JP5711879B2 - Fibroblast growth factor-7 production promoter, scalp / hair cosmetic containing the same, and food and drink - Google Patents

Description

  The present invention relates to an FGF-7 production promoter that enhances the expression of fibroblast growth factor-7 (hereinafter referred to as FGF-7) in hair papilla cells, and hair growth / feeding containing the FGF-7 production promoter. The present invention relates to scalp and hair cosmetics effective for hair, and food and drink.

  Due to irregular lifestyles, changes in social environment such as stress, and changes in dietary habits, hair loss, hair loss, fine hair, and thinning hair are spreading not only to older men but also to young people and women. Social expectations for cosmetics for nurturing hair are growing. In response to this, many hair-growing agents for the purpose of promoting hair growth, moisturizing, preventing dandruff and itching, anti-inflammatory, and preventing hair loss have been put on the market.

  FGF-7 (also known as KGF), which is a kind of cell growth factor, is called keratinocyte growth factor, keratinocyte growth factor, fibroblast growth factor, etc., and is known to decrease in the thin hair region of the hair. .

  In this connection, a method for maintaining and promoting hair thickening by enhancing the expression of keratinocyte growth factor (FGF-7) in hair follicle cells, and FGF-7 containing adenosine or a derivative thereof. A document disclosing a composition that enhances expression (Patent Document 1), a document disclosing hair cosmetics that have a production promoting effect such as fibroblast growth factor-7 (FGF-7) by the combination of corosolic acid (patent) Document 2), a document (Patent Document 3) that discloses a method for treating chemotherapy-induced alopecia with KGF is known.

  FGF-7 is an extremely effective factor for improving fine hair and thinning hair, and various methods for enhancing the FGF-7 production promoting effect have been proposed. Even with these methods, fine hair and thinning hair can be improved. The effect was not sufficient.

WO2005 / 044205 WO 2006/090613 JP-T-2002-526026

  The present invention has been made to solve the above problems, and provides an FGF-7 production promoter having an excellent effect on FGF-7 production, and a scalp / hair cosmetic using the same, and drinking The purpose is to provide goods.

  As a result of intensive studies to solve the above problems, the present inventors have found that forskolin, a plant-derived component, has an effect of promoting FGF-7 production, and a specific plant extract is used in combination therewith. Thus, the present inventors have found that the ability of forskolin to produce FGF-7 dramatically increases.

  That is, the present invention provides an FGF-7 production promoter comprising (A) forskolin and (B) an ogi extract and / or a chimpi extract, and further an FGF-7 production promoting effect comprising the FGF-7 production promoter. The present invention provides cosmetics for scalp and hair, and food and drink.

  The FGF-7 production promoter comprising forskolin and an extract of an ogi and / or chimpi of the present invention has an effect of dramatically promoting the FGF-7 production ability of hair papilla cells. By using it in cosmetics for foods or foods and drinks, it is possible to prevent fine hair and thin hair, and to regenerate hair.

  The FGF-7 production promoter of the present invention comprises forskolin and at least one plant extract selected from an ogi extract and a chimpan extract. All of these are pharmaceuticals or plant extracts or components obtained by purifying them, and are generally used as components of pharmaceuticals, folk medicines, foods, and cosmetics.

  Forskolin used in the present invention is a substance whose structure has been separated, purified and determined from the extract of tuberous roots of Lamiaceae plants such as Coleus forskohlii. As forskolin, an extract from the root of the plant can be used, and further, a commercially available biochemical reagent can be used.

  The barley extract used in the present invention is an extract obtained from the dry roots of yellow-bellied, nayomous or other legumes.

  The chimney extract used in the present invention is an extract obtained from the mature peel of Citrus unshiu.

  Plant extract extracts such as ogi extract, chimpi extract, and Coleus forskori extract used in the present invention can be obtained by solvent extraction from various parts of the above-mentioned plants or crushed materials thereof.

  There are no particular limitations on the extraction solvent, water, lower monohydric alcohols such as methanol, ethanol, propanol, and butanol, polyhydric alcohols such as propylene glycol, dipropylene glycol, butylene glycol, glycerin, and 1,3-butanediol, acetic acid Esters such as methyl and ethyl acetate, ketones such as acetone and methyl ethyl ketone, halogenated hydrocarbons such as chloroform and carbon tetrachloride, ethers such as diethyl ether and tetrahydrofuran, hydrocarbons such as hexane, heptane and cyclohexane The organic solvent generally used can be mentioned, 1 type chosen from these, or 2 or more types can be mixed and used, and the mixed solvent of water and an organic solvent can be used.

  As the organic solvent used in combination with water, a lower alcohol having 4 or less carbon atoms is preferable, and a mixed solvent of water and ethanol is particularly preferable. When using the mixed solvent of water and an organic solvent, it is preferable that the mixing ratio shall be water: organic solvent = 10: 90-80: 20 on a mass basis. As extraction temperature, 15-100 degreeC is preferable and extraction at 15-50 degreeC is more preferable. By making extraction temperature 50 degrees C or less, decomposition | disassembly and alteration of a plant extract can be suppressed. Although there is no restriction | limiting in extraction time, when extraction temperature exceeds 50 degreeC, 30 second-5 hours are preferable, and when extracting at 50 degrees C or less, 5 minutes-7 days are preferable.

  Each plant extract can be used as a liquid product of a plant extract in which a solvent has been volatilized, a lyophilized powder product, or a liquid product dissolved in a solvent. When used as a liquid product dissolved in a solvent, a solvent having low skin irritation such as ethanol or 1,3-butylene glycol is preferably used as the extraction solvent, and a mixed solvent of these and water can also be used as the extraction solvent. .

  The FGF-7 production promoter of the present invention comprises the forskolin and at least one selected from an ogi extract and a chimpi extract. Forskolin alone has the effect of promoting FGF-7 production of dermal papilla cells, but because it is a substance that is sparingly soluble in water, the amount allocated to scalp and hair cosmetics is limited, and FGF-7 production of dermal papilla cells is limited. The promotion effect is also limited thereby. However, the combined use of the ogi extract and / or the chimney extract can provide an effect of dramatically promoting FGF-7 production in hair papilla cells.

  The FGF-7 production promoter of the present invention activates dermal papilla cells and contributes to hair thinning and thinning hair prevention and hair regeneration. The FGF-7 production promoter of the present invention is used as it is as a nourishing hair growth agent. Alternatively, it can be directly added to the scalp / hair cosmetic to directly activate the hair papilla cells of the scalp. The FGF-7 production promoter of the present invention can also be used in combination with a drug or the like used in a normal scalp / hair external preparation, and the effect of the present invention is more easily exhibited by the combined drug.

  There is no limitation on the dosage form of the scalp / hair cosmetic that can contain the FGF-7 production promoter of the present invention. For example, shampoo, conditioner, tonic, styling agent, paste agent, cream, gel, ointment, lotion, emulsion, It can be used on the scalp and hair as packs, powders, and haptics.

  There is no restriction | limiting in particular in the compounding quantity to the scalp and hair cosmetics of the FGF-7 production promoter of this invention, Although it can be used by arbitrary density | concentrations, the preferable compounding quantity of forskolin is 0. It is 001-2 mass%, More preferably, it is 0.1-1 mass%.

  The preferred compounding amounts of the ogi extract and the chimpi extract are both 0.001 to 5% by mass, and more preferably 0.5 to 5% by mass. If the blending amount of the plant extract is less than the lower limit, the hair-growth effect due to the promotion of FGF-7 production cannot be expected so much, and even if it is used in excess of the upper limit, the effect commensurate with the blending amount may not be obtained.

  The preferred blending amount of the ogi extract and the chimney extract when both the ogi extract and the chimney extract are used in combination with forskolin is 0.001 to 5% by mass, more preferably 0.5 to 5%, respectively. % By mass.

  There is no restriction | limiting in particular in the mixing | blending ratio of an ogi extract and a chimney extract when using an ogi extract and a chimpi extract simultaneously, It can mix | blend in arbitrary ratios.

  When the FGF-7 production promoter of the present invention is blended in a scalp / hair cosmetic, it can be dissolved in an organic solvent as required. As the organic solvent used here, the ethanol, 1,3-butylene glycol and the like having low skin irritation are preferable.

  In the scalp / hair cosmetic of the present invention, in addition to the FGF-7 production promoter, known functional ingredients conventionally used as a scalp / hair cosmetic, for example, within a range not impairing the effects of the present invention, , Moisturizers, emollients, blood circulation promoters, cell activators, antioxidants, anti-inflammatory agents, antibacterial agents, whitening agents, peroxide inhibitors and the like.

  Known functional ingredients include humectants such as glycerin, butylene glycol, urea and amino acids; emollients such as squalane, macadamia nut oil, olive oil, jojoba oil, and silicone oil; blood circulation promoters such as vitamin E and red pepper tincture; Cell activating agents such as dibutylhydroxytoluene (BHT), dibutylhydroxyanisole (BHA), tocopherol acetate, etc .; anti-inflammatory agents such as glycyrrhizin, allantoin; hinokitiol, benzalkonium chloride, chlorhexidine salt, parahydroxy Various functional components such as antibacterial agents such as benzoates, whitening agents such as ascorbic acid, peroxide inhibitors such as superoxide dismutase (SOD), etc. can be blended, ougon extract, ginkgo biloba extract, placenta extract , Lactic acid bacteria culture extraction Various extracts from plants, animals, and microorganisms like or the like can be used by adding without limitation.

  A known hair-growth component such as minoxidil can also be added to the scalp / hair cosmetic containing the FGF-7 production promoter of the present invention. Thereby, an effective hair-growth effect is expected.

  The FGF-7 production promoter of the present invention can also be blended in foods and drinks, and in addition to the FGF-7 production promoter, various materials usually used in foods can be used in combination. In addition to being used as a scalp / hair cosmetic, it is incorporated into the body as a food and drink to activate the hair papilla cells more and promote the production of FGF-7. There is no restriction | limiting in particular in the compounding quantity to food-drinks, Although it can use by arbitrary density | concentrations, the preferable compounding quantity of forskolin is 0.001-2 mass% in a dosage form, More preferably, it is 0.00. It is 1-1 mass%. The preferred compounding amounts of the ogi extract and the chimpi extract are both 0.001 to 5% by mass, and more preferably 0.5 to 5% by mass. If the blended amount of the plant extract is less than the lower limit, the hair-growing effect due to the promotion of FGF-7 production cannot be expected so much, and even if it is used in excess of the upper limit, an effect commensurate with the amount used may not be obtained.

  When both an ogi extract and a chimpi extract are used in combination with forskolin, a preferable blending amount of the ogi extract and the chimpi extract is 0.001 to 5% by mass in the dosage form, and more preferably 0.5 to 5% by mass, respectively. %. There is no particular limitation on the mixing ratio of the ogi extract and the chimpi extract when the ogi extract and the chimpi extract are used at the same time, and they can be mixed at an arbitrary ratio.

  There is no limitation on the dosage form of the food and drink of the present invention, and examples include solid preparations such as biscuits, cookies, candies, gums, powders, tablets, capsules, liquid preparations such as beverages, semi-solid preparations such as jelly, and the like. be able to.

  In addition, the scalp / hair cosmetics and foods and beverages of the present invention include base ingredients such as surfactants and fats and oils, and, if necessary, thickeners, preservatives, isotonic agents. Various additives conventionally used for scalp / hair cosmetics or foods and drinks, such as an agent, an antioxidant, an ultraviolet absorber, a chelating agent, a fragrance, and a coloring agent can be used in combination.

  The surfactant that can be used in the present invention is not particularly limited, and general nonionic surfactants, anionic surfactants, cationic surfactants, and amphoteric surfactants can be used.

  For example, alkylene oxide adduct of higher alcohol, alkylene oxide adduct of higher alkylamine, alkylene oxide adduct of higher fatty acid, alkylene oxide adduct of higher fatty acid amide, fatty acid ester of polyhydric alcohol, alkylene oxide adduct of hardened castor oil , Nonionic surfactants such as polyethylene oxide sorbitan alkyl esters, alkylene oxide adducts such as sterols; anions such as sodium alkyl sulfate, sodium alkyloxymethyl taurate, sodium α-olefin sulfonate, sodium polyoxyalkylene alkyl ether sulfate Surfactants; Cationic surfactants such as alkylpyridinium chloride and distearyl dimerylammonium chloride; Sodium aminopropionate, Al Le poly aminoethyl amphoteric surface active agents such as glycine and the like. And these surfactant can select and use 1 type (s) or 2 or more types.

  There are no particular restrictions on the base component that can be used in the present invention, and examples include generally known fats and oils such as olive oil, camellia oil, avocado oil, macadamia nut oil, apricot oil, jojoba oil, squalane, squalene, and horse oil. Can be used.

  The thickener that can be used in the present invention is not particularly limited, and examples thereof include polyvinyl alcohol, polyvinyl acrylamide, polyethylene glycol, and various derivatives thereof; celluloses such as hydroxyalkyl cellulose and derivatives thereof; dextran, gelatin, gum arabic, Gums such as tragacanth gum; water-soluble polymers such as carboxyvinyl polymer can be used.

  There is no restriction | limiting in particular in the preservative which can be used in this invention, For example, parahydroxybenzoic acid ester, paraoxybenzoic acid salt and its derivative (s), phenoxyethanol, hinokitiol, benzalkonium chloride, chlorhexidine salt etc. can be used.

  There is no restriction | limiting in particular as an isotonic agent which can be used in this invention, For example, inorganic salts, such as sodium chloride, potassium chloride, calcium chloride, can be used.

  There is no restriction | limiting in particular as an ultraviolet absorber which can be used in this invention, For example, a paraamino benzoic acid, a benzophenone series ultraviolet absorber, a benzotriazole type ultraviolet absorber etc. can be used.

  There is no restriction | limiting in particular as a chelating agent which can be used in this invention, For example, ethylenediaminetetraacetic acid, phytic acid, a citric acid, these water-soluble salts, etc. can be used.

  Hereinafter, the present invention will be described in more detail with reference to examples. However, the present invention is not limited to these examples.

-Production method of ogi extract 50g of roots of Echinocera were collected and shaken with 375ml of 50 mass% ethanol aqueous solution at 25 ° C for 24 hours. This was filtered, and water and ethanol were distilled off from the obtained extract under reduced pressure, followed by freeze-drying to obtain an ogi extract. The obtained barley extract was used in the following examples.
-Method for producing chimpi extract 50 g of persimmon peel was collected and shaken with 375 ml of a 50 mass% ethanol aqueous solution at 25 ° C for 24 hours. This was filtered, water and ethanol were distilled off from the resulting extract under reduced pressure, and then lyophilized to obtain a chimney extract. The obtained chimp extract was used in the following examples.
-Method for Producing Coleus Forskori Extract 50 g of tuberous root of Coleus forskori was collected and shaken with 375 ml of a 50 mass% aqueous ethanol solution at 25 ° C for 24 hours. This was filtered, and water and ethanol were distilled off from the resulting extract under reduced pressure, followed by lyophilization to obtain a Coleus forskori extract. The obtained Coleus forskori extract was used in the following examples.
・ Forskolin (reagent)
Forskolin manufactured by Sigma Aldrich Japan Co., Ltd. was used.

(I) FGF-7 production promoter Cultivation of cells Human hair hair papilla cells (HFDPC, 500,000 cells / ml / product, manufactured by TOYOBO) 250,000 cells containing GIBCO Dulbecco's modified Eagle medium (D-MEM) containing 10% fetal bovine serum (FBS) And inoculated in a petri dish at 37 ° C. under 5% CO ₂ for 6 days (medium was changed every other day).

  Subconfluent dermal papilla cells were detached by trypsin treatment, seeded with 4,000 cells in each well of a 24-well plate treated with bovine type I collagen, and cultured for 6 days (during this period, the medium was changed every other day). ).

  D-MEM medium (without FBS) appropriately added with forskolin, coleus forskori extract, ogi extract, and chimpi extract prepared as shown in Table 1 was added to the hair papilla cells cultured for 6 days and cultured for 24 hours.

  Forskolin (reagent) was dissolved in dimethyl sulfoxide and added to the medium so that the final concentration of dimethyl sulfoxide was 0.1% by mass. For the ogi extract, chimpi extract and coleus forskori extract, a solution of 25% by mass, 12.5% by mass, 10% by mass and 2.5% by mass was prepared using a 50% by mass ethanol aqueous solution, and the final concentration of ethanol was 0.2. It added in the culture medium so that it might become mass%. A medium supplemented with one or more of these was sterilized and filtered using a 0.22 μm membrane filter in a clean bench.

2. Measurement of FGF-7 Amount “Quantikine (registered trademark) Human KGF (FGF-7) IMMUNOASSAY KIT” (manufactured by R & D System) was used for quantification of FGF-7.

  To the well coated with the FGF-7 antibody, 100 μL of the medium after 24 hours of culture was added and allowed to stand at room temperature. Three hours after the completion of the antigen-antibody binding reaction, each well was washed 5 times with a washing solution attached to KIT to remove unreacted substances, and then 200 μL of KGF Conjugate reaction solution (FGF-7 detection antibody attached to KIT) was added. The detection antibody was allowed to bind to FGF-7 in the well by allowing to stand at room temperature for 105 minutes.

  After completion of the binding reaction, the unbound FGF-7 detection antibody is washed and removed, and 200 μL of a luminescent reagent (tetramethylbenzidine) is added to cause color development. After standing at room temperature for 30 minutes, 50 μL of the reaction stop solution supplied with KIT is added. It added and it was set as the measurement sample. Absorbance at an absorption wavelength of 450 nm (control wavelength: 540 nm) was measured using a microplate reader (Model 550, manufactured by Bio-Rad Laboratories), and the FGF-7 concentration in the measurement sample was calculated based on the calibration curve.

The results of the above test are shown in Table 1.

  As shown in Table 1, the production amount of FGF-7 was 1.5 times with 0.004 mass% forskolin and 3.2 times with 0.1 mass% forskolin.

  The amount of FGF-7 produced by the ogi extract is 0.1 to 0.05% by mass, 1.1 times, and the amount of FGF-7 produced by the chimney extract is only 1.2 times by 0.1 to 0.05% by mass. did not become.

  However, the amount of FGF-7 produced is increased by using an ogi extract and / or a chimpi extract in combination with forskolin, and the amounts of FGF-7 produced in Examples 3, 6, 9, and 13 in which 0.1% by mass of each is used in combination. Reached 6-7 times.

  As described above, a synergistic effect of promoting FGF-7 production in human hair dermal papilla cells was confirmed by using forskolin in combination with an ogi extract and / or a chimney extract.

(II) Scalp / Hair Cosmetic A FGF-7 production promoter comprising the plant extract of the present invention was blended in a scalp / hair cosmetic, and the effect on hair was confirmed.
The compositions of cosmetics (shampoos, conditioners, hair tonics) containing FGF-7 production promoters are shown in Table 2-1, Table 2-2, and Table 2-3. The plant extracts of ogi and chimpi were lyophilized, and reagents were used for forskolin. The unit of the blending amount is g, and the “remaining amount” of purified water in the table is an amount that makes the total amount 100 g.

1. Shampoo The component A in Table 2-1 was heated to 75 ° C. after mixing and cooled to 35 ° C. with stirring. Then, B component was added, continuing stirring, and pH was adjusted to 4.5-6, and the viscosity was adjusted to 1,000-2,000 mPa * s. Further, the C component was added to complete the adjustment.

2. Conditioner D component and E component of Table 2-2 were each heated to 75 degreeC, and E component was added little by little, stirring D component with a paddle mixer. Then, it cooled, stirring with a paddle mixer, and F component was added at 45 degrees C or less, and adjustment was complete | finished.

3. Hair tonic G component, H component, and I component of Table 2-3 were all heated to 40 ° C. and mixed.

Evaluation Regarding the scalp and hair cosmetics of Examples 14 to 43 and Comparative Examples 9 to 11, 5 men and women (11 groups x 3 prescriptions) each complaining of 30-50 years of hair thinning, totaling 330 people For shampoos and conditioners, use the appropriate amount for the hair at the time of daily bathing, and for hair tonics, use the appropriate amount for the scalp or hair after daily bathing or in the morning. Evaluation was performed based on the criteria. During this period, the subject of the shampoo monitor test used the shampoo of the present invention only for the shampoo, and used the hair shampoo other than that used in the usual manner.

  The conditioner and tonic monitor test subjects also used the usual hair cosmetics except for the conditioner and tonic, respectively.

  Evaluation is performed by measuring the diameter of 50 hairs before and after use with a thickness gauge 7301 (manufactured by Mitutoyo Co., Ltd.) and comparing the average hair diameter by using the temporal region as a test site. did.

  None of the patients complained of skin abnormalities during the period of use.

  The results are shown in Table 2-1, Table 2-2, and Table 2-3.

Effective: Increase in average hair diameter by 10% or more compared to before use Slightly effective: Increase in average hair diameter from 5% to less than 10% compared to before use No effect: Hair diameter compared to before use The average increase in hair is less than 5% Deterioration: The average hair diameter decreases by 5% or more compared to before use

In the scalp / hair cosmetics of Examples 14 to 43 containing the FGF-7 production promoter of the present invention, the hair diameter becomes thicker or slightly thicker, and an improvement in hair thinning is recognized. In Examples 23, 33, and 43 in which 5 % forskolin and 5% by weight ogi extract and chimpi extract were blended, the effects were confirmed for all subjects. On the other hand, in the scalp / hair cosmetics of Comparative Examples 9 to 11, almost no change was observed.

(III) Food / Beverage Formulation Examples Foods / drinks (jellys, supplements (tablets)) containing FGF-7 production promoters were prepared with the compositions shown in Tables 3-1 and 3-2. The adjustment method is as follows.
The plant extracts of ogi and chimpi were lyophilized, and reagents were used for forskolin.
The unit of the blending amount is g, and the “remaining amount” of purified water in the table is an amount that makes the total amount 100 g.

1. Jelly The J component in Table 3-1 was dissolved in 80 ° C. hot water of the L component, the K component was dissolved, and then mixed well. After pouring 10 g into the mold, it was hardened in a refrigerator to complete the adjustment.

2. Supplements (tablets)
What mixed M component and N component of Table 3-2 well was pressed and hardened using the tableting machine, and the tablet was formed.

For the foods and drinks of Evaluation Examples 44 to 63 and Comparative Examples 12 and 13, a monitor test was conducted on women in their 30s and 40s who have trouble with thinning hair.

  For each food and drink, 10 women (11 groups x 2 prescriptions) for a total of 220 people, for jelly, take 100g after daily dinner, for supplements (tablets), after daily dinner, 5 Except for taking tablets (1.5 g), the monitor test for normal life was continued for 6 months. The evaluation is performed by measuring the diameter of 50 hairs before and after use with a thickness gauge 7301 (manufactured by Mitutoyo Corporation) using the temporal region as a test site, and obtaining and comparing the average hair diameter. Verified.

  None of the patients complained of poor physical condition or abnormal skin during the period of use.

  The results are shown in Table 3-1 and Table 3-2.

Effective: Increase in average hair diameter by 10% or more compared to before use Slightly effective: Increase in average hair diameter from 5% to less than 10% compared to before use No effect: Hair diameter compared to before use The average increase in hair is less than 5% Deterioration: The average hair diameter decreases by 5% or more compared to before use

In the foods and drinks of Examples 44 to 63 formulated with the FGF-7 production promoter of the present invention, the hair diameter becomes thicker or slightly thicker, and an improvement in hair thinning is observed. In Examples 53 and 63 in which 5% by mass of an ogi extract and a chimpi extract were blended, the effect was confirmed for all subjects. On the other hand, in the foods and drinks of Comparative Examples 12 and 13, almost no change was observed in the hair.

  A plant extract composed of forskolin and an extract of ogi and / or chimpi is useful as an FGF-7 production promoter. The FGF-7 production promoter comprising forskolin of the present invention and an extract of ogi and / or chimpi extract increases the amount of FGF-7 produced in hair papilla cells, and as a result, prevention, alleviation and improvement of fine hair and thin hair. And hair regeneration, and can be used for various scalp / hair cosmetics and foods.

Claims (1)

  A fibroblast growth factor-7 (FGF-7) production promoter comprising (A) forskolin and (B) ogi extract and / or chimpi extract.