KR100523540B1 - Composition Inhibiting Activity of 5α-Reductase and Antimicrobial Activity to Propionibacterium Acnes - Google Patents

Abstract

The present invention strongly inhibits the activity of testosterone 5α-reductase, and contains one or two or more extracts selected from the group consisting of Gobon, rhubarb, betel nut and sculptor having excellent antibacterial activity against propionibacterium acnes. The present invention relates to a composition having excellent preventive and therapeutic effects on sebum-related diseases such as acne, hair loss, seborrheic dermatitis, and dandruff caused by seborrheic dermatitis.

Description

Composition having inhibitory activity of 5α-reductase and antimicrobial activity on propionibacterium acnes

The present invention strongly inhibits the activity of testosterone 5α-reductase, and has one or more extracts selected from the group consisting of bovine, rhubarb, betel nut and flakes having excellent antimicrobial activity against propionibacterium acnes. The present invention relates to a composition having excellent preventive and therapeutic effects against sebum-related diseases such as acne, hair loss, seborrheic dermatitis, and dandruff caused by seborrheic dermatitis.

Sebum-related disorders, such as masculine alopecia, acne, seborrheic dermatitis and dandruff caused by seborrheic dermatitis, are testosterone dependent chronic skin diseases (Van Luu-The et al. 5; Characterization, Expression, and Immunohistochemical Localization of 5α-Reductase in Human Skin) , J. Invest.Dermatol, 102, 221-226, 1994). Among them, male-type hair loss, which can cause serious mental damage to middle-aged men, is directly related to the amount of testosterone. Recently, many studies on the prevention and treatment of hair loss through the development of testosterone inhibitors have been reported.

The sebum production mechanism of testosterone is briefly described as follows.

Testosterone, one of the male hormones, is converted to the active male hormone dihydrotestosterone by 5α-reductase, and the abnormal overaction of this hormone acts as a substance that causes male hair loss while at the same time overproducing sebum in sebum cells. It acts as a main cause of substances. If the sebum is abnormally overproduced or secreted by the above mechanism, sebum-related diseases are caused. As a result, the sebum-related disease is due to the overproduction of dihydrotestosterone by the action of 5α-reductase, and if the activity of 5α-reductase is inhibited, the disease may be fundamentally and effectively prevented and treated.

In the case of acne, a typical sebum-related disease, several important factors besides the excessively produced sebum are important to exacerbate the disease. Among them, the mechanism of acne exacerbation caused by bacteria is as follows. If the sebum produced by the mechanism described above is not discharged out of the pores due to the hyperkeratosis of the pores, the primary microsurface is formed and propionibacterium acnes (hereinafter referred to as P. acnes) are anaerobic epidermal bacteria existing in the pores of the pores. ) By the action of chronic inflammatory diseases such as papules, pustules, cysts, nodules, and if severe, will cause scars. As a result, in the case of acne, excessive production of sebum, hyperkeratosis of pores and blood. It is described as a disease caused by several complex factors such as the action of Acnes.

Many studies have reported to inhibit the activity of 5α-reductase to prevent or treat sebum-related diseases such as acne, male hair loss, seborrheic dermatitis, and dandruff caused by seborrheic dermatitis (see Yasuro Sugimoto et al. 3; Cations). Inhibit Specifically Type I 5α-Reductase Found in Human Skin, J. Invest.Dermatol, 104, 775-778, 1995) and several substances have been found, but their effectiveness and practicality are small and considerable care is required for their use. In addition, acne, which is a representative sebum-related disease, is used to treat blood. When antibiotics such as tetracycline are used as an antibacterial substance against Acnes, it is known that it is highly likely to cause side effects such as the appearance of resistant bacteria or photosensitive effects.

In view of these problems, the present inventors consider the problem of 5α-reducta, an enzyme that is directly involved in the production of male hormones, which are the main cause of sebum-related diseases such as acne, androgenetic alopecia, seborrheic dermatitis and dandruff caused by seborrheic dermatitis. In order to uncover the excellent efficacy of natural extracts that strongly inhibit the activity of the azease, we continued to study, and finally, Bonbon, rhubarb, betel nut and sculptural extracts strongly inhibited the activity of 5α-reductase at low concentrations. It was found that there is a strong antibacterial effect against Acnes and completed the present invention.

The present invention relates to 5α-reductase activity inhibitory activity comprising one or two or more extracts selected from the group consisting of Bonbon, rhubarb, betel nut and flakes. It relates to a composition having an antibacterial action on Acnes.

The present invention is described in detail below.

〈General materials of the original, rhubarb, betel nut and sculptor〉

General data on ancient texts used in the present invention are as follows. The scientific name is Ligusticum tenuissimum and its root is used as a herbal medicine. The roots are 2 to 3 cm in diameter and the roots are split and the length is about 5 to 20 cm and the taste is slightly sweet. It has been used for headache or embryonic pain since ancient times. General data on rhubarb include: The scientific name is Rheum palmatum, and the root stem is a herbal medicine. The cross section of rhubarb is grayish brown to pale brownish brown or brown to blackish brown, and has been used as a laxative since ancient times. Representative main component is reanthros, with about 5% of oxanthraquinoids. General data about the betel is as follows. The scientific name is Areca cathecu, and the skin is removed from the seeds of betel nut as a herbal medicine. Its shape is flat spherical shape is about 3 to 4 cm in length and 2 to 3 cm in diameter. The outer surface is reddish brown or greyish brown with pale net pattern, and the taste is light and slightly bitter. Alkaloids are the most representative of them, such as arecholine and arecaidine, which contain about 15% tannin. It has been reported that it is used in the treatment of glaucoma, in the treatment of glaucoma, mucosa and skin diseases. General data on sculptors are as follows. The spines of the main tree are dried and long, but they are usually branched and have very pointed tips, containing a small amount of alkaloids, and have been used for skin diseases such as swelling since ancient times.

〈Preparation of Gobon, Rhubarb, Betel Nut and Carving Extracts〉

First, the original bone, rhubarb, betel nut and flakes are purified, powdered and chilled for 5 days in about 10 times the amount of the extraction solvent, and then the raw extract, rhubarb and betel nut are filtered, concentrated and lyophilized. And dried powder of flake extract was obtained. The extraction solvent used was selected from the group consisting of purified water, methanol, ethanol, propanol, butanol, glycerol, propylene glycol, 1,3-butylene glycol, methyl acetate, ethyl acetate, benzene, hexane, diethyl ether and dichloromethane. One kind or a mixture of two or more kinds of solvents were used.

<Evaluation of 5α-Reductase Inhibitory Activity of Gobon, Rhubarb, Betel Nut and Sculpture Extracts>

5α-reductase used in 5α-reductase inhibition experiments was obtained from livers of rats (Sprague-Dawley mature male rats (8 to 10 weeks old)) and a certain amount of protein suspension was prepared by protein quantification. In addition, the enzyme reaction solution was prepared by a general method. Radiolabeled testosterone ( ³ H testosterone) was used as the reactor for 5α-reductase, and enzyme reaction solution: protein suspension: botanical, rhubarb, betel and flake extract = 70:20:10 for 2 minutes. After reacting in a thermostat, the reaction solvent is blown out, the remaining material is dissolved in a developing solvent and developed in thin layer chromatography (TLC), and the amount of testosterone and dihydrotestosterone developed are quantitatively analyzed using a densitometer. The conversion rate of testosterone to dihydrotestosterone by reductase was measured, and the result was compared with the control group (conversion rate without addition of botanical, rhubarb, betel nut and engraver extract) to evaluate 5α-reductase inhibition rate. It was. The inhibition rate calculation method is as follows, and the results are shown in Table 1 and 2 as the average value of the three experiments.

% Inhibition = [(A-B) / A] × 100

In the above formula,

A = conversion of testosterone to dihydrotestosterone without extract

B = conversion of testosterone to dihydrotestosterone upon addition of the extract

As described above, when tested using one or more extracts of Gobon, rhubarb, betel nut and sculptor, it was evaluated to significantly inhibit the activity of 5α-reductase even at low concentrations, and the ratio of extracts on two species was constant. When mixed with the experiments showed similar or slightly stronger activity inhibitory effect than when used alone. This means that the activity inhibition rate for 5α-reductase is excellent irrespective of the type of extract, and it is clear that the excellent activity inhibition force is not limited to the composition of the above-mentioned extract.

〈Evaluation of Antimicrobial Activity on Blood and Arces of Gobon, Rhubarb, Betel Nut and Sculpture Extracts〉

The antimicrobial activity of the extract obtained by the above method was added to a certain concentration of pear, rhubarb, betel nut and sculptural extracts in P. acnes cultured in a liquid medium, followed by culturing in an anaerobic culture tank, and then the growth of P. acnes. The minimum inhibitory concentration (MIC) was calculated. As a result, the minimum inhibitory concentration ranges of P. acnes of extracts of botanical, rhubarb, betel nut and flakes according to each extraction solvent are shown in Table 3 below.

According to the above results, the extract of Gobon, Rhubarb, Betel nut and Sculpture, which strongly inhibited the activity of 5α-reductase, has a strong antibacterial activity against P. acnes, which is one of the main causes of acne among sebum-related diseases. You can see the amazing fact.

In addition, through the animal experiments to explore the efficacy of the extract of Gobon, rhubarb, betel nut and sculptural extract revealed a new fact that the hair loss prevention effect and wool (hair loss treatment) effect is also excellent.

The composition of the present invention preferably contains from 0.01 to 10% by weight of a dry powder of one or two or more extracts selected from Gobon, rhubarb, betel nut and flakes based on the total amount of the composition. Less than 0.01% by weight of the extract of rhubarb, rhubarb, betel nut and flakes showed less activity inhibition of 5α-reductase, and when it exceeds 10% by weight, the activity inhibitory ability is excellent but there is difficulty in manufacturing.

Compositions such as cleansing agents, soaps and creams prepared by including one or more extracts of Gobon, rhubarb, betel nut and sculptor according to the present invention were subjected to 5α-reductase activity inhibition test and acne treatment effect evaluation test (cleanser). Results In acne, a typical sebum-related disease, the acne treatment effect was excellent without showing side effects such as skin redness.

The face wash, soap and cream composition of the present invention can be easily prepared by a conventional manufacturing method, it is easy to apply to any of the different formulations, such as liquid, cream, paste or solid phase.

Hereinafter, the present invention will be described in detail based on Examples and Comparative Examples, but these Examples do not limit the technical scope of the present invention.

A) Preparation and efficacy test of facial cleanser composition containing one paper among Gobon, rhubarb, betel nut and flakes

Examples 1-8 and Comparative Examples 1-8

Table 4 to 11 of the composition and the dry powder of the paper-based extract selected from gobon, rhubarb, betel nut and sculptural composition in a homo-mixer through a process such as stirring, heating, degassing, cooling to mix the composition material uniformly The face wash composition was prepared by a conventional convenient method. Workability and stability in Examples and Comparative Examples means the ease of work (the solubility in the product of the extract) and the phase stability (with or without phase separation) after the preparation of the face wash by mixing the extract.

5α-리덕타아제 활성 억제력 실험:

5α-reductase activity inhibitory experiment:

In order to confirm the effect of preventing and treating acne on the cleansing composition prepared in Examples and Comparative Examples, each composition was diluted to a specific concentration using purified water, and the inhibition rate of 5α-reductase activity was evaluated by the above-described method. . The inhibition rate of 5α-reductase activity is shown in Tables 12a, 12b, 12c and 12d as the average of three experiments.

As shown in the table, it was found that the face wash containing one or more extracts of Gobon, Rhubarb, Betel nut and Sculptor inhibits the activity of 5α-reductase more strongly than it does not contain them. Clinical results of face washes containing both betel nut and sculptural extracts showed very good acne treatment. In addition, as shown in the above results, the addition of less than 0.01% by weight of the extract of Gobon, rhubarb, betel nut and flakes showed a low activity inhibition rate of 5α-reductase, and when it exceeds 10% by weight, the activity inhibition was excellent. There was a difficulty in manufacturing. Therefore, the content of the extracts of botanical, rhubarb, betel nut and flakes in the face wash used in the present invention was found to be very excellent in the activity inhibitory activity and workability for 5α-reductase within the range of 0.01 to 10% by weight.

B) Preparation and efficacy test of soap composition containing one paper phase among Gobon, Rhubarb, Betel nut and Carving

Examples 9-12 and Comparative Examples 9-12

Table 14 to 17 of the composition of the soap base and dry powder of one paper extract selected from the original, rhubarb, betel nut and sculptural well mixed in a mixer, and then extruded, cut, and molded in a soap manufacturing machine soap in the form of a solid soap The composition was prepared, and the extract may be prepared by including not only general soap, but also synthetic soap and complex soap by a conventional soap manufacturing method. Workability and stability means ease of operation (solubility in the product of the extract) when mixing the extract to produce a soap.

5α-reductase activity inhibitory experiment :

In order to confirm the effect of preventing and treating acne on the soap compositions prepared in Examples and Comparative Examples, each composition was diluted to a specific concentration using purified water, and the inhibition rate of 5α-reductase activity was evaluated by the method described above. . 5α-reductase activity inhibition rate is shown in Table 18a and b as the average value of the three experiments.

As shown in the experimental results (Tables 18a and b), soaps containing at least one extract of Gobon, rhubarb, betel nut and sculptural extracts were strongly and significantly inhibited the activity of 5α-reductase than those without them. appear. In addition, as shown in the above results, in the case of soap containing at least one extract of Gobon, rhubarb, betel nut and engraver extract, if the total content of the extract is less than 0.01% by weight, the degree of inhibiting the activity of 5α-reductase is somewhat When it exceeds 10% by weight, the activity inhibitory power is excellent, but there are many difficulties in workability. Therefore, the content of the extract of Gobon, rhubarb, betel nut and flakes in the soap used in the present invention was found to be very good activity inhibitory activity and workability for 5α-reductase within the range of 0.01 to 10% by weight.

C) Preparation and efficacy test of cream composition containing one paper phase among Gobon, rhubarb, betel nut and flakes

Examples 13-16 and Comparative Examples 13-16

To prepare a cream composition by combining the cream base of the composition of Table 19 to 22 with a dry powder of one paper extract selected from Gobon, rhubarb, betel nut and flakes in a mixer, degassed, filtered, and cooled. At this time, the prescription was prepared in the oil-in-water type (O / W) so that a small amount of oily components present. The extract can be conveniently added to basic cosmetics such as foam cleansing, lotion, essence and the like and can be used as an acne prevention and treatment. Workability and stability mean ease of operation (solubility in the product of the extract) when preparing the soap by mixing the extract and phase stability (with or without phase separation) after preparation.

5α-reductase activity inhibitory experiment :

In order to confirm the effect of preventing and treating acne for the cream compositions prepared in Examples and Comparative Examples, each composition was diluted to a specific concentration using purified water, and the inhibition rate of 5α-reductase activity was evaluated by the method described above. . 5α-reductase activity inhibition rate is shown in Table 23 a and b as the average value of the three experiments.

As shown in the experimental results (Tables 23a and b), creams containing at least one extract of Gobon, Rhubarb, Betel nut and Engraver extracts showed stronger and significantly inhibiting the activity of 5α-reductase than those without appear. In addition, as shown in the above results, in the case of the cream containing at least one extract of gobon, rhubarb, betel nut and engraver extract, if the total content of the extract is less than 0.01% by weight, the degree of inhibiting the activity of 5α-reductase is somewhat When it exceeds 10% by weight, the activity inhibitory power is excellent, but there are many difficulties in workability. Therefore, the content of the extract of Bonbon, rhubarb, betel nut and flakes in the cream used in the present invention was found to be very good activity inhibitory activity and workability for 5α-reductase within the range of 0.01 to 10% by weight.

As described above, compositions such as face washes, soaps and creams containing 0.01 to 10% by weight of one or two or more extracts selected from the group consisting of gobon, rhubarb, betel nut and engraver according to the present invention are 5α-reducta. It strongly inhibited the activity of the enzyme, and was effective in preventing and treating sebum-related diseases such as acne, hair loss, seborrheic dermatitis and dandruff caused by seborrheic dermatitis.

Claims (6)

It contains one or two or more dry powders of extracts selected from the group consisting of rhubarb, betel nut and flakes to inhibit the activity of 5α-reductase and have an antimicrobial effect against propionibacterium acnes. A composition for preventing and treating sebum-related diseases selected from the group consisting of dandruff caused by acne, hair loss, seborrheic dermatitis and seborrheic dermatitis. The composition of claim 1, which contains 0.01 to 10% by weight of a dry powder of an extract selected from the group consisting of rhubarb, betel nut and flakes. The composition according to claim 1 or 2, which is liquid, cream, paste or solid. The composition according to claim 1, further comprising a solid extract. The composition according to claim 4, which contains 0.01 to 10% by weight of dry powder of the extract of Gobon. A composition according to claim 4 or 5, characterized in that it is liquid, cream, paste or solid.