WO2018128104A1 - Hair growth promoter - Google Patents

Hair growth promoter Download PDF

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Publication number
WO2018128104A1
WO2018128104A1 PCT/JP2017/046295 JP2017046295W WO2018128104A1 WO 2018128104 A1 WO2018128104 A1 WO 2018128104A1 JP 2017046295 W JP2017046295 W JP 2017046295W WO 2018128104 A1 WO2018128104 A1 WO 2018128104A1
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hair
fulvic acid
acid
humus
hair restorer
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PCT/JP2017/046295
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French (fr)
Japanese (ja)
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金川シーラ
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株式会社スタイルアンドバリュージャパン
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Publication of WO2018128104A1 publication Critical patent/WO2018128104A1/en

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/02—Medicinal preparations containing materials or reaction products thereof with undetermined constitution from inanimate materials
    • A61K35/10—Peat; Amber; Turf; Humus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/14—Drugs for dermatological disorders for baldness or alopecia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00—Preparations for affecting hair growth

Definitions

  • the present invention relates to a hair restorer, and more particularly to a hair restorer containing a humus extract.
  • Non-patent Document 1 hair growth occurs by proliferation and differentiation of hair matrix cells and is regulated by hair papilla cells.
  • the dermal papilla which is an aggregate of dermal papilla cells, grows greatly during the growth phase of the hair. Therefore, it is considered that the proliferation of dermal papilla cells plays an important role in forming thick and firm hair.
  • the increase in dermal papilla cells is a type of male hormone that is promoted by cell growth factors such as EGF and FGF, and is considered to suppress the production of dihydrotestosterone (DHT), which is known as a cell growth inhibitor in animal studies. It is done. Therefore, conventionally, methods for activating cell growth factors such as EGF and FGF, methods for suppressing cell growth inhibitors such as DHT, and the like have been studied as methods for promoting hair growth.
  • Finasteride which is known as an antiandrogen used as a positive control in Examples described later, is more effective as a 5 ⁇ -reductase inhibitor than EGF or FGF production promotion. It is thought to be involved in the androgen receptor contained in the papillary cells and showed cell proliferation. Minoxidil also appears to have a similar mechanism of action as finasteride.
  • Patent Document 1 discloses a hair restorer characterized by containing a humus soil extract. According to Patent Document 1, it is said that it is possible to provide a hair restorer that is gentle to the human body and that has excellent usability and moisturizing effect.
  • Patent Document 2 discloses that a hair thickener and a hair restorer are produced using an aqueous liquid containing a humus extract material.
  • the humus soil extract used in the examples of Patent Document 1 and Patent Document 2 is an extract of humus soil collected from Kara Nishina, Moriyama-machi, Kitakaku-gun, Nagasaki Prefecture. This humus soil extract is contained in the commercially available hair restorer used in Comparative Example 2 described later.
  • JP 2006-327978 hair restorer
  • Patent No. 3507347 humus soil extractable aqueous solution
  • Humus is generally a fertile soil that contains many nutrients approximately 100 million years old and remains as organic matter without being transformed into oil or coal. More specifically, when the plant that inhabited the period entered the ice age, it was buried underground, changed to peat moss by microorganisms such as bacteria, and new organic matter accumulated on top of it, and again decomposed by bacteria etc. A deposited layer is formed as the process proceeds.
  • Humus is an amorphous organic polymer such as fulvic acid or humic acid, which is formed by the decomposition of carbohydrates and proteins in plant residues and microbial remains in the soil by microorganisms, and the decomposition products are condensed. Contains minerals.
  • Humic acid is a red-brown or black-brown amorphous high-molecular organic acid that is soluble in alkali and insoluble in acid
  • fulvic acid is an amorphous high-molecular organic acid that is soluble in alkali and acid.
  • Amorphous polymeric organic acids such as fulvic acid and humic acid vary depending on factors such as the soil of the humus production area and the age of its generation. The effect of humus is also considered to change due to the difference in the structure and physical properties of the amorphous polymer organic acid.
  • an object of the present invention is to provide a hair restoring agent containing a humus extract substance and having an excellent hair restoring action.
  • the inventor of the present invention has hitherto been known to have a hair growth action like finasteride on a fulvic acid having a structure based on specific infrared absorption among fulvic acids having various molecular structures and substituents. Furthermore, the present invention was completed by discovering that it exhibited an excellent hair growth action even when compared with a conventionally known humus extract-containing hair restorer. That is, the present invention provides an effective amount of a humus extract containing fulvic acid having infrared absorption peaks at wave numbers 3362, 2875, 1675, 1559, 1360, 1200, 1047 and 835 cm ⁇ 1 in the infrared absorption spectrum in the FT-IR method. And a hair restorer comprising cosmetic, dermatological and / or pharmaceutically acceptable additives or food additives.
  • the “hair growth agent” is used in the meaning including a hair growth effect in addition to the hair growth effect.
  • the humus extract contains fulvic acid having an infrared absorption spectrum shown in FIG.
  • the humus extract does not have a naphthalene ring structure.
  • the average molecular weight of fulvic acid in the humus extract is less than 4,000.
  • the hair restorer of the present invention is for example for transdermal administration.
  • the form of the hair growth agent for transdermal administration is, for example, a liquid agent, a liquid agent, an emulsion, an emulsion, an emulsion, a cream, a powder, or a clay pack.
  • the hair restorer of the present invention is for oral administration, for example.
  • the form of the hair restorer for oral administration is, for example, powder, granule, capsule, pill, tablet, chewable tablet, drop, liquid, syrup, or drink.
  • the hair restorer of the present invention which contains a humus extract containing a fulvic acid defined by a specific infrared absorption wavelength, the hair restoring action is exerted like finasteride, and its effect is humus It is significantly higher than known humic substance-containing hair restorers containing extracts.
  • FIG. 2 is a diagram of an FT-IR absorption spectrum based on an ATR method of a fulvic acid fraction of a humus extract (product name: Humicle (registered trademark)) used in Example 1.
  • FIG. 5 is an FT-IR absorption spectrum diagram based on the ATR method for standard fulvic acid and standard humic acid produced in Danto used in Comparative Example 3.
  • 2 is a three-dimensional fluorescence spectrum diagram of a 4% aqueous solution of humus extract used in Example 1.
  • FIG. 1 is a diagram of an FT-IR absorption spectrum based on an ATR method of a fulvic acid fraction of a humus extract (product name: Humicle (registered trademark)) used in Example 1.
  • FIG. 5 is an FT-IR absorption spectrum diagram based on the ATR method for standard fulvic acid and standard humic acid produced in Danto used in Comparative Example 3.
  • 2 is a three-dimensional fluorescence spectrum diagram of a 4%
  • the hair restorer of the present invention is an artificially synthesized fulvic acid product (Comparative Example 1), an existing hair restorer product (Comparative Example 2) or a humus extract containing a humus extract. It can be seen that the hair papilla cell proliferation rate is higher than that of the standard product (Comparative Examples 3 and 4).
  • the hair restorer of the present invention effectively uses a humus extract containing fulvic acid having infrared absorption peaks at wave numbers 3362, 2875, 1675, 1559, 1360, 1200, 1047 and 835 cm ⁇ 1 in the infrared absorption spectrum in the FT-IR method. Including quantity.
  • humus extract having the above-described specific infrared absorption peak among humus extracts.
  • a humus extract will not ask
  • the humus extract containing the humus extract having the infrared absorption peak is mixed with water (for example, distilled water, ion exchange water, reverse osmotic pressure water, etc.) to extract the humus extract into the water.
  • water for example, distilled water, ion exchange water, reverse osmotic pressure water, etc.
  • the humus is usually mixed at a ratio of 5 to 35 parts by weight, preferably 15 to 25 parts by weight, particularly preferably 17 to 18 parts by weight with respect to 100 parts by weight of water.
  • the mixture is left at room temperature, usually for 24 to 96 hours, preferably 48 to 72 hours. During the standing, the mixture may be appropriately stirred.
  • the supernatant or filtrate of the above mixture is used as a humus extract.
  • the pH of the liquid humus extract is usually 3.0. This liquid humus extract may be dried to a powder.
  • the average molecular weight of fulvic acid in the humus extract is less than 4,000, preferably not more than 3,500, particularly preferably not more than 3,000, and more preferably 3,000 to 1,000. is there.
  • the humus extract may be commercially available, and is available in Japan under the product name “Humicle (registered trademark) HC fulvic acid powder” from, for example, Style and Value Japan Co., Ltd. Table 1 shows the component analysis results (content in the sample wet weight).
  • the fulvic acid was fractionated by extracting the fumaric alkali (0.1N sodium hydroxide) and acid (hydrochloric acid, pH 2) soluble components.
  • the physical property test method and analysis results of the fumicle or fulvic acid fraction are shown below.
  • FIG. 3 shows a three-dimensional excitation-fluorescence spectrum (measuring apparatus JASCO FP-8200) of a 4% aqueous solution of Humicle.
  • fulvic acid and humic acid extracted and refined from Danto forest soil in Aichi Prefecture (both are distributed as “Standard Material of the Japanese Humic Society” by the Japanese Humic Society, respectively)
  • FIG. 4 shows three-dimensional fluorescence spectra of fulvic acid and corrugated humic acid.
  • the GPC-UV / TC analysis method separates dissolved organic substances in water at a high speed according to the size of the molecule and the degree of exclusion, and separates the separated dissolved molecules into a UV detector and a TC detector (Total Carbon). (Analyzer) is a monitoring method.
  • GPC-TC device GPC: Shodex GPC SYSTEM 21 Separation column TOSO HW-50S Eluent 30 mM Na 2 HPO 4 UV absorption (220 nm) detector: GL7450 (manufactured by GL Sciences) TC detector: LCT-100 (manufactured by Toray Engineering) was used to measure the molecular weights of the fumicle and the fulvic acid from Dando.
  • the peak position of Danto fulvic acid was 51 minutes, whereas it was 54 minutes for the 4% humicule solution.
  • the retention time at the peak position is converted into the exclusion characteristics of the polysaccharide and PEG (polyethylene glycol) of the separation column used, the molecular weight of the terraced fulvic acid is about 4,000, and the molecular weight of the organic matter in the Humicle solution was estimated to be about 1,000 to 3,000.
  • the UV / TC value of the Humicle solution is almost similar to that of the Danto fulvic acid solution.
  • the similarity in ultraviolet absorption (220 nm) derived from the molecular structure of organic matter indicates that there is similarity in the skeleton and functional group types of both molecular structures.
  • FT-IR Fourier transform infrared spectrophotometer method
  • FIG. 2 shows infrared absorption spectra of fulvic acid and humic acid produced in Danto. Major infrared absorption peaks were extracted from FIG. 1 (Humicle) and FIG. 2 (Stepbo fulvic acid), and the results are shown in Table 3 in terms of wave number.
  • the fulvic acid contained in Humicle and the fulvic acid produced in Dando have a carboxyl group (C—O) absorption peak at 1200 cm ⁇ 1 in common, but the level of Humicle is higher than that of Danfu fulvic acid. small. That fulvic acid in Hyumikuru is clearly different spectrum of Danto producing fulvic acids are 1559,1047 and tri-substituted benzene type signals were observed at 835 cm -1, and phenol or an alcohol type 3362 and 1360 cm -1 Is observed.
  • C—O carboxyl group
  • the result of infrared spectroscopic analysis suggests that the fulvic acid in the humicle has fewer carboxyl groups than the dansted fulvic acid, and the structure of the tri-substituted benzene type phenolic compound is greater.
  • this difference in molecular structure is reflected in a difference in the proliferation rate of hair papilla cells as shown in Examples and Comparative Examples described later. That is, the hair restorer to which an effective amount of a humus extract containing fulvic acid having the specific infrared absorption spectrum characteristic specified in the present invention is added has an effect superior to that of a conventional hair restorer containing humic substances. .
  • humus extract those which are generally used as cosmetically, dermatologically and / or pharmaceutically acceptable additives are added to the hair growth agent for transdermal use of the present invention.
  • water ethylene glycol, polyethylene glycol, propylene glycol, 1,3-butylene glycol, 1,4-butylene glycol, dipropylene glycol, glycerin, diglycerin, polyglycerin, pentylene glycol, isoprene glycol, glucose, maltose, Polyhydric alcohols such as fructose, xylitol, sorbitol, maltotriose, erythritol; lower alcohols such as methanol, ethanol, propyl alcohol, isopropyl alcohol, butyl alcohol, isobutyl alcohol; oleic acid, isostearic acid, lauric acid, myristic acid, palmitic acid Higher fatty acids such as acid, stearic acid, behe
  • transdermal hair restorer of the present invention examples are a liquid agent, a liquid agent, an emulsion, an emulsion, an emulsion, a cream, a powder, and a clay pack.
  • the hair growth agent for transdermal use is preferably in the form of a solution, solution, emulsion, emulsion, emulsion or cream.
  • the transdermal hair restorer of the present invention is contained in hair cosmetics such as shampoos, rinses and rinse-in shampoos; hair cosmetics such as hair mists, hair sprays, hair foams, hair liquids, and the like. A hair restoring action may be added.
  • the content of the humus extract (containing about 3% fulvic acid) in the transdermal hair restorer of the present invention may be an effective amount, usually 0.001 to 20% by weight, preferably 0.00. It is 01 to 20% by weight, more preferably 0.05 to 15% by weight, and particularly preferably 0.1 to 10% by weight.
  • the applied amount of the percutaneous hair restorer of the present invention may be an effective amount depending on age, hair growth status, individual differences and the like.
  • General-purpose food additives may be added to the oral hair restorer of the present invention.
  • general-purpose excipients for example, depending on the form of oral administration, general-purpose excipients, disintegrants, binders, lubricants, vitamins, xanthine derivatives, amino acids, pH adjusters, cooling agents, suspending agents, thickeners, Solubilizing agents, antioxidants, coating agents, plasticizers, surfactants, water, alcohols, water-soluble polymers, sweeteners, corrigents, acidulants, fragrances, coloring agents, etc. It is possible to add in the target and quantitative range.
  • the form of the oral hair restorer of the present invention is different from ordinary foods such as powders, granules, capsules, pills, tablets, chewable tablets, drops, liquids, syrups and drinks. It is processed into an agent.
  • the content of the humus extract (containing about 3% of fulvic acid) in the oral hair restorer of the present invention may be an effective amount, usually 0.1 to 70% by weight, preferably 0.1%. -30% by weight, more preferably 0.1-15% by weight.
  • the daily intake of the oral hair restorer of the present invention may be an effective amount depending on age, hair growth status, individual differences, and the like.
  • Example 1 Comparative Examples 1 to 4
  • Whether or not the hair-restoring agent of the present invention has a hair-growing action was examined by a hair papilla cell proliferation effect test (in vitro), which is an experimental model system for hair papilla cells.
  • the hair growth agent of the present invention was added to the hair papilla cells, the cell growth promotion rate of the hair papilla cells was measured by MTT assay, and the hair papilla cell growth rate was calculated.
  • Example 1 Preparation of Hair Growth Agent Test Product
  • a humus extract product “Humicle” obtained by drying an aqueous extract of humus produced in Utah, USA was prepared.
  • the physical properties of the fulvic acid fraction contained in the vehicle are as described above.
  • Comparative Example 1 100% fulvic acid obtained by fermentation of fruits and plants, health drink manufactured by M Company
  • Comparative Example 2 Company N containing humus extract (fulvic acid) from Karabi, Moriyama-cho, Kitakagi-gun, Nagasaki Prefecture Hair-growth comparative example 3: Danto fulvic acid (humic acid reference material, manufactured by the Japan Humic Society)
  • Comparative example 4 Lake Biwa fulvic acid (humic acid reference material, manufactured by Japanese Humic Society)
  • test article solution The hair growth agent test articles of Example 1 and Comparative Examples 1 to 4 were tested at a concentration of 125, 31.25, 7.81, 1.95, 0.48, or 0.12 ⁇ g / 0.1%, respectively. Diluted sequentially with hair papilla cell culture medium to a volume of ml. The positive control Finasteride was diluted to 3 ng / mL.
  • MTT assay The medium of the plate after completion of the culture was discarded, and 0.1 mL of MTT reagent-containing medium (1 mg MTT / mL medium) was newly added to each well. The color reaction was performed by culturing in a CO 2 incubator (37 ° C., CO 2 5%) for 3 hours. MTT solubilized solution (isopropanol) was added to each well in an amount of 0.1 mL to extract MTT taken up by living cells. The absorbance of the MTT extract was measured at 570 nm using a microplate reader. As shown in the following formula, the cell growth rate was calculated as a percentage when the absorbance of the control (untreated cells of the test product) was 100.
  • Test data and statistical analysis An analysis of variance was performed on the obtained data. When equal variance was confirmed, an uncorresponding t-test was performed as a statistical analysis, and a comparison with a control group was performed. The test results are shown in Table 4 and FIG.
  • the hair restorer of the present invention (Example 1) showed a cell growth rate of 107.4 to 116.2% at a concentration of 0.48 to 125 ⁇ g / ml.
  • Comparative Example 3 stepped acid fulvic acid
  • Comparative Example 4 Lake Lake acid
  • Comparative Examples 3 and 4 showed a tendency similar to Example 1 at a fulvic acid concentration of 0.48 to 125 ⁇ g / ml, but the cell growth rate was 99.99. 8-106.7% (Comparative Example 3) and 96.4-102.7% (Comparative Example 4), inferior to Example 1.
  • Comparative Example 1 is a fulvic acid artificially synthesized using fruits and plants as starting materials, unlike the humus extract used in the present invention.
  • Comparative Example 2 is presumed to be a humus extract produced in Karabi, Moriyama-cho, Moritaka-machi, Kitakagi-gun, Nagasaki Prefecture, which was used in Examples of Patent Documents 1 and 2.
  • the cell growth rates of Comparative Examples 1 and 2 were 86.1 to 104.4% and 94.2 to 101.2%, respectively. Obviously inferior to 1.
  • the hair restorer of the present invention containing a specific humus extract is more effective than finasteride, a humus extract standard product, and an existing hair restorer product containing a humus extract, which are known to have hair papilla cell proliferation activity. It was found to have high hair papilla cell proliferation activity. Accordingly, the hair growth agent of the present invention is expected to be industrially useful as a hair growth agent having an excellent hair growth action.

Abstract

[Problem] To provide a hair growth promoter containing a humus extract and having an excellent hair growth function. [Solution] The present invention provides a hair growth promoter, which has infrared absorption peaks at wave numbers of 3362, 2875, 1675, 1559, 1360, 1200, 1047, and 835 cm-1 in an infrared absorption spectrum obtained by FT-IR technique, includes an effective amount of a fulvic acid-containing humus extract having an average molecular weight of less than 4,000, and includes cosmetically, dermatologically and/or pharmaceutically acceptable additives or food additives.

Description

育毛剤Hair restorer
　本発明は、育毛剤に関し、より詳細には腐植抽出物を含有する育毛剤に関する。 The present invention relates to a hair restorer, and more particularly to a hair restorer containing a humus extract.
　毛髪の成長は、毛母細胞の増殖と分化によって起こり、そして毛乳頭細胞によって調節されていることが知られている（非特許文献１）。毛乳頭細胞の集合体である毛乳頭は、毛髪の成長期に大きく成長することから、毛乳頭細胞の増殖が、太くてしっかりした毛髪を形成する重要な役割を果たしていると考えられる。 It is known that hair growth occurs by proliferation and differentiation of hair matrix cells and is regulated by hair papilla cells (Non-patent Document 1). The dermal papilla, which is an aggregate of dermal papilla cells, grows greatly during the growth phase of the hair. Therefore, it is considered that the proliferation of dermal papilla cells plays an important role in forming thick and firm hair.
　毛乳頭細胞の増加は、ＥＧＦやＦＧＦといった細胞増殖因子によって促進される、男性ホルモンの一種であり、動物試験等で細胞増殖抑制物質として知られているジヒドロテストステロン（ＤＨＴ）の産生抑制等が考えられる。したがって、育毛促進方法として、従来、ＥＧＦ、ＦＧＦ等の細胞増殖因子を活性化させる方法、ＤＨＴ等の細胞増殖抑制物質を抑制させる方法等が検討されている。後述の実施例で陽性対照として使用した、抗アンドロゲン薬として知られるフィナステリド（Ｆｉｎａｓｔｅｒｉｄｅ）は、ＥＧＦやＦＧＦの産生促進というよりも、５αリダクターゼ阻害剤として作用が強いため、阻害作用の結果として、毛乳頭細胞に含まれるアンドロゲンレセプターへ関与し、細胞増殖を示したと考えられている。ミノキシジルもまた、フィナステリドと同様の作用機序と思われる。 The increase in dermal papilla cells is a type of male hormone that is promoted by cell growth factors such as EGF and FGF, and is considered to suppress the production of dihydrotestosterone (DHT), which is known as a cell growth inhibitor in animal studies. It is done. Therefore, conventionally, methods for activating cell growth factors such as EGF and FGF, methods for suppressing cell growth inhibitors such as DHT, and the like have been studied as methods for promoting hair growth. Finasteride, which is known as an antiandrogen used as a positive control in Examples described later, is more effective as a 5α-reductase inhibitor than EGF or FGF production promotion. It is thought to be involved in the androgen receptor contained in the papillary cells and showed cell proliferation. Minoxidil also appears to have a similar mechanism of action as finasteride.
　特許文献１には、腐植土抽出物を含むことを特徴とする育毛剤が開示されている。特許文献１によれば、人体に優しく、かつ、使用感、保湿効果に優れた育毛剤を提供可能であるとされる。特許文献２には、腐植土抽出物質含有水性液を用いて増毛剤・育毛剤を製造することが開示されている。特許文献１及び特許文献２の実施例で使用された腐植土抽出液は、長崎県北高来郡森山町唐比西名で採取された腐植土の抽出物である。この腐植土抽出物が、後述の比較例２で使用した市販の育毛剤に含まれている。 Patent Document 1 discloses a hair restorer characterized by containing a humus soil extract. According to Patent Document 1, it is said that it is possible to provide a hair restorer that is gentle to the human body and that has excellent usability and moisturizing effect. Patent Document 2 discloses that a hair thickener and a hair restorer are produced using an aqueous liquid containing a humus extract material. The humus soil extract used in the examples of Patent Document 1 and Patent Document 2 is an extract of humus soil collected from Kara Nishina, Moriyama-machi, Kitakaku-gun, Nagasaki Prefecture. This humus soil extract is contained in the commercially available hair restorer used in Comparative Example 2 described later.
特開２００６－３２７９７８（育毛剤）JP 2006-327978 (hair restorer) 特許第３５０７３４７（腐植土抽出物質含有水性液）Patent No. 3507347 (humus soil extractable aqueous solution)
　腐植は、一般に、約１億年前の多くの栄養素が含まれた肥沃な土壌が石油や石炭に変性することなく、有機物として残存したものである。より詳細には、前記時代に生息した植物が、氷河期に入ると地下に埋没し、バクテリア等の微生物によってピートモスに変化し、その上に新しい有機物が積み重なって、再度、バクテリア等で分解され、時間の経過とともに堆積層を形成したものである。腐植は、土壌中で植物残渣や微生物遺体の中の炭水化物及びタンパク質が微生物によって分解され、さらにその分解産物が縮合してできたフルボ酸やフミン酸といった無定形有機高分子重合体や、多種類のミネラルを含有する。フミン酸は、アルカリに可溶であって酸に不溶な赤褐色ないし黒褐色無定形高分子有機酸であり、フルボ酸は、アルカリ及び酸に可溶な無定形高分子有機酸である。 Humus is generally a fertile soil that contains many nutrients approximately 100 million years old and remains as organic matter without being transformed into oil or coal. More specifically, when the plant that inhabited the period entered the ice age, it was buried underground, changed to peat moss by microorganisms such as bacteria, and new organic matter accumulated on top of it, and again decomposed by bacteria etc. A deposited layer is formed as the process proceeds. Humus is an amorphous organic polymer such as fulvic acid or humic acid, which is formed by the decomposition of carbohydrates and proteins in plant residues and microbial remains in the soil by microorganisms, and the decomposition products are condensed. Contains minerals. Humic acid is a red-brown or black-brown amorphous high-molecular organic acid that is soluble in alkali and insoluble in acid, and fulvic acid is an amorphous high-molecular organic acid that is soluble in alkali and acid.
　フルボ酸やフミン酸のような無定形重合高分子有機酸は、腐植の産地の土壌やその生成年代期等の要因によって変化する。腐植の効能もまた、無定形重合高分子有機酸の構造や物性の相違によって変化すると考えられる。 Amorphous polymeric organic acids such as fulvic acid and humic acid vary depending on factors such as the soil of the humus production area and the age of its generation. The effect of humus is also considered to change due to the difference in the structure and physical properties of the amorphous polymer organic acid.
　そこで、本発明の課題は、腐植抽出物質を含有し、育毛作用に優れた育毛剤を提供することである。 Therefore, an object of the present invention is to provide a hair restoring agent containing a humus extract substance and having an excellent hair restoring action.
　本発明者は、上記課題を鋭意検討した結果、多種多様な分子構造と置換基を有するフルボ酸の中でも特定の赤外線吸収に基づく構造を有するフルボ酸には、従来、フィナステリドのように育毛作用を発揮し、さらに、従来公知の腐植抽出物含有育毛剤と対比しても優れた育毛作用に発揮することを発見し、本発明を完成させた。すなわち、本発明は、ＦＴ－ＩＲ法における赤外線吸収スペクトルにおいて波数３３６２，２８７５，１６７５，１５５９，１３６０，１２００，１０４７及び８３５ｃｍ－１に赤外線吸収ピークを有するフルボ酸を含有する腐植抽出物を有効量含み、そして化粧品学的、皮膚病学的及び／又は薬学的に許容される添加剤あるいは食品添加物を含んでなる育毛剤を提供する。本明細書において、「育毛剤」は、育毛効果のほかに発毛効果を含む意味で使用される。 As a result of intensive studies on the above problems, the inventor of the present invention has hitherto been known to have a hair growth action like finasteride on a fulvic acid having a structure based on specific infrared absorption among fulvic acids having various molecular structures and substituents. Furthermore, the present invention was completed by discovering that it exhibited an excellent hair growth action even when compared with a conventionally known humus extract-containing hair restorer. That is, the present invention provides an effective amount of a humus extract containing fulvic acid having infrared absorption peaks at wave numbers 3362, 2875, 1675, 1559, 1360, 1200, 1047 and 835 cm −1 in the infrared absorption spectrum in the FT-IR method. And a hair restorer comprising cosmetic, dermatological and / or pharmaceutically acceptable additives or food additives. In the present specification, the “hair growth agent” is used in the meaning including a hair growth effect in addition to the hair growth effect.
　前記腐植抽出物は、より特定的には、図１に示す赤外線吸収スペクトルを示すフルボ酸を含有する。 More specifically, the humus extract contains fulvic acid having an infrared absorption spectrum shown in FIG.
　前記腐植抽出物は、ナフタレン環構造を有さないことが好ましい。 It is preferable that the humus extract does not have a naphthalene ring structure.
　前記腐植抽出物中のフルボ酸の平均分子量は、４，０００よりも小さいことを特徴とする。 The average molecular weight of fulvic acid in the humus extract is less than 4,000.
本発明の育毛剤は、例えば経皮投与用である。 The hair restorer of the present invention is for example for transdermal administration.
　前記経皮投与用の育毛剤の形態は、例えば水剤、液剤、乳剤、乳液、エマルション、クリーム、粉体、又はクレイパックである。 The form of the hair growth agent for transdermal administration is, for example, a liquid agent, a liquid agent, an emulsion, an emulsion, an emulsion, a cream, a powder, or a clay pack.
　本発明の育毛剤は、例えば経口投与用である。 The hair restorer of the present invention is for oral administration, for example.
　前記経口投与用の育毛剤の形態は、例えば散剤、顆粒剤、カプセル剤、丸剤、錠剤、チュアブル錠、ドロップ、水剤、シロップ、又はドリンク剤である。 The form of the hair restorer for oral administration is, for example, powder, granule, capsule, pill, tablet, chewable tablet, drop, liquid, syrup, or drink.
　特定の赤外線吸収波長によって規定されるフルボ酸を含有する腐植抽出物を含有することを特徴とする本発明の育毛剤によれば、フィナステリドのように育毛作用が発揮され、しかも、その効能は腐植抽出物を含有する公知の腐植物質含有育毛剤よりも顕著に高い。 According to the hair restorer of the present invention, which contains a humus extract containing a fulvic acid defined by a specific infrared absorption wavelength, the hair restoring action is exerted like finasteride, and its effect is humus It is significantly higher than known humic substance-containing hair restorers containing extracts.
実施例１で使用した腐植抽出物（製品名：ヒューミクル（登録商標））のフルボ酸分画のＡＴＲ法に基づくＦＴ－ＩＲ吸収スペクトルの図である。FIG. 2 is a diagram of an FT-IR absorption spectrum based on an ATR method of a fulvic acid fraction of a humus extract (product name: Humicle (registered trademark)) used in Example 1. 比較例３で使用した段戸産の標準フルボ酸及び標準フミン酸のＡＴＲ法に基づくＦＴ－ＩＲ吸収スペクトル図である。FIG. 5 is an FT-IR absorption spectrum diagram based on the ATR method for standard fulvic acid and standard humic acid produced in Danto used in Comparative Example 3. 実施例１で使用した腐植抽出物の４％水溶液の３次元蛍光スペクトル図である。2 is a three-dimensional fluorescence spectrum diagram of a 4% aqueous solution of humus extract used in Example 1. FIG. 比較例３で使用した段戸産フルボ酸の水溶液（濃度１０μｇ／ｍＬ）及び段戸産フミン酸の水溶液（濃度１０μｇ／ｍＬ）の３次元蛍光スペクトル図である。It is a three-dimensional fluorescence spectrum figure of the aqueous solution (concentration 10 microgram / mL) of the terraced fulvic acid used in the comparative example 3, and the aqueous solution (concentration 10 microgram / mL) of the terraced humic acid. 実施例１、並びに比較例１～４において、Ｘ軸に腐植抽出物の濃度（対数目盛）を、そしてＹ軸にヒト毛乳頭細胞の増殖率をプロットした図である。増殖率１００％は、コントロール（試験品添加無し）を意味する。図５から、本発明の育毛剤（実施例１）は、人工的に合成されたフルボ酸製品（比較例１）、腐植抽出物を含む既存の育毛剤製品（比較例２）や腐植抽出物標準品（比較例３及び４）よりも高い毛乳頭細胞増殖率を示すことがわかる。In Example 1 and Comparative Examples 1 to 4, the humus extract concentration (logarithmic scale) is plotted on the X axis, and the growth rate of human hair papilla cells is plotted on the Y axis. A growth rate of 100% means a control (no test article added). From FIG. 5, the hair restorer of the present invention (Example 1) is an artificially synthesized fulvic acid product (Comparative Example 1), an existing hair restorer product (Comparative Example 2) or a humus extract containing a humus extract. It can be seen that the hair papilla cell proliferation rate is higher than that of the standard product (Comparative Examples 3 and 4).
　以下、本発明の実施の形態を詳細に説明する。本発明の育毛剤は、ＦＴ－ＩＲ法における赤外線吸収スペクトルにおいて波数３３６２，２８７５，１６７５，１５５９，１３６０，１２００，１０４７及び８３５ｃｍ－１に赤外線吸収ピークを有するフルボ酸を含有する腐植抽出物を有効量含む。 Hereinafter, embodiments of the present invention will be described in detail. The hair restorer of the present invention effectively uses a humus extract containing fulvic acid having infrared absorption peaks at wave numbers 3362, 2875, 1675, 1559, 1360, 1200, 1047 and 835 cm −1 in the infrared absorption spectrum in the FT-IR method. Including quantity.
　本発明の育毛剤には、腐植抽出物の中でも、上記した特定の赤外線吸収ピークを有する腐植抽出物を使用することを必須とする。腐植抽出物は、上記の赤外線吸収特性を有するものであれば、その由来を問わない。 For the hair restorer of the present invention, it is essential to use a humus extract having the above-described specific infrared absorption peak among humus extracts. A humus extract will not ask | require the origin, if it has said infrared absorption characteristic.
　上記赤外線吸収ピークを有する腐植抽出物を含んだ腐植を水（例えば蒸留水、イオン交換水、逆浸透圧水等）と混合することにより、腐植抽出物が水内に抽出される。その際、腐植を、水１００重量部に対して通常、５～３５重量部、好ましくは１５～２５重量部、特に好ましくは、１７～１８重量部の割合で混合する。上記混合物を、室温で、通常、２４～９６時間、好ましくは４８～７２時間日間放置する。上記放置中、適宜、混合物を撹拌してもよい。次いで、上記混合物の上澄液又は濾液を腐植抽出物とする。液状の腐植抽出物のｐＨは、通常、３．０である。この液状の腐植抽出物を乾固して、粉末としてもよい。 The humus extract containing the humus extract having the infrared absorption peak is mixed with water (for example, distilled water, ion exchange water, reverse osmotic pressure water, etc.) to extract the humus extract into the water. At that time, the humus is usually mixed at a ratio of 5 to 35 parts by weight, preferably 15 to 25 parts by weight, particularly preferably 17 to 18 parts by weight with respect to 100 parts by weight of water. The mixture is left at room temperature, usually for 24 to 96 hours, preferably 48 to 72 hours. During the standing, the mixture may be appropriately stirred. Next, the supernatant or filtrate of the above mixture is used as a humus extract. The pH of the liquid humus extract is usually 3.0. This liquid humus extract may be dried to a powder.
　上記腐植抽出物中のフルボ酸の平均分子量は、４，０００よりも小さく、好ましくは３，５００以下であり、特に好ましくは３，０００以下であり、さらに好ましくは３，０００～１，０００である。 The average molecular weight of fulvic acid in the humus extract is less than 4,000, preferably not more than 3,500, particularly preferably not more than 3,000, and more preferably 3,000 to 1,000. is there.
　前記腐植抽出物は、市販のものでもよく、日本では例えば株式会社スタイルアンドバリュージャパンより製品名「ヒューミクル（登録商標）ＨＣフルボ酸パウダー」として入手可能である。ヒューミクルの成分分析結果（試料湿重量中の含有量）を、表１に示す。 The humus extract may be commercially available, and is available in Japan under the product name “Humicle (registered trademark) HC fulvic acid powder” from, for example, Style and Value Japan Co., Ltd. Table 1 shows the component analysis results (content in the sample wet weight).
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
　ヒューミクルの４％水溶液の全有機炭素（ＴＯＣ）の測定、及びフルボ酸分画の全有機炭素（ＴＯＣ）測定の結果から、ヒューミクル中の炭素のほぼ全量が有機炭素で占められ、そして有機炭素のほぼ全量がフルボ酸を構成していることが確認された。そして、ヒューミクル中のフルボ酸含有量は、約３％と推定された。 From the results of the total organic carbon (TOC) measurement of the 4% aqueous solution of Humicle and the total organic carbon (TOC) measurement of the fulvic acid fraction, almost all of the carbon in the Humicle is occupied by organic carbon, and the organic carbon It was confirmed that almost the entire amount constituted fulvic acid. The fulvic acid content in the fumicle was estimated to be about 3%.
　ヒューミクルのアルカリ（０．１Ｎ水酸化ナトリウム）及び酸（塩酸、ｐＨ２）可溶成分を抽出することにより、フルボ酸を分画した。ヒューミクル又はフルボ酸分画の物性試験方法とその分析結果を以下に示す。 The fulvic acid was fractionated by extracting the fumaric alkali (0.1N sodium hydroxide) and acid (hydrochloric acid, pH 2) soluble components. The physical property test method and analysis results of the fumicle or fulvic acid fraction are shown below.
（１）３次元分光蛍光光度法
　ヒューミクルの４％水溶液の３次元励起－蛍光スペクトル（測定装置ＪＡＳＣＯ　ＦＰ－８２００）を図３に示す。比較のため、愛知県段戸森林土壌から抽出精製されたフルボ酸及びフミン酸（いずれも、日本腐植物質学会から「日本腐植物質学会　標準資料」として頒布されている、以下、それぞれ、段戸産フルボ酸及び段戸産フミン酸という）の３次元蛍光スペクトルを図４に示す。ヒューミクル及び段戸産フルボ酸の３次元励起－蛍光スペクトルには、フルボ酸由来の蛍光の特徴である、励起２５０ｎｍ付近－蛍光４３０ｎｍ付近のピーク及び、励起３２０ｎｍ付近－蛍光４３０ｎｍ付近のピークが出現している。 (1) Three-dimensional spectrofluorometry FIG. 3 shows a three-dimensional excitation-fluorescence spectrum (measuring apparatus JASCO FP-8200) of a 4% aqueous solution of Humicle. For comparison, fulvic acid and humic acid extracted and refined from Danto forest soil in Aichi Prefecture (both are distributed as “Standard Material of the Japanese Humic Society” by the Japanese Humic Society, respectively) FIG. 4 shows three-dimensional fluorescence spectra of fulvic acid and corrugated humic acid. In the three-dimensional excitation-fluorescence spectra of Humicle and Danto's fulvic acid, the peaks near excitation 250 nm-fluorescence around 430 nm and the excitation around 320 nm-fluorescence near 430 nm appear as characteristics of fluorescence derived from fulvic acid. ing.
（２）ＧＰＣ－ＵＶ／ＴＣ分析
　ＧＰＣ－ＵＶ／ＴＣ分析法は、水中溶存有機物を分子の大きさや排除の程度によって高速に分離し、分離した溶存分子をＵＶ検出器及びＴＣ検出器（Ｔｏｔａｌ　Ｃａｒｂｏｎ　Ａｎａｌｙｚｅｒ）でモニタリングする手法である。以下ＧＰＣ－ＴＣ装置：
ＧＰＣ：Ｓｈｏｄｅｘ　ＧＰＣ　ＳＹＳＴＥＭ　２１
分離カラム　ＴＯＳＯ　ＨＷ－５０Ｓ
溶離液　３０ｍＭ　Ｎａ２ＨＰＯ４
ＵＶ吸収（２２０ｎｍ）検出器：ＧＬ７４５０（ＧＬ　サイエンス製）
ＴＣ検出器：ＬＣＴ－１００（東レエンジニアリング製）
を用いて、ヒューミクル及び段戸産フルボ酸の分子量を測定した。 (2) GPC-UV / TC analysis The GPC-UV / TC analysis method separates dissolved organic substances in water at a high speed according to the size of the molecule and the degree of exclusion, and separates the separated dissolved molecules into a UV detector and a TC detector (Total Carbon). (Analyzer) is a monitoring method. The following GPC-TC device:
GPC: Shodex GPC SYSTEM 21
Separation column TOSO HW-50S
Eluent 30 mM Na 2 HPO 4
UV absorption (220 nm) detector: GL7450 (manufactured by GL Sciences)
TC detector: LCT-100 (manufactured by Toray Engineering)
Was used to measure the molecular weights of the fumicle and the fulvic acid from Dando.
　両者のＴＣクロマトグラムでは、段戸産フルボ酸のピーク位置が５１分であるのに対して、ヒューミクル４％溶解液では５４分であった。ピーク位置の保持時間を、使用した分離カラムの多糖類やＰＥＧ（ポリエチレングリコール）の排除特性で換算すると、段戸フルボ酸の分子量は、約４，０００であり、ヒューミクル溶解液中の有機物の分子量は、約１，０００～３，０００と推定された。 In both TC chromatograms, the peak position of Danto fulvic acid was 51 minutes, whereas it was 54 minutes for the 4% humicule solution. When the retention time at the peak position is converted into the exclusion characteristics of the polysaccharide and PEG (polyethylene glycol) of the separation column used, the molecular weight of the terraced fulvic acid is about 4,000, and the molecular weight of the organic matter in the Humicle solution Was estimated to be about 1,000 to 3,000.
　ピークトップとなった保持時間でのＴＣ出力値（ｍＶ）とＵＶ（２２０ｎｍ）吸収での出力値（ｍＶ）、及びＵＶ出力値／ＴＣ出力値（単位有機物量（炭素量）当たりＵＶ吸収の強さ）を表２に示す。 TC output value (mV) at the retention time at the peak top, output value (mV) at UV (220 nm) absorption, and UV output value / TC output value (intensity of UV absorption per unit organic substance amount (carbon amount)) The results are shown in Table 2.
Figure JPOXMLDOC01-appb-T000002
Figure JPOXMLDOC01-appb-T000002
　表２から、ヒューミクル溶解液のＵＶ／ＴＣ値は、段戸産フルボ酸溶解液のものにほぼ近い。有機物の分子構造に由来する紫外吸光（２２０ｎｍ）に類似性があることは、両者の分子構造の骨格や官能基の種類に類似性があることを示している。 From Table 2, the UV / TC value of the Humicle solution is almost similar to that of the Danto fulvic acid solution. The similarity in ultraviolet absorption (220 nm) derived from the molecular structure of organic matter indicates that there is similarity in the skeleton and functional group types of both molecular structures.
（３）フーリエ変換赤外分光光度計法（ＦＴ－ＩＲ）
　前記フルボ酸分画のＡＴＲ法（Ａｔｔｅｎｕａｔｅｄ　Ｔｏｔａｌ　Ｒｅｆｌｅｃｔｉｏｎ、全反射吸収法）にて赤外線吸収スペクトルを取得した。具体的には、前記フルボ酸分画をＤａｘ－８樹脂（Ｓｐｅｌｃｏ社製）に施用し、そこに吸着した有機物をアルカリ性溶液で脱着した。脱着した有機物を、さらにイオン交換樹脂に通して不要な塩類を取り除いた。得られた試料をＡＴＲ法に基づくＦＴ－ＩＲ分光分析（ＰｅｒｋｉｎＥｌｍｅｒ　Ｓｐｅｃｔｒｕｍ　６５）に供した。 (3) Fourier transform infrared spectrophotometer method (FT-IR)
An infrared absorption spectrum was obtained by the ATR method (Attenuated Total Reflection, total reflection absorption method) of the fulvic acid fraction. Specifically, the fulvic acid fraction was applied to Dax-8 resin (manufactured by Spelco), and the organic matter adsorbed thereon was desorbed with an alkaline solution. The desorbed organic substance was further passed through an ion exchange resin to remove unnecessary salts. The obtained sample was subjected to FT-IR spectroscopic analysis (PerkinElmer Spectrum 65) based on the ATR method.
　腐植抽出物（ヒューミクル）に含有されるフルボ酸の赤外線吸収スペクトルを図１に示す。比較のため、段戸産のフルボ酸及びフミン酸の赤外線吸収スペクトルを図２に示す。図１（ヒューミクル）及び図２（段戸産フルボ酸）から主要な赤外線吸収ピークをそれぞれ抽出し、その結果を波数で表３に示す。 The infrared absorption spectrum of fulvic acid contained in the humus extract (Humicle) is shown in FIG. For comparison, FIG. 2 shows infrared absorption spectra of fulvic acid and humic acid produced in Danto. Major infrared absorption peaks were extracted from FIG. 1 (Humicle) and FIG. 2 (Stepbo fulvic acid), and the results are shown in Table 3 in terms of wave number.
Figure JPOXMLDOC01-appb-T000003
Figure JPOXMLDOC01-appb-T000003
　ヒューミクルに含有されるフルボ酸及び段戸産フルボ酸は、共通して１２００ｃｍ－１にカルボキシル基（Ｃ－Ｏ）吸収ピークを有するが、そのレベルは、ヒューミクルの方が段戸産フルボ酸よりも小さい。ヒューミクル中のフルボ酸が段戸産フルボ酸のスペクトルと明確に相違する点は、１５５９、１０４７及び８３５ｃｍ－１にトリ置換ベンゼンタイプのシグナルが観測され、そして３３６２及び１３６０ｃｍ－１にフェノールあるいはアルコールタイプのシグナルが観測されることである。 The fulvic acid contained in Humicle and the fulvic acid produced in Dando have a carboxyl group (C—O) absorption peak at 1200 cm −1 in common, but the level of Humicle is higher than that of Danfu fulvic acid. small. That fulvic acid in Hyumikuru is clearly different spectrum of Danto producing fulvic acids are 1559,1047 and tri-substituted benzene type signals were observed at 835 cm -1, and phenol or an alcohol type 3362 and 1360 cm -1 Is observed.
　赤外分光分析の結果は、ヒューミクル中のフルボ酸が段戸産フルボ酸よりもカルボキシル基が少なく、トリ置換ベンゼンタイプのフェノール化合物の構造を多いことを示唆する。発明を限定する意図ではないが、この分子構造の違いが、後述の実施例と比較例に示すように、毛乳頭細胞の増殖率の相違に反映したと考えられる。すなわち、本発明で特定する特定の赤外線吸収スペクトル特性を有する中のフルボ酸を含有する腐植抽出物が有効量添加された育毛剤は、腐植物質を含む従来の育毛剤よも優れた効能を有する。 The result of infrared spectroscopic analysis suggests that the fulvic acid in the humicle has fewer carboxyl groups than the dansted fulvic acid, and the structure of the tri-substituted benzene type phenolic compound is greater. Although not intended to limit the invention, it is considered that this difference in molecular structure is reflected in a difference in the proliferation rate of hair papilla cells as shown in Examples and Comparative Examples described later. That is, the hair restorer to which an effective amount of a humus extract containing fulvic acid having the specific infrared absorption spectrum characteristic specified in the present invention is added has an effect superior to that of a conventional hair restorer containing humic substances. .
　本発明の経皮用育毛剤には、上記の腐植抽出物以外に、化粧品学的、皮膚病学的及び／又は薬学的に許容される添加剤として汎用されるものが添加される。例えば、水；エチレングリコール、ポリエチレングリコール、プロピレングリコール、１，３－ブチレングリコール、１，４－ブチレングリコール、ジプロピレングリコール、グリセリン、ジグリセリン、ポリグリセリン、ペンチレングリコール、イソプレングリコール、グルコース、マルトース、フルクトース、キシリトール、ソルビトール、マルトトリオース、エリスリトール等の多価アルコール；メタノール、エタノール、プロピルアルコール、イソプロピルアルコール、ブチルアルコール、イソブチルアルコール等の低級アルコール；オレイン酸、イソステアリン酸、ラウリン酸、ミリスチン酸、パルミチン酸、ステアリン酸、ベヘン酸、ウンデシレン酸等の高級脂肪酸類；オリーブ油、トウモロコシ油、ツバキ油、マカデミアナッツ油、アボカド油、ナタネ油、ゴマ油、ヒマシ油、サフラワー油、綿実油、ホホバ油、ヤシ油、パーム油等の油脂；カルナバロウ、キャンデリラロウ、ミツロウ、ラノリン等のロウ類；ソルビトール、マンニトール、グルコース、ショ糖、ラクトース、トレハロース等の糖類；カラギーナン、キサンタンガム、ゼラチン、ペクチン、アガロース、アルギン酸塩、デキストリン、メチルセルロース、エチルセルロース、ヒドロキシプロピルセルロース、ヒドロキシエチルセルロース、カルボキシメチルセルロース、カルボキシビニルポリマー、ポリビニルアルコール、ポリビニルピロリドン、アラビアガム、カラヤガム、トラガントガム、タマリンドガム等の増粘剤；フェノキシエタノール、メチルパラベン、エチルパラベン、プロピルパラベン、ブチルパラベン、パラオキシ安息香酸エステル、安息香酸、サリチル酸とその塩類、ソルビン酸とその塩類、デヒドロ酢酸とその塩類、クロルクレゾール、ヘキサクロロフェン等の防腐剤；ラウロイル硫酸ナトリウム、モノオレイン酸ポリオキシエチレンソルビタン等の非イオン界面活性剤、アルキルサルフェート塩、ノルマルドデシルベンゼンスルホン酸ナトリウム等の陰イオン界面活性剤、ポリオキシエチレンドデシルモノメチルアンモニウムクロライド等の陽イオン界面活性剤；ステロイド系及び非ステロイド系抗炎症剤；ビタミンＡ、ビタミンＤ、ビタミンＥ、ビタミンＦ、ビタミンＫ等のビタミン類やジカプリル酸ピリドキシン、ジパルミチン酸ピリドキシン、ジパルミチン酸アスコルビル、モノパルミチン酸アスコルビル、モノステアリン酸アスコルビル等のビタミン誘導体；フラボノイド、カロテノイド等の抗酸化剤；スクワラン、スクワレン、流動パラフィン等の高級脂肪族炭化水素類；セラミド、セレブロシド、スフィンゴミエリン等のスフィンゴ脂質；コレステロール、フィトステロール等のステロール類；メチルポリシロキサン、メチルフェニルポリシロキサン、メチルシクロポリシロキサン、オクタメチルシクロテトラシロキサン、オクタメチルシクロペンタシロキサン、デカメチルシクロペンタシロキサン、メチルハイドロジェンポリシロキサン等のシリコーン類；パラアミノ安息香酸、パラアミノ安息香酸モノグリセリンエステル、アントラニル酸メチル、ホモメンチル－Ｎ－アセチルアントラニレート、パラメトキシケイ皮酸オクチル、エチル－４－イソプロピルシンナメート等の紫外線吸収剤；ベントナイト、スメクタイト、バイデライト、ノントロナイト、サポナイト、ヘクトライト、ソーコナイト、スチーブンサイト等の鉱物；ベンガラ、黄酸化鉄、黒酸化鉄、酸化コバルト、群青、紺青、酸化チタン、酸化亜鉛等の無機顔料；赤色２０２号、黄色４号、青色４０４号等の着色料；香料；香油等が挙げられる。 In addition to the above-mentioned humus extract, those which are generally used as cosmetically, dermatologically and / or pharmaceutically acceptable additives are added to the hair growth agent for transdermal use of the present invention. For example, water; ethylene glycol, polyethylene glycol, propylene glycol, 1,3-butylene glycol, 1,4-butylene glycol, dipropylene glycol, glycerin, diglycerin, polyglycerin, pentylene glycol, isoprene glycol, glucose, maltose, Polyhydric alcohols such as fructose, xylitol, sorbitol, maltotriose, erythritol; lower alcohols such as methanol, ethanol, propyl alcohol, isopropyl alcohol, butyl alcohol, isobutyl alcohol; oleic acid, isostearic acid, lauric acid, myristic acid, palmitic acid Higher fatty acids such as acid, stearic acid, behenic acid, undecylenic acid; olive oil, corn oil, camellia oil, macadamia Oil, avocado oil, rapeseed oil, sesame oil, castor oil, safflower oil, cottonseed oil, jojoba oil, coconut oil, palm oil, etc .; waxes such as carnauba wax, candelilla wax, beeswax, lanolin; sorbitol, mannitol, glucose Sugars such as sucrose, lactose, trehalose; carrageenan, xanthan gum, gelatin, pectin, agarose, alginate, dextrin, methylcellulose, ethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, carboxymethylcellulose, carboxyvinyl polymer, polyvinyl alcohol, polyvinylpyrrolidone, Thickeners such as gum arabic, karaya gum, tragacanth gum, tamarind gum; phenoxyethanol, methyl paraben, ethyl paraben, propyl parabe , Butylparaben, paraoxybenzoic acid ester, benzoic acid, salicylic acid and its salts, sorbic acid and its salts, dehydroacetic acid and its salts, chlorcresol, hexachlorophene, etc., preservatives: sodium lauroyl sulfate, polyoxyethylene sorbitan monooleate Nonionic surfactants such as alkyl sulfate salts, anionic surfactants such as sodium normal dodecylbenzenesulfonate, and cationic surfactants such as polyoxyethylene dodecyl monomethylammonium chloride; steroidal and nonsteroidal anti-inflammatory agents Vitamins such as vitamin A, vitamin D, vitamin E, vitamin F, vitamin K, pyridoxine dicaprylate, pyridoxine dipalmitate, ascorbyl dipalmitate, ascorbyl monopalmitate, Vitamin derivatives such as ascorbyl nostearate; antioxidants such as flavonoids and carotenoids; higher aliphatic hydrocarbons such as squalane, squalene and liquid paraffin; sphingolipids such as ceramide, cerebroside and sphingomyelin; sterols such as cholesterol and phytosterols Silicones such as methylpolysiloxane, methylphenylpolysiloxane, methylcyclopolysiloxane, octamethylcyclotetrasiloxane, octamethylcyclopentasiloxane, decamethylcyclopentasiloxane, methylhydrogenpolysiloxane; paraaminobenzoic acid, paraaminobenzoic acid Acid monoglycerin ester, methyl anthranilate, homomenthyl-N-acetylanthranilate, octyl paramethoxycinnamate, ethyl -UV absorbers such as isopropyl cinnamate; minerals such as bentonite, smectite, beidellite, nontronite, saponite, hectorite, soconite, stevensite; bengara, yellow iron oxide, black iron oxide, cobalt oxide, ultramarine, bitumen, Inorganic pigments such as titanium oxide and zinc oxide; coloring agents such as red 202, yellow 4 and blue 404; fragrances; fragrance oils and the like.
　本発明の経皮用育毛剤の形態の例は、水剤、液剤、乳剤、乳液、エマルション、クリーム、粉体、及びクレイパックである。皮膚への直接の効果を引き出すために、経皮用育毛剤は、水剤、液剤、乳剤、乳液、エマルション、又はクリームの形態が好ましい。 Examples of the form of the transdermal hair restorer of the present invention are a liquid agent, a liquid agent, an emulsion, an emulsion, an emulsion, a cream, a powder, and a clay pack. In order to bring out a direct effect on the skin, the hair growth agent for transdermal use is preferably in the form of a solution, solution, emulsion, emulsion, emulsion or cream.
　本発明の経皮用育毛剤は、シャンプー、リンス、リンスインシャンプー等の頭髪用入浴剤；ヘアミスト、ヘアスプレー、ヘアフォーム、ヘアリキッド等の頭髪用化粧品に含有させ、これらの入浴剤や化粧品にさらに育毛作用を付加してもよい。 The transdermal hair restorer of the present invention is contained in hair cosmetics such as shampoos, rinses and rinse-in shampoos; hair cosmetics such as hair mists, hair sprays, hair foams, hair liquids, and the like. A hair restoring action may be added.
　本発明の経皮用育毛剤中の腐植抽出物（フルボ酸を約３％含有）の含有量は、有効量であればよく、通常、０．００１～２０重量％でよく、好ましくは０．０１～２０重量％であり、さらに好ましくは０．０５～１５重量％であり、特に好ましくは０．１～１０重量％である。 The content of the humus extract (containing about 3% fulvic acid) in the transdermal hair restorer of the present invention may be an effective amount, usually 0.001 to 20% by weight, preferably 0.00. It is 01 to 20% by weight, more preferably 0.05 to 15% by weight, and particularly preferably 0.1 to 10% by weight.
　本発明の経皮用育毛剤の１回当たりの適用量もまた、年齢、発毛状況、個人差等に応じて有効量であればよい。 </ RTI> The applied amount of the percutaneous hair restorer of the present invention may be an effective amount depending on age, hair growth status, individual differences and the like.
　本発明の経口用育毛剤は、汎用の食品添加物を添加してもよい。例えば、経口投与の形態に応じて、汎用の賦形剤、崩壊剤、結合剤、滑沢剤、ビタミン、キサンチン誘導体、アミノ酸、ｐＨ調整剤、清涼化剤、懸濁化剤、粘稠剤、溶解補助剤、抗酸化剤、コーティング剤、可塑剤、界面活性剤、水、アルコール類、水溶性高分子、甘味料、矯味剤、酸味料、香料、着色剤等を発明の効果を損なわない質的及び量的範囲で添加することが可能である。 General-purpose food additives may be added to the oral hair restorer of the present invention. For example, depending on the form of oral administration, general-purpose excipients, disintegrants, binders, lubricants, vitamins, xanthine derivatives, amino acids, pH adjusters, cooling agents, suspending agents, thickeners, Solubilizing agents, antioxidants, coating agents, plasticizers, surfactants, water, alcohols, water-soluble polymers, sweeteners, corrigents, acidulants, fragrances, coloring agents, etc. It is possible to add in the target and quantitative range.
　本発明の経口用育毛剤の形態は、例えば、散剤、顆粒剤、カプセル剤、丸剤、錠剤、チュアブル錠、ドロップ、水剤、シロップ、及びドリンク剤のような通常の食品とは異なる経口投与剤に加工される。 The form of the oral hair restorer of the present invention is different from ordinary foods such as powders, granules, capsules, pills, tablets, chewable tablets, drops, liquids, syrups and drinks. It is processed into an agent.
　本発明の経口用育毛剤中の腐植抽出物（フルボ酸を約３％含有）の含有量は、有効量であればよく、通常、０．１～７０重量％でよく、好ましくは０．１～３０重量％であり、より好ましくは０．１～１５重量％である。 The content of the humus extract (containing about 3% of fulvic acid) in the oral hair restorer of the present invention may be an effective amount, usually 0.1 to 70% by weight, preferably 0.1%. -30% by weight, more preferably 0.1-15% by weight.
　本発明の経口用育毛剤の１日当たりの摂取量もまた、年齢、発毛状況、個人差等に応じて有効量であればよい。 The daily intake of the oral hair restorer of the present invention may be an effective amount depending on age, hair growth status, individual differences, and the like.
　以下に、本発明の実施例及び比較例を示すことにより、本発明をより詳細に説明する。しかし、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 in more detail by showing examples and comparative examples of the present invention. However, the present invention is not limited to the following examples.
〔実施例１、比較例１～４〕
　本発明の育毛剤が育毛作用を有するか否かを、毛乳頭細胞の実験モデル系である毛乳頭細胞増殖効果試験（ｉｎ　ｖｉｔｒｏ）で調べた。具体的には、毛乳頭細胞へ本発明の育毛剤を添加し、ＭＴＴアッセイによって毛乳頭細胞の細胞増殖促進率を測定し、さらに毛乳頭細胞増殖率を算出した。 [Example 1, Comparative Examples 1 to 4]
Whether or not the hair-restoring agent of the present invention has a hair-growing action was examined by a hair papilla cell proliferation effect test (in vitro), which is an experimental model system for hair papilla cells. Specifically, the hair growth agent of the present invention was added to the hair papilla cells, the cell growth promotion rate of the hair papilla cells was measured by MTT assay, and the hair papilla cell growth rate was calculated.
１．育毛剤試験品の準備
　実施例１として、米国ユタ産の腐植の水性抽出物を乾固した腐植抽出物製品「ヒューミクル」（株式会社スタイルアンドバリュージャパン製）を用意した。ヒューミクルに含まれるフルボ酸分画の物性は、上記したとおりである。 1. Preparation of Hair Growth Agent Test Product As Example 1, a humus extract product “Humicle” (manufactured by Style and Value Japan Co., Ltd.) obtained by drying an aqueous extract of humus produced in Utah, USA was prepared. The physical properties of the fulvic acid fraction contained in the vehicle are as described above.
　また、本発明の育毛剤の効果を評価するための陽性対照として、従来、育毛作用の知られているフィナステリドを用意した。また、コントロール（陰性対照）として、培地（試験品添加無し）を採用した。さらに、本発明を満たさない腐植物質を含む育毛剤と本発明の育毛剤とを対比するために、以下に示す腐植抽出物を含む育毛剤製品、及び標準フルボ酸を用意した。
比較例１：果物や植物の発酵により得られたフルボ酸１００％のＭ社製健康飲料
比較例２：長崎県北高来郡森山町唐比西産の腐植抽出物（フルボ酸）を含んだN社製育毛剤
比較例３：段戸産フルボ酸（腐植酸標準物質、日本腐植物質学会製）
比較例４：琵琶湖産フルボ酸（腐植酸標準物質、日本腐植物質学会製） As a positive control for evaluating the effect of the hair restorer of the present invention, finasteride, which has been conventionally known for its hair restoring action, was prepared. As a control (negative control), a medium (no test product added) was employed. Furthermore, in order to contrast the hair restorer containing humic substances that do not satisfy the present invention and the hair restorer of the present invention, hair restorer products containing the following humus extracts and standard fulvic acid were prepared.
Comparative Example 1: 100% fulvic acid obtained by fermentation of fruits and plants, health drink manufactured by M Company Comparative Example 2: Company N containing humus extract (fulvic acid) from Karabi, Moriyama-cho, Kitakagi-gun, Nagasaki Prefecture Hair-growth comparative example 3: Danto fulvic acid (humic acid reference material, manufactured by the Japan Humic Society)
Comparative example 4: Lake Biwa fulvic acid (humic acid reference material, manufactured by Japanese Humic Society)
２．ヒト頭髪毛乳頭細胞の基礎培養
　試験用細胞には、ヒト頭髪毛乳頭細胞（タカラバイオ社製）を用いた。培養フラスコ（培養面積７５ｃｍ２）にヒト頭髪毛乳頭細胞培地及びヒト頭髪毛乳頭細胞懸濁液を培養液中の細胞の最終濃度が２．５×１０４ｃｅｌｌｓ／ｍＬ、全量１０ｍＬとなるように添加し、ＣＯ２インキュベーター（３７℃、ＣＯ２　５％）で、７日培養して必要細胞数を確保した。 2. Basic culture of human hair papilla cells Human hair papilla cells (manufactured by Takara Bio Inc.) were used as test cells. In a culture flask (culture area 75 cm 2 ), the human hair dermal papilla cell culture medium and the human hair dermal papilla cell suspension are adjusted to a final concentration of 2.5 × 10 4 cells / mL in the culture solution and a total volume of 10 mL. The cells were added and cultured in a CO 2 incubator (37 ° C., CO 2 5%) for 7 days to ensure the necessary number of cells.
３．試験品溶液の調製
　実施例１及び比較例１～４の育毛剤試験品を、それぞれ、試験品濃度が１２５、３１．２５、７．８１、１．９５、０．４８、又は０．１２μｇ／ｍｌとなるように、順次、毛乳頭細胞培地で希釈した。陽性対照のＦｉｎａｓｔｅｒｉｄｅは、３ｎｇ／ｍＬとなるように希釈した。 3. Preparation of test article solution The hair growth agent test articles of Example 1 and Comparative Examples 1 to 4 were tested at a concentration of 125, 31.25, 7.81, 1.95, 0.48, or 0.12 μg / 0.1%, respectively. Diluted sequentially with hair papilla cell culture medium to a volume of ml. The positive control Finasteride was diluted to 3 ng / mL.
４．細胞増殖能評価試験
４．１　ヒト頭髪毛乳頭細胞の培養
　培養したヒト頭髪毛乳頭細胞をＴｒｙｐｓｉｎ処理により培養フラスコから回収し、細胞数をカウントした。細胞を毛乳頭細胞培地で懸濁し、細胞濃度が１×１０４ｃｅｌｌｓ／ｍＬの細胞懸濁液を調製した。調製した細胞懸濁液を試験プレート（９６ｗｅｌｌ　ｍｉｃｒｏ　ｐｌａｔｅ）に０．２ｍＬずつ、各ｗｅｌｌに添加し、室温で２０分静置した。ＣＯ２インキュベーター（３７℃、ＣＯ２　５％）にて１８時間の前培養した。前培養後、試験プレート各ウェルの培地と調製した試験品溶液を置き換え、さらにＣＯ２インキュベーター（３７℃、ＣＯ２　５％）にて７２時間培養した。７２時間後、ＭＴＴアッセイによる生存率を確認した。※独立３回にて試験結果を算出した。 4). 4. Cell Proliferation Evaluation Test 4.1 Culture of human hair dermal papilla cells Cultured human hair dermal papilla cells were collected from the culture flask by trypsin treatment, and the number of cells was counted. Cells were suspended in a hair papilla cell medium to prepare a cell suspension having a cell concentration of 1 × 10 4 cells / mL. 0.2 mL of the prepared cell suspension was added to each well on a test plate (96 well micro plate), and allowed to stand at room temperature for 20 minutes. Pre-cultured for 18 hours in a CO 2 incubator (37 ° C., CO 2 5%). After the preculture, the medium in each well of the test plate was replaced with the prepared test solution, and further cultured in a CO 2 incubator (37 ° C., CO 2 5%) for 72 hours. After 72 hours, viability was confirmed by MTT assay. * Test results were calculated three times independently.
４．２　ＭＴＴアッセイ
　培養終了後のプレートの培地を捨て、新たにＭＴＴ試薬含有培地（１ｍｇＭＴＴ／ｍＬ培地）を０．１ｍＬずつ各Ｗｅｌｌに添加した。ＣＯ２インキュベーター（３７℃、ＣＯ２　５％）にて３時間培養し、呈色反応を行った。ＭＴＴ可溶化溶液（イソプロパノール）を０．１ｍＬずつ各ｗｅｌｌに添加し、生細胞に取り込まれたＭＴＴを抽出した。マイクロプレートリーダーを使用してＭＴＴ抽出液の吸光度を５７０ｎｍで測定した。下記式に示すように、コントロール（試験品未処理細胞）の吸光度を１００とした場合の百分率で細胞増殖率を算出した。
Figure JPOXMLDOC01-appb-M000004
 4.2 MTT assay The medium of the plate after completion of the culture was discarded, and 0.1 mL of MTT reagent-containing medium (1 mg MTT / mL medium) was newly added to each well. The color reaction was performed by culturing in a CO 2 incubator (37 ° C., CO 2 5%) for 3 hours. MTT solubilized solution (isopropanol) was added to each well in an amount of 0.1 mL to extract MTT taken up by living cells. The absorbance of the MTT extract was measured at 570 nm using a microplate reader. As shown in the following formula, the cell growth rate was calculated as a percentage when the absorbance of the control (untreated cells of the test product) was 100.
Figure JPOXMLDOC01-appb-M000004
４．３　試験データ及び統計解析
　得られたデータについて、分散分析を行い、等分散が確認された場合には統計解析として対応のないｔ検定を実施し、対照区との比較を実施した。試験結果を表４及び図５に示す。 4.3 Test data and statistical analysis An analysis of variance was performed on the obtained data. When equal variance was confirmed, an uncorresponding t-test was performed as a statistical analysis, and a comparison with a control group was performed. The test results are shown in Table 4 and FIG.
Figure JPOXMLDOC01-appb-T000005
Figure JPOXMLDOC01-appb-T000005
　陽性対照である濃度（３ｎｇ／ｍｌ）のフィナステリドは、コントロール（細胞増殖率１００％）に対して、１０６．８±０．６％の毛乳頭細胞増殖率を示し、毛乳頭細胞増加活性が確認された。 Finasteride at a concentration (3 ng / ml), which is a positive control, showed a hair papillary cell proliferation rate of 106.8 ± 0.6% relative to the control (cell growth rate 100%), confirming hair papillary cell increasing activity. It was done.
　それに対して、本発明の育毛剤（実施例１）は、濃度０．４８～１２５μｇ／ｍｌにおいて、１０７．４～１１６．２％の細胞増殖率を示した。特に、実施例１の濃度１．９５μｇ／ｍｌでの毛乳頭細胞増殖率１１６．２％は、陽性対照に対して１．０９倍（＝１１６．２／１０６．８）上回る増殖活性を示した。 In contrast, the hair restorer of the present invention (Example 1) showed a cell growth rate of 107.4 to 116.2% at a concentration of 0.48 to 125 μg / ml. In particular, the dermal papilla cell proliferation rate of 116.2% at a concentration of 1.95 μg / ml in Example 1 showed 1.09 times (= 116.2 / 106.8) greater proliferation activity than the positive control. .
　次に、比較例３（段戸酸フルボ酸）及び比較例４（琵琶湖酸）は、日本腐植学会標準品のフルボ酸である。比較例３及び４を実施例１と対比すると、比較３及び４は、フルボ酸濃度０．４８～１２５μｇ／ｍｌにおいて実施例１と似た傾向を示したが、その細胞増殖率は、９９．８～１０６．７％（比較例３）及び９６．４～１０２．７％（比較例４）と、実施例１よりも劣った。 Next, Comparative Example 3 (stepped acid fulvic acid) and Comparative Example 4 (Lake Lake acid) are fulvic acids that are standard products of the Japanese Humic Society. Comparing Comparative Examples 3 and 4 with Example 1, Comparatives 3 and 4 showed a tendency similar to Example 1 at a fulvic acid concentration of 0.48 to 125 μg / ml, but the cell growth rate was 99.99. 8-106.7% (Comparative Example 3) and 96.4-102.7% (Comparative Example 4), inferior to Example 1.
　比較例１は、本発明に使用する腐植抽出物と違って、果物や植物を出発材料として人工的に合成したフルボ酸である。比較例２は、特許文献１及び２の実施例で使用された長崎県北高来郡森山町唐比西産の腐植抽出物と推定される。これらの比較例１及び２を、実施例１と対比すると、比較例１及び２の細胞増殖率は、それぞれ、８６．１～１０４．４％、及び９４．２～１０１．２％と実施例１よりも明らかに劣った。 Comparative Example 1 is a fulvic acid artificially synthesized using fruits and plants as starting materials, unlike the humus extract used in the present invention. Comparative Example 2 is presumed to be a humus extract produced in Karabi, Moriyama-cho, Moritaka-machi, Kitakagi-gun, Nagasaki Prefecture, which was used in Examples of Patent Documents 1 and 2. When these Comparative Examples 1 and 2 were compared with Example 1, the cell growth rates of Comparative Examples 1 and 2 were 86.1 to 104.4% and 94.2 to 101.2%, respectively. Obviously inferior to 1.
　以上の結果から、特定の腐植抽出物を含む本発明の育毛剤は、毛乳頭細胞増殖活性が知られているフィナステリド、腐植抽出物標準品、及び腐植抽出物を含む既存の育毛剤製品よりも高い毛乳頭細胞増殖活性があることが判明した。したがって、本発明の育毛剤は、優れた育毛作用を有する育毛剤としての産業上の利用性が期待される。 From the above results, the hair restorer of the present invention containing a specific humus extract is more effective than finasteride, a humus extract standard product, and an existing hair restorer product containing a humus extract, which are known to have hair papilla cell proliferation activity. It was found to have high hair papilla cell proliferation activity. Accordingly, the hair growth agent of the present invention is expected to be industrially useful as a hair growth agent having an excellent hair growth action.

Claims (7)

  1. ＦＴ－ＩＲ法における赤外線吸収スペクトルにおいて波数３３６２，２８７５，１６７５，１５５９，１３６０，１２００，１０４７及び８３５ｃｍ－１に赤外線吸収ピークを有し、４，０００よりも小さい平均分子量を有するフルボ酸を含有する腐植抽出物を有効量含み、そして化粧品学的、皮膚病学的及び／又は薬学的に許容される添加剤あるいは食品添加物を含んでなる育毛剤。 Contains fulvic acid having infrared absorption peaks at wave numbers 3362, 2875, 1675, 1559, 1360, 1200, 1047 and 835 cm −1 in the infrared absorption spectrum in the FT-IR method and having an average molecular weight of less than 4,000 A hair restorer comprising an effective amount of a humus extract and comprising a cosmetically, dermatologically and / or pharmaceutically acceptable additive or food additive.
  2. 　前記腐植抽出物は、図１に示す赤外線吸収スペクトルを示すフルボ酸を含有する、請求項１に記載の育毛剤。 The hair restoring agent according to claim 1, wherein the humus extract contains fulvic acid having an infrared absorption spectrum shown in FIG.
  3. 　前記腐植抽出物は、ナフタレン環構造を有さないことを特徴とする、請求項１に記載の育毛剤。 The hair restoring agent according to claim 1, wherein the humus extract does not have a naphthalene ring structure.
  4. 経皮投与用である、請求項１に記載の育毛剤。 The hair restorer according to claim 1, which is for transdermal administration.
  5. 　水剤、液剤、乳剤、乳液、エマルション、クリーム、粉体、又はクレイパックの形態である、請求項４に記載の育毛剤。 The hair restorer according to claim 4, which is in the form of a liquid preparation, liquid preparation, emulsion, emulsion, emulsion, cream, powder, or clay pack.
  6. 経口投与用である、請求項１に記載の育毛剤。 The hair restorer according to claim 1, which is for oral administration.
  7. 散剤、顆粒剤、カプセル剤、丸剤、錠剤、チュアブル錠、ドロップ、水剤、シロップ、又はドリンク剤の形態である、請求項６に記載の育毛剤。 The hair restorer according to claim 6, which is in the form of a powder, granule, capsule, pill, tablet, chewable tablet, drop, solution, syrup, or drink.
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JP2006327978A (en) * 2005-05-25 2006-12-07 Myubio Co Ltd Hair grower
WO2007102813A1 (en) * 2006-03-07 2007-09-13 Advantage Marketing, Inc. Compositions and methods for human use containing fulvic acid
JP2013107857A (en) * 2011-11-22 2013-06-06 Funao Kurosawa Skin external preparation

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Publication number Priority date Publication date Assignee Title
JP2006327978A (en) * 2005-05-25 2006-12-07 Myubio Co Ltd Hair grower
WO2007102813A1 (en) * 2006-03-07 2007-09-13 Advantage Marketing, Inc. Compositions and methods for human use containing fulvic acid
JP2013107857A (en) * 2011-11-22 2013-06-06 Funao Kurosawa Skin external preparation

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112972313A (en) * 2021-03-08 2021-06-18 德利宝(广州)香料有限公司 Preparation method of modified humus extract and shampoo composition containing modified humus extract

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