JP2008044855A - Activator comprising biosurfactant as active ingredient - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an activator and an anti-aging agent having excellent activating and anti-aging effects on cells and safety sufficiently withstanding use over a long period and to provide a cosmetic, a quasi-drug, a medicine and a food and drink comprising the same as an active ingredient. <P>SOLUTION: The activator is obtained by formulating a biosurfactant, especially at least one kind selected from the group consisting of MEL (mannosyl erythritol lipid), MML (mannosyl mannitol lipid), a triacyl derivative of the MEL (mannosyl erythritol lipid) and a triacyl derivative of the MML (mannosyl mannitol lipid) as the active ingredient. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to an activator comprising a biosurfactant as an active ingredient, and in particular, a cosmetic, a quasi-drug containing a biosurfactant that activates various cells and is effective in preventing aging and preventing hair growth and hair loss, It relates to medicines and foods and drinks.

  Individual aging and the various diseases that accompany this are closely related to the aging of all dividing cells (decrease in division rate and cell function). For example, the skin is composed of epidermal cells, fibroblasts, and extracellular matrices such as elastin and collagen that support these extracellular skin structures. In young skin, moisture retention, flexibility, and elasticity are ensured by maintaining the constancy of the interaction between these skin tissues, and the skin has a firm and glossy appearance and is kept fresh. However, aging, ultraviolet rays, drying, stress, etc. cause deterioration of the function of the extracellular matrix and fibroblasts in particular. As a result, the skin's flexibility and moisturizing function are reduced, and the skin loses its tension and gloss and becomes rough. Aging symptoms such as wrinkles and dullness occur.

  Searching for an activator and an anti-aging agent has been carried out for the purpose of preventing or suppressing aging at the cellular level. For example, connective tissue hydrolysates (Patent Document 1), thymus / spleen-derived water-soluble protein (Patent Document 2), bovine placenta extract (Patent Document 3) and the like are known as animal-derived activators. Examples of plant-derived activators include sesame seeds, sayaks, capsicum, toki, dokudami, bakumondo (patent document 4), almonds, dandelion, elderberry, cucumber, assembly, perch, carrots, carrots, hops, mokuge, and yokoinin (patents) Document 5, Patent Document 6), extracts of Ginger family Turmeric (Patent Document 7), Hanayoriaceae Hanayasuri (Patent Document 8) and the like are known. Some of these are used as activating agents and anti-aging agents in quasi-drugs and cosmetics, but no activating agents or anti-aging agents that exhibit satisfactory effects have been obtained.

  Mannosyl erythritol lipid (MEL) is a natural surfactant produced by yeast, and various physiological actions have been reported (Non-patent Document 1). Recently, mannosyl mannitol lipid (MML) in which erythritol replaces mannitol has been found (Patent Document 9). Uses as external preparations and cosmetics are useful as anti-inflammatory agents and antiallergic agents (Patent Document 10), hair nourishing and hair-restoring agents (Patent Document 11), antibacterial action (Patent Document 12), and surface tension reduction. The action (Patent Document 13) is known.

However, the activation effect of MEL on cells was not known at all. Moreover, the effect of the hair-growth action described in Patent Document 11 has been confirmed using animals, and it has not been reported to activate human hair hair papilla cells.
JP-A-62-84024 Japanese Patent Laid-Open No. 63-188867 Japanese Patent Laid-Open No. 03-141299 Japanese Patent Laid-Open No. 10-45615 Japanese Patent Laid-Open No. 10-036279 Japanese Patent Laid-Open No. 10-36279 JP 2004-75632 A JP 2005-89375 A JP 2005-104837 A JP 2005-68015 A JP 2003-261424 A JP-A-57-145896 JP-A-61-205450 Journal of Bioscience and Bioengineering, 94,187 (2002)

  Giving activation and anti-aging to mammals, especially humans, is an extremely important issue, and various animal-derived and plant-derived activators and anti-aging agents have been found, but they can actually be used industrially. A sufficient and stable effect has not been obtained to date, and new activators and anti-aging agents are currently being searched. Accordingly, an object of the present invention is to provide an activator and an anti-aging agent that have excellent activation and anti-aging effects on cells and have safety sufficient to withstand long-term use, and cosmetics comprising these as active ingredients・ To provide quasi-drugs, pharmaceuticals, and food and drinks.

  As a result of diligent efforts to achieve the above object, the present inventors have found that MEL and triacyl MEL are effective for cell activation, and have completed the present invention. That is, the present invention includes the following inventions.

  (1) An activator comprising a biosurfactant as an active ingredient.

  (2) The biosurfactant is at least 1 selected from the group consisting of mannosyl erythritol lipid (MEL), mannosyl mannitol lipid (MML), manacyl erythritol lipid (MEL) triacyl, and mannosyl mannitol lipid (MML) triacyl. The activator according to (1), which is a seed.

  (3) An anti-aging agent comprising the activator according to (1) or (2) as an active ingredient.

  (4) A hair restorer comprising the activator according to (1) or (2) as an active ingredient.

  (5) An external preparation for skin, comprising as an active ingredient the activator according to (1) or (2), the anti-aging agent according to (3), or the hair restorer according to (4). Agent.

  (6) A cosmetic comprising the activator according to (1) or (2), the anti-aging agent according to (3), or the hair-restoring agent according to (4) as an active ingredient.

  (7) A pharmaceutical part comprising the activator according to (1) or (2) above, the anti-aging agent according to (3), or the hair restorer according to (4) as an active ingredient. Foreign goods.

  (8) A pharmaceutical comprising the activator according to (1) or (2) above, the anti-aging agent according to (3), or the hair restorer according to (4) as an active ingredient.

  The biosurfactant used as an active ingredient of the activator according to the present invention has a significant activation effect on various cells. Therefore, the activator according to the present invention exhibits excellent effects as an anti-aging agent and a hair restorer. Moreover, since biosurfactant is a biologically derived natural surfactant, it is excellent in safety, and the activator according to the present invention has an effect that it can sufficiently withstand long-term use. Furthermore, since biosurfactants can be produced by culturing microorganisms, raw material costs are low, and mass production is possible. Therefore, the activator according to the present invention has an effect that it can be provided at a low price.

[Activator]
In this specification, “activation” is intended to maintain or enhance cell function or cell activity. As a result, a decrease in cell function or cell activity can be suppressed, that is, cell aging can be suppressed. Therefore, “activator” is synonymous with “cell activator” and has utility as “anti-aging agent”.

  For example, “activation, anti-aging” in skin cells means skin wrinkles, sagging, hardening, etc. by reducing the decrease in skin cell function associated with the accumulation of structural changes in the underlying membrane due to aging and photoaging. This refers to maintaining a youthful, healthy skin condition with prevention and improvement. In addition, for example, in dermal papilla cells or hair matrix cells, it is possible to suppress hair loss by maintaining the hair cycle by reducing the functional degradation of dermal papilla cells or hair matrix cells due to aging, stress, hormone balance, etc. pointing.

  “Biosurfactant” is a general term for substances having surface-active ability and emulsifying ability produced by living organisms, and not only exhibits excellent surface activity and high biodegradability, but also has various physiological functions. Therefore, there is a possibility of developing different behaviors and functions from synthetic surfactants. Biosurfactants can be produced in large quantities by culturing microorganisms and may be used as premixed products.

  A “premix product” is a product obtained by adding a dispersing agent or the like in addition to a functional material, or diluting with a solvent so that it can be easily used during cosmetic production.

  Examples of the biosurfactant include mannosyl erythritol lipid (MEL), mannosyl mannitol lipid (MML), trehalose lipid, rhamnolipid, sophorolipid, surfactin, spiculsporic acid, emalzan, and any of them can be used as the activator according to the present invention. . Among these, it is preferable to use a biosurfactant that forms a lamellar structure, and MEL and MML are particularly preferable.

Four types of MELs are known, MEL-A, MEL-B, MEL-C and MEL-D, depending on the presence or absence of acetyl groups at the 4th and 6th positions of mannose. Formula (1) shows the structure of MEL-A. In formula (1), R1 and R2 represent a hydrocarbon group. That is, MEL-A is a compound having an alkanoyl group having 5 to 19 carbon atoms at the 2nd and 3rd positions of mannose and the acetyl group at the 4th and 6th positions of mannose in the formula (1). In MEL-B, mannose 4-position acetyl group (CH ₃ CO) in formula (1) is H, and MEL-C is mannose 6-position acetyl group (CH ₃ CO) in formula (1). H, and MEL-D is H in the acetyl group (CH ₃ CO) at the 4-position and 6-position of mannose in the formula (1).

The structure of MML is shown in Formula (2). In formula (2), R1 and R2 represent a hydrocarbon group. In Formula (2), either one or both of the acetyl groups (CH ₃ CO) at the 4th and 6th positions of mannose may be H.

  The biosurfactant used in the activator according to the present invention may be a MEL triacyl or MML triacyl. The triacyl biosurfactant is a biosurfactant having a novel structure having higher hydrophobicity than MEL and MML. For example, when a large amount is obtained from other than the culture solution of MEL-producing bacteria, it can be produced by reacting MEL with various vegetable oils using enzymes.

  The triacyl form of MEL, that is, triacyl mannosyl erythritol lipid (sometimes referred to as triacyl MEL) has a structure represented by the formula (3).

  In the formula (3), R1, R2 and R3 each independently represent a hydrocarbon group or an oxygen atom-containing hydrocarbon group, and one or both of the hydroxyl groups at the 4-position and 6-position of mannose are acetylated. It may be substituted with a group. The hydrocarbon group may have only a saturated bond or may have an unsaturated bond. When it has an unsaturated bond, it may have a plurality of double bonds. The carbon chain may be linear or branched. In the case of an oxygen atom-containing hydrocarbon group, the number and position of oxygen atoms contained are not limited.

  In formula (3), R1 and R2 preferably have 6 to 20 carbon atoms, and have an ester bond with the hydroxyl groups at the 2nd and 3rd positions of mannose as the aliphatic acyl group (RCO-), An acetyl group may be ester-bonded to the hydroxyl group. R3 preferably has 6 to 20 carbon atoms and has an ester bond with a primary hydroxyl group of erythritol as an aliphatic acyl group (RCO-).

  Triacyl MEL has a structure in which a fatty acid ester is added and has high hydrophobicity, and therefore is superior as an emollient in that it can be easily combined with various oil components as compared with conventional MEL.

  These biosurfactants may be used alone, or two or more biosurfactants can be used in combination.

  The method for producing the biosurfactant is not particularly limited, and a fermentation method using a known biosurfactant-producing microorganism may be arbitrarily selected. For example, MEL can be produced by culturing Pseudozyma antarctica NBRC 10736 according to a conventional method. In addition to the above, Candida antarctica, Candida sp., Etc. can be used as the MEL-producing microorganism. It is well known to those skilled in the art that MEL can be easily obtained by culturing these microorganisms. The biosurfactant-producing microorganism is not particularly limited and can be appropriately selected depending on the purpose.

  Fermentation media for producing biosurfactants are generally composed of N sources such as yeast extract and peptone, C sources such as glucose and fructose, and inorganic salts such as sodium nitrate, dipotassium hydrogen phosphate and magnesium sulfate heptahydrate. A medium with a typical composition can be used, including oils and fats such as olive oil, soybean oil, sunflower oil, corn oil, canola oil and coconut oil, and water-insoluble substrates such as hydrocarbons such as liquid paraffin and tetradecane. These can be used alone or in combination of two or more.

  Fermentation conditions such as pH and temperature, culture time, and the like can be arbitrarily set, and the culture solution after fermentation can be used as it is as the biosurfactant of the present invention. In addition, it is possible to appropriately add any operation such as filtration, centrifugation, extraction, purification, sterilization and the like to the culture solution after fermentation, and the obtained extract can be diluted, concentrated and dried. .

  As oils and fats used as raw materials, vegetable oils and fats are preferable. Vegetable fats and oils are not particularly limited, and can be appropriately selected according to the purpose. For example, soybean oil, rapeseed oil, corn oil, peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, palm oil, etc. Among them, soybean oil is a biosurfactant (especially MEL) production efficiency (production quantity, production) It is particularly preferable in that the speed and yield) can be improved. These may be used alone or in combination of two or more.

  There is no restriction | limiting in particular as an inorganic nitrogen source, Although it can select suitably according to the objective, For example, ammonium nitrate, urea, sodium nitrate, ammonium chloride, ammonium sulfate, etc. are mentioned.

  There are no particular limitations on the method for recovering and purifying the biosurfactant, and it can be appropriately selected according to the purpose. For example, it can be recovered by centrifuging the culture solution to recover the oil, and extracting and concentrating with an organic solvent such as ethyl acetate.

  Examples of the extraction solvent include water, alcohols (for example, lower alcohols such as methanol, absolute ethanol, and ethanol, or polyhydric alcohols such as propylene glycol and 1,3-butylene glycol), ketones such as acetone, diethyl ether, and dioxane. , Esters such as acetonitrile and ethyl acetate, and organic solvents such as xylene, benzene, and chloroform can be used alone or in any combination of two or more kinds, and each solvent extract is combined. Can also be used.

  There are no particular limitations on the extraction method, but usually it may be in the range of the boiling point of the solvent from room temperature to normal pressure. After extraction, it is filtered or adsorbed, decolored and purified using an ion exchange resin to form a solution. , Paste, gel, and powder. In many cases, it can be used as it is, but if necessary, further purification treatment such as deodorization and decolorization may be added as long as the effect is not affected. As a purification treatment means such as deodorization and decolorization, an activated carbon column or the like may be used, and a normal means generally applied depending on the extracted substance may be arbitrarily selected. If necessary, a high-purity biosurfactant can be obtained by purification using a silica gel column.

  A method for obtaining a biosurfactant triacyl form will be described by taking a method for producing a MEL triacyl form as an example, but the biosurfactant triacyl form used in the present invention is not limited to a triacyl MEL.

  For example, in order to obtain a triacyl MEL, a triacyl MEL fraction can be purified from a culture solution produced by fermenting a microorganism as described above. In order to obtain a large amount, MEL is dissolved in an organic solvent, a fatty acid derivative such as vegetable oil is added, and esterification or transesterification is performed in the presence of a hydrolase.

  The fatty acid introduced into the erythritol part of MEL may be a long-chain hydrocarbon monovalent carboxylic acid. Further, it may be a saturated fatty acid or an unsaturated fatty acid. In the case of an unsaturated fatty acid, it may have a plurality of double bonds. The carbon chain may be linear or branched. Furthermore, a fatty acid derivative that is a derivative of a fatty acid may be used in the present invention, or a mixture of a fatty acid and a fatty acid derivative may be used in the present invention. The fatty acid or fatty acid derivative introduced into the erythritol part of MEL is preferably derived from oils, higher fatty acids, and synthetic esters.

  The “oils” may be vegetable oils, animal oils, mineral oils, and hardened oils thereof. Specifically, avocado oil, olive oil, sesame oil, camellia oil, evening primrose oil, turtle oil, macadamian nut oil, corn oil, mink oil, rapeseed oil, egg yolk oil, persic oil, wheat germ oil, sasanqua oil, castor oil , Linseed oil, safflower oil, cottonseed oil, eno oil, soybean oil, peanut oil, tea seed oil, kaya oil, rice bran oil, kiri oil, jojoba oil, cacao butter, palm oil, horse oil, palm oil, palm kernel oil Animal and vegetable oils such as beef tallow, sheep fat, pork tallow, lanolin, whale wax, beeswax, carnauba wax, molasses, candelilla wax, squalane and their hardened oils. Examples thereof include mineral oil such as liquid paraffin and petrolatum, and synthetic triglycerin such as glycerin tripalmitate. Preferably avocado oil, olive oil, sesame oil, camellia oil, evening primrose oil, turtle oil, macadamia nut oil, corn oil, mink oil, rapeseed oil, egg yolk oil, persic oil, wheat germ oil, southern oil, castor oil, flaxseed oil , Safflower oil, cottonseed oil, eno oil, soybean oil, peanut oil, tea seed oil, kaya oil, rice bran oil, and more preferably olive oil and soybean oil.

  Examples of the “higher fatty acid” include caproic acid, caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, oleic acid, linoleic acid, linolenic acid, stearic acid, behenic acid, 12-hydroxystearic acid, isostearic acid, Examples include undecic acid, tolic acid, eicosapentaenoic acid, docosahexaenoic acid, and the like. Preferred are lauric acid, myristic acid, palmitic acid, oleic acid, linoleic acid, linolenic acid, stearic acid and undecylenic acid, and more preferred are oleic acid, linoleic acid and undecylenic acid.

  Examples of the “synthetic ester” include methyl caproate, methyl caprylate, methyl caprate, methyl laurate, methyl myristate, methyl palmitate, methyl oleate, methyl linoleate, methyl linolenate, methyl stearate, undecine. Methyl acid, ethyl caproate, ethyl caprylate, ethyl caprate, ethyl laurate, ethyl myristate, ethyl palmitate, ethyl oleate, ethyl linoleate, ethyl linolenate, ethyl stearate, ethyl undecinate, vinyl caproate , Vinyl caprylate, vinyl caprate, vinyl laurate, vinyl myristate, vinyl palmitate, vinyl oleate, vinyl linoleate, vinyl linolenate, vinyl stearate, vinyl undecinate, cetyl octanoate , Octyldodecyl myristate, isopropyl myristate, myristyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, Oren'i acid decyl dimethyl octanoate, cetyl lactate, myristyl lactate, and the like. Preferred are methyl laurate, methyl myristate, methyl palmitate, methyl oleate, methyl linoleate, methyl linolenate, methyl stearate, methyl undecylate, more preferably methyl oleate, methyl linoleate, and methyl undecylate. .

  Triacyl MEL can be produced by dissolving MEL in an organic solvent and reacting as described above. The organic solvent is not limited as long as it can solubilize MEL. What is necessary is just to be able to solubilize a part even if not all can be solubilized. The organic solvent may be a mixture of a plurality of organic solvents. Specifically, for example, methanol, ethanol, propanol, butanol, acetone, propanone, butanone, pentan-2-one, 1,2-ethanediol, 2,3-butanediol, dioxane, acetonitrile, 2-methyl-butane -2-ol, tertiary butanol, 2-methylpropanol, 4-hydroxy-2-methylpentanone, tetrahydrofuran, hexane, DMF, DMSO, pyridine, methyl ethyl ketone and the like. Acetone, tetrahydrofuran, tertiary butanol, acetonitrile and dioxane are preferable, and acetone is more preferable.

  Examples of hydrolases include lipases, proteases, and esterases. It is preferable to use at least one selected from these, and a plurality of hydrolases may be used. Lipase and esterase are preferable, and lipase is more preferable.

  Specifically, for example, MEL purified from a culture solution of MEL-producing microorganisms is dissolved in an organic solvent (for example, acetone), and commercially available lipase (for example, Novozyme 435 (manufactured by Novozymes) etc.) and vegetable oils and fats are dissolved therein. Added.

  In the case of this production method, the reaction temperature is 10 to 100 ° C., preferably 20 to 50 ° C., more preferably 25 to 40 ° C., and stirring may be performed for 1 to 7 days. Further, molecular sieves may be added to the reaction solution. By this manufacturing method, MEL added as a material becomes a triacyl body almost quantitatively.

  The purification of triacyl MEL can be performed according to the above-described purification of MEL.

  The biosurfactant obtained as described above can be used as an activator as it is, but it is preferable to use it in cosmetics, quasi drugs, pharmaceuticals, and foods. The concentration of the biosurfactant is appropriately selected depending on the degree of absorption, the degree of action, the product form, the frequency of use, etc., and is not particularly limited. What is necessary is just to select a mixing | blending density | concentration in the range which does not impair a cell activation effect | action, 0.001-50 mass% is preferable normally with respect to the activator total weight, 0.1-20 mass% is more preferable, 1-15 % By mass is more preferable, and 3 to 10% by mass is particularly preferable.

  Here, the use form of the biosurfactant to be blended in the activator is arbitrary. For example, the biosurfactant may be used as it is as an extract from the culture solution, or after being purified, purified or suspended in water, or dissolved in an organic solvent such as ethanol.

The method for producing the activator according to the present invention using a biosurfactant is not particularly limited,
The method for producing the activator according to the present invention using a biosurfactant is not particularly limited, but since biosurfactant is highly hydrophobic, a nonionic surfactant, a lower alcohol, a polyhydric alcohol, or It is preferable to use it by dissolving in natural oils such as olive oil, squalane and fatty acids.

  Nonionic surfactants include, for example, sorbitan fatty acid esters (for example, sorbitan monooleate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan sesquioleate, sorbitan trioleate). Glycerol, penta-2-ethylhexyl diglycerol sorbitan, tetra-2-ethylhexyl diglycerol sorbitan, etc.); glycerin polyglycerin fatty acids (eg mono cottonseed oil fatty acid glycerin, monoerucic acid glycerin, sesquioleate glycerin, glyceryl monostearate) , Α, α′-oleic acid pyroglutamate glycerin, monostearate glycerin malate, etc.); propylene glycol fatty acid esters (for example, monos Propylene glycol tea acrylate, etc.); hardened castor oil derivative; glycerin alkyl ether and the like.

  Examples of the POE-based hydrophilic nonionic surfactant include POE-sorbitan fatty acid esters (for example, POE-sorbitan monooleate, POE-sorbitan monostearate, POE-sorbitan monooleate, POE-sorbitan tetraoleate). POE sorbite fatty acid esters (eg, POE-sorbite monolaurate, POE-sorbite monooleate, POE-sorbite pentaoleate, POE-sorbite monostearate, etc.); POE-glycerin fatty acid esters (eg, POE-glycerol monostearate, POE-glycerin monoisostearate, POE-monooleate such as POE-glycerol triisostearate, etc.); POE-fatty acid esters (for example, POE-distearate) POE-alkyl ethers (for example, POE-lauryl ether, POE-oleyl ether, POE-stearyl ether, POE-behenyl ether, POE-2-octyldodecyl ether), POE-monodiolate, ethylene glycol distearate, etc. POE-cholestanol ether, etc.); Pluronic type (for example, Pluronic, etc.); POE • POP-alkyl ethers (for example, POE • POP-cetyl ether, POE • POP-2-decyltetradecyl ether, POE • POP−) Monobutyl ether, POE / POP-hydrogenated lanolin, POE / POP-glycerin ether, etc.); tetra-POE / tetra-POP-ethylenediamine condensates (for example, Tetronic, etc.); POE-castor oil-cured castor Oil derivatives (eg POE-castor oil, POE-hardened castor oil, POE-hardened castor oil monoisostearate, POE-hardened castor oil triisostearate, POE-hardened castor oil monopyroglutamic acid monoisostearic acid diester, POE -Hardened castor oil maleic acid, etc.); POE-beeswax lanolin derivatives (eg POE-sorbite beeswax etc.); alkanolamides (eg coconut oil fatty acid diethanolamide, lauric acid monoethanolamide, fatty acid isopropanolamide etc.); POE- Examples thereof include propylene glycol fatty acid ester; POE-alkylamine; POE-fatty acid amide; sucrose fatty acid ester; alkylethoxydimethylamine oxide; trioleyl phosphate.

  Examples of the lower alcohol include ethanol, propanol, isopropanol, isobutyl alcohol, t-butyl alcohol and the like.

Examples of the polyhydric alcohol include divalent alcohols (for example, ethylene glycol, propylene glycol, trimethylene glycol, 1,2-butylene glycol, 1,3-butylene glycol, tetramethylene glycol, 2,3-butylene glycol, Pentamethylene glycol, 2-butene-1,4-diol, hexylene glycol, octylene glycol, etc.); trivalent alcohol (eg, glycerin, trimethylolpropane, etc.); tetravalent alcohol (eg, 1, 2, 6) Pentaerythritol such as hexanetriol); pentavalent alcohol (for example, xylitol); hexavalent alcohol (for example, sorbitol, mannitol, etc.); polyhydric alcohol polymer (for example, diethylene glycol, dipropylene glycol, triol) Tylene glycol, polypropylene glycol, tetraethylene glycol, diglycerin, polyethylene glycol, triglycerin, tetraglycerin, polyglycerin, etc.); divalent alcohol alkyl ethers (for example, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol) Monobutyl ether, ethylene glycol monophenyl ether, ethylene glycol monohexyl ether, ethylene glycol mono 2-methylhexyl ether, ethylene glycol isoamyl ether, ethylene glycol benzyl ether, ethylene glycol isopropyl ether, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, ethylene glycol Dibutyl Dihydric alcohol alkyl ethers (for example, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monobutyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, diethylene glycol butyl ether, diethylene glycol methyl ethyl ether, triethylene glycol monomethyl ether, triethylene glycol) Monoethyl ether, propylene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol monobutyl ether, propylene glycol isopropyl ether, dipropylene glycol methyl ether, dipropylene glycol ethyl ether, dipropylene glycol Dibutyl alcohol ether ester (for example, ethylene glycol monomethyl ether acetate, ethylene glycol monoethyl ether acetate, ethylene glycol monobutyl ether acetate, ethylene glycol monophenyl ether acetate, ethylene glycol diazebate, ethylene glycol disuccine) Diethylene glycol monoethyl ether acetate, diethylene glycol monobutyl ether acetate, propylene glycol monomethyl ether acetate, propylene glycol monoethyl ether acetate, propylene glycol monopropyl ether acetate, propylene glycol monophenyl ether acetate, etc.); glycerin monoalkyl ether (example) Sugar alcohol (eg, sorbitol, maltitol, maltotriose, mannitol, sucrose, erythritol, glucose, fructose, amylolytic sugar, maltose, xylitol, starch decomposition) Sugar-reduced alcohol, etc.); glycolide; tetrahydrofurfuryl alcohol; POE-tetrahydrofurfuryl alcohol; POP-butyl ether; POP / POE-butyl ether; tripolyoxypropylene glycerin ether; POP · POE-pentane erythritol ether, polyglycerin and the like.

  Oils include avocado oil, olive oil, sesame oil, camellia oil, evening primrose oil, turtle oil, macadamian nut oil, corn oil, mink oil, rapeseed oil, egg yolk oil, persic oil, wheat germ oil, sasanca oil, castor oil , Linseed oil, safflower oil, cottonseed oil, eno oil, soybean oil, peanut oil, tea seed oil, kaya oil, rice bran oil, kiri oil, jojoba oil, cacao butter, palm oil, horse oil, palm oil, palm kernel oil Animal and vegetable oils such as beef tallow, sheep fat, pork tallow, lanolin, whale wax, beeswax, carnauba wax, molasses, candelilla wax, squalane and their hardened oils. There are mineral oils such as liquid paraffin and petrolatum, and synthetic triglycerins such as glycerin tripalmitate.

  Examples of higher fatty acids include lauric acid, myristic acid, palmitic acid, oleic acid, linoleic acid, linolenic acid, stearic acid, behenic acid, 12-hydroxystearic acid, isostearic acid, undecylic acid, tallic acid, eicosapentaenoic acid, docosahexaene. There are acids. Examples of higher alcohols include lauryl alcohol, cetyl alcohol, stearyl alcohol, behenyl alcohol, myristyl alcohol, oleyl alcohol, cetostearyl alcohol, jojoba alcohol, lanolin alcohol, batyl alcohol, 2-decyltetrathececinol, cholesterol, phytosterol, and isostearyl. There is alcohol. Synthetic esters include, for example, cetyl octanoate, octyldodecyl myristate, isopropyl myristate, myristyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, decyl orenate, dimethyl octanoate, cetyl lactate, myristyl lactate, etc. There is. Examples of silicone include linear polysiloxanes such as dimethylpolysiloxane and methylphenylpolysiloxane, cyclic polysiloxanes such as decamethylcyclopolysiloxane, and three-dimensional network structures such as silicone resins.

  As described above, the activator according to the present invention is preferably carried out in the form of a composition by blending a biosurfactant, which is an active ingredient, with cosmetics, quasi drugs, pharmaceuticals, and foods.

  When implemented in the form of cosmetics, quasi-drugs, and pharmaceuticals, it is preferable to use external preparations. However, since biosurfactants can be taken orally, they are not limited to external preparations, and may be internal preparations and foods and drinks.

  When the activator according to the present invention is used as a pharmaceutical, since the biosurfactant has demonstrated the human hair papilla cell activating effect, it can be used as a pharmaceutical for promoting hair growth and preventing progression of hair loss.

  The dosage form is not limited and can be various such as ampules, capsules, powders, granules, pills, tablets, solids, liquids, gels, bubbles, emulsions, creams, ointments, sheets, mousses, bath preparations, etc. .

  Specifically, cosmetics, quasi-drugs, and pharmaceuticals include basic cosmetics such as internal and external pharmaceutical preparations, lotions, emulsions, creams, ointments, lotions, oils, packs, facial cleansers and skin cleansers. , Shampoo, rinse, hair treatment, hair cream, pomade, hair spray, hair conditioner, perm, hair nick, hair dye, hair growth, hair restorer, foundation, white powder, funny, lipstick, blusher, eye shadow Makeup cosmetics such as eyeliner, mascara, eyebrows, eyelashes, cosmetics for finishing such as beauty nails, perfumes, bath preparations, toothpastes, mouth fresheners, gargles, liquid odors and deodorants , Sanitary products, sanitary cotton, wet tissue and the like.

  Specifically, as food and drink, for example, soft drinks, carbonated drinks, nutritional drinks, fruit drinks, lactic acid drinks and other beverages, ice cream, ice sherbet, shaved ice and other frozen desserts, soba, udon, harusame, gyoza skin, Noodles such as sweet husk, Chinese noodles, instant noodles, candy, candy, gum, chocolate, tablet confectionery, snack confectionery, biscuits, jelly, jam, cream, baked confectionery, bakery confectionery, crab, salmon, clams, tuna , Sardines, shrimp, skipjack, mackerel, whales, oysters, saury, squid, scallops, scallops, abalone, sea urchin, salmon roe, sea cucumbers, fishery products such as kamaboko, ham, sausage, processed milk, fermented milk Oil such as dairy products such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, dressing Fat and oil processed foods, sauces, sauces and other seasonings, curry, stew, oyakodon, rice cakes, miscellaneous cooking, Chinese rice, bonito, tempura, eel rice, hayashi rice, oden, mabodorf, beef bowl, meat sauce, egg soup, omelet rice Retort pouch foods such as dumplings, shumai, hamburger, meatballs, various forms of health / nutritional supplements, health functional foods, tablets, capsules, drinks, troches and the like.

  The activator according to the present invention is suitably applied to humans, but can also be applied to animals other than humans as long as each effect can be expected.

  In addition to the biosurfactant which is an active ingredient, the activator according to the present invention includes ingredients used in cosmetics, quasi drugs, pharmaceuticals, foods and drinks as long as the effects of the present invention are not impaired as necessary. Additives can be used in combination.

  For example, as fats and oils, avocado oil, almond oil, fennel oil, sesame oil, olive oil, orange oil, orange rafa oil, sesame oil, cocoa butter, chamomile oil, carrot oil, cucumber oil, beef fat, beef tallow fatty acid, cucumber nut oil, Safflower oil, soybean oil, camellia oil, corn oil, rapeseed oil, persic oil, castor oil, cottonseed oil, peanut oil, turtle oil, mink oil, egg yolk oil, cacao butter, palm oil, palm kernel oil, molasses, palm oil Beef tallow, pork tallow, hydrogenated oil, hydrogenated castor oil, and the like.

  Examples of waxes include beeswax, carnauba wax, whale wax, lanolin, liquid lanolin, reduced lanolin, hard lanolin, candelilla wax, montan wax, shellac wax, and the like.

  Examples of mineral oils include liquid paraffin, petrolatum, paraffin, ozokelide, ceresin, microcristan wax, polyethylene powder, squalene, squalane, and pristane.

  For example, fatty acids include lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, 12-hydroxystearic acid, undecylenic acid, tall oil, lanolin fatty acid and other natural fatty acids, isononanoic acid, caproic acid, Examples include synthetic fatty acids such as 2-ethylbutanoic acid, isopentanoic acid, 2-methylpentanoic acid, 2-ethylhexanoic acid, and isopentanoic acid.

  For example, as alcohols, natural alcohols such as ethanol, isopropylanol, lauryl alcohol, cetanol, stearyl alcohol, oleyl alcohol, lanolin alcohol, cholesterol, phytosterol, synthetic alcohols such as 2-hexyldecanol, isostearyl alcohol, 2-octyldodecanol, etc. , Ethylene oxide, ethylene glycol, diethylene glycol, triethylene glycol, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, polyethylene glycol, propylene oxide, propylene glycol, polypropylene glycol, 1,3-butylene Glycol, glycerin Batyl alcohol, pentaerythritol, sorbitol, mannitol, glucose, polyhydric alcohols such as sucrose and the like.

  For example, esters include isopropyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, oleyl oleate, decyl oleate, octyldodecyl myristate, hexyl decyl dimethyloctanoate, cetyl lactate, lactic acid Examples include myristyl, diethyl phthalate, dibutyl phthalate, lanolin acetate, ethylene glycol monostearate, propylene glycol monostearate, propylene glycol dioleate, and the like.

  For example, examples of the metal soap include aluminum stearate, magnesium stearate, zinc stearate, calcium stearate, zinc palmitate, magnesium myristate, zinc laurate, and zinc undecylate.

  For example, gum and water-soluble polymer compounds include gum arabic, benzoin gum, danmar gum, guaiac oil, Irish moss, Karaya gum, tragacanth gum, carob gum, quinseed, agar, casein, dextrin, gelatin, pectin, starch, carrageenan, Carboxyalkylchitin, chitosan, hydroxyalkylchitin, low molecular chitosan, chitosan salt, sulfated chitin, phosphorylated chitin, alginic acid and its salt, hyaluronic acid and its salt, chondroitin sulfate, heparin, ethylcellulose, methylcellulose, carboxymethylcellulose, carboxyethylcellulose , Sodium carboxyethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, nitrocellulose, crystalline cellulose Scan, polyvinyl alcohol, polyvinyl methyl ether, polyvinyl pyrrolidone, polyvinyl methacrylate, polyacrylic acid salts, polyalkylene oxide or crosslinked polymer thereof such as polyethylene oxide or polypropylene oxide, carboxyvinyl polymers, such as polyethyleneimine.

  For example, as the surfactant, anionic surfactant (carboxylate, sulfonate, sulfate ester salt, phosphate ester salt), cationic surfactant (amine salt, quaternary ammonium salt), amphoteric surfactant ( Carboxylic acid type amphoteric surfactant, sulfate ester type amphoteric surfactant, sulfonic acid type amphoteric surfactant, phosphate ester type amphoteric surfactant), nonionic surfactant (ether type nonionic surfactant, ether ester) Type nonionic surfactant, ester type nonionic surfactant, block polymer type nonionic surfactant, nitrogen-containing type nonionic surfactant), other surfactants (natural surfactants, protein hydrolysates) Derivatives, polymer surfactants, surfactants containing titanium and silicon, fluorocarbon surfactants, and the like.

  For example, vitamins such as retinol, retinal (vitamin A1), dehydroretinal (vitamin A2), carotene, lycopene (provitamin A), vitamin B group, thiamine hydrochloride, thiamine sulfate (vitamin B1) ), Riboflavin (vitamin B2), pyridoxine (vitamin B6), cyanocobalamin (vitamin B12), folic acid, nicotinic acids, pantothenic acids, biotins, choline, inositols, vitamin C, ascorbic acid and its derivatives, vitamin D In the group, ergocalciferol (vitamin D2), cholecalciferol (vitamin D3), dihydrotaxosterol, in vitamin E group, tocopherol and its derivatives, ubiquinones, in vitamin K group, phytonadione (vitamin K1), me Naquinone (vitamin K2), menadione (vitamin K3), menadiol (vitamin K4) and the like.

  For example, amino acids include valine, leucine, isoleucine, threonine, methionine, phenylalanine, tryptophan, lysine, glycine, alanine, asparagine, glutamine, serine, cysteine, cystine, tyrosine, proline, hydroxyproline, aspartic acid, glutamic acid, hydroxylysine , Arginine, ornithine, histidine, and the like, and sulfates, phosphates, nitrates, citrates, and amino acid derivatives such as pyrrolidone carboxylic acid.

  For example, whitening agents include ascorbic acid or a derivative thereof, sulfur, placental hydrolyzate, ellagic acid or a derivative thereof, kojic acid or a derivative thereof, glucosamine or a derivative thereof, arbutin or a derivative thereof, hydroxycinnamic acid or a derivative thereof, glutathione , Arnica extract, Ogon extract, Sakuhakuhi extract, Psycho extract, Bowfu extract, Manntake mycelium culture or extract thereof, Linden extract, Peach leaf extract, Ages extract, Kujin extract, Jiuyu extract, Toki extract, Yakuinin extract, Oyster leaf extract, Examples thereof include diatomite extract, button pi extract, hamamelis extract, marronnier extract, hypericum extract, and oil-soluble licorice extract.

  For example, moisturizers include hyaluronic acid, polyglutamic acid, serine, glycine, threonine, alanine, collagen, hydrolyzed collagen, hydronectin, fibronectin, keratin, elastin, royal jelly, chondroitin sulfate heparin, glycerophospholipid, glyceroglycolipid, sphingo Phospholipid, glycosphingolipid, linoleic acid or esters thereof, eicosapentaenoic acid or esters thereof, pectin, bifidobacteria fermentation product, lactic acid fermentation product, yeast extract, litchi mycelium culture or extract thereof, wheat germ oil , Avocado oil, rice germ oil, jojoba oil, soybean phospholipid, γ-oryzanol, bellows oyster extract, yokuinin extract, geranium extract, tisoiso extract, gypsophila extract, prickly aloe extract, burdock extract, man Nrouekisu, arnica extract, such as wheat bran, and the like.

  For example, as a hair growth agent, pentadecanoic acid glyceride, coleus extract, gentian extract, pine coconut extract, royal jelly extract, coumza extract, t-flavanone, 6-benzylaminopurine, assembly extract, carpronium chloride, minoxidil, finasteride, adenosine, nicotinic acid Examples include amide, mulberry root extract, diau extract, and 5-aminolevulinic acid.

  For example, as an extract or extract of an animal or plant, herbal medicine, Asenyaku (Asen Yaku), Ashitaba, Acerola, Altea, Arnica, Avocado, Achacha (Amacha), Aloe, Aloe Vera, Nettle, Ginkgo (Ginkgo leaf, Ginkgo), Fennel (cage), turmeric (red gold), usba saishin (spicy), Japanese apricot (salmon plum), Japanese white beetle, waurusushi, green rose (fruit), hikiokoshi (life-prolonging grass), Japanese oak (yellow cocoon), Koganebana (Ogon), Yamazakura ( Cherry bark), yellowfin, yellow orchid, ginseng, carrot, helicopter, licorice, Dutch pepper, orange, sagebrush (long-distance), crabs (summer hay), tsurudokudami (what neck shark), enju (槐花）, mugwort (guy leaf), scallops (莪 朮), kudu (kazune), kanoko Cormorant (Valgarine), Chamomile, Kikarasuuri (Gurone), Kawara-momogi (Cervus chinensis), Licorice (licorice), Fukidan Popo (Cavity Winter Flower, Clover Winter Leaves), Raspberry, Kiwi Fruit, Japanese Clover (Kikkyo), Chrysanthemum (Chrysanthemum Flower) ), Catalpa (fruit), Citrus fruit (fruit), Tachibana (tachibana skin), Cucumber, Udo or Shishido (fruitful, solitary), apricot, wolfberry (bone crust, coconut, coconut leaf) , Clara, bittersweet, Kumazasa, grapefruit fruit, Nikkei (Kei-Kai), Keigai (Kai-Gai), Ebisugua (Keiko), Maruba morning glory or morning glory (Ken cow), safflower (Safflower), Gobaishi (Pyper), Confrey , Copaiba, gardenia, gentian, honoki (shock), hinata kozuchi (cow knee), goshuyu (burdock), burdock, kosen Garbage, rice, rice bran, wheat, Mishima Saiko (Saiko), saffron, savonso, hawthorn (Yamazako), salamander, salvia, sanchinin ginseng (37 ginseng), shiitake (shiitake), Jiou (geo yellow), Sikunshi (messenger), Murasaki (purple root), perilla (purple leaves, purple soko), oysters (柿蒂), peonies (glaze), psyllium (car forerunner, car front grass), ginger (ginger), Shobu (Japanese cypress), Japanese horned potato (Sadako), Shimotsuke, Shiraba, Honeysuckle (Gin and silver flowers, Shinobu), Ivy, Achillea millefolium, Elderberry, Azuki (Red Azuki), Elderberry (Bone), Zeniaoi, Senkyu ), Assembly (this medicine), mulberry (mulberry white skin, mulberry leaf), jujube (daegu), soybean, taranoki, chiketsu carrot (bamboo ginseng), Eggplant (Welcome mother), Warmoko (earth), Dokudami (10 medicines), Fuyumushinatsusatake (Cycium caterpillar), Pepper, Japanese physalis (Torone), Tachikakuso, Ryokucha (green tea), Kocha (tea), Choji (chome) ), Citrus unshiu (Chen bark), camellia, camellia, capsicum (Sanban), Touki (Tochigi), red bellflower, Daidai (Orange bark), Warmoko (dianthus), corn (Southern fur), Tochu (Tochu, Tochu) Leaf), tomato, Nanten (Southern fruit), garlic (large sun), barley (malt), hakusen (white birch), janohi (barley winter), parsley, grasshopper, mint (light load), hamamelis, rose, loquat Leaves (bamboo leaves), Matsuhodo (bamboo leopard), grapes or their leaves, loofah, bodaiju, buttons (peony skin), hops, maikai (my buds), pine Leaves, Marronnier, Mannenrou, Mukuroji, Melissa, Merirot, Bokeh (Kiso), Palms, Peach (Momojin, Peach), Hagi (Giraffe), Binroju (Mariko), Mejijiki (Masame), Cornflower, Yukinoshita ), Bayberry (Yellow Plum), Yashabushi (Yagari), pearl barley (Yokuinin), mugwort, sagebrush, lavender, apple fruit, garlic mushroom (reishi), lemon fruit, forsythia (ream), forsythia, ginkgo biloba Hasidorokoro (roth root), chicken tosaka, bovine / human placenta extract, pig / cow stomach, duodenum, or intestinal extract or its degradation product, water-soluble collagen, water-soluble collagen derivative, collagen hydrolyzate, elastin , Elastin hydrolyzate, water-soluble elastin derivative, silk protein, silk protein Hydrolyzate, and the like bovine hemocyte protein hydrolyzate.

  Examples of microbial culture metabolites include yeast extract, zinc-containing yeast extract, germanium-containing yeast extract, selenium-containing yeast extract, magnesium-containing yeast extract, rice fermentation extract, Euglena extract, and lactic acid fermented milk powder. .

  For example, examples of the α-hydroxy acid include glycolic acid, citric acid, malic acid, tartaric acid, and lactic acid.

  For example, inorganic pigments include anhydrous silicic acid, magnesium silicate, talc, kaolin, bentonite, mica, titanium mica, bismuth oxychloride, zirconium oxide, magnesium oxide, zinc oxide, titanium oxide, calcium carbonate, magnesium carbonate, yellow oxide Examples include iron, bengara, black iron oxide, gunjo, chromium oxide, chromium hydroxide, carbon black, and calamine.

  For example, UV absorbers include p-aminobenzoic acid derivatives, salicylic acid derivatives, anthranilic acid derivatives, coumarin derivatives, amino acid compounds, benzotriazole derivatives, tetrazole derivatives, imidazoline derivatives, pyrimidine derivatives, dioxane derivatives, camphor derivatives, furans. Derivatives, pyrone derivatives, nucleic acid derivatives, allantoin derivatives, nicotinic acid derivatives, vitamin B6 derivatives, oxybenzone, benzophenone, guaiazulene, shikonin, baicalin, baicalein, berberine and the like.

  For example, astringents include lactic acid, tartaric acid, succinic acid, citric acid, allantoin, zinc chloride, zinc sulfate, zinc oxide, calamine, zinc p-phenolsulfonate, potassium aluminum sulfate, resorcin, ferric chloride, tannic acid Etc.

  For example, as an antioxidant, ascorbic acid and its salt, stearic acid ester, tocopherol and its ester derivative, nordihydrogua cetelenic acid, butylhydroxytoluene (BHT), butylhydroxyanisole (BHA), parahydroxyanisole, gallic acid Examples include propyl acid, sesamol, sesamorin, gossypol and the like.

  For example, anti-inflammatory agents include ictamol, indomethacin, kaolin, salicylic acid, sodium salicylate, methyl salicylate, acetylsalicylic acid, diphenhydramine hydrochloride, d or dl-camphor, hydrocortisone, guaiazulene, camazulene, chlorpheniramine maleate, glycyrrhizic acid and the like Examples thereof include salts, glycyrrhetinic acid and salts thereof.

  Examples of the bactericidal / disinfectant include acrinol, sulfur, benzalkonium chloride, benzethonium chloride, methyl rosaniline chloride, cresol, calcium gluconate, chlorhexidine gluconate, sulfamine, mercurochrome, lactoferrin or a hydrolyzate thereof.

  For example, selenium disulfide, alkylisoquinolinium bromide, zinc pyrithione, biphenamine, thianthol, castari tincture, ginger tincture, pepper tincture, quinine hydrochloride, strong ammonia water, potassium bromate, sodium bromate And thioglycolic acid.

  For example, as perfumes, natural animal perfumes such as musk, civet, castorium, ambergris, anise essential oil, angelica essential oil, Iran essential oil, Iris essential oil, fennel essential oil, orange essential oil, cananga essential oil, caraway essential oil, cardamom essential oil, guayakwood essential oil , Cumin essential oil, black letter essential oil, cinnamon essential oil, cinnamon essential oil, geranium essential oil, copaiba balsam essential oil, coriandel essential oil, perilla essential oil, cedarwood essential oil, citronella essential oil, jasmine essential oil, gingergrass essential oil, cedar essential oil, spearmint essential oil, western peppermint essential oil , Otsuka perfume essential oil, tuberose essential oil, clove essential oil, orange flower essential oil, winter green essential oil, trout balsam essential oil, buttery essential oil, rose essential oil, palmarosa essential oil, persimmon essential oil, hiba essential oil, sandalwood essential oil, petitgren essential oil, bay essential oil, vetiva essential oil, bell Vegetable fragrances such as Mott essential oil, Peruvian balsam essential oil, Boad Rose essential oil, melamine essential oil, mandarin essential oil, eucalyptus essential oil, lime essential oil, lavender essential oil, linaloe essential oil, lemongrass essential oil, lemon essential oil, rosemary essential oil, Japanese seed mint essential oil, Other synthetic fragrances can be mentioned.

  For example, as a dye / colorant, a red cabbage dye, a red rice dye, an akane dye, an anato dye, an squid dye, a turmeric dye, an enju dye, a krill dye, an amber dye, a caramel, a gold, a silver, a gardenia dye, a corn dye, Examples include onion pigment, tamarind pigment, spirulina pigment, buckwheat whole plant pigment, cherry pigment, laver pigment, hibiscus pigment, grape juice pigment, marigold pigment, purple potato pigment, purple yam pigment, lac pigment and rutin.

  Examples of sweeteners include sugar, sweet tea, fructose, arabinose, galactose, xylose, mannose, maltose, honey, glucose, miraculin, monelin and the like.

  For example, examples of the nutrient fortifier include shell calcined calcium, cyanocolabamine, yeast, wheat germ, soybean germ, egg yolk powder, hemicellulose, heme iron and the like.

  Others, hormones, sequestering agents, pH adjusters, chelating agents, antiseptic / antibacterial agents, refreshing agents, stabilizers, emulsifiers, animal / plant proteins and their degradation products, animal / plant polysaccharides and their Degradation product, animal / plant glycoprotein and its degradation product, blood flow promoter, anti-inflammatory agent / antiallergic agent, cell activator, keratolytic agent, wound treatment agent, foam enhancer, thickener, oral preparation, Deodorizing / deodorizing agents, bittering agents, seasonings, enzymes and the like.

[Anti-aging method]
By using a biosurfactant which is an active ingredient of the activator according to the present invention, an anti-aging method can be provided. That is, the present invention includes an anti-aging method using a biosurfactant.

  The anti-aging method according to the present invention is characterized by including (i) a step of bringing a biosurfactant into contact with an animal. The biosurfactant is at least one selected from the group consisting of manacyl erythritol lipid (MEL), mannosyl mannitol lipid (MML), manacyl erythritol lipid (MEL) triacyl, and mannosyl mannitol lipid (MML) triacyl. It is preferable.

  The animal is not particularly limited as long as the anti-aging effect of the biosurfactant can be expected, but mammals are preferable, and humans are particularly preferable.

  “Contacting an animal” is intended to bring the biosurfactant into contact with an area to which an external preparation is applied, such as the skin and mucous membrane of an animal.

  The anti-aging method according to the present invention is further characterized in that it further comprises (ii) a step of activating cells with a biosurfactant. By activating cells with a biosurfactant that has a cell activation effect, for example, preventing and improving skin wrinkles, sagging, hardening, etc., and maintaining an elastic and youthful healthy skin state It is possible to exert an effect.

  It should be noted that the specific embodiments and the following examples made in the section of the best mode for carrying out the invention are intended to clarify the technical contents of the present invention, and to such specific examples. It is not to be construed as limiting in any way whatsoever, and those skilled in the art can implement the invention within the spirit of the invention and the scope of the appended claims.

  EXAMPLES The present invention will be described more specifically with reference to the following examples. However, these are merely examples and do not limit the scope of the present invention.

[Example 1: Cell activation effect of MEL using normal human skin fibroblasts]
Normal human dermal fibroblasts were cultured by a conventional method using a normal human dermal fibroblast total kit (CA106K05, manufacturer: Cell Applications Inc. USA, import sales company: Toyobo Co., Ltd.).

Normal human skin fibroblasts were seeded in a 48-well microplate so that the number of normal human skin fibroblasts was 2.0 × 10 ⁴ per well. The seeding medium used was Dulbecco's modified Eagle medium (DMEM) supplemented with 10% fetal bovine serum. After culturing at 37 ° C. in a carbon dioxide concentration of 5 vol% for 24 hours, the culture medium was replaced with a test medium supplemented with MEL-A having a final concentration of 1 ng / ml to 0.01 mg / ml, and further cultured for 48 hours. MEL-A was dissolved in ethanol, diluted serially with ethanol, and added to each medium so that the final concentration of ethanol was 0.5%. As a solvent control, an ethanol group (final concentration 0.5%) was provided. In addition, an SDS-added group (final concentration 0.1%) was provided in order to confirm that cell growth was inhibited by cytotoxic substances. Next, the medium containing 3- (4,5-dimethyl-2-thiazolyl) -2,5-diphenyltetrazolium bromide (MTT) was replaced with a medium containing 100 μg / mL and cultured for 3 hours. Extraction was performed with 2-propanol, and absorbance at 550 nm was measured with a microplate reader. At the same time, the absorbance at 650 nm was measured as turbidity, and the cell activation effect was evaluated by the difference between the two measured values.

  The evaluation results are shown in FIG. 1 as relative values with the cell activation effect in the ethanol group (solvent control group) as 100.

  As is clear from FIG. 1, the MEL-A addition group showed a higher cell activation effect than normal ethanol on normal human skin fibroblasts at any concentration. In particular, when MEL-A having a final concentration of 1 ng / ml was added, a significant cell activation effect of 65% or more was observed compared to the ethanol group. From this result, it is clear that MEL has an excellent cell activating effect, and by applying MEL to the skin, it exhibits an extremely excellent anti-aging effect, and skin wrinkles caused by aging, UV exposure, etc. It was suggested that sagging can be effectively improved.

[Example 2: Cell activation of MEL using human hair papilla cells]
(1) Human head hair nipple cell culture method Human head hair nipple cells (THPC-001) total kit (HDPC total kit: THPCK-001, manufacturer: Cell Applications Inc. USA, import sales company: Toyobo Co., Ltd.) Was used to culture human hair papilla cells by a conventional method. In addition, the human hair hair papilla cell is a cell that is widely used for the evaluation of the drug efficacy of the hair restorer (see, for example, JP-A-2006-83084, JP-A-2003-81793, and JP-A-2000-159640).

  Specifically, a PCGM medium for suspending thawed cells is dispensed into 10 mL and 15 mL centrifuge tubes and cooled on ice. A vial containing frozen human hair dermal papilla cells (THPC-001) is thawed rapidly in a 37 ° C. constant temperature bath. About 1 mL of PCGM medium is gradually dropped into this vial to dilute DMSO, and the entire amount is transferred to a centrifuge tube containing PCGM medium and suspended. The floating cells are centrifuged at 4 ° C. and 1000 rpm for 5 minutes in a cooled low speed centrifuge. Carefully aspirate the precipitated cells and resuspend in 1 mL PCGM medium. This whole amount is implanted in a T-75 flask coated with a collagen solution, and placed in an incubator kept at 37 ° C. under a carbon dioxide concentration of 5 vol% under humidification, and subjected to stationary culture. After 1 day, the medium is changed. Thereafter, the culture medium is changed every other day and subcultured.

  As PCGM medium, 250 mL of PCGM basal medium containing 1% FBS, 2.5 mL of 100-fold diluted bovine pituitary extract (BPE), 2.5 mL of 100-fold diluted fetal bovine serum (FCS), insulin -Transferrin-triiodothyronine solution (ITT) 200-fold diluted solution was added with 1.25 mL, and siloprotein solution (Cyp) 200-fold diluted solution added with 1.25 mL.

(2) Evaluation of human hair dermal papilla cell activation effect Human hair dermal papilla cells were seeded in a 48-well microplate so as to be 2.0 × 10 ⁴ cells per well. The seeding medium used was Dulbecco's modified Eagle medium (DMEM) supplemented with 10% fetal bovine serum. After culturing for 24 hours, the medium was replaced with a test medium supplemented with MEL-A having a final concentration of 1 ng / ml to 0.01 mg / ml, and further cultured for 48 hours. MEL-A was dissolved in ethanol, diluted serially with ethanol, and added to each medium so that the final concentration of ethanol was 0.5%. As a solvent control, an ethanol group (final concentration 0.5%) was provided. Subsequently, the medium containing 100 μg / mL of 3- (4,5-dimethyl-2-thiazolyl) -2,5-diphenyltetrazolium bromide (MTT) was replaced and cultured for 3 hours. Formazan produced by the opening of the tetrazolium ring was removed. Extraction was performed with 2-propanol, and absorbance at 550 nm was measured with a microplate reader. At the same time, the absorbance at 650 nm was measured as turbidity, and the cell activation effect was evaluated by the difference between the two measured values.

  The evaluation results are shown in FIG. 2 as relative values with the cell activation effect in the ethanol group (solvent control group) as 100.

  As is clear from FIG. 2, the MEL-A addition group showed a higher cell activation effect than the ethanol group on human hair hair papilla cells in the range of 1 ng / ml to 1 μg / ml. In particular, when MEL-A having a final concentration of 1 ng / ml was added, a significant cell activation effect of 50% or more was observed compared to the ethanol group. From these results, it was suggested that by applying MEL to the scalp, the hair papillary cell activating effect can be exhibited and the hair growth effect can be described.

[Example 3: Cell activation effect of triacyl MEL using normal human skin fibroblasts]
Pseudozyma antarctica NBRC 10736 as triacyl MEL in a medium supplemented with soybean oil (3% soybean oil, 0.02% MgSO ₄ .H ₂ O, 0.02% KH ₂ PO ₄ , 0.1% yeast extract) A product obtained by adding oleic acid to the hydroxyl group of the erythritol part of MEL-A obtained by culture (OL-MEL (SB)) was used.

  Normal human dermal fibroblasts were cultured by a conventional method using a normal human dermal fibroblast total kit (CA106K05, manufacturer: Cell Applications Inc. USA, import sales company: Toyobo Co., Ltd.).

Normal human skin fibroblasts were seeded in a 48-well microplate so that the number of normal human skin fibroblasts was 2.0 × 10 ⁴ per well. The seeding medium used was Dulbecco's modified Eagle medium (DMEM) supplemented with 10% fetal bovine serum. After culturing at 37 ° C. in a carbon dioxide concentration of 5 vol% for 24 hours, the culture medium was replaced with a test medium supplemented with triacyl MEL (OL-MEL (SB)) having a final concentration of 0.01 ng / ml to 0.01 mg / ml. Cultured for 48 hours. Triacyl MEL was dissolved in ethanol, serially diluted with ethanol, and added to each medium so that the final concentration of ethanol was 0.5%. As a solvent control, an ethanol group (final concentration 0.5%) was provided. In addition, an SDS-added group (final concentration 0.1%) was provided in order to confirm that cell growth was inhibited by cytotoxic substances. Next, the medium containing 3- (4,5-dimethyl-2-thiazolyl) -2,5-diphenyltetrazolium bromide (MTT) was replaced with a medium containing 100 μg / mL and cultured for 3 hours. Extraction was performed with 2-propanol, and absorbance at 550 nm was measured with a microplate reader. At the same time, the absorbance at 650 nm was measured as turbidity, and the cell activation effect was evaluated by the difference between the two measured values.

  The evaluation results are shown in FIG. 3 as relative values with the cell activation effect in the ethanol group (solvent control group) as 100.

  As is clear from FIG. 3, the triacyl MEL addition group showed a higher cell activation effect on normal human skin fibroblasts than the ethanol group at any concentration. In particular, when triacyl MEL having a final concentration of 1 ng / ml was added, a significant cell activation / anti-aging effect of about 50% was observed compared to the ethanol group. From this result, it is clear that triacyl MEL has an excellent cell activating effect like MEL-A. By applying triacyl MEL to the skin, it exhibits an extremely excellent anti-aging effect, aging, UV exposure It was suggested that the wrinkles and sagging of the skin caused by the above can be effectively improved.

  Below, the formulation example of the cell activator based on this invention of various dosage forms is shown in Examples 4-6.

[Example 4: Cosmetic liquid]
A cosmetic liquid having the following composition was produced by a conventional method.
(Composition) (wt%)
Sorbit 4.0
Dipropylene glycol 6.0
Polyethylene glycol 1500 5.0
POE (20) oleyl alcohol ether 0.5
Sucrose fatty acid ester 0.2
Methylcellulose 0.2
MEL 1.0
Purified water Total amount of 100 [Example 5: Emulsion]
An emulsion having the composition shown below was produced by a conventional method.
(Composition) (wt%)
Glyceryl ether 1.5
Sucrose fatty acid ester 1.5
Sorbitan monostearate 1.0
Squalane 7.5
Dipropylene glycol 5.0
MEL 1.0
Purified water Total amount of 100 [Example 6: Cream]
A cream having the following composition was produced by a conventional method.
(Composition) (wt%)
Propylene glycol 6.0
Dibutyl phthalate 19.0
Stearic acid 5.0
Glycerol monostearate 5.0
Sorbitan monostearate 12.0
Polyethylene sorbitan monostearate 38.0
Sodium edetate 0.03
MEL 1.0
Purified water Amount of 100 in total [Example 7: Sensory evaluation]
Sensory evaluation was performed using the above Examples 4-6. A comparative example containing no biosurfactant was also evaluated at the same time. For sensory evaluation, six panelists aged 26 to 48 who are worried about aging symptoms such as wrinkles are used as a group, and each of the Examples and Comparative Examples is used twice a day for three months continuously. A questionnaire survey was conducted on the skin condition.

  As a result of sensory evaluation, the number of evaluators in each item is shown in Table 1. More than 70% of the panel responded that the elasticity of the skin was improved and wrinkles were improved in the example, compared to the comparative example that did not contain biosurfactant. It was shown that.

  According to the present invention, a cell activating action and an anti-aging action excellent in safety derived from a biosurfactant can be expected, and a cosmetic / quasi-drug (cell external preparation, bath preparation, hair growth agent) containing the cell activating and anti-aging ingredients as active ingredients Drugs), foods and drinks, and pharmaceuticals are also expected to contribute greatly to the industry.

It is a graph which shows the result of having examined the cell activation effect of MEL using normal human skin fibroblasts. It is a graph which shows the result of having examined the cell activation effect of MEL using a human head hair papilla cell. It is a graph which shows the result of having examined the cell activation effect | action of the triacyl MEL using a normal human skin fibroblast.

Claims (9)

  An activator comprising a biosurfactant as an active ingredient.   The biosurfactant is at least one selected from the group consisting of mannosyl erythritol lipid (MEL), mannosyl mannitol lipid (MML), mannosyl erythritol lipid (MEL) triacyl, and mannosyl mannitol lipid (MML) triacyl. The activator according to claim 1.   An anti-aging agent comprising the activator according to claim 1 as an active ingredient.   A hair restorer comprising the activator according to claim 1 or 2 as an active ingredient.   An external preparation comprising the activator according to claim 1, the anti-aging agent according to claim 3, or the hair restorer according to claim 4 as an active ingredient.   A cosmetic comprising the activator according to claim 1 or 2, the anti-aging agent according to claim 3, or the hair restorer according to claim 4 as an active ingredient.   A quasi-drug containing the activator according to claim 1 or 2, the anti-aging agent according to claim 3, or the hair-restoring agent according to claim 4 as an active ingredient.   A pharmaceutical comprising the activator according to claim 1, the anti-aging agent according to claim 3, or the hair restorer according to claim 4 as an active ingredient. A food or drink comprising the activator according to claim 1 or 2, the anti-aging agent according to claim 3, or the hair restorer according to claim 4 as an active ingredient.

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