JPH10175854A - External preparation for skin for improving water (of chinese medicine idea) - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a skin preparation for external use, improving water (of Chinese medicine idea), useful for stimulating organs controlling the secretion of water in the body to the outside of the body, promoting the secretion of water in the body to the outside of the body and bettering and improving correcting effects on water action, by using estrone, etc. SOLUTION: This skin preparation for external use for improving water uses a compound of the formula (A is N, NR11 , etc.; B is carbonyl, CR12 , etc.; R1 to R12 are each H, OH, an alkyloxy, etc. ; (n) and (m) are 0 or 1) (estrone or estradiol). In the objective skin preparation for external use, the content of the compound of the formula is preferably 0.001-20wt.% based on the total of the skin preparation for external use.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to an external preparation for skin such as cosmetics and medicines, which is useful for improving the action of tsukusu.

[0002]

2. Description of the Related Art The concept of qi, blood, and water in Chinese medicine has long been studied because of its uniqueness in understanding its pharmacological action and a rational index for selecting Chinese medicine. Of these, many have been elucidated about the meanings of qi and blood. For example, it is known that blood is a keyword that represents the supply and metabolism mainly of energy such as oxygen and nutrition, and ki is a keyword that represents the status of the homeostasis of life activity and the status of the driving force of life activity. Have been.

[0003] However, only the metabolism and excretion of waste products is known for the function of water (tsu liquor).
Since the recognition was delayed in the logical form of water, the elucidation of its true action (Tsukumi action) was incomplete. Also, little is known about the relationship between the pulp action and the various pharmacological actions recognized in modern medicine, and the role of pulp in modern medicine. The development of cosmetics, medicines, etc. that bring about such problems has been desired.

[0004]

DISCLOSURE OF THE INVENTION The present invention has been made in view of such circumstances, and has as its object to clarify the true function of a tsuju and to provide an external preparation for skin used to improve the action of a tsuku. And

[0005]

Means for Solving the Problems In view of such a situation, the present inventors have conducted intensive studies in search of the true function of tsuju. It was found that it stimulates the organs responsible for extracorporeal secretion and promotes the secretion of body water out of the body. Then, as a result of examining substances capable of stimulating such secretory organs and promoting / improving the action of the pulp, the present invention was completed.

[0006] That is, the present invention provides a skin for improving a tsunami containing one or more active ingredients selected from the group consisting of a compound represented by the following general formula (I) and a physiologically acceptable salt thereof. It provides an external preparation.

[0007]

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[In the formula (I), A is a nitrogen atom, -NR
₁₁ -, - CR ₁₁ - or -CHR ₁₁ -, B stands carbonyl group, -CR ₁₂ - or -CHR ₁₂ - represents, R _1,
R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₉ , R ₁₀ ,
R ₁₁ and R ₁₂ each independently represent a hydrogen atom, a hydroxyl group, an alkyloxy group, an acyloxy group, an oxygen atom which may form a carbonyl group, a carboxyl group which may be esterified, a carbonyl group or the same compound. And a carbon atom to be bonded may represent a low-chain-length alkyl group which may be multiple-bonded, and n,
m represents 0 or 1 each independently. ]

[0009] The present inventors have found that the tsuyu action promotes the secretion of water from the dermis to the epidermis and causes the epidermis to retain sufficient moisture, resulting in a beautiful skin action, atopic dermatitis, eczema,
Dermatomycosis, warts, pigmentation, psoriasis vulgaris, senile xeroderma, senile keratoma, therapeutic effects on various skin diseases such as burns,
It has been found that the action is related to a hair growth promoting action, a sweat promoting action, a digestive juice secretion promoting action, a diuretic action and a bowel movement promoting action caused by promoting water secretion in the stomach wall, kidney and intestinal tract.

That is, the medicinal classification of Chinese herbal medicines was examined in detail, and compared with modern medicine classifications.
It is said that the effects of the herbs such as shampoo, irrigation, conduction and prosthesis are related to beautiful skin effect, atopic dermatitis treatment, and dermatitis group treatment represented by eczema in the modern pharmaceutical classification. , Dermatomycosis treatment, wart treatment, pigmentation such as hepatitis, psoriasis vulgaris, senile xeroderma, senile keratoma treatment, skin damage treatment due to physical causes It has been found that it is closely related to the action, the hair growth promoting action, the digestive juice secretion promoting action, the sweating promoting action, the diuretic action and the bowel movement promoting action.

Based on this finding, screening was carried out on various substances based on the indicators of skin beautiful action, atopic dermatitis treatment action, hair growth promotion action, eczema treatment action, digestive juice secretion promotion action and sweating promotion action. It has been found that a compound selected from the group consisting of the compound represented by the general formula (I) and a physiologically acceptable salt thereof is excellent in such action. Even more surprisingly, by externally administering a compound selected from the group consisting of the compound represented by the general formula (I) and a physiologically acceptable salt thereof, secretion of digestive juice such as stomach acid is promoted. The present inventors have found that the present invention has such effects as described above, and have completed the present invention.

It is known that the compound represented by the above general formula (I) or a physiologically acceptable salt thereof has a percutaneous absorption promoting action, a liver function improving action and an immune function improving action. However, there was no way to know that there was a true improvement of the tsuyu. Further, the compound represented by the above general formula (I) or a physiologically acceptable salt thereof may be used as a beautifying agent, atopic dermatitis, eczema, dermatomycosis, warts, pigmentation,
It has no action to treat skin diseases such as psoriasis vulgaris, senile xeroderma, senile keratoma, burns, etc., hair growth promoting action, sweat sweat promoting action, digestive juice secretion promoting action, diuretic action, and bowel movement promoting action. Was not known.

[0013]

Embodiments of the present invention will be described below. The skin external preparation for tsumuage improvement of the present invention contains, as an active ingredient, one or more selected from the group consisting of the compound represented by the general formula (I) and a physiologically acceptable salt thereof. In formula (I), A is a nitrogen atom, -NR ₁₁ -, - CR
₁₁ - or -CHR ₁₁ -, B stands carbonyl group, -C
R ₁₂ — or —CHR ₁₂ — represents R ₁ , R ₂ , R ₃ , R ₄ ,
R ₅ , R ₆ , R ₇ , R ₈ , R ₉ , R ₁₀ , R ₁₁ , and R ₁₂ each independently represent a hydrogen atom, a hydroxyl group, an alkyloxy group, an acyloxy group, or an oxygen which may form a carbonyl group. Atom, a carboxyl group which may be esterified, a carbonyl group or a low chain alkyl group which may be bonded to another atom in the same compound and which may be multiple-bonded to the carbon atom to be bonded. And n and m each independently represent 0 or 1. Here, as the low chain length alkyl group,
It is preferably a straight-chain or branched alkyl group having 1 to 10 carbon atoms, and more preferably 1 to 4 carbon atoms.

The compound represented by the general formula (I) includes
Specifically, estrone, estradiol, estriol, androsterone, stilbesterol, 3,4
-Bis (4-hydroxyphenyl) hexane-2,4-
Diene, 4- (N- (4-hydroxyphenyl) aminocarbonyl) phenol, deoxystilbestrol, 3- (4-hydroxyphenyl) -4-phenylhexane-2,4-diene, or 4- (N-phenyl) Derivatives such as aminocarbonyl) phenol and acylated products and alkyl ethers thereof can be exemplified, and all of them can be used. Among them, the acylated product can be easily obtained by reacting with an acid chloride in the presence of an alkali. The alkyl ether compound can be easily obtained by reacting with an alkyl halide such as methyl iodide in the presence of an alkali. Among them, particularly preferred are estrone represented by the following general formula (II), estradiol represented by the following general formula (III), estriol represented by the following general formula (IV),
Androsterone represented by the following general formula (V), stilbesterol represented by the following general formula (VI), 3,4-bis (4-hydroxyphenyl) hexane represented by the following general formula (VII) 2,4-diene having the following general formula (V
4- (N- (4-hydroxyphenyl) aminocarbonyl) phenol represented by the formula (III):
Deoxystilbestrol represented by X), 3- (4-hydroxyphenyl)-represented by the following general formula (X)
4-phenylhexane-2,4-diene, 4- (N-phenylaminocarbonyl) phenol represented by the following general formula (XI), or an acylated product thereof, or a derivative such as an alkyl ether compound.

[0015]

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[0016]

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[0017]

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[0018]

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[0019]

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[0020]

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[0021]

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[0022]

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[0023]

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[0024]

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The physiologically acceptable salts of the compounds represented by the above general formula (I) include, for example, alkali metal salts such as sodium and potassium, alkaline earth metal salts such as calcium and magnesium, and ammonium salts. Preferred are organic amine salts such as triethylamine and triethanolamine, and basic amino acid salts such as lysine and arginine. These counterbases may be used alone or in combination of two or more.

The compound represented by the general formula (I) and / or a physiologically acceptable salt thereof are all commercially available. Examples of the external preparation for skin of the present invention include cosmetics such as basic cosmetics, make-up cosmetics, hair cosmetics, bath preparations and the like, and skin external pharmaceutical compositions such as anti-inflammatory external preparations. Formula (I) in the external preparation for skin of the present invention
The preferable content of the compound represented by the formula or a physiologically acceptable salt thereof is 0.001 to 20 with respect to the whole skin external preparation.
%, More preferably 0.01 to 10% by weight, even more preferably 0.01 to 5% by weight.

The external preparation for skin of the present invention is preferably prepared by the above-mentioned general formula (I)
In addition to the compound represented by the formula (I) or a physiologically acceptable salt thereof, the composition may contain optional components commonly used in cosmetics, skin external pharmaceutical compositions and the like. Such optional components include hydrocarbons such as petrolatum and microcrystalline wax, esters such as jojoba oil and gay wax, triglycerides such as tallow, olive oil, higher alcohols such as cetanol and oleyl alcohol, and stearic acid. , Fatty acids such as oleic acid, glycerin and 1,
Polyhydric alcohols such as 3-butanediol, nonionic surfactants, anionic surfactants, cationic surfactants,
Examples include amphoteric surfactants, thickeners such as ethanol and carbopol, preservatives, ultraviolet absorbers, antioxidants, pigments, and powders. The external preparation for skin of the present invention can be produced by treating these optional components with the compound represented by the above general formula (I) or a physiologically acceptable salt thereof in a conventional manner.

The skin external preparation for improving tidal fluid of the present invention is used for promoting / improving the action of liquor. It is known that the tsuju action is expressed in a living body as a mode of expression, such as a shampooing action, a water-supplying action, a prosthesis action, and a conduction action. As a herbal crude drug having these effects, if it is a shampooing effect, rhubarb, banshayou, rokai, machinin, kengoshi, Kansui, Genka, Zokuzuishi, kyukyu compi, etc. Chorei, Bukuryo, Taksha, Inchinko, Jokuinin, Toukanin, Difushi, Tokhihi, Kinsenso and the like are known, and as herbal crude drugs having a prosthetic effect, Shajin, Eurasia, Tenmondou, Bakumondou,
Ginseng, arctic, antelope, sycamore, renren, jotenishi, sesame, kokuzu, kiban, bekko are known, and as a herbal crude drug having an antidepressant effect, hawthorn, krenkonpi, hishi, kakushitsu, reigan, areca, nankashi, Taisan and the like are known.

Examining the literature and the like about these,
It has been found that pharmacological actions such as beautifying action, hair growth-promoting action, anti-allergic action, anti-inflammatory action, and digestion promoting action overlap. Here, the present inventors pay attention, and consider "water" (Tsu liquid).
Works in modern medicine to treat skin disorders such as skin beautification, atopic dermatitis, eczema, dermatomycosis, warts, pigmentation, psoriasis vulgaris, senile xeroderma, senile keratoma and burns It has been found that the action, the hair growth promoting action, the therapeutic action of pimples, the digestive juice secretion promoting action, the sweat promoting action, the diuretic action, the bowel movement promoting action and the like can be used as indices. Substances that have one of these actions also have greater or lesser other actions. Therefore, if screening is performed using one of these actions as an index, other actions can be estimated.

The skin external preparation for improving tsukusu according to the present invention is represented by a skin beautifying effect, an atopic dermatitis treatment effect, a dermatitis group treatment effect represented by eczema, a dermatomycosis treatment effect, a wart treatment effect, and hepatitis. Therapeutic action for pigmentation disease, psoriasis vulgaris, senile xeroderma, senile keratoma, skin damage treatment due to physical causes, hair growth promoting action, digestive secretion promoting action, sweat promoting action Has a function to improve at least one selected from the group consisting of a bowel movement promoting action, and a urination promoting (diuretic) action, and by using this,
Exhibits the effects of preventing and improving skin deterioration, treating atopic dermatitis and preventing the onset and worsening, promoting hair growth and preventing hair loss, improving and preventing eczema, promoting bowel movements and promoting urination. Is done.

The preferred dosage of the external preparation for skin of the present invention is
The appropriate amount may be applied once or several times a day to a part or the whole of the affected skin or healthy skin, depending on the kind of the disease and the characteristics of the patient.

It should be noted that the compound represented by the above general formula (I) or a physiologically acceptable salt thereof according to the present invention is capable of secreting digestive juices such as gastric acid by transdermal administration. It has the effect of being accelerated and the like, and a substance that can simultaneously expect such an effect by transdermal administration has not been known yet.

[0033]

Embodiments of the present invention will be described below. In addition, the unit of the numerical value of the prescription in the table is all parts by weight.

[0034]

Examples 1 to 5 <Formulation Examples> Skin external preparations (creams) were prepared according to the formulations shown in Table 1 below. That is, each of the component groups (a), (b) and (c) is heated at 80 ° C., (a) is kneaded well, (b) is added thereto, diluted, and (c) Was gradually added and emulsified, followed by stirring and cooling to obtain a skin external preparation.
It is highly safe and has an excellent essence as shown in the following test examples, and is therefore useful as a pharmaceutical composition and as a cosmetic.

[0035]

[Table 1]

[0036]

Examples 6 to 10 <Formulation Examples> Skin external preparations (creams) were prepared according to the formulations shown in Table 2 below. That is, each of the component groups (a), (b) and (c) is heated at 80 ° C., (a) is kneaded well, (b) is added thereto, diluted, and (c) Was gradually added and emulsified, followed by stirring and cooling to obtain a skin external preparation.
It is highly safe and has an excellent essence as shown in the following test examples, and is therefore useful as a pharmaceutical composition and as a cosmetic.

[0037]

[Table 2]

[0038]

Examples 11 to 15 <Formulation Example> A skin external preparation (ointment) was prepared using the components shown in Table 3 below and according to the formulation. That is, each prescription component was weighed into a kneader and kneaded well to obtain an ointment.

[0039]

[Table 3]

[0040]

Examples 16 to 20 <Formulation Examples> Using the ingredients shown in Table 4 below, external preparations for hair skin (hair tonics) were prepared according to the formulation. That is, each formulation component was stirred and solubilized at room temperature to obtain a hair tonic.

[0041]

[Table 4]

[0042]

Examples 21 to 25 <Formulation Examples> Bath ingredients were prepared using the components shown in Table 5 below and according to the formulations. That is, the respective components were kneaded with a kneader to obtain a bath agent.

[0043]

[Table 5]

[0044]

Example 26 <Test Example 1: Improving Skin Beauty> Ten panelists, 22 to 32 years old, suffering from rough skin, applied the skin external preparations (0.02 g) of Examples 1 to 7 twice daily in the morning and evening. Each was applied to the affected area for two months, and the effect of improving skin roughness was evaluated. The evaluation criteria were very improved (gradation 5) to not improved (gradation 0). As a control, a compound represented by the above general formula (I), which is an active ingredient of the present invention, or a physiologically acceptable salt thereof was replaced with water. The results are shown in Table 6 as average scores. This indicates that the external preparation for skin of the present invention has an effect of improving rough skin, that is, has a skin beautiful effect. This shows that the compound of the present invention represented by the above general formula (I) or a physiologically acceptable salt thereof has such an effect.

[0045]

[Table 6]

[0046]

Example 27 <Test Example 2: Hair growth promoting action> The back of a group of 5 C3H mice was shaved, and 10 mg of a sample shown in Table 7 below was dissolved or dispersed in 200 µl of physiological saline and applied. The hair growth promoting effect was evaluated by observing the hair growth. The control was vehicle saline only. The evaluation criteria are ++ (score 4): significantly earlier than the control, + (score 2): earlier than the control, ± (score 1): slightly earlier than the control,
-(Score 0): Not earlier than control. The results are shown in Table 7 as average scores. This shows that the compound represented by the above general formula (I) or a physiologically acceptable salt thereof, which is an active ingredient of the external preparation for skin of the present invention, is excellent in hair growth promoting action.

[0047]

[Table 7]

The derivatives 1 to 4 in Table 7 were produced by the following methods. (1) Acylation of estradiol 1 g of pentadecanoic acid was dissolved in 100 ml of chloroform, 10 ml of thionyl chloride was added thereto, the mixture was stirred at room temperature for 1 hour, and distilled under reduced pressure to obtain acid chloride. This was dissolved in 100 ml of chloroform, and 500 mg of estradiol was added thereto with 1000 ml of chloroform under ice-cooling for 20 ml.
l was added dropwise to a solution dissolved in triethylamine. After returning to room temperature and stirring for 2 hours, the solvent was distilled off and silica gel column chromatography (elution solvent: benzene: chloroform: methanol = 50: 50: 0 → 0:
100: 0 → 0: 80: 20), 121 mg of 3-pentadecanoyloxyestradiol (derivative 1), 78 mg of 17-pentadecanoyloxyestradiol (derivative 2) and 256 mg of estradiol dipentadenanoate (Derivative 3) was obtained.

(2) Acylation of estrone 270 mg of estrone was dissolved in 50 ml of pyridine, and 10 ml of acetic anhydride was added under ice cooling. After returning to room temperature and stirring for 24 hours to distill off the solvent, silica gel column chromatography (elution solvent: hexane: ethyl acetate = 100: 0).
→ 50: 50 → 30: 70 → 0: 100).
98 mg of estrone acetate (derivative 4) was obtained.

[0050]

Example 28 <Test Example 3: Effect on atopic dermatitis> Ten groups of 20-42 year old panelists suffering from atopic dermatitis
The skin external preparations (0.02 g) of the above Examples 1 to 7 were applied to the affected part twice a day and twice a day for 2 months to evaluate the effect of improving atopic dermatitis. The evaluation criteria were very improved (gradation 5) to not improved (gradation 0). As a control, a compound of the present invention represented by the above general formula (I) or a physiologically acceptable salt thereof was replaced with water. The results are shown in Table 8 as average scores. This indicates that the external preparation for skin of the present invention has an effect of improving atopic dermatitis. That is, it is understood that the compound represented by the above general formula (I) of the present invention or a physiologically acceptable salt thereof has such an effect.

[0051]

[Table 8]

[0052]

Example 29 <Test Example 4: Eczema treatment> 19-29 suffering from breakout
Ten year-old panelists in one group applied the skin external preparations (0.02 g) of Examples 1 to 7 twice a day for two months each day for two months to evaluate the eczema improving effect. The evaluation criteria were very improved (gradation 5) to not improved (gradation 0).
As a control, a compound of the present invention represented by the above general formula (I) or a physiologically acceptable salt thereof was replaced with water. The results are shown in Table 9 as average scores. This indicates that the compound represented by the above general formula (I) or a physiologically acceptable salt thereof, which is an active ingredient of the external preparation for skin of the present invention, has an effect of improving eczema.

[0053]

[Table 9]

[0054]

Example 30 <Test Example 5: Gastric secretion promoting action> The secretion of gastric juice was examined using an anesthetized dog. That is, an endoscope with an administration device was introduced into the stomach of a dog anesthetized with a pentobarbitur, and a sample was prepared as shown in Table 1.
10 mg of a compound represented by the above general formula (I) or a physiologically acceptable salt thereof, which is an active ingredient of the external preparation for skin of the present invention shown in FIG. It was administered dermally, and the secretion of gastric juice before and after the administration was observed to evaluate the gastric secretion promoting action. As a control, only physiological saline was used. Evaluation criteria are ++ (score 4):
Gastric secretion significantly increased compared to the control, + (Score 2): Gastric secretion increased compared to the control, ± (Score 1): Slightly increased compared to the control,-(Score 0): Secreted compared to the control It did not increase in comparison with that. Table 10 shows the results. The derivatives 1 to 4 in Table 10 are the same as those produced in Example 27 above.

From these results, it can be seen that the compound represented by the above general formula (I) or a physiologically acceptable salt thereof, which is an active ingredient of the present invention, has an excellent gastric secretion promoting action.

[0056]

[Table 10]

[0057]

Example 31 <Test Example 6: Promotion of bowel movement and urination> ICR mice were bred in metabolic cages. In the administration group, the skin external preparations of Examples 1 to 7 were applied to the shaved back skin as a sample at a rate of 1 g / day / animal, 0.5 g twice daily in the morning and evening, for 7 days, and then transdermally administered. . The amount of urine and feces 24 hours after the last dose was monitored. The control group received no specimen. Each group consisted of 10 animals. Table 11 shows the value obtained by dividing the total urine volume of the sample administration group by the total urine volume of the control group and the value obtained by dividing the total fecal volume of the sample administration group by the total fecal volume of the control group. This shows that the compound represented by the above general formula (I) or a physiologically acceptable salt thereof of the present invention is excellent in the bowel movement promoting action and the urination promoting action (diuretic action).

[0058]

[Table 11]

[0059]

According to the present invention, a beautiful skin effect, a therapeutic effect on atopic dermatitis, a therapeutic effect on a dermatitis group represented by eczema,
Treatment for dermatomycosis, treatment for warts, treatment for pigmentation such as hepatitis, treatment for psoriasis vulgaris, treatment for senile xeroderma, senile keratoma, treatment for skin damage due to physical causes It is possible to provide a skin external preparation capable of improving a tsukusu action selected from the group consisting of a hair growth promoting action, a digestive juice secretion promoting action, a sweating promoting action, a bowel movement promoting action, and a diuretic action.

────────────────────────────────────────────────── ─── Continued on the front page (51) Int.Cl. ⁶ Identification code FI A61K 31/165 ADS A61K 31/165 ADS C07J 1/00 C07J 1/00 (72) Inventor Nobuhiro Ando Takashima, Kanagawa-ku, Yokohama, Kanagawa Prefecture 271-2 Daila Kasei Kogyo Co., Ltd. Yokohama Research Center (72) Inventor Yoshie Muramatsu 27-1 Takashimadai, Kanagawa-ku, Kanagawa-ku, Yokohama-shi, Kanagawa Prefecture Yokohama Co., Ltd. Polar Research Co., Ltd. (72) Inventor Mitsuo Kawai Yokohama-shi, Kanagawa Prefecture 560 Kashio-cho, Totsuka-ku Pola Kasei Kogyo Co., Ltd.

Claims (6)

[Claims] 1. A skin external preparation for improving tsumucus containing one or more active ingredients selected from the group consisting of a compound represented by the following formula (I) and a physiologically acceptable salt thereof. Embedded image [In formula (I), A is a nitrogen _{atom, -NR 11 -, - CR 11} -
Or -CHR ₁₁ -, B stands carbonyl group, -CR ₁₂
— Or —CHR ₁₂ —, wherein R ₁ , R ₂ , R ₃ , R ₄ ,
R ₅ , R ₆ , R ₇ , R ₈ , R ₉ , R ₁₀ , R ₁₁ , and R ₁₂ each independently represent a hydrogen atom, a hydroxyl group, an alkyloxy group, an acyloxy group, or an oxygen which may form a carbonyl group. Atom, a carboxyl group which may be esterified, a carbonyl group or a low chain alkyl group which may be bonded to another atom in the same compound and which may be multiple-bonded to the carbon atom to be bonded. And n and m each independently represent 0 or 1. ] 2. The compound represented by the general formula (I)
Estrone represented by the following general formula (II), estradiol represented by the following general formula (III), estriol represented by the following general formula (IV), and the following general formula (V)
Androsterone represented by the following general formula (VI), stilbesterol represented by the following general formula (VII), 3,4-bis (4-hydroxyphenyl) hexane-2,4-diene represented by the following general formula (VII), 4- (N- (4-hydroxyphenyl) aminocarbonyl) phenol represented by the following general formula (VIII), deoxystilbestrol represented by the following general formula (IX), and represented by the following general formula (X) 3- (4-hydroxyphenyl) -4-phenylhexane-2,4-diene, 4- (N-phenylaminocarbonyl) phenol represented by the following general formula (XI), or a derivative thereof. Item 4. An external skin preparation for tsumugi according to Item 1. Embedded image Embedded image Embedded image Embedded image Embedded image Embedded image Embedded image Embedded image Embedded image Embedded image 3. The composition according to claim 1, which comprises 0.001 to 20% by weight of one or more selected from the group consisting of the compound represented by the general formula (I) and a physiologically acceptable salt thereof. 3. A skin external preparation for improving tsumugi according to 1 or 2. 4. The external preparation for skin according to claim 1, which is a cosmetic. 5. The external preparation for skin according to claim 1, which is a medicament. 6. A beautiful skin effect, an atopic dermatitis treatment effect,
Dermatitis group treatment, dermatomycosis treatment, wart treatment, pigmentation treatment, psoriasis vulgaris, senile xerosis, senile keratoma treatment, skin damage treatment, hair growth The external preparation for skin according to any one of claims 1 to 5, which is used for improving a tsutsuma action selected from the group consisting of a promoting action, a digestive juice secretion promoting action, a sweating promoting action, a bowel movement promoting action, and a diuretic action.