KR20020008268A - Testosterone 5 alpha-reductase inhibitors containing extracts of galla rhois - Google Patents

Abstract

PURPOSE: Provided is testosterone 5 alpha-reductase inhibitors containing extracts of Galla Rhois as an active ingredient, which inhibitor can be useful for therapeutic agents in depilation, pimple, benign prostatic hyperplasia and the like. CONSTITUTION: The testosterone 5 alpha-reductase inhibitor contains the extract of Galla Rhois as an active ingredient. A therapeutic agent in depilation is characterized by containing 0.001-10 wt.% of the extract of Galla Rhois as an active ingredient, which extract inhibits testosterone 5 alpha-reductase.

Description

Testosterone 5 alpha-reductase inhibitors containing extracts of Galla Rhois

The present invention relates to novel testosterone 5 alpha-reductase inhibitors that can be used for the treatment of enlarged prostate, acne, and alopecia areata. More specifically, the present invention relates to a testosterone 5 alpha-reductase inhibitor containing an extract of the gall bladder as an active ingredient.

Testosterone 5 alpha-reductase is an enzyme found in the prostate, the dermis, sebaceous glands, and hair follicles. It acts to convert testosterone, a male hormone, into active dihydrotestosterone (DHT). However, in the tissues of patients with prostatic hyperplasia, it is known that the content of dihydrotestosterone is significantly higher than that of normal prostate tissue. In addition, dihydrotestosterone causes a decrease in energy production around the hair follicles and inhibition of protein synthesis, thereby inhibiting hair cell proliferation. It is known to be one of the major inducers of male hair loss by inducing proteins that inhibit and cause hair loss. Furthermore, recent studies have shown that sebaceous cells induce excessive production of sebum and are also involved in diseases such as acne, exacerbation and seborrheic dermatitis. Therefore, inhibiting the production of dihydrotestosterone in the tissue by inhibiting the action of this testosterone 5 alpha-reductase may be a method that can effectively prevent and treat the disease. Some of these inhibitors have already been clinically applied to treat prostatic hyperplasia and to treat male hair loss. Finasteride (MSD ltd.), A representative testosterone 5-alpha-reductase inhibitor, has already been used in the United States as a prescription drug for the treatment of enlarged prostate and hair loss.

However, Finasteride has side effects such as decreased libido, decreased ejaculation and erectile dysfunction, and it is prohibited to use for women and children. It is true.

Accordingly, the present invention is to solve the above problems, the present inventors conducted an intensive study by selecting a material with excellent human safety in order to find an inhibitor that can effectively inhibit testosterone 5 alpha-reductase without side effects As a result, it was confirmed that the extract of Gallja showed strong inhibitory activity of testosterone 5 alpha-reductase and completed the present invention.

The present invention will be described in more detail as follows.

The gall bladder extract according to the present invention can be used for various pharmaceutical preparations, cosmetics, and the like for the prevention and treatment of symptoms related to the activity of testosterone 5 alpha-reductase. Specifically, it can be used for cosmetics for skin, cosmetics for hair growth of hair, acne prevention, therapeutic agent and the like. In addition to the above, it can be used for the prevention or treatment of diseases caused by the action of testosterone 5-alpha-reductase, and is not limited to external skin, and can be applied to both oral and parenteral formulations, and also suitable diluents and excipients depending on the purpose of use. You may mix | blend etc.

When the inhibitor of the present invention is applied to hair growth cosmetics, other ingredients blended with conventional hair growth promoters, for example, pepper tink, tocopherol acetate, benzyl nicotinate, hair root stimulation, and glycemic agents for cell activity Extracts, ginseng extract, red ginseng extract, oyster extract, cloves extract, hinokthiol, nicotinic acid amide, el-menthol, pyrotonolamine for sterilization or keratin dissolution, salicylic acid, and other humectants can be used together to enhance the effect.

When used as a composition for pharmaceuticals, quasi-drugs, cosmetics as described above, the application amount is not limited because it may vary depending on the form or purpose of use, but is generally about 5 ~ 10mL per day. Specifically, the extract obtained according to the method described in Examples later is blended so as to be 0.001 to 10% by weight. If it is less than 0.001% by weight, it is difficult to fully expect the effect of the present invention, and when it exceeds 10% by weight, it is not found to be proportional to the dose and difficult to maintain the dosage form.

As a result of preparing and testing the liquid composition as mentioned above, the test result showed a good effect in the testosterone 5 alpha-reductase inhibition test, and the hair growth efficacy test, the animal test, and the alopecia In clinical trials, it was evaluated that the hair growth promoting effect was excellent without any side effects such as skin redness.

Hereinafter, the specific configuration and operation of the present invention will be described in more detail on the basis of reference examples, experimental examples and examples. However, the present invention is not limited to the following examples. Unless otherwise stated in the following table, the unit is% by weight.

The scientific name of the gallant used in the present invention is Gala Rhois, and the larvae of the gallant aphid (Melaphis chinensis B., cotton aphid and Erilosomatidae) stimulate the young eggplant stagnation of Rhus japonica L., Anacardiaceae. It is a herbaceous herb that originated in Korea, Japan, and China. The gallnut tannin (50-70%) and gallic acid are used as main ingredients of astringents, molar assets, and raw materials for pyrogallol.

Reference Example: Preparation of Mellitus Extract

Referring to the extraction method of the five gall used in the present invention.

First, 5 ~ 10 times the amount of the extraction solvent is added to the dried sample, followed by cold extraction for 5 ~ 7 days, or extract extracted by heating for 1 ~ 5 hours. Got. The extraction solvent used at this time is one or two of purified water, methanol, ethanol, propanol, butanol, glycerol, propylene glycol, 1,3-butylene glycol, methyl acetate, ethyl acetate, benzene, hexane, diethyl ether, dichloromethane It is preferable to mix and use the above solvent for extraction.

Experimental Example 1 Evaluation of Testosterone 5 Alpha-Reductase Activity Inhibitory Activity of Mellitus Extract

Testosterone 5 alpha-reductase activity was used in the test of inhibition of testosterone 5 alpha-reductase activity. The testosterone 5 alpha-reductase was obtained from rat liver (adult, Sprague-Dawley, mature male rats (8-10 weeks old)). Protein suspensions were prepared. In addition, the enzyme reaction solution was prepared in a general manner. Radiolabeled testosterone ( ³ H testosterone) was used as a reaction substrate of testosterone 5 alpha-reductase, and the reaction was carried out in an incubator for 2 minutes at the ratio of enzyme reaction solution: protein suspension: gallnut extract = 70: 20: 10. Blow off the solvent and dissolve the remaining material in the developing solvent and develop it on the thin layer chromatography (TLC). The conversion of testosterone to dihydrotestosterone was measured and the results were compared with the control (conversion rate without the addition of the gall bladder extract) to evaluate the testosterone 5 alpha-reductase inhibition rate. The inhibition rate calculation method is as follows.

% Inhibition = [(A-B) / A] × 100

In the above formula,

A = conversion of testosterone to dihydrotestosterone (without extract)

B = conversion of testosterone to dihydrotestosterone (extract added)

Experimental results by the above inhibition rate calculation method are shown in Table 1 below.

Testosterone 5 alpha-reductase inhibition rate Gallnut Extract Concentration (%) 0.1 0.01 0.001 0.0001 % Inhibition 100.0% 100.0% 67.8% 35.1%

As can be seen from the results of Table 1, the inhibitory effect on the testosterone 5 alpha-reductase of the gall bladder extract is clear.

Examples 1-5 and Comparative Examples 1-2

Using a gall bladder extract and other auxiliary ingredients according to the present invention to prepare a liquid wool formulation containing a gall bladder extract of the ingredients and ratios shown in Table 2.

Ingredients and proportions of liquid wool Raw material name Example 1 Example 2 Example 3 Example 4 Example 5 Comparative Example 1 Comparative Example 2 ethanol 40.0 40.0 40.0 40.0 40.0 40.0 40.0 Gall bladder extract 5 0.01 0.1 One 5 - - Hinoki Thiol - 0.03 0.03 0.03 0.03 - 0.03 Pepper Tink - 0.5 0.5 0.5 0.5 - 0.5 Benzyl nicotinate - 0.02 0.02 0.02 0.02 - 0.02 Sugar extract - 0.5 0.5 0.5 0.5 - 0.5 Ginseng Extract - 0.5 0.5 0.5 0.5 - 0.5 Red Ginseng Extract - 0.5 0.5 0.5 0.5 - 0.5 Righteous extract - 0.5 0.5 0.5 0.5 - 0.5 Clove Extract - 0.5 0.5 0.5 0.5 - 0.5 Tocopherol Acetate - 0.1 0.1 0.1 0.1 - 0.1 Nicotinic acid amide - 0.1 0.1 0.1 0.1 - 0.1 Pyrotonolamine - 0.1 0.1 0.1 0.1 - 0.1 Salicylic acid - 0.3 0.3 0.3 0.3 - 0.3 L-menthol 0.3 0.3 0.3 0.3 0.3 0.3 0.3 Twin 20 0.5 0.5 0.5 0.5 0.5 0.5 0.5 Spices Quantity Quantity Quantity Quantity Quantity Quantity Quantity Pigment Quantity Quantity Quantity Quantity Quantity Quantity Quantity water Add until 100% by weight

Experimental Example 2 Test of Hair Growth Promotion Effect Using Animals

Hair growth promoting effect test was used to remove the hair of the back region using a mouse (C57BL / 6, male) 42 days to 56 days old, and once a day at the dorsal area per subject for each of the 10 Examples and Comparative Examples, 100 microliters were applied for 28 days. The results are shown in Table 3 below by comparing the ratio of the area where the newborn hair was grown with respect to the area from which hair was removed using an image analyzer.

Growth area ratio of new mother division Example 1 Example 2 Example 3 Example 4 Example 5 Comparative Example 1 Area ratio (%) 58.3 69.4 73.6 78.5 82.3 36.9

As shown in Table 3, the composition of Examples 1 to 5 containing the gall bladder extract showed a significantly higher hair growth promoting effect compared to Comparative Example 1, and the case of additionally containing other auxiliary components. Higher effect.

Experimental Example 3 Clinical Trial of Hair Growth Promoting Effect

In order to confirm the superior activity inhibitory effect of testosterone 5 alpha-reductase and the hair growth promoting effect shown in the animal test of the gall extract extracted in the above experiments, the subjects with alopecia were selected and tested.

Persons with alopecia of adult male hair loss from 30 to 50 years old or persons with an average number of hair loss of 100 or more per day to determine the clinical effect of promoting hair growth using Example 5 containing the gall bladder extract and Comparative Example 1 not containing Ten people each.

The method of use was to apply water droplets (about 2ml) 2 ~ 3 times a day to the hair loss site and used for at least 1 month up to 3 months depending on the degree of effect checking.

The determination of the effect was evaluated in five stages according to the evaluation scale of Table 4, and the average daily hair loss, visual judgment, and improvement in subjective symptoms were triturated, and overall improvement was taken as the average of the evaluation scale. The final judgment was that the overall improvement was 3.0 points or more, and the results are shown in Table 5 below.

Rating scale Phase division Hair Loss at Tricycle Subjective symptoms Visual judgment 54321 Significant Decrease Moderate Decrease Hardness Decrease Significant improvement Moderate improvement Hardness improvement Unchanged Significant improvement Moderate improvement Hardness improvement Unchanged

Overall overall improvement Phase division Hair Loss at Tricycle Subjective symptoms Visual judgment Overall improvement Example 5 Comparative Example 1 3.92.4 3.62.6 3.62.4 3.72.5

As shown in the results of Table 5, Example 5 containing the gall bladder extract showed a marked improvement compared to Comparative Example 1 and did not find any side effects from all the subjects during the use period was found to be a safe composition to the human body.

All.

As described above and described through the examples, the testosterone 5 alpha-reductase inhibitor containing the gall bladder extract of the present invention has a strong testosterone 5 alpha-reductase activity inhibitory effect, such as pharmaceuticals, quasi-drugs, cosmetics, etc. It can be effectively used in the field of androgenetic alopecia treatment, anti-acne treatment, prostatic hypertrophy.

Claims (3)

Testosterone 5 alpha-reductase inhibitor containing the extract of the gall bladder as an active ingredient. A composition for the treatment of androgenetic alopecia comprising 0.001-10% by weight of a gall bladder extract that inhibits testosterone 5 alpha-reductase as an active ingredient. The method according to claim 2, which is selected from hinokithiol, red pepper tincture, ginseng extract, red ginseng extract, oyster extract, sugar extract, clove extract, tocopherol acetate, nicotinic acid amide, nicotinic acid benzyl, pyroxtonolamine, salicylic acid, and el-menthol. Or a composition for treating androgenetic alopecia, further comprising two or more kinds.