JP2548941B2 - Testosterone 5α-reductase inhibitor - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [A] Object of the Invention The present invention relates to a testosterone 5α-reductase inhibitor.

“Industrial field of application” The testosterone 5α-reductase inhibitor (hereinafter referred to as “Ts-red inhibitor” for convenience) according to the present invention is used in the form of ingestion or external use, and is used during the prescription of pharmaceutical quasi drugs and cosmetics It is useful for treating male-type baldness and baldness.

"Prior Art" Studies on Ts-red inhibitors have recently been published, for example, in the following publications.

In-vivo role of Ts-red inhibitor, or as a mechanism of action, for example, in terms of male-type baldness, and relationship with osteoporosis, testosterone, which is the main androgen, is testosterone 5α-reductase (hereinafter, For convenience, it will be abbreviated as Ts-red.), And as a result, the state due to the excess of dihydrotestosterone produced will continue. Then, it is known that this induces hair loss.

Therefore, substances capable of suppressing the production of dihydrotestosterone from testosterone are said to be able to improve these symptoms, and the development of Ts-red inhibitors is progressing.

In addition to the above-mentioned hair loss mechanism, acne (acne vulgaris)
It is said that it is also involved in the onset of, for example, when the production of dihydrotestosterone is increased, sebum secretory capacity is enhanced, and therefore, the Ts-red inhibitor is acne or, by suppressing sebum secretory capacity, oil Application to alopecia areata, seborrheic alopecia, seborrheic eczema, and seborrheic pruritus (soyo) is considered.

"Publications on Known Ts-red Inhibitors" (1) Journal of Cosmetics Industry VOL.9 No.2 P101-107 Yasuo Asada (19
85) (2) Published patent publication: Sho 58-193689 (3) Published patent publication: Sho 60-028925 (4) Published patent publication: Sho 60-064910 (5) Published patent publication: Sho 60-081122 (6) Published patent publication: Sho 60-126218 (7) Published patent publication: Sho 60-142908 (8) Published patent publication: Sho 60-146829 "Problems to be solved by the invention" As described above, the inventors have developed a substance that can be a novel Ts-red inhibitor for the purpose of effective use in the fields of application to pharmaceuticals, quasi drugs, and cosmetics.

(B) Structure of the invention The Ts-red inhibitor according to the present invention is limited to the following botanical herbs and consists of an extract obtained therefrom.

(Notes on limited plants) The starting materials used in the present invention are cashew, mocca,
It is a salamander and a sardine. The sources of the herbal medicines used are shown below.

・ Kashu is a dried tuberous root of Polygonaceae.

・ Mokka is a dried orientated piece of mature bokeh of the Rosaceae that is divided horizontally or vertically.

-Sansho refers to pericarp seeds of Rutaceae or other plants of the same genus.

-The side leaf is a dried branch of the leaves of the cypress family Konotega wrinkle. Alternatively, it is a leaf of a Japanese lacquer tree of the family Periwinkle or a leaf with young branches.

"Means for Solving Problems" The present inventors have been particularly concerned with effective use of animal- and plant-derived components, especially in cosmetics and pharmaceuticals.
Furthermore, this time, it was further found that the extract of the herbal medicine as described above is effective as a Ts-red inhibitor.

Hereinafter, the search method and the like according to the present invention will be specifically described in detail by way of experimental examples.

"Experimental Example 1" Testosterone 5α-reductase extracted from the liver of an SD male rat (7 weeks old) was used and measured under the conditions of the following reaction.

(Reaction system) 3.0 μM of testosterone was dissolved in 10 drops of propylene glycol, 5 ml of Tris-HCl buffer (pH 7.2) was added, and then 5 mg of NADPH and 1 ml of testosterone 5α-reductase solution were sequentially added, and the mixture was kept at 37 ° C for 30 minutes. React. After the reaction,
Dichloromethane is added to stop the reaction, and the whole is extracted with 50 ml of dichloromethane to obtain a dichloromethane layer. Next, dichloromethane is distilled off under reduced pressure, and the reaction amount is measured by gas chromatography.

The test substance (the substance obtained in the example) is added to the reaction system after dropping testosterone, and the extraction solvent is distilled off before the reaction.

(GC: column OV-17, column length 2m: column temperature 250
(° C, FID) [Explanation of Table 1] Inhibition rate: The reaction rate of the control is regarded as 100% (inhibition rate 0%), and the reaction amount including the inhibitor is calculated to obtain the inhibition rate. The formula is as shown below.

a: Control (peak area of testosterone) b: Control (peak area of dehydrotestosterone and androstanediol) a ': Peak area of testosterone (inhibitor addition) b': Peak area of dehydrotestosterone and androstanediol (inhibitor Addition) In addition, dehydrotestosterone is further metabolized,
Androstanediol was also included in the calculation in the peak area (amount) of the 5α-reductase metabolite for producing androstanediol.

“Experimental Results” Among the extracts obtained based on many plant materials, based on the above-mentioned Experimental Example 1, as a result of searching for those exhibiting Ts-red inhibitory activity, the plants as shown in Table 1 were obtained. It was found that crude drugs could eventually become Ts-red inhibitors.

Therefore, further, the present inventors
We examined the characteristics of salamander and sakuhakyou based on various corresponding extraction solvents.

And, for example, according to the examples shown below, although a simple method, in the resulting extract, excellent Ts-
It was possible to find that a component with a red action was included.

The Ts-red inhibitor in the present invention may be any of the crude drug extract described in Table 1 (crude drug extract obtained by the method described below), its diluted solution, its concentrated solution, or its dry powder. May be used.

"Example 1" After crushing Kashi, to 1 part of Kash powder,
After adding 5 parts of water, ethanol or a mixed solution thereof and immersing the mixture at room temperature, filtration is performed, and the filtrate is frozen (-
After 20 ° C to -10 ° C), the mixture is filtered again, and the obtained Kashi extract is used as a Ts-red inhibitor. The effects (actions) of this agent are as shown in Table 1 above. In addition, this agent may be used or a dried one. Furthermore, as the solvent used for extraction, an extract obtained by using methanol, acetone, ethyl acetate or the like instead of ethanol can also be used as the Ts-red inhibitor.

[Example 2] Kash was crushed, and 10 parts of various water-immiscible organic solvents (for example, n-hexane, benzene, chloroform, ether, etc.) were added to 1 part of kash powder, and the mixture was stirred at room temperature. After soaking, filtration is performed, then the organic solvent is distilled off, and the obtained Kashi extract is used as a Ts-red inhibitor.

Hereinafter, in Examples 1 and 2 as well, extracts of mocca, salmon and soybean tannin are obtained by the same extraction method and used as Ts-red inhibitors.

[C] Effect of the invention The present invention has found that, from among a wide variety of plants, it is used as a Ts-red inhibitor based on extracts obtained from cactus mosquitoes, salamanders, and sorghums. It is in.

According to the present invention, the use thereof can be applied to cosmetics and pharmaceuticals in view of the action shown in Table 1, and these extracts can be used, for example, for hair growth, hair growth, or acne, seborrhea. It is considered that the therapeutic effect thereof is expected when used externally for sexual skin disorders, alopecia, etc., or in a dosage form such as internal administration.

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Claims (1)

(57) [Claims] 1. A testosterone 5α-reductase inhibitor, which comprises an extract obtained from a crude drug of any one of cashew, mocca, salamander, and soybean.