JPH03178916A - Skin external agent - Google Patents

Abstract

PURPOSE:To provide the title agent good in penetrability into the skin, developing no irritation, having excellent effects on dermatitis seborrheica coming of excessive sebum secretion, containing a tannin compound(s) as an active ingredient. CONSTITUTION:The objective skin external agent containing a tannin compound(s) as an active ingredient. In its application, the tannin compound(s) is incorporated in the whole composition at such an amount as to be 0.0001-5 (pref. 0.001-2)wt.%. In addition to this active ingredient, an antifungal agent(s) such as sulfur, hinokitiol, triclosan and/or trichlorocarbanilide, vitamin preparation(s), oil component(s), surfactant(s), etc., are incorporated into a form of cream, ointment, etc. The above-mentioned active ingredient compound(s) is expressed by formula I, II and/or III (G is galloyl group of formula IV; n+k+l+m=1-6), being obtained by extracting, in general, paeonia albiflora, Japanese gall, paeonia suffruticosa or cranesbill. It can also be produced by chemical synthesis.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to an external preparation for skin. More specifically, the present invention relates to an external skin preparation containing a tannin compound as an active ingredient and having excellent effects on seborrheic diseases such as dermatitis caused by excessive secretion of sebum.

[Prior Art] Tannin is well known as a component of various crude drugs that have been used as Chinese herbal medicine since ancient times, and is listed as tannic acid in the Japanese Pharmacopoeia. Medicinal effects include astringent action,
Antioxidant effects have been reported. Further, gallotannin is composed of glucose and gallic acid, and is usually a mixture of various compounds in which the gallic acid is bound at different positions.

On the other hand, to date, no compound has been known that specifically inhibits sebum secretion and does not affect other organs.

The sebum suppressant sibrothyrone acedate is available for oral administration, but oral administration often has greater side effects than topical use. Also, due to its anti-androgenic properties, sibrothyrone acetate can only be used by women.

Problems to be Solved by Invention F] The present inventors conducted intensive research to obtain a compound that specifically inhibits sebum secretion and does not affect other organs, and found that a tannin compound was blended as an active ingredient. discovered that a topical preparation consisting of
The present invention has now been completed.

[Means for Solving the Problems] That is, the present invention is an external skin preparation characterized by containing a tannin compound as an active ingredient.

Hereinafter, the configuration of the present invention will be explained in detail.

The tannin compound according to the present invention usually refers to a compound in which a hydroxyl group such as gallic acid and a phenolic carboxylic acid is bonded to an ester. For example, a tannin compound in which gallic acid is bonded to a catechol by an ester bond such as gallocatechin, evika chicken, gallocatechin gallate, etc. Examples include hydrolyzed tannins such as gallotannin (= galloylglucose), in which gallic acid is ester-bonded with glucose.

The tannin compound used in the present invention may be any of the above compounds, but is represented by the following general formula: tetra-GG penta-GG hexa-GG counter GG In addition to using extracts from plants such as Gobaiko, Botanpi, Gennoshoko, etc., it is also produced by chemical synthesis.

For example, if you want to obtain gallotannin from a medicine, add 5
After extraction with 0% acetone solution, saturated saline and ethyl acetate are added to the resulting extracted solution. The solvent in the ethyl acetate transfer zone is distilled off to obtain gallotannin. Separate and purify using high performance liquid chromatography, etc., if necessary.

The amount of the tannin compound incorporated in the skin external preparation of the present invention is not particularly limited, but it is preferably 0.0001 to 5% by weight, preferably 0.001.2% by weight based on the total composition. 0
．． If it is less than 0,001% by weight, the sufficient sebum-suppressing effect of the present invention cannot be obtained, and if it exceeds 5% by weight, it will be colored, which is not preferable in terms of formulation.

In addition to tannin compounds, the skin external preparation of the present invention includes sulfur, hinokitiol, triclosan, trichlorocarbanilide, chlorhexidine hydrochloride, chlorhexidine gluconate, helocarban, chlorophenesin, benzethonium chloride, benzalkonium chloride, Antibacterial agents such as lysodem, alkyldiaminoethylglydine hydrochloride, isopropylmethylphenol, benzoic acid, photosensor No. 201, thymol, hexachlorophene, berberine, deoxolone, and vitamins A, B2, B6, B12,
C1DXE1 Vitamins such as biotin and nicotinic acid, exfoliating agents such as zarydylic acid and resorcinol, glycyrrhetinic acid, glycyrrhizic acid, allantoin, epsilon aminocaproic acid, butyl flufenamate, azulene, camphor, zinc chloride, zinc white, menthol, Anti-inflammatory agents such as indomethacin, ibuprofen piconol, mefenamic acid and their derivatives, sebum suppressants such as edinyl estradiol, as well as zinc and its compounds,
Although it varies depending on the lactic acid and its properties, oils, surfactants, water, ethanol, humectants, thickeners, fragrances, pigments, and the like can be appropriately blended within the range that does not impair the effects of the present invention.

The skin external preparation of the present invention may be in any form as long as it can be applied to the skin, such as a cream, ointment, or lotion.

[Effects of the Invention] The skin external preparation of the present invention exhibits a very good reversible and local sebum suppressing effect. Furthermore, the tannin compounds according to the present invention penetrate the skin very well and cause little irritation, so they are particularly suitable for the treatment of seborrheic diseases. This activity is specifically directed towards sebum and has no effect on other organs.

[Example] Next, the present invention will be described in more detail with reference to Examples. The present invention is not limited thereto.

[Sebum synthesis inhibition rate test] Testosterone 0.5μg/group to 5 female hamsters
20 ml of acetone/day was applied to stimulate sebum synthesis in the ear sebaceous glands, and after 24 hours, 100 μg/acetone/day of the tannin compound of the present invention was applied, and the inhibition rate of sebum synthesis was measured. In addition, a control group was defined as t=1 to which testosterone was applied and a control group to which no tannin compound was applied.

The degree of sebum synthesis is determined by incubation of ear biopsies with radioactive acetate [(Hall D.

W, R, et al., Hormonal control of otic sebaceous gland lipid formation in hamsters, Arch, Dermatol, Res, 27
5.1 (1,983)]. The test was based on the conversion of radioactive acetate added into the lipids, which was measured in a cindersion counter after extraction with hexane. The results are shown in Table-1. The percentage can exceed 100%.

Thus, highly active compounds suppress both the testosterone-stimulated activity and the basal sebum synthesis of the sebaceous glands.

As shown in Table 1, the formula for calculating the sebum synthesis inhibition rate (%) shows that the tannin compound of the present invention has an excellent ability to inhibit sebum synthesis. Furthermore, among them, galloylglucose has a particularly excellent ability to inhibit sebum synthesis.

Example 1 Weight % 1) Solid paraffin 10.02) Peace wax 10.03) Squalane 10.04) Pentagalloylglucose 1.05) Fragrance
Appropriate amount 6) Vaseline
69.0" Mix the two components,
After heating and dissolving the mixture at 80° C., the mixture was stirred and cooled to obtain an ointment.

[Sebum Suppression Effect Test] An ointment-type skin external preparation obtained by the above-mentioned formulation and manufacturing method was used.

(Targets for use and observation period) Twenty patients with seborrheic dermatitis aged 15 to 28 years were used for two weeks.

(How to use) After thoroughly washing the face with cosmetic soap, the above-mentioned ointment-type skin preparation for external use was applied only on the sebum 1 to 3 times a day.

(81J of sebum) The total amount of sebum before use and after 2 weeks of use was collected using the glass cup method and weighed using the gravimetric method [Ohokawa, H., et al.
l,,Anal,Biochem,,95.35135
8 (1979)]. The amount of sebum was expressed as a relative ratio as shown in the following formula.

Reduction rate E - '-'s ×100 Total sebum volume before use (general improvement level) Compared to before use, the degree of improvement in symptoms due to topical agent application was reduced (廿), somewhat reduced (+), and unchanged (±) , exacerbation (-) of 4
Divided into stages.

2 8 Male 0 廿2 Male 1 廿4 Male 15 Male + 8 Male ± 5 Male 2 廿8 Male + 1 Female + 2 Female ± 0 7 Female 2 + 1 3 Female ± 2 2 Female + 10 males, 10 females The results of clinical tests on 20 famous people showed that the average sebum reduction rate was 8.9%, and the degree of improvement of symptoms by applying topical preparations was mild (25%), mild (40″X), and unchanged (35%). , exacerbation (0%), demonstrating the effectiveness of the skin external preparation of the present invention.

Example 2 Lotion 1) Glycerin 2) Citric acid 3) Sodium citrate 4) Allantoin Weight % 5.0 0.03 0.05 0.1 4 5) Ethanol (95%) ],
0.06) Polyoxyethylene (hereinafter referred to as POE)
(15 mol) oleyl alcohol ether
1.07) Bentaga 1 Coil Glucose 1゜08) Ultraviolet absorber
0.19) Fragrance
0.110) Preservatives
0.111) Pigment
Appropriate amount 12) Purified water Remainder 5
) 6) 9) 10) were mixed and dissolved at room temperature, and 1) 2) 3) 4)? )8) 11)1
2) A lotion was obtained by stirring and adding to the solution.

Example 3 Lotion 1) Sorbitol (70%) 2) Glycerin 3) Water 4) Glycyrrhizic acid 5) Vitamin B2 6) Botanpi extracted tannin weight % 3.0 5.0 70.899 0.5 0.07 0, O3 5 7) P OE hydrogenated castor oil derivative 0.5
8) Ethanol 20.09
) Ethinylestradiol 0.00110
) Fragrance appropriate amount 1,) 2
)3)4. ) are mixed and dissolved, and added to this 5)6)?
) 8) 9) The mixed solution of 10) was added with stirring to obtain a lotion as a homogeneous solution.

Example 4 Emulsion 1) Setanol 2) Stearic acid 3) Palmitic acid 4) Liquid lanolin 5) Squalane 6) Isopropyl myridate 7) Glyceryl monostearate 8) POE (20 mol) Sorbitan monolaurate 9) Allantoin 10) Propylene Glycol weight % 1.5 0.1 0.1 1.0 2.0 1.0 1.5 0.5 0.5 3.0 6 1]) Polyethylene glycol 400 2.
012) l-liethanolamine 1.
013) Catechin 0.0
114) Galloylglucose mixture 0.09
15) Purified water 84.81
) to 9) were mixed to obtain a mixture. Separately, 10
) to 14) were mixed to obtain a mixture. Each mixture was heated and dissolved separately at 70°C, mixed and emulsified using an emulsifier, and then cooled by heat exchange to obtain an emulsion.

Example 5 Cream 1) Glycerin 2) Polyethylene glycol (molecular weight 400) 3) Glydyllidic acid monoammonium salt 4) Allantoin 5) Peony extract tannin mixture 6) Cetanol 7) Squalane weight % 5.0 2.0 0.1 0. 1 5.0 4.0 5.0 7 8) Stearic acid 1.09
) Beeswax 1.010
) Vaseline non 1.01
],) P OE (25 mol) Cedyl alcohol
2.0 Ether 12) Grillceryl Monostearate 1.51
3) Preservative 0.1514
)Fragrance 0.1515)
Purified water 67.0 Manufacturing method 5) to 14) were mixed and dissolved, and 1) and 2 were similarly mixed and dissolved.
) Stir and mix into 3) 4N and 5) to emulsify. The emulsified particles were prepared using a homogenizer, and then cooled to room temperature using a heat exchanger to obtain W10 type cream.

Example 6 Pack 1) Polyvinyl alcohol 2) Polyethylene glycol (molecular weight 400) 3) Glycerin 4) Ethanol (95%) Weight% 10.0 0.4 3.0 8.0] 5) Geranin 0.16
) Pentagalloylglucose 0.27) Preservatives 0.18) Flavorings
0.19) Purified water
78.1 Manufacturing method Mix and dissolve 4) to 8) at room temperature, 1) 2) 3) and 9
) was mixed and dissolved at 80° C. and then added with stirring, and then allowed to cool to room temperature to obtain a pack.

Example? Ointment Weight% 1) Solid paraffin 10.02) Peace wax 10.03) Squalane 10.04) -\Quizagaloylglucose 1.05) Resorcinol 0.16) Zinc white
0.57) Fragrance
Appropriate amount 8) Vaseline
68.4 Mix the above ingredients and make the mixture 8
After heating and dissolving at 0° C., the mixture was stirred and cooled to obtain an ointment.

Example 8 Hair tonic Weight% 1) Ethanol 52.02) Hinokidiol 0.53) Vitamin EO13 4) POE (60 mol) 1.0 Hydrogenated castor oil 5 Fragrance Appropriate amount 6 Epigallocatechin 0.27 Purified water
45.08 Glycerin
1.09 dye
Appropriate amounts of 1) 2) 3) 4) and 5) were dissolved at room temperature to obtain an alcohol phase. The mixed solution of 6), 7), 8), and 9) was dissolved under heating and cooled to obtain an aqueous phase. The alcohol phase was added to the aqueous phase and solubilized to obtain a hair tonic.

Example 9 Lotion Weight% 1) Tetragalloylglucose 1.00 2) P OE (60 mol) Hardened Mustard Oil
2.03) Glycerin 10.
04) Dipropylene glycol 10.05
) 1.3-Butylene glycol 5.06) Polyethylene glycol 1500 5.07) Cedyl isooctanate 10.08) Squalane 5.09) Methylparaben 1.010) Carboxyvinyl polymer 0.311) Sodium hexametaphosphate 0. 0812) Ion exchange water
11.013) Potassium hydroxide
0.1214) Ion exchange water
39.51)2)3)4. )5)6) at 60℃
Heat and dissolve. Add and mix 7), 8), and 9) heated and dissolved at <60°C, and process with a homomixer to form a gel. Next, add 10), 11) and 12 to this gel.
) was gradually added and dispersed with a homomixer, then the solution of 13) and 14) was added and mixed, and emulsified with a homomixer.

Claims (2)

[Claims] (1) A skin external preparation characterized by containing a tannin compound as an active ingredient. (2) The skin external preparation according to claim 1, wherein the tannin compound is a gallotannin represented by the following formulas 1 to 3. Tetra-GG Penta-GG Hexa-GG- Undeca-GG Formula 1 Formula 2 Formula 3 ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼▲ There are mathematical formulas, chemical formulas, tables, etc. ▼▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ n + k + l + m = 1 to 6 G: galloyl group ▲ Numerical formulas, chemical formulas, tables, etc. are available ▼ G-Gk-, G-Gl, G-Gm-, -G-Gn-,:
Polygalloyl group GG: gallotannin