JP6718202B2 - Topical skin - Google Patents

Description

The present invention relates to an external preparation for skin, which is obtained from a plant extract and contains a component having a cell activity and a cell proliferating 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 the maintenance of cells, but also in the activity and maintenance of the function of cells that adhere to them. 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 present in the mesenchyme. 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 type of sugar chain distributed in animal tissues, that is, a type of glucosaminoglycan (a polysaccharide having D-glucosamine, D-glucuronic acid, and L-iduronic acid as constituent sugars), and In the extracellular matrix, it exists as a proteoglycan bound to the 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 to 7, epidermal growth factor (EGF), vascular endothelial cell growth). It has also been clarified that cells around the basement membrane are proliferated and activated by binding to the factor (VEGF) and storing those factors around the basement membrane (Patent Document 1, Non-Patent Documents 1 and 2). ). Heparan sulfate proteoglycans can also regulate cytokine migration between 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 findings, the technology for promoting the production of heparan sulfate to improve skin wrinkles and pigmentation (Patent Document 1) and the activity of heparanase for degrading heparan sulfate chains of heparan sulfate proteoglycans are demonstrated. Techniques for inhibiting (Patent Document 2 and Non-Patent Document 3) have been proposed.

JP, 2013-203725, A 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 an object thereof is to provide a skin external preparation containing a component that is excellent in biosafety and 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 proteoglycan in the skin basement membrane.
In the present invention, the heparan sulfate proteoglycan is preferably collagen type XVIII.

According to the present invention, there is provided a skin external preparation which is derived from a natural product and has excellent biosafety, and which has the effect of proliferating and activating cells around the skin basement membrane based on the synthetic promoting action of heparan sulfate proteoglycan. can do.

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

In the present invention, the term "rice" is obtained from plants belonging to the genus Poaceae (Oryza), and in the present invention, brown rice, germinated brown rice, pigmented rice (black rice, red rice, purple rice). It is possible to use rice, green rice, etc.), or polished rice obtained by removing bran from them, sprouted rice, or red bran or white bran obtained in the process of polishing brown rice, sprouted brown rice, and pigmented rice.

Further, in the present invention, the term “peach” refers to a plant of the genus Prunus of the Rosaceae family. Examples of sites that can be used in the present invention include whole plants, fruits, flowers, seeds, leaves, stems, roots and the like. When using fruits, immature fruits can be used.

To prepare the extract, first, the use site of each plant is washed with water beforehand to remove foreign matter, if necessary, and then dried as it is or after it is finely chopped or crushed, and contacted with an extraction solvent. It can be prepared by a method of performing extraction (for example, a dipping method, a countercurrent extraction method, or other appropriate means). Alternatively, a supercritical extraction method may be used. Further, it may be prepared by squeezing the used part (fruit, etc.) as it is, or by crushing the used part and then crushing the crushed material. It is also prepared by drying the use part and then pulverizing it into a dry pulverized product, or by extracting the dry powder obtained by freeze-drying the use part, or in some cases squeezed juice, with a solvent. be able to.

As the 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. Examples include 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, which may be used alone or in admixture of two or more. Used.

In the present invention, hydrophilic solvents such as water, lower alcohols or polyhydric alcohols are suitable. Preferable examples of the case where this hydrophilic solvent is used include, for example, water, lower alcohols (particularly ethanol), or polyhydric alcohols (particularly 1,3-butylene glycol) used alone, or water and lower alcohols. The use of a mixed solvent with (particularly ethanol) or a mixed solvent with water and a polyhydric alcohol (particularly 1,3-butylene glycol, glycerin) and the like can be mentioned. Among them, water alone or water and 1,3 -A mixed solvent of butylene glycol is particularly preferred.

When a mixed solvent is used, for example, in the case of a mixed solvent of water and 1,3-butylene glycol, the volume ratio (hereinafter the same) is 1:10 to 20:1, and the mixed solvent of water and ethanol is 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.

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

When preparing the extract, the pH is not particularly limited, but it is generally preferable to set it in the range of 3 to 9. In this sense, if necessary, the extraction solvent may be mixed with an alkaline modifier such as sodium hydroxide, sodium carbonate or potassium hydroxide, or an acidic modifier such as citric acid, hydrochloric acid, phosphoric acid or sulfuric acid to obtain a desired amount. You may adjust so that it may become pH.

The extraction conditions such as the extraction temperature and the extraction time vary depending on the type and pH of the solvent used, but for example, immersion using water or 1,3-butylene glycol or a mixed liquid of water and 1,3-butylene glycol as the solvent. In the case of the method, the extraction temperature is generally 0 to 90°C, preferably 4°C to 80°C. The extraction time is in the range of 0.5 to 3 days, preferably 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 if necessary. This may allow the extract to be used more effectively. Examples of the hydrolyzing method include acid treatment, alkali treatment, and enzyme treatment. Among them, enzyme treatment is most preferable. Examples of the enzyme used include one or more selected from proteolytic enzymes, starch degrading enzymes, fibrinolytic enzymes and lipolytic enzymes.

The proteolytic enzyme may be any of an animal-derived enzyme, a plant-derived enzyme, and a microorganism-derived enzyme. For example, actinases, pepsin such as pepsin, trypsin such as trypsin, papain, papain such as chymopapain, glycylglycine peptidase, carboxypeptidase, peptidases such as aminopeptidase, and bromelain, and the like. One or more of are used. Further, examples of the starch degrading enzyme include glucoamylase and α-amylase. Examples of fibrinolytic enzymes include cellulase, hemicellulase, pectinase and the like. Moreover, lipase etc. are mentioned as a lipolytic enzyme. As the enzyme to be used, one kind or two kinds or more selected from any of the enzyme groups may be used, or one kind or two kinds or more selected from each of the enzyme groups may be used in combination. ..

The amount of 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.

The extract prepared as described above may generally be adjusted to a pH of 3 to 8 and then used as it is as a compounding agent for external preparations for the skin. You may use it. Further, the extract may be a dried product by a conventional method such as a spray drying method.

The extract prepared as described above can be applied as a compounding ingredient of an external preparation for skin (cosmetics, quasi drugs, etc.).

For example, as cosmetics or quasi drugs containing the extract according to the present invention, emulsion, cream, lotion, essence, pack, lipstick, foundation, liquid foundation, makeup press powder, blusher, white powder, face wash, body Examples include shampoos, shampoos for hair, soaps and the like, and hair restorers, bath agents and the like, but of course the present invention is not limited thereto.

The amount of the extract of the present invention as a component for the external preparation for skin is preferably 0.0001 to 1.0% by weight (solid content% by 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 for cosmetics or quasi drugs, in addition to the essential component extract, for example, an oily component, a surfactant (synthetic system, natural product system), a moisturizer A thickener, an emulsifier or an emulsification aid, an antiseptic/bactericidal agent, a powder component, an ultraviolet absorber, an antioxidant, a pigment, a fragrance, and other physiologically active components can be appropriately blended as necessary. Further, the extract according to the present invention may be blended in combination with other physiologically active ingredients as long as the effectiveness and characteristics of the extract are not impaired.

Here, as the oil component, for example, olive oil, jojoba oil, castor oil, soybean oil, rice oil, rice germ oil, coconut oil, palm oil, cocoa oil, meadow foam oil, shea butter, tea tree oil, avocado oil, Plant-derived oils and fats such as macadamia nut oil, yuzu seed oil, citrus-derived oil, plant-derived squalane; animal-derived oils and fats such as mink oil and turtle oil; beeswax, carnauba wax, rice wax, lanolin and other waxes; liquid 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; synthetic esters such as isopropyl myristate, isopropyl palmitate, butyl oleate, 2-ethylhexyl glyceride, higher fatty acid octyldodecyl (octyldodecyl stearate, etc.), synthetic triglycerides and the like can be mentioned.

As the surfactant, for example, 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, poly Nonionic surfactant such as oxyethylene sorbitol fatty acid ester; fatty acid salt, alkyl sulfate, alkylbenzene sulfonate, polyoxyethylene alkyl ether sulfate, polyoxyethylene fatty amine sulfate, polyoxyethylene alkylphenyl ether sulfate, 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, tris Cationic surfactants such as alkylbenzyl ammonium salts, alkyl pyridinium salts, 2-alkyl-1-alkyl-1-hydroxyethyl imidazolinium salts, N,N-dialkyl morpholinium 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'- An amphoteric surfactant such as β-hydroxypropylammoniosulfobetaine can be used.

As the emulsifier or emulsification aid, a stevia derivative such as enzyme-treated stevia, saponin or a derivative thereof, casein or a salt thereof (sodium, etc.), a complex of sugar and protein, sucrose or an ester thereof, lactose, a soybean-derived Water-soluble polysaccharides, soybean-derived protein-polysaccharide complexes, lanolin or its derivatives, 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 bacterium fermented rice, lactic acid bacterium fermented germinated rice, lactic acid bacterium fermented cereals (wheat, beans, millet etc.) and the like can also be blended.

Moisturizers include, for example, glycerin, propylene glycol, dipropylene glycol, 1,3-butylene glycol, polyethylene glycol, sorbitol, xylitol, sodium pyrrolidonecarboxylate, and sugars such as trehalose and mucopolysaccharides (for example, hyaluronic acid). Acid and its derivatives, chondroitin and its derivatives, heparin and its derivatives, etc.), elastin and its derivatives, collagen and its derivatives, NMF-related substances, lactic acid, urea, higher fatty acid octyldodecyl, seaweed extract, silane root (Hakuo) Examples include extracts, various amino acids and their derivatives.

Examples of the thickener include alginic acid, agar, carrageenan, fucoidan-derived brown algae, green algae or red algae-derived components; silane root (white and white) extracts; pectin, locust bean gum, aloe polysaccharides, alcaligenes-producing polysaccharides and the like. Polysaccharides; gums such as xanthan gum, tragacanth gum and guar gum; cellulose derivatives such as carboxymethyl cellulose and hydroxyethyl cellulose; synthetic polymers such as polyvinyl alcohol, polyvinyl pyrrolidone, carboxy vinyl polymer, acrylic acid/methacrylic acid copolymers; hyaluronic acid And derivatives thereof; polyglutamic acid and derivatives thereof and the like.

Examples of antiseptic/bactericidal agents include urea; paraoxybenzoic acid esters such as methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate and butyl paraoxybenzoate; phenoxyethanol, dichlorophen, hexachlorophene, chlorhexidine hydrochloride, benza chloride. There are ruconium, salicylic acid, ethanol, undecylenic acid, phenols, jamal (imidazodinylurea), 1,2-pentanediol, various essential oils, bark distillate, radish fermentation broth and the like.

Examples of the powder component include sericite, titanium oxide, talc, kaolin, bentonite, zinc oxide, magnesium carbonate, magnesium oxide, zirconium oxide, barium sulfate, silicic acid anhydride, mica, nylon powder, polyethylene powder, silk powder, and cellulose. System powder, grains (rice, wheat, corn, millet, etc.) powder, beans (soybean, adzuki beans, etc.) powder, etc.

Examples of the ultraviolet absorber include ethyl paraaminobenzoate, ethylhexyl paradimethylaminobenzoate, amyl salicylate and its derivatives, 2-ethylhexyl paramethoxycinnamate, 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 the antioxidant include butylhydroxyanisole, butylhydroxytoluene, propyl gallate, vitamin E and its derivatives (eg, vitamin E nicotinate, vitamin E linoleate, etc.), peony extract, silane root (white oak) extract, etc. There is.

Whitening agents include 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 (rhododenol, 4-(4-hydroxyphenyl)-4-butanol)), hydroxybenzoic acid And derivatives thereof, vitamin E and derivatives thereof, α-hydroxy acid, and AMP (adenosine monophosphate, adenosine monophosphate), and these may be blended alone or in combination.

As the above kojic acid derivative, for example, kojic acid monobutyrate, kojic acid monocaprate, kojic acid monopalmitate, kojic acid esters such as kojic acid dibutyrate, kojic acid ethers, kojic acid glucosi testee, etc. However, examples of the ascorbic acid derivative include L-ascorbic acid-2-phosphate sodium salt, L-ascorbic acid-2-phosphate magnesium salt, L-ascorbic acid-2-sulfate sodium salt, and L-ascorbic acid-2. -Ascorbic acid ester salts such as magnesium sulfate ester, L-ascorbic acid-2-glucoside, L-ascorbic acid-5-glucosi, which ascorbic acid sugar derivative, and the 6-position acylated product of these ascorbic acid sugar derivatives (acyl group: Hexanoyl group, octanoyl group, decanoyl group, etc.), L-ascorbic acid tetraisopalmitic acid ester, L-ascorbic acid tetralauric acid ester and other L-ascorbic acid tetrafatty acid esters, 3-O-ethylascorbic acid, L- Ascorbic acid-2-phosphate-6-O-palmitate sodium, glyceryl ascorbic acid or an acylated derivative thereof, and an ascorbic acid glycerin derivative such as bisglyceryl ascorbic acid are arbutin (hydroquinone-β-D- Glucopyranoside), α-arbutin (hydroquinone-α-D-glucopyranoside) and the like, as a tranexamic acid derivative, tranexamic acid ester (for example, tranexamic acid lauryl ester, tranexamic acid hexadecyl ester, tranexamic acid cetyl ester or a salt thereof), Examples of the amide of tranexamic acid (for example, tranexamic acid methylamide) and the like, examples of the resorcinol derivative include 4-n-butylresorcinol, 4-isoamylresorcinol and the like, and examples of the 2,5-dihydroxybenzoic acid derivative include 2,5-diacetoxybenzoic acid, 2-acetoxy-5-hydroxybenzoic acid, 2-hydroxy-5-propionyloxybenzoic acid and the like, and examples of the nicotinic acid derivative include nicotinic acid amide, benzyl nicotinate and the like, α- Examples of hydroxy acids include lactic acid, malic acid, succinic acid, citric acid, and α-hydroxyoctanoic acid.

As the physiologically active component, as a whitening component, for example, placenta extract, sow apricot extract, Yukinoshita extract, perilla extract, white mustard extract or its hydrolyzate, fermented white mustard extract, Damask rose extract, peonies Extract or its hydrolyzate, soybean extract or its hydrolyzate, lactic acid bacteria fermented rice, lotus seed extract or its hydrolyzate, lotus seed fermented product, ginseng extract, pearl barley hydrolyzate, coix seed fermented product, Fermented royal jelly, fermented sake lees, Pandanus amaryllifolius Roxb. extract, Arcangelicia flava Merrilli extract, chamomile extract, etc. were raised, and coral grass as an anti-aging component. Extract, rice leaf extract or its hydrolyzate, eggplant (water eggplant, long eggplant, Kamo eggplant, rice eggplant, etc.) extract or its hydrolyzate, seaweed extract such as caterpillar ginseng, eelgrass, etc. Marine flowering plant extract, soy milk fermented product, jellyfish water, rice fermentation extract, linoleic acid and its derivatives or processed products (eg liposomal linoleic acid), animal or fish-derived collagen and its derivatives, elastin and its derivatives , Glycyrrhizic acid and its derivatives (dipotassium salts, etc.), t-cycloamino acid derivatives, vitamin A and its derivatives, allantoin, diisopropylamine dichloroacetate, γ-amino-β-hydroxybutyric acid, gentian extract, licorice extract, carrot extract Substance, aloe extract, honeysuckle extract, sardine extract, Zizyphus joazeiro extract, kiwi extract, loofah extract, murasakisikib extract and the like.

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

Production Example 1. Preparation of Rice Extract To 250 g of polished rice, 1000 g of 0.1% sodium hydroxide aqueous solution was added, and the mixture was extracted with stirring for 1 day, and then coarse filtration was performed with a filter cloth to remove the remaining rice residue. After neutralizing the extract with dilute hydrochloric acid, proteolytic enzymes (actinase AS 0.02%, papain 0.02%) were added to the volume, and the enzyme was decomposed at 40°C for 2 hours and then at 80°C. The enzyme was inactivated by heating for 1 hour at room temperature and cooled to room temperature. The enzyme-treated 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 peach extract 60 g of immature fruit of peach (Prunus persica Batsch) was mixed with 600 g of purified water, and the mixture was allowed to stand still for 2 hours at 80° C. to obtain an extract solution (455.7 g). .. After that, the obtained extract solution is filtered, 1% of activated carbon (manufactured by Wako Pure Chemical Industries, Ltd.) is further added to the filtered solution, and activated carbon treatment is performed for 1 hour to obtain an immature pale brown peach. 446.1 g of a fruit extract solution was obtained (pH 4.1, solid content concentration 3.61).

Prescription example 1. Lotion [A component] part Olive oil 1.0
Polyoxyethylene (5.5) cetyl alcohol 5.0
Butylparaben 0.1
[B Component] Part 5.0 Extract Solution of Production Example 1
Ethanol 5.0
Glycerin 5.0
1,3-butylene glycol 5.0
Potassium hydroxide Suitable amount Purified water Total amount of 100 parts [C component]
Fragrance Appropriate amount Each of the components A and B was heated to 80° C. or higher, then the component B was added to the component A, and the mixture was stirred, and further homogenized with a hyscotron (5000 rpm) for 2 minutes. After cooling this to 50° C., component C was added and mixed with stirring, and 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 Formulation Example 1 except that 5.0 parts of the extract solution in Production Example 2 was used in place of the extract solution in Production Example 1 contained in the component B of Formulation Example 1. ..

Prescription example 3. Emulsion [A component] part Liquid paraffin 6.0
Hexalan 4.0
Jojoba oil 1.0
Polyoxyethylene (20) sorbitan monostearate 2.0
Soy lecithin 1.5
[B Component] Part 3.0 Extract Solution of Production Example 2
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
Amount of purified water 100 parts [C component]
Fragrances Appropriate amount The above components A and B were each heated to 80° C. or higher, and then mixed with stirring. After cooling this to 50° C., the component C was added and further stirred and mixed to obtain an emulsion.

Prescription example 4. Emulsion A milky lotion was prepared in the same manner as in Formulation Example 10 except that 2.0 parts of L-ascorbic acid-2-glucoside and 3.0 parts of arbutin were used instead of 2.0 parts of L-ascorbic acid-2-glucoside in Component B of Formulation Example 3. Obtained.

Prescription example 5. Emulsion Emulsion in the same manner as in Prescription Example 10 except that 2.0 parts of L-ascorbic acid-2-glucoside and 2.0 parts of potassium hydroxide in the B component of Prescription Example 3 were used instead of 2.0 parts of tranexamic acid. Got

Prescription example 6. Emulsion In the same manner as in Formulation Example 10 except that 2.0 parts of L-ascorbic acid-2-glucoside and 3.0 parts of potassium hydroxide were used in Component B of Formulation Example 3 instead of 3.0 parts of nicotinic acid amide. An emulsion was obtained.

Prescription example 7. Emulsion [A component] part Liquid paraffin 6.0
Hexalan 4.0
Jojoba oil 1.0
Polyoxyethylene (20) sorbitan monostearate 2.0
Soy lecithin 1.5
[B component] Part Extraction 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
Carboxymethyl cellulose 0.3
Sodium hyaluronate 0.01
Amount of purified water 100 parts

Prescription example 8. Lotion [ingredient] part Extraction 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
Carboxy vinyl polymer 0.1
Fragrance Suitable amount Potassium hydroxide Suitable amount Purified water Amount such that the total amount becomes 100 parts The above ingredients were mixed to obtain a lotion.

Prescription example 9. Essence [ingredient] 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 Total amount is 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.

Example 10. 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] Part 5.0 Extract Solution of Production Example 1
Carboxymethyl cellulose sodium 0.2
Bentonite 0.5
Propylene glycol 4.0
Triethanolamine 1.1
Methylparaben 0.1
Purified water Total amount is 100 parts [C component] part Titanium oxide 8.0
Talc 4.0
Coloring Pigments Appropriate amounts The above-mentioned components A and B were each heated, and then mixed and stirred. This was reheated, the above-mentioned C component was added, and the mixture was poured into a mold and stirred until it reached room temperature to obtain a liquid foundation.

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

Prescription example 12. Hair growth ingredient [ingredient] part Dipotassium glycyrrhizinate 0.1
Mononitroguaiacol sodium 0.02
Pyridoxine hydrochloride 0.03
l-menthol 0.8
Tamasaki Tsuduji 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 proper amount ethanol 20
Amount of purified water to be 100 parts The above ingredients were thoroughly mixed with stirring to obtain a hair restorer.

Prescription example 13. Hair shampoo [A component] part N-coconut oil fatty acid methyl taurine sodium 10.0
Polyoxyethylene (3) alkyl ether sodium sulfate 20.0
Lauryl dimethylamino acetic acid betaine 10.0
Coconut 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 is 100 parts Component A and component B are each heated to 80°C to dissolve them evenly, then component B is added to component A and stirring is continued to cool to room temperature to obtain a hair shampoo. It was

Example 14. Hair conditioner [A component] part Polyoxyethylene (10) hydrogenated castor oil 1.0
Distearyl dimethyl ammonium chloride 1.5
Stearyl trimethyl ammonium chloride 2.0
Glyceryl 2-ethylhexanoate 1.0
Cetanol 3.2
Stearyl alcohol 1.0
Methylparaben 0.1
[B Component] Part 2.0 Extract Solution of Production Example 2
1,3-butylene glycol 5.0
Purified water Total amount is 100 parts Component A and component B are each heated to 80° C. and dissolved uniformly, then component B is added to component A, and stirring is 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 basement membrane A heparanase inhibitor (2-[4-[[3-(4-Bromophenyl)-1-] was added to the culture medium of a three-dimensional model of cultured skin (EFT-400; MatTek Corporation). 10 μmol/L of oxo-2-propenyl]amino]-3-fluorophenyl]-5-benzoxazoleacetic acid; Tocris Bioscience) was added and cultured. 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. The sample solution was prepared so that the final concentration of the solution was 2.0% with respect to the total amount. Further, a group to 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 frozen embedding was performed using an OCT compound (manufactured by Miles). Then, a continuous skin section having a thickness of 5 μm was prepared. This continuous skin section was treated with 0.2 M HCl for 10 minutes and then washed twice with PBS. After further treatment with protease (sigma F-4658; 125 μg/ml in H ₂ O) at 37° C. for 10 minutes, the plate was washed twice with PBS. Then, a commercially available primary antibody (anti-Perlecan antibody, anti-XVIII type collagen antibody, anti-EGF receptor antibody, anti-EGF phosphorylation receptor antibody) was reacted at room temperature for 2 hours. After removing the various primary antibodies by washing twice with PBS, a secondary antibody (sigma; anti rabbit IgG biotin conjugated, diluted 1:300 with PBS) against the various primary antibodies was reacted at room temperature for 30 minutes. Then, the cells were washed 3 times with PBS and stained with ABC kit (Vector Laboratories, Inc).

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

Next, the results of using an anti-XVIII type collagen antibody 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 extract of Production Examples 1 and 2 according to the present invention was found to have an effect of accelerating the synthesis of basement membrane type XVIII collagen. ..

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

Next, the results of detecting an activated EGF receptor using an anti-EGF phosphorylation receptor antibody as the primary antibody will be described. Using this antibody, EGF receptor activation was observed in fibroblasts near the basement membrane in the dermis. Incidentally, EGF phosphorylated antibody, EGF which is a ligand to the EGF receptor is bound, because it is to detect the activated receptor, by this test system, collagen XVIII and activated EGF receptor A correlation was found.

The three-dimensional cultured skin model of Test Example 1 is a model in which a dermis composed of collagen and fibroblasts, an epidermis formed by overlaying epidermal cells on the dermis, and further exposed to air form a stratum corneum. As a result of Test Example 1 using this three-dimensional model of cultured skin, by adding the extracts of Production Examples 1 and 2 according to the present invention from the epidermis side, the reaction of the type XVIII collagen of the basement membrane becomes strong, that is, , XVIII type collagen synthesis promoting effect was confirmed. Moreover, the activation of the EGF receptor accompanying it was also observed. Further, since XVIII type collagen binds to not only EGF but also cell growth factors such as FGF, PDGF, 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, by promoting the synthesis of type XVIII collagen present in the basement membrane, supplement the basement membrane components, cell growth factor (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 are promoted, activation of fibroblasts in the dermis and normalization of turnover of the epidermis, and concomitantly, improvement of wrinkles and rough skin can be achieved.

Claims (1)

Rosaceae XVIII type collagen synthesis promoter containing as an active ingredient the extract of immature fruit of peach belonging to the genus Prunus of Rosaceae .