JPS6028920A - External preparation for skin - Google Patents

Abstract

PURPOSE:An external preparation for the skin useful for remedying and preventing skin diseases such as humid tetter, acne, wound, or protecting the skin as a drug, quasi-drug, or cosmetic, containing dipyruvic triureide. CONSTITUTION:An external preparation for the skin containing dipyruvic triuredie as an active ingredient. The external preparation for the skin has remedy promoting action on damaged parts such as wound, ulcer, burn, etc., astringent action, and covering action. It is useful for remedying erosion of the skin or mucosa, ulcer, and skin diseases such as humid tetter, etc., and used as drug or guasi-drug having the above-mentioned medicinal effects. Since the active ingredient has no irritation to the skin, it may be blended with cosmetic, it prevents skin irritations of lips and chapped skin, is expected to have soft feeling in use, to make people undergo rejuvenation, etc. An amount of the active ingredient added is 0.01-20wt% based on the whole amount of pharmaceutical preparation, preferably 0.01-5wt% in the case of cosmetic, and 1-20wt% in the case of quasi-drug.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides a method for incorporating dibilvic triureide into Ir! It is classified as a topical skin preparation for treating f symptoms.

dibilvic triureide
For example, Bulletin of
t,he C1+cmj,cal 5ocietyo
f Japan (Pretin of the Fist of Chemical Science Op Japan) Volume 39 Page 1559 (1
Although it has been known for a long time, as its production method was described in 1996), its pharmacological effects had not been reported.

The present inventors have synthesized various allantoin-related compounds and conducted intensive research on their physiological activities and physical properties, and have previously discovered that 5-methylallantoin has an extremely excellent therapeutic effect on peptic ulcers, and is currently applying for a patent. (Japanese Patent Application No. 57-48129), but we have now discovered that its intermediate, dibilbic triureide, has excellent effects on the skin. In other words, dibilbic triureide is effective for treating eczema, acne, and damaged areas, as well as for suppressing keratin and for other general skin moxibustion treatments.Furthermore, it has found applications in cosmetics, and further research is needed. This led to the completion of the present invention.

Therefore, the skin external preparation of the present invention containing dibilbic triureide exhibits a healing promoting effect on damaged areas such as wounds, ulcers, and burns, and also has an astringent and covering effect, and has an effect on the skin, mucous membranes, etc. A drug that is beneficially used in the treatment of ulcers, and is also used for dermatological diseases such as eczema, and has medicinal properties.

Non-pharmaceutical applications are possible. Furthermore, dibilubitric triureide does not cause skin irritation, so it can be incorporated into many cosmetic products. For example, if we take a lipstick as an example, the lipstick tip is 1.L: L. In addition, it is possible to cleanly repair wrinkles and cracks on the lips.

To obtain the skin external preparation of the present invention, dibilbic triureide is added to @drugs, quasi-drugs, cosmetic ointments, and 1. Emulsification is achieved by adding directly to a base such as an emulsion, gel 9 solution, 1) K agent, or by pre-dissolving it in the oil phase thereof and blending it with a solvent such as A or alcohol. , by performing processes such as mixing, dispersion, and dissolution. In the case of a powder, dibilbic triureide is directly added, and the powder can be obtained by ordinary processing such as mixing and dispersion. In the manufacturing method of these companies, pharmaceuticals,
Known methods in the field of quasi-drugs and cosmetics η can be employed.

The thus obtained external preparation of the present invention can be used as a medical product, quasi-drug, or cosmetic for humans or mammals for the purpose of treating and preventing skin diseases, protecting the skin surface, and the like.

The blending amount of dibilbic triureide in the present invention is:
The amount is in the range of 0.01 to 20 parts by weight based on the entire formulation, but the amount can be selected as appropriate depending on the form and usage method of the cosmetic or external pharmaceutical preparation. Generally, it is preferably 0.01 to 5% by weight for cosmetics and 1 to 20% by weight for external pharmaceutical preparations. When added to external pharmaceutical preparations, the above-mentioned medicinal effects can be expected, and when added to cosmetics, for example, it prevents skin roughness, provides a moist feeling, and provides a youthful and fresh feeling with fine elasticity. You can expect it to improve your skin.

To synthesize the dibilvic triureide of the present invention, a method is employed in which urea and pyruvic acid are reacted in the presence of a dehydrating agent (preferably an acid catalyst). This reaction is carried out at room temperature or under slight heating, and an inorganic acid such as hydrochloric acid or sulfuric acid is used as the acid catalyst. The reaction usually completes in 3 days, and after the reaction, the desired product is extracted by means known per se (extraction, washing).

"C" is easily isolated by recrystallization, etc.). The dibilibic triuret r-do obtained here is
! Since there are only descriptions of dots and elemental analysis, we confirmed this structure by measuring the spectra and got 7.

Next, LTL! of the skin external preparation of the present invention! The manufacturing method and effects will be explained using examples.

Synthesis example Method for producing dipyribinoctriurene f-do Concentrated hydrochloric acid 8
．． 5 ml 7.5 g of K urea was dissolved, and 5.0 g of pyruvic acid was added dropwise to the solution at room temperature with stirring, followed by further stirring. The reaction mixture became cloudy in about 10 hours and almost solidified after about 3 days.

By combining the colorless solid dilute ammonia water obtained by filtration with acetic acid, 69 g of colorless sword-shaped crystals with a decomposition point of 300 U or more were obtained. %) (!oHx2N60i・21hn calculated value C
,33,75;H,5,o3;,! ? , 26. a4 Experimental value c, 34. oo;n, 4.6a;n, 2a:58 thin layer chromatography (developing solvent n-butanol:dioxane:water = 4:1:2) Rf value = 0.
50 Nuclear magnetic resonance spectrum δ(rn, +5o-ds)1.
33 (- double line, CBS) 6.62. 'i', 90 and 10.27 (each - double line.

NH) Example 1 Powder for external use Dibilbic triureide 60 parts Magnesium carbonate 4073 (part 2 parts by weight Ethyl paraoxybenzoate ii 1.000 parts by weight Corn starch previously dried at 60 pK for 16 hours and each raw material Weigh and ■combine.

Example 2 External ointment 1 g of dibilvic triureide O was uniformly dispersed in a water-absorbing ointment prepared in accordance with the prescription and manufacturing method of the Pharmacopoeia ``Fueju Revised 1'' to give a total of 1 g of ICl.

The prescription for the water-absorbing ointment is as follows.

White petrolatum 4g, tentanol: t, sg, sorbitan hiskioleate 0.5g, lauromacrogol o, o
sg, 001 g of ethyl benzoate, 001 g of butyl benzoate, and 15) purified water with the whole view as log.

Example 3 Lipstick Beeswax 10 Carnauba wax 5 Candelilla wax 4 Lanolin 8 Liquid paraffin 2() Een probilimiristate 15 2-octyldodecyl myristate 10 Pigment 1.
4 Fragrance 15 Antioxidant Appropriate amount Example 4 Skin cream Divirpic triureide 1.0% Squalane 100 Vaseline 9.0 Beeswax 4.0 Microwax 8.0 Isopropyl myristate 5. 0 2-octyldodecyl myristate 10.0 Polyoxyethylene monostearate 4.0 Sorbitan monostearate) a, O Propylene glycol 10.0 Distilled water 35.0 Example 5 Effect on pharmacological wound treatment .

A circular skin defect was created on rat back skin scraps, and the external preparation obtained in Example 1 and Example f? + Apply only the base excluding 5-mebulallantoin of 1 to the wound surface 0.0
The wound healing effect was investigated by spraying 4g with a healing agent, and the result was 2.

Treatment with the external preparation obtained in Example 1 accelerated the healing of the wound, shortened the healing time, and showed better results than the base group in terms of the degree of effect. The result is the first
Shown in the table.

Table 1: Impact on wound healing time.

Note) [N, s, J no significant difference [P<0. Ol and P<0.05J mean "significant difference at risk rates of 1% and 5%", respectively.

"s, E, J standard error Example 6 Local irritation Example 1 was carried out using ocular mucosa, healthy skin, and injured skin from which the stratum corneum was removed from rabbits, which are highly sensitive to irritating substances.
The local irritation effect of the external preparation obtained was observed. As a result, some cases of slight temporary redness of the conjunctiva were observed in the ocular mucosa, but no effect on the cornea was observed.

In a batch test on the skin, slight redness was observed in some cases, but it was only temporary, and no bleeding or irritation was observed even on damaged skin.

From the above results, the external preparation obtained in Example 1 does not exhibit any worrying local irritation effects.

Acute Toxicity of Dibilpic Triureide (ddY Pine Mouse 1! FF10 Patent Applicant: Grelan Pharmaceutical Co., Ltd. Permagam Asia Co., Ltd.

Claims (1)

[Claims] External skin preparation characterized by containing dibilvic triureide