TWI743747B - External agent for hair growth and growth - Google Patents

Abstract

The subject of the present invention is to provide an external agent for hair growth and hair growth, and a therapeutic agent for hair loss, which is highly safe and has excellent hair growth and hair growth effects. The solution is that the external preparation for hair growth, hair growth, or hair loss treatment agent of the present invention contains a fermented koji mold or an extract of the fermentation product of koji mold.

Description

External agent for hair growth and growth

The present invention relates to an external skin agent for hair growth and hair growth, and a therapeutic agent for hair loss that contains fermented koji fungus or extracts of fermented koji fungus.

Recently, the number of men and women suffering from so-called head hair loss and thinning hair loss symptoms is increasing. In order to improve such symptoms, research has been conducted on the mechanism of hair growth and hair circulation, and the development of effective ingredients that promote hair growth and inhibit hair loss is underway. At present, a representative one can include minoxidil (minoxidil, refer to Patent Document 1), and a large number of them have been developed and formulated into cosmetics for hair, such as external skin preparations for hair growth and hair growth, and the like incorporated therein.

On the other hand, in recent years, the value of traditional Japanese koji fermented foods using koji, such as Japanese sake, shochu, sweet sake, miso, and soy sauce, has been recognized again, and the popularity of koji has increased. The so-called koji is a person who steams rice, rice bran, wheat, or beans, and causes the koji bacteria to multiply. For example, the koji bacteria that multiply on the rice are called rice koji. It is known that Koji has the function of producing a variety of enzymes that can produce fermented food. However, it is not limited to this field. The research on new functions of Koji and the development of applications based on it have progressed due to the inventors of this case. Patent Document 2 reports that feed obtained by fermenting grains with koji bacteria promotes the growth of animals; Patent Document 3 reports that the koji fermentation composition obtained by inoculating koji bacteria on tea leaves and culturing them has antioxidant activity.

Advanced technical literature Patent literature Patent Document 1: Japanese Patent No. 2733980 Patent Document 2: Japanese Patent No. 6111416 Patent Document 3: International Publication No. 2015/119036

The problem to be solved by the invention However, Minoxidil, which is a hair growth ingredient described in Patent Document 1, was originally used as a component of a drug for treating hypertension, and therefore, it is reported that it may cause side effects such as lowering blood pressure. Therefore, it is expected to provide a new material with higher safety, excellent hair growth and hair growth effects.

In addition, Patent Document 2 and Patent Document 3 respectively describe koji fermented products obtained by fermenting grains and tea leaves with koji bacteria, but they have not discussed the use of the koji fermented products to treat alopecia, promote hair growth, and grow hair. The validity is unknown.

Therefore, the present invention was made in view of the above-mentioned points, and its object is to provide an external agent for hair growth and hair growth, and a therapeutic agent for hair loss that has high safety, excellent hair growth and hair growth effects.

Means to solve the problem In order to solve the above-mentioned problems, the external agent for hair growth or hair growth or the treatment agent for hair loss of the present invention contains a fermented aspergillus fermented by aspergillus or an extract of the aspergillus hair.

The fermented koji fungus and the extract of the fermented koji fungus have an excellent hair growth promoting effect, and further, the treatment and prevention of the so-called male pattern hair loss (androgenetic alopecia) and the alopecia of senile alopecia Or improvement is also useful.

In addition, the above-mentioned fermented koji fungus is also suitable to use raw materials derived from tea, grains or beans as fermentation raw materials. In this way, a more suitable raw material for the fermented koji fungus can be selected.

In addition, the above-mentioned aspergillus is also preferably aspergillus nigricans or aspergillus spp. Thereby, a suitable koji mold can be selected, and the koji mold fermentation product of the active ingredient of the external agent for hair growth and hair growth or the therapeutic agent for hair loss of the present invention can be obtained from the koji mold.

In addition, the external preparation for hair growth or hair growth or the therapeutic agent for hair loss of the present invention further preferably contains lactic acid bacteria. As a result, when the koji fungus fermented product is produced, the proliferation of koji fungus can be promoted, and the fermentation using the koji fungus can be stably performed, and a koji fungus fermentation product with high activity can be obtained.

In addition, the extract of the fermented koji fungus in the present invention is preferably a water or water-containing alcohol extract of the fermented koji fungus. Thereby, an external agent for hair growth, hair growth, or hair loss treatment agent with excellent hair growth promoting effect can be easily obtained at low cost.

In addition, the method for producing an external agent for hair growth and hair growth or a hair loss treatment agent of the present invention has the following steps: a step of inoculating fermented raw materials derived from tea, grains or beans with koji bacteria, and using the koji bacteria to ferment the raw materials The step of obtaining fermented koji bacteria by fermentation. Thereby, it is possible to obtain an external agent for hair growth or hair growth or a therapeutic agent for hair loss, which has an excellent hair growth promoting effect and is useful for the treatment, prevention, or improvement of so-called androgenetic alopecia and senile alopecia.

In addition, the method for producing an external agent for hair growth and hair growth or a depilatory treatment agent of the present invention has the following steps: a step of inoculating fermented raw materials derived from tea, grains or beans with koji bacteria and lactic acid bacteria, and using the koji bacteria with The step of fermenting the aforementioned fermentation raw material by the lactic acid bacteria to obtain a fermented koji mold. Thereby, it is possible to obtain an external agent for hair growth or hair growth or a therapeutic agent for hair loss which has an excellent hair growth promoting effect. Furthermore, by co-cultivating lactic acid bacteria and koji bacteria, the proliferation of koji bacteria can be promoted and the fermentation using the koji bacteria can be stably performed, so a stable and highly active fermentation product of koji bacteria can be obtained, and the fermentation time can also be shortened.

In addition, in the method for producing the external preparation for hair growth or hair growth or the therapeutic agent for hair loss of the present invention, the above-mentioned aspergillus is also preferably aspergillus or white aspergillus. Thereby, a suitable koji mold can be selected, and the koji mold fermentation product of the active ingredient of the external agent for hair growth and hair growth or the therapeutic agent for hair loss of the present invention can be obtained from the koji mold.

In addition, the method for manufacturing the external preparation for hair growth and hair growth or the treatment agent for depilation of the present invention preferably has the following steps: extracting the obtained fermented koji fungus with water or water-containing alcohol to obtain the extraction of the fermented koji fungus The steps of things. Thereby, an external agent for hair growth, hair growth, or hair loss treatment agent with excellent hair growth promoting effect can be easily obtained at low cost.

Invention effect According to the present invention, it is possible to provide an external agent for hair growth or hair growth or a therapeutic agent for hair loss which has the following excellent effects. (1) It is excellent in promoting hair growth and hair growth. (2) It can treat, prevent or improve alopecia. (3) Since it uses the fermented product of koji fungus that can also be used in food manufacturing as an active ingredient, it is highly safe. (4) Only by extracting the fermented koji fungus with water or water-containing alcohol, a lotion-type external agent for hair growth and hair growth or a hair loss treatment agent can be obtained, so it is easy to manufacture.

The form used to implement the invention

First, referring to FIG. 1, the method for producing the fermented koji fungus P1 contained in the external preparation for hair growth and hair growth or the treatment agent for hair loss according to the present invention will be described.

As shown in Fig. 1, the method for producing the fermented koji fungus P1 according to the embodiment of the present invention is roughly composed of the following steps: step S0 of preparing fermentation raw materials, step S0 of adding water to the fermentation raw materials and making them absorb water, and cooking the fermentation raw materials Step S2, step S3 of inoculating the fermented raw materials with koji, and step S4 of fermenting.

(Prepare fermentation ingredients) First, the step S0 of preparing fermentation raw materials shown in FIG. 1 will be described. The fermentation raw materials in the present invention can be selected from plant-derived raw materials, and plant leaves, stems, roots, flowers and fruits can be used as fermentation raw materials. Among them, it is preferable to use tea leaves, grains or beans, and it is particularly preferable to use tea leaves as a fermentation raw material. Cereals include rice, corn, wheat, barley, rye, oats, sorghum, buckwheat and other miscellaneous cereals. In addition, tea leaves include not only tea leaves, but also stems and branches taken from tea plants. The tea used as the raw material of the fermented koji fungus of the present invention can be suitably used as raw tea in the state after being taken directly, but it can also be tea that is heated immediately after being taken, and oxidized by the oxidizing enzyme contained in the tea after being taken. Fermented oolong tea or black tea, and post-fermented tea. Moreover, the tea dregs after brewing these green tea, oolong tea, black tea, etc. can also be used. In addition, in order to improve the efficiency of subsequent steaming and koji culturing, the tea leaves and tea stems should also be broken to a certain extent so that they are not too large.

(Water absorption treatment) Next, the water absorption treatment step S1 will be described. In this step, water can be added to the fermentation raw material, or the fermentation raw material can be immersed in water to make it absorb water. The amount of water absorption, for example, when using tea leaves as a fermentation raw material, can be adjusted so that the moisture content of the tea leaves becomes 20-60%, and preferably 30-50%.

(Steaming treatment) Next, the retort treatment step S2 will be described. Put the fermented raw materials that have absorbed water in the above steps into the digester and cover the lid, and heat the fermented raw materials directly by steam through the heating digester. The cooking time is preferably about 30 minutes to 120 minutes, preferably about 45 minutes to 90 minutes, and more preferably about 60 minutes. By performing this step, the miscellaneous bacteria in the raw materials can be sterilized, and in the subsequent fermentation step, the koji bacteria can be used as the dominant species for fermentation. In addition, when raw tea leaves are used as raw materials for fermentation, this step can sterilize the miscellaneous bacteria in the tea and at the same time deactivate the oxidase contained in the tea. Therefore, in the subsequent steps, the koji bacteria can be used. Efficient reproduction on tea leaves. The raw materials that have finished cooking are taken out from the digester, spread out evenly on the table, and cooled to about 30-40°C. In this way, the fermented raw materials can be inoculated with koji bacteria.

(Inoculation of Koji bacteria) Next, the step S3 of inoculating (seeding) the koji bacteria to the fermentation raw material will be described. This step is to inoculate the fermented raw materials that have undergone the above-mentioned cooking step and have been cooled with koji bacteria. The koji bacteria in the present invention are mainly microorganisms used in the production of koji fermented foods, and specifically, black koji fungi, white koji fungi, or yellow koji fungi can be mentioned. Among them, the so-called black koji mold refers to a type of mold of the koji mold that is used in the production of distilled liquors such as Awamori in Okinawa and taro shochu from Kagoshima, and forms black or dark brown conidia (a type of asexual spores). Group. It is not particularly limited, and examples include Aspergillus awamori var. kawachii, Aspergillus awamori var. In addition, the so-called white koji mold refers to a group of molds of the genus Koji that form white yellow soil-colored conidia, specifically, for example, Aspergillus kawachii (Aspergillus kawachii). Furthermore, the so-called yellow koji mold refers to a group of molds of the genus Koji that form yellow or yellow-green conidia, and are mainly microorganisms that can be used in the production of sake, miso, and soy sauce. It is not specifically limited in particular, Aspergillus oryzae, Aspergillus sojae, etc. are mentioned. In the present invention, from the viewpoint of the excellent hair growth promoting effect, and the viewpoint that the koji mold itself produces citric acid and therefore has a pH adjustment effect, it is preferable to use the black koji mold or the white koji mold. Among them, it is more suitable to use Aspergillus awamori var. kawachii, Aspergillus luchuensis or Aspergillus inuii, Aspergillus kawachii, and combinations thereof , And particularly suitable for Aspergillus awamori var. kawachii. The inoculation of these koji bacteria can be carried out, for example, by mixing and stirring the koji bacteria in the fermentation raw materials placed in the sterilized bag. Koji bacteria is preferably inoculated with its spores, and 1 g (dry weight) of the fermentation raw material, the spores of Koji bacteria are preferably added to 500,000 or more, and preferably 1 million or more for inoculation. For example, when the number of spores contained in 1 g of seed koji is 2 billion, about 0.5 g (0.05% by weight) of seed koji may be added to 1 kg of fermentation raw material. After the koji bacteria are inoculated into the fermentation raw materials, it is advisable to stir thoroughly to disperse the koji bacteria to the whole raw material.

In addition, in the inoculation step S3 of koji bacteria, it is also suitable to further inoculate lactic acid bacteria to co-culture the koji bacteria and lactic acid bacteria. By co-cultivating koji bacteria and lactic acid bacteria, the proliferation of koji bacteria can be promoted and stable fermentation treatment can be carried out, and the fermentation time can be shortened. At the same time, the inoculated bacteria will become the dominant species, so the growth of other miscellaneous bacteria can be inhibited. Lactic acid bacteria can be used in lactic acid bacteria fermented foods. Examples include Lactobacillus casei, Lactobacillus fermentum, or Lactobacillus bulgaricus. bifidum) and other Bifidobacterium, Lactococcus lactis and other Lactococcus genera, Enterococcus faecium and other Enterococcus genera. The lactic acid bacteria to be inoculated are those that have been pre-cultured first, and about 0.1% by weight of the bacteria is added to 1kg of the fermentation raw material. The fermented koji bacteria obtained by fermenting with koji bacteria and lactic acid bacteria contains not only the various enzymes produced by koji bacteria and lactic acid bacteria, but also koji bacteria, its spores and lactic acid bacteria.

(Fermentation) Next, step S4 of cultivating and fermenting the koji bacteria inoculated into the fermentation raw material will be described. This step is to make the koji bacteria multiply in the raw material that has been inoculated with the koji bacteria. First, put the fermented raw materials of koji bacteria into the culture room that has been kept at around 30°C. As time elapses, the temperature of fermentation raw materials such as tea leaves will rise. However, it is generally difficult for koji bacteria to proliferate if it exceeds 40°C. Therefore, ventilation is performed to lower the temperature of the raw materials, and the amount of ventilation is adjusted to make the raw materials fermented. The temperature is maintained at 30℃~42℃, and preferably 30℃~40℃. In addition, the fermentation temperature can be appropriately adjusted according to the type of koji bacteria used in the fermentation. Specifically, when selecting black koji or white koji for koji bacteria, as an example, 12 to 30 hours from the start of culture, the temperature of fermentation raw materials such as tea leaves is adjusted to 35°C to 40°C by ventilation. After that, adjust the ventilation rate in the same way, adjust the temperature to a slightly lower 30°C to 35°C, and incubate for a total of 1 to 4 days, preferably 36 to 72 hours, and 40 to 60 hours from the start of the culture. The right time is the best time point, and it is set as the completion of the koji fungus fermentation product P1.

Furthermore, in the manufacturing steps S1 to S4 of the above-mentioned koji fermentation product P1, the washing of raw materials, water absorption, steaming, inoculation and fermentation (koji production) of koji bacteria can also be carried out by a machine that can be carried out in the same device (for example, , Drum-type automatic koji making device, etc.).

(Koji fungus fermentation product) The obtained koji fermentation product P1 is the so-called "Koji" in which the koji bacteria have grown in the fermentation raw material. The fermented koji fungus P1 is excellent in hair growth and hair growth promotion, and can treat, prevent or ameliorate alopecia. The fermented product P1 of koji bacteria obtained by the above steps is in a state of containing a certain amount of moisture, and the moisture can be removed by drying it naturally or dehumidifying and drying it at a low temperature. In addition, the fermented koji fungus P1 from which moisture has been removed may be crushed into a powder form or into a granular form. By reducing the moisture content of the koji fermentation product P1, the activity and growth of the koji bacteria and lactic acid bacteria in the koji fermentation product P1 can be inhibited, and furthermore, the koji bacteria fermentation product P1 can be stored for a long time by refrigerating storage. Even when moisture is temporarily removed, it can effectively maintain the hair growth and hair growth promotion function as the fermented koji fungus P1.

Next, the method for producing the extract P2 of the fermented koji fungus contained in the external preparation for hair growth and hair growth or the hair loss treatment agent of the present invention will be described. As shown in Figure 1, the method for producing the extract P2 of the fermented koji fungus related to the embodiment of the present invention is roughly composed of the following steps: adding an extraction to the fermented koji fungus P1 obtained in the above steps S1 to S4 Solvent, and proceed to extraction step S5.

(extraction) Hereinafter, the extraction step S5 will be described in detail. In the extraction step S5, an extraction solvent is added to the koji fungus fermentation product P1 and an extraction process is performed to obtain an extract P2 of the koji fungus fermentation product. The extraction solvent is not particularly limited as long as it can extract the hair growth promoting effect from the koji fermentation product P1. However, from the viewpoint of extraction efficiency and ease of operation, water or a hydrous alcohol is preferable. Among them, the alcohol used for the water-containing alcohol includes, for example, ethanol, isopropanol, 1,3-butanediol, propylene glycol, glycerin, etc., and one of these or a combination of two or more of them can also be used. Furthermore, as the above-mentioned ethanol, a fermentation broth obtained by fermenting alcohol can also be used. Specifically, distilled alcohol obtained by brewing and distilling the alcohol can be used, and among them, distilled alcohol can be preferably used. Examples of distilled spirits include those derived from grain raw materials such as rice, wheat, and corn, those derived from roots or tubers, those derived from sugar cane, and those derived from the fruit (date) of the date palm. Among them, the distilled wine derived from the date palm fruit contains ethyl palmitate, which is a component that is particularly less irritating to the skin and gentle on the skin, so it can be selected as a preferable extraction solvent for the manufacture of external preparations. The alcohol concentration of the water-containing alcohol is preferably 1-50v/v%, preferably 3-30v/v%, and particularly preferably 5-15v/v%. In addition, when water is used as the extraction solvent, it is preferable to use water that has been sterilized by high-pressure steam sterilization, filter sterilization, or the like. By using sterilized water, the mixing of miscellaneous bacteria can be prevented, and useful components including various proteins and enzymes contained in the fermented koji fungus P1 can be stably extracted. In addition, the extraction solvent may contain other components such as pH adjusters, preservatives, extraction aids, etc., in addition to the above-mentioned water or water-containing alcohol, within a range that does not hinder the extraction of useful components from the koji fermentation product P1.

As the extraction method of the koji fungus fermentation product P1, it is advisable to add the koji fungus fermentation product P1 to the extraction solvent to immerse it, and then perform extraction, and the water content of the koji fungus fermentation product P1 is less than 10% relative to 1L of the extraction solvent. In the case of dry matter, it is advisable to add 1g~300g, and 5g~150g is preferred, and 10g~100g is especially preferred. In addition, as extraction conditions, in order to maintain the activity of various proteins and enzymes contained in the koji fermentation product P1, the extraction temperature is preferably set at about 0-30°C, preferably at 2-20°C, and at 4 ~10°C is particularly preferred. Moreover, the extraction time is preferably set at about 2 hours to 5 days, and is preferably set at about 6 hours to 3 days, and particularly preferably set at about 12 hours to 1.5 days.

After the above-mentioned extraction treatment, the residue is removed by decantation, centrifugal separation or filtration, etc., and the extract P2 of the fermented koji fungus can be obtained. As the extract P2 of the fermented koji fungus of the present invention, in addition to the extract P2 of the fermented koji fungus obtained in the extraction step S5, the extract P2 is made into a concentrated liquid by a concentration treatment such as reduced pressure concentration. Those: The extract P2 of the fermented koji bacteria is subjected to drying treatments such as freeze-drying treatment to make it into a solid replacement form or a powder form.

The external agent for hair growth or hair growth or the therapeutic agent for hair loss of the present invention contains the above-mentioned aspergillus fermented aspergillus fermented product P1 or the aspergillus fermented extract P2 as an effective ingredient; and has a hair-growing effect, Hair growth promotion, treatment, prevention or amelioration of various types of hair loss such as male alopecia and senile alopecia. Therefore, the external preparation containing the fermented koji fungus of the present invention or the extract of the fermented koji fungus of the present invention can be used as medicines, quasi-drugs, and quasi-medicinal products for preventing, treating, or ameliorating the symptoms of so-called thinning of hair, hair loss, and alopecia. Hair hair with cosmetics. The external preparation of the present invention uses the fermented product of koji bacterium that can also be used in food manufacturing as an active ingredient, so it is highly safe and can be used safely and easily regardless of age, sex, chronic disease, etc.

The content of the fermented koji fungus P1 in the external preparation for hair growth and hair growth of the present invention or the therapeutic agent for hair loss is preferably about 0.1% to 20% by weight, and preferably about 0.3% to 10% by weight. About 1% by weight to 5% by weight is particularly preferred. In addition, for the extract P2 of the fermented koji fungus, the extract P2 of the fermented koji fungus obtained in the extraction step S5 (extract solution) itself can be used as an external agent for hair growth, hair growth, or a hair loss treatment agent; From the viewpoint of extraction efficiency and hair growth effect, it is preferable to add 0.1g~30g of the fermented aspergillus fermented product P1 (dried) to the extraction solvent 100mL, and add 0.5g~15g The extract obtained from the fermented koji fungus P1 (dried substance) is preferable, and the extract obtained by adding 1 g~10g of the fermented koji fungus P1 (dried substance) is particularly preferable. In addition, when the extract (extract solution) P2 of the fermented koji fungus itself is not used as an external agent for hair growth and hair growth, etc., it is advisable to mix 0.1g~30g of the fermented koji fungus P1 (dry物) The extract P2 obtained by extraction, and preferably the extract P2 obtained by blending 0.5g~15g of the fermented koji fungus P1 (dried), and preferably the extract P2 obtained by blending 1g~10g of the fermented koji fungus P1 (Dry) The extract P2 obtained by extraction is particularly preferred.

Since the amount of the external agent for hair growth and hair growth or the therapeutic agent for alopecia of the present invention varies according to the improvement goal or therapeutic effect, symptoms, size of the affected area, administration method, age, or dosage form of the external preparation, etc., It cannot be stipulated in general, but the daily dosage is usually 0.1~20mL(g), and 0.3~10mL(g) is preferred, and 0.5~5mL(g) is particularly preferred.

In consideration of the safety to the skin, the pH of the external preparation for hair growth and growth or the treatment agent for hair loss of the present invention should be adjusted to 4.0-6.5. In the range that does not impair the effects of the present invention, an appropriate acid or base usually blended in an external agent can be used to adjust the pH of the external agent. Examples of such pH adjusting agents include acids such as hydrochloric acid, lactic acid, phosphoric acid, tartaric acid, malic acid or gluconic acid, alkalis such as diisopropanolamine, triisopropanolamine, sodium hydroxide, sodium citrate or arginine, Furthermore, one type can be used, or two or more types can be used in combination. In addition, when the koji fungus fermented product is obtained, when the koji fungus or white koji fungus that produces citric acid is used as the koji fungus, since the koji fungus fermentation product contains citric acid, it can be easily made into a weakly acidic preparation.

In addition, the external agent for hair growth and growth or the therapeutic agent for hair loss of the present invention can be blended with various components that are generally used in external agents 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, moisturizers, preservatives, antibacterial agents, fragrances, and pigments. In addition, the external agent of the present invention may also incorporate hair-growing and hair-growth ingredients other than the fermented koji mold P1 and the extract P2 of the fermented koji mold. Other hair-growing and hair-growing ingredients include minoxidil, adenosine, or swertia herb essence.

Furthermore, the external preparation for hair growth and growth or the treatment agent for hair loss of the present invention can be made into a dosage form that can be applied to the scalp and skin, and can be applied to various external preparations by conventional methods, such as Liquid agents such as tonic and lotion, aerosol, gel, ointment, cream or lotion. In addition, it can also be applied to shampoos, soaps, or conditioners.

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

[Example] [Example 1] 1. Preparation of fermented koji bacteria In this embodiment, raw tea leaves are used as the fermentation raw material. The water content of the tea leaves is about 50%, water is added, and water absorption is performed. After that, the tea leaves are placed in a pressurized steam kettle and steamed. The conditions of the retort treatment were set at 115°C for 60 minutes, and the retort treatment was performed twice with one cooling. Then, after cooling the tea leaves to 30°C, the seed koji of Aspergillus awamori var. kawachii (Aspergillus awamori var. kawachii) (the number of spores is 2 billion/the seed koji 1g) is added to the tea so that the weight of the tea leaves relative to the fermentation raw material is 0.1% by weight, Lactobacillus casei was added to 0.1% by weight, mixed, and koji was prepared for 3 days. In addition, the temperature of koji making is adjusted by ventilation for 24 hours after adding seed koji so that the temperature of the tea leaves becomes 35°C to 40°C. For the next 48 hours, the same ventilation rate is adjusted to adjust the temperature of the tea leaves to a slightly lower temperature. 30℃~35℃. After that, the koji mold fermented product obtained from koji preparation for 3 days was dried to have a moisture content of 8%, and it was pulverized to obtain a powdery koji mold fermentation product.

[Example 2] 2. Preparing the extract of the fermented koji fungus (1) In this embodiment, water is used as the extraction solvent. To 100 mL of sterilized water, the fermented koji mold obtained in Example 1 (powder after drying) was added at a ratio of 2 g. It was placed in a refrigerator at 4°C and subjected to extraction treatment for 20 hours. The supernatant was collected to obtain the koji fungus fermentation product extract (1) used in the following examples.

[Example 3] 3. Preparing the extract of the fermented koji fungus (2) In this example, an alcohol-containing extraction solvent was used to obtain the koji fungus fermentation product extract (2). First, add water sterilized by autoclaving at 135°C to a distilled liquor made from date palm fruits (trade name: Hayato no Ryu, product of Kintan Shuzo Co., Ltd., alcohol content 30) to prepare a water with an ethanol concentration of 10v/v% Extraction solvent. The koji fungus fermented product obtained in Example 1 was added to 100 m of the extraction solvent at a ratio of 2 g. It was placed in a refrigerator at 4°C and subjected to extraction treatment for 20 hours. The supernatant was collected to obtain the koji fungus fermentation product extract (2) used in the following examples.

[Example 4] 4. Promotion of hair growth in mice caused by the fermented extract of koji fungus (1) Four C3H/HeN female mice at the age of 8 weeks after birth were assigned to the two groups shown in Table 1 below. The back hair of the mouse was shaved with a hair clipper, and the sample solution was applied to the shaved part once a day for 30 days. The coating amount was set to 0.15 mL/day. As shown in Table 1 below, the sample solution of the control group used the sterilized water used as the extraction solvent in the preparation of the koji fungus fermentation extract (1) in Example 2, and the sample solution of the test group used the example 2 The obtained extract of the fermented koji fungus (1).

[Table 1] Content Control group (4) Sterilized water (extract solvent used in Example 2) Coated 0.15mL/day, 30 days Test group (4 animals) The fermented koji bacteria extract obtained in Example 2 (1) was coated with 0.15 mL/day for 30 days

On the next day after the 30th coating, and on the 31st day from the start of the test, the body hair density and body hair elongation of the shaved part of each mouse were observed with the naked eye, and the birth was determined according to the standards shown in Table 2 below. Gross score. In addition, the evaluation of the hair growth score is performed by people who cannot distinguish between the control group and the test group, so as to eliminate the bias caused by the experimenter. Regarding the hair growth scores of the control group and the test group, the significant difference was evaluated using the significance level of 5% and the Mann-Whitney U test. The results are shown in Figure 2 and Table 3 below.

[Table 2] Raw gross score The skin condition of the shaving part (hair growing condition) 1 More than 90% of the skin is pink 2 More than 30% of the skin is gray, but no obvious hair extension is observed 3 More than 30% of the skin is gray, and obvious hair extension is observed 4 More than 60% of the skin is gray, and obvious hair extension is observed 5 More than 90% of the skin is gray, and obvious hair extension is observed

[table 3] Hair growth score Control group test group Hair growth score of each mouse 1 3 1 4 2 2 2 3 average value 1.5 3 Standard deviation 0.6 0.8

Based on these results, it was shown that the mice of the test group coated with the fermented koji fungus extract (1) were significantly better than the mice of the control group in terms of hair growth and hair elongation. In addition, the p value of the comparison between the two is p<0.05, which shows that it is significant.

[Example 5] 5. Promotion of hair growth in mice caused by the fermented koji fungus extract (2) Five C3H/HeN female mice aged 8 weeks after birth were assigned to the two groups shown in Table 4 below. The mouse's back hair was shaved with a hair clipper, and the sample solution was applied to the shaved part once a day for 30 days. The coating amount was set to 0.15 mL/day. As shown in Table 4 below, in the sample solution of the control group, the extraction solvent used when preparing the koji fungus fermented product extract (2) in Example 3 (for distilled spirits using date palms as raw materials (trade name: Hayato) Zhizhu, a product of Kintan Distillery Co., Ltd., with an alcohol content of 30) add sterilized water and make the ethanol concentration into a solution of 10v/v%); the sample solution of the test group uses the fermented koji bacteria obtained in Example 3 Extract (2).

[Table 4] Content Control group (5) The extraction solvent used in Example 3 (10v/v% ethanol aqueous solution) was coated with 0.15mL/day for 30 days Test group (5 animals) The fermented koji bacteria extract obtained in Example 3 (2) was coated with 0.15 mL/day for 30 days

On the next day after the 30th coating, and on the 31st day from the start of the test, the body hair density and body hair elongation of the shaved part of each mouse were observed with the naked eye, and the birth hair was obtained according to the standards shown in Table 2 above. Fraction. In addition, the evaluation of the hair growth score is performed by people who cannot distinguish between the control group and the test group, so as to eliminate the bias caused by the experimenter. Regarding the hair growth scores of the control group and the test group, the significant difference was evaluated using the significance level of 5% and the Mann-Whitney U test. The results are shown in Figure 3 and Table 5 below.

[table 5] Raw gross score Control group test group Hair growth score of each mouse 3 4 3 4 3 4 2 4 3 4 average value 2.8 4 Standard deviation 0.4 0.0

According to these results, the mice in the test group coated with the fermented koji fungus extract (2) were significantly better in hair growth and hair elongation than the control mice. In addition, the p value of the comparison between the two is p<0.01, which shows extremely high significance.

[Example 6] 6. Promotion of human hair growth caused by the fermented koji fungus extract (1) The koji fungus fermentation product extract (1) obtained in Example 2 was placed in a spray bottle, and three subjects A~C shown in Table 6 below were sprayed with koji bacteria on their heads twice a day in the morning and in the evening. The fermented product extract (1) is administered several times and rubbed with hands. The period of administration is 1 to 3 months. The photos taken from the top of the head of each subject before and after the administration are shown in Fig. 4. Figure 4(A) shows subject A, Figure 4(B) shows subject B, and Figure 4(C) shows subject C. The lower side of each photo represents the front side, and the upper side faces the back side.

[Table 6] Subject Age and gender State before casting Period of investment A 45 years old Androgenetic alopecia. Hair loss can be observed mainly on the top of the head. 3 months B 45 years old Androgenetic alopecia. The receding of the forehead can be observed. 37th C 60 years old Elderly alopecia. Thinning of hair can be observed on the entire head. 50 days

Subject A was able to observe male-type alopecia with alopecia mainly on the top of the head before the administration, but after using the koji fermentation extract (1) for about 3 months, the reduction in the range of hair loss on the top of the head could be observed And hair growth within the range of hair loss. In addition, no skin abnormalities were observed during the 3-month period of use. Subject B was able to observe significant androgenetic alopecia, especially in the receding area between the forehead, before the administration. The subject B used the fermented koji bacteria extract (1), and obvious hair growth was observed on the hairline part of the forehead. In addition, no skin abnormalities were observed during use, and the scalp was in good condition. Subject C was able to observe senile alopecia that tends to thin hair on the entire head before the administration. However, through the use of the fermented koji bacteria extract (1), the overall growth of hair can be observed and the hair develops toughness and volume. Increase. In addition, no skin abnormalities were observed during use. In this way, by using the fermented koji fungus extract of the present invention, hair growth occurs, and alopecia can be improved. In addition, it is also known that hair loss will be reduced, and the hair will appear tenacity and volume increase. The scalp of any subject has no abnormalities and is in the same condition as or better than before the administration. Based on these results, it is shown that the fermented koji mold and the extract of the fermented koji mold of the present invention are excellent in hair growth and hair growth promotion, and can treat, prevent, or improve alopecia.

[Example 7] 7. Discussion on the promotion of hair growth in mice induced by the fermented extract of Koji bacteria and the concentration of the fermentation product of Koji bacteria The C3H/HeN female mice at the age of 8 weeks after birth were assigned 5 to 6 mice in each of the 4 groups shown in Table 7 below. The back hair of the mouse was shaved with a hair clipper, and each sample solution was applied to the shaved part once a day for 28 days. The coating amount was set to 0.15 mL/day. As shown in Table 7 below, the sample solution of the control group (control area) was sterilized water. In addition, the sample solution in the 2% area of the test group uses the following supernatant: to 100 mL of sterilized water, add the koji fungus fermented product (in powder form after drying) obtained in Example 1 at a ratio of 2 g to 100 mL of sterilized water at 4°C. After the lower refrigerator is allowed to stand still and subjected to extraction treatment for 20 hours, the supernatant liquid (extract liquid) is recovered. Similarly, the sample solution in the 4% area of the test group is the supernatant (extract) obtained by adding 4 g of sterile water to 100 mL of sterilized water; the sample solution in the 8% area of the test group is used To 100 mL of sterile water, the supernatant (extract) obtained by adding the fermented koji fungus at a ratio of 8 g.

[Table 7]

On the next day after the 28th coating, and on the 29th day from the start of the test, observe the body hair density and body hair elongation of the shaved part of each mouse with the naked eye, and determine the birth according to the standards shown in Table 8 below. Gross score. In addition, the evaluation of the hair growth score is performed by people who cannot distinguish between the control group and the test group, so as to eliminate the bias caused by the experimenter. The results are shown in Figure 5 and Table 9 below.

[Table 8]

[Table 9]

According to these results, the mice in the test group coated with the fermented koji bacteria extract were significantly better than the mice in the control group in terms of hair growth and hair elongation. In addition, when preparing the koji fungus fermentation product extract, even when using a sample solution prepared by adding 2 g (2% area) to 4 g (4% area) of the koji fungus fermentation product of the extract per 100 ml of solvent, there is still Sufficient hair growth effect, however, when using a sample solution adjusted by adding 8 g (8% area) of the fermented koji bacteria of the extract per 100 ml of solvent, the hair growth score is further improved, and it can be seen that the hair growth effect will be improved The concentration-dependent manner of the fermented koji bacteria rises.

Industrial availability The present invention provides an external agent for hair growth and hair growth or a hair loss treatment agent that is excellent in hair growth and hair growth promotion, and can treat, prevent, or ameliorate hair loss. It has a wide range of uses in industries such as foreign products.

The present invention is not limited to the above-mentioned embodiments or examples, and is also included in the technical scope of various design changes without departing from the scope of the invention described in the scope of the patent application.

Fig. 1 is a flow chart schematically showing the method of manufacturing the fermented koji fungus and the extract of the fermented koji fungus related to the embodiment of the present invention. Figure 2 is a graph showing the hair growth scores of the control group and the test group in Example 4. Fig. 3 is a graph showing the hair growth scores of the control group and the test group in Example 5. FIG. 4 is a photograph showing the hair growth state of the test subject in Example 6. FIG. Fig. 5 is a graph showing the hair growth scores of the control group (control area) and the test group (2% area, 4% area, and 8% area) in Example 7.

Claims (6)

An external agent for hair growth and hair growth or a therapeutic agent for depilation, characterized in that it contains a fermented product of fermented koji of tea leaves that has been fermented with koji bacteria and lactic acid bacteria for 1 to 4 days or an extract of a fermented product of koji of the tea, and the koji The bacteria are selected from Aspergillus niger or Aspergillus sp. According to claim 1, the external agent for hair growth or hair growth or the therapeutic agent for hair loss, wherein the aforementioned aspergillus is Aspergillus niger. According to claim 1 or 2, the external agent for hair growth or hair growth or the treatment agent for hair loss, wherein the extract of the fermented koji fungus of the tea leaves is a water or water-alcoholic extract of the fermented koji fungus of the tea leaves. A method for manufacturing an external agent for hair growth and hair growth or a hair loss treatment agent, characterized in that it has the following steps: inoculating tea leaves with koji bacteria and lactic acid bacteria, and the koji bacteria are selected from black koji bacteria or white koji bacteria; and The koji mold and lactic acid bacteria ferment the aforementioned tea leaves for 1 to 4 days to obtain a koji mold fermentation product of the tea leaves. According to claim 4, the method for producing an external preparation for hair growth or hair growth or a hair loss treatment agent, wherein the above-mentioned aspergillus is aspergillus niger. According to Claim 4 or 5, the method for producing an external preparation for hair growth or hair growth or a hair loss treatment agent further has the following step: extracting the fermented koji fungus of the tea leaves with water or water-containing alcohol to obtain the tea leaves The extract of the fermented koji fungus.

Images