JP2005330238A - Epigallocatechin-containing hair tonic - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To prepare a safely usable hair tonic exhibiting excellent hair-growing and hair-restoring effects and a depilation-preventing effect. <P>SOLUTION: The activities of a fibroblast growth factor 5 (FGF-5) comprise the activities for retarding the growth of the hair in a hair-mother cell, and shifting the hair cycle from the growth period to the involutional period. Epigallocatechin, epigallocatechin gallate, and a plant extract containing them, preferably, an extract obtained by the extraction of tea with water or a solvent other than the water have activities for inhibiting the FGF-5 activities. As a result, the hair tonic containing one or more kinds of the epigallocatechin, the epigallocatechin gallate, and the plant extract containing them exhibits excellent hair growing and hair restoring effects based on the control of the hair cycle by the FGF-5 because the hair tonic contains the component maintaining the proliferation of the hair-mother cell and directly promoting the growth of the hair. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a hair restorer containing epigallocatechin or epigallocatechin gallate, further comprising epigallocatechin or epigallocatechin gallate, and exhibiting an activity of inhibiting the action of fibroblast growth factor 5 (FGF-5). The present invention relates to a plant extract and a hair restorer containing the same.

  Many of the hair growth and hair nourishing agents that have been developed so far promote hair growth by suppressing excessive sebum secretion that inhibits hair growth, eliminating poor blood circulation such as the scalp, or suppressing the action of male hormones It aims to. On the other hand, as seen in pine extracts, plant-derived hair growth agents have existed since ancient times, and the substance of the hair growth action is not known in detail, but has been used in folk remedies. As described above, there are a large number of hair-growth / hair-restoring agents, but there is no one that has a universal effect on hair / hair removal because of the large individual differences in the effects of the types of hair / hair removal.

  Although search for a substance having a hair-growth / hair-growth effect as a new hair-growth / hair-growth ingredient has been made energetically, a truly effective new substance is not easily found. Given this situation, the need for hair restoration and hair nourishing agents that have a universal effect on thinning hair and hair loss reflecting the aging and multi-stress society is still high.

By the way, hair does not grow constantly at a constant speed, but grows by repeating a growth period and a rest period. The hair growth and hair loss cycle (hair cycle) from the growth period to the rest period is different for each body part and for each human hair. Transforming growth factor (TGF) β, which is one of the substances that affect the hair cycle of hair matrix cells, exhibits the action of shifting the hair cycle from the growth phase to the regression phase and the resting phase. An antagonist that suppresses the action has been found and proposed as a novel hair-growth component.

The present inventors have found that the biological activity of a cytokine, fibroblast growth factor 5 (hereinafter also referred to as “FGF-5”), which is different from TGFβ, has control of the hair cycle. The FGF-5 protein belongs to the fibroblast growth factor (FGF) family that exhibits various physiological actions. Our study revealed that FGF-5 has the action of inhibiting hair growth and shifting the hair cycle from the growth phase to the regression phase. FGF-5S (short chain molecule of FGF-5) expressed in a large amount in growing hair follicles exhibits an antagonist activity against FGF-5, thereby delaying the transition from the growth phase to the regression phase, and hair growth It has also been clarified that (see Non-Patent Documents 1 to 4). The applicant of the present application has previously found that by administering fibroblast growth factor 5 to an animal, an abnormality in the hair cycle can be induced at the administration site to become an alopecia model, and the alopecia model based on this discovery (Patent Document 1).
JP 2001-343383 A Ozawa K, Suzuki S, Asada M et al. J. Biol. Chem. 273: 29262-29271 (1998) Suzuki S, Kato T, Takimoto H et al. J. Invest. Dermatol. 111: 963-972 (1998) Suzuki S, Ota Y, Ozawa K, Imamura T J. Invest. Dermatol. 114: 456-463 (2000) Ota Y, Saitoh Y, Suzuki S et al. Biochem. Biophys. Res. Commun. 290: 169-176 (2002)

  In the process of studying FGF-5 action, the present inventors have obtained the idea that a substance having an activity that inhibits this action can be used as a hair-restoring agent that exhibits an excellent effect, and acts to suppress hair growth. In order to find a substance having an inhibitory action or an antagonist with respect to the action of FGF-5, intensive research was advanced. As a result, the present inventors have found that epigallocatechin and epigallocatechin gallate are substances meeting the purpose and completed the present invention.

  The present invention provides an epigallocatechin having FGF-5 inhibitory action as an active ingredient, a hair restorer containing epigallocatechin gallate, or a hair restorer containing these active ingredients and having low side effects and less side effects. Objective.

The plant extract of the present invention contains epigallocatechin or epigallocatechin gallate and is characterized by exhibiting an activity of inhibiting the action of FGF-5.
The plant extract is preferably an extract obtained by extracting tea with water or a solvent other than water.

The hair restorer of the present invention is characterized by containing epigallocatechin or epigallocatechin gallate as an active ingredient.
Furthermore, the hair restorer characterized by including said plant extract is also contained in this invention.

  FGF-5 has the action of inhibiting hair growth and shifting the hair cycle from the growth phase to the regression phase in the hair matrix cells. Epigallocatechin or epigallocatechin gallate inhibits the action of FGF-5. The hair-restoring agent containing the plant extract of the present invention contains epigallocatechin or epigallocatechin gallate as a component that directly acts on hair matrix cell growth, so that it has excellent hair-growth / hair-restoration effect and hair loss prevention Demonstrate the effect. Since the active ingredient is an extract from a plant, it can be used safely and has almost no side effects.

[Detailed Description of the Invention]
The plant extract according to the present invention is a plant extract containing epigallocatechin and epigallocatechin gallate, preferably an extract obtained by extracting tea with water or a solvent other than water, and has an FGF-5 action. It has the activity which inhibits. If such an extract is blended with a hair growth agent, the hair growth effect is exhibited.

The role of FGF-5 in the hair growth cycle According to the study by the present inventors, it is clear for the first time that FGF-5 has an action of inhibiting hair growth and shifting the hair cycle from the growth phase to the regression phase. It became. On the other hand, the hair papilla at the base of the hair follicle controls hair growth by regulating the growth and differentiation of hair matrix cells. In the regression phase, the hair matrix cells disappear, but the number of dermal papilla cells decreases but does not decrease. In the next growth phase, the hair papilla cells are activated again, and the hair matrix cells begin to proliferate and differentiate anew due to the action. Since the dermal papilla cell itself has not changed, hair of the same thickness as the previous growth period can be made. Therefore, if the action of FGF-5, which plays the role of a trigger that shifts from the growth period to the regression / rest period, is suppressed by some method, only the growth period is extended. Substances that increase the growth period in this way are expected to exhibit excellent hair-growth and hair-restoring effects. Such a substance, or a plant extract containing the substance, suppresses the action of FGF-5 that induces abnormal hair cycle, that is, has a hair growth / hair growth effect.

In fact, FGF-5S, which is a short-chain molecule of FGF-5 expressed in large quantities in the growing follicle,
It has been reported that by exhibiting antagonist activity against FGF-5, the transition from the growth phase to the regression phase is delayed and hair growth is promoted. The present inventors have further studied and found that an extract obtained from a plant or seaweed has an activity of inhibiting FGF-5 action. As described later, the inhibitory action by the extract was confirmed by examining the suppression of the cell growth promoting action by FGF-5 using cultured cells.

Plant extracts such as tea and ages have antagonist activity similar to FGF-5S1
Species or substances may be included, or there may be inhibitors that have a direct inhibitory effect on FGF-5. The mechanism of FGF-5 inhibition by such an extract and the substance of the active substance must wait for future research results, and epigallocatechin and epigallocatechin gallate described below are also candidate substances.

It is clear by the present inventor that epigallocatechin and epigallocatechin gallate, which are inhibitors of fibroblast growth factor 5 (FGF-5), have the activity of inhibiting the above action of FGF-5. It was made. Epigallocatechin and epigallocatechin gallate are represented by the following formulae.

  Epigallocatechin and epigallocatechin gallate belong to a group of compounds generally referred to as catechins contained in tea leaves and the like. The reason why the tea extract has the activity of inhibiting the FGF-5 action is that the components that are considered to be FGF-5 inhibitors, epigallocatechin and epigallocatechin gallate, are contained in the tea extract. Tea catechins occupy most of the soluble components in the green tea infusion, (−)-epigallocatechin gallate, (−)-epicatechin gallate, (−)-epigallocatechin, (−)-epicatechin, (+ ) -Gallocatechin and (+)-catechin. Of these, (-)-epigallocatechin gallate ((-)-EGCG) is the most abundant. These catechins are known to have physiological effects such as anti-oxidation, antibacterial and deodorizing effects. The present inventors have shown for the first time that epigallocatechin and epigallocatechin gallate also have a hair-growth effect through inhibiting the action of FGF-5.

Epicatechin and gallic acid esters of epigallocatechin contained in green tea are referred to as “green tea tannins”. Oolong tea and black tea contain catechin oligomers, which are typical condensed tannins, whereas green tea contains mainly catechin monomers and almost no oligomers.

Inhibition of FGF-5 action by epigallocatechin and epigallocatechin gallate It was confirmed by an in vitro measurement method that epigallocatechin and epigallocatechin gallate have the activity of inhibiting the action of FGF-5. The method uses cultured cells that are sensitive to both FGF-5 and interleukin-3 (IL-3) and uses FGF-
5 This test examines inhibition of action. When such FGF-5-dependent growth of cultured cells is suppressed, the plant extract or substance of the subject added to the cell culture solution has inhibited the stimulating effect of FGF-5 on cell growth. .

In the in vitro evaluation method, cultured cells sensitive to both FGF-5 and growth promoting substances other than FGF-5, such as cytokines, for example, IL-3, specifically, FR-Ba / F3 cells are used. Is done. This FR-Ba / F3 cell is a cell line that stably expresses "FGF-Receptor 1c" by introducing "FGF-Receptor 1c" cDNA with an expression cassette into "Ba / F3 cell". is there. Here, FGF-Receptor 1c (hereinafter abbreviated as “FR”) is
It means a receptor for FGF-5 (FGF-Receptor). The parent cell line “Ba / F3 cell line (mouse IL-3-dependent proB cell)” of FR-Ba / F3 cells can be obtained from various places including RIKEN Cell Bank. For those skilled in the art, it is within the scope of normal genetic engineering operations to obtain cDNA expressing “FGF-Receptor 1c” using existing genetic engineering techniques and to introduce the gene into the parent cell line.

The FR-Ba / F3 cells are IL-3 dependent, similar to its parent strain “Ba / F3 cells” (IL-3, a different kind of cytokine that stimulates and promotes the proliferation of a wide range of cells, like FGF-5) Otherwise, it cannot survive or proliferate). In addition, FR-Ba / F3 cells acquired responsiveness to FGF-5 (also FGF-1 and 2) by expressing FR, and even in the absence of IL-3, FGF-5 and If heparin is present (if FGF binds to FR and its signal is input into the cell, heparin binding is also required), it has the feature that it can survive and proliferate.

Plant Extract The plant extract of the present invention contains epigallocatechin or epigallocatechin gallate and is characterized by exhibiting an activity of inhibiting the action of FGF-5. A plant extract containing epigallocatechin or epigallocatechin gallate can be obtained by extracting water from a plant with a solvent other than water. As used herein, “plant extract” refers to a part of a plant, such as leaves, stems, flowers, fruits, roots, whole plants or sap, or is dried or dried, and further if necessary. It means various solvent extracts obtained by extraction with water or a solvent described later, a diluted solution thereof, a concentrated solution thereof, or a dried powder thereof after necessary processing such as pulverization and heat treatment. Whether such a plant extract has an activity of inhibiting the action of FGF-5 is evaluated by the above-described in vitro measurement method using cultured cells.

  The step of preparing the plant extract is for removing impurities or coexisting substances, or selecting them, and techniques commonly used in the industry such as washing, crushing, peeling, polishing, pressing, sieving. Other methods can be used. The step of producing an extract from a plant can be performed using water, a solution containing salts, or an appropriate extraction solvent.

Extraction is performed by immersing in an extraction solvent. To increase efficiency, continuous or intermittent stirring may be used, or homogenization may be performed in the extraction solvent. The extraction temperature is usually 5 ° C. to the boiling point of the extraction solvent. Although the extraction time varies depending on the properties of the extraction raw material, the type of extraction solvent, the extraction temperature, etc., it is generally appropriate to be about 1 to 14 days. The extraction operation may be performed continuously using an extraction device such as a Soxhlet extractor. The extraction method is not particularly limited, and may be an ordinary method, for example, heat extraction or normal temperature extraction. Furthermore, in addition to normal pressure, extraction may be performed under pressure.

As a solvent used for extraction, in addition to water, lower alcohol solvents such as methanol, ethanol, propanol and isopropanol, polyhydric alcohols such as polyethylene glycol, 1,3-butylene glycol, propylene glycol, dipropylene glycol and glycerin Polar organic solvents such as solvents, ether solvents such as ethyl ether and propyl ether, ketone solvents such as acetone and ethyl methyl ketone, and ester solvents such as ethyl acetate and butyl acetate can be used. In particular, a solvent having excellent solubility of a substance and having a relatively low freezing point and boiling point is preferably used. One or more of the above solvents are selected and used for extraction. What is necessary is just to select an extraction solvent suitably according to the kind, site | part, property, etc. of the plant to extract. For example, in the case of a plant that contains a large amount of calcium oxalate that causes dermatitis, the extraction operation is performed by alternately using a plurality of solvents in combination of water and the above organic solvent, or by distribution using a mixed solvent. Extraction from which inappropriate components have been selectively removed can also be obtained by extraction. Alternatively, physiological saline, phosphate buffer, phosphate buffered saline, or the like can be used. If necessary, for example, a method using a fluid in a supercritical state of carbon dioxide disclosed in Japanese Patent Application Laid-Open No. 62-172096 may be employed.

  The crude extract thus obtained can be contained as an active ingredient in the hair restorer according to the present invention even if it is used as it is. In consideration of formulation requirements such as storage and hair restorer, fractionation treatment such as concentration under reduced pressure, dilution, and filtration may be performed as appropriate to provide a fraction having an active substance for hair growth and hair restoration. . The degree of the fractionation process is arbitrary and is performed as necessary. That is, operations such as concentration, drying, or re-dissolution in water or a polar solvent, or purification treatment such as decolorization, deodorization, and desalting by known methods, fractionation treatment by column chromatography, etc. within a range that does not impair physiological effects Further purification by may be performed. Alternatively, the extracted solution may be subjected to a treatment such as concentration, spray drying, or freeze drying to obtain a dried product.

Although it does not specifically limit as a plant used as a raw material in order to prepare the plant extract of this invention, Most preferably, it selects from green tea processed from raw tea and tea leaves. Tea (scientific name: Camellia sinensis) is a plant belonging to the family Camellia. In the tea extract used in the present invention,
In addition to extracts obtained by direct extraction from tea leaves collected from tea trees, extracts obtained from green tea, which is a tea product, are also included. Tea may be subjected to an extraction process as it is, but in consideration of extraction efficiency, it is desirable to perform extraction after processing such as shredding, drying, and pulverization. The extraction method is not particularly limited, and the above method may be used.

Hair growth agents Hair growth and hair growth agents that are based on the function of the dermal papilla cells, which are responsible for the physiological mechanism of hair growth and hair growth, and the molecules that control them, can only be achieved with a hair growth and hair growth agent that contains active ingredients. . The hair restorer of the present invention completed from such a viewpoint contains one or more plant extracts that inhibit the action of the above FGF-5, or epigallocatechin and epigallocatechin gallate as active ingredients. Similarly, the plant extract can be used as a cosmetic composition containing one or more kinds of plant extracts, or epigallocatechin or epigallocatechin gallate as an active ingredient. These hair restorers and cosmetics are characterized in that the action of the active ingredients contained is supported by the molecular mechanism of hair growth, and the ingredients are derived from natural materials.

  As a hair growth agent of the present invention, a preferred embodiment is obtained by extracting tea with water or a solvent other than water, and containing epigallocatechin or epigallocatechin gallate, and containing fibroblast growth factor 5 (FGF-5). A hair restorer containing an extract characterized by exhibiting an activity that inhibits the action.

  Along with epigallocatechin, epigallocatechin gallate selected as an active ingredient, or one or more of the above plant extracts, the following components are produced by performing operations such as mixing in predetermined amounts in accordance with conventional methods. Can do.

The amount of the plant extract added to the total amount of the hair restorer varies depending on the type of plant used, the extraction solvent and extraction conditions, the treatment after extraction, and the like. The amount with respect to the total amount of the liquid hair restorer is preferably 0.001 to 5.0% by weight, more preferably 0.1 to 1% by weight in the state of the supernatant obtained by immersing the plant in the extraction solvent after the pulverization treatment and extracting. . Here, as described later, the state of the supernatant is based on a supernatant obtained by extracting 1 liter of an extraction solvent with respect to 100 g of a dried plant and leaving the extract at rest or after centrifugation. And If it is less than 0.001%, the desired hair growth promoting effect cannot be obtained. Conversely, if it exceeds 5%, the effect only reaches its peak, but the cost only increases. When the hair-growth agent is semi-solid or fluid, such as milk, jelly, or paste, the plant extract powder or the like may be added at a rate converted based on the amount of the supernatant. In the case where epigallocatechin or epigallocatechin gallate is blended as a simple substance, the amount added may be less than that of plant extracts.

  The above hair-restoring agents and cosmetics can take various dosage forms such as liquid, emulsion, gel, cream, ointment, foam, mist, and gel. Specifically, the hair restorer is provided in the form of hair tonic, hair gel, hair cream, hair treatment lotion, hair foam, hair mist, hair shampoo, hair rinse, and the like.

  In the hair restorer of the present invention, an oily component, a moisturizer such as hyaluronic acid and ceramide, an antioxidant such as α-tocopherol and an ascorbic acid derivative, in addition to the essential components described above, in a range not impairing the action of the extract. Addition for general hair growth agents such as surfactants, UV absorbers, local stimulants, hair follicle activators, fragrances, pigments, antibacterial and antifungal agents, pH adjusters, thickeners, excipients, and refreshing agents Items can be arbitrarily combined and appropriately contained. Furthermore, stabilizers such as chelating agents, transdermal absorption enhancers, and the like may be added. The same applies to cosmetics.

  In addition, by combining with other hair growth promoting components that are effective in normalizing the scalp state, a synergistic effect of hair growth and hair restoration effects can be achieved. This purpose includes conventional blood circulation promoters, antiseborrheic agents, keratolytic agents and the like.

  The hair restorer of the present invention promotes hair growth regardless of symptoms and constitution, and exhibits remarkable effects on marked improvement in hair removal, treatment, and various alopecia. The main target of application is human hair, but it can also be used to improve the fur of pets such as dogs, cats, canaries and parakeets. In addition, hair or fur products can be obtained by collecting hair or applying it to animals such as menyou, cashmere goat, alpaca, angora rabbit, mink, fox etc. It helps to improve the quality.

  The above cosmetics include general skin cosmetics, quasi-drugs, medicinal cosmetics, etc., oil / water type, water / oil type emulsified cosmetics, creams, cosmetic emulsions, oily cosmetics, It can be used in various forms and applications such as lotion, foundation, and pack agent.

The amount of the above extract of the present invention added to the total amount of cosmetics varies depending on the type of plant used, extraction solvent and extraction conditions, treatment after extraction, etc. According to the concentration in the case of the above hair restorer. That is, 0.001 to the total amount of liquid cosmetics
-5.0% by weight, preferably 0.1-1% by weight. When the cosmetic is semi-solid or fluid, such as milk, jelly, or paste, a plant extract powder or the like is added at a ratio converted based on the amount of the supernatant.

〔Example〕
EXAMPLES Hereinafter, although an Example is given and this invention is further demonstrated, this invention is not limited only to such an Example. Unless otherwise stated,% is% by weight.

Preparation of plant extract Epigallocatechin was a commercially available product from Wako Pure Chemical Industries, and epigallocatechin gallate was from SIGMA. As an extract of tea, the “tea extract” (Tokiwa Plant Chemistry Laboratories Co., Ltd., trade name “tea extract S”), which is recorded and marketed in the “Composition Standards by Cosmetic Variety (Cosmetics)”, is used as it is. Diluted as appropriate.

Detection of FGF-5 inhibitor using cultured cells FR-Ba / F3 cells responsive to FGF-5 and interleukin-3 (IL-3) were cultured in a culture medium containing 10% fetal bovine serum. . At least several doses of “tea extract” or epigallocatechin / epigallocatechin gallate were set by changing the dilution factor, and the effect of addition was examined from the dose-dependence. A 96-well culture plate (Falcon) was seeded at 10,000 cells / well, and 1 μg / ml FGF-5 or 10 ng / ml IL-3 (for positive control) was further diluted appropriately in the culture medium. A test substance (epigallocatechin, epigallocatechin gallate and “tea extract” of Example 1) and vehicle 50% ethanol were added and cultured for 3 days. Thereafter, a cell counting kit (manufactured by Wako Pure Chemical Industries, Ltd.) was added to each well, and after culturing for 3 hours, cell proliferation was examined using a microplate reader. The result is shown in FIG. Epigallocatechin, epigallocatechin gallate and “tea extract” all inhibited FGF-5-dependent growth of FR-Ba / F3 cells at a lower concentration than IL-3-dependent growth. From these results, it was shown that epigallocatechin, epigallocatechin gallate and tea extract have selective FGF-5 inhibitory activity.

Preparation of hairic agent 55 parts by weight of ethanol, 2 parts by weight of polyoxyethylene (8) oleyl alcohol ether, 36 parts by weight of purified water (or epigallocatechin or epigallocatechin gallate) obtained in Example 1 Mix 1 part by weight. Furthermore, according to a conventional method, a hair tonic type hair restorer is formed by blending appropriate amounts of a fragrance such as menthol, an antioxidant such as tocopherol acetate, a preservative such as salicylic acid, a colorant and a pH adjuster.

FIG. 1 shows the inhibitory effect of epigallocatechin, epigallocatechin gallate and “tea extract” on FGF-5-dependent and IL-3-dependent growth of FR-Ba / F3 cultured cells. The horizontal axis represents the concentration (μg / ml) of the substance as the analyte in the medium or the concentration of the plant extract (unit:% (V / V)). In both figures, FGF-5 and IL-3 are displayed as follows. ■: FGF-5 □: IL-3

Claims (4)

  A plant extract comprising epigallocatechin or epigallocatechin gallate and exhibiting an activity of inhibiting the action of fibroblast growth factor 5 (FGF-5).   The plant extract according to claim 1, which is obtained by extracting tea with water or a solvent other than water.   A hair restorer comprising epigallocatechin or epigallocatechin gallate as an active ingredient.   A hair restorer comprising the plant extract according to claim 1 or 2.

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