JP7170357B2 - External agent for hair growth - Google Patents

Description

TECHNICAL FIELD The present invention relates to a skin preparation for external use for hair restoration and hair growth, and a therapeutic agent for alopecia, containing an Aspergillus oryzae fermented product or an extract of an Aspergillus fermented product.

Recently, an increasing number of men and women suffer from hair loss symptoms such as hair loss and thinning on the head. In order to ameliorate such symptoms, research on the mechanism of hair growth and hair cycle has been conducted, and active ingredients that promote hair growth and suppress hair loss are being developed. At present, a typical example is minoxidil (see Patent Document 1), etc., and a large number of topical skin preparations and hair cosmetics containing this for hair restoration and hair growth have been developed and commercialized.

On the other hand, in recent years, the value of traditional Japanese koji-fermented foods using koji such as sake, shochu, amazake, miso, and soy sauce has been recognized again, and the popularity of koji has increased. Koji is produced by steaming rice, rice bran, barley, beans, or the like to propagate koji mold. For example, rice grown with koji mold is called rice koji. Aspergillus oryzae is known to have the ability to produce a wide variety of enzymes that enable the production of fermented foods. The inventor of the present application is proceeding with the development of applications based on the above. Patent Document 2 reports that a feed obtained by fermenting cereals with Aspergillus oryzae promotes the growth of animals. Patent Document 3 describes a koji-fermented composition obtained by inoculating and culturing tea leaves with Aspergillus oryzae. has been reported to have antioxidant activity.

Patent No. 2733980 Patent No. 6111416 WO2015/119036

However, since minoxidil, which is a hair growth ingredient described in Patent Document 1, was originally used as a therapeutic agent for hypertension, it has been reported that side effects such as hypotension may occur. Therefore, it is expected to provide a new material that is safer and has excellent hair growth and hair restoration effects.

In addition, Patent Documents 2 and 3 each describe a koji fermented product obtained by fermenting grains or tea leaves with koji mold. There was no study to use it for this purpose, and its effectiveness was unknown.

Accordingly, the present invention has been made in view of the above-mentioned problems, and an object of the present invention is to provide a highly safe external preparation for hair restoration and a therapeutic agent for alopecia, which have excellent hair growth and hair restoration effects. That's what it is.

In order to solve the above problems, the external preparation for hair growth/hair growth or the therapeutic agent for alopecia of the present invention contains an Aspergillus fermented product fermented with Aspergillus oryzae or an extract of this Aspergillus fermented product.

This aspergillus fermented product and the extract of this aspergillus fermented product have an excellent hair growth promoting action, and are effective for alopecia such as male pattern hair loss (androgenetic alopecia) and senile alopecia. It is also useful for treatment, prevention or amelioration.

In addition, it is also preferable that the above-mentioned koji mold fermented product uses raw materials derived from tea leaves, grains, or beans as fermentation raw materials. As a result, suitable raw materials for the fermented product of Aspergillus oryzae are selected.

Moreover, it is also preferable that the above-mentioned koji mold is black koji mold or white koji mold. As a result, a suitable aspergillus oryzae that produces the aspergillus fermented product, which is the active ingredient of the external preparation for hair restoration/hair growth or the therapeutic agent for alopecia of the present invention, is selected.

Moreover, it is also preferable that the external preparation for hair restoration/hair growth or the therapeutic agent for alopecia of the present invention further contain lactic acid bacteria. As a result, when producing an aspergillus fermented product, the growth of the aspergillus oryzae is promoted, fermentation by the aspergillus oryzae is stably performed, and a highly active aspergillus fermented product is obtained.

It is also preferable that the extract of the fermented product of Aspergillus in the present invention is a water or hydroalcoholic extract of the fermented product of Aspergillus. As a result, an external preparation for hair restoration/hair growth or a therapeutic agent for alopecia having an excellent hair growth-promoting effect can be obtained easily and at low cost.

In addition, the method for producing the external preparation for hair growth and hair growth or the therapeutic agent for alopecia of the present invention includes the steps of inoculating a fermented raw material derived from tea leaves, grains or beans with koji mold, and fermenting the fermented raw material with this koji mold. It has a step of obtaining a koji mold fermented product. As a result, an external preparation for hair growth/hair growth or a therapeutic agent for alopecia, which has an excellent hair growth-promoting effect and is useful for the treatment, prevention, or improvement of alopecia such as androgenic alopecia and senile alopecia, can be obtained. can get.

In addition, the method for producing the external preparation for hair growth/hair growth or the therapeutic agent for alopecia of the present invention comprises the steps of: inoculating a fermented raw material derived from tea leaves, grains or beans with Aspergillus oryzae and lactic acid bacteria; It has a step of fermenting the fermentation raw material to obtain an aspergillus fermented product. As a result, an external preparation for hair growth/hair growth or a therapeutic agent for alopecia having an excellent hair growth promoting action can be obtained. Furthermore, by co-cultivating lactic acid bacteria with Aspergillus oryzae, the growth of Aspergillus oryzae is promoted and fermentation by Aspergillus oryzae is stably performed, so that Aspergillus oryzae fermented product with stable and high activity is obtained, and the fermentation period is shortened.

In addition, in the method for producing the external preparation for hair growth/hair growth or the therapeutic agent for alopecia of the present invention, it is also preferable that the koji mold described above is black koji mold or white koji mold. As a result, a suitable aspergillus oryzae that produces the aspergillus fermented product, which is the active ingredient of the external preparation for hair restoration/hair growth or the therapeutic agent for alopecia of the present invention, is selected.

Moreover, the method for producing the external preparation for hair growth/hair growth or the therapeutic agent for alopecia of the present invention may comprise a step of extracting the obtained fermented product of Aspergillus oryzae with water or hydrous alcohol to obtain an extract of the fermented product of Aspergillus oryzae. preferable. As a result, an external preparation for hair restoration/hair growth or a therapeutic agent for alopecia having an excellent hair growth-promoting effect can be obtained easily and at low cost.

INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide an external preparation for hair restoration/hair growth or a therapeutic agent for alopecia having the following excellent effects.
(1) It is excellent in hair restoration and promotion of hair growth.
(2) Alopecia can be treated, prevented or improved.
(3) It is highly safe because it contains, as an active ingredient, a fermented product by Aspergillus oryzae, which is also used in food production.
(4) Only by extracting the fermented product of Aspergillus oryzae with water or water-containing alcohol, it is possible to obtain a liquid preparation for external use for hair growth and hair growth or a therapeutic agent for alopecia, so that it is easy to manufacture.

BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a flow chart schematically showing a method for producing an Aspergillus fermented product and an Aspergillus fermented product extract according to an embodiment of the present invention. 10 is a graph showing hair growth scores of control group and test group in Example 4. FIG. 10 is a graph showing hair growth scores of control group and test group in Example 5. FIG. 10 is a photograph showing the state of hair growth of a subject in Example 6. FIG. 10 is a graph showing hair growth scores of a control group (control group) and test groups (2% group, 4% group and 8% group) in Example 7. FIG.

First, referring to FIG. 1, a method for producing an Aspergillus fermented product P1 fermented with Aspergillus oryzae, which is contained in the external preparation for hair restoration/hair growth or the therapeutic agent for alopecia of the present invention, will be described.

As shown in FIG. 1, the method for producing an aspergillus fermented material P1 according to the embodiment of the present invention comprises a step S0 of preparing fermentation raw materials, a step S1 of adding water to the fermentation raw materials to absorb water, a step S2 of steaming the fermentation raw materials, It is roughly composed of a step S3 of inoculating koji mold into the steamed fermentation raw material and a step S4 of performing fermentation.

(Preparation of raw materials for fermentation)
First, the step S0 of preparing fermentation raw materials shown in FIG. 1 will be described. Plant-derived raw materials are selected as fermentation raw materials in the present invention, and plant leaves, stems, roots, flowers and fruits can be used as fermentation raw materials. Among these, tea leaves, grains or beans are preferably used, and tea leaves are particularly preferably used as fermentation raw materials. Cereals broadly include rice, corn, wheat, barley, rye, oats, sorghum, buckwheat and other millet grains. Tea leaves include not only tea leaves but also stems and branches collected from tea plants. As for the tea leaves used as raw materials for the aspergillus fermented product of the present invention, raw tea leaves in the state of being harvested are preferably used, but tea leaves that have been heat-treated immediately after harvesting, and oxidizing enzymes contained in tea leaves after harvesting are preferably used. It may be oolong tea or black tea obtained by oxidizing and fermenting tea leaves in , or post-fermented tea. In addition, tea residue obtained by brewing green tea, oolong tea, black tea, or the like can also be used. In addition, in order to enhance the efficiency of the subsequent steaming process and the cultivation of koji mold, it is preferable that the tea leaves and tea stems are crushed to a certain size so as not to be too large.

(water absorption treatment)
Next, the water absorption treatment step S1 will be described. In this step, water is added to the fermented raw material, or the fermented raw material is immersed in water to absorb water. For example, when tea leaves are used as a raw material for fermentation, the water absorption is adjusted so that the moisture content of tea leaves is 20 to 60%, preferably 30 to 50%.

(Steamed treatment)
Next, the steaming treatment step S2 will be described. The fermented raw material absorbed in the above process is placed in a steamer, covered with a lid, and the steamer is heated to apply steam to the fermented raw material for heating. The steaming time is preferably about 30 minutes to 120 minutes, more preferably about 45 minutes to 90 minutes, and particularly preferably about 60 minutes. By performing this step, various bacteria in the raw material are sterilized, and in the subsequent fermentation step, fermentation is performed using koji mold as the dominant species. In addition, when raw tea leaves are used as the raw material for fermentation, this step sterilizes various bacteria in the tea leaves and deactivates the oxidizing enzymes contained in the tea leaves. Aspergillus oryzae can be propagated efficiently. After steaming, the ingredients are taken out from the steamer, spread evenly on a table, and cooled to about 30-40°C. This makes it possible to inoculate the fermentation raw material with the koji mold.

(Inoculation of Aspergillus oryzae)
Next, the step S3 of inoculating (seeding) the fermentation raw material with koji mold will be described. In this step, aspergillus oryzae is inoculated to the fermented raw material that has been cooled through the above steaming step. Aspergillus oryzae in the present invention is a microorganism that is mainly used when producing koji-fermented foods, and specifically includes black aspergillus, white aspergillus or yellow aspergillus. Among these, black koji mold is a fungus of the genus Aspergillus that forms black or dark brown conidia (a kind of asexual spores) used in the production of distilled liquor such as awamori in Okinawa and potato shochu in Kagoshima. refers to a group. Specifically, but not limited to, Aspergillus awamori var kawachi (Kawachi black koji mold), Aspergillus ryukyuensis, Aspergillus awamori, Aspergillus saitoi, Aspergillus inui, Aspergillus usami, Aspergillus aures and the like. mentioned. White koji mold refers to a group of fungi belonging to the genus Aspergillus that form white-ocher conidia, and specific examples thereof include Aspergillus kawachii. Furthermore, yellow koji mold refers to a group of fungi belonging to the genus Aspergillus that form yellow or yellow-green conidia, and is a microorganism mainly used in the production of sake, miso, soy sauce, and the like. Specific examples include, but are not limited to, Aspergillus oryzae, Aspergillus sojae, and the like. In the present invention, it is preferable to use black koji mold or white koji mold from the viewpoint of excellent hair growth promoting effect and from the viewpoint of pH adjustment because koji mold itself produces citric acid. Among these, the black koji mold Aspergillus awamori var. kawachii, Aspergillus luchuensis or Aspergillus inuii, the white koji mold Aspergillus kawachii and these A combination is preferably used, and Kawachi black koji mold (Aspergillus awamori var. kawachii) is particularly preferred. The inoculation of these koji molds can be carried out, for example, by mixing the koji mold with the fermented raw materials put in a sterilized bag and stirring the mixture. Aspergillus oryzae is preferably inoculated with its spores, and it is preferable to add and inoculate the aspergillus oryzae spores in an amount of 500,000 or more, preferably 1,000,000 or more per 1 g (dry weight) of the fermentation raw material. For example, when the number of spores contained in 1 g of koji starter is 2 billion, about 0.5 g (0.05% by weight) of koji starter may be added to 1 kg of fermentation raw material. After the koji mold is inoculated into the raw material for fermentation, it is preferable to stir the koji mold well to disperse the koji mold throughout the raw material.

In addition, it is also preferable to inoculate lactic acid bacteria in the aspergillus inoculation step S3 to co-culture the aspergillus and lactic acid bacteria. By co-cultivating koji mold and lactic acid bacteria, the growth of koji mold is promoted, stable fermentation is performed, and the fermentation period is shortened. breeding is suppressed. As lactic acid bacteria, lactic acid bacteria used in lactic acid fermented foods can be used, such as Lactobacillus casei, Lactobacillus fermentum or Lactobacillus bulgaricus. Bifidobacterium such as Bifidobacterium bifidum, Lactococcus such as Lactococcus lactis, and Enterococcus such as Enterococcus faecium. The lactic acid bacteria to be inoculated should be those that have been cultured in advance, and about 0.1% by weight of bacterial cells may be added to 1 kg of the fermentation raw material. Aspergillus fermented product obtained by fermentation with Aspergillus oryzae and lactic acid bacteria contains various enzymes produced by Aspergillus oryzae and lactic acid bacteria, aspergillus oryzae, its spores and lactic acid bacteria.

(fermentation)
Next, the step S4 of performing fermentation by culturing the koji mold inoculated into the fermentation raw material will be described. In this step, aspergillus oryzae is propagated on the raw material inoculated with aspergillus oryzae. First, the fermentation raw material to which the koji mold is added is placed in a culture chamber maintained at around 30°C. Fermentation progresses as time passes, and the temperature of the raw materials for fermentation such as tea leaves rises. Generally speaking, it is difficult for Aspergillus oryzae to grow when the temperature exceeds 40°C. The amount of ventilation is adjusted so that the temperature is maintained between 30°C and 42°C, preferably between 30°C and 40°C. The fermentation temperature is appropriately adjusted depending on the type of koji mold used for fermentation. Specifically, when black koji mold or white koji mold is selected as the koji mold, as an example, the temperature of the raw material for fermentation such as tea leaves is adjusted to 35° C. to 40° C. by ventilation for 12 to 30 hours from the start of cultivation. do. Thereafter, the temperature is adjusted slightly lower to 30° C.-35° C. by similarly adjusting the amount of ventilation, etc., for a total of 1 to 4 days, preferably 36 to 72 hours, more preferably 36 to 72 hours from the start of culture. The aspergillus fermented product P1 is completed at the time of culturing for about 40 to 60 hours.

In addition, in the manufacturing steps S1 to S4 of the koji mold fermented product P1 described above, a machine (for example, a drum-type automatic It is also possible to carry out using a koji-making apparatus, etc.).

(Aspergillus fermented product)
The obtained koji mold fermented product P1 is so-called "koji" in which koji mold propagates in the fermentation raw material. This koji mold fermented product P1 is excellent in promoting hair growth and hair growth, and can treat, prevent, or improve alopecia. The aspergillus fermented product P1 obtained by the above-described process contains a certain amount of water, but the water can be removed by natural drying or low-temperature dehumidification drying. Moreover, it is also possible to pulverize the koji mold fermented material P1 from which moisture has been removed into powder or granules. By reducing the water content of the aspergillus fermented product P1, it is possible to suppress the activity and growth of the aspergillus oryzae and lactic acid bacteria in the aspergillus fermented product P1 and preserve it for a long period of time. becomes. Even if the water is once removed, the function of promoting hair growth and promoting hair growth as the fermented product P1 of Aspergillus oryzae can be effectively maintained.

Next, the method for producing the extract P2 of the fermented product of Aspergillus oryzae contained in the external preparation for hair restoration/hair growth or the therapeutic agent for alopecia of the present invention will be described. As shown in FIG. 1, the method for producing an extract P2 of an aspergillus fermented material according to the embodiment of the present invention includes a step S5 of adding an extraction solvent to the aspergillus fermented material P1 obtained in the above-described steps S1 to S4 for extraction. It is roughly composed of

(extract)
The extraction step S5 will be described in detail below. In this extraction step S5, an extracting solvent is added to the Aspergillus fermented material P1 and an extraction process is performed to obtain an extract P2 of the Aspergillus fermented material. The extraction solvent is not particularly limited as long as it can extract a component having a hair growth promoting effect from the fermented product P1 of Aspergillus oryzae, but from the viewpoint of extraction efficiency and ease of handling, water or hydrous alcohol is preferable. Among these, alcohols used for hydrous alcohols include, for example, ethanol, isopropanol, 1,3-butylene glycol, propylene glycol, glycerin, etc. It is also possible to use one or more of these in combination. be. Furthermore, as the ethanol mentioned above, it is also possible to use a fermented liquid obtained by alcoholic fermentation. Specifically, brewed liquor and distilled liquor obtained by distilling it can be used, and among these, distilled liquor can be preferably used. Distilled liquors include those derived from grain raw materials such as rice, wheat, and corn, those derived from potatoes, those derived from sugar cane, and those derived from dates. Among these, distilled liquor derived from date palm fruit contains ethyl palmitate, which is a component that is gentle on the skin with particularly low skin irritation, and therefore can be selected as a suitable extraction solvent for the production of external preparations. The alcohol concentration of the hydrous alcohol is preferably 1 to 50 v/v%, more preferably 3 to 30 v/v%, and particularly preferably 5 to 15 v/v%. Moreover, when water is used as the extraction solvent, it is preferable to use water that has been sterilized by high-pressure steam sterilization, filtration sterilization, or the like. By using sterilized water, it is possible to prevent contamination with various bacteria, and it is possible to stably extract useful ingredients such as various proteins and enzymes contained in the fermented product P1 of Aspergillus oryzae. In addition to the water or hydrous alcohol described above, the extraction solvent contains other ingredients such as pH adjusters, preservatives, and extraction aids within a range that does not interfere with the extraction of useful ingredients from the Aspergillus fermented product P1. is also possible.

As a method for extracting the Aspergillus fermented material P1, it is preferable to extract the Aspergillus fermented material P1 by adding it to the extraction solvent and soaking it. In some cases, it is preferable to add 1 g to 300 g, more preferably 5 g to 150 g, and particularly preferably 10 g to 100 g. As for the extraction conditions, the extraction temperature is preferably about 0 to 30°C, more preferably about 2 to 20°C, in order to maintain the activities of various proteins and enzymes contained in the koji mold fermented product P1. is more preferable, and 4 to 10°C is particularly preferable. The extraction time is preferably about 2 hours to 5 days, more preferably about 6 hours to 3 days, and particularly preferably about 12 hours to 1.5 days.

After the extraction treatment described above, the residue is removed by decantation, centrifugation, filtration, or the like to obtain an extract P2 of the fermented product of Aspergillus oryzae. As the extract P2 of the Aspergillus fermented product of the present invention, in addition to the extract P2 itself of the Aspergillus fermented product obtained in the extraction step S5, a concentrated liquid obtained by concentrating the extract P2 by concentration treatment such as vacuum concentration, or Aspergillus fermentation Also included are those obtained by subjecting the extract P2 of the substance to a drying treatment such as a freeze-drying treatment to obtain a solid or powder form.

The hair-restoring/hair-growth external preparation or alopecia therapeutic agent of the present invention contains as an active ingredient the Aspergillus fermented product P1 fermented with Aspergillus oryzae or the Aspergillus fermented product extract P2 as described above, and has a hair-restoring effect and a hair-regenerating effect. It has a hair-promoting action and an action to treat, prevent or improve various types of alopecia such as male pattern baldness and senile alopecia. Therefore, the external preparation containing the Aspergillus fermented product or the extract of the Aspergillus fermented product of the present invention is a drug, quasi-drug, and hair product for preventing, treating, or improving symptoms such as thinning hair and hair loss, and alopecia. Can be used as cosmetics. Since the external preparation of the present invention contains, as an active ingredient, a fermented product of Aspergillus oryzae, which is also used in food production, it is highly safe and can be used easily with peace of mind regardless of age, gender, chronic disease, etc. is.

The content of the Aspergillus fermented product P1 in the external preparation for hair growth/hair growth or the therapeutic agent for alopecia of the present invention is preferably about 0.1% to 20% by weight, more preferably about 0.3% to 10% by weight. More preferably, about 1% by weight to 5% by weight is particularly preferred. As for the extract P2 of the fermented product of Aspergillus oryzae, the extract (extract liquid) P2 itself of the fermented product of Aspergillus oryzae obtained through the extraction step S5 may be applied as an external preparation for hair growth/regeneration or a therapeutic agent for alopecia. From the viewpoint of extraction efficiency and hair growth effect, it is preferable to be an extract obtained by adding 0.1 g to 30 g of Aspergillus oryzae fermented product P1 (dry product), which is the object to be extracted, to 100 mL of the extraction solvent. Preferably, it is an extract obtained by adding 0.5 g to 15 g of Aspergillus fermented product P1 (dried matter), and more preferably an extract obtained by adding 1 g to 10 g of Aspergillus fermented product P1 (dried matter). A liquid is particularly preferred. In addition, when the extract (extract liquid) P2 of the fermented koji mold is not used as a topical preparation for hair growth, 0.1 g to 30 g of the fermented koji mold P1 (dry product) is used per 100 mL of the topical preparation. It is preferable that the extract P2 obtained by extraction is blended, and more preferably the extract P2 obtained by extracting 0.5 g to 15 g of the aspergillus fermented product P1 (dry matter) is blended. It is particularly preferred that an extract P2 obtained by extracting 1 g to 10 g of the koji mold fermented product P1 (dry product) is blended.

The amount of the external preparation for hair growth/hair growth or the therapeutic agent for alopecia of the present invention to be used varies depending on the desired improvement or therapeutic effect, symptoms, size of the affected area, administration method, age, dosage form of the external preparation, and the like. Although it cannot be defined unconditionally, the daily usage amount is preferably 0.1 to 20 mL (g), more preferably 0.3 to 10 mL (g), and particularly preferably 0.5 to 5 mL (g).

The external preparation for hair growth/hair growth or the therapeutic agent for alopecia of the present invention is preferably adjusted to a pH of 4.0 to 6.5 in consideration of safety to the skin. The pH of the external preparation can be adjusted by using a suitable acid or base usually blended in the external preparation within the range that does not impair the effects of the present invention. Examples of such pH adjusters include acids such as hydrochloric acid, lactic acid, phosphoric acid, tartaric acid, malic acid or gluconic acid, bases such as diisopropanolamine, triisopanolamine, sodium hydroxide, sodium citrate or arginine. It is also possible to use one type or a combination of two or more types. In addition, when black koji mold or white koji mold that produces citric acid is used as the koji mold to obtain the koji mold fermented product, the koji mold fermented product contains citric acid, so it is easy to prepare a weakly acidic preparation. be able to.

In addition, various components commonly used in external preparations can be added to the hair restoration/growth topical preparation or alopecia therapeutic agent of the present invention within a range that does not impair the effects of the present invention. Examples include vasodilators, blood circulation promoters, surfactants, antihistamines, anti-inflammatory agents, thickeners, vitamins, amino acids, moisturizing agents, preservatives, antibacterial agents, fragrances and pigments. In addition, the external preparation of the present invention can be blended with a hair growth/restoration component other than the Aspergillus fermented product P1 and the Aspergillus fermented product extract P2. Other hair growth/restoration ingredients include, for example, minoxidil, adenosine, or assembly extract.

Furthermore, the external preparation for hair growth/hair growth or the therapeutic agent for alopecia of the present invention can be applied to various dosage forms of external preparations by conventional methods as dosage forms that are usually applied to the scalp and skin. Examples include liquids such as tonics and lotions, aerosols, gels, ointments, creams or emulsions. It can also be applied to shampoos, soaps, conditioners, and the like.

Next, the present invention will be described in more detail with reference to Examples, but the present invention is not limited by these Examples.

[Example 1]
1. Preparation of Aspergillus Fermented Product In this example, raw tea leaves were used as a raw material for fermentation. Water was added to the tea leaves so that the water content of the tea leaves became about 50%, and after the water absorption treatment, the tea leaves were placed in a pressurized steam kettle and steamed. The conditions for the steaming treatment were 115° C. and 60 minutes, and the steaming treatment was performed twice with one cooling intervening. After that, the tea leaves were cooled to 30°C, and Kawachi black koji mold (Aspergillus awamori var. 0.1% by weight of lactic acid bacteria (Lactobacillus casei) was added to the tea leaves so as to be 0.1% by weight, mixed, and koji making was carried out for 3 days. The koji-making temperature is adjusted so that the temperature of the tea leaves is 35°C to 40°C by ventilation for 24 hours after the koji starter is added, and the amount of ventilation is adjusted in the same way for the next 48 hours. Then, the temperature of the tea leaves was adjusted to a slightly lower temperature of 30°C to 35°C. After that, the koji mold fermented product obtained by koji making for 3 days was dried to a moisture content of 8%, and pulverized to obtain a powdered koji mold fermented product.

[Example 2]
2. Preparation of Aspergillus Fermented Product Extract (1) In this example, water was used as an extraction solvent. The fermented product of Aspergillus oryzae obtained in Example 1 (powder after drying) was added at a rate of 2 g to 100 mL of sterilized water. This was allowed to stand in a refrigerator at 4° C. for 20 hours for extraction. The supernatant was recovered to obtain the Aspergillus fermented product extract (1) used in the following examples.

[Example 3]
3. Preparation of Aspergillus Fermented Product Extract (2) In this example, an aspergillus fermented product extract (2) was obtained using an extraction solvent containing alcohol. First, water sterilized by high-pressure steam sterilization at 135 ° C. was added to distilled liquor (trade name: Hayato Namida, product of Kinnada Shuzo Co., Ltd., alcohol content 30) made from date palm fruit, and the ethanol concentration was 10 v / v% extraction solvent was prepared. 2 g of the koji mold fermented product obtained in Example 1 was added to 100 mL of this extraction solvent. This was allowed to stand in a refrigerator at 4° C. for 20 hours for extraction. The supernatant was collected to obtain the Aspergillus fermented product extract (2) used in the following examples.

[Example 4]
4. Promotion of Hair Growth in Mice by Aspergillus Fermented Product Extract (1) Eight-week-old C3H/HeN female mice were divided into two groups shown in Table 1 below, with four mice each. The hair on the back of the mouse was shaved with clippers, and the sample solution was applied to the shaved area once a day for 30 days. The application amount was 0.15 mL/day. As shown in Table 1 below, the sample solution of the control group was sterilized water, which was used as the extraction solvent in producing the Aspergillus fermented product extract (1) in Example 2, and the sample solution of the test group was The Aspergillus fermented product extract (1) obtained in Example 2 was used.

On the day after the 30th application, and 31 days after the start of the test, each mouse was observed with the naked eye for the color density and elongation of the body hair in the shaved area. sought based on The evaluation of the hair growth score was performed by those who could not distinguish between the control group mice and the test group mice to exclude experimenter bias. A significant difference between the control group and the test group was evaluated by the Mann-Whitney U test at a significance level of 5%. The results are shown in FIG. 2 and Table 3 below.

These results revealed that the mice in the test group to which the Aspergillus fermented product extract (1) was applied were clearly superior to the mice in the control group in terms of hair growth and hair elongation. In addition, the p-value comparing the two was p<0.05, indicating that there was significance.

[Example 5]
5. Promotion of Hair Growth in Mice by Aspergillus Fermented Product Extract (2) Eight-week-old C3H/HeN female mice were divided into two groups shown in Table 4 below, each containing five mice. The hair on the back of the mouse was shaved with clippers, and the sample solution was applied to the shaved area once a day for 30 days. The application amount was 0.15 mL/day. As shown in Table 4 below, the sample liquid of the control group contained the extraction solvent (distilled liquor made from date palm (trade name: Hayato Tears, a product of Kinnada Shuzo Co., Ltd., alcohol content 30), sterilized water was added to make the ethanol concentration 10 v / v%), and the test group sample solution was the koji mold fermentation obtained in Example 3. The product extract (2) was used.

On the day after the 30th application, and 31 days after the start of the test, each mouse was observed with the naked eye for the density of the body hair in the shaved area and the degree of growth of the body hair, and the hair growth score is shown in Table 2 above. calculated based on the standard. The evaluation of the hair growth score was performed by those who could not distinguish between the control group mice and the test group mice to exclude experimenter bias. A significant difference between the control group and the test group was evaluated by the Mann-Whitney U test at a significance level of 5%. The results are shown in FIG. 3 and Table 5 below.

These results revealed that the mice in the test group to which the Aspergillus fermented product extract (2) was applied were clearly superior to the mice in the control group in hair growth and hair elongation. In addition, the p-value comparing the two was p<0.01, indicating extremely high significance.

[Example 6]
6. Human hair growth promotion by Aspergillus fermented product extract (1) The Aspergillus fermented product extract (1) obtained in Example 2 was put in a spray bottle, and three subjects A to C shown in Table 6 below were given Aspergillus fermentation. The animal extract (1) was administered twice a day, morning and evening, by spraying it several times on the head and applying it by hand. The dosing period was 1-3 months. FIG. 4 shows photographs taken from above of the head of each subject before and after administration. 4(A) shows subject A, FIG. 4(B) shows subject B, and FIG. 4(C) shows subject C. FIG. In each photograph, the lower side is the face side, and the upper side is the back side.

Subject A had androgenetic alopecia with hair loss mainly on the parietal region before administration. A reduction in hair size and hair growth in the depilated area were observed. In addition, during the 3 months of use, no skin abnormality was observed. Subject B had androgenetic alopecia, particularly marked receding of the hairline on the forehead, before the administration. By using the Aspergillus fermented product extract (1), this subject B was found to have clearly grown hair on the hairline of the forehead. In addition, no abnormality of the skin was observed during the period of use, and the condition of the scalp was good. Subject C had senile alopecia with a tendency toward thinning hair over the entire head before administration. A volume increase was observed. In addition, no skin abnormality was observed during the period of use. Thus, by using the Aspergillus fermented product extract of the present invention, hair growth occurred and improvement of alopecia was observed. It was also found that the amount of hair falling out was reduced, and the hair became stiff and voluminous. None of the subjects had any abnormalities in the scalp, and the condition was the same as before administration or better than before administration. These results indicate that the Aspergillus fermented product and the Aspergillus fermented product extract of the present invention are excellent in promoting hair growth and hair growth, and can treat, prevent, or improve alopecia.

[Example 7]
7. Examination of mouse hair growth promotion by Aspergillus fermented product extract and concentration of Aspergillus fermented product Eight-week-old C3H/HeN female mice were divided into four groups shown in Table 7 below, each containing 5 to 6 mice. The hair on the back of the mouse was shaved with clippers, and each sample solution was applied to the shaved area once a day for 28 days. The application amount was 0.15 mL/day. As shown in Table 7 below, sterilized water was used as the sample solution for the control group (control group). In addition, 2 g of the fermented aspergillus oryzae (powder after drying) obtained in Example 1 was added to the sample solution of the test group 2% section per 100 mL of sterilized water. After standing in a refrigerator for 20 hours for extraction, the recovered supernatant (extract) was used. Similarly, the sample solution of the 4% test group was the supernatant (extract) extracted by adding 4 g of the fermented koji mold to 100 mL of sterilized water, and the sample solution of the 8% test group was A supernatant (extract) obtained by adding 8 g of the fermented product of Aspergillus oryzae to 100 mL of sterilized water was used.

On the day after the 28th application, and on the 29th day from the start of the test, each mouse was observed with the naked eye for the density of the body hair in the shaved area and the degree of growth of the body hair, and the hair growth score was determined according to the criteria shown in Table 8 below. sought based on The evaluation of the hair growth score was performed by those who could not distinguish between the control group mice and the test group mice to exclude experimenter bias. The results are shown in FIG. 5 and Table 9 below.

These results revealed that the mice in the test group to which the extract of the fermented koji mold was applied were clearly superior to the mice in the control group in hair growth and hair elongation. Also, when preparing the Aspergillus fermented product extract, a sample solution prepared by adding 2 g (2% group) to 4 g (4% group) of the Aspergillus fermented product to 100 mL of the solvent was used. In addition, there is a sufficient hair growth effect, but when using a sample solution prepared by adding 8 g (8% section) of the fermented product of Aspergillus oryzae per 100 mL of the solvent, the hair growth score is further improved. It was found that the hair growth effect increased depending on the concentration of the fermented product of koji mold.

INDUSTRIAL APPLICABILITY The present invention is intended to provide a hair-restoring/hair-restoring external preparation or alopecia therapeutic agent that is excellent in hair-restoring and promoting hair growth and capable of treating, preventing, or improving alopecia. It is widely useful in industries such as foreign goods.

The present invention is not limited to the above-described embodiments or examples, and includes various design changes within the scope of the invention within the scope of the invention described in the claims. .

Claims (4)

1. An external preparation for hair growth or hair growth or a therapeutic agent for alopecia, characterized by containing an aspergillus fermented product of tea leaves fermented with black koji mold and lactic acid bacteria for 1 to 4 days or an extract of the aspergillus fermented product of the tea leaves. 2. The external preparation for hair growth/restoration or the therapeutic agent for alopecia according to claim 1 , wherein the extract of the koji mold fermented product of tea leaves is a water extract of the koji mold fermented product of tea leaves. A method for growing hair, comprising a step of inoculating tea leaves with black koji mold and lactic acid bacteria, and a step of fermenting the tea leaves with the koji mold and the lactic acid bacteria for 1 to 4 days to obtain an aspergillus fermented product of tea leaves. A method for producing an external preparation or a treatment for alopecia. 4. The topical preparation for hair restoration or treatment of alopecia according to claim 3 , further comprising a step of extracting the koji mold fermented product of tea leaves with water to obtain an extract of the koji mold fermented product of tea leaves. A method for producing the agent.

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