JPH10175859A - External preparation for skin for improving water (of chinese medicine idea) - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject external preparation capable of stimulating organs controlling the secretion of water to the outside of the body, promoting and improving water (of Chinese medicine idea) action for promoting the secre tion of water in the body to the outside of the body, comprising a specific compound as an active ingredient. SOLUTION: This external preparation comprises one or more selected from the group consisting of a compound of formula I (R1 to R8 are each H, a short- chain alkyloxy, OH, an acyloxy or a short-chain alkyl; A is H or a carbon atom bonded to OH; B and D are each O or carbonyl), its physiologically permissible salt and its glycoside as an active ingredient. Preferably, to be concrete, quercetin of formula II, campherol of formula III, etc., are used as the compound. The content of the compound is preferably, for example, is 0.001-10 wt.% based on the total of the external preparation.

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.

That is, the present invention provides a compound represented by the following general formula (I), a physiologically acceptable salt of the compound,
And a skin external preparation for tsumugi improvement comprising one or more active ingredients selected from the group consisting of glycosides of the above compounds.

[0007]

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In the formula (I), R ₁ , R ₂ , R ₃ , R ₄ ,
R ₅ , R ₆ , R ₇ , and R ₈ each independently represent a hydrogen atom, a low-chain alkyloxy group, a hydroxyl group, an acyloxy group or a low-chain alkyl group, and A represents a carbon atom or a hydroxyl group to which a hydrogen atom is bonded. Represents a bonded carbon atom, and B and D each independently represent an oxygen atom or a carbonyl group. ]

[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 the compound represented by the general formula (I), a physiologically acceptable salt thereof, or a glycoside thereof is excellent in such an action. Even more surprisingly, external administration of the compound represented by the above general formula (I), a physiologically acceptable salt thereof, or a glycoside thereof promotes secretion of digestive juices such as stomach acid. Have been found to have the effect described above, and have completed the present invention.

The compound represented by the above general formula (I), a physiologically acceptable salt thereof or a glycoside thereof has a transdermal absorption promoting action, a liver function improving action and an immune function improving action. Although it was known, there was no way to know that there was a true improvement effect on tsukusu. Furthermore, the compound represented by the above general formula (I), a physiologically acceptable salt thereof or a glycoside thereof may be used as a beautifying effect, atopic dermatitis, eczema, dermatomycosis, warts, pigmentation, vulgaris It is known that it has a skin psoriasis, senile xeroderma, senile keratomas, skin diseases such as burns, hair growth promotion, sweating promotion, digestive secretion promotion, diuresis, and bowel movement. Had not been.

[0013]

Embodiments of the present invention will be described below. The skin external preparation for improving a tanning solution of the present invention is one or more selected from the group consisting of a compound represented by the general formula (I), a physiologically acceptable salt of the compound, and a glycoside of the compound. Two or more are the active ingredients. In the formula (I), R
₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ , and R ₈ each independently represent a hydrogen atom, a low-chain alkyloxy group, a hydroxyl group, an acyloxy group or a low-chain alkyl group; A represents a carbon atom to which a hydrogen atom is bonded or a carbon atom to which a hydroxyl group is bonded, and B and D each independently represent an oxygen atom or a carbonyl group. Here, the low chain length preferably has 1 to 1 carbon atoms.
4 linear or branched alkyl groups. In the present invention, R ₃ and R ₆ are preferably hydroxyl groups.

The compound represented by the general formula (I) includes
Quercetin, campherol, gencaine, genistein, soybean, baicalein, deoxyquercetin, deoxycampferol, deoxygencaine,
Deoxygenistein, deoxysoydein, isofelelin, 7-O-ethyl isofelelin, respedeol C, isosatibanone, neouralenol, 6-
Methoxycampherol can be exemplified, and any of these can be used.

Among these, preferred are quercetin represented by the following general formula (II) and quercetin represented by the following general formula (II)
Camperol represented by I), Genkain represented by the following general formula (IV), genistein represented by the following general formula (V), soybean represented by the following general formula (VI), and the following general formula (VII) ), Deoxyquercetin represented by the following general formula (VIII), deoxycampferol represented by the following general formula (IX), deoxygencaine represented by the following general formula (X), Deoxygenistein represented by the formula (XI), deoxydaidzuin represented by the following general formula (XII), or an acylated product thereof.

[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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[0025]

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[0026]

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Examples of the physiologically acceptable salt of the compound represented by formula (I) include 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.

Examples of glycosides of the compound represented by the above general formula (I) include α-glucoside, β-glucoside, α-galactoside, β-galactoside and the like. Preferred examples include genistin, which is a body, and soybean, which is a glycoside of soybean.
Many of these are commercially available themselves, and can also be obtained by extracting from natural products such as soybeans, or by glycosylating aglycone and sugar with an enzyme such as galactosidase or glucosidase.

Compounds represented by these general formulas (I):
Both physiologically acceptable salts and glycosides are commercially available and 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. The preferred content of the compound represented by the general formula (I), the physiologically acceptable salt thereof, or the glycoside thereof in the skin external preparation of the present invention is 0.001 to 10% by weight based on the whole skin external preparation. %, More preferably 0.01 to 10% by weight, and still more preferably 0.1 to 10% by weight.
01 to 5% by weight.

The external preparation for skin of the present invention is usually used in cosmetics, external pharmaceutical compositions for skin, etc., in addition to the compounds represented by the general formula (I), physiologically acceptable salts thereof, and glycosides thereof. Optional components used can be included. 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, polyhydric alcohols such as glycerin and 1,3-butanediol, nonionic surfactants, anionic surfactants, cationic surfactants, amphoteric surfactants, ethanol, carbopol, etc. Examples include a thickener, a preservative, an ultraviolet absorber, an antioxidant, a pigment, and powders. These optional components and general formula (I)
And a physiologically acceptable salt thereof or a glycoside thereof can be treated according to a conventional method to produce the skin external preparation of the present invention.

The skin external preparation for improving tidal fluid of the present invention is used for promoting and improving the action of tidal fluid. 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. In addition, substances having one of these actions often have other actions to a greater or lesser degree. 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 skin beautiful action, atopic dermatitis treatment action, dermatitis group treatment action represented by eczema, dermatomycosis treatment action, wart treatment action, 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 dose 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.

In particular, it should be noted that the compound of the present invention represented by the above general formula (I), the physiologically acceptable salt of the compound, or the glycoside of the compound is preferably transdermal. The administration has the effect of promoting the secretion of digestive juices such as stomach acid and the effect of promoting bowel movement and urination, and there is no known substance capable of simultaneously expecting such an effect by transdermal administration.

[0036]

Embodiments of the present invention will be described below. The unit of the numerical value of the prescription in the table is part by weight.

[0037]

Examples 1 to 5 <Formulation Examples> Using the ingredients shown in Table 1 below, skin external preparations (creams) were prepared according to the formulations. That is, (a),
Each component group represented by (b) and (c) is heated at 80 ° C., and (a) is kneaded well, (b) is added thereto, diluted, and (c) is gradually added thereto. The mixture was emulsified, stirred and cooled to obtain an external preparation for skin. Since it is highly safe and has an excellent essence as shown in the following Test Examples, it is useful as both a pharmaceutical composition and a cosmetic.

[0038]

[Table 1]

[0039]

Examples 6 to 10 <Formulation Examples> In accordance with Table 2 below, skin external preparations (ointments) were prepared. That is, each prescription component was weighed into a kneader and kneaded well to obtain an ointment.

[0040]

[Table 2]

[0041]

Examples 11 to 15 <Formulation Example> According to Table 3 below, a skin external preparation for hair (hair tonic) was prepared. That is, each formulation component was stirred and solubilized at room temperature to obtain a hair tonic.

[0042]

[Table 3]

[0043]

Examples 16 to 20 <Formulation Examples> Bath agents were prepared according to Table 4 below. That is, the ingredients were kneaded with a kneader to obtain a bath agent.

[0044]

[Table 4]

[0045]

Example 21 <Test Example 1: Effect of improving skin beautifulness> Ten panelists, 21 to 32 years old, suffering from rough skin, applied the skin external preparations (0.02 g) of Examples 1 to 5 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 obtained by substituting the compound represented by the general formula (I), which is an active ingredient of the present invention, with water was used. The results are shown in Table 5 as average scores. Thus, that the external preparation for skin of the present invention has the effect of improving rough skin,
That is, it can be seen that it has a beautiful skin effect. That is, it is understood that the compound represented by the general formula (I) of the present invention has such an effect.

[0046]

[Table 5]

[0047]

Example 22 <Test Example 2: Hair growth promoting action> The back of 5 mice per group of C3H mice was shaved, and 10 mg of a sample shown in Table 6 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 6 as average scores. This indicates that the compound represented by the general formula (I), which is an active ingredient of the external preparation for skin of the present invention, has an excellent hair growth promoting action.

[0048]

[Table 6]

[0049]

Example 23 <Test Example 3: Effect on atopic dermatitis> Ten groups of panelists aged 20 to 42 years old suffering from atopic dermatitis
The external preparation for skin (0.02 g) of the above Examples 1 to 5 was applied to the affected area 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, one obtained by replacing the active ingredient of the present invention with water was used.
The results are shown in Table 7 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 general formula (I) of the present invention has such an effect.

[0050]

[Table 7]

[0051]

Example 24 <Test Example 4: Eczema therapeutic action> 18-26 suffering from breakout
A group of 10 year-old panelists applied the skin external preparations (0.02 g) of the above Examples 1 to 5 twice a day and two nights for two months to evaluate the effect of improving eczema. The evaluation criteria were very improved (gradation 5) to not improved (gradation 0).
As a control, one obtained by replacing the active ingredient of the present invention with water was used. The results are shown in Table 8 as average scores. Than this,
The above general formula (I) which is an active ingredient of the external preparation for skin of the present invention.
It can be seen that the compound represented by the formula has an effect of improving eczema.

[0052]

[Table 8]

[0053]

Example 25 <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 the specimen was used as a sample.
10% of the active ingredient of the external preparation for skin of the present invention shown in
It was dissolved or dispersed in 200 μl of an aqueous ethanol solution and transdermally administered to the back, and the secretion of gastric juice before and after the dissolution was observed to evaluate the gastric secretion promoting action. As a control, only physiological saline was used. Evaluation criteria were as follows: ++ (score 4): gastric secretion increased significantly compared to control, + (score 2): increased gastric secretion compared to control, ± (score 1): slightly increased compared to control ,-(Score 0): the secretion did not increase compared to the control. Table 9 shows the results. This shows that the compound represented by the above general formula (I), which is an active ingredient of the present invention, has an excellent gastric secretion promoting action.

[0054]

[Table 9]

[0055]

Example 26 <Test Example 6: Effect of promoting bowel movement and urination> ICR mice were bred in metabolic cages. In the administration group, the skin external preparations of Examples 1 to 5 were applied to the shaved back skin as a specimen at a rate of 1 g / day / animal, 0.5 g twice daily in the morning and evening, for 7 days, and 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 10 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 feces volume of the sample administration group by the total feces volume of the control group. This shows that the compound of the present invention represented by the general formula (I), a physiologically acceptable salt thereof or a glycoside thereof is excellent in defecation promoting action and urination promoting action (diuretic action).

[0056]

[Table 10]

[0057]

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.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁶ Identification code FI A61K 31/70 ABE A61K 31/70 ABE ABF ABF ACM ACM ACR ACR ADZ ADZ C07H 17/07 C07H 17/07 // C07D 311/30 C07D 311/30 311/36 311/36 (72) Inventor Nobuhiro Ando 27-1, Takashimadai, Kanagawa-ku, Kanagawa-ku, Kanagawa Prefecture Inside the Yokohama Research Laboratory, Polar Kasei Kogyo Co., Ltd. (72) Inventor Yoshie Muramatsu Kanagawa-ku, Yokohama-shi, Kanagawa Prefecture 27-1 Takashimadai 1 Pola Chemical Industry Co., Ltd. Yokohama Research Center (72) Inventor Mitsuo Kawai 560 Kashio-cho, Totsuka-ku, Yokohama-shi, Kanagawa Prefecture Pola Chemical Industry Co., Ltd. Totsuka Research Center

Claims (6)

[Claims] 1. An active ingredient comprising one or more selected from the group consisting of a compound represented by the following general formula (I), a physiologically acceptable salt of the compound, and a glycoside of the compound. , An external preparation for skin use for improving tsu liquid. Embedded image [In the formula (I), R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ ,
And R ₈ each independently represent a hydrogen atom, a low-chain alkyloxy group, a hydroxyl group, an acyloxy group or a low-chain alkyl group; A represents a carbon atom to which a hydrogen atom is bonded or a carbon atom to which a hydroxyl group is bonded; And D each independently represent an oxygen atom or a carbonyl group. ] 2. The compound represented by the general formula (I)
Quercetin represented by the following general formula (II), campherol represented by the following general formula (III), genkine represented by the following general formula (IV), genistein represented by the following general formula (V), Soy ain represented by the general formula (VI), baicalein represented by the following general formula (VII), deoxyquercetin represented by the following general formula (VIII), deoxycampferol represented by the following general formula (IX), A deoxygencaine represented by the following general formula (X), a deoxygenistein represented by the following general formula (XI), a deoxydaizuein represented by the following general formula (XII), or an acylated product thereof An external preparation for skin according to claim 1. Embedded image Embedded image Embedded image Embedded image Embedded image Embedded image Embedded image Embedded image Embedded image Embedded image Embedded image 3. One or more compounds selected from the group consisting of the compound represented by the general formula (I), a physiologically acceptable salt of the compound, and a glycoside of the compound. 0
3. The skin external preparation for tsumugi improvement according to claim 1 or 2, which contains from 01 to 10% by weight. 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.