JPH07316058A - Metabolic activator, skin preparation for external use and bathing agent - Google Patents

Abstract

PURPOSE:To obtain a metabolic activator excellent in promoting actions on metabolic activities of the skin and further in safety, a skin preparation for external use, containing the activator blended therein and having improving actions on the conditions of the skin and reducing actions on winkles and a bathing agent. CONSTITUTION:This metabolic activator comprises a steroid derivative expressed by formula I [R is a group having a carbon skeleton expressed by formula II (the bonds indicated by the dotted line may be present or absent)]. Groups expressed by formulas III to V, etc., are preferred as the group R. The compound expressed by formula I is preferably polyporusterone A in which R is expressed by formula III or polyporusterone B in which R is expressed by formula IV. This compound expressed by formula I is present in Polyporus umbellatus Fries which is one species of fungi and obtained by extracting, e.g. the Polyporus umbellatus Fries with a polar solvent, separating and purifying the resultant extract. Furthermore, the metabolic activator is preferably used in a content of 0.01-10wt.% based on the total amount in blending the metabolic activator in the skin preparation for the external use or the bathing agent.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a metabolic activator, a skin external preparation containing the same, and a bath preparation, and more particularly, a metabolic activator comprising a steroid derivative, a skin external preparation containing the same, and a bath preparation. .

[0002]

2. Description of the Related Art Beautiful, fine-grained skin is something that everyone seeks. However, it is widely accepted that due to the aging phenomenon due to aging, the connective tissue in the skin tissue is remarkably cross-linked and loses elasticity, or the water retention ability is decreased due to the inactivation of metabolism, and the skin becomes dry. This is the reason why the lack of elasticity of the skin and the reduction of water retention are mentioned as one index of aging.

As described above, there are many people who lament that the skin loses its elasticity and becomes dry due to aging. Various makeup cosmetics for hiding the lack of elasticity and the dryness of the skin Various cosmetics have been developed to improve.

However, none of the above-mentioned makeup cosmetics only hides the lack of elasticity of the skin with powder having a high concealing property, and does not improve the condition of the skin. In addition, it has been widely attempted to apply a substance having a high water retention property such as hyaluronic acid to improve the dryness of the skin, but when these substances are removed from the skin, these effects disappear, so I had to say that it was a transitory effect. Therefore, by eliminating the skin's elasticity and improving the inactivation of metabolism that causes the skin to become dry, it is possible to restore the skin's elasticity and improve the dryness of the skin. It was desired to develop a drug that can do it.

On the other hand, it is not known that the steroid derivative represented by the general formula (I) has an action of stimulating the metabolism of the skin, and these are compounded in a skin external preparation or a bath preparation. Thus far, no attempt has been made to improve skin aging.

[0006]

The present invention has been made from the above point of view, and a metabolic activator excellent in the action of promoting the metabolic activity of the skin and further excellent in safety, and a compound thereof Therefore, it is an object to provide a skin external preparation and a bath preparation having a skin condition improving action.

[0007]

Means for Solving the Problems In order to solve the above problems, the present inventor has extensively screened various compounds using the metabolic activation action as an index, and as a result, the general formula (I)
The present invention has been completed by finding that the steroid derivative represented by the formula (5) has an excellent metabolic activation effect.

That is, the present invention is a metabolic activator comprising a steroid derivative represented by the following general formula (I), a skin external preparation and a bath preparation containing the same.

[0009]

[Chemical 10]

However, in the formula (I), R represents a group having a carbon skeleton represented by Chemical formula 11.

[0011]

[Chemical 11]

However, in Chemical formula 11, the bond indicated by the dotted line may or may not exist. Hereinafter, the present invention will be described in detail.

<1> Metabolic Activator of the Present Invention The metabolic activator of the present invention comprises a steroid derivative represented by the general formula (I). As the steroid derivative used in the present invention, preferably, R in the formula (I) is polyporsterone A represented by Chemical formula 12, and similarly, R is represented by Chemical formula 13, polyporsterone B and R are represented by Chemical formula 14. Polyporsterone C represented by R, polyporsterone D represented by Chemical Formula 15,
R is the chemical formula 16 and polyporsterone E is the chemical formula 17
And polyporsterone G in which R is represented by Chemical formula 18, which may be used alone or in combination of two or more. Good.

[0014]

[Chemical 12]

[0015]

[Chemical 13]

[0016]

[Chemical 14]

[0017]

[Chemical 15]

[0018]

[Chemical 16]

[0019]

[Chemical 17]

[0020]

[Chemical 18]

These steroid derivatives represented by the general formula (I) used in the present invention are all known compounds, and one of the fungi, boar (Polyporus umbellatus FRI).
ES) is known to exist.

The above-mentioned steroid derivative can be easily obtained from a boletus extract by, for example, extracting the boletus with a polar solvent by the following method and purifying the obtained extract by a usual separation and purification means. To be

After extracting the boar with a 50% aqueous solution of ethanol by heating and refluxing, the solvent-insoluble matter is removed from the extract by filtration and the solvent is removed by concentration under reduced pressure.
The obtained extract concentrate was separated with diethyl ether and water,
Take out only the diethyl ether layer. The diethyl ether layer is concentrated under reduced pressure and then purified by column chromatography using a mixed solution of chloroform-methanol as an elution solvent and silica gel as a carrier. Alternatively, an acetonitrile aqueous solution having a concentration gradient of 10 to 50% is used as an elution solvent, and O
Purify by column chromatography using DS as a carrier.

According to the above-mentioned method, the steroid derivative represented by the general formula (I) used as the metabolic activator of the present invention, that is, polyporsterone A, polyporsterone B, polyporsterone C, polyporsterone C Porsterone D, polyporsterone E, polyporsterone F, and polyporsterone G are obtained. Further, among these polyporsterone, polyporsterone A and polyporsterone B are preferable in terms of yield and the like.

<2> Skin external preparation of the present invention The skin external preparation of the present invention contains one or more of the above-mentioned metabolic activators as a component having a skin condition improving action. The compounding amount is 0.01 with respect to the total amount of the external preparation.
It is preferably from 10 to 10% by weight. Blending amount 0.01
If it is less than 10% by weight, the effect of improving the skin condition may not be sufficient, and if it exceeds 10% by weight, the effect may reach the ceiling and it is economically undesirable. Further, when the content of the metabolic activator is 0.1 to 1% by weight, the effect of improving the skin is excellent and there is little change in the appearance. Therefore, the more preferable content is 0.1% with respect to the total amount of the external preparation. It is 1 to 1% by weight.

The dosage form of the external preparation for skin of the present invention is not particularly limited, and examples thereof include those commonly used as external preparations for skin, such as lotions, creams, ointments and aqueous gels. These skin external preparations, except for incorporating a metabolic activator consisting of the above steroid derivative,
It can be produced in the same manner as a usual external preparation for skin.

In addition to the above-mentioned metabolic activator, the external preparation for skin of the present invention includes liquid paraffin, hydrocarbons such as petrolatum and the like which are usually applied to external preparations for skin, waxes such as carnauba wax and mokuro, Oils and fats such as olive oil and jojoba oil, esters such as octadecyl palmitate and neopentyl glycol diisooctanate, higher fatty acids such as stearic acid and palmitic acid, higher alcohols such as cetyl alcohol and stearyl alcohol, nonion, anion , Cations, amphoteric surfactants, natural or synthetic fragrances and pigments, parabens, preservatives such as chlorhexidine gluconate, antioxidants such as vitamin E and BHT, UV absorbers such as benzophenone and aminobenzoic acid, Alcohols such as ethanol and propanol, citrate, acetate and other p Modifiers, and the like medicinal ingredients according to various purposes are formulated are selected as appropriate.

<3> Bath Agent of the Present Invention The bath agent of the present invention contains one or more of the above metabolic activators as a component having a skin condition improving action. The blending amount is 0.01 to 1 with respect to the total amount of the bath agent.
It is preferably 0% by weight. If the blending amount is less than 0.01% by weight, the effect of improving the skin condition may not be sufficient, and if the blending amount exceeds 10% by weight, the effect may reach the ceiling and it is not economically preferable. Further, when the content of the metabolic activator is 0.1 to 1% by weight, the effect of improving the skin condition is excellent and there is little change in the appearance. Therefore, the more preferred content is 0 based on the total amount of the bath agent. 0.1 to 1% by weight.

The dosage form of the bath agent of the present invention is not particularly limited, and examples thereof include soft capsules, powders, granules, liquids and the like which are usually used as bath agents. These bath agents can be produced in the same manner as in ordinary bath agents except that the metabolic activator comprising the above steroid derivative is added.

In addition to the above-mentioned metabolic activators, the bath agents of the present invention also include inorganic salts such as sodium sulfate and sodium carbonate which are usually applied to bath agents, fragrances and herbal extracts.
Nonionic, anionic, cationic, amphoteric surfactants,
Polyhydric alcohols, sugars, oils, preservatives, pigments, etc. are appropriately selected and added.

[0031]

EXAMPLES Examples of the present invention will be described below. First, a production example of polyporsterones A to G used as the metabolic activator of the present invention will be described.

[0032]

Example 1 Production of Polyporsterones To 100 kg of boar, 10 times amount of 50% aqueous ethanol solution was added, and the mixture was heated under reflux for 2 hours with stirring to extract soluble components. The obtained extract was filtered to remove insoluble matter, and the filtrate was concentrated to obtain an extract concentrate.

After this was dispersed in 20 L of water, an equal amount of diethyl ether was further added to separate the layers. Only the diethyl ether layer was taken out from this, and after concentration under reduced pressure, a silica gel column (elution solvent; chloroform: methanol =
1: 0 → 0: 1) followed by preparative liquid chromatography equipped with an ODS column.
8 mg Polyporsterone A, 276 mg Polyporsterone B, 31 mg Polyporsterone C, 7 mg Polyporsterone D, 19 mg Polyporsterone E, 1
0 mg of polyporsterone F and 11 mg of polyporsterone G were obtained.

<Evaluation of Metabolism Activator of the Present Invention> With respect to polyporsterones A to G which are the metabolite activators of the present invention obtained in Example 1 above, a test for safety and skin metabolism activating action was conducted. went.

(1) Safety test: The backs of 7 groups of Hartley white guinea pigs (male, weight 300 to 350 g) were shaved on each group, 6 animals per group, and 10 of each polyporsterone was placed on the shaved part of each group. % Aqueous solution was subjected to a closed patch for 24 hours to conduct a transdermal irritation test. The determination was performed 2 hours after the closed patch was released, using the following Japanese patch test standards (Japanese Dermatological Association).

-: No reaction ±: Weak reaction +: Positive reaction ++: Edema reaction

As a result, all guinea pigs showed-(no reaction). This shows that all of the above 7 types of polyporsterone used as the metabolic activator of the present invention are excellent in safety.

(2) Skin metabolism activating action The turnover time of the skin stratum corneum was measured by the following method,
Using this as an index, the skin metabolism activating action of each of the above polyporsterones was evaluated.

Ten Hartley white guinea pigs (male, weight 300-350 g), 5 per group, 10 on the left and right ears
Vaseline containing wt% dansyl chloride was closed-patched for 24 hours and fluorescently dyed on the stratum corneum of the skin, and then the guinea pigs in each group were treated with a 10% aqueous solution of each polyporsterone obtained in the above Example on the right ear. 05 ml was administered (single administration), the left ear was not treated, and the subsequent time-dependent change in fluorescence intensity was measured every other day until the fluorescence disappeared. As a control, after the dansyl chloride was dyed, the time course of the fluorescence intensity was similarly measured for a group of guinea pigs to which no treatment was applied to the left and right ears.

A value obtained by dividing the number of days required until the fluorescence of the left ear disappears (turnover time) by the number of days required until the fluorescence of the right ear disappears (turnover time) is evaluated as the degree of skin metabolism activation. Used for. Table 1 shows the average value of the skin metabolism activation degree of 5 animals together with the standard deviation value.

[0041]

[Table 1]

From these results, it is understood that the above seven kinds of polyporsterone used as the metabolic activator of the present invention promote turnover of the stratum corneum of the skin and are excellent in the action of activating the metabolism of the skin. .

Next, examples of the skin external preparation and bath preparation of the present invention, in which the polyporsterones A to G obtained in the above-mentioned Example 1 are blended as a metabolic activator, will be described. In addition, all compounding amounts used below are% by weight.

[0044]

Examples 2 to 6 Lotion Agent The components shown in Table 2 were stirred at room temperature and solubilized to produce a lotion agent.

[0045]

[Table 2]

[0046]

Examples 7 to 13 Cream Components A, B, and C shown in Table 3 were melted by heating at 80 ° C., A component was well kneaded, B component was added and dispersed well, and C component was added thereto. In addition, it was emulsified and cooled to obtain a cream.

[0047]

[Table 3]

[0048]

Examples 14 to 17 Bath Agents The components shown in Table 4 were kneaded with a kneader to produce bath agents.

[0049]

[Table 4]

[0050]

INDUSTRIAL APPLICABILITY The metabolic activator of the present invention is excellent in the skin metabolic activation action, and is also excellent in safety. Further, the external preparation for skin and bath preparation of the present invention containing this metabolic activator have a skin condition improving action and can be safely used for a long period of time.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification number Internal reference number FI Technical indication location A61K 7/50 C07J 9/00 9051-4C (72) Inventor Masaki Okada Takashima, Kanagawa-ku, Yokohama No. 27, 1 Polar Chemical Industry Co., Ltd., Yokohama Laboratory (72) Inventor Junichi Shibatani Takashima, Kanagawa-ku, Kanagawa Prefecture Takashimadai No. 27, 1 Polar Chemical Industry Co., Ltd., Yokohama Laboratory (72) Inventor Hirai Yoshikazu Kanagawa Yokohama Institute, Yokohama City, Kanagawa-ku, Yokohama, Japan 1-Polar Chemical Industry Co., Ltd. (72) Inventor Norie Muramatsu No. 27 Takashimadai, Kanagawa-ku, Yokohama, Kanagawa-shi, Polar Chemical Industry Co., Ltd. (72) ) Inventor Yasunori Inaoka 560, Kashio-cho, Totsuka-ku, Yokohama-shi, Kanagawa Pola Chemical Industry Co., Ltd. Totsuka Research Laboratory (72) Inventor Toshiyuki Fukuda 560 POLA CHEMICAL INDUSTRIES CO., LTD., Kashio-cho, Totsuka-ku, Yokohama, Yokohama, Japan (72) Inventor Masayoshi Yagi 560 Kashio-cho, Totsuka-ku, Yokohama, Yokohama, Japan Pola Chemical Industry Co., Ltd.

Claims (7)

[Claims] 1. A metabolic activator comprising a steroid derivative represented by the following general formula (I). [Chemical 1] However, in the formula (I), R represents a group having a carbon skeleton represented by Chemical formula 2. [Chemical 2] However, in Chemical formula 2, the bond indicated by the dotted line may or may not exist. 2. R in the general formula (I) is a group represented by Chemical formula 3, Chemical formula 4, Chemical formula 5, Chemical formula 6, Chemical formula 7, Chemical formula 8 or Chemical formula 9. Item 2. The metabolic activator according to item 1. [Chemical 3] [Chemical 4] [Chemical 5] [Chemical 6] [Chemical 7] [Chemical 8] [Chemical 9] 3. The steroid derivative represented by the general formula (I) is polyporsterone A in which R in the formula (I) is chemical formula 3 or polyporsterone B in which R is chemical formula 4. The metabolic activator according to claim 1, which is characterized. 4. A skin external preparation containing one or more of the metabolic activators according to any one of claims 1 to 3. 5. The external preparation for skin according to claim 4, wherein the content of the metabolic activator is 0.01 to 10% by weight based on the total amount of the external preparation for skin. 6. A bath agent containing one or more of the metabolic activators according to any one of claims 1 to 3. 7. The bath agent according to claim 6, wherein the content of the metabolic activator is 0.01 to 10% by weight based on the total amount of the bath agent.