JPH11199503A - Testosterone-5alpha-reductase inhibitor and food and drink - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a means for suppressing the formation of dihydroxytestosterone without using a steroid agent causing much safety problems. SOLUTION: Bergenia crassifolia or Bergenia perpurascens is extracted with water, a hydrophilic organic solvent or their mixture and the testosterone-5α-reductase inhibiting action of the extract is utilized to obtain the objective inhibitor.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to testosterone.
5α-reductase inhibitors and testosterone-5α-
The present invention relates to a food or drink having a reductase inhibitory action.

[0002]

2. Description of the Related Art Male pattern baldness, alopecia, benign prostatic hyperplasia, seborrhea caused by increased sebum secretion, and purulent sweat glanditis caused by apocrine gland dysfunction are caused by testosterone, a type of male hormone. Or it is thought to be an exacerbation factor. In other words, after the male hormone testosterone secreted from the male genital organs is transported to the target organ by the bloodstream and selectively taken up, the intracellular testosterone-
It is converted to highly active dihydroxytestosterone by 5α-reductase, which combines with the intracellular receptor and acts on the nucleus. In hair matrix cells, it inhibits cell division and prevents hair growth, The mechanism of action has been confirmed to promote proliferation and sebum secretion. It is also known that prostatic hypertrophy is caused by hormonal imbalance with aging, but the main cause is an increase in the concentration of dihydroxytestosterone in the prostate, which causes prostatic hypertrophy. It is considered.

[0003] Therefore, administration of a substance that inhibits the action of testosterone-5α-reductase or a substance that has an antiandrogenic action for the treatment of various diseases in which testosterone is involved has been proposed and used in part. .

However, conventional testosterone-5α-
None of the substances proposed as reductase inhibitors were widely used because of their inadequate effects or safety issues. For example, steroidal antiandrogens such as oxendrone, diproterone acetate, and chloryadinone acetate often show side effects when administered for a long period of time, and have a problem in terms of safety.

[0005]

SUMMARY OF THE INVENTION An object of the present invention is to provide a means for suppressing the production of dihydroxytestosterone without relying on steroids which are problematic in safety as described above.

Another object of the present invention is to provide a novel testosterone-5 which is effective in suppressing the production of dihydroxytestosterone.
An object of the present invention is to provide an α-reductase inhibitor.

[0007] Still another object of the present invention is to provide a novel means which enables treatment and prevention of various diseases caused by dihydroxytestosterone.

[0008]

SUMMARY OF THE INVENTION The present invention is directed to a Bergenia
An object of the present invention is to provide a testosterone-5α-reductase inhibitor comprising an extract obtained by subjecting Classifolia (Bergenia crassifolia) or Bergenia purpurascens to an extraction treatment with water, a hydrophilic organic solvent or a mixture thereof.

[0009] The present invention also provides a food or drink characterized by imparting a testosterone-5α-reductase inhibitory action by adding the above plant extract.

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION Bergenia crassifolia (Japanese name: Naganoyukinosita) and Bergenia purpurasc (Bergenia purpurasc)
ens) is a plant belonging to the genus Himalayan Saxifragaceae. In China, the former is used as a crude drug under the name of Atsubaiwa Chinese cabbage, and the latter is known as Iwachina cabbage. It is said to be effective against frail constitution, hemoptysis, hemoptysis, inflammatory swelling, etc., and uses whole plants. In addition, there are regions that use it as tea (Heibonsha, World Dictionary of Useful Plants). However,
This plant was not known to contain testosterone-5α-reductase inhibitors.

Japanese Unexamined Patent Publication (Kokai) No. 5-17365 discloses that Saxifraga has a testosterone-5α-reductase inhibitory activity, which belongs to the genus Saxifraga and has a different genus from Bergenia classifolia. It is a completely unrelated plant.

The testosterone-5α-reductase inhibitor is contained abundantly in the root of the plant of the genus Himalaya. Extraction of the active ingredient is desirably performed on a dried product, and fresh one has poor extraction efficiency. As the extraction solvent, water, a hydrophilic organic solvent or a mixture thereof can be used. As the hydrophilic organic solvent, lower aliphatic alcohols such as methanol and ethanol, and ethyl acetate are preferable.

The extraction method is not limited, and the extraction can be carried out at room temperature or under reflux with any apparatus. Briefly, an extraction raw material is charged into a treatment tank filled with an extraction solvent, and a soluble component is eluted with occasional stirring. The obtained extract is concentrated and dried to give testosterone-5.
An extract having an α-reductase inhibitory action is obtained.

This extract is used directly as testosterone-5.
Although it can be used as an α-reductase inhibitor, if necessary, it can be subjected to a purification treatment effective for improving its activity and removing coloring, unpleasant odor, off-taste, etc., and can be used as a powder, granule, tablet, capsule, syrup , An enteric agent, a troche, a chewable and the like can be formulated and provided for use.

Extracts having an inhibitory effect on testosterone-5α-reductase can be obtained from other plants of the genus Himalayan, such as Bergenia syriata, Bergenia cordifolia, Bergenia ligrata, etc.
Its importance as a raw material plant is low.

The extract and the testosterone-5α-reductase inhibitor comprising the extract have been confirmed to be safe because the raw materials of the genus Himalayan saxifrage have been used for medicinal purposes since ancient times as described above. Because
Formulated in prostatic hyperplasia preventive agent, hair restorer, sebum secretion inhibitor, hair tonic, hair cream, hair liquid, hair lotion, pomade, hair shampoo, hair rinse, cream, lotion, milky lotion, and various other cosmetics ,
It can be used without fear of side effects.

A Himalayan Saxifraga plant extract containing a testosterone-5α-reductase inhibitor also comprises:
You may make it add to arbitrary foods and drinks, and use the useful effect in the occasion of daily eating and drinking. The extract of the Himalayan Saxifraga plant is light brown and does not significantly change the original flavor or properties of the food or drink even when added to the food or drink, so general foods and drinks, such as seasonings,
It can be widely added to Japanese and Western confections, frozen desserts, soft drinks, tea, spreads, pastes, pickles, processed meats, processed marine products, dairy products, processed eggs, processed vegetables and fruits, processed cereals, and the like. The preferred addition level varies depending on the quality and the substance to be added, but it is usually 0.01 to 10% by weight when a standard extract of the genus Himalayan saxifrage is used.

[0018]

The present invention will be described below with reference to examples. In each example, “parts” means parts by weight.

Production Example 1 500 ml of an extraction solvent was added to 100 g of dried root of Bergenia classifolia, and the mixture was heated under reflux for 1 hour to extract testosterone-5α-reductase inhibitor twice. The obtained extracts are combined, concentrated under reduced pressure, and further dried to obtain an extract.

Table 1 summarizes the results of the above-mentioned extraction experiments with six types of extraction solvents and the results of the same extraction of Bergenia perprusens.

[0021]

TABLE 1 Extraction yield (wt%) Extraction solvent B · crush cordifolia extract B · Papurasensu extract water 16.8 17.3 50% ethanol 21.5 20.8 Ethanol 28.0 27.1 Ethyl acetate 8.6 9.5 Acetone 5.3 6.5 n-Hexane 3.2 3.8

Test Example 1 The testosterone-5α-reductase inhibitory activity of the extract of the genus Himalayan safflower obtained in Production Example 1 was tested by the following method.

Test method: About 4.2 mg of testosterone (Tokyo Kasei) was dissolved in 1 ml of propylene glycol.
1 mg / NADPH (Oriental Yeast Co., Ltd.)
5 mM Tris-HCl buffer (pH 7.
13) 825 μl was added and mixed to obtain a reaction solution. To this reaction solution, 80 μl of the sample solution and 75 μl of S-9 (rat liver homogenate; manufactured by Oriental Yeast) were mixed,
Incubated at 37 ° C. for 30 minutes. Separately, the same solution was added instead of the sample solution to the same amount of the solvent alone, and the same treatment was performed as a control. After the reaction, 1 ml of chloroform was added, and the mixture was vigorously shaken to extract testosterone as a substrate and its reaction products (dihydroxytestosterone, androstanediol, etc.), and the reaction was stopped. Then, the organic solvent layer was separated by centrifugation at 3000 rpm for 10 minutes, concentrated three times, and analyzed by gas chromatography. The testosterone-5α-reductase inhibition rate was determined from the ratio of the amount of the reaction product when the sample was added to the amount of the reaction product when the sample was not added.

In the above method, the testosterone-5α-reductase inhibition rate at each concentration is determined by variously changing the sample concentration in the reaction solution. From the results, the sample concentration that inhibits the enzyme activity by 50% is determined by interpolation. .

Table 2 shows the results. From the results in Tables 1 and 2, it can be seen that testosterone-5α-reductase inhibitor is well extracted by water, a hydrophilic organic solvent and a mixture thereof. Extraction with acetone or n-hexane not only reduces the yield of the extract, but also exhibits almost no testosterone-5α-reductase inhibitory activity.

[0026]

Table 2 50% inhibitory concentration (ppm) B. classifolia extract B. perplacense extract water extract 847 774 50% ethanol extract 403 391 ethanol extract 382 401 ethyl acetate extract 900 930 acetone extract> 2000 > 2000 n-hexane extract>2000> 2000

Example 1 5 of Bergenia classifolia according to Production Example 1
A hair tonic having the following composition was produced using the 0% ethanol extract. B. classifolia extract 0.1 g pyridoxine hydrochloride 0.1 g resorcinol 0.01 g D-pantothenyl alcohol 0.1 g menthol 0.05 g polyoxyethylene softened castor oil 0.2 g 1,3-butylene glycol 5.0 g ethanol 30 2.0g distilled water balance (total of 10
0 ml)

Next, 10 males, aged 25 to 35, having symptoms of male pattern baldness and seborrheic dermatitis of the head were divided into a test group and a control group each consisting of five men. Was used for one month, and a hair tonic of the control group, which did not contain the extract of Bergenia classifolia, was used for one month. During the test period, an appropriate amount of hair tonic was sprayed on the head once each morning and evening, and then massaged with a fingertip for 1 minute.

From the day before the start of the test to the end of the test, the subjects were washed every two days under the same conditions, and the number of hair loss during the washing was recorded on the day before the start of the test and on the end of the test. The results are shown in Table 3, and it was confirmed that the testosterone-5α-reductase inhibitory effect of the Bergenia classifolia extract significantly reduced the number of hair loss.

[0030]

TABLE 3 depilation number subject test start date end of test test groups A 71 46 B 95 43 C 59 33 D 101 79 E 78 47 Mean 80.8 49.6 control group F 82 75 G 96 90 H 88 77 I 78 69 J 103 92 Average 89.4 80.9

Example 2 A soft drink having the following composition was prepared using the ethanol extract of Bergenia classifolia according to Preparation Example 1. B. classifolia extract 5.0 g Cyclodextrin 0.01 g Liquid sugar 8.0 g Citric acid 0.3 g Sodium citrate 0.03 g Apple flavor 0.05 g Water Remainder (total amount is 100 m
l)

Example 3 A lotion having the following composition was prepared using the ethanol extract of Bergenia perprusens according to Preparation Example 1. B. purple extract 0.1 g glycerin 4.0 g 1,3-butylene glycol 4.0 g ethanol 7.0 g polyoxyethylene oleyl alcohol 0.05 g methyl paraben 0.05 g citric acid 0.01 g sodium citrate 0.1 g fragrance 0 .05g distilled water balance (total amount 100ml)

[0033]

EFFECT OF THE INVENTION The testosterone-5α-reductase inhibitor according to the present invention is composed of an extract of a plant belonging to the genus Bergenia, which has been used in beverages for a long time. Can be added with confidence.

Continued on the front page (51) Int.Cl. ⁶ Identification symbol FI C12N 9/99 C12N 9/99 (72) Inventor Shigetake Matsumoto 3-14-22 Kubo, Onomichi, Hiroshima Prefecture

Claims (2)

[Claims] [1] Bergenia classifolia (Bergen)
a testosterone-5α-reductase inhibitor comprising an extract obtained by subjecting ia crassifolia) or Bergenia purpurascens to extraction with water, a hydrophilic organic solvent or a mixture thereof. 2. The Bergenia classifolia (Bergen)
ia crassifolia) or a food or drink comprising a testosterone-5α-reductase inhibitor extracted from Bergenia purpurascens.