyes, and the like can be appropriately compounded as necessary.

The external preparation for skin of the present invention may be in any form, for example, a solution, an emulsion, a cream, an ointment, a gel preparation, a spray, an aerosol, a solid, a poultice, Packing agents, tape agents, sheet agents and the like can be exemplified, but not limited thereto.
In addition, the preparation method is not particularly limited,
For example, appropriate components such as known excipients necessary for preparing formulations of various dosage forms can be blended with the above essential components and optional components, and can be prepared by a conventional method of each formulation.

The amount and usage of the external preparation for skin of the present invention are not particularly limited, and can be appropriately selected depending on the above-mentioned dosage forms and the like, and the dryness represented by atopic dermatitis, housewife eczema, etc. Dry skin disease and inflammatory skin several times a day with the usual amount of various skin external preparations such as conventional drugs, quasi-drugs, and cosmetics used for itching associated with skin disease and inflammatory skin disease By applying it evenly to the affected area of the disease and its vicinity, it is applied to the skin with itching to synergistically improve the antipruritic effect of antihistamines, and to improve dry skin disease and inflammatory Excellent improvement or prevention of intense itch associated with skin diseases and the like can be achieved.

As described above, according to the external preparation for skin of the present invention, a remarkable improvement effect and a preventive effect can be obtained with respect to strong itch accompanying dry skin disease and inflammatory skin disease.

[0022]

EXAMPLES Hereinafter, the present invention will be described in detail with reference to Examples and Comparative Examples, but the present invention is not limited to the following Examples.

[Example 1 and Comparative Examples 1 to 4] For the compositions shown in Table 1, the oil phase A and the water phase B were each dissolved by heating at 70 ° C., and the water phase B was gradually added to the oil phase A. And then emulsified to prepare cream preparations (external preparations for skin) of Example 1 and Comparative Examples 1 to 4, and the following tests were performed. Table 2 shows the results.

[Itching Test] About 0.2 g of a sample was applied to a range of about 4 cm in diameter on the forearm flexion side of five healthy persons (panels). Fifteen minutes later, the sample was thoroughly wiped off with alcohol cotton, and the skin was dried. Then, about 0.5 g of freshly ground yam was applied as an antipruritic agent to rub it. Immediately after itching, the degree of itching was scored every 20 seconds according to the following criteria until the itching disappeared, and the total score (cumulative score) was taken as the result. The same treatment was performed 30 minutes before the application of the antipruritic agent. At the beginning of the test,
The test was started after confirming that a very strong itch was felt when the same pruritic agent was applied without treatment. Itching of the criteria score-size constant based on the quasi-4 very itchy, painful itchy (want very scratching) 3 (bearable scraped want, but somehow) quite itchy 2 itchy (can be put up without scratched) 1 slightly itchy, clearly itching No, but there is discomfort 0 Itching and discomfort are not present

[0025]

[Table 1]

[0026]

[Table 2]

According to the results shown in Table 2, the skin external preparation of the present invention (Example 1) in which an antihistamine and a heparin-like substance were used in combination showed a 15-minute application test before pruritus and a 3
An excellent antipruritic effect was shown in any evaluation of the 0-minute application test. On the other hand, in the case of the external preparation for skin in which the antipruritic component was not used in combination with the heparin-like substance (Comparative Example 1), the antipruritic effect was inferior to Example 1 in all tests. This is considered to be because the absorption of the antihistamine into the skin was improved by using the antihistamine and the heparin-like substance in combination. The antipruritic effect of the skin external preparation containing a large amount of the heparin-like substance (Comparative Example 3) was not different from that of Example 1. In addition, the antipruritic effect of the skin external preparation containing a heparin-like substance but not containing an antihistamine (Comparative Example 2) and the skin external preparation (Comparative Example 4) containing an extremely small amount of the antihistamine was extremely low. .

From the above results, the external use of the skin of the present invention containing 0.01 to 2.0% by weight of a heparin-like substance in an antihistamine-containing preparation shows a dryness characteristic represented by atopic dermatitis and housewife eczema. It was found to be very useful for improving and preventing intense itch associated with skin diseases and inflammatory skin diseases.

Hereinafter, the present invention will be described more specifically with reference to examples.

The above components were dissolved to obtain a liquid preparation.

Example 3 Emulsion A: Oil Phase Composition (%) Diphenhydramine 1.0 Stearyl glycyrrhetinate 0.5 Sorbitan monostearate 3.0 Polyoxyethylene (20) Sorbitan monostearate 4.0 Stearyl alcohol 5.0 Diisopropyl adipate 1.0 B: Aqueous phase part Heparin-like substance 0.3 1,3-butylene glycol 5.0 Methylparaben 0.2 Carboxyvinyl polymer 0.2 Potassium hydroxide Appropriate amount Purified water Balance total 100.0

The above A and the B component excluding potassium hydroxide are dissolved by heating at 65 ° C., and B is gradually added to A, followed by emulsification and cooling.
The emulsion was neutralized with potassium hydroxide.

[0033]

After dissolving each of the above components except sodium hydroxide, the mixture was neutralized with sodium hydroxide to obtain a gel ointment.

Example 5 Cream A: Oil Phase Composition (%) Stearyl Alcohol 3.0 Squalane 27.0 Sorbitan Monostearate 3.0 Polyoxyethylene (20) Sorbitan Monostearate 4.0 Adipic Acid Diisopropyl 1.0 butylparaben 0.1 B: aqueous phase Chlorpheniramine maleate 0.5 Heparin analogue 0.3 1,3-butylene glycol 5.0 methylparaben 0.2 Purified water 55.9 Total 100.0

The above components A and B are dissolved by heating at 70 ° C.
B was gradually added to A and emulsified and cooled to obtain a cream.

[0037]

The above components were dissolved to obtain a liquid preparation.

[Example 7] Composition of oily ointment (%) Diphenhydramine lauryl sulfate 3.0 Heparin analogue 0.2 Stearyl alcohol 5.0 Purified water 2.0 Glycerin monostearate 2.0 Polyoxyethylene (20) Sorbitan monostearate 0.3 Gelled hydrocarbon 85.5 Total 100.0

Diphenhydramine lauryl sulfate, stearyl alcohol, glyceryl monostearate, sorbitan monooxyethylene (20)
After heating and dissolving at 0 ° C., a heparin-like substance and a gelled hydrocarbon previously dissolved in purified water were kneaded to obtain an oily ointment.

An antipruritic test was carried out on the external preparations for Examples 2 to 7 in the same manner as in Example 1, and all the preparations showed excellent antipruritic effects.

[0042]

As described above, the skin external preparation of the present invention enhances the antipruritic effect of an antihistamine by using a combination of an antihistamine and a heparin-like substance, and is typified by atopic dermatitis and housewife eczema. It is possible to provide an external preparation for skin having an excellent effect of improving and preventing intense itch accompanying dry skin disease, inflammatory skin disease and the like as well as an effect of improving skin roughness due to skin disease.

Claims (2)

[Claims] The present invention relates to an antihistamine-containing preparation, wherein
An external preparation for skin, characterized by containing 2.0% by weight of a heparin-like substance. 2. The external preparation for skin according to claim 1, wherein an antihistamine is contained in an amount of 0.1 to 5.0% by weight based on the whole preparation.