JP2009108023A - Hair grower - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new useful hair grower high in hair growing effect and safety. <P>SOLUTION: The hair grower comprises (A) one or more selected from the group consisting of glycyrrhizinic acid, glycyrrhetinic acid, their derivatives and salts, and (B) a thermolysin decomposition product of soybean protein or a thermolysin-like protease decomposition product of the soybean protein, and has hair growing activity equivalent to that of the thermolysin decomposition product. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a hair restorer, and more particularly to a hair restorer containing glycyrrhizic acids and a protease degradation product of soybean protein. The present invention also relates to a preparation containing the hair restorer.

  In recent years, interest in hair has become stronger regardless of age or sex. Particularly in terms of beauty, a reduction in the amount of hair often produces a mental complex and tends to cause a deterioration in QOL (= Quality of Life).

  The hair tissue of animals including humans is constantly changing with a cycle called a hair cycle (also called a hair cycle). It is said that the hair papilla cells derived from the mesenchymal tissue located at the center bottom of the hair tissue that govern this hair cycle and deeply influence the transition of each stage. In recent years, it has also been known that the dermal papilla cell affects the size of the hair follicle and, consequently, the thickness of the hair that grows from the hair follicle (Non-patent Document 1, etc.).

  In the hair tissue, follicular epithelial cells exist so as to surround the dermal papilla cells. Hair follicle epithelial cells are in contact with hair papilla cells and are hair matrix cells. During the growth phase of the hair cycle, the hair matrix cells proliferate to produce hair. In addition, the outer root sheath cells surrounding the hair of the hair follicle epithelial cells play an important role in supplying new cells to the hair matrix and promoting the hair cycle smoothly. It is known that there is a function to keep it from falling out.

  In the hair cycle, when the growth phase is full, apoptosis is induced in the hair matrix cells. The hair cycle then proceeds to the regression phase and then to the resting phase, and hair growth stops. In the resting phase, the dermal papilla cells become obscure and the hair follicles are short atrophied and located shallow in the skin. After a certain period of time, the hair matrix cells proliferate again, leading to an early growth period in which old hair is lost and new hair grows. As time goes on, the hair follicles become larger and longer and become late growth hair follicles located deep in the skin. In healthy hair tissue, this cycle is repeated to produce hair.

  In general, it is considered that the thickness of the hair is approximately proportional to the size of the hair follicle that grows in the growing period, and the length of the hair is determined in proportion to the length of the growing period. About 90% or more of healthy hair is said to be in the growth phase, and during this period, the hair matrix cells actively divide and proliferate, and the hair grows thick and long. On the other hand, if this period is shortened, the hairs are thin and cannot grow sufficiently, causing thin hairs. It is known that the hair falls off before it grows sufficiently, the hair becomes thinner and becomes like a vellus hair, and the number of hair follicles that do not gradually shift to the growth stage gradually increases, eventually leading to a hair loss state. It has been. Thus, “alopecia” develops in close relation to hair growth and inhibition of hair growth.

  The most common alopecia is androgenetic alopecia (mature alopecia), about half of men (male pattern baldness) and 10-20% of women (female pattern baldness) androgenetic alopecia It takes. Genetic predisposition is largely involved, and in men it is common to have complete or partial alopecia from typical hair loss, but in women it is common for hair to be thin overall. Alopecia is also induced by toxic alopecia caused by physical and mental stress, rapid weight loss and severe illness, surgery, and cancer (cancer) chemotherapeutic drugs. Furthermore, alopecia areata, scarring alopecia and the like are known.

  In order to prevent or improve these thinning / hair loss states, various hair growth agents have been developed conventionally. For example, in order to promote metabolism of tissues around hair follicles or increase blood flow in tissues around hair follicles to promote proliferation of hair follicle epithelial cells such as hair matrix cells, placenta extract, carrot extract, assembly extract, Pantothenic acid, vitamin E, red pepper tincture, nicotinic acid derivative, minoxidil, glycyrrhizic acid, glycyrrhetinic acid, or salts thereof are used as hair restorers. It has also been reported that the hair-growth effect of glycyrrhizic acid, glycyrrhetinic acid, or a salt thereof is enhanced by the combined use with a plant extract or a drug (Patent Documents 1 and 2).

  As described above, there are various causes of hair loss, hair growth and hair growth inhibition, and alopecia is manifested not only in healthy individuals but also in patients suffering from some kind of disease. On the other hand, hair growth agents are usually used continuously on a daily basis. From such a point of view, there is a strong demand for the development of a hair restoration agent that has both an excellent hair restoration effect and high safety. However, the conventional hair restorer does not necessarily meet such demand. For example, although glycyrrhizic acid is applied to alopecia and the like, it is said that it may cause pseudoaldosteronism, and there is a strong demand for the development of a formulation that exhibits its hair-restoring effect safely and effectively. .

  Application of protease degradation products of soy protein has been attempted in various fields such as foods, pharmaceuticals, and cosmetics. For example, as the thermolysin degradation product of soybean protein promotes the production of a substance selected from the group consisting of collagen and hyaluronic acid, prevention, treatment, or the like of diseases and physical conditions caused by a decrease in the amount of collagen and / or hyaluronic acid, or The use in improvement etc. is reported (patent document 3). However, Patent Document 3 does not describe any hair-growth effect or hair-growth activity of the thermolysin degradation product of soybean protein.

Colin A.B.Jahoda, Development 115, 1103-1109, 1992 JP 05-279228 A Japanese Patent Laid-Open No. 06-135821 International Publication No. 2007/049400 Pamphlet

An object of the present invention is to provide a hair-restoring agent that can be safely used for a wide range of subjects and has high hair-restoring effect and high safety.
Specifically, an object of the present invention is to provide a safer hair restoration agent in which the hair restoration effect of glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and salts thereof is improved. Another object of the present invention is to provide a preparation containing the hair restorer.

  As a result of intensive investigations to solve the above problems, the present inventors have improved the hair-growth effect of glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and salts thereof obtained by decomposing soybean protein with thermolysin. And the present invention has been completed.

Accordingly, the present invention provides the following.
(1) The following ingredients:
(A) One or more selected from the group consisting of glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and salts thereof, and (B) a thermolysin degradation product of soybean protein or a thermolysin-like protease degradation product of soybean protein A hair restorer containing a product having an activity equivalent to that of a thermolysin degradation product.
(2) The hair restorer according to (1), wherein the component (A) is dipotassium glycyrrhizinate.
(3) The hair restorer according to (1) or (2), wherein the component (B) is a thermolysin degradation product of soybean protein.
(4) The amount of component (A) is 0.01 to 99% by weight, and the amount of component (B) is 0.0001 to 99% by weight, according to any one of (1) to (3) The hair restorer described.
(5) The hair restorer according to any one of (1) to (4), wherein the component (B) has an average molecular weight of 300 to 10,000.
(6) Furthermore, as a component (C), a cell activator, a blood circulation promoter, an anti-androgen hormone agent, a sebum secretion inhibitor, an immunosuppressant, an antihistamine, a bactericidal disinfectant, a local stimulant, a keratin softener, an anti-inflammatory agent, and The hair restorer according to any one of (1) to (5), which also contains one or more selected from the group consisting of anti-apoptotic agents.
(7) A preparation comprising the hair-restoring agent according to any one of (1) to (6).
(8) The preparation according to (7), which is a pharmaceutical, a quasi-drug, a cosmetic, or a food.
(9) Shampoo, hair conditioner, scalp lotion, scalp cream, hair tonic, whole body cream, whole body lotion, facial cream, facial lotion, eyeliner, eyebrow, either (7) or (8) The preparation described in 1.

  According to the present invention, a new and useful hair restoring agent having a significantly high hair restoring effect is provided. The hair-growth agent of the present invention has an enhanced hair-growth effect such as glycyrrhizic acid by blending a degradation product of soybean protein with thermolysin or thermolysin-like protease. Wide range of users can use it with peace of mind. The enzyme degradation product of soybean protein used in the present invention is widely used as a food additive and the like, and is also a preferable material in that it is safe for a living body.

  Hereinafter, the present invention will be described in detail. Throughout this specification, it should be understood that expression in the singular also includes the concept of the plural unless specifically stated otherwise. In addition, it is to be understood that the terms used in the present specification are used in the meaning normally used in the art unless otherwise specified.

  The hair restorer of the present invention comprises (A) one or more selected from the group consisting of glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and salts thereof, and (B) a thermolysin degradation product of soybean protein or soybean It is a thermolysin-like protease degradation product of a protein, and a product having an activity equivalent to that of the thermolysin degradation product.

  The hair-restoring agent of the present invention can be suitably used for various alopecia, including the adolescent alopecia that accounts for most alopecia. Specifically, the thermolysin degradation product of soybean protein is one or more selected from the group consisting of glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and salts thereof [hereinafter also referred to as “glycyrrhizic acids”] From the viewpoint of enhancing the hair-growth effect of glycyrrhizic acids when used in combination, it can be more suitably used for alopecia (for example, alopecia areata) to which glycyrrhizic acids are applied, but is not limited thereto.

One or more selected from the group consisting of glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and salts thereof used in the hair restorer of the present invention are those usually used in pharmaceuticals and quasi drugs. If there is no particular limitation, it can be used.
Glycyrrhizic acids can be synthesized by known methods or can be obtained as commercial products.

  Examples of derivatives of glycyrrhizic acid or glycyrrhetinic acid used in the hair restorer of the present invention include ester derivatives with fatty acids such as stearyl acid.

  Examples of the salt of glycyrrhizic acid or glycyrrhetinic acid used in the hair restorer of the present invention include alkali metal salts such as sodium and potassium, ammonium salts and the like.

Specific examples of glycyrrhizic acids used in the hair restorer of the present invention include glycyrrhizic acid, monoammonium glycyrrhizinate, stearyl glycyrrhizinate, dipotassium glycyrrhizinate, glycyrrhetinic acid, stearyl glycyrrhetinate.
Moreover, glycyrrhizic acids may be blended in the hair restorer of the present invention as herbal medicines such as licorice, herbal powders or herbal extracts containing them.
The glycyrrhizic acid is preferably a salt of glycyrrhizic acid, more preferably an alkali metal salt of glycyrrhizic acid, and particularly preferably dipotassium glycyrrhizinate.

  The amount of glycyrrhizic acid compounded in the hair restorer of the present invention is not particularly limited, but is usually 0.01 to 99% by weight, preferably 0.05 to 50% by weight, based on the total amount of the hair restorer of the present invention. More preferably, it is 0.1 to 10% by weight.

  “Thermolysin degradation product of soybean protein” is a product (degradation product) obtained by degrading soybean protein with thermolysin, which is a kind of heat-resistant protease. The thermolysin degradation product of soybean protein used in the present invention can be produced, for example, according to the method described in Patent Document 3.

  As long as the soybean protein as a raw material is a protein derived from soybean (Glycin max), which is an annual plant of the leguminous family, the variety and part thereof are not particularly limited. The site may be soybean plant itself, soybean plant seed itself, or the plant or a crushed or crushed product of the seed. Preferably, protein components are separated and purified from all components in the soybean plant. More preferably, a product obtained by separating and purifying protein components from all components in the seeds of soybean plants is used. Soy protein obtained by separation and purification as described above is substantially contained in soybean plant or soybean plant seeds as long as the product obtained by decomposing it with thermolysin enhances the hair growth effect of glycyrrhizic acids. All types of proteins may be included, or some types of proteins may be included. However, in view of availability and the like, seeds are preferable.

  In the present specification, the seeds of soybean plants not only refer to the whole structure commonly referred to as soybean seeds, but are obtained from, for example, dehulled soybean seeds, defatted soybean seeds (powdered ones, etc.) and whole soybean seeds. Snow flowers, soy milk, etc. may be used.

  As the soybean protein, commercially available products can also be suitably used. For example, Nisshin Cosmo Foods Co., Ltd., ADM Far East Co., Ltd., Showa Sangyo Co., Ltd., Fuji Oil Co., Ltd., Koyo Shokai Co., Ltd. Readily available from manufacturers or suppliers.

  Thermolysin (EC3.4.24.27) used in the present invention is well known as a heat-resistant protease produced by Bacillus thermoproteolyticus, which is a heat-resistant bacterium, and its gene has also been cloned. Thermolysin is generally known to cleave peptide bonds on the amino group side of hydrophobic amino acid residues having large side chains (for example, isoleucine, leucine, valine, phenylalanine, methionine, alanine, etc.). In the present invention, either wild type or recombinant thermolysin may be used. Moreover, a commercial item can also be used suitably, for example, it can obtain easily from manufacturers, such as Yamato Kasei Co., Ltd.

“Thermolysin-like protease” means an enzyme similar in thermochemical and physicochemical properties to thermolysin, specifically a protease similar in cleavage characteristics, cleavage sequence specificity, and the like. Examples of such proteases include neutral metalloproteases produced by microorganisms and amino acid variants of thermolysin. A thermolysin variant can be produced, for example, with reference to the method described in JP-T-11-501501.
The selected thermolysin-like protease is applied to soybean protein under reaction conditions suitable for the enzyme, and the hair growth promoting activity of the resulting soybean protein degradation product is tested by the method described in the examples below, thereby promoting hair growth. A soybean protein degradation product of thermolysin-like protease having activity can be obtained.

Hereinafter, thermolysin will be described as an example. When thermolysin-like protease is used, the desired degradation product can be obtained by treating soybean protein in the same manner under conditions suitable for the enzyme.
The thermolysin degradation product can be produced by treating soybean protein with thermolysin according to a conventional method under appropriate reaction conditions. For example, in the case of commercially available thermolysin, the reaction is performed according to the instruction manual. As a specific example, soybean protein concentration in a solvent such as water is generally 0.1 to 30% (w / v), preferably 1 to 10% (w / v). A raw material containing protein or soybean protein is suspended, and the suspension generally has a concentration of about 0.001 to 3% (w / v), preferably about 0.01 to 0.125% (w / v). Add thermolysin so that the reaction proceeds. Usually, at a reaction temperature of 30 to 80 ° C., preferably 40 to 70 ° C., more preferably 50 to 60 ° C., 2 to 30 hours, preferably 3 to 24 hours, more preferably 10 to 20 hours, still more preferably 12 When reacted for ˜18 hours, an appropriately fragmented soybean protein degradation product is obtained. The pH of the reaction solution is preferably near the optimum pH of thermolysin, and is preferably around 7.0 to 8.5, for example.

  The reaction stopping means is not particularly limited, and known means such as heat treatment can be used. For example, the thermolysin contained in the reaction product is deactivated by heat-treating the reaction product at a temperature of about 80 to 100 ° C. for 3 to 20 minutes, preferably 5 to 15 minutes. Examples of the heat treatment include a heat treatment at 85 ° C. for 15 minutes and a heat treatment at 100 ° C. for 5 minutes.

  The thermolysin degradation product obtained by the above degradation reaction may be further processed by any method known to those skilled in the art, if necessary. For example, it is preferable to remove large solid particles in the decomposition product by a treatment such as filtration using a filter aid or the like. Filtration conditions and the like are not particularly limited, and can be appropriately selected by those skilled in the art according to technical common sense and according to the purpose. Further, when the filter paper is likely to be clogged, it is preferable to use a filter aid or the like.

  Further, the decomposition product can be pulverized by concentrating under reduced pressure and then freeze-drying. The conditions and equipment used for concentration under reduced pressure and lyophilization are not particularly limited, and can be appropriately selected by those skilled in the art according to common technical knowledge. The decomposition product pulverized in this way is used as it is or after being dissolved in a solvent such as water.

  The soybean protein degradation product by thermolysin used in the present invention may contain substantially all of a wide variety of peptides obtained by the degradation reaction of soybean protein by thermolysin, or such a wide variety of peptides. The peptide may be a portion obtained by further fractionation and purification by a known method using the presence or absence of the hair-growth effect of the present invention as an index. As a part obtained by such fractionation / purification, for example, a part extracted with water or a hydrophilic organic solvent (such as methanol or ethanol) or a general extraction solvent such as a mixed solvent thereof is used. For example, a portion obtained by extraction by 90 volume% ethanol extraction method, 80 volume% ethanol extraction method, 70 volume% ethanol extraction method, 50 volume% ethanol extraction method, 30 volume% ethanol extraction method, etc. Can be used. However, for convenience, the soy protein is used as it is in a state of containing substantially all of a wide variety of peptides obtained by decomposing the protein with thermolysin. The hair-growth effect (activity) of the thermolysin decomposition product of soybean protein can be confirmed, for example, according to the method described in Examples and the like described later.

The average molecular weight of the thermolysin degradation product of soybean protein used in the present invention is preferably 300 to 10,000. The average molecular weight is more preferably 400 to 5000, further preferably 500 to 3500, and still more preferably 550 to 3200, from the viewpoint of increasing the permeability to cells and obtaining a higher effect. . The average molecular weight of the degradation product can be measured by any method known to those skilled in the art, and for example, it can be easily measured by gel permeation chromatography (GPC) as described in the Examples below. .
The content of the thermolysin degradation product of soybean protein in the present hair restorer is, for example, 0.0001 to 99% by weight, more preferably 0.001 to 80% by weight, still more preferably 0.01 to 50% by weight, particularly preferably. Is 0.1 to 30% by weight.

The application amount of the hair restorer of the present invention is not particularly limited, and is appropriately adjusted according to the state. Normally, however, the dosage of glycyrrhizin acids, amounts such that 1~2000μg / cm ² / day, preferably in an amount amount the administered such that 10~1000μg / cm ² / day, more preferably the an amount such that the dosage is 50-500 / cm ² / day, and such dosage thermolysin hydrolyzate of soy protein contained therein, the 0.001~1000μg / cm ² / day The amount is preferably such that the dosage is 0.01 to 500 μg / cm ² / day, more preferably the dosage is 0.1 to 300 μg / cm ² / day. Good.

  As shown in Examples described later, it has been confirmed that the hair-growth effect of glycyrrhizic acids is remarkably enhanced by the combined use of glycyrrhizic acids and a thermolysin degradation product of soybean protein.

  In this specification, the term “hair growth” is a broad meaning including all concepts such as hair growth, hair restoration, and hair loss prevention. For example, in hair follicles, which promotes new generation of hair. It includes all actions that advantageously work to promote the growth and growth of hair, such as healthy growth of generated hair. Here, the hair means any hair that grows on the body of animals including humans, for example, all body hair such as hair, head hair, eyebrows, eyelashes, mustache, beard, chest hair, and back hair.

  Confirmation of having a hair-growth effect (or hair-growth activity) is a method known per se, for example, applying a test substance to a living body (for example, human scalp or mouse back hair) (for example, application or spraying), A method for observing an increase in the amount and rate of hair generation, an increase in the number of cells by causing the test substance to act on hair papilla cells and hair follicle epithelial cells (including hair matrix cells and outer root sheath cells), etc. It can be performed by a method of observing. Alternatively, as described in the Examples below, it is also possible to cause the test substance to act on a hair follicle organ culture system (for example, rat's heel organ culture hair) and observe the elongation of the culture hair. .

  The hair restorer of the present invention may contain only glycyrrhizic acids and a thermolysin degradation product of soybean protein as active ingredients, but may contain various other active ingredients as necessary. Examples of such other active ingredients include cell activators, blood circulation promoters, anti-androgen hormone agents, sebum secretion inhibitors, immunosuppressants, antihistamines, bactericidal antiseptics, local stimulants, keratin softeners, anti-inflammatory agents. , Anti-apoptotic agents and the like, but are not limited thereto. Specifically, for example, pantothenic acid and derivatives thereof, placenta extract, photosensitizer, carrot extract, biotin, mononitroguaiacol, carpronium chloride or hydrate thereof, vitamin E and derivatives thereof, assembly extract, red pepper tincture, cephalanthin, Nicotinic acid and its derivatives, estradiol, ethinylestradiol, landic acid, minoxidil and its analogs and derivatives, 5α reductase inhibitor, 12-tetradecanoylphorbol-13-acetate (12-Tetradecanoylphorbol-13-acetate), goose Herbal medicines such as katsura, milk thistle, henna, estradiol benzoate, diphenhydramine, resorcin, hinokitiol, l-menthol, red pepper tincture, salicylic acid, ginger component, prickly carrot component, pante , Selenium disulfide, pyridoxine hydrochloride, octopirox, zinc pyrithione, sulfur, piroctone olamine, stearyl glycyrrhetinate, allantoin, dialkyl monoamine derivatives, assembly extract, perilla extract, buccal extract, miconazole nitrate, benzoic acid, sodium salicylate , Phytosterols, wine yeast extract, takanal, ethinylestradiol, isopropylmethylphenol, cephalanthin biotin, D-pantothenyl alcohol, dialkyl monoderivatives, marsh extract, button extract, shinano extract, epine extract, sophora extract, clara extract, kudin extract , Ginger extract, 6-benzylaminopurine, pentadecanoic acid glyceride, t-flavanone, quachalate extract, amacha One or a combination of two or more selected from extracts, adenosine, fucoidan, pantothenyl ethyl ether and the like can be used.

  Further, the content of other active ingredients as described above can be appropriately varied depending on various effects such as desired effects and age, sex, and condition of the subject to be applied. On the other hand, it is 0.001 to 50% by weight, preferably 0.001 to 10% by weight, more preferably 0.001 to 5% by weight. However, it is not limited to these.

  The hair restorer of the present invention is a pharmaceutical, quasi-drug, cosmetic, depending on the use or dosage form in addition to the above components, as long as the effects of the invention, formulation stability, safety to the living body, etc. are not impaired. Any component that can be generally used in foods may be appropriately blended. Although it does not restrict | limit especially as a component which can be mix | blended, For example, a support | carrier, a base, an additive etc. are mentioned. Specifically, for example, saccharides (e.g., mannitol, lactose, dextran, etc.), celluloses (e.g., hydroxypropylcellulose, methylcellulose, crystalline cellulose, etc.), poorly water-soluble gums (e.g., gum arabic, gum tragacanth, etc.), Cross-linked vinyl polymers, lipids, water, fats and oils, mineral oils, waxes, fatty acids, silicone oils, sterols, esters, metal soaps, alcohol, surfactants, solubilizing components, emulsifiers, oil content , Stabilizers, thickeners, preservatives, binders, lubricants, dispersants, pH adjusters, moisturizers, UV absorbers, chelating agents, transdermal absorption promoters, antioxidants, disintegrants, plastics One or two or more selected from agents, buffers, vitamins, amino acids, colorants, fragrances and the like can be used. Furthermore, the hair restorer of the present invention is also preferably used with a known DDS carrier such as a liposome.

  The surfactant is not particularly limited as long as it is used as a component of an external preparation in the pharmaceutical, quasi-drug or cosmetic field, and may be any kind of anionic, cationic, amphoteric and nonionic. Any surfactant can be used. Anionic surfactants include soap bases, fatty acid soaps such as sodium laurate, sodium palmitate, coconut oil fatty acid potassium, alkyl ether carboxylates, fatty acid amide ether carboxylates, acyl lactates, N-acyl sarcosine salts N-acyl glutamate, N-acyl alanine salt, N-acyl methyl alanine salt, N-acyl methyl taurine salt, N-acyl-ω-amino acid salt, alkane sulfonate, α-olefin sulfonate, α- Sulfo fatty acid methyl ester salt, alkyl sulfosuccinate, acyl isethionate, alkyl glycidyl ether sulfonate, monolauroyl monoethanolamide sodium polyoxyethylene sulfosuccinate, sodium lauryl polypropylene glycol sulfosuccinate , Sodium di-2-ethylhexyl sulfosuccinate, disodium lauryl POE sulfosuccinate, alkyl sulfoacetate, alkyl benzene sulfonate, alkyl naphthalene sulfonate, N-acylmethyl taurate, formalin condensation sulfonate, alkyl sulfate Ester salt, alkyl ether sulfate, alkyl aryl ether sulfate, fatty acid alkanolamide sulfate, monoacylglycerol sulfate, monoalkyl phosphate, polyoxyethylene alkyl ether phosphate, alkyl aryl ether phosphate Examples thereof include salts and fatty acid amide ether phosphates. Particularly preferably, N-acyl glutamate, N-acyl alanine, N-acyl methyl alanine, α-olefin sulfonate, alkyl sulfate, alkyl ether sulfate, polyoxyethylene alkyl ether phosphate are used. Can be mentioned.

  Examples of cationic surfactants include alkylamine salts, fatty acid amide amine salts, amine salts such as ester-containing tertiary amines, archebel type tertiary amines, alkyl quaternary ammonium salts, monoalkyl type quaternary annimmonium salts, and dialkyl types. Quaternary ammonium salts, trialkyl type quaternary ammonium salts, benzalkonium type quaternary annimonium salts, alkyl quaternary ammonium salts such as monoalkyl ether type quaternary ammonium salts, alkyl pyridinium salts, alkyl isoquinolium salts, chloride And cyclic quaternary annimonium salts such as benzethonium. Particularly preferred are monoalkyl type quaternary ammonium salts, dialkyl type quaternary annimmonium salts, and benzalkonium type quaternary annimonium salts.

  As the amphoteric surfactant, amino acid such as aminoacetic acid betaine type amphoteric surfactant, betaine type amphoteric surfactant such as sulfobetaine type amphoteric surfactant, glycine type amphoteric surfactant, aminopropionic acid type amphoteric surfactant, etc. Type surfactants. Particularly preferred are aminoacetic acid betaine-type amphoteric surfactants and glycine-type amphoteric surfactants.

  Nonionic surfactants include, for example, propylene glycol monofatty acid esters such as propylene glycol monostearate, ethylene glycol monofatty acid ester, mono cottonseed oil fatty acid glycerin, monoerucic acid glycerin, sesquioleate glycerin, monostearate glycerin, polyglycerin fatty acid Esters, sorbitan fatty acid esters, sucrose fatty acid esters, methyl glucoside fatty acid esters, fatty acid esters of polyhydric alcohols such as alkyl polyglucosides, polyhydric alcohol alkyl ethers, POE alkyl ethers, POE alkyl phenyl ethers, POE phytosterols, POE cholestanols , POE ether such as POE polyoxypropylene alkyl ether, POE mono-fatty acid ester, POE group Cold di fatty acid ester, polyoxyethylene glycerin fatty acid ester, POE sorbitan fatty acid ester, POE sorbitol fatty acid ester, POE methyl glucoside fatty acid ester, POE castor oil, POE hydrogenated castor oil, POE animal and vegetable oil, POE alkyl ether fatty acid ester, POE polyoxypropylene Examples include ether esters such as glycol, and palm oil fatty acid diethanolamide. Particularly preferably, glyceryl monostearate, polyglycerin fatty acid ester, sorbitan fatty acid ester, sucrose fatty acid ester, POE alkyl ether, POE alkylphenyl ether, POE polyoxypropylene alkyl ether, POE sorbitan fatty acid ester, POE sorbitol fatty acid ester, POE Examples include hydrogenated castor oil and coconut oil fatty acid diethanolamide.

  Other surfactants include POE alkylamines, POE fatty acid amides, alkyldiethanolamides, alkylamine oxides, POE alkyl mercaptans, polymer surfactants, fluorosurfactants, silicone surfactants, polypeptide derivatives, And natural surfactants.

  Examples of the salt of the surfactant include ammonium salts, alkali metals (such as sodium and potassium), alkaline earth metals (such as calcium and magnesium), zinc, and aluminum.

  The hair restorer of the present invention is blended with a thermolysin degradation product of soybean protein using any method known in the art, and further, if necessary, other active ingredients, carriers, bases, additions as described above It can be manufactured by a conventional method by blending an agent and the like.

  The hair-restoring agent of the present invention can be any preparation that can be widely used as a pharmaceutical, quasi-drug, food, cosmetic, etc., but is preferably a preparation that can be used as a pharmaceutical, quasi-drug, or cosmetic. .

  The dosage form of the hair restorer of the present invention is not particularly limited. For example, the hair restorer of the present invention can take any dosage form such as an internal preparation, an external preparation, and an injection, but an external preparation is preferred.

  As an external preparation, it can take any general form for pharmaceuticals, quasi drugs, cosmetics, etc., for example, liquid, emulsion, cream, lotion, paste, mousse, gel, sheet ( Substrate), aerosol, spray, oil, pack, gel, ointment and the like, but is not limited thereto.

  Examples of the preparation containing the hair restorer of the present invention include preparations that can be used as, for example, pharmaceuticals, quasi drugs, cosmetics, foods, and the like. Cosmetics (eg shampoo, hair conditioner, scalp lotion, scalp cream, hair tonic), skin care cosmetics (eg lotion, lotion, cream, facial cream, facial lotion, milky lotion, pack, liquid facial cleanser, Soap), body care cosmetics (eg whole body cream, whole body lotion, soap, liquid cleaning agent, bath preparation), UV protection cosmetics (eg sunscreen cream, sunscreen lotion, suntan cream, suntan lotion), makeup cosmetics ( For example, eyeliner, eyebrow), preferably shampoo, haircon Ishona, scalp lotions, scalp creams, hair tonic, whole body cream, whole body lotions, face creams, face lotions, eye liner, but may be an eyebrow, but are not limited to these.

  Further, the content of glycyrrhizic acids in the above-mentioned preparation can be appropriately varied depending on various factors such as desired effects and the preparation to be used, but for example, 0.01 to 99% by weight with respect to the total weight of the preparation Preferably, it is 0.05 to 50% by weight. However, it is not limited to these.

  Moreover, the content of the thermolysin degradation product of soybean protein in the above-mentioned preparation can be appropriately varied depending on various factors such as a desired effect and a preparation to be used. -99 wt%, preferably 0.001-80 wt%, more preferably 0.01-50 wt%. However, it is not limited to these.

  The hair restorer of the present invention and the preparation containing the hair restorer are used in accordance with conventional methods. For example, in the case of an external preparation, it is applied to the body where the hair-growth effect is desired (for example, head hair, eyebrows, eyelashes, mustache, beard, chest hair, back hair, eyelashes, pubic hair, hand and arm hair, shank hair, etc. It can be applied by direct application or spraying on the skin of any hair). In addition, the hair restorer of the present invention can be administered in one to several times (for example, twice, three times, etc.) per day depending on the form and the degree of desired effect.

  EXAMPLES The present invention will be described in detail below based on examples, but the present invention is not limited to these examples.

Preparation Example 1: Preparation of Thermolysin Degradation Product of Soy Protein 50 g of powdered soy protein (product name “PR-800”, manufactured by Fuji Oil Co., Ltd.) was dispersed in 2 L of distilled water, and pH 8.0 with 0.1 N NaOH. Adjusted. 500 mg of thermolysin (EC3.4.24.27, derived from Bacillus thermoproteolyticus, product name “Samorose PC10F”, manufactured by Daiwa Kasei Co., Ltd., 100 units / mg) was added, and degradation was performed at 60 ° C. for 15 hours. After the reaction, the thermolysin was inactivated by boiling at 100 ° C. for 10 minutes. After allowing to cool, 25 g of filter aid (Radiolite 500, Showa Chemical Industry Co., Ltd.) was added and stirred, followed by filtration. The obtained filtrate was concentrated under reduced pressure to 500 ml, and then freeze-dried to finally obtain about 26 g of a thermolysin degradation product of soybean protein.

The average molecular weight of the decomposition product thus obtained was measured by the GPC method. A soybean protein thermolysin degradation product was dissolved in 25 mM Tris-HCl buffer (containing 150 mM NaCl, pH 7.5) to prepare a 1 mg / mL test solution. HPLC column Superdex peptide HR (10 mm ID × 30 cm, manufactured by Amersham Biosciences) was equilibrated with the same buffer, and 100 μL of the test solution was injected into this column. The flow rate of the column was 0.5 mL / min, the column temperature was room temperature, and the peptide was detected at 214 nm.
As peptide preparations with known molecular weights, Cytochrome C (Sigma, molecular weight 12327), Aprotinin (Sigma, molecular weight 6518), Hexaglycine (Sigma, molecular weight 360), Triglycine (Sigma, molecular weight 189), and Glycine (manufactured by Sigma, molecular weight 75) was used. Molecular weight distribution and peak average molecular weight were estimated from the elution time.
As a result, it was estimated that the peak average molecular weight of Collaplus N was 711 and the molecular weight distribution was 100-30000.
Here, “peak average molecular weight” means the molecular weight corresponding to the elution time of the peak top (the strongest peak) of the chromatograph.

Preparation Example 2: Preparation of Thermolysin Degradation Product (Ethanol Extract) of Soy Protein 50 g of powdered soy protein (product name “PR-800”, manufactured by Fuji Oil Co., Ltd.) was dispersed in 2 L of distilled water and 0.1 N The pH was adjusted to 8.0 with NaOH. 500 mg of thermolysin (EC3.4.24.27, derived from Bacillus thermoproteolyticus, product name “Samorose PC10F”, manufactured by Daiwa Kasei Co., Ltd., 100 units / mg) was added, and degradation was performed at 60 ° C. for 15 hours. After the reaction, the thermolysin was inactivated by boiling at 100 ° C. for 10 minutes. After allowing to cool, 8.0 L of ethanol was added and mixed (final concentration of ethanol: 80%). 25 g of filter aid (Radiolite 500, Showa Chemical Industry Co., Ltd.) was added and stirred, followed by filtration. The obtained filtrate was concentrated under reduced pressure to 500 mL and then freeze-dried to finally obtain about 20.2 g of a soybean protein thermolysin degradation product (ethanol extract).

Example 1 Test for Promoting Growth of Rat Vaginal Organ Culture Hair The hair growth effect of the thermolysin degradation product of the present invention was confirmed using rat vaginal organ culture hair as a hair follicle organ culture system.
The ciliary organs of Wistar newborn rats were surgically removed. A medium (RPMI 1640) (0.4 mL) containing each test drug adjusted to the concentration shown in Table 1 was added to an organ culture petri dish (Falcon 3037) containing a stainless steel grid, and the eyelashes excised thereon Ten wrapping organs were arranged. The cells were cultured at 31 ° C. under aseptic conditions in a gas phase of 5% CO ₂ and 90% O ₂ . After 5 days, the length of the hair shaft was measured, and the elongation amount of the hair shaft was calculated from the difference from the measured value before the start of the test. As a control group, the same experiment was performed using a medium containing no test drug. The results are shown in Table 1 and FIG. In FIG. 1, Control means control, and Glytyl means dipotassium glycyrrhizinate.

  As shown in Table 1 and FIG. 1, it was confirmed that the thermolysin degradation product of the present invention remarkably enhances the growth promoting effect of glycyrrhizic acids on the growing hair in the organ culture system. This result shows that the hair-restoring agent of the present invention can exhibit a significantly high hair-restoring effect in the living body as well.

Formulation examples are given below, but the present invention is not limited to these examples.
Formulation Example 1 (External hair restorer)
The following components were weighed and adjusted to 100 mL with purified water.
Dipotassium glycyrrhizinate 0.1 g
Thermolysin degradation product of soybean protein (peak average molecular weight about 1500) 1.0 g
Resorcin 1.0 g
Pantothenyl ethyl ether 0.1 g
Propylene glycol 10.0 g
95% ethanol 60.0 g
100 mL total volume with purified water

Formulation Example 2 (External hair restorer)
The following components were weighed and adjusted to 100 mL with 95% ethanol.
Dipotassium glycyrrhizinate 0.1 g
Thermolysin degradation product of soybean protein (peak average molecular weight about 1000) 1.0 g
Hinokitiol 0.05 g
Tocopherol acetate 0.5 g
Propylene glycol 10.0 g
Total volume 100 mL with 95% ethanol

Formulation Example 3 (External hair restorer)
The following components were weighed and adjusted to 100 mL with purified water.
Dipotassium glycyrrhizinate 0.1 g
Thermolysin degradation product of soybean protein (peak average molecular weight about 1200) 1.0 g
Hinokitiol 0.05 g
Propylene glycol 10.0 g
95% ethanol 50.0 g
100 mL total volume with purified water

Formulation Example 4 (External hair restorer)
The following components were weighed and adjusted to 100 mL with purified water.
Dipotassium glycyrrhizinate 0.1 g
Thermolysin degradation product of soybean protein (peak average molecular weight about 1800) 1.0 g
Cephalanthin 0.05 g
Propylene glycol 10.0 g
95% ethanol 50.0 g
100 mL total volume with purified water

Formulation Example 5 (External hair restorer)
The following components were weighed and adjusted to 100 mL with purified water.
Dipotassium glycyrrhizinate 0.1 g
Thermolysin degradation product of soybean protein (peak average molecular weight about 1500) 1.0 g
L-Menthol 0.01 g
Propylene glycol 10.0 g
95% ethanol 60.0 g
100 mL total volume with purified water

Formulation Example 6 (External hair restorer)
The following components were weighed and adjusted to 100 mL with purified water.
Dipotassium glycyrrhizinate 0.1 g
Thermolysin degradation product of soybean protein (peak average molecular weight about 2000) 1.0 g
Pyridoxine hydrochloride 5.0 mg
Pantothenyl ethyl ether 0.1 g
Propylene glycol 10.0 g
95% ethanol 60.0 g
100 mL total volume with purified water

Formulation Example 7 (External hair restorer)
The following components were weighed and prepared according to a conventional method.
Dipotassium glycyrrhizinate 0.1 g
Thermolysin degradation product of soybean protein (peak average molecular weight about 1800) 1.0 g
Carboxyvinyl polymer 0.1 g
Edetate sodium hydrate 0.05 g
Polyvinyl alcohol 1.0 g
Triethanolamine 0.5 g
Purified water 54.75 g
(End of water phase component)
l-Menthol 1.0 g
Tocopherol acetate 0.1 g
Ethanol 40.0 g
Polysorbate 80 0.6 g
Propylene glycol 0.2 g
Ethoxydiglycol 0.5 g
Phospholipid 0.1 g
(End of oil phase component)
100 g total

Formulation Example 8 (External hair restorer)
The following components were weighed and prepared according to a conventional method.
Dipotassium glycyrrhizinate 0.1 g
Thermolysin degradation product of soybean protein (peak average molecular weight about 1500) 1.0 g
Carboxyvinyl polymer 0.4 g
Fucoidan 0.5 g
Edetate sodium hydrate 0.05 g
Polyvinyl alcohol 0.3 g
Triethanolamine 1.0 g
Purified water 53.15 g
(End of water phase component)
l-Menthol 2.0 g
Tocopherol acetate 0.1 g
Ethanol 40.0 g
Polysorbate 80 0.6 g
Propylene glycol 0.2 g
Ethoxydiglycol 0.5 g
Phospholipid 0.1 g
(End of oil phase component)
100 g total

Formulation Example 9 (Shampoo)
The following components were weighed and prepared according to a conventional method.
Dipotassium glycyrrhizinate 0.5 g
Thermolysin degradation product of soybean protein (peak average molecular weight about 1800) 1.0 g
N-cocoyl methyl taurine sodium (30% aqueous solution) 10.0 g
POE (2) sodium lauryl ether sulfate (27% aqueous solution) 20.0 g
Lauryldimethylaminosulfate betaine (35% aqueous solution) 10.0 g
Palm oil fatty acid diethanolamide 4.0 g
Dipropylene glycol 2.0 g
Citric acid 0.1 g
Methylparaben 0.2 g
100 mL total volume with purified water

Formulation Example 10 (Shampoo)
The following components were weighed and prepared according to a conventional method.
Dipotassium glycyrrhizinate 0.1 g
Soy protein thermolysin degradation product (peak average molecular weight about 2000) 0.5 g
Sodium tetradecenesulfonate 10.0 g
N-acyl-L-glutamic acid triethanolamine (30% aqueous solution) 5.0 g
Sodium N-acyl-methylalanine (30% aqueous solution) 5.0 g
Coconut oil fatty acid diethanolamide 1.0 g
Trimethylglycine 1.0 g
PEG-190 distearic acid 0.5 g
Methylparaben 0.2 g
100 mL total volume with purified water

Formulation Example 11 (Shampoo)
The following components were weighed and prepared according to a conventional method.
Dipotassium glycyrrhizinate 0.1 g
Thermolysin degradation product of soybean protein (peak average molecular weight about 1500) 1.0 g
POE (2) sodium lauryl ether sulfate (27% aqueous solution) 10.0 g
Lauric acid amidopropyl betaine (30% aqueous solution) 15.0 g
N-acyl-L-glutamic acid triethanolamine (30% aqueous solution) 5.0 g
1,3-butylene glycol 3.0 g
Glycol distearate 2.0 g
Polyquaternium-10 0.2 g
Hydrogenated lecithin 0.2 g
Methylparaben 0.2 g
100 mL total volume with purified water

Formulation Example 12 (hair conditioner)
The following components were weighed and prepared according to a conventional method.
Dipotassium glycyrrhizinate 0.5 g
Soy protein thermolysin degradation product (peak average molecular weight about 1800) 0.5 g
Zinc pyrithione 0.01 g
Methylphenylpolysiloxane 1.0 g
Dimethylpolysiloxane 3.0 g
Hardened rapeseed oil alcohol 2.0 g
Isopropyl myristate 2.0 g
Propylene glycol 3.0 g
(Adipic acid, 2-ethylhexanoic acid, stearic acid) Glyceryl 2.0 g
Distearyldimethylammonium chloride 0.5 g
Cetanol 1.0 g
Methylparaben 0.2 g
100 mL total volume with purified water

Formulation Example 13 (hair conditioner)
The following components were weighed and prepared according to a conventional method.
Dipotassium glycyrrhizinate 0.5 g
Thermolysin degradation product of soybean protein (peak average molecular weight about 1500) 1.0 g
Dipotassium glycyrrhizinate 0.1 g
Cyclopentasiloxane 3.0 g
Stearyl alcohol 2.0 g
Ethylhexyl palmitate 2.0 g
Dipropylene glycol 3.0 g
Glyceryl triethylhexanoate 2.5 g
Cetanol 1.0 g
Methylparaben 0.2 g
100 mL total volume with purified water

Formulation Example 14 (hair conditioner)
The following components were weighed and prepared according to a conventional method.
Dipotassium glycyrrhizinate 0.1 g
Thermolysin degradation product of soybean protein (peak average molecular weight about 2000) 1.0 g
Dimethylpolysiloxane 3.0 g
Cetyl alcohol 1.5 g
Stearyl alcohol 1.0 g
Glycerin 3.0 g
Liquid paraffin 1.0 g
Stearyltrimethylammonium chloride 0.7 g
Methylparaben 0.2 g
100 mL total volume with purified water

Formulation Example 15 (hair conditioner)
The following components were weighed and prepared according to a conventional method.
Dipotassium glycyrrhizinate 0.5 g
Thermolysin degradation product of soybean protein (peak average molecular weight about 1200) 2.0 g
Dimethylpolysiloxane 2.0 g
Stearyl alcohol 1.5 g
Behenyl alcohol 0.5 g
Propylene glycol 3.0 g
Behenyltrimethylammonium chloride 2.0 g
Distearyldimethylammonium chloride 1.0 g
Hydroxyethylcellulose 0.3 g
Cetanol 2.0 g
Methylparaben 0.2 g
100 mL total volume with purified water

Formulation Example 16 (Scalp lotion)
The following components were weighed and prepared according to a conventional method.
Dipotassium glycyrrhizinate 0.1 g
Thermolysin degradation product of soybean protein (peak average molecular weight about 2000) 1.0 g
Glyceryl stearate 1.0 g
PEG-5 glyceryl stearate 1.0 g
Polyether-modified silicone 0.4 g
Stearic acid K 0.4 g
Behenyl alcohol 0.4 g
Squalane 2.0 g
Cetyl ethylhexanoate 2.0 g
1,3-butylene glycol 10.0 g
Glycerin 5.0 g
Carbomer (Carbopol ETD2050) 0.1 g
Polyvinyl alcohol 0.3 g
Methylparaben 0.2 g
100 g in purified water

Formulation Example 17 (Scalp Cream)
The following components were weighed and prepared according to a conventional method.
Dipotassium glycyrrhizinate 0.1 g
Thermolysin degradation product of soybean protein (peak average molecular weight about 1500) 1.0 g
PEG-40 stearic acid 2.0 g
Glyceryl monostearate (self-emulsifying) 5.0 g
MC stearic acid 5.0 g
Behenyl alcohol 0.5 g
Squalane 15.0 g
Cetyl isooctanoate 5.0 g
Methylparaben 0.1 g
Butylparaben 0.1 g
1,3-butylene glycol 5.0 g
100 g in purified water

  As described above, the present invention has been described using the preferred embodiments of the present invention. However, it should be readily understood that the scope of the present invention should be construed in accordance with the description of the appended claims. The patents, patent applications and literature cited herein are to be incorporated herein by reference in the same way that their contents are specifically described herein. That will be understood.

  The hair-growth agent of the present invention has enhanced the hair-growth effect of glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and salts thereof by blending a thermolysin degradation product of soybean protein or a thermolysin-like protease degradation product of soybean protein, Since it is a hair-growth agent with high hair-growth effect and safety, it has high industrial utility value.

It is a figure which shows the result of the expansion | extension acceleration | stimulation test after 5 days of rat wing organ culture hair.

Claims (9)

The following ingredients:
(A) One or more selected from the group consisting of glycyrrhizic acid, glycyrrhetinic acid, derivatives thereof, and salts thereof, and (B) a thermolysin degradation product of soybean protein or a thermolysin-like protease degradation product of soybean protein A hair restorer containing a product having hair growth activity equivalent to that of a thermolysin degradation product.   The hair restorer according to claim 1, wherein component (A) is dipotassium glycyrrhizinate.   The hair restorer according to claim 1 or 2, wherein component (B) is a thermolysin degradation product of soybean protein.   The hair restorer according to any one of claims 1 to 3, wherein the amount of component (A) is 0.01 to 99% by weight and the amount of component (B) is 0.0001 to 99% by weight.   The hair restorer in any one of Claims 1-4 whose average molecular weights of a component (B) are 300-10000.   Furthermore, as a component (C), a cell activator, a blood circulation promoter, an anti-androgen hormone agent, a sebum secretion inhibitor, an immunosuppressant, an antihistamine, a bactericidal disinfectant, a local stimulant, a keratin softener, an anti-apoptotic agent, and an anti-apoptotic agent The hair restorer in any one of Claims 1-5 which also contains the 1 type (s) or 2 or more types selected from the group which consists of an agent.   The formulation containing the hair restorer as described in any one of Claims 1-6.   The preparation according to claim 7, which is a pharmaceutical, a quasi-drug, a cosmetic, or a food.   The preparation according to any one of claims 7 and 8, which is shampoo, hair conditioner, scalp lotion, scalp cream, hair tonic, whole body cream, whole body lotion, facial cream, facial lotion, eyeliner, eyebrow.

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