WO2008044636A1

WO2008044636A1 - Anti-wrinkle agent and skin preparation for external use

Info

Publication number: WO2008044636A1
Application number: PCT/JP2007/069569
Authority: WO
Inventors: Yukiko Matsunaga; Michio Shibata; Shunsuke Iriyama; Satoshi Amano; Ken Kusakari; Masahiro Ota; Kenichi Umishio
Original assignee: Shiseido Company, Ltd.
Priority date: 2006-10-10
Filing date: 2007-10-05
Publication date: 2008-04-17
Also published as: JP2008094734A

Abstract

It is intended to provide an anti-wrinkle agent which improves wrinkles, in particular fine wrinkles, induced by lowering of the skin barrier function due to drying, etc. An anti-wrinkle agent which comprises one or more plants selected from among Quercus lanata Sm. belonging to the family of Fagaceae, Elaeocarpus sphaericus belonging to the family of Elaeaocarpaceae, Quercus lineata Blume belonging to the family of Fagaceae, Pinus wallichiana A.B. Jacks belonging to the family of Pinaceae, Dioscorea esculenta Burkill belonging to the family of Dioscoreaceae, Cochlospermum religiosum (L.) Alston belonging to the family of Cochlospermaceae, Coriaria nepalensis Wall. belonging to the family of Coriariaceae and Cinnamomum bejolghota belonging to the family of Lauraceae or a solvent-extract thereof.

Description

Specification

Anti-wrinkle and skin preparations

Technical field

[0001] The present invention relates to an anti-wrinkle agent, and in particular, suppresses and improves wrinkles, particularly fine wrinkles caused by the decrease in the function of the skin, by suppressing the thickening of the skin caused when the barrier function is decreased due to drying or the like. It relates to anti-wrinkle agents.

Background art

[0002] The stratum corneum located at the outermost layer of the skin protects the living body from contact and penetration of foreign substances such as bacteria and harmful substances, and keeps the skin healthy by preventing moisture evaporation from the body. Has a barrier function. When the barrier function decreases due to excessive water work, dry winter, and excessive cooler in summer, the transepidermal water loss (TEWU) increases from the skin surface. When stratum corneum consisting of crevice and cuticle becomes irregular due to a decrease in water content, the skin becomes bulky and rough (see Non-Patent Document 1).

Minor wrinkles are thought to be caused by irregular skin crests flowing in a certain direction due to the chronic rough skin, and the area ratio of fine wrinkles is actually reduced for people with skin conditions with low stratum corneum moisture. It is reported that it is high (see Non-Patent Document 2). In general, it is said that the formation of fine lines is promoted when the dry state continues. In addition to seasonal influences, modern women are kept in a dry environment in summer due to the widespread use of air conditioners. The worries about fine wrinkles increase from the late 20s.

In order to prevent this skin barrier function deterioration and prevent or improve moisture transpiration from the skin surface, and in turn, rough skin and fine lines, moisturizing ingredients such as glycerin, NMF (natural moisturizing fact or) related ingredients, collagen derivatives, etc. A method for increasing moisture retention of the skin by applying to the skin and a method for promoting turnover of keratinocytes using cell activation components such as bracent extract and vitamins have been proposed. However, there are many mechanisms related to aging and wrinkles! /, Because there were many parts, conventional cosmetics! / It is only a way of trying, and that As described above, the present state is that it exhibits a sufficient effect.

[0003] Non-Patent Document 1: Toshiro Sone et al., Cosmetic Society Journal Vol.15 No.2 P.60_65 (1991)

Non-patent document 2: Genji Ayukawa et al., Fragrance Journal 1992-11, 29-42

Disclosure of the invention

Problems to be solved by the invention

[0004] The present invention has been made in view of the above-described conventional circumstances, and an object of the present invention is to provide an anti-wrinkle agent that improves wrinkles induced when the barrier function is lowered by drying or the like, in particular, fine wrinkles. There is to do.

Means for solving the problem

[0005] The present applicant has established an animal model (barrier destruction wrinkle model) with fine wrinkles by continuously tape stripping the hairless mouse back to reduce the noria function. . In this model animal, the stratum corneum water content was reduced to about 60% compared to the control. In the tissue, thickening of the epidermis and dermis is prominent, and when wrinkles recover, the thickening also subsides. Therefore, it was considered that there was a correlation between wrinkle formation and thickening of the epidermis and dermis. .

[0006] In addition, the present applicant has also found that in a nodal destruction wrinkle model, ADA M (a disintegrin and metalloprotease) having a disintegrin and meta-oral protease domain such as ADAM-9, ADAM-10, and ADAM-17. Proteins belonging to the family (hereinafter referred to as ADAM), and HB-EGF (heparin-binding EGF-like growth factor; h sign arin-binding epidermal growth fact or-) like growth factor) and Amphiregulin gene expression in the epidermis, and by applying ADAM inhibitors, it is possible to suppress thickening and wrinkle formation of the epidermis and dermis, human or animal skin, skin A test substance is brought into contact with the tissue or cell, and the enzyme activity or gene expression level of ADAM in the skin, tissue or cell is detected; A method for evaluating the anti-wrinkle effect of a test substance using the enzyme generation or gene expression level of ADAM as an index has already been found (see Japanese Patent Application Nos. 2005-299524 and 2005-296219).

[0007] On the other hand, as an ADAM inhibitor, TAPI-l {N- (R)-(2- (Hydroxyaminocarbonyl) methyl) -4 -Methylpentanoyl-L-Nal-L-Alanine2-Aminoethyl amide (L_Nal: L_3_ (2 '-NaphthyOal anine)} or ゝ TAPI-2 {N- (R)-(2- (Hydroxyaminocarbonyl) methyl) -4-Methylpentanoyl- L-t-Butyl-Glycyl-L-Alanine2-Aminoethyl amide} is known! /, The strength of these substances is not enough to inhibit ADAM, and safety as a skin external preparation has been confirmed There is a need to develop safer and more effective drugs.

[0008] The present inventors searched for a novel herbal medicine that inhibits ADAM activity using a cell-based ADAM inhibitor drug screening method, and examined the effect of a fine wrinkle-improving drug using a noria-destroying wrinkle model. However, the present inventors have found that a specific herbal medicine is excellent in the action of improving fine lines, and have reached the present invention.

[0009] The present invention relates to Quercus lanata Sm. (Scientific name: Quercus lanata Sm.), Elaeocarpus sphaericus (scientific name: Elaeocarpus sphaericus), Quercus lineata Blume. (Scientific name: Quercus lineata Blume. ), Pinus to Orichiana A. B. Jatas (scientific name: Pinus wallichiana ABJacks), Dioscorea Escrenta Bunorekinore (scientific name: Dioscorea esculenta Burkill) Scientific name: Cochlospermum religiosum (Shi) Alston), Corian ria nepalensis Wall. (Scientific name: Cinnamomum bej olghota), one or more selected from the power of Cinnamomum bej olghota Plants, or these solvent extracts An anti-wrinkle agent characterized by having.

[0010] Further, the present invention relates to Quercus lanata Sm. (Scientific name: Quercus lanata Sm.), Quercus lineata Blume. (Scientific name: Quercus lineata Blume.), Pinus suluciana A. b. (Scientific name: Pinus wallichiana ABJacks), Dioscorea esculenta Burkill (scientific name: Dioscorea esculenta Burkill), cinnamomum bejo noregota (scientific name: Cinnamomum bejolghota), or two or more kinds of plants selected from these An external preparation for skin characterized by comprising a solvent extract.

The invention's effect

[0011] The anti-wrinkle agent of the present invention is a wrinkle induced when the barrier function is reduced by drying or the like. Prevents fine wrinkles.

[0012] Further, the external preparation for skin of the present invention is capable of preventing and improving wrinkles induced when the barrier function is lowered by drying or the like, in particular fine wrinkles, and is excellent in usability and safety. is there.

Brief Description of Drawings

[0013] FIG. 1 is a diagram showing measurement results of the state of wrinkle generation when the plant extract of the present invention is used.

Yes

FIG. 2 is a graph showing the measurement result of transepidermal water loss (TEWL) when the plant extract of the present invention is used.

BEST MODE FOR CARRYING OUT THE INVENTION

[0014] The best mode of the present invention will be described below.

Elaeocarp sphaericus (scientific name: Elaeocarp us sphaericus) used in the present invention is a plant belonging to the genus Hortonaceae, and is referred to as holonoki, kongo, kongoju, juzubodaiju, indonesia, etc. It is known to have an active oxygen scavenging action, a hyaluronidase inhibitory action, an elastase inhibitory action, a collagenase inhibitory action, and a tyrosinase inhibitory action (see JP 2003-95857 A).

Quercus lineata Blume. (Scientific name: Quercus lineata Blume.) Used in the present invention is called Mempening! /.

Quercus lanata Sm. (Scientific name: Quercus lanata Sm.) Used in the present invention is a plant belonging to the genus Quercus lanata Sm.

The Pinus wallichiana A.B.Jacks (Scientific name: Pinus wallichiana A.B.Jacks) used in the present invention is a plant belonging to the genus Pinus wallaceae and is called Himalayan. Dioscorea esculenta Burkill (scientific name: Dioscorea esculenta Burkill) used in the present invention is a plant belonging to the genus Dioscorea esculenta Burkill, and is called the Togedoko mouth.

The reediosum (El.) Aarston (scientific name: Cochlospermum religiosum (Shi) Alston) used in the present invention is a general genus of the genus Tarimodokuri, yellow sik-cotton tree, silk cotton tree, yellow called cotton tree Yes.

Coriania nepalensis wall (scientific name: Coriari a nepalensis Wall.) Used in the present invention is a plant belonging to the genus Dokutsugi.

Cinnamomum bej olghota (scientific name: Cinnamomum bej olghota) used in the present invention is a plant belonging to the genus Tasnaceae.

[0015] Each plant used in the present invention can be used either raw or dried.

1 From the viewpoint of usability and formulation, it is preferable to use it as a dry powder or a solvent extract.

[0016] Preferable when each plant is used as a dry powder or solvent extract! / Used sites are as follows.

For example, Elaeocarpus sphaericus (Scientific name: Elaeocarpus sphaericus) is preferred to use fruit, but other parts can also be used.

For the Quercus lineata Blume. (Scientific name: Quercus lineata Blume.) It is preferable to use the bark, but other parts can also be used.

For the beech family Quercus lanata Sm. (Scientific name: Quercus lanata Sm.), It is preferable to use seeds, but other sites can also be used.

For the Pinus wallichiana A.B.Jacks, it is preferable to use bark, but other parts can also be used.

For Dioscorea esculenta Burkill (Scientific name: Dioscorea esculenta Burkill), bulbs are preferred, but other sites can also be used. For bark beetles, the bark is preferred for Cochlosper rmum religiosum (scientific name: Alston), but other parts can be used.

Coriania nepalensis wall (scientific name: Coriaria n mark alensis Wall.)! /, And it is preferable to use whole plants other than roots! /.

Cinnamomum Beshonoregota (scientific name: Cinnamomum bejolghota ritsu! /, I prefer to use bark, but other parts can also be used.

[0017] The solvent extract of each plant can be obtained by a conventional method, for example, together with the extraction solvent. After soaking or heating to reflux, it can be obtained by filtration and concentration. As the extraction solvent, any solvent that is usually used for extraction can be used. For example, water, methanol, ethanol, propylene glycol, 1,3-butylene glycol, alcohols such as glycerin, hydrous alcohol, and the like. , Organic solvents such as chloroform, formaldehyde, dichloroethane, carbon tetrachloride, acetone, ethyl acetate, hexane, etc., can be used alone or in combination. Preferred as the extraction solvent are ethanol, hydrous ethanol, 1,3-butylene glycol, and hydrous 1,3-butylene glycol.

The extract obtained by extraction with the above solvent is used as it is, or the concentrated extract is adsorbed by a method such as removing impurities using an ion exchange resin, or a column of porous polymer (for example, Amberlite XAD-2). It is possible to use a product that has been adsorbed and then dissolved in methanol or ethanol and concentrated. Further, a partition method, for example, an extract obtained by separation / extraction with water / ethyl acetate is also used.

[0018] The plant extract thus obtained has an excellent ADAM activity inhibitory effect and wrinkle prevention / improving effect with high safety. The anti-wrinkle agent of the present invention has a very wide application range and can be applied to various fields. Specific examples include cosmetics including quasi-drugs, pharmaceuticals, and foods.

[0019] The anti-wrinkle agent of the present invention is substantially a blended raw material consisting of one or more of the above plant extracts, but may contain other components. This anti-wrinkle agent is blended with the external preparation for skin to provide the external preparation for skin of the present invention.

[0020] the case of a plant extract used by blending into the skin external preparation, preferably a force to 0. 000001- 5.0 mass ^_0/0 Rooster himself if a dry weight in the total amount of the external preparation <, more preferably <the 0. 00001- 3 • 0 mass ^_0/0, and particularly preferably 0 - 00001 - 1. 0 mass ^_0/0.

[0021] When the above plant extract is used in a skin external preparation, in addition to these extracts, it is usually used for a skin external preparation such as cosmetics and pharmaceuticals within the range not impairing the effects of the present invention. Other ingredients such as oils, surfactants, alcohol, thickeners, chelating agents, active oxygen scavengers, UV absorbers, moisturizers, wetting agents, various medicinal ingredients, preservatives, neutralizers, pH adjusters Antioxidants, fragrances, water and the like can be appropriately blended as necessary.

[0022] Among the above optional ingredients, the oil component includes lauryl alcohol, cetyl alcohol, Higher grades such as straight chain alcohols such as stearyl alcohol, myristinoleanolecole, oleyl alcohol, branched chain alcohols such as monostearino glycerine etherole, lanolin sanoleconole, cholesterol, and sterol alcohol Higher fatty acids such as alcohol, lauric acid, myristic acid, noremitic acid, stearic acid, waxes such as solid paraffin, beeswax, hydrogenated castor oil, carnauba wax, noricowax, beef tallow, lard, sheep fat, squalane, Palm oil, palm oil, palm kernel oil, soybean oil, olive oil, cottonseed oil, jojoba oil, castor oil, lanolin and other animal and vegetable oils, liquid paraffin, petrolatum and other mineral oils, trimethylpropane triisostearate, isopropyl Myristate, glycerol tri 2-Ethylhexanate, Pentaerythritol tetra-2-Ethylhexanate, Cyclic or linear silicone oil, Polyoxyethylene (hereinafter also referred to as POE) Polyoxypropylene (hereinafter also referred to as POP) Pentaerythritol ether And other synthetic oils.

Surfactants include soap bases, fatty acid soaps such as sodium laurate and sodium normitate, higher alkyl sulfates such as sodium lauryl sulfate and potassium lauryl sulfate, POE lauryl sulfate triethanolamine, POE ralyl sulfate sodium, etc. Alkyl ether sulfate ester salt, N-acyl sarcosine acid such as lauroyl sarcosine sodium, N-myristoyl N-methyl taurine sodium, coconut oil fatty acid methyl tauride sodium and other higher fatty acid amide sulfonic acid, POE stearyl ether phosphorus Phosphate esters such as acids, monolauroyl monoethanolamide, sulfosuccinates such as sodium POE sulfosuccinate, sodium lauryl polypropylene glycol sulfosuccinate, linear dodecylbenzenes Alkylbenzene sulfonates such as sodium phonate, linear dodecylbenzene sulfonate triethanolamine, N-acyl glutamate such as N-stearoyl glutamate monosodium, N-stearoyl glutamate monosodium, hydrogenated coconut oil fatty acid sodium glycerine sulfate, etc. Higher fatty acid ester sulfate ester salt, sulfated oil such as funnel oil, POE alkyl ether carboxylic acid, POE alkyl aryl ether carboxylate, higher fatty acid ester sulfonate, secondary alcohol sulfate ester salt, higher fatty acid alkylol Anionic surfactants such as amidosulfuric acid ester salt, sodium lauroyl monoethanolamide succinate, sodium caseinate; Alkyltrimethylammonium salts such as tearyltrimethylammonium, lauryltrimethylammonium chloride, dialkyldimethylammonium salts such as distearyldimethylammonium chloride, alkylpyridinium salts such as cetylpyridinium chloride, Alkyl quaternary ammonium salts, alkyl dimethyl methyl benzyl ammonium salts, alkyl isoquinoline salts, dialkyl morphonium salts, POE anolequinoleamines, anolequinoleamine salts, polyamine fatty acid derivatives, amyl alcohol Fatty acid derivatives, powers such as benzalkonium chloride, thione surfactants; 2-cocoyl 2-imidazolinium hydroxydo 1 carboxylic acid imidazoline amphoteric surfactants such as shetiloxini sodium salt, amide betaine, sulfobetaine, etc. Betaine world Amphoteric surfactants such as surfactants; sorbitan monooleate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan fatty acid esters such as sorbitan trioleate, mono cottonseed oil fatty acid glycerin, Glyceryl monostearate, glyceryl sesquioleate, glycerin polyglycerin fatty acids such as monostearic acid glycerin malate, propylene glycol fatty acid esters such as propylene glycol monostearate, hardened castor oil derivative, darisylene alkyl ether, ΡΟΕ Lipophilic nonionic surfactant such as methylpolysiloxane copolymer; POE sorbitan fatty acid esters such as POE sorbitan monooleate, POE sorbitan monostearate, POE sorbit monolaurate POE sorbite fatty acid esters such as POE sorbite monooleate, POE sorbite monostearate, etc. POE fatty acid esters, POE lauryl ether, POE oleyl ether, POE alkyl ethers such as POE cholesterol ester, POE alkyl phenyl ethers such as POE octyl phenyl ether, POE alkyl phenyl ethers, pluroni POE, POP monobutyl ether, POE, POP alkyl ether, POE castor oil, POE hydrogenated castor oil, POE hydrogenated castor oil monoisostearate, POE hydrogenated castor oil maleic acid, etc. Oil-hardened castor oil derivative POE beeswax 'lanolin derivatives such as POE sorbite beeswax, coconut oil fatty acid diethanolamide, alanol amides such as fatty acid isopropanolamide, POE propylene glycol fat Examples thereof include hydrophilic nonionic surfactants such as acid esters, POE fatty acid amides, POE anolenoleamines, sucrose fatty acid esters, and alkylethoxydimethylamine oxides.

[0024] Examples of alcohols include methanol, lower alcohols such as ethanol, propanol, and isopropanol, sitosterol, and lanosterol.

[0025] Thickeners include plant gums such as gum arabic, tragacanth gum, galactan, ginger gum, guar gum, carrageenan, pectin, agar, starch (corn, wheat, potato, rice), microorganisms such as dextran, pullulan, etc. Polymers, carboxymethyl starch, starch polymers such as methylhydroxypropyl starch, animal polymers such as collagen, casein, gelatin, methinoresenorelose, nitrosenorelose, ethinoresenorose, hydroxyethinoresenore Cholesterol polymers such as loin, sodium cenorelose, hydroxypropenoresenololose, canolepoxy methinorescenellose, crystalline cenorelose, algin such as sodium alginate, propylene glycol ester of alginate High molecular weight polymers, polybutyl methyl ether, bulbu polymers such as carboxybulu polymers, POE polymers, POE'POP copolymer polymers, acrylic polymers such as sodium polyacrylate and polyacryloamide, polyethylene And water-soluble polymers such as inorganic water-soluble polymers such as imine, cationic polymer, bentonite, magnesium aluminum kainate, labonite, hectorite, and anhydrous caustic acid.

[0026] Examples of the chelating agent include citramalic acid, fagaric acid, glyceric acid, shikimic acid, hinokitiol, gallic acid, tannic acid, caffeic acid, ethylenediammine tetraacetic acid, ethylene glycol diaminetetraacetic acid, diethylenetriaminepentaacetic acid, phytic acid, polyphosphorus Examples thereof include acids, metaphosphoric acids, analogs thereof, and alkali metal salts and carboxylic acid esters thereof.

[0027] As the active oxygen scavenger, superoxide dismutase, mannitol, force tarase, β-carotene, baicalin, neucarlein, hydroquinone derivative, vinorelin, cholesterol, tryptophan, histidine, taercetin, quercitrin, catechin , Catechin derivative, gallic acid, gallic acid derivative, 2 -—- ethylscorbic acid, proanthocyanidin, sesamin, epicesamine, Melissa extract, Enmeiso extract, sage extract, rosemary extract, Eloute mouth Kok extract, yew extract, jyoji extract , Kujin extract, hamamelis extract, sohakuhi extract, basil extract, ginseng extract, toki extract, gongon extract, senki extract and the like.

[0028] Examples of the ultraviolet absorber include benzoic acid-based ultraviolet absorbers such as paraaminobenzoic acid; anthranilic acid-based ultraviolet absorbers such as methyl anthranilate; salicylic acid-based ultraviolet absorbers such as octyl salicylate; Key cinnamate UV absorbers such as isopropyl acid and normethoxy key cinnamate; benzophenone UV absorbers such as 2,4-dihydroxybenzophenone and 2-hydroxy-4-methoxybenzophenone; urocanic acid and urocanic acid For example, strong ethyl ninlate.

[0029] As the humectant, polyethylene glycol, propylene glycol, dipropylene glycol, 1,3-butylene glycol, glycerin, diglycerin, xylitol, maltitol, maltose, D-mannitol, glucose, fructose, chondroitin sulfate Examples include sodium, sodium hyaluronate, sodium lactate, darcosamine, cyclodextrin and the like.

[0030] Medicinal ingredients include vitamin A oil, retinol, retinol normitate, pyridoxine hydrochloride, benzyl nicotinate, nicotinamide, nicotinic acid dl—a-tocophenol, magnesium ascorbate phosphate, vitamin D2, dl — Vitamins such as α-tocopherol, pantothenic acid, biotin; anti-inflammatory agents such as azulene and glycyrrhizin; whitening agents such as arbutin; hormonal agents such as estradiol; astringents such as zinc oxide and tannic acid; L-menthol, It is possible to combine a refreshing agent such as camphor; other lysozyme chloride, pyridoxine hydrochloride, io, etc. Furthermore, various extracts showing various medicinal effects can be blended. In other words, there are Dokudami extract, Aubata extract, Kanzo extract, Peonies extract, Button pie kiss, Hechima extract, Yukinoshita extract, Eucalyptus extract, Chii-jiji extract, Maroniex, cornflower extract, seaweed extract, thyme extract and the like.

[0031] As preservatives, paraoxybenzoates such as methylparaben, ethylparaben, and butylparaben, benzoic acid, salicylic acid, sorbic acid, parachlormetatalesol, hexacloguchiphene, benzalkonium chloride, chlorhexidine chloride, trichloro Canolenolide, photosensitizer, phenoxyethanol and the like.

[0032] As neutralizing agents, 2-amino-2-methyl-1-propanol, 2-amino-2-methyl

1,3-propanediol, potassium hydroxide, potassium hydroxide, triethanolamine, Sodium carbonate etc. are mentioned.

[0033] Examples of the pH adjuster include lactic acid, citrate, glycolic acid, succinic acid, tartaric acid, malic acid, sodium hydrogen carbonate, ammonium hydrogen carbonate and the like.

[0034] Examples of the antioxidant include ascorbic acid, α-tocopherol, carotenoid and the like.

[0035] The above-described components are illustrative and are not limited thereto. Further, these components can be appropriately combined and blended according to a prescription according to a desired form.

[0036] Further, the external preparation for skin of the present invention can be widely applied to cosmetics, pharmaceuticals, quasi-drugs and the like applied to the outer skin, and particularly preferably to cosmetics. Any solution system, solubilization system, emulsification system, powder dispersion system, water-oil two-layer system, water-oil-powder three-layer system, ointment, gel, aerosol, etc. Any dosage form is applied

Yes

[0037] Further, the form of use of the external preparation for skin of the present invention is also arbitrary. For example, in addition to facial cosmetics and foundations such as lotions, emulsions, tames, packs, makeup cosmetics, aromatic cosmetics, It can be used for bathing agents. In addition, the form which the skin external preparation of this invention can take is not limited to said dosage form and usage form.

[0038] The topical skin preparation containing the agent of the present invention includes pharmaceuticals, quasi-drugs (ointments, dentifrices, etc.) and cosmetics such as facial cleansers, emulsions, creams, jewels, essences (beauty liquids), packs, It can be widely applied to basic cosmetics such as masks; makeup cosmetics such as foundations and lipsticks; oral cosmetics, aromatic cosmetics, hair cosmetics, body cosmetics and the like. In addition, the form which the said skin external preparation can take is not limited to these forms.

[0039] In addition, the dosage form can be a wide range of dosage forms such as an aqueous solution system, a solubilization system, an oil liquid system, a gel system, an ointment system, an aerosol system, a water oil two layer system, and a water oil powder three layer system.

[0040] By using the external preparation for skin containing the anti-wrinkle agent of the present invention, it is possible to prevent and improve wrinkles, particularly fine wrinkles, and to provide youthful and fresh skin!

Example

[0041] Next, the present invention will be described in more detail with reference to examples. The present invention is not limited thereby. Here, a compounding quantity is the mass%. Prior to Examples, the wrinkle prevention of the present invention Demonstrate the effectiveness of the improving agent!

[0042] A. Preparation of plant extract

The following plants were used from Nepal!

(l) 50% ethanol aqueous extract of Elaeocarpus sphaericus

Elaeocarpus sphaericus fruit 10 · Og was immersed in 150 ml of 50% aqueous ethanol at room temperature for 1 week, the extract was filtered and the solvent was distilled off to obtain 3.3 g of 50% aqueous ethanol extract.

[0043] (2) Quercus lineata Blume. Methanol extract

Quercus lineata Blume. Bark 50 · 3 g was immersed in 500 ml of methanol for 1 week at room temperature, the extract was filtered and the solvent was distilled off to obtain 6.55 g of methanol extract.

[0044] (3) 70% ethanol aqueous extract of Quercus lanata Sm.

Quercus lanata Sm. Seeds (10-2 g) were immersed in 100 ml of 70% aqueous ethanol at room temperature for 1 week, the extract was filtered and the solvent was distilled off to obtain 6.3 g of 70% aqueous ethanol extract.

[0045] (4) Ethanol extract of Pinus wallichiana A.B.Jacks

51. lg of Pinus wallichiana A.B. Jacks bark was soaked in 500 ml of ethanol for 1 week at room temperature, the extract was filtered and the solvent was distilled off to obtain 10.4 g of ethanol extract.

[0046] (5) 80% aqueous ethanol extract of Dioscorea esculenta Burkill

Dioscorea esculenta Burkill bulb (10 g) was immersed in 100 ml of 80% ethanol aqueous solution for 1 week at room temperature, the extract was filtered and the solvent was distilled off to obtain 1.1 g of 80% ethanol aqueous extract.

[0047] (6) Cochlospermum religiosum

Cochlospermum religiosum (Nishi) Alston bark (10.0 g) was immersed in 100 ml of ethanol for 1 week at room temperature, the extract was filtered and the solvent was distilled off to obtain 0.84 g of ethanol extract.

[0048] (7) Coriaria nepalensis Wall. (7) 50% 1,3-butylene glycol aqueous solution extract

Coriaria nepalensis Wall. 10.2 g whole plant is immersed in 150 ml of 50% 1,3-butylene glycol aqueous solution at room temperature for 1 week, filtered, the solvent is distilled off, 50% 1,3 butylene glycol Aqueous extract: L 72 g was obtained. [0049] (8) Cinnamomum bejolghota (7) 30% 1,3-butylene glycol aqueous solution extract

Cinnamomum bejolghota bark 10.9 g is immersed in 150 ml of 30% 1,3-butylene glycol aqueous solution for 1 week at room temperature, the extract is filtered, the solvent is distilled off, 30% 1, 3-butylene glycol aqueous solution Extract 1.23 g was obtained.

[0050] B. Screening for ADAM activity inhibitors

First, HB-EGF-AP / HT-1080 (derived from human fibrosarcoma modified to forcibly express a fusion protein with the addition of thermostable alkaline phosphatase (AP) to the N-terminus of human HB-EGF) The cultured cells (HT-1080) were used to screen for compounds having ADAM enzyme inhibitory activity. The full-length HB-EGF molecule is expressed on the cell surface of the cell line HB-EGF-AP / HT-1080 in the form fused with alfa phosphatase! /. When these cells are stimulated with phorbol esters, ADAM enzymes on the cell membrane surface are activated and cleave HB-EGF molecules. Since cleaved free HB-EGF is bound with alkaline phosphatase, the ADAM enzyme inhibitory activity of the compound can be indirectly measured by measuring the alkaline phosphatase activity in the culture supernatant.

[0051] Specifically, seeded by 0.2 ml / well of HB-EGF-AP / HT- 10 80 adjusted for cell number to be 2.0xl0 ⁵ cells / ml in microplates for 96 Ueru culture, 37 Cultivation was carried out at ° C. After removing the medium and washing with PBS (—), the medium containing the test substance was supplemented with 0.1 ml / well and pretreated by incubation at 37 ° C. for 30 minutes. Thereafter, the culture supernatant is removed, and 0.2 ml / well of a medium containing the test substance and 60 nM TPA (phorbol ester: 12-o-Tetradecanoylphorbo 卜 acetate; Sigma P8139) is added again, and further incubated for 60 minutes. I was treated. The final concentration of each test substance was tested at both 10 g / ml and 5011 g / ml

Yes

[0052] After completion of the treatment, 0.1 ml of the culture supernatant of each well was transferred to the well of the microphone plate for alkaline phosphatase activity measurement and incubated at 65 ° C for 10 minutes to inactivate endogenous alkaline phosphatase. I let you. lmg / ml AP substrate (p-nitrophenylphosphate, Wako; 141-023 41) was added to each well 0.1 ml / well, and the absorbance of each well was measured immediately at 405 nm. After incubation for 2 hours at room temperature in the dark, the absorbance of each well at 405 nm was measured again. Absorbance immediately after addition of AP substrate from absorbance after 2 hours incubation The absorbance of each well was obtained by subtracting the degree. The absorbance of the 0% inhibition control (medium containing only TPA) is A0, the absorbance of the 100% inhibition control (medium only) is A100, and the absorbance of the sample is AS. .

[0053] Inhibition rate (%) = (80-8) / (80-8) 100

The results are shown in Table 1. Table 1 Power, et al, Elaeocarpus sphaericus from the family Alasciaceae, Quercus lineata Blume. From the beech family, Quercus lanata Sm. From the pine family, Pinus wallichiana ABJacks from the pine family, Dioscorea esculenta Burkill from the pine family, Cochlosper muco m religiosum (Shi) Alston, Coriaria nepalensis Wall of Dokutsu Toshi Cinna momum bejolghota has a high inhibitory effect on HB—EGF release, suggesting that it inhibits ADAM activity.

[0055] [Table 1]

[0056] C. Effect test of wrinkle improving agent (Measurement method of fine wrinkle improvement effect using barrier destruction wrinkle model)

TEWL (measured using a water transpiration measuring device Meeco (Meeco, USA)) on the left back of a hairless mouse (HR-1, male 6 week old, Hoshino experimental animal) 7 ~; Omg / m ² / h Tape stripping 3 times a week for 4 weeks while adjusting to 1% Cochlospermum religiosum (1) Alston / ethanolol solution or 1% Que reus lanata Sm./ A 100% 70% aqueous ethanol solution was applied one by one. The n number was 6-7.

[0057] The occurrence of wrinkles after 4 weeks was scored by four examiners by visual observation. Wrinkled Occurrence status is “no wrinkles; 0”, “light wrinkles; 1”, “obvious wrinkles; 2”, “deep wrinkles; 3”, 0

. Scored in 5 increments. The larger the score, the deeper the wrinkle. The mean and standard deviation of each group was calculated and the effect of the drug is shown in Fig. 1.

In FIG. 1, “Vehicle” indicates no drug (ethanol solution or 70% ethanol aqueous solution).

Figure 1 shows that Cochlospermum religiosum Alston ^ Quercus lanata Sm. Has a significant wrinkle suppression effect compared to Vehicle.

[0059] Simultaneously, transepidermal water transpiration (Trans mark idermal Water Loss; TEWL) was measured using a ^ Vapometer (Del fm, Finland). TEWL is an index of rough skin. The higher the value, the worse the skin condition. The right back of the same individual (= tape stripping

The ratio of the TEWL value (TS) of the left dorsal part (= tape stripping! / The part where the tape is stripped) to the TEWL value (NT) of V, NA! Deviation was calculated. The result is shown in Fig.2.

As shown in Fig. 2, in the vehicle application group, TEWL was increased by about 1.5 times the force S, 1% Cochlos permum religiosum (Lj Alston / Ethananol or 1% Quercus lanata Sm./ ί0% ethanol aqueous solution was applied. In the group, it was found that the TEWL increase caused by tape stripping was significantly suppressed.

[0060] These resulting forces, et al. Cochlospermum religiosum Alston, Quercus lanata Sm. AD

It was revealed that fine wrinkle formation was prevented by inhibiting AM enzyme activity and suppressing epidermal thickening associated with rough skin.

[0061] Formulation examples (formulation examples) of external preparations for skin using the anti-wrinkle agent according to the present invention are shown below. In addition, skin preparations for V and misalignment have excellent wrinkle prevention and improvement effects!

[0062] Formulation Example 1: Wrinkle prevention 'improvement cream

Ingredient Compounding amount (mass%)

Liquid paraffin 8

Vaseline 3

Dimethinorepolysiloxane 2

Stearino Reano Recone 3

To: ^ Noreano Reconole 2 Five

Dipropylene glycol 4

Trueno porridge 1

Tetra 2-ethylhexanoate pentaerythritol 4

2

Lipophilic mold 2

0. 05

0. 05 Potassium hydroxide 0.015 Quercus lanata Sm. 70% ethanol extract 2.0

Elaeocarpus sphaericus 50% Etanore Taide ί 夜 0. 001 Tocopheronole acetate 0.

Paraoxybenzoic acid

Phenoxy ethanol

Edetate trisodium 0.05-4-tert-butyl 4-,-0. 01 paramethoxycinnamic acid 2-ethyl hexyl 0. 1 β-strength rotin 0. 01 Polyvinylenorenoreconole 0.5

0.5 canolepoxivininopolymer 0.5.5 Purified water

Fragrance

Formulation Example 2: Wrinkle prevention · Cream for improvement

Ingredient Blending amount (mass%) Vaseline

Three

Sun 5

Ten

2

1 Norre 2 Glycerin fatty acid ester eicosane diacid condensate 0.

2-etinorehexanoic acid cetinole 5

Sodium chloride 0.5

Sodium hexametaphosphate 0. 05

0. 05

0. 1

Phosphoric acid 2

Tocopherol acetate 0.5

Cinnamomum bejolghotadO% l, 3 Cole extract 0 Quercus lineata Blume.

DL—Sodium pyrrolidonecarboxylate

Edetic acid trisodium 0 ·

Paraben

purified water

Fragrance

Formulation Example 3: Wrinkle prevention Vaseline 5

To: T Reanoreco Nore 0. 5

Call 0.5

3-Butylene glycol 7

2-Pentangi-Nore

Three

Polyethylene glycolore 20000 2

Hardened oil 2

Jojoba oil 2

Five

0.5

Tetra 2-ethylhexanoic acid pentaerythritol 2

Polyoxyethylene hydrogenated castor oil 0.5

Lauryldimethylaminoacetic acid betaine 0.4

Potassium hydroxide appropriate amount

Sodium pyrosulfite 0.01

Sodium hexametaphosphate 0. 05

Dipotassium glycyrrhizinate 0. 05

Dioscorea esculenta Burkill 80% ethanol extract 1. 0 Cochlospermum relgiousum Yoshi Alston etenore タ 0. 05

Three

Yeast extract 0.1

Tocopheronol acetate 0.

Bengala

Queen Seed Extract 0.

Canolepoxy bininole polymer 0.2

Phenoxyethanol purified water

Formulation Example 4: Wrinkle prevention

Ingredient Compounding amount (mass%)

-Sun 15

Five

Polyoxyethylene 'methylpolysiloxane copolymer 5

Glycerin 5

1, 3—Butyleneglycanol 5

Manoleto Tonore ί 夜 2

Macadamia nut oil 2

2

Acid Cholesterinore 0.5

2-Ethinolehexanoic acid cetinole 2

L-ascorbic acid sulfate disodium 0.1

α-Tocopherol 2-L-ascorbic acid potassium phosphate diester 0. Tocopherol acetate 0. 05

Fish collagen 0.4

Sodium chondroitin sulfate 0 · 01

Sodium hyaluronate 0.1

Coriaria nepalensis Wall. 50% 1, 3-Butylene glycol extract 1.0 Pinus wallichiana A. B. Jacks Ethanore Yuki ί 夜 1.0

Edetate trisodium 0. 05

Diparamethoxycinnamic acid mono-2-ethylglyceryl hexylate 0 · 05 Anoleminium magnesium kaylate 0 · 3

Paraben appropriate amount

purified water

Claims

The scope of the claims

[1] Quercus lanata Sm. (Scientific name: Quercus lanata Sm.), Elaeocarpus sphaericus (scientific name: Elaeocarpus sphaericus), Taerukas lineata Blume. (Scientific name: Quercus lineata Blume.), Pine family Pinus wallichiana ABJacks (Scientific name: Pinus wallichiana ABJacks), Dioscorea esculenta Burkill (scientific name: Dioscorea esculenta Burkill) Alston), Coriania nepalensis wall (Scientific name: Coriaria nepale nsis Wall.), Schiff's shrimp 'Momamu Heshonorekota' (name: Cinnamomum bejolghota force, one or more plants selected from these, or these Containing a solvent extract of Anti-wrinkle agent characterized.

[2] Taenolecus lanata Sm. Of the beech family (scientific name: Quercus lanata Sm.), Tae norecus linata blum of the beech family (scientific name: Quercus lineata Blume.), Pinus s. Pinus wallichiana ABJacks), Dioscorea esculenta Burkill (Scientific name: Dioscorea esculenta Burkill), Cinnamomum bejolggota (Scientific name: Cinnamomum bejolghota), or a solvent extract of these. A skin external preparation characterized by being formulated.