JP7406787B2 - Stem cell function maintenance agent - Google Patents

Description

The present invention relates to a composition obtained from a plant extract and having an excellent effect of inhibiting oxidative damage to stem cells, and an external preparation for skin containing such a composition.

Stem cells are cells that have the ability to produce a variety of cells, and among them, mesenchymal stem cells have the potential to generate cells that belong to the mesenchymal system, such as osteoblasts, adipocytes, muscle cells, and chondrocytes. These cells are said to have the ability to differentiate, and are expected to be applied to regenerative medicine such as the reconstruction of bones, blood vessels, and heart muscle. It has also been confirmed that mesenchymal stem cells exist in the dermis, and these stem cells are known to have a high ability to generate fibroblasts. It has become clear that these mesenchymal stem cells decrease and function poorly due to factors such as aging and oxidative stress, resulting in a decline in cell and tissue regeneration and repair abilities. For this reason, for example, research has been conducted on maintaining the function of mesenchymal stem cells in the dermis (Patent Document 1).

Japanese Patent Application Publication No. 2013-147479

The object of the present invention was made in view of the above background, and the object is to find a component derived from a natural product that maintains the function of mesenchymal stem cells.

The present invention is a stem cell function maintenance agent containing as an active ingredient an extract or a hydrolyzate of one or more plants selected from the group consisting of loofah, peach, soybean, purple loofah, apricot, and silverwort.

According to the present invention, it is possible to provide a mesenchymal stem cell function maintenance agent that is derived from natural products and has excellent biosafety.

Hereinafter, preferred embodiments of the present invention will be described in detail.
The present invention is a stem cell function maintenance agent containing as an active ingredient an extract or a hydrolyzate of one or more plants selected from the group consisting of rice, loofah, peach, soybean, red bean, apricot, and silver leaf moth.

In the present invention, "rice" is obtained from plants of the Poaceae family, the genus Oryza. It is possible to use rice bran or white bran obtained in the process of milling brown rice, germinated brown rice, or colored rice.

In the present invention, "loofah" is a plant of the Cucurbitaceae family, the genus Luffa. Parts that can be used in the present invention include the whole plant, fruits, flowers, seeds, leaves, stems, roots, etc.

Furthermore, in the present invention, "peach" is a plant of the Rosaceae family Prunus genus. Parts that can be used in the present invention include the whole plant, fruits, flowers, seeds, leaves, stems, roots, etc. Moreover, when using fruits, immature fruits can also be used.

In addition, in the present invention, "soybean" refers to a plant of the Fabaceae family, soybean genus (Glycine), and any of white soybeans, black soybeans, red soybeans, green soybeans, etc. can be used. be. Parts that can be used in the present invention include the whole plant, flowers, seeds, stems, leaves, and roots.

Furthermore, in the present invention, "purple kibu" refers to a plant belonging to the genus Callicarpa, such as Callicarpa japonica, Callicarpa japonica var. etc. are known. Parts that can be used in the present invention include the whole plant, flowers, seeds, stems, leaves, roots, etc.

Furthermore, the "apricot" used in the present invention is an apricot (Prunus armeniaca) belonging to the genus Prunus in the family Rosaceae, and may be of any variety (variant, subspecies, or hybrid). Alternatively, plum (Prunus salicina) or plum (Prunus mume), which are plants closely related to apricot, may be used. As the parts that can be used in the present invention, any of the whole plant, fruits, pericarp, leaves, flowers, stems, seeds, roots, etc. may be used.

In addition, the "Cybernata" used in the present invention is a plant of the genus Alchemilla in the family Rosaceae. Parts that can be used in the present invention include whole plants, fruits, pericarp, leaves, flowers, stems, seeds, roots, and the like.

To prepare the extract, first wash the part of each plant to be used with water to remove foreign matter if necessary, leave it as is or dry it, cut it into pieces or crush it if necessary, and bring it into contact with an extraction solvent. It can be prepared by an extraction method (eg, immersion method, countercurrent extraction method, or other suitable means). Alternatively, a supercritical extraction method may be used. Furthermore, it may be prepared by pressing the part to be used (such as fruit) as it is, or by crushing the part to be used and then compressing the crushed product. It can also be prepared by drying the part to be used and then pulverizing it to obtain a dry and pulverized product, or by subjecting the part to be used or, in some cases, the squeezed liquid, to freeze-drying, etc. and extracting the dry powder obtained with a solvent. be able to.

Extraction solvents include water; lower alcohols such as methanol, ethanol, and propanol; polyhydric alcohols such as ethylene glycol, propylene glycol, 1,3-butylene glycol, and glycerin; and ethyl acetate, butyl acetate, and methyl propionate. Esters; ketones such as acetone and methyl ethyl ketone; ethers such as ethyl ether and isopropyl ether; hydrocarbon solvents such as n-hexane, toluene, and chloroform; these may be used alone or in combination of two or more. used.

In the present invention, hydrophilic solvents such as water, lower alcohols, or polyhydric alcohols are suitable. Preferred examples of using this hydrophilic solvent include water, lower alcohols (especially ethanol), or polyhydric alcohols (especially 1,3-butylene glycol) alone, or water and lower alcohols. Examples include using a mixed solvent with water (especially ethanol), or a mixed solvent with water and polyhydric alcohols (especially 1,3-butylene glycol, glycerin). - A mixed solvent of butylene glycol is particularly preferred.

When using a mixed solvent, the mixing ratio is, for example, 1:10 to 20:1 by volume (the same applies hereinafter) for a mixed solvent of water and 1,3-butylene glycol, and 1:10 to 20:1 for a mixed solvent of water and ethanol. If so, it is preferably in the range of 1:10 to 25:1, and in the case of a mixed solvent of water and glycerin, it is preferably in the range of 1:10 to 20:1.

Further, the weight ratio of each plant to the extracting solvent used is preferably in the range of 1:1 to 1:50, more preferably in the range of 1:3 to 1:35.

There are no particular limitations on the pH when preparing the extract, but it is generally preferred to keep it in the range of 3 to 9. In this sense, if necessary, an alkaline regulator such as sodium hydroxide, sodium carbonate, or potassium hydroxide, or an acidic regulator such as citric acid, hydrochloric acid, phosphoric acid, or sulfuric acid may be added to the extraction solvent as desired. The pH may be adjusted to .

Extraction conditions such as extraction temperature and extraction time vary depending on the type and pH of the solvent used, but for example, immersion using water, 1,3-butylene glycol, or a mixture of water and 1,3-butylene glycol as the solvent. In the case of a method, the extraction temperature generally ranges from 0 to 90°C, preferably from 4°C to 80°C. The extraction time ranges from 0.5 to 3 days, preferably from 1 to 6 hours.

In addition, prior to the extraction treatment of the present invention, in parallel with the extraction treatment, or after the extraction treatment, a hydrolysis treatment may be performed as necessary. This may allow for more efficient use of the extract. Examples of the hydrolysis treatment include acid treatment, alkali treatment, and enzyme treatment, among which enzyme treatment is the most preferred. Examples of the enzyme to be used include one or more selected from proteolytic enzymes, starch-degrading enzymes, fibrinolytic enzymes, and lipolytic enzymes.

The protease may be any of animal-derived enzymes, plant-derived enzymes, and microbial-derived enzymes. Examples include actinases, pepsins such as pepsin, trypsins such as trypsin, papains such as papain and chymopapain, peptidases such as glycylglycine peptidase, carboxypeptidase, and aminopeptidase, and bromelain. One or more of these are used. Further, examples of starch degrading enzymes include glucoamylase, α-amylase, and the like. In addition, examples of fibrinolytic enzymes include cellulase, hemicellulase, and pectinase. Moreover, lipase etc. are mentioned as a lipolytic enzyme. As the enzyme to be used, one or more enzymes selected from any enzyme group may be used, or one or two or more enzymes selected from each enzyme group may be used in combination. .

The amount of enzyme added is preferably in the range of 0.01 to 10% by weight in total, more preferably in the range of 0.1 to 2.0% by weight, based on the solid content of the part of each plant used. be.

The extract prepared as described above may be used as it is as a formulation for external skin preparations, generally after adjusting the pH to 3 to 8, or it may be concentrated to a desired concentration by vacuum concentration, etc. May be used. Further, the extract may be dried by a conventional method such as spray drying.

The extract prepared as described above can be applied to humans or animals as a compounding agent for cosmetics or quasi-drugs, or can be applied to humans or animals as a compounding agent for pharmaceuticals. It can also be blended into various cosmetic or health-promoting foods and drinks, feeds, etc., and ingested by humans and animals.

For example, cosmetics or quasi-drugs containing the extract according to the present invention include milky lotions, creams, lotions, essences, packs, lipsticks, foundations, liquid foundations, makeup press powders, blushers, white powders, facial cleansers, and body washes. Examples include shampoos, hair shampoos, soaps, hair growth agents, bath additives, etc., but are not limited to these, of course.

The blending amount of the extract of the present invention as a compounding agent for cosmetics, quasi-drugs, or pharmaceuticals is preferably 0.0001 to 1.0% by weight (solid content weight%, the same hereinafter) as the solid content of the extract. . Further, the amount of the extract in the cosmetic or health promotion composition is preferably in the range of 0.1 to 15% by weight as the solid content of the extract.

When the extract according to the present invention is used as a compounding agent for cosmetics or quasi-drugs, in addition to the essential components of the extract, for example, oily components, surfactants (synthetic type, natural product type), moisturizing agent, etc. , a thickener, an emulsifier or an emulsifying aid, a preservative/sterilizer, a powder component, an ultraviolet absorber, an antioxidant, a pigment, a fragrance, and other physiologically active ingredients can be appropriately blended as necessary. Further, as long as the effectiveness and characteristics of the extract according to the present invention are not impaired, it may be blended in combination with other physiologically active ingredients.

Here, examples of oily ingredients include olive oil, jojoba oil, castor oil, soybean oil, rice oil, rice germ oil, coconut oil, palm oil, cacao oil, meadowfoam oil, shea butter, tea tree oil, avocado oil, Plant-derived oils and fats such as macadamia nut oil and plant-derived squalane; Animal-derived oils and fats such as mink oil and turtle oil; Waxes such as beeswax, carnauba wax, rice wax, and lanolin; liquid paraffin, petrolatum, paraffin wax, squalane, etc. hydrocarbons; fatty acids such as myristic acid, palmitic acid, stearic acid, oleic acid, isostearic acid, and cis-11-eicosenoic acid; higher alcohols such as lauryl alcohol, cetanol, and stearyl alcohol; isopropyl myristate, palmitic acid Examples include synthetic esters such as isopropyl, butyl oleate, 2-ethylhexylglyceride, higher fatty acid octyldodecyl (octyldodecyl stearate, etc.), and synthetic triglycerides.

Examples of the surfactant include polyoxyethylene alkyl ether, polyoxyethylene fatty acid ester, polyoxyethylene sorbitan fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyoxyethylene hydrogenated castor oil, and polyoxyethylene fatty acid ester. Nonionic surfactants such as oxyethylene sorbitol fatty acid esters; fatty acid salts, alkyl sulfates, alkylbenzene sulfonates, polyoxyethylene alkyl ether sulfates, polyoxyethylene fatty amine sulfates, polyoxyethylene alkyl phenyl ether sulfates, Anionic surfactants such as polyoxyethylene alkyl ether phosphates, α-sulfonated fatty acid alkyl ester salts, polyoxyethylene alkylphenyl ether phosphates; quaternary ammonium salts, primary to tertiary fatty amine salts, Cationic surfactants such as alkylbenzylammonium salts, alkylpyridinium salts, 2-alkyl-1-alkyl-1-hydroxyethylimidazolinium salts, N,N-dialkylmorphonium salts, polyethylene polyamine fatty acid amide salts; N, N-dimethyl-N-alkyl-N-carboxymethylammoniobetaine, N,N,N-trialkyl-N-alkyleneammoniocarboxybetaine, N-acylamidopropyl-N',N'-dimethyl-N'- Amphoteric surfactants such as β-hydroxypropylammoniosulfobetaine and the like can be used.

As emulsifiers or emulsification aids, stevia derivatives such as enzyme-treated stevia, lecithin and its derivatives (hydrogenated lecithin, etc.), lactic acid bacteria-fermented rice, lactic acid bacteria-fermented germinated rice, lactic acid bacteria-fermented grains (wheat, beans, millet, etc.), etc. It can also be blended.

Examples of humectants include glycerin, propylene glycol, dipropylene glycol, 1,3-butylene glycol, polyethylene glycol, sorbitol, xylitol, sodium pyrrolidone carboxylate, and saccharides such as trehalose, mucopolysaccharides (e.g., hyaluronic acid, etc.). acid and its derivatives, chondroitin and its derivatives, heparin and its derivatives), elastin and its derivatives, collagen and its derivatives, NMF-related substances, lactic acid, urea, higher fatty acid octyldodecyl, seaweed extract, silane root (white) Examples include extracts, various amino acids, and derivatives thereof.

Examples of thickeners include ingredients derived from brown algae, green algae, or red algae such as alginic acid, agar, carrageenan, and fucoidan; extracts of silane root; pectin, locust bean gum, aloe polysaccharides, and alcaligenes-producing polysaccharides; Polysaccharides; Gums such as xanthan gum, tragacanth gum, and guar gum; Cellulose derivatives such as carboxymethylcellulose and hydroxyethylcellulose; Synthetic polymers such as polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, and acrylic acid/methacrylic acid copolymer; Hyaluronic acid and derivatives thereof; polyglutamic acid and derivatives thereof, and the like.

Examples of preservatives and disinfectants include urea; paraoxybenzoic acid esters such as methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, and butyl paraoxybenzoate; phenoxyethanol, dichlorophene, hexachlorophene, chlorhexidine hydrochloride, and benzyl chloride. Examples include ruconium, salicylic acid, ethanol, undecylenic acid, phenols, jamal (imidazodeinyl urea), 1,2-pentanediol, various essential oils, bark dry distillate, and fermented radish liquid.

Examples of powder components include sericite, titanium oxide, talc, kaolin, bentonite, zinc oxide, magnesium carbonate, magnesium oxide, zirconium oxide, barium sulfate, silicic anhydride, mica, nylon powder, polyethylene powder, silk powder, and cellulose. There are powders from grains (rice, wheat, corn, millet, etc.), and powders from legumes (soybeans, adzuki beans, etc.).

Examples of ultraviolet absorbers include ethyl para-aminobenzoate, ethylhexyl para-dimethylaminobenzoate, amyl salicylate and its derivatives, 2-ethylhexyl para-methoxycinnamate, octyl cinnamate, oxybenzone, 2,4-dihydroxybenzophenone, 2-hydroxy-4 -Methoxybenzophenone-5-sulfonate, 4-tert-butyl-4-methoxybenzoylmethane, 2-(2-hydroxy-5-methylphenyl)benzotriazole, urocanic acid, ethyl urocanate, aloe extract, etc. .

Examples of antioxidants include butylated hydroxyanisole, butylated hydroxytoluene, propyl gallate, vitamin E and its derivatives (e.g., vitamin E nicotinate, vitamin E linoleate, etc.), peony extract, silane root extract, etc. There is.

As whitening agents, t-cycloamino acid derivatives, kojic acid and its derivatives, ascorbic acid and its derivatives, hydroquinone or its derivatives, ellagic acid and its derivatives, nicotinic acid and its derivatives, resorcinol derivatives, tranexamic acid and its derivatives, 4 -Methoxysalicylic acid potassium salt, magnolignan (5,5'-dipropyl-biphenyl-2,2'-diol), 4-HPB (rhodenol, 4-(4-hydroxyphenyl)-4-butanol)), hydroxybenzoic acid and its derivatives, vitamin E and its derivatives, α-hydroxy acid, AMP (adenosine monophosphate, adenosine monophosphate), and these may be blended alone or in combination of two or more.

Examples of the above-mentioned kojic acid derivatives include kojic acid esters such as kojic acid monobutyrate, kojic acid monocaprate, kojic acid monopalmitate, and kojic acid dibutyrate, kojic acid ethers, and kojic acid sugar derivatives such as kojic acid glucoside. However, examples of ascorbic acid derivatives include sodium L-ascorbic acid-2-phosphate, magnesium L-ascorbic acid-2-phosphate, sodium L-ascorbic acid-2-sulfate, and sodium L-ascorbic acid-2-phosphate. -Ascorbic acid ester salts such as magnesium sulfate ester, ascorbic acid sugar derivatives such as L-ascorbic acid-2-glucoside, L-ascorbic acid-5-glucoside, and 6-position acylated products of these ascorbic acid sugar derivatives (the acyl group is (hexanoyl group, octanoyl group, decanoyl group, etc.), L-ascorbic acid tetrafatty acid esters such as L-ascorbic acid tetraisopalmitate ester, L-ascorbic acid tetralaurate ester, 3-O-ethyl ascorbic acid, L- Ascorbic acid glycerin derivatives such as sodium ascorbic acid-2-phosphate-6-O-palmitate, glyceryl ascorbic acid or its acylated derivatives, bisglyceryl ascorbic acid, and hydroquinone derivatives include arbutin (hydroquinone-β-D- glucopyranoside), α-arbutin (hydroquinone-α-D-glucopyranoside), etc.; examples of tranexamic acid derivatives include tranexamic acid esters (for example, tranexamic acid lauryl ester, tranexamic acid hexadecyl ester, tranexamic acid cetyl ester or salts thereof), Examples of amide derivatives of tranexamic acid (for example, tranexamic acid methylamide) include resorcinol derivatives such as 4-n-butylresorcinol and 4-isoamylresorcinol, and examples of 2,5-dihydroxybenzoic acid derivatives include, for example. 2,5-diacetoxybenzoic acid, 2-acetoxy-5-hydroxybenzoic acid, 2-hydroxy-5-propionyloxybenzoic acid, etc.; examples of nicotinic acid derivatives include nicotinic acid amide, benzyl nicotinate, etc.; Examples of hydroxy acids include lactic acid, malic acid, succinic acid, citric acid, and α-hydroxyoctanoic acid.

As a physiologically active ingredient, as a whitening ingredient, for example, placenta extract, sagebrush extract, saxifrage extract, perilla extract, white mustard extract or its hydrolyzate, fermented white mustard, damask rose extract, peony Extract or hydrolyzate thereof, lactic acid bacteria-fermented rice, lotus seed extract or hydrolyzate thereof, fermented lotus seed, ginseng extract, hydrolyzed coix seed, fermented coix seed, fermented royal jelly, fermented sake lees, pandanus・Amaryllifolius (Pandanus amaryllifolius Roxb.) extract, Arcangelicia flava Merrilli (Arcangelicia flava Merrilli) extract, chamomile extract, etc. are listed, and anti-aging ingredients include coral grass extract and rice leaf extract. or its hydrolyzate, eggplant (water eggplant, long eggplant, Kamo eggplant, rice eggplant, etc.) extract or its hydrolyzate, extract of seaweed such as Katamenkirinsai, extract of marine flowering plants such as eelgrass, soy milk. Fermented products, jellyfish water, fermented rice extract, linoleic acid and its derivatives or processed products (e.g. liposomal linoleic acid, etc.), animal or fish-derived collagen and its derivatives, elastin and its derivatives, glycyrrhizic acid and its derivatives (dipotassium salt) etc.), t-cycloamino acid derivatives, vitamin A and its derivatives, allantoin, diisopropylamine dichloroacetate, γ-amino-β-hydroxybutyric acid, gentian extract, licorice extract, carrot extract, aloe extract, honeysuckle extract , Ulva extract, Zizyphus joazeiro extract, etc.

Next, the present invention will be explained in more detail with reference to production examples, formulation examples, and test examples, but the present invention is not limited thereto. In addition, in the following, all parts mean parts by weight, and all percentages mean weight %.

Manufacturing example 1. Preparation of rice extract (1)
1000 g of purified water and 1 g of lactic acid were added to 200 g of germinated brown rice, stirred and extracted for 1 day, and then coarsely filtered with a filter cloth to remove the remaining germinated brown rice residue. After neutralizing the extract with an aqueous sodium hydroxide solution, liquefying enzyme (α-amylase 0.1%) was added to the liquid volume, enzymatic decomposition was performed at 70°C for 1 hour, and then at 80°C for 1 hour. After inactivating the enzyme by heating for a period of time, proteolytic enzymes (actinase AS 0.1%, papain 0.1%) were further added to the liquid volume, enzymatic decomposition treatment was performed at 40°C for 2 hours, and then The enzyme was inactivated by heating at °C for 1 hour and cooled to room temperature. The enzyme-treated liquid thus obtained was purified and filtered to obtain 783 g of a pale yellow germinated brown rice hydrolyzate solution (solid content concentration: 1.9%).

Production example 2. Preparation of rice extract (2)
1000 g of 0.1% aqueous sodium hydroxide solution was added to 250 g of polished black rice, stirred and extracted for 1 day, and then coarsely filtered with a filter cloth to remove the remaining black rice residue. After neutralizing the extract with dilute hydrochloric acid, proteolytic enzymes (actinase AS 0.02%, papain 0.02%) were added to the liquid volume, enzymatic decomposition treatment was performed at 40°C for 2 hours, and then at 80°C. The enzyme was inactivated by heating for 1 hour, and the mixture was cooled to room temperature. The enzyme-treated liquid thus obtained was purified and filtered to obtain 817 g of a light brown and transparent black rice hydrolyzate solution (solid content concentration: 1.71%).

Production example 3. Preparation of rice extract (3)
1000 g of 0.1% aqueous sodium hydroxide solution was added to 250 g of polished rice, stirred for extraction for 1 day, and then coarsely filtered with a filter cloth to remove remaining rice residue. After neutralizing the extract with dilute hydrochloric acid, proteolytic enzymes (actinase AS 0.02%, papain 0.02%) were added to the liquid volume, enzymatic decomposition treatment was performed at 40°C for 2 hours, and then at 80°C. The enzyme was inactivated by heating for 1 hour, and the mixture was cooled to room temperature. The enzyme-treated liquid thus obtained was purified and filtered to obtain 805 g of a light brown and transparent rice hydrolyzate solution (solid content concentration: 1.69%).

Manufacturing example 4. Preparation of loofah extract (1)
100 g of purified water was added to 10 g of dried loofah fruits, stems, and leaves, and extracted at 40° C. for 3 hours. The resulting solution was filtered to obtain 73.2 g of a brown transparent solution (solid content concentration 2.6%). This was used as a loofah extract solution.

Manufacturing example 5. Preparation of loofah extract (2)
After cutting 200 g of raw loofah fruits, the juice was squeezed, and the resulting solution was heated at 40° C. for 1 hour. After heating, it was filtered to obtain 113 g (solid concentration 4.4%). It was diluted 2 times with purified water to obtain a pressed loofah extract solution.

Production example 6. Preparation of peach extract 600 g of purified water was mixed with 60 g of immature fruit of peach (Prunus persica Batsch), and the mixture was allowed to stand for 2 hours at 80°C for extraction to obtain 456.2 g of an extract solution. . After that, the obtained extract solution was filtered, and further, 1% activated carbon (manufactured by Wako Pure Chemical Industries, Ltd.) was added to the filtered solution and activated carbon treatment was performed for 1 hour. 445.1 g of fruit extract solution was obtained (pH 4.2, solid content concentration 3.58%).

Manufacturing example 7. Preparation of Soybean Extract 200 g of purified water was added to 10 g of dry pulverized black soybean seeds (black soybean), and extracted at 80° C. for 1 hour. After rough filtration of the obtained extract, the pH was adjusted to 5 using diluted hydrochloric acid, and then Neurase (manufactured by Amano Enzyme Co., Ltd.) was added to a concentration of 0.01%, and the mixture was heated at 40°C for 3 hours. Made it work. Next, the mixture was treated at 80° C. for 1 hour to inactivate the enzyme, and then filtered to obtain 158 g of a light brown transparent hydrolyzate solution of black soybean extract (solid content concentration 1.14%).

Production example 8. Preparation of Murasakikibu extract 30g of purified water was added to 3.0g of Murasakikibu fruit, and extracted at 40°C for 3 hours. The obtained solution was filtered to obtain 15.4 g of a brown transparent solution (solid content concentration 1.90%). This was diluted 10 times with purified water to obtain an extract solution.

Production example 9. Preparation of apricot extract The skin and seeds were removed from the fruit of Hong apricot, a member of the Rosaceae family, Prunus genus, and ground into a paste using a grinder. 210 g of 1,3-butylene glycol was added to 90 g of this fruit paste and extracted at 4°C. After adding 405 g of purified water to this, it was filtered to obtain 587 g of a brown and transparent Honguan fruit extract solution (solid content concentration 1.63%).

Production example 10. Preparation of Leafwort extract 100g of purified water was added to 10g of Leafwort leaves and extracted at 40°C for 2 hours. The obtained extract solution was filtered, and further, 1% activated carbon (manufactured by Wako Pure Chemical Industries, Ltd.) was added to the filtered solution, and activated carbon treatment was performed for 1 hour to obtain a light brown color of the extract solution (solid). 2.30%) 60g was obtained. This was diluted 10 times with purified water to obtain an extract solution.

Prescription example 1. Lotion [Ingredient A] Part Olive oil 1.0
Polyoxyethylene (5.5) Cetyl Alcohol 5.0
Butylparaben 0.1
[B component]
Extract solution of Production Example 1 5.0
Ethanol 5.0
Glycerin 5.0
1,3-butylene glycol 5.0
Potassium hydroxide Appropriate amount Purified water Amount to make 100 parts [Component C]
Perfume Appropriate amount After heating component A and component B to 80° C. or higher, component B was added to component A, stirred, and further homogenized for 2 minutes using a Hiscotron (5000 rpm). After cooling this to 50°C, component C was added and mixed with stirring, and the mixture was further cooled to 30°C or lower to obtain a lotion.

Prescription example 2. Lotion A lotion was obtained in the same manner as in Prescription Example 1, except that 5.0 parts of the extract solution in Preparation Example 2 was used instead of the extract solution in Preparation Example 1 contained in component B of Prescription Example 1. .

Prescription example 3. Lotion A lotion was obtained in the same manner as in Prescription Example 1, except that 5.0 parts of the extract solution in Preparation Example 3 was used in place of the extract solution in Preparation Example 1 contained in component B of Prescription Example 1. .

Prescription example 4. Lotion A lotion was obtained in the same manner as in Prescription Example 1, except that 5.0 parts of the extract solution in Preparation Example 4 was used in place of the extract solution in Preparation Example 1 contained in component B of Prescription Example 1. .

Prescription example 5. Lotion A lotion was obtained in the same manner as Prescription Example 1, except that 5.0 parts of the extract solution of Production Example 5 was used instead of the extract solution of Production Example 1 contained in component B of Prescription Example 1. .

Prescription example 6. Lotion A lotion was obtained in the same manner as in Prescription Example 1, except that 5.0 parts of the extract solution in Preparation Example 6 was used instead of the extract solution in Preparation Example 1 contained in component B of Prescription Example 1. .

Prescription example 7. Lotion A lotion was obtained in the same manner as in Prescription Example 1, except that 5.0 parts of the extract solution in Preparation Example 7 was used in place of the extract solution in Preparation Example 1 contained in component B of Prescription Example 1. .

Prescription example 8. Lotion A lotion was obtained in the same manner as in Prescription Example 1, except that 5.0 parts of the extract solution in Preparation Example 8 was used instead of the extract solution in Preparation Example 1 contained in component B in Prescription Example 1. .

Prescription example 9. Lotion A lotion was obtained in the same manner as in Prescription Example 1, except that 5.0 parts of the extract solution in Preparation Example 9 was used instead of the extract solution in Preparation Example 1 contained in component B of Prescription Example 1. .

Prescription example 10. Lotion A lotion was obtained in the same manner as in Prescription Example 1, except that 5.0 parts of the extract solution in Preparation Example 10 was used in place of the extract solution in Preparation Example 1 contained in component B in Prescription Example 1. .

Prescription example 11. Emulsion [Component A] Part Liquid paraffin 6.0
Hexalan 4.0
Jojoba oil 1.0
Polyoxyethylene (20) Sorbitan Monostearate 2.0
Soybean lecithin 1.5
[B component]
Extract solution of Production Example 6 3.0
L-ascorbic acid-2-glucoside 2.0
Potassium hydroxide 0.5
Glycerin 3.0
1,3-butylene glycol 2.0
Carboxymethyl cellulose 0.3
Sodium hyaluronate 0.01
Purified water Amount that makes the total amount 100 parts [Component C]
Perfume Appropriate amount The above A component and B component were each heated to 80° C. or higher, and then mixed with stirring. After cooling this to 50° C., component C was added and further stirred and mixed to obtain a milky lotion.

Prescription example 12. Emulsion Prepare an emulsion in the same manner as in Formulation Example 10, except that 3.0 parts of arbutin is used in place of 2.0 parts of L-ascorbic acid-2-glucoside and 0.5 parts of potassium hydroxide in component B of Formulation Example 11. Obtained.

Prescription example 13. Emulsion A milky lotion was prepared in the same manner as in Formulation Example 10, except that 2.0 parts of tranexamic acid was used in place of 2.0 parts of L-ascorbic acid-2-glucoside and 0.5 parts of potassium hydroxide in component B of Formulation Example 11. I got it.

Prescription example 14. Emulsion Proceed as in Formulation Example 10, except that 3.0 parts of nicotinic acid amide is used in place of 2.0 parts of L-ascorbic acid-2-glucoside and 0.5 parts of potassium hydroxide in component B of Formulation Example 11. A milky lotion was obtained.

Prescription example 15. Emulsion [Component A] Part Liquid paraffin 6.0
Hexalan 4.0
Jojoba oil 1.0
Polyoxyethylene (20) Sorbitan Monostearate 2.0
Soybean lecithin 1.5
[B component]
Extract solution of Production Example 9 5.0
L-ascorbic acid-2-glucoside 2.0
Potassium hydroxide 0.5
Arbutin 3.0
Glycerin 3.0
1,3-butylene glycol 2.0
Carboxymethyl cellulose 0.3
Sodium hyaluronate 0.01
Purified water Amount that makes the total amount 100 parts

Prescription example 16. Lotion [Ingredients] Part Extract solution of Production Example 2 10.0
Ethanol 10.0
Glycerin 3.0
1,3-butylene glycol 2.0
Methylparaben 0.2
Citric acid 0.1
Sodium citrate 0.3
Carboxyvinyl polymer 0.1
Perfume: Appropriate amount Potassium hydroxide: Appropriate amount Purified water: Amount to make a total of 100 parts The above ingredients were mixed to obtain a lotion.

Prescription example 17. Essence [Ingredients] Part Ethanol 2.0
Glycerin 5.0
1,3-butylene glycol 5.0
Methylparaben 0.1
Hyaluronic acid 0.1
Extract solution of Production Example 3 5.0
Citric acid 0.3
Sodium citrate 0.6
Purified water Amount to make the total amount 100 parts After dissolving hyaluronic acid in purified water, the remaining raw materials were sequentially added and dissolved with stirring to obtain a transparent essence.

Prescription example 18. Essence An essence was obtained in the same manner as in Formulation Example 17, except that 5.0 parts of the extract solution in Production Example 4 was used in place of the extract solution in Production Example 1 in the components of Formulation Example 17.

Example 19. Liquid foundation [A component] Part Stearic acid 2.4
Propylene glycol monostearate 2.0
Cetostearyl alcohol 0.2
liquid lanolin 2.0
Liquid paraffin 3.0
Isopropyl myristate 8.5
Propylparaben 0.05
[B component]
Extract solution of Production Example 5 5.0
Sodium carboxymethylcellulose 0.2
bentonite 0.5
Propylene glycol 4.0
Triethanolamine 1.1
Methylparaben 0.1
Purified water Amount that makes the total amount 100 parts [Component C]
Titanium oxide 8.0
Talc 4.0
Coloring Pigment Appropriate Amount The above A component and B component were respectively heated and then mixed and stirred. This was rewarmed, the above component C was added, poured into a mold, and stirred until it reached room temperature to obtain a liquid foundation.

Prescription example 20. Body shampoo [Ingredient A] Part N-lauroylmethylalanine sodium 25.0
Coconut oil fatty acid potassium solution (40%) 26.0
Coconut oil fatty acid diethanolamide 3.0
Methylparaben 0.1
[B component]
Extract solution of Production Example 8 5.0
1,3-butylene glycol 2.0
Purified water Amount to make the total amount 100 parts After heating component A and component B to 80°C and uniformly dissolving them, add component B to component A, continue stirring, and cool to room temperature to obtain body shampoo. Ta.

Prescription example 21. Hair growth agent [Ingredients] Part: Dipotassium glycyrrhizinate 0.1
Mononitroguaiacol sodium 0.02
Pyridoxine hydrochloride 0.03
l-menthol 0.8
Tamasakitsudurafuji root extract 0.3
Brown algae extract 0.3
Panax ginseng extract 0.3
Gentiana extract 2.0
Extract of Production Example 6 3.5
Trimethylglycine 0.5
Lactic acid 0.2
1,3-butylene glycol 10.0
Phenoxyethanol 0.2
Polyoxyethylene hydrogenated castor oil 0.4
L-Arginine Appropriate amount Ethanol 20.0
Purified water Amount to make the total amount 100 parts The above ingredients were sufficiently stirred and mixed to obtain a hair growth agent.

Prescription example 22. Hair shampoo [Ingredient A] Part N-coconut oil fatty acid methyltaurine sodium 10.0
Polyoxyethylene (3) alkyl ether sodium sulfate 20.0
Lauryldimethylaminoacetic acid betaine 10.0
Coconut oil fatty acid diethanolamide 4.0
Methylparaben 0.1
[B component]
Citric acid 0.1
Extract of Production Example 1 2.0
1,3-butylene glycol 2.0
Purified water Amount to make the total amount 100 parts After heating component A and component B to 80°C and uniformly dissolving them, add component B to component A, continue stirring, and cool to room temperature to obtain hair shampoo. Ta.

Example 23. Hair conditioner [Ingredient A] Part Polyoxyethylene (10) Hydrogenated castor oil 1.0
Distearyldimethylammonium chloride 1.5
Stearyltrimethylammonium chloride 2.0
Glyceryl 2-ethylhexanoate 1.0
Setanol 3.2
Stearyl alcohol 1.0
Methylparaben 0.1
[B component]
Extract of Production Example 1 2.0
1,3-butylene glycol 5.0
Purified water Amount to make the total amount 100 parts After heating component A and component B to 80°C and uniformly dissolving each component, component B was added to component A, continued stirring, and cooled to room temperature to obtain a hair rinse. .

Prescription example 24. Beverage [Ingredients] Part Extract of Production Example 1 10.0
Collagen 8.0
Citric acid 0.1
Sweetener (sucrose) 0.01
Antioxidant (vitamin C) 0.01
Purified water Amount that makes the total amount 100 parts

Prescription example 25. Tablet [Ingredients] Part Extract of Production Example 3 20.0
Vitamin C 20.0
Fatty acid ester 10.0
Calcium lactate 20.0
Lactose 30.0
After mixing the above weight parts of each component, the mixture was press-molded to form a tablet.

Test example 1. Stem Cell Oxidative Damage Suppression Evaluation Human skin-derived mesenchymal stem cells (Yub637s) were seeded at 8 x ¹⁰ cells/well in a 96-well microplate containing a special medium (M-061101: manufactured by Glyco Technica Co., Ltd.), and 37 After pre-culturing for 1 day under the conditions of 5.0% CO2 at ℃, each extract of Production Examples 1 to 10 was added to the medium as a sample solution, and cultured for another 1 day under the same conditions. Here, the sample solution was prepared so that the final concentration as a solution based on the total amount of the medium was 2.0%. Next, the medium was removed, and a hydrogen peroxide solution adjusted to a final concentration of 1 mM using Hank's buffered saline solution was added, and the mixture was allowed to stand for 1 hour at 37° C. and 5.0% CO 2 . After that, the solution was removed, 0.03% MTT was added and kept at 37°C for 1 hour, and the formed formazan was extracted with isopropanol, and the wavelength MTT values were measured at 570-630 nm. Two groups were set up in which PBS (-) was added instead of the sample solution and no sample was added. One group was "Control (1)" (unexposed control) which was not exposed to hydrogen peroxide, and the other was "Control (1)" which was exposed to hydrogen peroxide. The same operation as above was performed as "Control (2)" (exposed control), and the relative value of the MTT value at the time of each sample addition to the MTT value of the control unexposed control group was determined, and this was determined as the survival rate (%) of the stem cells. In addition, in order to confirm whether the test system was functioning normally, a similar test was also conducted when 1 mM ascorbic acid phosphate magnesium salt (APM) was added as a positive control instead of the sample solution.

The results of Test Example 1 are shown in Table 1.
[Table 1]

As shown in Table 1, it was shown that the extracts of Production Examples 1 to 10 according to the present invention significantly suppressed oxidative damage to hepatocytes caused by hydrogen peroxide and increased cell survival rate. Furthermore, since the positive control "APM" also showed an increase in cell survival rate, it was confirmed that this test system was carried out normally.

As described above, according to the present invention, it is possible to suppress oxidative damage to mesenchymal stem cells and maintain their functions. Therefore, the present invention is useful for skin repair/regeneration, maintenance of function, cell repair/regeneration, anti-fibrosis, prevention/treatment of various diseases such as multiple sclerosis and diabetes, and various diseases based on chronic inflammation such as metabolic syndrome. It is extremely useful as an agent for preventing and improving conditions.

Claims (1)

Extracts of immature peach fruits with water, a mixed solvent of water and lower alcohols (excluding methanol) , or mixed solvents of water and polyhydric alcohols; Extracts of mixed solvents or mixed solvents of water and polyhydric alcohols; An oxidative damage inhibitor for mesenchymal stem cells, which contains any one or more extracts as an active ingredient.