KR20070056207A - Testosterone 5alpha-reductase inhibitor containing vitis radix extract - Google Patents

Abstract

A composition comprising an extract of Vitis Radix is provided to show excellent testosterone 5 alpha-reductase activity inhibition effect, thereby being usefully used for therapeutic agents of alopecia, prophylactic and therapeutic agents of dermatitis, and therapeutic agents of prostatic hypertrophy in the field of medicines, quasi-drug and cosmetics. The composition for inhibiting testosterone 5 alpha-reductase comprises an extract of Vitis Radix as an effective ingredient. The content of the extract of Vitis Radix based on the dried weight is 0.001-10 wt.%. The alopecia treating composition comprises the extract of Vitis Radix and at least one selected from the group consisting of capsicum tincture, vitamin E acetate, an extract of Asarum sieboldii MIQ., an extract of Swertia pseudo-chinensis, an extract of red ginseng, hinokitiol, nicotinic acid amide, L-menthol, piroctone olamine and salicylic acid.

Description

Testosterone 5 alpha-reductase inhibitor containing grape root extract {TESTOSTERONE 5ALPHA-REDUCTASE INHIBITOR CONTAINING VITIS RADIX EXTRACT}

The present invention relates to a testosterone 5-alpha-reductase inhibitor containing an extract of Vitis Radix as an active ingredient. A new testosterone 5 alpha-reductase inhibitor containing grape root extract can be used for the treatment of.

Testosterone 5 alpha-reductase is an enzyme found in the prostate, the dermis, sebaceous glands, and hair follicles. It acts to convert testosterone, a testosterone, to active dihydrotestosterone (DHT). It is known that the dihydrotestosterone content is significantly higher in tissues of patients with prostatic hyperplasia than in normal prostate tissues. In addition, dihydrotestosterone is known to be one of the main inducers of male hair loss by inhibiting cell proliferation of hair cells by inducing energy production and suppressing protein synthesis around hair follicles, and inducing proteins causing hair loss. Furthermore, recent studies have shown that dihydrotestosterone causes excessive sebum production in sebum cells and is also involved in diseases such as acne, exacerbation and seborrheic dermatitis. Therefore, inhibiting the production of dihydrotestosterone in tissues by inhibiting the action of this testosterone 5 alpha-reductase may be a method of effectively preventing and treating these related diseases.

These testosterone 5-alpha-reductase inhibitors have already been clinically applied, in part, as agents for the treatment of enlarged prostate and for the treatment of 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 treating prostatic hyperplasia and male hair loss. However, finasteride has side effects such as decreased libido, decreased ejaculation, and erectile dysfunction, and has many restrictions on use and usage. Therefore, the effect and practicality are low and considerable care is required for use.

Accordingly, attempts have been made to obtain 5-alpha-reductase inhibitors from natural herbs with low side effects and high safety. Korean Patent Publication No. 10-1999-0055304 (July 15, 1999) discloses a 5 alpha-reductase activity inhibiting composition containing a clove extract, and Korean Patent Publication No. 10-2003-0016818 (2003. 3. In 3), the acne cosmetic composition containing natural ointment of oak leaves is disclosed, and in Korean Patent Publication No. 10-2003-0068647 (August 25, 2003), a cosmetic composition for preventing hair loss comprising pomegranate extract, and Patent Publication No. 10-2004-0015917 (February 21, 2004) discloses an external preparation for acne prevention and treatment containing one or more herbal extracts selected from Dodu, white porcelain, and yellow lotus.

In the present invention, in consideration of the conventional problem, in order to find an inhibitor that can effectively inhibit testosterone 5 alpha-reductase without side effects, an intensive study was conducted by selecting a material with excellent human safety, and as a result the grape root extract was It was confirmed that the testosterone 5 alpha-reductase exhibits inhibitory activity and completed the present invention.

The vine root is Vitis belonging to the family Vitaceae. vinifera ), Scattered grapes, Vitis amurensis ) is a herbal medicine used to dry the roots of the sun in the sun or freshly used. Consent of the agreement, “Daling this and drink the water, the nausea and hiccups stop. And after pregnancy, Tajigi comes down when you drink it when you dense it. ”From ancient times, it has the effect of having a huge wind and stool. (腫 腸), has been used for the treatment of urinary bulge (小 便 不 利) and the like.

Korean Patent Publication No. 10-2005-0086169 (August 30, 2005) discloses a method of extracting heineanol A from the root of Vitis amurensis and its anticancer activity. Lower alcohol is used here as an extraction solvent. Heineanol A extracted from it is described as effective in preventing and treating cancer, and mentions the function related to testosterone 5 alpha-reductase of grape root. It is not.

It is an object of the present invention to provide a composition which is excellent in human safety and has strong testosterone 5 alpha-reductase inhibitory activity and is useful as a treatment for androgenetic alopecia, acne and prostatic hyperplasia.

In order to achieve the above object, the present invention provides a testosterone 5 alpha-reductase inhibitor composition containing Vitis Radix extract as an active ingredient.

Here, the content of the grape root extract is preferably 0.001 to 10% by weight on a dry weight basis.

Such a composition of the present invention can be used for the treatment of alopecia, prevention and treatment of acne and seborrheic dermatitis, and for the treatment of enlarged prostate, especially when used as a treatment for masculine alopecia, pepper tink, tocopherol acetate, benzyl nicotinate, sesine extract, sugar extract It may further comprise one or more selected from red ginseng extract, hinokthiol, nicotinic acid amide, el-menthol, pyroxtonolamine and salicylic acid.

Hereinafter, the present invention will be described in more detail.

Grape approximating to the present invention is grape (Vitis vinifera) belongs to the vitaceae (葡萄科, Vitaceae), scatter plots (Vitis amurensis, Vitis amurensis ) is a herbal medicine used to dry the roots of the sun in the sun or freshly used. It has been used for the treatment of rheumatism, longevity, urinary bulge, etc., and Heineanol A extracted from the root of Vitis amurensis has anticancer activity. Although reported, the study of the present invention is the first for the inhibitor-related function of testosterone 5 alpha-reductase.

Grape root extract according to the present invention can be used for various pharmaceutical preparations and cosmetics in the field of medicines and cosmetics for the prevention and treatment of symptoms related to the activity of testosterone 5alpha-reductase. Specifically, it can be used for hair growth cosmetics, cosmetics for skin, preparations for the prevention and treatment of acne, and the like, and can be used for the prevention or treatment of diseases caused by the action of testosterone 5 alpha-reductase.

In addition, the composition of the present invention is not limited to the external preparation for the skin and can be applied to both oral and parenteral formulations, and suitable diluents, excipients, etc. may be added according to the purpose of use. Specifically, the composition of the present invention can be prepared in any form, such as liquid, cream, paste, or solid form, for example, hair products, such as shampoo, hair conditioner, hair lotion, liquid wool type, etc. And aerosol types of these formulations.

When the composition of the present invention is applied to hair growth cosmetics, other ingredients formulated in conventional hair growth promoters, such as pepper tink, tocopherol acetate, benzyl nicotinate, etc., for promoting blood circulation, for hair root stimulation and cellular activity Sessin extract, medicinal extract, red ginseng extract, hinokitiol, nicotinic acid amide, el-menthol and the like, and other moisturizing agents, such as pyrotonolamine and salicylic acid for sterilization or keratin dissolution, may be used together to enhance the effect.

Grape root extract used in the composition of the present invention is prepared as follows:

After extracting by adding 5 to 10 times the amount of the extraction solvent to the dried herbal medicine by cold soaking for 5 to 7 days, or extract obtained by heating extraction for 1 to 5 hours, filtration, concentration and freeze-drying of the extract of grape root extract Obtain dry powder.

At this time, the extraction solvent is not particularly limited in the selection, purified water; Lower alcohols such as methanol, ethanol, propanol and butanol; Polyhydric alcohols such as glycerol, propylene glycol and 1,3-butylene glycol; And hydrocarbon solvents such as methyl acetate, ethyl acetate, benzene, hexane, diethyl ether, dichloromethane, and the like. It is preferable to use 1 type, or 2 or more types of solvent in these solvents, and to mix and extract.

Grape root extract prepared as described above is preferably included as a solid content in 0.001 to 10% by weight of the total weight of the composition of the present invention. If it is less than 0.001% by weight, it is difficult to fully expect the effect of the present invention, and if it exceeds 10% by weight, it is not preferable because it does not show an effect proportional to the dose and it is difficult to maintain the formulation.

When the composition of the present invention is used for medicines, quasi-drugs, and cosmetics, the application amount thereof is not limited because it may vary depending on the form or purpose of use, but in general, about 3 to 10 ml per day is appropriate.

The composition comprising the grape root extract according to the present invention showed a good effect in the testosterone 5 alpha-reductase inhibition test produced by the liquid phase test, hair growth efficacy test, animal test and alopecia In the clinical trials, the skin growth promoting effect was evaluated with no side effects such as skin redness.

Hereinafter, the specific configuration and effect of the present invention through the examples will be described in more detail. However, these Examples are only illustrative of the present invention, and the scope of the present invention is not limited to these. In the tables of the examples below, the units are by weight unless otherwise indicated.

Production Example : Grape root  Preparation method of the extract

The grape root extract used in the examples of the present invention was prepared as follows: 500 g of the dried grape root was cut into pieces, and 5000 ml of the ethanol for the drug was added thereto, followed by cooling for 5 days. The filtered extract was completely evaporated at 45 ° C. using a vacuum concentrator to obtain a dried extract. Yield was about 2.7%.

Effect Test Example  One: Grape root  Testosterone Of Extract 5 alpha - Reductase  Activity inhibition

Experimental method firstly, 1) 3 alpha-androstanediol, 2) 3 beta-androstanedio1, 3) androsterone, 4) dihydrotestosterone, 5) androstanedione, 6) testosterone and 7) androstenedione standard compounds were precisely weighed in about 1 mg each and dissolved in ethanol to 10 ml. This was subjected to gas chromatography to calculate the concentration per peak area from the precisely taken amount and the peak area.

To about 4.2 mg of testosterone, 1 ml of propylene glycol was added to dissolve it, and 20 µl was taken. To this was added 825 µl of 5 mM Tris hydrochloric acid buffer (pH 7.13) in which NADPH was dissolved to 1 mg / ml.

80 µl of the sample solution and 75 µl of S-9 (rat liver homogenate: Oriental®) were mixed with the reaction solution and incubated at 37 ° C for 30 minutes. The sample solution was used by diluting the concentrated solid of the grape root extract prepared in Preparation Example to various concentrations in a solvent. Separately, only the same amount of the solvent was added instead of the sample as a reference drug. After the reaction, exactly 1 ml of methylene chloride was added and mixed vigorously to extract the testosterone and the reaction product of the substrate and to complete the reaction. The organic layer was separated by centrifugation at 3000 rpm for 10 minutes and analyzed by gas chromatography.

Then, the concentration of each compound extracted in the organic layer after the enzymatic reaction was calculated by the following equation:

Peak area at the time of concentration / calibration line making at concentration = peak area X calibration line making

Next, the conversion rate by 5-alpha-reductase was calculated. Standard compounds 6) and 7) are compounds which are reaction substrates by 5 alpha-reductase and 1) to 5) are products. It predicted the decomposition of each compound at the time of reaction, and converted into the mass (testosterone) at the start of reaction which match | combined the product quantity with the residual mass.

Conversion ratio = (total amount of 1) to 5) in the organic layer / total amount of 1) to 7) in the organic layer) x 100

This result was compared with the control (conversion rate when no component was added) to evaluate the inhibition rate of 5 alpha-reductase. The method for calculating the inhibition rate is as follows:

Inhibition Rate (%) = [(A-B) / A] × 100

Where

A = conversion of testosterone to dihydrotestosterone (without extract)

B = conversion of testosterone to dihydrotestosterone (extract added)

The testosterone 5 alpha-reductase inhibition rate of the grape root extract obtained by the above calculation method is shown in Table 1 below.

Grape root extract concentration (%) 0.1 0.01 0.001 0.0001 % Inhibition 100.0% 92.0% 58.8% 32.2%

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

Example  1 to 5 and Comparative example  1 to 2

Using a grape root extract and other auxiliary components according to the present invention to prepare a liquid wool having a component and content as shown in Table 2 according to a conventional method.

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 Grape Root Extract 5.0 0.01 0.1 1.0 5.0 - - Hinoki Thiol - 0.05 0.05 0.05 0.05 - 0.05 Pepper Tink - 0.5 0.5 0.5 0.5 - 0.5 Benzyl nicotinate - 0.01 0.01 0.01 0.01 - 0.01 Sessin Extract - 1.0 1.0 1.0 1.0 - 1.0 Sugar extract - 0.5 0.5 0.5 0.5 - 0.5 Red Ginseng 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 - 0.1 0.1 0.1 0.1 - 0.1 L-menthol 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Twin 20 0.5 0.5 0.5 0.5 0.5 0.5 0.5 Spices Quantity Quantity Quantity Quantity Quantity Quantity Quantity water Add until 100% by weight

Effect Test Example  2: Animal Hair Growth Promoting Effect Test

Animal hair growth promoting effect test was used 42 to 56 days old mice (C57BL / 6, male). First, the hair on the back of the mouse was removed using an electric razor, and each mouse was weighed and divided into 12 pieces so that the weight was evenly distributed. From the next day after the adaptation period for one day, the hair preparation prepared in Examples and Comparative Examples was applied to the hair removal site. 100 µl was applied to the back of the mouse once per day for 30 days to observe the hair growth promoting effect. As a result, the ratio of the area in which the newborn hair was grown with respect to the area from which hair was removed using an image analyzer was evaluated, and the average value was evaluated. The following Table 3 shows the growth area ratio of newborn hair to the wool agent prepared in each Example and Comparative.

division Example 1 Example 2 Example 3 Example 4 Example 5 Comparative Example 1 Comparative Example 2 Area ratio (%) 60.4 64.6 72.4 88.6 92.8 26.0 59.8

As shown in Table 3 above, the composition of Examples 1 to 5 containing the grape root extract showed a significantly higher hair growth promoting effect compared to Comparative Example 1, in particular, further containing other auxiliary components It can be seen that the case of 2 to 5 shows a higher effect than Example 1 which is not.

Effect Experiment Example  3: Evaluation of clinical trials of hair growth promoting effect

In order to confirm the superior testosterone 5 alpha-reductase activity inhibitory effect and the hair growth promoting effect shown in the animal test of the grape root extract confirmed in the above experimental example, alopecia subjects were selected and tested.

The clinical effect of promoting hair growth was measured using the wool preparation containing the grape root extract prepared in Example 5 and the formulation of Comparative Example 1 not containing it. The test subjects were 24 males and females with male or female alopecia from 20 to 50 years of age or who had an average number of baldness of 100 or more per day. Ml) was applied and used for at least 1 month up to 4 months depending on the degree of effect confirmation.

As for the determination of the effect, the average daily hair loss at trituration, gross findings, and improvement in subjective symptom improvement were evaluated in five stages according to the evaluation scale of Table 4, and overall improvement was taken as the average of the evaluation scale. The final judgment made the overall improvement of 3.0 points or more effective, and the result is shown in following Table 5.

Phase division Hair Loss at Tricycle Subjective symptoms Visual judgment 5 4 3 2 1 Significant decrease moderate decrease hardness hardness worse (increase) Significant Improvement Moderate Improvements Hardness Improvements Constant Deterioration Significant Improvement Moderate Improvements Hardness Improvements Constant Deterioration

division Hair Loss at Tricycle Subjective symptoms Visual judgment Overall improvement Example 5 Comparative Example 1 4.0 2.4 4.2 2.8 3.6 2.4 3.9 2.5

As shown in Table 5, the formulation of Example 5 containing the grape root extract showed a degree of improvement over moderate improvement compared to the formulation of Comparative Example 1, it was found that the hair loss prevention and hair growth promoting effect is very excellent. In addition, no adverse effects were found in all subjects during the trial period, indicating that the composition is safe for humans.

As described above and looked through the examples, the testosterone 5 alpha-reductase inhibitor containing the grape root extract of the present invention has a strong testosterone 5 alpha-reductase activity inhibitory effect, drugs, quasi drugs In the field of cosmetics, etc., it can be effectively used for the treatment of alopecia, prevention and treatment of acne and seborrheic dermatitis, prostatic hypertrophy.

Claims (6)

Testosterone 5 alpha-reductase inhibitor composition containing Vitis Radix extract as an active ingredient. The composition of claim 1, wherein the grape root extract contains 0.001 to 10% by weight on a dry weight basis. The composition for treating alopecia of claim 1. The composition of claim 1 for preventing and treating acne and seborrheic dermatitis. The composition for treating prostatic hyperplasia according to claim 1. According to claim 3, further comprising one or more selected from pepper tink, tocopherol acetate, benzyl nicotinate, secinin extract, medicinal extract, red ginseng extract, hinokithiol, nicotinic acid amide, el-menthol, pyroxtonolamine and salicylic acid Characterized in that the composition.