JPH10175860A - Water (of chinese medicine idea) improver and composition for oral administration containing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject composition capable of stimulating organs con trolling the secretion of water to the outside of the body, promoting and improv ing water (of Chinese medicine idea) action for promoting the secretion 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 0.001-50 wt.% based on the total of the composition in the case of a food composition.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an agent for improving tsunami which has an effect of improving the effect of tsunami, and a composition containing the same for oral administration of foods, medicines and the like.

[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 foods, medicines, etc. that bring about this has been desired.

[0004]

DISCLOSURE OF THE INVENTION The present invention has been made in view of such circumstances, and clarifies the true action of tsuju, and can improve the tsuju action, and foods, medicines and the like containing the same. It is an object of the present invention to provide a composition for oral administration.

[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, they found a tsumuco-ameliorating agent, which is a substance capable of stimulating such secretory organs and promoting / improving the action of tsumuju, and completed the present invention.

That is, the present invention provides a compound represented by the following general formula (I), a physiologically acceptable salt of the compound,
Another object of the present invention is to provide a tsumumo improver comprising a glycoside of the compound.

[0007]

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, 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. In addition, the present invention provides a composition for oral administration containing the above-mentioned tsuyu improving agent.

[0009] The tsumuco-ameliorating agent of the present invention is a substance having an effect of stimulating an organ responsible for secretion of water to the outside of the body to promote secretion of body water to the outside of the body, thereby promoting / improving the tsukumu effect, that is, a substance having a tsumuju-improving effect. Say. The present inventors have proposed a tanning effect that promotes the secretion of water from the dermis to the epidermis and retains sufficient water in the epidermis, a beautiful skin effect, atopic dermatitis, eczema, dermatomycosis, warts, and pigmentation. It is caused by promoting the treatment of various skin diseases such as psoriasis vulgaris, senile xeroderma, senile keratoma, and burns, promoting hair growth, promoting sweating, and promoting water secretion in the stomach wall, kidneys and intestinal tract. It has been found that it is an action related to digestive juice secretion promoting action, diuretic action, and bowel movement promoting action.

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. It is known that the compound represented by the 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. Despite the fact, there was no way to know that there was a true improvement of tsuyu. 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 Senile psoriasis, senile xeroderma, senile keratoma,
It was not known at all that it had an action of treating skin diseases such as burns, an action of promoting hair growth, an action of promoting perspiration, an action of promoting digestive juice secretion, an action of diuresis, and an action of promoting bowel movement.

[0012]

Embodiments of the present invention will be described below. (1) Tsutsumi-improving agent of the present invention The tsumumo-improving agent of the present invention comprises a compound represented by the above general formula (I), a physiologically acceptable salt of the compound, or a glycoside of the compound. 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 to which a hydrogen atom is bonded. Represents a carbon atom to which an atom or a hydroxyl group is bonded, and B and D each independently represent an oxygen atom or a carbonyl group.
Here, the low chain length is preferably a linear or branched alkyl group having 1 to 4 carbon atoms.

In the general formula (I), R ₃ and R ₆ are preferably a hydroxyl group in the rubbing improver of the present invention.
Examples of the compound represented by the general formula (I) include quercetin, campherol, gencaine, genistein, soybean, baicalein, deoxyquercetin, deoxycampherol, deoxygencaine, deoxygenistein, deoxydaizuein, isoferrein, and 7-O-. Examples include ethylisoferrein, respedeol C, isosativanone, neouralenol, and 6-methoxycampherol, all of which can be used.

Among these, 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.

[0015]

Embedded image

[0016]

Embedded image

[0017]

Embedded image

[0018]

Embedded image

[0019]

Embedded image

[0020]

Embedded image

[0021]

Embedded image

[0022]

Embedded image

[0023]

Embedded image

[0024]

Embedded image

[0025]

Embedded image

The acylation may be carried out according to a conventional method, for example, by reacting an acid chloride or an acid anhydride derived by reacting an acid with thionyl chloride or the like in the presence of an alkali. Examples of the physiologically acceptable salt of the compound represented by the general formula (I) include alkali metal salts such as sodium and potassium, alkaline earth metal salts such as calcium and magnesium, ammonium salts, triethylamine and triethylamine. Organic amine salts such as ethanolamine and basic amino acid salts such as lysine and arginine can be preferably exemplified. These counterbases may be used alone or in combination of two or more.

Examples of glycosides of the compound represented by the 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, and can also be obtained by extracting from soybeans or the like, 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. The compound of the present invention represented by the above general formula (I), a physiologically acceptable salt of the compound, or a tsunami improving agent composed of a glycoside of the compound has an effect of promoting and improving the tsunami action. .

It is known that the tsuju action is expressed in the living body as a mode of expression, such as a subcutaneous action, a water-supply action, a prosthesis action, and a conduction action. As a herbal medicine having these effects, if it is a depressant effect, rhubarb, banshayou, rokai, machinin, kengoshi, kansui, genka,
Zokuzi-ishi, kyukyu-compi, and the like are known, and as herbal crude drugs having a water-utilizing effect, chorei, bukuro,
Taksha, chinko, yokuinin, toucanin, difushi, tokhihi, calendula, etc. are known, and as herbal crude drugs having a prominence action, shajin, seijin, tenmondou, bakkumondou, sekikoku, goktyku, zyaku, sukiyase, kanrensou, jyoseishi , Sesame, kokuzuku, kiban, bekko, etc. are known, and as a herbal medicine having an antidepressant action, hawthorn, cren compi, hishi, kakushitsu, ligan, 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 often 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 essence improving agent of the present invention can be used as a beautifying agent, atopic dermatitis treatment, dermatitis group represented by eczema, dermatomycosis treatment, wart treatment, and pigmentation represented by hepatitis. Therapeutic action, psoriasis vulgaris treatment, senile xeroderma, senile keratomas treatment, skin damage treatment due to physical causes, hair growth promoting action, digestive juice secretion promoting action, sweat promoting action, promotion of bowel movement It has an effect of improving at least one selected from the group consisting of an action and a urination-promoting (diuretic) action, and by administering it, prevents and ameliorates skin deterioration, and treats atopic dermatitis. Effects such as prevention of onset and deterioration, promotion of hair growth and prevention of hair loss, improvement of eczema and prevention of deterioration, promotion of bowel movement and promotion of urination are exhibited. The preferred dose of the tsukumo ameliorating agent varies depending on the type of disease and the characteristics of the patient, but is preferably 1 to 1000 per adult per day.
0 mg may be orally administered once or divided into several times.

It should be noted that the compound represented by the above general formula (I), the physiologically acceptable salt of the compound, or the glycoside of the compound of the present invention is orally administered. It is possible to simultaneously provide a plurality of actions such as making the skin beautiful and promoting hair growth. That is, preferably, the Tsutsumi improver of the present invention,
Beautifying skin, atopic dermatitis, dermatitis represented by eczema, dermatomycosis, wart, pigmentation represented by hepatitis, psoriasis vulgaris, elderly Selected from the group consisting of xeroderma sclerosis, senile keratoma treatment, treatment of skin damage due to physical causes, hair growth promotion, digestive secretion promotion, sweat perspiration, bowel movement promotion, and diuresis It has the effect of improving two or more actions. There is no known substance capable of simultaneously achieving such an effect by oral administration.

(2) The composition for oral administration of the present invention The composition for oral administration of the present invention is characterized by containing one or more selected from the above-mentioned tsukusu improver of the present invention. Examples of the composition for oral administration include food compositions and pharmaceutical compositions processed into granules, powders, tablets, capsules, candies, gums, gummy gums, and the like. In the case of a food composition, the preferred content of the tsukusui improver of the present invention is 0.001 to 50% by weight based on the whole composition, and
-20% by weight is more preferred, and 0.01-15% by weight is even more preferred. Further, in the case of a pharmaceutical composition, 0.1 to 60
% By weight, preferably 0.5 to 50% by weight, and more preferably 1 to 30% by weight.

The composition of the present invention may contain, in addition to the above-mentioned tsutsumi-improving agent, optional components usually used in food compositions or pharmaceutical compositions. As such an optional component, if it is a pharmaceutical composition, an excipient, a binder, a coating agent, a lubricant, a sugar coating, a disintegrant, a bulking agent, a flavoring agent, an emulsifying / solubilizing / dispersing agent, Stabilizers, pH adjusters, isotonic agents, etc. can be exemplified, and in the case of food compositions, antioxidants, flavoring agents, thickeners, emulsion stabilizers, preservatives, flavoring agents, sweeteners, sour agents Etc. can be exemplified. The composition of the present invention can be produced by treating these optional components and the above-mentioned tsukumo improver according to a conventional method.

The composition of the present invention can be used for improving the essence of a liquor. Specifically, beautiful skin action, atopic dermatitis treatment action, dermatitis group treatment action 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 can be used for improving an action selected from the group consisting of a hair growth promoting action, a digestive juice secretion promoting action, a sweat promoting action, a bowel movement promoting action, and a diuretic action.

[0036]

Embodiments of the present invention will be described below. In addition, all the numerical values of the prescription in a table represent a weight part.

[0037]

Examples 1 to 5 <Formulation Examples> Tablets were prepared using the components shown in Table 1 according to the formulation. That is, each prescription component was weighed in a grading granulator, and mixed by spraying 50 parts by weight of a 20% aqueous ethanol solution to prepare coarse granules. Coarse granules at 40 ° C 4
It was blow-dried for 8 hours, and was tableted with a tableting machine to obtain 250 mg tablets. The units of the numerical values in Table 1 represent parts by weight.

[0038]

[Table 1]

[0039]

Examples 6 to 10 <Formulation Examples> Candies were prepared using the components shown in Table 2 according to the formulation. That is, the prescription components were heated and melted at 120 ° C. and molded while cooling to obtain a candy.
The units of the numerical values in Table 2 represent parts by weight.

[0040]

[Table 2]

[0041]

Examples 11 to 15 <Formulation Examples> Candies were prepared using the components shown in Table 3 according to the formulation. That is, the prescription components were heated and melted at 120 ° C. and molded while cooling to obtain a candy.
The units of the numerical values in Table 3 represent parts by weight.

[0042]

[Table 3]

[0043]

Example 16 <Test Example 1: Effect of improving skin beautifulness> Ten groups of panelists aged 21 to 33 years old suffering from rough skin,
g tablets) was evaluated twice a day in the morning and evening twice, one tablet only for two months, to evaluate the effect of improving skin roughness. The evaluation criteria were very improved (gradation 5) to not improved (gradation 0). As a control, lactose was used in place of the liquor improving agent of the present invention. The results are shown in Table 4 as average scores. From this, it can be seen that the rubbing liquid improving agent of the present invention has an effect of improving skin roughness by internal use, that is, has a beautiful skin effect.

[0044]

[Table 4]

[0045]

Example 17 <Test Example 2: Hair growth promoting action> The back of five C3H mice per group was shaved, and 10 mg of a sample shown in Table 5 below was dissolved or dispersed in 200 µl of physiological saline and orally administered. The subsequent hair growth was observed to evaluate the hair growth promoting action. The control was vehicle saline only. Evaluation criteria are ++
(Score 4): significantly faster than control, + (score 2):
Earlier than control, ± (score 1): slightly earlier than control,-(score 0): not earlier than control. The results are shown in Table 5 as average scores. From this, it can be seen that the tsukumo improver of the present invention is excellent in hair growth promoting action.

[0046]

[Table 5]

[0047]

Example 18 <Test Example 3: Effect on Atopic Dermatitis> A group of 20 to 33-year-old panelists suffering from atopic dermatitis,
The ameliorating effects of atopic dermatitis were evaluated for the tablets (1 g tablets) of the above Examples 1 to 5 twice a day and twice a day only for two months. The evaluation criteria were very improved (gradation 5) to not improved (gradation 0). As a control, lactose was used in place of the liquor improving agent of the present invention. The results are shown in Table 6 as average scores. From this, it can be seen that the tsumugi improver of the present invention has an effect of improving atopic dermatitis by taking it internally.

[0048]

[Table 6]

[0049]

Example 19 <Test Example 4: Eczema treatment> 19-29 suffering from breakout
A group of 10-year-old panelists evaluated the eczema-improving effect of the tablets (1 g tablets) of Examples 1 to 5 twice a day, twice a day for two months. The evaluation criteria were very improved (gradation 5) to not improved (gradation 0). As a control, lactose was used in place of the liquor improving agent of the present invention. The results are shown in Table 7 as average scores. From this, it can be seen that the tsukutsu improver of the present invention has an effect of improving eczema by taking it internally.

[0050]

[Table 7]

[0051]

Example 20 <Test Example 5: Gastric secretion promoting effect> 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 sample was treated as shown in Table 8.
10 mg of the tsukumo improver of the present invention shown in
The solution was administered by dissolving or dispersing the solution in the gastric acid, 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 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 8 shows the results. From this, it can be seen that the tsumugi improving agent of the present invention is excellent in gastric secretion promoting action.

[0052]

[Table 8]

[0053]

Example 21 <Test Example 6: Promotion of bowel movement and urination> ICR mice were bred in metabolic cages. In the administration group, the compositions of Examples 1 to 5 were orally administered at a dose of 0.5 g twice a day in the morning and evening at 1 g / day / 1 animal. 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 9 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.
Shown in 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 a bowel movement promoting action and a urination promoting action (diuretic action).

[0054]

[Table 9]

[0055]

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 The present invention can provide a tsumucolytic agent having an effect of improving a tsukusei effect 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 7/06 A61K 7/06 31/335 ADT 31/335 ADT 31/70 ACJ 31/70 ACJ ACQ ACQ ACX ACX // C07C 50 / 32 C07C 50/32 C07D 311/30 C07D 311/30 311/36 311/36 C07H 17/07 C07H 17/07 (72) Inventor Shin Fukushima 560 Kashio-cho, Totsuka-ku, Yokohama-shi, Kanagawa Prefecture Pola Chemical Industry Co., Ltd. Inside the laboratory (72) Inventor Yasunori Inaoka 27-1, Takashimadai, Kanagawa-ku, Yokohama-shi, Kanagawa Pref. Inside the Yokohama Research Laboratory (72) Inventor Takehiro Okuda 27-1, Takashimadai, Kanagawa-ku, Yokohama-shi, Kanagawa Pref. Inside Yokohama Research Laboratory

Claims (7)

[Claims] 1. An agent for improving essence comprising a compound represented by the following general formula (I), a physiologically acceptable salt of the compound, or a glycoside of the compound. 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 deoxydaidzuin represented by the following general formula (XII), or an acylated product thereof. Item 4. The tsumumo improver according to Item 1. Embedded image Embedded image Embedded image Embedded image Embedded image Embedded image Embedded image Embedded image Embedded image Embedded image Embedded image 3. A composition for oral administration, comprising the tsukumo ameliorating agent according to claim 1 or 2. 4. The composition according to claim 3, which is a food composition. 5. The composition according to claim 3, which is a pharmaceutical composition. 6. The method according to claim 3, which is used for improving a tsufluid action.
The composition according to any one of claims 1 to 5. 7. The tanning solution is effective for beautifying skin, treating atopic dermatitis, treating dermatitis, treating dermatomycosis, treating warts, treating pigmentation, treating psoriasis vulgaris, and the elderly. Xeroderma sclerosis, senile keratoma treatment action, skin damage treatment action, hair growth promotion action, digestive secretion promotion action, perspiration promotion action, bowel movement promotion action, and an action selected from the group consisting of diuretic action, A composition according to claim 6.