JPH07316057A - 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 (R1, R2 and R3 are independently each H or hydroxyl group; R3 is H or an acyl of a short-chain length). For example, ecdysone expressed by formula II and 20-hydroxyecdysone expressed by formula III are cited as the compound expressed by formula I. This compound expressed by formula I is known as a molting hormone of insects and a commercially available product can be used as the compound. Furthermore, the content of the metabolic activator is preferably 0.01-10wt.% based on the total amount of the skin preparation for 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, 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 capacity is decreased due to the inactivation of metabolism, leading to dryness of the skin. It is widely accepted that wrinkles are formed. 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, many people lament that the skin loses its elasticity due to aging, that the skin becomes dry, and that wrinkles occur. Various makeup cosmetics for hiding the lack of elasticity of the skin, and Various cosmetics have been developed to improve the dryness of the skin.

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. Also, substances for improving wrinkles have been researched and developed, but no substance having sufficient effect has been obtained so far. Therefore, by eliminating the skin's elasticity, making the skin dry, and improving the inactivation of metabolism that is the cause of wrinkle formation, the skin's elasticity is restored and the skin's dryness and wrinkles are removed. It has been desired to develop a drug that can be improved.

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 and a wrinkle 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 (1) has an excellent metabolic activation effect, and that the external skin preparation and bath preparation containing the same have an improving effect on the skin condition.

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 7]

However, in the formula (I), R ₁ , R ₂ and R ₄ are
Each independently represent a hydrogen atom or a hydroxyl group, and R ₃ is
A hydrogen atom or a short chain acyl group is shown. 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). Here, R _{3 in the} formula (I) represents a hydrogen atom or a short chain long acyl group, and the carbon number of the alkyl portion of this short chain long acyl group is preferably 1 to 10, and more preferably 1 to 10. 6 and more preferably 1 to 4. Preferred examples of such short-chain acyl groups include acetyl group, ethylcarbonyl group, propylcarbonyl group and butylcarbonyl group.

As the steroid derivative used in the present invention,
Preferably, ecdysone represented by Chemical formula 8, 20-hydroxyecdysone represented by Chemical formula 9, and 2- represented by Chemical formula 10
Deoxy-20-hydroxyecdysone, 22-acetoxy-20-hydroxyecdysone represented by Chemical formula 11,
Polypodin B represented by Chemical formula 12 may be used, and one of these compounds may be used alone, or two or more thereof may be used in combination.

[0013]

[Chemical 8]

[0014]

[Chemical 9]

[0015]

[Chemical 10]

[0016]

[Chemical 11]

[0017]

[Chemical 12]

All the steroid derivatives represented by the general formula (I) used in the present invention are known compounds,
It is known as the molting hormone of insects. Moreover, since these steroid derivatives are commercially available as reagents, it is possible to use these commercially available products in the present invention.

<2> External preparation for skin of the present invention The external preparation for skin 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 skin external preparation of the present invention is not particularly limited, and examples thereof include those commonly used as a skin external preparation 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 activators, the external preparation for skin of the present invention generally includes hydrocarbons such as liquid paraffin, petrolatum and the like, waxes such as carnauba wax and mokuro, which are applied to external preparations for skin. 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, herb extracts,
Nonionic, anionic, cationic, amphoteric surfactants,
Polyhydric alcohols, sugars, oils, preservatives, pigments, etc. are appropriately selected and added.

[0025]

The steroid derivatives represented by the general formula (I) used as the metabolic activator of the present invention include ecdysone, 20-hydroxyecdysone and 2-deoxy-20.
-Hydroxyecdysone, 22-acetoxy-20-hydroxyecdysone, and Polypogin B (all manufactured by Sigma) were used to evaluate safety and metabolic activation.

(1) Safety test The backs of 5 groups of Hartley white guinea pigs (male, weight 300-350 g) were shaved at 6 groups per group, and 10 parts by weight of each of the above steroid derivatives was shaved at each group. A percutaneous irritation test was conducted by closed patching each of the liquid paraffin solutions for 24 hours. 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

The results showed that all guinea pigs were-(no reaction). This shows that all of the above-mentioned 5 kinds of steroid derivatives used as the metabolic activator of the present invention are excellent in safety.

(2) Metabolic activation action The turnover time of the skin stratum corneum is measured by the following method,
Using this as an index, the metabolic activation action of each steroid derivative was evaluated.

Ten Hartley white guinea pigs (male, weighing 300 to 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 ethanol containing the above-mentioned steroid derivatives at various concentrations as shown in Table 1 in the right ear of the guinea pigs of each group. Solution 0.05
ml was administered (once administration), the left ear was not treated, and the change in fluorescence intensity with time was measured every other day until the fluorescence disappeared.

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 metabolic activation. Used for. The values of skin metabolism activation obtained in Table 1 are shown as an average value of 5 animals.

[0032]

[Table 1]

From these results, it is understood that the above five kinds of steroid derivatives 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.

[0034]

EXAMPLES Examples of the skin external preparation and bath preparation containing the steroid derivative represented by the general formula (I) as a metabolic activator will be described below. In addition, all compounding amounts used below are% by weight. In addition, ecdysone, 20-hydroxyecdysone, 2-deoxy-20-hydroxyecdysone, and 2 used as metabolic activators in the examples of the present invention.
2-Acetoxy-20-hydroxyecdysone and Polypogin B were all manufactured by Sigma.

[0035]

Examples 1 to 8 Lotion Agent The components shown in Table 2 were stirred at room temperature to be solubilized to produce a lotion agent. Similarly, a lotion preparation of Comparative Example containing no metabolic activator of the present invention was produced.

[0036]

[Table 2]

[0037]

[Examples 9 to 15] Creams Components A, B, and C shown in Table 3 were each melted by heating at 80 ° C, component A was well kneaded, component B was added and dispersed well, and component C was added to this. In addition, it was emulsified and cooled to obtain a cream.

[0038]

[Table 3]

[0039]

Examples 16 to 22 Bath Agents The ingredients shown in Table 4 were kneaded with a kneader to produce bath agents.
Also, in the same manner, a bath agent of Comparative Example containing no metabolic activator of the present invention was produced.

[0040]

[Table 4]

<Evaluation of skin external preparation and bath preparation of the present invention>
Using the lotions and bath preparations obtained in the above examples, the skin condition improving action and wrinkle improving action were evaluated. For comparison, the same evaluation was performed on the lotion and the bath agent of the comparative example which did not contain the metabolic activator of the present invention.

(1) Test of actual use of external preparation for skin 20 female panelists suffering from wrinkles were divided into 2 groups of 10 persons each, and one group was given Example 1
And the other group was used with the lotion of Comparative Example 1 twice a day for 3 months. Three months after the start of use, a questionnaire was given to answer the degree of improvement in skin condition and the degree of improvement in wrinkles. The results are shown in Table 5.

[0043]

[Table 5]

From the above, the lotion of the comparative example does not improve the skin condition so much, whereas the lotion of the present invention, due to the metabolic activation action of the steroid derivative represented by the above general formula (I), It is clear that it changes the skin to a favorable condition and improves wrinkles.

(2) Test for Actual Use of Bath Agents 40 panelists selected arbitrarily were divided into two groups of 20 persons each, and one group was given Example 1
No. 6 bath agent and the other group had the bath agent of Comparative Example 2 used once a day for 2 consecutive weeks. After the end of the use period, we asked them to answer a questionnaire regarding the degree of improvement in their skin condition. The results are shown in Table 6.

[0046]

[Table 6]

From these results, the bath agents of the comparative examples do not improve the skin condition so much, whereas the bath agents of the present invention are due to the metabolic activation action of the steroid derivative represented by the general formula (I). , It is clear that the skin condition is improved.

[0048]

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 an action of improving the condition of the skin and an action of improving wrinkles, 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 (6)

[Claims] 1. A metabolic activator comprising a steroid derivative represented by the following general formula (I). [Chemical 1] However, in the formula (I), R ₁ , R ₂ , and R ₄ each independently represent a hydrogen atom or a hydroxyl group, and R ₃ represents a hydrogen atom or a short-chain acyl group. 2. The steroid derivative represented by the general formula (I) is ecdysone represented by Chemical formula 2, 20-hydroxyecdysone represented by Chemical formula 3, and 2-deoxy-20- represented by Chemical formula 4. Hydroxyecdysone, 2 represented by Chemical formula 5
The metabolic activator according to claim 1, which is selected from 2-acetoxy-20-hydroxyecdysone and polypodin B represented by Chemical formula 6. [Chemical 2] [Chemical 3] [Chemical 4] [Chemical 5] [Chemical 6] 3. A skin external preparation containing the metabolic activator according to claim 1 or 2. 4. The external preparation for skin according to claim 3, 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. 5. A bath agent containing the metabolic activator according to claim 1 or 2. 6. The bath agent according to claim 5, wherein the content of the metabolic activator is 0.01 to 10% by weight based on the total amount of the bath agent.