WO2017195841A1 - Hair pigment enhancer - Google Patents

Hair pigment enhancer Download PDF

Info

Publication number
WO2017195841A1
WO2017195841A1 PCT/JP2017/017756 JP2017017756W WO2017195841A1 WO 2017195841 A1 WO2017195841 A1 WO 2017195841A1 JP 2017017756 W JP2017017756 W JP 2017017756W WO 2017195841 A1 WO2017195841 A1 WO 2017195841A1
Authority
WO
WIPO (PCT)
Prior art keywords
hair
tannin
gallic acid
hair pigment
pigment enhancer
Prior art date
Application number
PCT/JP2017/017756
Other languages
French (fr)
Japanese (ja)
Inventor
幸蔵 佐藤
佐藤 忠久
哲郎 小島
Original Assignee
株式会社Nil
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from JP2017074040A external-priority patent/JP6562469B2/en
Application filed by 株式会社Nil filed Critical 株式会社Nil
Priority to CN201780028545.5A priority Critical patent/CN109069385B/en
Publication of WO2017195841A1 publication Critical patent/WO2017195841A1/en

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36Carboxylic acids; Salts or anhydrides thereof
    • A61K8/365Hydroxycarboxylic acids; Ketocarboxylic acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/192Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/21Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7024Esters of saccharides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36Carboxylic acids; Salts or anhydrides thereof
    • A61K8/368Carboxylic acids; Salts or anhydrides thereof with carboxyl groups directly bound to carbon atoms of aromatic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60Sugars; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/63Steroids; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00Preparations for care of the hair
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H13/00Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
    • C07H13/02Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids
    • C07H13/08Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids having the esterifying carboxyl radicals directly attached to carbocyclic rings

Definitions

  • the present invention relates to a hair pigment enhancer that activates cells involved in hair pigment formation to promote hair pigment formation.
  • Patent Document 1 discloses a melanin production promoter mainly composed of one or two or more plant extracts selected from ginseng, ginseng, tanjin, yucca, loquat, goldfish, and the like, and its melanin production promotion.
  • a gray hair improving agent comprising an agent is described.
  • Patent Document 2 discloses a composition for promoting tyrosinase activity or a composition for preventing gray hair, which comprises a plant extract as an active ingredient, and the active ingredients thereof are those belonging to the genus Salvia and Anemarrhena.
  • a composition comprising at least one extract derived from a plant belonging to the genus selected from the group consisting of the genus Ipomoea.
  • Patent Document 3 describes that 6-benzylaminopurine and Nanbange extract containing the substance are useful as an active ingredient of an external preparation for preventing white hair.
  • Patent Document 4 describes that sterubin and an extract of Yerba Santa and Chinese mugwort containing the substance are useful for the prevention and improvement of white hair.
  • Patent Document 5 describes that peonyol and a button pie extract containing the substance have a melanin producing ability, and blending this provides an external preparation excellent in the effect of improving white hair prevention.
  • the melanin production promoter and the gray hair prevention composition as described in the above patent document have certain effects such as a melanin production promotion effect, they are still not sufficient to prevent and improve gray hair, and are more excellent.
  • the emergence of materials having the effect of preventing and improving gray hair has been desired.
  • the present invention has been made in view of the above circumstances, promotes the production of hair pigments by acting on cells involved in hair pigment formation, and more than conventional melanin production promoters and white hair prevention compositions. It is an object to provide a hair pigment enhancer capable of exhibiting excellent white hair prevention / improvement ability.
  • gallic acid and derivatives thereof are used as a hair dyeing agent by forming a black complex with an iron salt or the like (see JP-A-2001-270812), and used as a hair-restoring agent (JP-A-7-206644).
  • 2003-321330 or use as an anti-stain (whitening) agent (Japanese Patent Publication Nos. 5-28203 and 2004-175688), but the effect of preventing gallic acid and its derivatives alone has been reported. There was no report that specifically stated about.
  • Japanese Patent Application Laid-Open No. 2003-321330 there is a general description of the effect of improving gray hair in the text, but there is no description that supports the effect in Examples and the like.
  • the present inventors have intensively studied polyphenol compounds containing gallic acid in a test system using a human skin three-dimensional culture model. Test results were obtained that the derivative was a drug that activated the cells involved in hair pigment formation and promoted hair pigment formation. And when the human test was conducted, the knowledge that there was an effect of preventing and improving gray hair was obtained, and the present invention was completed. *
  • the hair pigment enhancer of the present invention is characterized by being a one-part type containing at least one of gallic acid and a gallic acid derivative as an active ingredient.
  • the hair pigment enhancer of the present invention contains the above-mentioned active ingredient, the effect of preventing or improving gray hair can be obtained by applying it to the scalp.
  • the gallic acid derivative is preferably a compound represented by the following general formula (I) or a hydrolyzable tannin.
  • the hydrolyzable tannin includes one or more hydrolyzed tannins selected from the group consisting of tara tannin, chestnut tannin, milabram tannin, pentaploid tannin (tannic acid), oak tannin, and tea tannin. Preferably there is.
  • the hair pigment enhancer of the present invention preferably further contains at least one saponin.
  • saponins By containing saponins, the effect of preventing and improving gray hair can be further improved.
  • the hair pigment enhancer of the present invention preferably further contains at least one of saccharides and / or amino acids. By containing them, the effect of preventing and improving gray hair can be further improved.
  • the hair pigment enhancer of the present invention preferably further contains at least one of vitamins and / or coenzymes. By containing them, the effect of preventing and improving gray hair can be further improved.
  • the hair pigment enhancer of the present invention preferably further contains at least one mineral.
  • at least one mineral By containing minerals, the effect of preventing and improving gray hair can be further improved.
  • the hair pigment enhancer of the present invention preferably further contains a plant extract of the leguminous family Mucuna.
  • a plant extract of the leguminous subfamily Mucuna genus plant By containing the plant extract of the leguminous subfamily Mucuna genus plant, the effect of preventing and improving gray hair can be further enhanced.
  • gallic acid and gallic acid derivatives act on cells such as pigment stem cells, hair follicle stem cells, melanocytes, hair matrix cells, hair papilla cells, and melanosomes involved in melanogenesis. It is possible to provide an excellent composition for preventing and improving white hair in the form of a one-component type such as a solution, gel, mousse or cream containing the composition that promotes the production.
  • the hair pigment enhancer of the present invention There are mainly two types of melanin pigments: black-brown true melanin (eumelanin) and yellow-orange submelanin (pheomelanin). It becomes black hair, brown hair, blond hair, and red hair at the ratio and amount.
  • the two melanin pigments are involved in pigment stem cells, hair follicle stem cells, melanocytes, hair matrix cells, hair papilla cells, melanosomes, etc.
  • the hair pigment enhancer of the present invention It can act to promote the production of hair pigments, i.e. to enhance hair pigments. Thereby, gray hair can be prevented or the state of gray hair can be improved.
  • prevention and improvement of gray hair are not normally understood by those skilled in the art, and specifically, prevention refers to, for example, black hair, brown hair, blond hair, red hair, and the like.
  • Applying preventively to hair and its scalp, and preventing the applied hair from becoming gray or more fading improvement means, for example, gray hair or fading It is applied to the hair and the scalp of the hair to make it the original black hair, chestnut hair, blond hair, red hair, etc., or to a more colored state.
  • the active ingredient in the present invention is an ingredient capable of exhibiting the above-described functionality of enhancing hair pigment, and hair such as pigment stem cells, hair follicle stem cells, melanocytes, hair matrix cells, hair papilla cells, and melanosomes It is a component that acts on any cell involved in the pigment and promotes the production of the hair pigment.
  • the hair pigment enhancer is used in a one-pack form in any of a solution, gel, mousse, cream and the like, but preferably in a one-pack form (for example, tonic or a solution) of a solution (including a dispersion). Lotion).
  • the one-drug form means that a single drug containing the hair pigment enhancer of the present invention is used in the form of a solution, gel, mousse, cream, etc., instead of exerting an effect by applying a plurality of drugs to the scalp. Means that.
  • the active ingredient in the present invention is at least one of gallic acid and gallic acid derivatives, which will be described.
  • Gallic acid is 3,4,5-trihydroxybenzoic acid or a salt thereof, and is a compound having the following structure (1).
  • X + other than hydrone (H + ) is an organic or inorganic cation. Typical examples are ammonium ions or alkali metal ions.
  • a gallic acid derivative refers to a compound derived from gallic acid, but it may be a chemical synthetic derivative or a derivative isolated from a natural product.
  • the gallic acid derivative of the present invention is preferably a compound that can liberate gallic acid by hydrolysis.
  • Preferred compounds of the present invention that can be derived by chemical synthesis are represented by the following general formula (I).
  • Ar in the general formula (I) represents a substituted or unsubstituted aryl group, preferably a substituted or unsubstituted phenyl group.
  • the substituent that may be contained is not particularly limited, but it is preferable that the phenol generated by hydrolysis does not adversely affect the living body.
  • the substituent which may be included are an alkyl group, an aryl group, a hydroxyl group, a carboxylic acid group, or an ester group, and a particularly preferable group is a hydroxyl group or a carboxylic acid group.
  • a plurality of the same or different substituents may be substituted on the aryl group.
  • Tannin is derived from “tanning”. The tanning effect from raw leather to leather is based on the interaction between collagen and tannin in the raw leather (forms a poorly soluble composite film on the surface). Tannin is a group of natural polyphenols having a strong affinity for polymer compounds such as proteins and polysaccharides, basic compounds such as alkaloids, heavy metals, etc., and having a property of easily forming complexes with them.
  • the tannin includes condensed tannin and hydrolyzed tannin. Among them, hydrolyzable tannin releases gallic acid by hydrolysis and is a preferred tannin in the present invention. (Reference: Journal of Synthetic Organic Chemistry, 2004, 62, 94-101)
  • Preferred hydrolyzable tannins in the present invention are tara tannin, chestnut tannin, milabram tannin, pentaploid tannin (tannic acid), oak tannin, tea tannin, etc., and particularly preferred hydrolyzable tannins are tara tannin and pento tannin.
  • Tara tannin is a hydrolyzable tannin extracted from the leguminous pods of the legume plant (scientific name: Caesalpinia spinosa Kuntze. English: Tara West: Tara).
  • the content of gallic acid and gallic acid derivatives is not particularly limited, but in the form of a solution (for example, tonic or lotion), 0.01 to
  • the content is preferably 20% by mass, particularly preferably 0.1 to 10% by mass.
  • it is preferably 0.05 to 50% by mass, particularly preferably 0.1 to 30% by mass. .
  • the hair pigment enhancer of the present invention When used in the form of a one-part solution (including a dispersion), gel, mousse, cream, etc., it contains at least one saponin to prevent or improve white hair. It is preferable for improving.
  • Saponin is a general term for glycosides composed of sapogenin and sugar, and is broadly classified into oleanane, dammarane, and steroidal saponins.
  • oleanane-based saponins examples include saponins such as Onji, Mokutsu, Kyokyo, Psycho, Senega, Licorice, Goshitsu, Chikutsuninjin V, and Kiraya.
  • saponins such as Japanese ogi, and steroidal saponins include saponins such as Yamanoimo, Timo, Bakumondou, Digitalis, and Salsa.
  • preferred saponins are saikosaponins, quillaja saponins, chikutsuninjin saponins and sarsa saponins, particularly preferably quillaja saponins and salsa saponins.
  • the amount of these added is preferably 0.05 to 10% by mass, particularly preferably 0.1 to 8% by mass.
  • saccharides include monosaccharides, disaccharides, and polysaccharides, and monosaccharides and disaccharides are preferable, with glucose, lactose, galactose, mannose, sucrose, maltose, and the like being particularly preferable.
  • Amino acids include essential amino acids and non-essential amino acids.
  • Preferred amino acids include glycine, L-histidine, L-isoleucine, L-lysine, L-methionine, L-phenylalanine, L-threonine, and L-tryptophan. , L-valine, L-arginine, L-cystine, L-glutamine, L-serine, L-tyrosine and the like. The amount of these added is preferably 0.05 to 20% by mass, and particularly preferably 0.1 to 10% by mass.
  • Vitamins and coenzymes include vitamin A, vitamin D, vitamin E, vitamin B1 (thiamine), B2 (riboflavin), B3 (niacin), B5 (pantothenic acid), B6 (pyridoxine), B8 (folic acid), B12 (Cobalamin), biotin, choline, lipoic acid, inositol and the like.
  • Vitamin B1 (thiamine), B2 (riboflavin), B3 (niacin), B5 (pantothenic acid), B6 (pyridoxine), B8 (folic acid), biotin, choline, lipoic acid, inositol, myo-inositol and the like can be mentioned.
  • the amount of these added is preferably 0.01 to 2% by mass, particularly preferably 0.05 to 1% by mass.
  • Examples of minerals include chlorides such as calcium, sodium, potassium, magnesium, zinc, and aluminum, hydrochlorides, carbonates, bicarbonates, nitrates, sulfates, monohydrogen phosphates, dihydrogen phosphates, etc. be able to.
  • calcium is particularly important, preferably 50 ppm or more, and more preferably 100 to 500 ppm.
  • the total content of minerals is preferably 0.3 to 12% by mass, particularly preferably 0.5 to 8% by mass.
  • a plant extract of the leguminous family Tovicazura is preferable among the legumes, and particularly, for example, Mucuna pulluliens (scientific name: mucuna pruriens, Japanese name: velvet bean), Hashhou bean (scientific name: Stizolobium hassjoo), cat bean (scientific name: Mucuna cochinchinensis), Tokakazura (scientific name: Mucuna japonica) and the like are preferable.
  • plant extracts extracts of all parts such as flowers, leaves, stems, roots and the like are used, but seed extracts are most effective.
  • Extraction for the preparation of the plant extract can be performed according to methods well known to those skilled in the art, for example, crushed undried or dried seeds, and water, alcohols (methanol, ethanol, isopropanol, etc.) ), Diols (propylene glycol, butylene glycol, etc.) or a mixed solvent thereof, and the solvent is distilled off after the extraction treatment.
  • the amount of these plant extracts of the genus Mucuna varies depending on the amount of the active ingredient in the extract, but is preferably 0.05 to 10% by mass, particularly preferably 0.1 to 3% by mass.
  • ком ⁇ онентs such as surfactants, penetration enhancers, moisturizers, blood circulation promoters, anti-inflammatory agents, antioxidants, UV inhibitors, antibacterial agents, cell proliferation promoters, cells
  • a differentiation inducer such as a fragrance
  • blood circulation promoters such as piperine and capsaicin
  • cell growth promoters such as naringenin
  • cell differentiation inducers such as forskolin
  • oils such as salmon oil and squalane
  • enzymes such as tyrosinase.
  • the addition amount of other preferable components is 0.01 to 10% by mass.
  • the content is preferably 0.1 to 5% by mass.
  • the main solvent used is water, but when the additive is difficult to dissolve in water, it is recognized that it is added to cosmetics.
  • Any organic solvent can be used.
  • an organic solvent such as ethanol, isopropanol, propylene glycol, butylene glycol or glycerin can be used, but the amount used is preferably less than 20% by mass.
  • the effect of the hair pigment enhancer of the present invention is inhibited by the presence of heavy metal ions, particularly iron ions.
  • heavy metal ions particularly iron ions.
  • the iron ions mainly form a colored complex, so that gallic acid and gallic acid derivatives are insolubilized and the absorption from the pores is inhibited.
  • the solution including the dispersion
  • gel, mousse, cream and the like of the present invention it is preferable that substantially no heavy metal ions are contained.
  • the additive to the hair pigment enhancer of the present invention is a compound that is extremely hardly soluble in water, it is necessary to form a solution by nano-dispersing in water.
  • nano-dispersed to a volume average particle size of 200 nm or less the permeability from the scalp to the hair root is improved, and the function can be suitably used.
  • the volume average particle diameter is more preferably 100 nm or less from the viewpoint of improving permeability.
  • Example 1 to 14 and Comparative Examples 1 to 4 -Melanine pigment production test using a human skin three-dimensional culture model- (1) Preparation of skin external preparation for producing melanin pigment Sample solutions (see Table 1) of each Example and each Comparative Example were prepared with the following composition.
  • Kirayasaponin used Maruzen Pharmaceutical's Kirayanin D-100
  • Salsa saponin used Maruzen Pharmaceutical's Sarakeep ALS.
  • Kirayanin D-100 is composed of Kirayasaponin: 25% by mass, propylene glycol: 15% by mass, and water: 60% by mass.
  • Sarakeep ALS is salsasaponin: 7.5% by mass, water: 42.5% by mass.
  • Ethanol 50% by mass, so pure conversion was performed.
  • the other active ingredient used the commercially available reagent.
  • Hair artnic A was prepared by diluting 2 g of taratannin with 200 ml of water (1% by mass solution as taratannin).
  • Heartonic B was prepared by diluting 2 g of Taratannin and 8 g of Kirayanin D-100 solution (25% of Kirayasaponin, 60% water, 15% aqueous solution of propylene glycol by Maruzen Pharmaceutical) with 200 ml of water (Taratannin and Kiraya) 1% by weight solution as saponin).
  • Hair artic C was prepared using an aqueous solution not containing an active ingredient.
  • Example 15 Fifteen males and females aged 40-60 years, whose hairs were 1/5 to 1/4 of their hair, were divided into three groups of 10 (each group consists of 5 males and 5 females).
  • Example 15 the hair art A was used for 5 men, and in Example 16, the hair art A was used for 5 women.
  • Example 17 the hair art B was used for 5 men, and in Example 18, the hair art B was used for 5 women.
  • Comparative Example 5 the hair artic C was used for 5 men, and in the comparative example 6, the hair artic C was used for 5 women.
  • each hair artic 1 ml / time applied to the top of the head for 3 months, massage the applied part and penetrate the scalp I let you.
  • the effect was judged by taking a photograph of the part close to the hair root (in the range of 3 cm from the scalp) before and after the test, and measuring the ratio of white hair blackening. % was black when it was black, and x when it was less than 30%.
  • Example 19 Preparation of hair pigment enhancer dispersion and human test 1.0 g of forskolin (cell differentiation inducer), which is extremely hardly soluble in water, was dissolved in 5 g of ethanol. Impurities such as dust were removed by passing through a 45 ⁇ m microfilter (manufactured by Sartorius) to prepare a liquid Ia (6.1 g). Next, 1.0 g of Kirayasaponin (using saponin made by Tokyo Kasei), which is a nonionic surfactant, is dissolved in distilled water (92.9 g) and then passed through a 0.45 ⁇ m microfilter (Sartorius). Thus, an Ib liquid (93.9 g) was obtained by removing impurities such as dust.
  • forskolin cell differentiation inducer
  • Impurities such as dust were removed by passing through a 45 ⁇ m microfilter (manufactured by Sartorius) to prepare a liquid Ia (6.1 g).
  • Kirayasaponin using saponin made by
  • the Ia liquid and Ib liquid were nano-dispersed by the following procedure using a T-shaped micromixer.
  • 1/16 inch Teflon (registered trademark) tubes are connected to the two inlets of a T-shaped micromixer with an equivalent diameter of 250 ⁇ m, and syringes containing Ia and Ib solutions are connected to the ends of the tubes.
  • a 1/16 inch Teflon tube was connected to the outlet, and a sample bottle for collection was set at the outlet.
  • the liquid Ia was sent out at a liquid sending speed of 0.20 g / min and the liquid Ib was fed out at a liquid feeding speed of 3.12 g / min for 20 minutes.
  • the transparent dispersion collected in the sample bottle was designated as Sample 15.
  • the concentration of taratannin is 1.0% by mass
  • the concentration of forskolin is 0.1% by mass
  • the concentration of Quillajasaponin is 1.0% by mass
  • the concentration of ethanol is 5.0% by mass.
  • a liquid Ia ′ (5.1 g), which is an ethanol solution containing forskolin, was prepared in the same manner except that taratannin was removed from the liquid Ia. Further, an Ib ′ solution (94.9 g) containing Kirayasaponin was prepared in the same manner except that the amount of water was increased by 1 g. They were set in a T-shaped micromixer in the same manner as described above, and the Ia ′ solution was sent out at a feed rate of 0.17 g / min and the Ib ′ solution was sent out at a feed rate of 3.15 g / min for 20 minutes. The transparent dispersion collected in the sample bottle was used as comparative sample 5.
  • the concentration of forskolin is 0.1% by mass
  • the concentration of Quillajasaponin is 1.0% by mass
  • the concentration of ethanol is 5.0% by mass.
  • the effect was judged by taking a photograph of the part close to the hair root (range 3 cm from the scalp) before and after the test, and measuring the ratio of white hair darkening. % was black when it was black, and x when it was less than 20%.
  • the results are shown in Table 4. It was confirmed that the tala tannin of the present invention has a clear gray hair improving effect even in elderly women with a high gray hair rate. In addition, it was confirmed that the effect of improving gray hair was improved by the addition of Kirayasaponin, sugars, amino acids, vitamins, coenzymes, minerals and the like. Furthermore, it was confirmed that the effect of improving gray hair was further enhanced when used together with the seed extract of Mucuna pullulence, a plant belonging to the genus Mucuna.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Birds (AREA)
  • Emergency Medicine (AREA)
  • Molecular Biology (AREA)
  • Cosmetics (AREA)

Abstract

Provided is a hair pigment enhancer that can act on cells participating in hair pigmentation and thus promote the synthesis of hair pigment to thereby prevent and/or reverse gray hair. A one-pack type hair pigment enhancer that comprises, as an active ingredient, at least one member selected from among gallic acid and gallic acid derivatives. As the gallic acid derivative, a hydrolyzed tannin such as Tara tannin or gallnut tannin is preferred. It is preferred that the hair pigment enhancer further comprises saccharides, amino acids, vitamins, coenzymes, minerals, saponins such as Quillaja saponin, an extract of seeds of a plant belonging to the genus Mucuna of Faboideae, etc.

Description

毛髪色素増強剤Hair pigment enhancer
 本発明は、毛髪色素形成に関与する細胞を活性化して毛髪色素の形成を促進する毛髪色素増強剤に関する。 The present invention relates to a hair pigment enhancer that activates cells involved in hair pigment formation to promote hair pigment formation.
 従来、老化(加齢)に伴う白髪化に対し、髪を黒髪へと変化させる方法として、染毛が主として行われてきた。ところが近年においては、白髪化は、頭皮の毛包中の毛髪色素細胞が老化やストレスにより機能が低下することで起こることが分かってきた。そして、白髪化については、毛髪色素細胞におけるメラニン産生を促進させる成分が見出され、そのような成分を用いた白髪防止用組成物が提案されている(特許文献1~5参照)。 Conventionally, hair dyeing has been mainly performed as a method of changing hair to black hair against graying due to aging (aging). In recent years, however, it has been found that gray hair occurs when the function of hair pigment cells in the hair follicles of the scalp decreases due to aging or stress. With regard to graying, components that promote melanin production in hair pigment cells have been found, and compositions for preventing white hair using such components have been proposed (see Patent Documents 1 to 5).
 例えば、特許文献1には、オタネニンジン、田七人参、タンジン、ユッカ、ビワ、およびキンギンカ等から選ばれる1種又は2種以上の植物抽出物を主成分とするメラニン産生促進剤及びそのメラニン産生促進剤からなる白髪改善剤が記載されている。
 また、特許文献2には、植物抽出物を有効成分として含んでなるチロシナーゼ活性促進用組成物ないしは白髪防止用組成物であって、その有効成分が、アキノタムラソウ属(Salvia)、ハナスゲ属(Anemarrhena)及びサツマイモ属(Ipomoea)からなる群より選ばれる属に属する植物由来の抽出物の少なくとも1種からなる組成物が記載されている。
 また、特許文献3には、6-ベンジルアミノプリン及び該物質を含むナンバンゲ抽出物が、白髪防止用外用剤の有効成分として有用である旨記載されている。
 また、特許文献4には、ステルビン及び該物質を含むヤーバサンタ及びカワラヨモギ抽出物が、白毛の予防・改善用に有用である旨記載されている。
 特許文献5には、ペオノール及び該物質を含むボタンピ抽出物がメラニン産生能を有し、これを配合することで白髪防止改善効果に優れた外用剤を提供することが記載されている。
For example, Patent Document 1 discloses a melanin production promoter mainly composed of one or two or more plant extracts selected from ginseng, ginseng, tanjin, yucca, loquat, goldfish, and the like, and its melanin production promotion. A gray hair improving agent comprising an agent is described.
Patent Document 2 discloses a composition for promoting tyrosinase activity or a composition for preventing gray hair, which comprises a plant extract as an active ingredient, and the active ingredients thereof are those belonging to the genus Salvia and Anemarrhena. And a composition comprising at least one extract derived from a plant belonging to the genus selected from the group consisting of the genus Ipomoea.
Patent Document 3 describes that 6-benzylaminopurine and Nanbange extract containing the substance are useful as an active ingredient of an external preparation for preventing white hair.
Patent Document 4 describes that sterubin and an extract of Yerba Santa and Chinese mugwort containing the substance are useful for the prevention and improvement of white hair.
Patent Document 5 describes that peonyol and a button pie extract containing the substance have a melanin producing ability, and blending this provides an external preparation excellent in the effect of improving white hair prevention.
特開2001-288098号公報JP 2001-288098 A 特開平9-263540号公報JP-A-9-263540 特開2013-159592号公報JP 2013-155952 A 特開2013-147491号公報JP 2013-147491 A 特開2005-015472号公報JP 2005-015472 A
 しかしながら、上記特許文献に記載のようなメラニン産生促進剤や白髪防止組成物は、メラニン産生促進効果等の一定の効果を有するものの、未だ白髪を防止・改善するには十分ではなく、さらに優れた白髪防止・改善効果を有する素材の出現が望まれていた。 However, although the melanin production promoter and the gray hair prevention composition as described in the above patent document have certain effects such as a melanin production promotion effect, they are still not sufficient to prevent and improve gray hair, and are more excellent. The emergence of materials having the effect of preventing and improving gray hair has been desired.
 本発明は、上記の事情に鑑みてなされたものであり、毛髪色素形成に関与する細胞に作用して毛髪色素の生成を促し、従来のメラニン産生促進剤や白髪防止組成物に比べて、より優れた白髪防止・改善能を発揮することができる、毛髪色素増強剤を提供することを課題とする。 The present invention has been made in view of the above circumstances, promotes the production of hair pigments by acting on cells involved in hair pigment formation, and more than conventional melanin production promoters and white hair prevention compositions. It is an object to provide a hair pigment enhancer capable of exhibiting excellent white hair prevention / improvement ability.
 従来、没食子酸およびその誘導体は、鉄塩等と黒色の錯体を形成させて染毛する薬剤としての使用(特開2001-270812号参照)、養育毛剤としての使用(特開平7-206644号、同2003-321330号)、またはシミ防止(美白)剤としての使用(特公平5-28203号、同2004-175688号)が報告されているが、没食子酸およびその誘導体のみでの白髪防止効果について具体的に述べた報告はなかった。前記の特開2003-321330号において、本文中に白髪改善効果の一般的記載があるが、実施例等でその効果を裏付ける記載はなかった。 Conventionally, gallic acid and derivatives thereof are used as a hair dyeing agent by forming a black complex with an iron salt or the like (see JP-A-2001-270812), and used as a hair-restoring agent (JP-A-7-206644). , 2003-321330), or use as an anti-stain (whitening) agent (Japanese Patent Publication Nos. 5-28203 and 2004-175688), but the effect of preventing gallic acid and its derivatives alone has been reported. There was no report that specifically stated about. In the above Japanese Patent Application Laid-Open No. 2003-321330, there is a general description of the effect of improving gray hair in the text, but there is no description that supports the effect in Examples and the like.
 本発明者らは、今回、高い毛髪色素増強能を有する薬剤の探索の一環として、没食子酸類を含むポリフェノール化合物類についてヒト皮膚三次元培養モデルを利用した試験系で鋭意検討したところ、没食子酸やその誘導体が、毛髪色素形成に関与する細胞を活性化して毛髪色素形成を促進する薬剤であるという試験結果を得た。そしてヒト試験を行ったところ白髪防止・改善効果があるとの知見を得て、本発明を完成するに至った。  As a part of the search for a drug having a high hair pigment enhancing ability, the present inventors have intensively studied polyphenol compounds containing gallic acid in a test system using a human skin three-dimensional culture model. Test results were obtained that the derivative was a drug that activated the cells involved in hair pigment formation and promoted hair pigment formation. And when the human test was conducted, the knowledge that there was an effect of preventing and improving gray hair was obtained, and the present invention was completed. *
 本発明の毛髪色素増強剤は、有効成分として、没食子酸及び没食子酸誘導体の少なくとも1種を含む、一剤型であることを特徴とする。本発明の毛髪色素増強剤は、上記有効成分を含むことにより、頭皮に付与することで白髪防止・改善効果が得られる。 The hair pigment enhancer of the present invention is characterized by being a one-part type containing at least one of gallic acid and a gallic acid derivative as an active ingredient. When the hair pigment enhancer of the present invention contains the above-mentioned active ingredient, the effect of preventing or improving gray hair can be obtained by applying it to the scalp.
 前記没食子酸誘導体としては、より具体的には、下記一般式(I)で表される化合物、又は加水分解型タンニンであることが好ましい。当該加水分解型タンニンとしては、タラタンニン、チェストナットタンニン、ミラボラムタンニン、五倍子タンニン(タンニン酸)、オークタンニン、及び茶タンニンからなる群から選ばれる1種又は2種以上の加水分解型タンニンであることが好ましい。 More specifically, the gallic acid derivative is preferably a compound represented by the following general formula (I) or a hydrolyzable tannin. The hydrolyzable tannin includes one or more hydrolyzed tannins selected from the group consisting of tara tannin, chestnut tannin, milabram tannin, pentaploid tannin (tannic acid), oak tannin, and tea tannin. Preferably there is.
Figure JPOXMLDOC01-appb-C000002
Figure JPOXMLDOC01-appb-C000002
 本発明の毛髪色素増強剤は、さらに、サポニン類の少なくとも1種を含むことが好ましい。サポニン類を含むことで、白髪防止・改善効果をより向上することができる。 The hair pigment enhancer of the present invention preferably further contains at least one saponin. By containing saponins, the effect of preventing and improving gray hair can be further improved.
 本発明の毛髪色素増強剤は、さらに、糖類及び/又はアミノ酸類の少なくとも1種を含むことが好ましい。それらを含むことで、白髪防止・改善効果をより向上することができる。 The hair pigment enhancer of the present invention preferably further contains at least one of saccharides and / or amino acids. By containing them, the effect of preventing and improving gray hair can be further improved.
 本発明の毛髪色素増強剤は、さらに、ビタミン類及び/又は補酵素類の少なくとも1種を含むことが好ましい。それらを含むことで、白髪防止・改善効果をより向上することができる。 The hair pigment enhancer of the present invention preferably further contains at least one of vitamins and / or coenzymes. By containing them, the effect of preventing and improving gray hair can be further improved.
 本発明の毛髪色素増強剤は、さらに、ミネラル類の少なくとも1種を含むことが好ましい。ミネラル類を含むことで、白髪防止・改善効果をより向上することができる。 The hair pigment enhancer of the present invention preferably further contains at least one mineral. By containing minerals, the effect of preventing and improving gray hair can be further improved.
 本発明の毛髪色素増強剤は、さらに、マメ亜科ムクナ属植物の植物エキスを含むことが好ましい。マメ亜科ムクナ属植物の植物エキスを含むことで、白髪防止・改善効果をより増強することができる。 The hair pigment enhancer of the present invention preferably further contains a plant extract of the leguminous family Mucuna. By containing the plant extract of the leguminous subfamily Mucuna genus plant, the effect of preventing and improving gray hair can be further enhanced.
 本発明の毛髪色素増強剤において、没食子酸や没食子酸誘導体は、メラニン形成に関与する色素幹細胞、毛包幹細胞、メラノサイト、毛母細胞、毛乳頭細胞、メラノソーム等の細胞に作用して毛髪色素の生成を促し、それを含有する溶液、ジェル、ムース、クリーム等の一剤型の形態での優れた白髪防止・改善用組成物を提供することができる。 In the hair pigment enhancer of the present invention, gallic acid and gallic acid derivatives act on cells such as pigment stem cells, hair follicle stem cells, melanocytes, hair matrix cells, hair papilla cells, and melanosomes involved in melanogenesis. It is possible to provide an excellent composition for preventing and improving white hair in the form of a one-component type such as a solution, gel, mousse or cream containing the composition that promotes the production.
実施例4,6,7,8,11及び比較例1,3におけるMatTek社製ヒト皮膚三次元培養モデルMEL-300Aカップ写真。Photographs of human skin three-dimensional culture model MEL-300A made by MatTek in Examples 4, 6, 7, 8, 11 and Comparative Examples 1 and 3.
 以下、本発明の具体的な実施形態について詳細に説明するが、本発明は以下の実施形態に何ら限定されるものではなく、本発明の目的の範囲内において、適宜変更を加えて実施することができる。 Hereinafter, specific embodiments of the present invention will be described in detail. However, the present invention is not limited to the following embodiments, and may be implemented with appropriate modifications within the scope of the object of the present invention. Can do.
 まず、本発明の毛髪色素増強剤によって奏される作用効果について説明する。毛髪色素には、主に黒褐色の真性メラニン(ユーメラニン)と、黄橙色の亜メラニン(フェオメラニン)の2種類のメラニン色素がある。その割合と量で黒髪、栗毛、金髪、赤毛になる。二つのメラニン色素形成に関与するのは、色素幹細胞、毛包幹細胞、メラノサイト、毛母細胞、毛乳頭細胞、メラノソーム等の細胞であり、本発明の毛髪色素増強剤によれば、それらの細胞に作用して毛髪色素の生成を促し、すなわち毛髪色素の増強を促すことができる。これにより、白髪を防止したり、白髪の状態を改善したりすることができる。なお、本明細書において、白髪の防止や改善とは、通常当業者に理解されるのと異ならずに、具体的には、防止とは、例えば、黒髪、栗毛、金髪、赤毛等の状態の毛髪やその頭皮部に予防的に適用して、その適用を受けた毛髪が白髪やより退色した状態になるのを防ぐこと等を意味し、改善とは、例えば、白髪や退色した状態となった毛髪やその頭皮部に適用して、もとの黒髪、栗毛、金髪、赤毛等の状態にしたり、より有色に着色した状態にしたりすること等を意味している。 First, the function and effect exhibited by the hair pigment enhancer of the present invention will be described. There are mainly two types of melanin pigments: black-brown true melanin (eumelanin) and yellow-orange submelanin (pheomelanin). It becomes black hair, brown hair, blond hair, and red hair at the ratio and amount. The two melanin pigments are involved in pigment stem cells, hair follicle stem cells, melanocytes, hair matrix cells, hair papilla cells, melanosomes, etc. According to the hair pigment enhancer of the present invention, It can act to promote the production of hair pigments, i.e. to enhance hair pigments. Thereby, gray hair can be prevented or the state of gray hair can be improved. In the present specification, prevention and improvement of gray hair are not normally understood by those skilled in the art, and specifically, prevention refers to, for example, black hair, brown hair, blond hair, red hair, and the like. Applying preventively to hair and its scalp, and preventing the applied hair from becoming gray or more fading, improvement means, for example, gray hair or fading It is applied to the hair and the scalp of the hair to make it the original black hair, chestnut hair, blond hair, red hair, etc., or to a more colored state.
 よって、本発明における有効成分とは、上記毛髪色素増強の機能性を発揮することができる成分のことであり、色素幹細胞、毛包幹細胞、メラノサイト、毛母細胞、毛乳頭細胞、メラノソーム等の毛髪色素に関与するいずれかの細胞に作用して、その毛髪色素の産生を促進する成分である。 Therefore, the active ingredient in the present invention is an ingredient capable of exhibiting the above-described functionality of enhancing hair pigment, and hair such as pigment stem cells, hair follicle stem cells, melanocytes, hair matrix cells, hair papilla cells, and melanosomes It is a component that acts on any cell involved in the pigment and promotes the production of the hair pigment.
 本発明において、毛髪色素増強剤は溶液、ジェル、ムース、クリーム等のいずれかで一剤型の形態で用いられるが、好ましくは溶液(分散液を含む)の一剤型の形態(例えばトニックやローション)で用いられる。尚、一剤型の形態とは、複数の薬剤を頭皮にかけて効果を発揮させるのではなく、本発明の毛髪色素増強剤を含む単一の薬剤を溶液、ジェル、ムース、クリーム等の形態で用いることを意味する。 In the present invention, the hair pigment enhancer is used in a one-pack form in any of a solution, gel, mousse, cream and the like, but preferably in a one-pack form (for example, tonic or a solution) of a solution (including a dispersion). Lotion). In addition, the one-drug form means that a single drug containing the hair pigment enhancer of the present invention is used in the form of a solution, gel, mousse, cream, etc., instead of exerting an effect by applying a plurality of drugs to the scalp. Means that.
 本発明における有効成分は、没食子酸及び没食子酸誘導体の少なくとも1種であるがそれらについて説明する。没食子酸は3,4,5-トリヒドロキシ安息香酸またはその塩であり、下記(1)の構造を有する化合物である。ヒドロン(H)以外のXは、有機もしくは無機のカチオンである。代表的なものはアンモニウムイオンもしくはアルカリ金属イオンである。 The active ingredient in the present invention is at least one of gallic acid and gallic acid derivatives, which will be described. Gallic acid is 3,4,5-trihydroxybenzoic acid or a salt thereof, and is a compound having the following structure (1). X + other than hydrone (H + ) is an organic or inorganic cation. Typical examples are ammonium ions or alkali metal ions.
Figure JPOXMLDOC01-appb-C000003
Figure JPOXMLDOC01-appb-C000003
 没食子酸誘導体は、没食子酸から誘導される化合物を指すが、それらは化学合成による誘導体でも、天然物から単離される誘導体でも構わない。本発明の没食子酸誘導体は加水分解により没食子酸を遊離できる化合物であることが好ましい。化学合成で誘導できる本発明の好ましい化合物は下記一般式(I)で表される。 A gallic acid derivative refers to a compound derived from gallic acid, but it may be a chemical synthetic derivative or a derivative isolated from a natural product. The gallic acid derivative of the present invention is preferably a compound that can liberate gallic acid by hydrolysis. Preferred compounds of the present invention that can be derived by chemical synthesis are represented by the following general formula (I).
Figure JPOXMLDOC01-appb-C000004
Figure JPOXMLDOC01-appb-C000004
 一般式(I)におけるArは、置換、無置換のアリール基を表し、好ましくは置換、無置換のフェニル基である。置換のアリール基の場合、有してもよい置換基に特に制限はないが加水分解して生ずるフェノールが生体に悪影響を与えないものであることが好ましい。有してもよい置換基の好ましい具体例をあげれば、アルキル基、アリール基、水酸基、カルボン酸基、もしくはエステル基であり、特に好ましい基は水酸基もしくはカルボン酸基である。置換基は同一のものもしくは異なるものがアリール基に複数置換していてよい。 Ar in the general formula (I) represents a substituted or unsubstituted aryl group, preferably a substituted or unsubstituted phenyl group. In the case of a substituted aryl group, the substituent that may be contained is not particularly limited, but it is preferable that the phenol generated by hydrolysis does not adversely affect the living body. Preferable specific examples of the substituent which may be included are an alkyl group, an aryl group, a hydroxyl group, a carboxylic acid group, or an ester group, and a particularly preferable group is a hydroxyl group or a carboxylic acid group. A plurality of the same or different substituents may be substituted on the aryl group.
 一般式(I)で表される好ましい化合物の具体例を以下に示すが、これらに限定されるものではない。 Specific examples of preferred compounds represented by the general formula (I) are shown below, but are not limited thereto.
Figure JPOXMLDOC01-appb-C000005
Figure JPOXMLDOC01-appb-C000005
 天然物から単離される没食子酸誘導体の中で、本発明において特に好ましい化合物は加水分解型タンニンである。タンニンの語源は、「皮なめし(tanning)」に由来している。生皮から皮革への皮なめし効果は、生皮のコラーゲンとタンニンとの相互作用(表面に難溶性複合体皮膜を形成)に基づくものである。タンニンは、タンパク質や多糖体などの高分子化合物、アルカロイドなどの塩基性化合物、重金属などに強い親和性を示し、それらとの複合体を形成しやすい性質を持つ天然ポリフェノール群である。そのタンニンには縮合型タンニンと加水分解型タンニンがある。その中で加水分解型タンニンは加水分解により没食子酸を遊離するものであり、本発明において好ましいタンニンである。(参照:有機合成化学協会誌、2004、62、94-101) Among gallic acid derivatives isolated from natural products, a particularly preferred compound in the present invention is hydrolyzed tannin. Tannin is derived from “tanning”. The tanning effect from raw leather to leather is based on the interaction between collagen and tannin in the raw leather (forms a poorly soluble composite film on the surface). Tannin is a group of natural polyphenols having a strong affinity for polymer compounds such as proteins and polysaccharides, basic compounds such as alkaloids, heavy metals, etc., and having a property of easily forming complexes with them. The tannin includes condensed tannin and hydrolyzed tannin. Among them, hydrolyzable tannin releases gallic acid by hydrolysis and is a preferred tannin in the present invention. (Reference: Journal of Synthetic Organic Chemistry, 2004, 62, 94-101)
 本発明において好ましい加水分解型タンニンは、タラタンニン、チェストナットタンニン、ミラボラムタンニン、五倍子タンニン(タンニン酸)、オークタンニン、茶タンニン等であり、特に好ましい加水分解型タンニンは、タラタンニンと五倍子タンニン(タンニン酸)である。タラタンニンは、南米ペルーで生育するタラ(学名:Caesalpinia spinosa Kuntze. 英語:Tara 西語:Tara)というマメ科の植物の実のさや(莢)から抽出される加水分解型タンニンであり、五倍子タンニンは、ウルシ科の落葉小喬木、ヌルデ並びに同属植物にアブラムシ科の昆虫(ヌルデニミミブシアブラムシ)が刺傷を作ることによって生じた虫こぶを乾燥させたものから得られる加水分解型タンニンである。両者とも多くの化合物の混合物であるが(概略の構造を下記に示した)、いずれもアリールエステルの形で結合した没食子酸部位を含有することが特徴である。 Preferred hydrolyzable tannins in the present invention are tara tannin, chestnut tannin, milabram tannin, pentaploid tannin (tannic acid), oak tannin, tea tannin, etc., and particularly preferred hydrolyzable tannins are tara tannin and pento tannin. (Tannic acid). Tara tannin is a hydrolyzable tannin extracted from the leguminous pods of the legume plant (scientific name: Caesalpinia spinosa Kuntze. English: Tara West: Tara). Is a hydrolyzable tannin obtained by drying a galling produced by the aphid insect (Nurdenimimibushiburamushi) stings on the deciduous deciduous oak tree, Nurde, and the same genus plant. Both are mixtures of many compounds (schematic structures are shown below), both of which are characterized by containing gallic acid moieties linked in the form of aryl esters.
Figure JPOXMLDOC01-appb-C000006
Figure JPOXMLDOC01-appb-C000006
 本発明の毛髪色素増強剤において、没食子酸および没食子酸誘導体(タラタンニンやタンニン酸など)の含有量には特に制限はないが、溶液(例えばトニックやローション)の形態の場合、0.01~20質量%であることが好ましく、特に好ましくは0.1~10質量%である。ジェル又はクリームの形態の場合は、沈殿等の問題がないためより高い含有量が可能となるが、好ましくは0.05~50質量%であり、特に好ましくは0.1~30質量%である。 In the hair pigment enhancer of the present invention, the content of gallic acid and gallic acid derivatives (such as taratannin and tannic acid) is not particularly limited, but in the form of a solution (for example, tonic or lotion), 0.01 to The content is preferably 20% by mass, particularly preferably 0.1 to 10% by mass. In the case of a gel or cream, there is no problem such as precipitation, so a higher content is possible. However, it is preferably 0.05 to 50% by mass, particularly preferably 0.1 to 30% by mass. .
 本発明の毛髪色素増強剤が一剤型の溶液(分散液を含む)、ジェル、ムース、クリーム等の形態で用いられる場合、サポニン類の少なくとも一つを含有することがその白髪防止・改善効果を向上させるために好ましい。サポニンとはサポゲニンと糖から構成される配糖体の総称であり、オレアナン系、ダンマラン系、およびステロイド系サポニンに大別される。 When the hair pigment enhancer of the present invention is used in the form of a one-part solution (including a dispersion), gel, mousse, cream, etc., it contains at least one saponin to prevent or improve white hair. It is preferable for improving. Saponin is a general term for glycosides composed of sapogenin and sugar, and is broadly classified into oleanane, dammarane, and steroidal saponins.
 オレアナン系サポニンとしては、オンジ、モクツウ、キキョウ、サイコ、セネガ、カンゾウ、ゴシツ、チクセツニンジンV、およびキラヤ等のサポニンがあり、ダンマラン系サポニンとしては、ニンジン、タイソウ、チクセツニンジンIII、トラガント、およびオウギ等のサポニンがあり、ステロイド系サポニンとしては、ヤマノイモ、チモ、バクモンドウ、ジギタリス、およびサルサ等のサポニンがある。 Examples of oleanane-based saponins include saponins such as Onji, Mokutsu, Kyokyo, Psycho, Senega, Licorice, Goshitsu, Chikutsuninjin V, and Kiraya. And saponins such as Japanese ogi, and steroidal saponins include saponins such as Yamanoimo, Timo, Bakumondou, Digitalis, and Salsa.
 本発明において、好ましいサポニンはサイコサポニン、キラヤサポニン、チクセツニンジンサポニンおよびサルササポニンであり、特に好ましくはキラヤサポニンとサルササポニンである。これらの添加量は、0.05~10質量%であることが好ましく、特に好ましくは0.1~8質量%である。 In the present invention, preferred saponins are saikosaponins, quillaja saponins, chikutsuninjin saponins and sarsa saponins, particularly preferably quillaja saponins and salsa saponins. The amount of these added is preferably 0.05 to 10% by mass, particularly preferably 0.1 to 8% by mass.
 本発明の毛髪色素増強剤の効果をさらに高めるためには、糖類、アミノ酸類、ビタミンおよび補酵素類、ミネラル類、あるいはピルビン酸等を含有することも好ましい。ここで糖類には、単糖類、二糖類および多糖類があるが、単糖類と二糖類が好ましく、特に好ましいものとして、グルコース、ラクトース、ガラクトース、マンノース、スクロース、マルトース等を挙げることができる。また、アミノ酸類としては、必須アミノ酸と非必須アミノ酸があるが、好ましいアミノ酸として、グリシン、L-ヒスチジン、L-イソロイシン、L-リシン、L-メチオニン、L-フェニルアラニン、L-トレオニン、L-トリプトファン、L-バリン、L-アルギニン、L-シスチン、L-グルタミン、L-セリン、L-チロシン等を挙げることができる。これらの添加量は、好ましくは0.05~20質量%であり、特に好ましくは0.1~10質量%である。 In order to further enhance the effect of the hair pigment enhancer of the present invention, it is also preferable to contain saccharides, amino acids, vitamins and coenzymes, minerals, pyruvic acid and the like. Here, saccharides include monosaccharides, disaccharides, and polysaccharides, and monosaccharides and disaccharides are preferable, with glucose, lactose, galactose, mannose, sucrose, maltose, and the like being particularly preferable. Amino acids include essential amino acids and non-essential amino acids. Preferred amino acids include glycine, L-histidine, L-isoleucine, L-lysine, L-methionine, L-phenylalanine, L-threonine, and L-tryptophan. , L-valine, L-arginine, L-cystine, L-glutamine, L-serine, L-tyrosine and the like. The amount of these added is preferably 0.05 to 20% by mass, and particularly preferably 0.1 to 10% by mass.
 ビタミンおよび補酵素類としては、ビタミンA,ビタミンD,ビタミンE、ビタミンB1(チアミン)、B2(リボフラビン)、B3(ナイアシン)、B5(パントテン酸)、B6(ピリドキシン)、B8(葉酸)、B12(コバラミン)、ビオチン、コリン、リポ酸、イノシトール等を挙げることができ、好ましいものとして、ビタミンB1(チアミン)、B2(リボフラビン)、B3(ナイアシン)、B5(パントテン酸)、B6(ピリドキシン)、B8(葉酸)、ビオチン、コリン、リポ酸、イノシトール、ミオイノシトール等を挙げることができる。これらの添加量は、好ましくは0.01~2質量%であり、特に好ましくは0.05~1質量%である。 Vitamins and coenzymes include vitamin A, vitamin D, vitamin E, vitamin B1 (thiamine), B2 (riboflavin), B3 (niacin), B5 (pantothenic acid), B6 (pyridoxine), B8 (folic acid), B12 (Cobalamin), biotin, choline, lipoic acid, inositol and the like. Vitamin B1 (thiamine), B2 (riboflavin), B3 (niacin), B5 (pantothenic acid), B6 (pyridoxine), B8 (folic acid), biotin, choline, lipoic acid, inositol, myo-inositol and the like can be mentioned. The amount of these added is preferably 0.01 to 2% by mass, particularly preferably 0.05 to 1% by mass.
 ミネラル類としては、カルシウム、ナトリウム、カリウム、マグネシウム、亜鉛、アルミニウム等の塩化物、塩酸塩、炭酸塩、炭酸水素塩、硝酸塩、硫酸塩、リン酸一水素塩、リン酸二水素塩等を挙げることができる。これらの中で、カルシウムが特に重要で、50ppm以上が好ましく、100~500ppmがより好ましい。また、ミネラル類の総含量としては0.3~12質量%が好ましく、特に好ましくは0.5~8質量%である。 Examples of minerals include chlorides such as calcium, sodium, potassium, magnesium, zinc, and aluminum, hydrochlorides, carbonates, bicarbonates, nitrates, sulfates, monohydrogen phosphates, dihydrogen phosphates, etc. be able to. Among these, calcium is particularly important, preferably 50 ppm or more, and more preferably 100 to 500 ppm. The total content of minerals is preferably 0.3 to 12% by mass, particularly preferably 0.5 to 8% by mass.
 本発明の毛髪色素増強剤の効果をさらに高めるためには、マメ亜科トビカズラ属植物の植物エキスを含有することも好ましい。マメ亜科トビカズラ属植物としては、その中でもムクナ属が好ましく、特に、例えば、ムクナプルリエンス(学名:mucuna pruriens,和名:ビロード豆)、ハッショウ豆(学名:Stizolobium hassjoo)、猫豆(学名:Mucuna cochinchinensis)、トビカズラ(学名:Mucuna japonica)等が好ましい。植物エキスは、花、葉、茎、根等すべての部位の抽出物が利用されるが、種子の抽出物が最も有効である。植物エキスの調製のための抽出は、適宜当業者に周知の方法に準じて行うことができ、例えば、未乾燥もしくは乾燥した種子を粉砕し、これに水、アルコール類(メタノール、エタノール、イソプロパノール等)、ジオール類(プロピレングリコール、ブチレングリコール等)もしくはそれらの混合溶媒を添加して、その抽出処理後に溶媒を留去する、等の方法が挙げられる。これらムクナ属植物の植物エキスの添加量は、そのエキス中の有効成分量によっても変動するが、好ましくは0.05~10質量%であり、特に好ましくは0.1~3質量%である。 In order to further enhance the effect of the hair pigment enhancer of the present invention, it is also preferable to contain a plant extract of the leguminous family Tovicazura. Of these, the Mucuna genus is preferable among the legumes, and particularly, for example, Mucuna pulluliens (scientific name: mucuna pruriens, Japanese name: velvet bean), Hashhou bean (scientific name: Stizolobium hassjoo), cat bean (scientific name: Mucuna cochinchinensis), Tokakazura (scientific name: Mucuna japonica) and the like are preferable. As plant extracts, extracts of all parts such as flowers, leaves, stems, roots and the like are used, but seed extracts are most effective. Extraction for the preparation of the plant extract can be performed according to methods well known to those skilled in the art, for example, crushed undried or dried seeds, and water, alcohols (methanol, ethanol, isopropanol, etc.) ), Diols (propylene glycol, butylene glycol, etc.) or a mixed solvent thereof, and the solvent is distilled off after the extraction treatment. The amount of these plant extracts of the genus Mucuna varies depending on the amount of the active ingredient in the extract, but is preferably 0.05 to 10% by mass, particularly preferably 0.1 to 3% by mass.
 本発明では必要に応じてさらに他の成分、例えば、界面活性剤、浸透促進剤、保湿剤、血行促進剤、抗炎症剤、抗酸化剤、紫外線防止剤、抗菌剤、細胞増殖促進剤、細胞分化誘導剤、香料、油脂、オイル、酵素、清涼剤等を添加してもよい。例えば、ピペリンおよびカプサイシンなどの血行促進剤、ナリンゲニンなどの細胞増殖促進剤、フォルスコリンなどの細胞分化誘導剤、椿油およびスクワランなどのオイル、チロシナーゼなどの酵素等である。好ましい他の成分の添加量は0.01~10質量%であり。好ましくは0.1~5質量%である。 In the present invention, if necessary, other components such as surfactants, penetration enhancers, moisturizers, blood circulation promoters, anti-inflammatory agents, antioxidants, UV inhibitors, antibacterial agents, cell proliferation promoters, cells You may add a differentiation inducer, a fragrance | flavor, fats and oils, oil, an enzyme, a refreshing agent, etc. Examples thereof include blood circulation promoters such as piperine and capsaicin, cell growth promoters such as naringenin, cell differentiation inducers such as forskolin, oils such as salmon oil and squalane, and enzymes such as tyrosinase. The addition amount of other preferable components is 0.01 to 10% by mass. The content is preferably 0.1 to 5% by mass.
 本発明の毛髪色素増強剤が溶液(分散液を含む)の場合、用いられる主要な溶媒は水であるが、前記添加物が水に溶解しにくい場合は化粧料に添加することが認められている有機溶媒を使用することができる。例えばエタノール、イソプロパノール、プロピレングリコール、ブチレングリコールもしくはグリセリンなどの有機溶媒を使用することができるが、その使用量は20質量%未満であることが好ましい。 When the hair pigment enhancer of the present invention is a solution (including a dispersion), the main solvent used is water, but when the additive is difficult to dissolve in water, it is recognized that it is added to cosmetics. Any organic solvent can be used. For example, an organic solvent such as ethanol, isopropanol, propylene glycol, butylene glycol or glycerin can be used, but the amount used is preferably less than 20% by mass.
 本発明の毛髪色素増強剤の効果は、重金属イオン、とりわけ鉄イオンの存在によって阻害される。重金属イオンが存在すると、おもにその鉄イオンが着色錯体を形成して没食子酸や没食子酸誘導体が不溶化し、それらの毛穴からの吸収が阻害されてしまうためと思われる。本発明の溶液(分散液を含む)、ジェル、ムース、クリーム等の形態においては、実質的に重金属イオンを含まないことが好ましい。 The effect of the hair pigment enhancer of the present invention is inhibited by the presence of heavy metal ions, particularly iron ions. When heavy metal ions are present, the iron ions mainly form a colored complex, so that gallic acid and gallic acid derivatives are insolubilized and the absorption from the pores is inhibited. In the form of the solution (including the dispersion), gel, mousse, cream and the like of the present invention, it is preferable that substantially no heavy metal ions are contained.
 本発明の毛髪色素増強剤への添加物が水に極めて難溶解な化合物の場合、水にナノ分散して溶液にすることが必要になる。体積平均粒径200nm以下にナノ分散させると頭皮から毛根への浸透性が向上し、その機能を好適に使用することができる。体積平均粒径は、浸透性向上の観点から100nm以下であることがより好ましい。 When the additive to the hair pigment enhancer of the present invention is a compound that is extremely hardly soluble in water, it is necessary to form a solution by nano-dispersing in water. When nano-dispersed to a volume average particle size of 200 nm or less, the permeability from the scalp to the hair root is improved, and the function can be suitably used. The volume average particle diameter is more preferably 100 nm or less from the viewpoint of improving permeability.
 以下に、実施例により本発明をさらに具体的に説明するが、本発明は以下の実施例に限定されるものではない。 Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited to the following examples.
 [実施例1~14、比較例1~4]~ヒト皮膚三次元培養モデルを用いたメラニン色素生成試験~
(1)メラニン色素生成用皮膚外用剤の調製
各実施例及び各比較例の試料溶液(表1参照)を下記の組成で調製した。
・有効成分            表1に記載の添加量
・プロピレングリコール      5質量%
・水               全量が100質量%になるように調整
タラタンニンは、川村通商製タラタンニンを用いた。
キラヤサポニンは、丸善製薬製キラヤニンD-100を、また、サルササポニンは、丸善製薬製サラキープALSを用いた。なお、キラヤニンD-100は、キラヤサポニン:25質量%、プロピレングリコール:15質量%、及び水:60質量%からなり、サラキープALSは、サルササポニン:7.5質量%、水:42.5質量%、エタノール:50質量%からなるため、純分換算を行った。
 また、その他の有効成分は市販試薬を使用した。
[Examples 1 to 14 and Comparative Examples 1 to 4] -Melanine pigment production test using a human skin three-dimensional culture model-
(1) Preparation of skin external preparation for producing melanin pigment Sample solutions (see Table 1) of each Example and each Comparative Example were prepared with the following composition.
-Active ingredient Addition amount listed in Table 1-Propylene glycol 5% by mass
-Tara tannin prepared by Kawamura Tsusho was used so that the total amount of water was 100% by mass.
Kirayasaponin used Maruzen Pharmaceutical's Kirayanin D-100, and Salsa saponin used Maruzen Pharmaceutical's Sarakeep ALS. In addition, Kirayanin D-100 is composed of Kirayasaponin: 25% by mass, propylene glycol: 15% by mass, and water: 60% by mass. Sarakeep ALS is salsasaponin: 7.5% by mass, water: 42.5% by mass. %, Ethanol: 50% by mass, so pure conversion was performed.
Moreover, the other active ingredient used the commercially available reagent.
 [ヒト皮膚三次元培養モデルの培養]
 MatTek社製ヒト皮膚三次元培養モデルMEL-300A(8mm)及び培地としてEPI-100NMM113を用い、5%二酸化炭素雰囲気下、37℃で3週間培養した。その間、第1日目から1日おきに試料溶液を50μlずつ添加すると共に培地を交換した。
[Culture of human skin three-dimensional culture model]
Using a 3D human skin model MEL-300A (8 mm) manufactured by MatTek and EPI-100NMM113 as a medium, the cells were cultured at 37 ° C. for 3 weeks in a 5% carbon dioxide atmosphere. Meanwhile, 50 μl of sample solution was added every other day from the first day, and the medium was changed.
 [吸光度の測定]
 ヒト皮膚三次元培養モデルを3週間培養後、培養カップ中のメンブレンを打ち抜き、1N-水酸化ナトリウム水溶液0.5mlを加え、90℃の湯浴中で3時間激しく振とうして細胞を分解した。0.45μのフィルターを通して濾過し、濾液をマイクロプレートリーダーで吸光度測定した(波長:405nm)。
[Measurement of absorbance]
After culturing the human skin three-dimensional culture model for 3 weeks, the membrane in the culture cup was punched out, 0.5 ml of 1N-sodium hydroxide aqueous solution was added, and the cells were decomposed by shaking vigorously in a 90 ° C. water bath for 3 hours. . The solution was filtered through a 0.45 μ filter, and the absorbance of the filtrate was measured with a microplate reader (wavelength: 405 nm).
Figure JPOXMLDOC01-appb-T000007
Figure JPOXMLDOC01-appb-T000007
 結果を表1に示したが、タラタンニン、タンニン酸は高い吸光度を示し、高濃度に発色したことが分かる。特に、タラタンニンとキラヤサポニンを併用したものは、さらに高い吸光度を示した。また、没食子酸と没食子酸フェニルも比較的高い吸光度を示した。 The results are shown in Table 1. It can be seen that taratannin and tannic acid showed high absorbance and developed a high concentration. In particular, the combination of taratannin and kirayasaponin showed a higher absorbance. Also, gallic acid and phenyl gallate also showed relatively high absorbance.
 一方、図1に示すように、実施例4,6,7,8,11及び比較例1,3におけるヒト皮膚三次元培養モデルMEL-300Aカップ写真の結果から、実施例4,6,7,8,11は、比較例1,3よりも発色濃度が極めて高いことが分かる。 On the other hand, as shown in FIG. 1, from the results of the human skin three-dimensional culture model MEL-300A cup photographs in Examples 4, 6, 7, 8, 11 and Comparative Examples 1 and 3, Examples 4, 6, 7, 8 and 11 show that the color density is extremely higher than those of Comparative Examples 1 and 3.
 [実施例15~18、比較例5~6]~ヒト試験~
「ヘアートニックの調製」
(1)タラタンニン2gを水200mlで希釈してヘアートニックAを調製した(タラタンニンとして1質量%溶液)。
(2)タラタンニン2gとキラヤニンD-100溶液(丸善製薬製キラヤサポニン25%、水60%、プロピレングリコール15%水溶液)8gを水200mlで希釈してヘアートニックBを調製した(タラタンニンおよびキラヤサポニンとして1質量%溶液)。
(3)有効成分を用いない水溶液を用いてヘアートニックCを調製した。
[Examples 15 to 18, Comparative Examples 5 to 6]
"Preparing hair art"
(1) Hair artnic A was prepared by diluting 2 g of taratannin with 200 ml of water (1% by mass solution as taratannin).
(2) Heartonic B was prepared by diluting 2 g of Taratannin and 8 g of Kirayanin D-100 solution (25% of Kirayasaponin, 60% water, 15% aqueous solution of propylene glycol by Maruzen Pharmaceutical) with 200 ml of water (Taratannin and Kiraya) 1% by weight solution as saponin).
(3) Hair artic C was prepared using an aqueous solution not containing an active ingredient.
 [ヒト試験]
 頭髪の1/5~1/4が白髪化した40~60歳の男女各15名を10名ずつの3つのグループ(各グループは男性5名と女性5名とからなる)に分けた。実施例15においては男性5名に対して前記ヘアートニックAを用い、実施例16においては女性5名に対して前記ヘアートニックAを用いた。また、実施例17においては男性5名に対して前記ヘアートニックBを用い、実施例18においては女性5名に対して前記ヘアートニックBを用いた。さらに、比較例5においては、男性5名に対して前記ヘアートニックCを用い、比較例6においては女性5名に対して前記ヘアートニックCを用いた。
 各実施例・比較例において、毎日、入浴後就寝前と起床後の2回/日、各ヘアートニックを1ml/回、3ヶ月間、頭頂部に塗布、塗布部のマッサージを行って頭皮に浸透させた。
[Human test]
Fifteen males and females aged 40-60 years, whose hairs were 1/5 to 1/4 of their hair, were divided into three groups of 10 (each group consists of 5 males and 5 females). In Example 15, the hair art A was used for 5 men, and in Example 16, the hair art A was used for 5 women. In Example 17, the hair art B was used for 5 men, and in Example 18, the hair art B was used for 5 women. Furthermore, in Comparative Example 5, the hair artic C was used for 5 men, and in the comparative example 6, the hair artic C was used for 5 women.
In each of the examples and comparative examples, every day, after bathing, before bedtime and after waking up, 2 times / day after each bath, each hair artic 1 ml / time, applied to the top of the head for 3 months, massage the applied part and penetrate the scalp I let you.
 効果の判定は、試験前後に、毛根に近い部分(頭皮から3cmの範囲)の写真撮影を行い、白毛が黒化した割合を測定して80%以上黒化した時は◎、30~80%が黒化した時は○、30%未満の場合は×とした。 The effect was judged by taking a photograph of the part close to the hair root (in the range of 3 cm from the scalp) before and after the test, and measuring the ratio of white hair blackening. % Was black when it was black, and x when it was less than 30%.
Figure JPOXMLDOC01-appb-T000008
Figure JPOXMLDOC01-appb-T000008
 結果を表2に示したが、本発明のタラタンニンおよびタラタンニン/キラヤサポニンの有無により明確な差異が認められ、本発明のタラタンニンが白髪改善効果を有することが認められた。特に、タラタンニンにキラヤサポニンを併用した場合に顕著な白髪改善効果が認められた。また、男女間で有意な差は認められなかった。 The results are shown in Table 2. A clear difference was observed depending on the presence or absence of taratannin and taratannin / kirayasaponin of the present invention, and it was confirmed that the taratannin of the present invention has an effect of improving gray hair. In particular, when Taratannin was used in combination with Kirayasaponin, a remarkable white hair improvement effect was observed. There was no significant difference between men and women.
 [実施例19]毛髪色素増強剤分散液の調製とヒト試験
 1.0gのタラタンニンと水に極めて難溶なフォルスコリン(細胞分化誘導剤)0.1gをエタノール5gに溶解した後、0.45μmのミクロフィルター(ザルトリウス社製)を通すことでごみ等の不純物を除きIa液(6.1g)を調製した。次に、ノニオン系界面活性剤である1.0gのキラヤサポニン(東京化成製サポニンを使用)を蒸留水(92.9g)に溶解した後、0.45μmのミクロフィルター(ザルトリウス社製)を通すことでごみ等の不純物を除きIb液(93.9g)とした。Ia液とIb液とをT字型マイクロミキサーを用いて下記の手順でナノ分散を行った。すなわち、等価直径250μmのT字型マイクロミキサーの二つの入り口に1/16インチのテフロン(商標登録)チューブを接続し、その先にそれぞれIa液とIb液を入れたシリンジを繋ぎ、シリンジポンプにセットした。出口には1/16インチのテフロンチューブを接続し、その出口には捕集用のサンプル瓶をセットした。Ia液を0.20g/min、Ib液を3.12g/minの送液速度にて20分間送り出した。サンプル瓶の捕集された透明な分散液を試料15とした。試料15におけるタラタンニンの濃度は1.0質量%、フォルスコリンの濃度は0.1質量%、キラヤサポニンの濃度は1.0質量%、そしてエタノールの濃度は5.0質量%である。試料15の粒子径測定を行ったところ体積平均粒径Mvは28nmであり、単分散性の指標である体積平均粒径Mv/個数平均粒径Mnの比は1.25であった。
[Example 19] Preparation of hair pigment enhancer dispersion and human test 1.0 g of forskolin (cell differentiation inducer), which is extremely hardly soluble in water, was dissolved in 5 g of ethanol. Impurities such as dust were removed by passing through a 45 μm microfilter (manufactured by Sartorius) to prepare a liquid Ia (6.1 g). Next, 1.0 g of Kirayasaponin (using saponin made by Tokyo Kasei), which is a nonionic surfactant, is dissolved in distilled water (92.9 g) and then passed through a 0.45 μm microfilter (Sartorius). Thus, an Ib liquid (93.9 g) was obtained by removing impurities such as dust. The Ia liquid and Ib liquid were nano-dispersed by the following procedure using a T-shaped micromixer. In other words, 1/16 inch Teflon (registered trademark) tubes are connected to the two inlets of a T-shaped micromixer with an equivalent diameter of 250 μm, and syringes containing Ia and Ib solutions are connected to the ends of the tubes. I set it. A 1/16 inch Teflon tube was connected to the outlet, and a sample bottle for collection was set at the outlet. The liquid Ia was sent out at a liquid sending speed of 0.20 g / min and the liquid Ib was fed out at a liquid feeding speed of 3.12 g / min for 20 minutes. The transparent dispersion collected in the sample bottle was designated as Sample 15. In sample 15, the concentration of taratannin is 1.0% by mass, the concentration of forskolin is 0.1% by mass, the concentration of Quillajasaponin is 1.0% by mass, and the concentration of ethanol is 5.0% by mass. When the particle diameter of sample 15 was measured, the volume average particle diameter Mv was 28 nm, and the ratio of volume average particle diameter Mv / number average particle diameter Mn, which is an index of monodispersibility, was 1.25.
[比較例7]
 上記Ia液からタラタンニンを除く以外は同様にしてフォルスコリンを含むエタノール溶液であるIa’液(5.1g)を調製した。さらに、水を1g増量する以外は同様にしてキラヤサポニンを含むIb’液(94.9g)を調製した。それらを上記と同様にT字型マイクロミキサーにセットしてIa’液を0.17g/min、Ib’液を3.15g/minの送液速度にて20分間送り出した。サンプル瓶の捕集された透明な分散液を比較試料5とした。比較試料5におけるフォルスコリンの濃度は0.1質量%、キラヤサポニンの濃度は1.0質量%、そしてエタノールの濃度は5.0質量%である。比較試料5の粒子径測定を行ったところ体積平均粒径Mvは27nmであり、単分散性の指標である体積平均粒径Mv/個数平均粒径Mnの比は1.26であった。
[Comparative Example 7]
A liquid Ia ′ (5.1 g), which is an ethanol solution containing forskolin, was prepared in the same manner except that taratannin was removed from the liquid Ia. Further, an Ib ′ solution (94.9 g) containing Kirayasaponin was prepared in the same manner except that the amount of water was increased by 1 g. They were set in a T-shaped micromixer in the same manner as described above, and the Ia ′ solution was sent out at a feed rate of 0.17 g / min and the Ib ′ solution was sent out at a feed rate of 3.15 g / min for 20 minutes. The transparent dispersion collected in the sample bottle was used as comparative sample 5. In the comparative sample 5, the concentration of forskolin is 0.1% by mass, the concentration of Quillajasaponin is 1.0% by mass, and the concentration of ethanol is 5.0% by mass. When the particle diameter of the comparative sample 5 was measured, the volume average particle diameter Mv was 27 nm, and the ratio of volume average particle diameter Mv / number average particle diameter Mn, which is an index of monodispersibility, was 1.26.
 [ヒト試験]
 実施例19の試料15と比較例7の比較試料5を用いて、実施例15~18に記載の方法と同様にしてヒト試験を行った。その結果、試料15を使用した場合は90%の黒化が観測され効果の評価は◎レベル、比較試料5を使用した場合は65%の黒化にとどまり効果の評価は○レベルであった。この結果より、タラタンニンを添加することにより白髪防止能が増強されることが明らかとなった。
[Human test]
Using the sample 15 of Example 19 and the comparative sample 5 of Comparative Example 7, human tests were conducted in the same manner as described in Examples 15-18. As a result, 90% blackening was observed when the sample 15 was used, and the evaluation of the effect was ◎ level, and when the comparative sample 5 was used, the blackening was only 65% and the evaluation of the effect was ◯ level. From this result, it was clarified that the ability to prevent gray hair is enhanced by adding taratannin.
 [実施例20~32、比較例8]~中規模ヒト試験(試験期間3ヶ月)~
(1)ヘアートニックの調製
 表3に示す各種有効成分を適宜選択し、その表に示す各成分の含有量となるように、精製水150mlおよびブチレングリコール50mlに溶解させて、後述の表4に示すヘアートニックA’、B’,D~Nを調製した。なお、表3、4において、タラタンニンをTT,キラヤサポニンをQS、糖類をS、アミノ酸類をAA、ビタミンおよび補酵素類をV、ミネラル類をM、ムクナプルリエンス種子エキスをMPと表記した。
[Examples 20 to 32, Comparative Example 8] -Medium scale human test (test period 3 months)-
(1) Preparation of hair art Various active ingredients shown in Table 3 are appropriately selected and dissolved in 150 ml of purified water and 50 ml of butylene glycol so as to obtain the contents of each ingredient shown in the table. The hair tonics A ′, B ′, DN shown were prepared. In Tables 3 and 4, Taratannin is expressed as TT, Quillajasaponin as QS, Saccharide as S, Amino acids as AA, Vitamin and coenzymes as V, Minerals as M, and Mucnapururiens seed extract as MP. .
(2)比較溶液の調製
 精製水150mlおよびブチレングリコール50mlの混合物を調製してヘアートニックC’とした。
(2) Preparation of comparative solution A mixture of 150 ml of purified water and 50 ml of butylene glycol was prepared and used as hair art C '.
Figure JPOXMLDOC01-appb-T000009
Figure JPOXMLDOC01-appb-T000009
 [ヒト試験]
 頭髪の1/3~2/3が白髪化した50~65歳の女性140名を10名ずつの14のグループに分けた。実施例20~32において、表4のヘアートニックA’、B’,D~~Nを用い、比較例8においては、有効成分を含まないヘアートニックC’を用いた。
 各実施例・比較例において、毎日、入浴後就寝前と起床後の2回/日、各ヘアートニックを1ml/回、3ヶ月間、白髪部に塗布、塗布部のマッサージを行って頭皮に浸透させた。
[Human test]
We divided 140 women aged 50-65 years old whose gray hair was 1/3 to 2/3 into 14 groups of 10 each. In Examples 20 to 32, hair arts A ′, B ′, and D to˜N in Table 4 were used, and in comparative example 8, hair artic C ′ containing no active ingredient was used.
In each of the examples and comparative examples, every day, after bathing, before bedtime and after waking up, twice a day, each hair artic 1 ml / time, applied to the white hair part for 3 months, massage the applied part and penetrate the scalp I let you.
 効果の判定は、試験前後に、毛根に近い部分(頭皮から3cmの範囲)の写真撮影を行い、白毛が黒化した割合を測定して50%以上黒化した時は◎、20~50%が黒化した時は○、20%未満の場合は×とした。 The effect was judged by taking a photograph of the part close to the hair root (range 3 cm from the scalp) before and after the test, and measuring the ratio of white hair darkening. % Was black when it was black, and x when it was less than 20%.
Figure JPOXMLDOC01-appb-T000010
Figure JPOXMLDOC01-appb-T000010
 結果を表4に示したが、白髪率の高い高齢女性においても、本発明のタラタンニンが明確な白髪改善効果を有することが認められた。また、キラヤサポニン、糖類、アミノ酸類、ビタミン類、補酵素類、ミネラル類などの添加により、白髪改善効果が向上することが認められた。さらに、マメ亜科ムクナ属植物であるムクナプルリエンスの種子エキスを併用すると白髪改善効果が一層増強されることが認められた。 The results are shown in Table 4. It was confirmed that the tala tannin of the present invention has a clear gray hair improving effect even in elderly women with a high gray hair rate. In addition, it was confirmed that the effect of improving gray hair was improved by the addition of Kirayasaponin, sugars, amino acids, vitamins, coenzymes, minerals and the like. Furthermore, it was confirmed that the effect of improving gray hair was further enhanced when used together with the seed extract of Mucuna pullulence, a plant belonging to the genus Mucuna.

Claims (7)

  1.  有効成分として、没食子酸及び没食子酸誘導体の少なくとも1種を含む、一剤型であることを特徴とする毛髪色素増強剤。 A hair pigment enhancer characterized by being a one-part type containing at least one of gallic acid and a gallic acid derivative as an active ingredient.
  2.  前記没食子酸誘導体が、下記一般式(I)で表される化合物であることを特徴とする請求項1に記載の毛髪色素増強剤。
    Figure JPOXMLDOC01-appb-C000001
    The hair pigment enhancer according to claim 1, wherein the gallic acid derivative is a compound represented by the following general formula (I).
    Figure JPOXMLDOC01-appb-C000001
  3.  前記没食子酸誘導体が、タラタンニン、チェストナットタンニン、ミラボラムタンニン、五倍子タンニン(タンニン酸)、オークタンニン、及び茶タンニンからなる群から選ばれる1種又は2種以上の加水分解型タンニンであることを特徴とする請求項1に記載の毛髪色素増強剤。 The gallic acid derivative is one or more hydrolyzed tannins selected from the group consisting of taratannin, chestnut tannin, milabram tannin, pentaploid tannin (tannic acid), oak tannin, and tea tannin. The hair pigment enhancer according to claim 1, wherein
  4.  前記加水分解型タンニンが、タラタンニン及び五倍子タンニンから選ばれる少なくとも1種であることを特徴とする請求項3に記載の毛髪色素増強剤。 4. The hair pigment enhancer according to claim 3, wherein the hydrolyzable tannin is at least one selected from tara tannin and pentaploid tannin.
  5.  サポニン類の少なくとも1種を含むことを特徴とする請求項1~4のいずれか1項に記載の毛髪色素増強剤。 The hair pigment enhancer according to any one of claims 1 to 4, comprising at least one saponin.
  6.  糖類、アミノ酸類、ビタミン類、補酵素類、及びミネラル類からなる群から選ばれる少なくとも1種を含むことを特徴とする請求項1~5のいずれか1項に記載の毛髪色素増強剤。 The hair pigment enhancer according to any one of claims 1 to 5, comprising at least one selected from the group consisting of sugars, amino acids, vitamins, coenzymes, and minerals.
  7.  マメ亜科ムクナ属植物の植物エキスを含むことを特徴とする請求項1~6のいずれか1項に記載の毛髪色素増強剤。 The hair pigment enhancer according to any one of claims 1 to 6, wherein the hair pigment enhancer comprises a plant extract of a legume subfamily Mucuna spp.
PCT/JP2017/017756 2016-05-13 2017-05-10 Hair pigment enhancer WO2017195841A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201780028545.5A CN109069385B (en) 2016-05-13 2017-05-10 Hair pigment enhancer

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
JP2016097220 2016-05-13
JP2016-097220 2016-05-13
JP2017074040A JP6562469B2 (en) 2016-05-13 2017-04-03 Hair pigment enhancer
JP2017-074040 2017-04-03

Publications (1)

Publication Number Publication Date
WO2017195841A1 true WO2017195841A1 (en) 2017-11-16

Family

ID=60267424

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2017/017756 WO2017195841A1 (en) 2016-05-13 2017-05-10 Hair pigment enhancer

Country Status (1)

Country Link
WO (1) WO2017195841A1 (en)

Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5899417A (en) * 1981-12-08 1983-06-13 Rooto Seiyaku Kk Remedy for poliosis
JPS6038314A (en) * 1983-08-10 1985-02-27 Osaka Chem Lab Hair tonic
JPS60152408A (en) * 1984-01-18 1985-08-10 Yanagiya Honten:Kk Hair dye composition
JPH0665031A (en) * 1991-12-04 1994-03-08 Wella Ag Application of inactivating substance to radical catcher and/or non-radical active oxygen for preventing or suppressing of
JPH06192053A (en) * 1992-12-25 1994-07-12 Hoyu Co Ltd Autoxidation-type hair dye
JPH08337516A (en) * 1995-06-13 1996-12-24 Lion Corp One pot-type hair dyeing composition
JP2003509529A (en) * 1999-09-09 2003-03-11 ギサルベルティ カルロ Synthetic vegetable melanin, method for producing the same, and composition containing the substance
JP2005179191A (en) * 2003-12-16 2005-07-07 Hoyu Co Ltd Semipermanent hair dye composition
JP2007326813A (en) * 2006-06-07 2007-12-20 Kao Corp Hair cosmetic
JP2014024766A (en) * 2012-07-25 2014-02-06 Riaru Kagaku Kk External preparation with unstable dye being stably admixed, for coloring skin and hair
JP2015533169A (en) * 2012-10-12 2015-11-19 ロレアル Cosmetic composition comprising at least one flavonoid and ferulic acid

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5899417A (en) * 1981-12-08 1983-06-13 Rooto Seiyaku Kk Remedy for poliosis
JPS6038314A (en) * 1983-08-10 1985-02-27 Osaka Chem Lab Hair tonic
JPS60152408A (en) * 1984-01-18 1985-08-10 Yanagiya Honten:Kk Hair dye composition
JPH0665031A (en) * 1991-12-04 1994-03-08 Wella Ag Application of inactivating substance to radical catcher and/or non-radical active oxygen for preventing or suppressing of
JPH06192053A (en) * 1992-12-25 1994-07-12 Hoyu Co Ltd Autoxidation-type hair dye
JPH08337516A (en) * 1995-06-13 1996-12-24 Lion Corp One pot-type hair dyeing composition
JP2003509529A (en) * 1999-09-09 2003-03-11 ギサルベルティ カルロ Synthetic vegetable melanin, method for producing the same, and composition containing the substance
JP2005179191A (en) * 2003-12-16 2005-07-07 Hoyu Co Ltd Semipermanent hair dye composition
JP2007326813A (en) * 2006-06-07 2007-12-20 Kao Corp Hair cosmetic
JP2014024766A (en) * 2012-07-25 2014-02-06 Riaru Kagaku Kk External preparation with unstable dye being stably admixed, for coloring skin and hair
JP2015533169A (en) * 2012-10-12 2015-11-19 ロレアル Cosmetic composition comprising at least one flavonoid and ferulic acid

Similar Documents

Publication Publication Date Title
JP5571897B2 (en) Vitamin C transporter production promoter
TWI735779B (en) Composition for treating skin pigmentation and related methods
CN106794136B (en) Deglycosylation of a combination of salvia miltiorrhiza extract and niacin and/or niacinamide
EP2200574B1 (en) Novel use of panduratin derivatives or extract of kaempferia pandurata comprising the same
US20150119347A1 (en) Composition for preventing or treating hair loss or promoting hair growth comprising secoiridoid glucoside derivatives
JP2007204426A (en) Hair growth promoter
CN101125155B (en) Application of erigeron breviscapus methanol extracts in skin-whitening and speckle eliminating prevention
JP6562469B2 (en) Hair pigment enhancer
JP2005029490A (en) Tyrosinase inhibitor, active oxygen retarder and skin care preparation for external use
JP2003160461A (en) Skin care preparation
WO2017195841A1 (en) Hair pigment enhancer
JP5171080B2 (en) Composition having antioxidative action
JP2017203012A (en) Hair remedy
JP2012162508A (en) Hair growth agent/hair tonic
JP2000128729A (en) Cosmetic
FR2825022A1 (en) Nontherapeutic treatment of the human or animal body comprises administering or applying olive polyphenols
JPH09315928A (en) Tyrosinase-activity inhibitor and beautifying cosmetics using the same
TWI687237B (en) Use of extract of victoria cruziana for inducing expression of keratin gene and hyaluronan synthase 2 gene, and enhancing moisture-retaining capacity of skin
CN103520471B (en) A kind of bitter taste masking agent of herb mixture
JP6883320B2 (en) Hair pigment enhancer
JP2007210965A (en) Tyrosinase activity inhibitor, manufacturing method and use thereof
JP5946510B2 (en) Melanin production inhibitor, cosmetic, and method for producing melanin production inhibitor
KR20150010810A (en) A functional compositoion comprising Chrysanthemum morifolium extract
JP2019214533A (en) Keratinocyte growth promoter
JP2012006902A (en) External preparation set for skin improvement, and beauty method using the same

Legal Events

Date Code Title Description
NENP Non-entry into the national phase

Ref country code: DE

121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 17796200

Country of ref document: EP

Kind code of ref document: A1

122 Ep: pct application non-entry in european phase

Ref document number: 17796200

Country of ref document: EP

Kind code of ref document: A1