JP2016008177A - External preparation for skin - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an external preparation for skin which contains a functional material excellent in biosafety derived from natural products, and has dermal health effects and anti-aging effects.SOLUTION: The invention relates to a functional material which promotes synthesis of heparan sulphate proteoglycan, XIII type collagen in a dermal basement membrane, the functional material being a component excellent in biosafety derived from one or more plant extract selected from rice and peach, or a hydrolysate thereof; and an external preparation for skin containing the same.

Description

  The present invention relates to an external preparation for skin which is obtained from a plant extract and contains a component having cell activity and cell proliferation action around the skin basement membrane.

  In recent years, various studies have been conducted on the structure of the skin and its mechanism. For example, the extracellular matrix such as collagen and elastin in the dermis and the basement membrane existing between the dermis and the epidermis is merely a structure of the skin. It has become clear that it is involved not only in maintaining the activity but also in maintaining the activity and functionality of cells that adhere to it. In particular, the basement membrane exists between epithelial cells and mesenchymal tissues, and is considered to have a great influence on the division of epithelial cells and the maintenance of the functionality of cells existing in the mesenchymal system. In addition, heparan sulfate is known as a factor that exists in the basement membrane and is involved in maintaining the function of the skin. This heparan sulfate is a kind of sugar chain distributed in animal tissues, that is, glucosaminoglycans (polysaccharides composed of D-glucosamine, D-glucuronic acid, and L-iduronic acid). In the extracellular matrix, it exists as a proteoglycan bound to a core protein. As this heparan sulfate proteoglycan, perlecan, agrin, type XVIII collagen and the like are known, and these are cell growth factors (fibroblast growth factor (FGF) 1-7, epidermal growth factor (EGF), vascular endothelial cell proliferation). It is also known that cells around the basement membrane are proliferated and activated by binding the factor (VEGF)) and storing these factors around the basement membrane (Patent Document 1, Non-Patent Documents 1 and 2). ). Heparan sulfate proteoglycans can also regulate cytokine movement between the epidermis and dermis by binding to cytokines (eg, IL-2,3,4,8, GM-CSF, TNF-α). It is known (Non-patent Document 3).

  Based on the above knowledge, the production of heparan sulfate is promoted to improve skin wrinkles and pigmentation (Patent Document 1) and the activity of heparanase that degrades the heparan sulfate chain of heparan sulfate proteoglycan. Techniques for inhibiting (Patent Document 2, Non-Patent Document 3) have been proposed.

JP2013-203725A WO2009 / 123215 J.Soc.Cosmet.Chem.Jpn. 48 (1) 35-40 (2014) www.nature.com/reviews/molcellbio AUGUST 2005, VOLUME 6, 646-656 Bulletin of Chiba University of Science 5.69-76.2012

  The present invention has been made in view of the above background, and its object is to provide an external preparation for skin that is excellent in biological safety and contains a component that promotes the synthesis of heparan sulfate proteoglycan present in the skin basement membrane. With the goal.

The present invention is an external preparation for skin containing a substance that promotes the synthesis of heparan sulfate proteoglycans in the skin basement membrane.
In the present invention, the heparan sulfate proteoglycan is preferably type XVIII collagen.

  ADVANTAGE OF THE INVENTION According to this invention, the skin external preparation which has the effect which proliferates and activates the cell surrounding a skin basement membrane based on the synthetic | combination acceleration | stimulation effect | action of heparan sulfate proteoglycan derived from a natural product and excellent in biological safety can do.

Hereinafter, preferred embodiments of the present invention will be described in detail.
The present invention comprises, as an active ingredient, an extract of one or more plants selected from the group consisting of rice and peach, or a hydrolyzate thereof.

  In the present invention, “rice” is obtained from a plant of the family Poaceae (Oryza), and in the present invention, brown rice, germinated brown rice, pigmented rice (black rice, red rice, purple rice) Rice, green rice, etc.), or polished rice from which rice bran is removed, germinated rice, or red rice bran or white rice obtained in the process of polishing brown rice, germinated brown rice, or pigmented rice can be used.

  Further, in the present invention, “peach” is a plant of the Rosaceae (Prunus) family. Examples of sites that can be used in the present invention include whole plants, fruits, flowers, seeds, leaves, stems, roots, and the like. Moreover, when using a fruit, an immature thing can also be used.

  For the preparation of the extract, first, if necessary, the site of use of each plant is washed with water in advance to remove foreign substances, and then directly or dried, and then minced or crushed as necessary, and contacted with an extraction solvent. It can prepare by the method (For example, appropriate means, such as a dipping method and a countercurrent extraction method) which performs extraction. A supercritical extraction method may also be used. Furthermore, you may prepare by pressing a use site | part (fruit etc.) as it is, or crushing a use site | part, and pressing the crushed material. It can also be prepared by drying the used part and then pulverizing it into a dry pulverized product, or extracting the dry powder obtained by lyophilizing the used part or, in some cases, the juice, with a solvent. be able to.

  As an extraction solvent, water; lower alcohols such as methanol, ethanol, propanol; polyhydric alcohols such as ethylene glycol, propylene glycol, 1,3-butylene glycol, glycerin; ethyl acetate, butyl acetate, methyl propionate, etc. 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, and the like. These may be used alone or in combination of two or more. Used.

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

  When the mixed solvent is used, for example, if the mixed solvent is water and 1,3-butylene glycol, the volume ratio (hereinafter the same) is 1:10 to 20: 1, and the mixed solvent is water and ethanol. If it exists, it is preferable to set it as the range of 1: 10-20: 1 if it is a mixed solvent of 1: 10-25: 1 and water and glycerol.

  The weight ratio of each plant to the use site extraction solvent is preferably in the range of 1: 1 to 1:50, more preferably in the range of 1: 3 to 1:35.

  In preparing the extract, the pH is not particularly limited, but it is generally preferably in the range of 3-9. In this sense, if necessary, the extraction solvent is blended with an alkaline adjusting agent such as sodium hydroxide, sodium carbonate or potassium hydroxide, or an acidic adjusting agent such as citric acid, hydrochloric acid, phosphoric acid or sulfuric acid. You may adjust so that it may become pH of.

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

  In addition, you may perform a hydrolysis process as needed before the extraction process of this invention or in parallel with an extraction process, or after an extraction process. As a result, the extract may be used more effectively. Examples of the hydrolysis treatment include acid treatment, alkali treatment, enzyme treatment, and the like, and among them, enzyme treatment is most preferable. Examples of the enzyme to be used include one or more selected from a proteolytic enzyme, a amylolytic enzyme, a fibrinolytic enzyme, and a lipolytic enzyme.

  The proteolytic enzyme may be any of an animal-derived enzyme, a plant-derived enzyme, and a microorganism-derived enzyme. 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. Examples of the amylolytic enzyme include glucoamylase and α-amylase. Examples of the fibrinolytic enzyme include cellulase, hemicellulase, pectinase and the like. Moreover, lipase etc. are mentioned as a lipolytic enzyme. As an enzyme to be used, one or two or more kinds selected from any enzyme group may be used, or one or two or more kinds of enzymes selected from those enzyme groups may be used in combination. .

  The amount of the enzyme added is preferably in the range of 0.01 to 10% by weight, and more preferably in the range of 0.1 to 2.0% by weight, based on the solid content of the use site of each plant. is there.

  In general, the extract prepared as described above may be adjusted to a pH of 3 to 8 and used as it is as a skin external preparation compound as it is, or as a desired concentration by vacuum concentration or the like. May be used. In addition, the extract may be dried by a conventional method such as spray drying.

  The extract prepared as described above can be applied as a component for external preparations for skin (such as cosmetics or quasi drugs).

  For example, cosmetics or quasi-drugs containing the extract according to the present invention include emulsions, creams, lotions, essences, packs, lipsticks, foundations, liquid foundations, makeup press powders, cheeks, white powders, face wash, body Shampoos, hair shampoos, soaps and the like can be mentioned, and hair restorers and further bath agents and the like can be mentioned, but of course not limited thereto.

  The blending amount of the extract of the present invention as a blending component of the external preparation for skin is preferably 0.0001 to 1.0% by weight (solid content weight%, hereinafter the same) as the solid content of the extract.

  When the extract according to the present invention is used as a blending component of cosmetics or quasi drugs, in addition to the essential component extract, for example, an oily component, a surfactant (synthetic or natural product), a humectant. , Thickeners, emulsifiers or emulsifying aids, preservatives / bactericides, powder components, ultraviolet absorbers, antioxidants, pigments, fragrances, other physiologically active components, and the like can be appropriately blended as necessary. Moreover, as long as the effectiveness and the characteristics of the extract according to the present invention are not impaired, it may be combined with other physiologically active ingredients.

  Here, as the oil component, for example, olive oil, jojoba oil, castor oil, soybean oil, rice oil, rice germ oil, palm oil, palm oil, cacao oil, meadow foam oil, sheer butter, tea tree oil, avocado oil, Macadamia nut oil, yuzu seed oil, oils derived from citrus fruits, plant-derived fats and oils such as plant-derived squalane; animal-derived fats and oils such as mink oil and turtle oil; waxes such as beeswax, carnauba wax, rice wax, lanolin; Hydrocarbons such as paraffin, petrolatum, paraffin wax, squalane; fatty acids such as myristic acid, palmitic acid, stearic acid, oleic acid, isostearic acid, cis-11-eicosenoic acid; higher grades such as lauryl alcohol, cetanol, stearyl alcohol Alcohols; isopropyl myristate, pa Michin isopropyl, butyl oleate, 2-ethylhexyl glycerides, higher fatty acid octyldodecyl (octyl stearate dodecyl and the like), and the synthetic esters and synthetic triglycerides such like.

  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, polyoxyethylene 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, Polyoxyethylene alkyl ether phosphates, α-sulfonated fatty acid alkyl ester salts, polyoxyethylene alkyl phenyl ether phosphates, Quaternary ammonium salt, primary to tertiary fatty amine salt, trialkylbenzylammonium salt, alkylpyridinium salt, 2-alkyl-1-alkyl-1-hydroxyethylimidazolinium salt, N N, N-dimethyl-N-alkyl-N-carboxymethylammoniobetaine, N, N, N-trialkyl-N-, N, N-dimethyl-N-alkyl-N-carboxymethylammoniobetaine Amphoteric surfactants such as alkylene ammoniocarboxybetaine and N-acylamidopropyl-N ′, N′-dimethyl-N′-β-hydroxypropylammoniosulfobetaine can be used.

  Examples of emulsifiers or emulsifiers include stevia derivatives such as enzyme-treated stevia, saponins or derivatives thereof, casein or salts thereof (sodium, etc.), sugar-protein complexes, sucrose or esters thereof, lactose, and soybeans. Water-soluble polysaccharides, soy-derived protein-polysaccharide complexes, lanolin or derivatives thereof, cholesterol, stevia derivatives (stevia enzyme-treated products, etc.), silicates (aluminum, magnesium, etc.), carbonates (calcium, sodium, etc.) saponins and Derivatives thereof, lecithin and derivatives thereof (hydrogenated lecithin, etc.), lactic acid bacteria fermented rice, lactic acid bacteria fermented germinated rice, lactic acid bacteria fermented cereals (wheat, beans, millet, etc.) and the like can also be blended.

  Examples of the humectant include glycerin, propylene glycol, dipropylene glycol, 1,3-butylene glycol, polyethylene glycol, sorbitol, xylitol, sodium pyrrolidone carboxylate, and sugars such as trehalose, mucopolysaccharides (for example, hyaluron). Acid and derivatives thereof, chondroitin and derivatives thereof, heparin and derivatives thereof, elastin and derivatives thereof, collagen and derivatives thereof, NMF related substances, lactic acid, urea, higher fatty acid octyldodecyl, seaweed extract, silane root (white and white) Examples include extracts, various amino acids, and derivatives thereof.

  Examples of the thickener include brown algae such as alginic acid, agar, carrageenan and fucoidan, green algae or red algae-derived components; silane root (white) extract; pectin, locust bean gum, aloe polysaccharides, alkaligenes-producing polysaccharides, etc. 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 its derivatives; polyglutamic acid and its derivatives.

  Examples of the antiseptic / bactericidal agent include urea; paraoxybenzoates such as methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, and butyl paraoxybenzoate; phenoxyethanol, dichlorophene, hexachlorophene, chlorhexidine hydrochloride, benzaza chloride Examples thereof include Luconium, Salicylic acid, Ethanol, Undecylenic acid, Phenols, Jamal (Imidazodenyl urea), 1,2-pentanediol, various essential oils, dry bark, radish fermentation liquor and the like.

  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. System powders, powders of cereals (rice, wheat, corn, millet, etc.), powders of beans (soybeans, red beans, etc.).

  Examples of the ultraviolet absorber include ethyl paraaminobenzoate, ethylhexyl paradimethylaminobenzoate, amyl salicylate and derivatives thereof, 2-ethylhexyl paramethoxycinnamate, octyl cinnamate, oxybenzone, 2,4-dihydroxybenzophenone, 2-hydroxy-4 -Methoxybenzophenone-5-sulfonate, 4-tertiarybutyl-4-methoxybenzoylmethane, 2- (2-hydroxy-5-methylphenyl) benzotriazole, urocanic acid, ethyl urocanate, aloe extract, etc. .

  Antioxidants include, for example, butylhydroxyanisole, butylhydroxytoluene, propyl gallate, vitamin E and its derivatives (eg, vitamin E nicotinate, vitamin E linoleate, etc.), peony extract, silane root (white) extract, etc. There is.

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

  Examples of the kojic acid derivative include kojic acid esters such as kojic acid monobutyrate, kojic acid monocaprate, kojic acid monopalmitate, kojic acid dibutyrate, kojic acid ethers, and kojic acid glucosi subject. However, as the ascorbic acid derivatives, for example, L-ascorbic acid-2-phosphate sodium, L-ascorbic acid-2-phosphate magnesium, L-ascorbic acid-2-sulfate sodium, L-ascorbic acid-2 -Ascorbic acid ester salts such as magnesium sulfate, L-ascorbic acid-2-glucoside, L-ascorbic acid-5-glucosi subject ascorbic acid sugar derivative, 6-position acylated product of these ascorbic acid sugar derivatives (acyl group is Hexanoyl group Octanoyl group, decanoyl group, etc.), L-ascorbic acid tetrafatty acid esters such as L-ascorbic acid tetraisopalmitate, L-ascorbic acid tetralaurate, 3-O-ethylascorbic acid, L-ascorbic acid- 2-phosphate-6-O-palmitate sodium, glyceryl ascorbic acid or acylated derivatives thereof, ascorbyl glycerol derivatives such as bisglyceryl ascorbic acid, as hydroquinone derivatives, arbutin (hydroquinone-β-D-glucopyranoside), α-Arbutin (hydroquinone-α-D-glucopyranoside) and the like as tranexamic acid derivatives include tranexamic acid esters (for example, tranexamic acid lauryl ester, tranexamic acid hexadecyl ester, Nexamic acid cetyl ester or a salt thereof), amides of tranexamic acid (for example, tranexamic acid methylamide), and the like. Examples of resorcinol derivatives include 4-n-butylresorcinol, 4-isoamylresorcinol, and the like. Examples of the -dihydroxybenzoic acid derivative include 2,5-diacetoxybenzoic acid, 2-acetoxy-5-hydroxybenzoic acid, and 2-hydroxy-5-propionyloxybenzoic acid. Examples of the nicotinic acid derivative include nicotinic acid amide. Examples of the α-hydroxy acid such as benzyl nicotinate include lactic acid, malic acid, succinic acid, citric acid, and α-hydroxyoctanoic acid.

  Examples of physiologically active ingredients include whitening ingredients such as placenta extract, Sakuhakuhi extract, Yukinoshita extract, perilla extract, white coconut extract or hydrolyzate thereof, white coconut fermented product, damask rose extract, peonies Extract or hydrolyzate thereof, soybean extract or hydrolyzate thereof, lactic acid bacteria fermented rice, lotus seed extract or hydrolyzate thereof, lotus seed fermented product, party extract, pearl hydrolyzate, pearl seed fermented product, Fermented royal jelly, fermented sake lees, Pandanus amaryllifolius Roxb. Extract, Arcangelicia flava Merrilli extract, chamomile extract, etc. Extract, rice leaf extract or hydrolyzate thereof, eggplant (water eggplant, long eggplant, Kamo eggplant, rice eggplant, etc.) extract or water Extracts from seaweeds such as demolition products, catamen giraffes, marine flowering plants such as sea cucumbers, fermented soymilk, jellyfish water, rice fermentation extract, linoleic acid and its derivatives or processed products (eg liposomal linoleic acid) Collagen derived from animal or fish and derivatives thereof, elastin and derivatives thereof, glycyrrhizic acid and derivatives thereof (dipotassium salt, etc.), t-cycloamino acid derivatives, vitamin A and derivatives thereof, allantoin, diisopropylamine dichloroacetate, γ-amino- β-hydroxybutyric acid, gentian extract, licorice extract, carrot extract, aloe extract, honey comb extract, anaoaosa extract, zizyphus joazeiro extract, kiwi extract, loofah extract, murasakikib extract, etc. is there.

  Next, the present invention will be described more specifically with reference to production examples, formulation examples, and test examples, but the present invention is not limited thereto. In the following, all parts are parts by weight, and all percentages are% by weight.

Production Example 1 Preparation of rice extract 1000 g of 0.1% sodium hydroxide aqueous solution was added to 250 g of polished rice, followed by stirring and extraction for 1 day, and then coarsely filtered with a filter cloth to remove the remaining rice residue. After neutralizing the extract with dilute hydrochloric acid, proteolytic enzyme (actinase AS 0.02%, papain 0.02%) is added to the liquid volume, followed by enzymatic degradation at 40 ° C for 2 hours, and then at 80 ° C. For 1 hour to inactivate the enzyme and cool to room temperature. The enzyme treatment solution thus obtained was purified and filtered to obtain 810 g of a light brown transparent rice hydrolyzate solution (solid content concentration: 1.71%).

Production Example 2 Preparation of extract of peach 60 g of immature fruit of peach (Prunus persica Batsch) was mixed with 600 g of purified water, and left to stand for 2 hours at 80 ° C. to obtain 455.7 g of extract solution. . Thereafter, the obtained extract solution is filtered, and further, 1% activated carbon (manufactured by Wako Pure Chemical Industries, Ltd.) is added to the filtered solution, and the activated carbon treatment is performed for 1 hour. 446.1 g of a fruit extract solution was obtained (pH 4.1, solid content concentration 3.61).

Formulation Example 1 Lotion [A component] part Olive oil 1.0
Polyoxyethylene (5.5) cetyl alcohol 5.0
Butylparaben 0.1
[Component B] Part 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 that makes the total amount 100 parts [C component]
Perfume Appropriate A component and B component were each heated to 80 ° C. or higher, then B component was added to A component and stirred, and further homogenized with Hiscotron (5000 rpm) for 2 minutes. After cooling this to 50 degreeC, C component was added and stirred and mixed, and also it cooled to 30 degrees C or less, and the lotion was obtained.

Formulation Example 2 Lotion Toner lotion was obtained in the same manner as in Formulation Example 1 except that 5.0 parts of the extract solution in Production Example 2 was used instead of the extract solution in Production Example 1 contained in Component B of Formulation Example 1. .

Formulation Example 3 Emulsion [Component A] Part Liquid paraffin 6.0
Hexalan 4.0
Jojoba oil 1.0
Polyoxyethylene (20) sorbitan monostearate 2.0
Soy lecithin 1.5
[Component B] part Extract solution of Production Example 2 3.0
L-ascorbic acid-2-glucoside 2.0
Potassium hydroxide 0.5
Glycerin 3.0
1,3-butylene glycol 2.0
Carboxymethylcellulose 0.3
Sodium hyaluronate 0.01
Purified water Amount that makes the total amount 100 parts [C component]
Fragrance Appropriate amount Each of the above components A and B was heated to 80 ° C. or higher, and then mixed by stirring. After cooling this to 50 ° C., component C was added and further stirred and mixed to obtain an emulsion.

Formulation Example 4 Emulsion In the component B of Formulation Example 3, the emulsion was prepared in the same manner as Formulation Example 10 except that 3.0 parts of arbutin was used instead of 2.0 parts of L-ascorbic acid-2-glucoside and 0.5 parts of potassium hydroxide. Obtained.

Formulation Example 5 Emulsion In the same manner as in Formulation Example 10, except that 2.0 parts of L-ascorbic acid-2-glucoside and 0.5 parts of potassium hydroxide are used instead of 2.0 parts of L-ascorbic acid-2-glucoside. Got.

Formulation Example 6 Emulsion In the same manner as in Formulation Example 10, except that 3.0 parts of nicotinamide is used instead of 2.0 parts of L-ascorbic acid-2-glucoside and 0.5 parts of potassium hydroxide in the B component of Formulation Example 3. An emulsion was obtained.

Formulation Example 7 Emulsion [Component A] Part Liquid paraffin 6.0
Hexalan 4.0
Jojoba oil 1.0
Polyoxyethylene (20) sorbitan monostearate 2.0
Soy lecithin 1.5
[Component B] Part Extract solution of Production Example 2 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
Carboxymethylcellulose 0.3
Sodium hyaluronate 0.01
Amount of purified water totaling 100 parts

Formulation Example 8 Lotion [Component] part Extract solution of Production Example 1 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 An amount that makes the total amount 100 parts.

Formulation Example 9 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 2 5.0
Citric acid 0.3
Sodium citrate 0.6
Purified water in an amount of 100 parts Hyaluronic acid was dissolved in purified water, and then the remaining raw materials were sequentially added and dissolved by stirring to obtain a transparent essence.

Example 10 Liquid foundation [component A] 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
[Component B] Part Extract solution of Production Example 1 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] Part Titanium oxide 8.0
Talc 4.0
Coloring pigment appropriate amount The components A and B were heated and mixed and stirred. This was reheated, the above C component was added, poured into a mold, and stirred until it reached room temperature to obtain a liquid foundation.

Formulation Example 11 Body shampoo [component A] part N-lauroylmethylalanine sodium 25.0
Palm oil fatty acid potassium liquid (40%) 26.0
Palm oil fatty acid diethanolamide 3.0
Methylparaben 0.1
[Component B] Part Extract solution of Production Example 2 5.0
1,3-butylene glycol 2.0
Purified water Amount to be 100 parts A component and B component are each heated to 80 ° C and dissolved uniformly, then B component is added to A component and stirring is continued to cool to room temperature to obtain a body shampoo It was.

Formulation Example 12. Hair restorer [ingredients] part Dipotassium glycyrrhizinate 0.1
Mononitroguaiacol sodium 0.02
Pyridoxine hydrochloride 0.03
l-Menthol 0.8
Japanese cypress raft root extract 0.3
Brown algae extract 0.3
Panax ginseng extract 0.3
Gentian extract 2.0
Extract solution of Production Example 2 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
The amount in which the total amount of purified water is 100 parts The above ingredients were sufficiently stirred and mixed to obtain a hair restorer.

Formulation Example 13 Hair shampoo [component A] part N-coconut oil fatty acid methyl taurine sodium 10.0
Polyoxyethylene (3) sodium alkyl ether sulfate 20.0
Lauryldimethylaminoacetic acid betaine 10.0
Palm oil fatty acid diethanolamide 4.0
Methylparaben 0.1
[B component]
Citric acid 0.1
Extract solution of Production Example 2 2.0
1,3-butylene glycol 2.0
Purified water Total amount of 100 parts A component and B component are each heated to 80 ° C and dissolved uniformly, then B component is added to A component, stirring is continued and cooled to room temperature to obtain a hair shampoo It was.

Example 14 Hair conditioner [Component A] Part Polyoxyethylene (10) hydrogenated castor oil 1.0
Distearyldimethylammonium chloride 1.5
Stearyltrimethylammonium chloride 2.0
Glyceryl 2-ethylhexanoate 1.0
Cetanol 3.2
Stearyl alcohol 1.0
Methylparaben 0.1
[Component B] Part Extract solution of Production Example 2 2.0
1,3-butylene glycol 5.0
Purified water in an amount of 100 parts A component and B component were each heated to 80 ° C. and dissolved uniformly, then B component was added to A component, and stirring was continued to cool to room temperature to obtain a hair rinse. .

Test Example 1 Confirmation test of heparan sulfate proteoglycan and cell growth factor in the basement membrane Heparanase inhibitor (2- [4-[[3- (4-Bromophenyl) -1- (EFT-400; MatTek Corporation)] oxo-2-propenyl] amino] -3-fluorophenyl] -5-benzoxazoleacetic acid (Tocris Bioscience) was added thereto at a concentration of 10 μmol / L. The extracts (sample solutions) of Production Examples 1 and 2 according to the present invention were added from the epidermis side and cultured for 2 weeks. In addition, the sample solution was prepared so that the final concentration as a solution might be 2.0% with respect to the whole quantity. In addition, a group in which purified water was added instead of the sample solution was set as a control group. After completion of the culture, the three-dimensional model was cut so that the surface area was about 1 cm ² and freeze-embedded using an OCT compound (manufactured by Miles). Thereafter, a continuous skin section having a thickness of 5 μm was prepared. The continuous skin section was treated with 0.2 M HCl for 10 minutes and then washed twice with PBS. Further, it was treated with protease (sigma F-4658; 125 μg / ml in H ₂ O) at 37 ° C. for 10 minutes, and then washed twice with PBS. Thereafter, commercially available primary antibodies (anti-perlecan antibody, anti-XVIII type collagen antibody, anti-EGF receptor antibody, anti-EGF phosphorylated receptor antibody) were reacted at room temperature for 2 hours. Various primary antibodies were removed by washing twice with PBS, and then secondary antibodies against various primary antibodies (sigma; anti rabbit IgG biotin conjugated, diluted 1: 300 with PBS) were reacted at room temperature for 30 minutes. Thereafter, the plate was washed three times with PBS and stained using ABC kit (Vector Laboratories, Inc).

The results of Test Example 1 will be described for each antibody used.
First, the results when an anti-Perlecan antibody is used as the primary antibody will be described. As a result of the staining reaction, the expression of perlecan was observed in the basement membrane, but there was almost no difference in the degree of staining between the control group and the sample solution addition group.

  Next, the results when anti-XVIII type collagen antibody is used as the primary antibody will be described. As a result of the staining reaction, a strong staining reaction was observed in the basement membrane. The strength of the reaction was stronger in the sample solution addition group than in the control group, that is, the effect of promoting the synthesis of type XVIII collagen in the basement membrane was recognized by the extracts of Production Examples 1 and 2 according to the present invention. .

  Next, the results when an anti-EGF receptor antibody is used as the primary antibody will be described. The EGF receptor showed a staining reaction in the entire epidermis and fibroblasts. However, there was almost no difference in the degree of staining between the control group and the sample solution addition group.

  Next, the results when an activated EGF receptor is detected using an anti-EGF phosphorylated receptor antibody as the primary antibody will be described. When this antibody was used, activation of the EGF receptor was observed in fibroblasts near the basement membrane in the dermis. Since EGF-phosphorylated antibody detects EGF receptor, which binds to EGF receptor and activates it, this test system is used to detect XVIII collagen and activated EGF receptor. Correlation was observed.

  The cultured skin three-dimensional model of Test Example 1 is a model in which a dermis composed of collagen and fibroblasts, an epidermis obtained by overlaying epidermis cells thereon, and a stratum corneum are formed by air exposure. As a result of Test Example 1 using this cultured skin three-dimensional model, by adding the extracts of Production Examples 1 and 2 according to the present invention from the epidermis side, the reaction of type XVIII collagen in the basement membrane becomes stronger, The effect of promoting the synthesis of type XVIII collagen was confirmed. Along with this, activation of the EGF receptor was also observed. Furthermore, since type XVIII collagen binds not only to EGF but also to cell growth factors such as FGF, PDGF, and VGEF (non-patent document 2), it is suggested that these factors are stored around the basement membrane.

From the above, the extracts of Production Examples 1 and 2 according to the present invention supplement the basement membrane components by promoting the synthesis of the type XVIII collagen present in the basement membrane, and thus the cell growth factors (EGF, FGF, PDGF) , VGEF, etc.) can be stored around the basement membrane. As a result, it is suggested that the proliferation and activation of cells around the basement membrane can be promoted, the activation of the dermal fibroblasts and the normalization of the turnover of the epidermis, and the improvement of wrinkles and rough skin can be achieved accordingly.

Claims (2)

A topical skin preparation containing a substance that promotes the synthesis of heparan sulfate proteoglycan in the skin basement membrane. The external preparation for skin according to claim 1, wherein the heparan sulfate proteoglycan is type XVIII collagen.