JP2008094734A - Anti-wrinkle and skin preparations - Google Patents

Abstract

An anti-wrinkle agent that improves wrinkles induced when the barrier function is lowered by drying or the like, particularly fine wrinkles, is provided.
SOLUTION: Ellaeocarpus sphaericus of the family Astragalus, Quercus lineata Blume. Of the beech family, Quercus lanata Sm. One or two or more kinds of plants selected from Coriaria nepalensis Wall. Belonging to the genus Euphoridae, Cinnamomum bejolghota belonging to the aceae family, or a solvent extract thereof.
[Selection] Figure 1

Description

  The present invention relates to an anti-wrinkle agent, and more particularly, to an anti-wrinkle agent that prevents and improves wrinkles caused by the decrease in the barrier function by suppressing skin thickening caused when the barrier function decreases due to drying or the like. Is.

The stratum corneum located in the outermost layer of the skin protects the living body from the contact and penetration of foreign substances such as bacteria and harmful substances, and has a barrier function to keep the skin in a healthy state by preventing moisture evaporation from the body. When the barrier function decreases due to excessive water work, dry winter, and excessive cooler in summer, the transepidermal water loss (TEWL) from the skin surface increases, which is relatively horny. Water content is reduced. When the crest (texture) composed of skin grooves and skin hills becomes irregular due to a decrease in the amount of moisture in the stratum corneum, the skin exhibits a bulky rough state (see Non-Patent Document 1).
Minor wrinkles are thought to be caused by the fact that irregular skin crests flow in a certain direction as this rough skin continues chronically, and those who actually have skin conditions with low stratum corneum moisture have a fine wrinkle area ratio. It is reported to be high (see Non-Patent Document 2). In general, it is said that the formation of fine lines is promoted when the dry state continues, but in addition to seasonal effects, modern women are placed in an environment where the skin is always dry even in summer due to the spread of air conditioning. And worries about fine wrinkles increase from around the late 20s.
In order to prevent this skin barrier function deterioration and prevent or improve the moisture transpiration from the skin surface, and also the occurrence of rough skin and fine lines, moisturizing ingredients such as glycerin and NMF (natural moisturizing factor) and collagen derivatives are applied to the skin. There have been proposed a method for enhancing moisture retention of the skin, a method for promoting turnover of keratinocytes using a cell activation component such as placenta extract and vitamins. However, since there are many unclear parts regarding the mechanisms related to aging and wrinkles, conventional cosmetics have only the method of retaining moisture for improving wrinkles as described above, which is also sufficient as described above. The current situation is that it does not show a positive effect.

Toshiro Sone et al., Cosmetic Society Vol.15 No.2 P.60-65 (1991) Genji Ayukawa et al., Fragrance Journal 1992-11, 29-42

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

  The applicant has established an animal model (barrier destruction wrinkle model) having fine wrinkles by continuously tape stripping the back of the hairless mouse to reduce the barrier 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 as wrinkles recover, the thickening also subsides. Therefore, it was considered that there is a correlation between wrinkle formation and thickening of the epidermis and dermis. .

  In addition, the applicant of the present invention, in the barrier destruction wrinkle model, has a protein belonging to the ADAM (a disintegrin and metalloprotease) family having disintegrin and metalloprotease domains (hereinafter referred to as ADAM) such as ADAM-9, ADAM-10, and ADAM-17. Furthermore, gene expression in the epidermis of HB-EGF (heparin-binding EGF-like growth factor) and Amphiregulin, which are released from the cell membrane and activated by ADAM, is enhanced. Furthermore, by applying an inhibitor of these ADAMs, it is possible to suppress thickening and wrinkle formation of the epidermis and dermis, contact the test substance with human or animal skin, skin tissue or cells, and the skin, ADAM in tissues or cells A method has already been found for detecting enzyme activity or gene expression level and evaluating the anti-wrinkle effect of a test substance using ADAM enzyme generation or gene expression level as an index (Japanese Patent Application Nos. 2005-299524 and 2005-296219). reference).

  On the other hand, as ADAM inhibitors, TAPI-1 {N- (R)-(2- (Hydroxyaminocarbonyl) methyl) -4-Methylpentanoyl-L-Nal-L-Alanine2-Aminoethyl amide (L-Nal: L-3- ( 2'-Naphthyl) alanine)} and TAPI-2 {N- (R)-(2- (Hydroxyaminocarbonyl) methyl) -4-Methylpentanoyl-Lt-Butyl-Glycyl-L-Alanine2-Aminoine amide} However, the ADAM inhibitory ability of these substances is not sufficient, and the safety as an external preparation for skin has not been confirmed. Therefore, development of safer and more effective drugs has been demanded.

  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 barrier destruction wrinkle model. Has been found to be excellent in the action of improving fine lines, and has led to the present invention.

  The present invention relates to Ellaocarpus sphaericus (scientific name: Elaeocarpus sphaericus), Quercus lineata bloom of Beechaceae. (Scientific name: Quercus lineata Blume.), Quercus lanata sm of the beech family. (Scientific name: Quercus lanata Sm.) Bee. Jacques (scientific name: Pinus wallichiana ABJacks), Dioscorea esculenta brukill (scientific name: Dioscorea esculenta Burkill) of the genus Myraceae, Kokolospermum religiosum (El.) Alston (scientific name: Cochlospermum religiosum (L. Characterized by containing one or more plants selected from the family Coralia nepalensis Wall (scientific name: Coriaria nepalensis Wall.), Cinnamomum bejolghota (scientific name: Cinnamomum bejolghota), or a solvent extract thereof It is an anti-wrinkle agent.

  The present invention also relates to a quercus lineata bloom. (Scientific name: Quercus lineata Blume.), Quercus lanata sm of the beech family. (Scientific name: Quercus lanata Sm.) Bee. One or more plants selected from jacks (scientific name: Pinus wallichiana ABJacks), Dioscorea esculenta brukill (scientific name: Dioscorea esculenta Burkill), cinnamom bejorggota (scientific name: Cinnamomum bejolghota), It is an external preparation for skin characterized by comprising a solvent extract.

  The anti-wrinkle agent of the present invention can prevent and improve wrinkles induced when the barrier function is lowered due to drying or the like, particularly fine wrinkles.

  In addition, the external preparation for skin of the present invention can prevent and improve wrinkles induced when the barrier function is lowered due to drying or the like, in particular fine wrinkles, and is excellent in usability and safety.

The best mode of the present invention will be described below.
The genus Ellaocarpus sphaericus (scientific name: Elaeocarpus sphaericus) used in the present invention is a plant belonging to the genus Hortonaceae, and is referred to as hortonol, kongo, kongo, jujubo daiju, indian genus. 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).
Cuercus lineata bloom used in the present invention. (Scientific name: Quercus lineata Blume.) Is called “Mempening”.
Cuercus lanata sm. (Scientific name: Quercus lanata Sm.) Is a plant belonging to the genus Quercus.
Pinus urariana A. of the Pinaceae used in the present invention. Bee. Jacks (scientific name: Pinus wallichiana ABJacks) 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 of the genus Dioscorea esculenta Burkill, and is referred to as Tedokoro.
Recognum (L.) Alston (Scientific name: Cochlospermum religiosum (L.) Alston) used in the present invention is a plant belonging to the genus Apiaceae, yellow silk-cotton tree, silk cotton tree, yellow cotton It is called tree.
The Coriaria nepalensis Wall (scientific name: Coriaria nepalensis Wall.) Used in the present invention is a plant belonging to the genus Cryaria.
Cinnamomum bejolghota (scientific name: Cinnamomum bejolghota) used in the present invention is a plant belonging to the genus Cynnamomum.

  Each plant used in the present invention can be used raw or dried, but is preferably used as a dry powder or a solvent extract from the viewpoints of usability and formulation.

The preferred site of use when each plant is used as a dry powder or solvent extract is as follows.
It is preferable to use fruit for Ellaeocarpus sphaericus (scientific name: Elaeocarpus sphaericus), but other parts can also be used.
Quercus lineata bloom from the beech family. (Scientific name: Quercus lineata Blume.) It is preferable to use bark, but other parts can also be used.
Cuercus lanata sm of the beech family. (Scientific name: Quercus lanata Sm.) It is preferable to use seeds, but other parts can also be used.
Pinus Walitiana a. Bee. For jacks (scientific name: Pinus wallichiana ABJacks), bark is preferably used, but other parts can also be used.
For Dioscorea esculenta Burkill (scientific name: Dioscorea esculenta Burkill), it is preferable to use bulbs, but other sites can also be used.
The bark is preferably used for the reediosum (El.) Alston (scientific name: Cochlospermum religiosum (L.) Alston), but other parts can also be used.
As for Coriania nepalensis Wall. (Scientific name: Coriaria nepalensis Wall.), It is preferable to use whole plants other than roots.
The bark is preferably used for Cinnamomum bejolghota (scientific name: Cinnamomum bejolghota), but other sites can also be used.

The above-mentioned solvent extract of each plant can be obtained by a conventional method. For example, it can be obtained by immersion or heating under reflux with an extraction solvent, followed 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, glycerin and other alcohols, hydrous alcohols, chloroform Organic solvents such as dichloroethane, carbon tetrachloride, acetone, ethyl acetate, and hexane 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 an adsorption method, for example, by removing impurities using an ion exchange resin, or by a porous polymer (for example, Amberlite XAD-2) column. Then, it can be used after elution with methanol or ethanol. Further, a partitioning method, for example, an extract obtained by separation / extraction with water / ethyl acetate can also be used.

  The plant extract thus obtained is highly safe and has an excellent ADAM activity inhibitory effect and wrinkle prevention / improvement effect. 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.

  In addition, although the anti-wrinkle agent of this invention is a mixing | blending raw material which consists of 1 type or 2 types or more of the said plant extract substantially, it may contain the other component. This anti-wrinkle agent is blended with the external preparation for skin to provide the external preparation for skin of the present invention.

  When the above-mentioned plant extract is blended and used in a skin external preparation, it is preferably blended in the total amount of the external preparation in a dry weight of 0.000001 to 5.0 mass%, more preferably 0.00001 to 3.0 mass%. Especially preferably, it is 0.00001-1.0 mass%.

  When using the above-mentioned plant extract in combination with an external preparation for skin, in addition to these extracts, other components usually used in external preparations for skin such as cosmetics and pharmaceuticals, within the range not impairing the effects of the present invention, For example, oil, surfactant, alcohol, thickener, chelating agent, active oxygen scavenger, ultraviolet absorber, moisturizer, wetting agent, various medicinal ingredients, preservatives, neutralizer, pH adjuster, antioxidant, A fragrance | flavor, water, etc. can be mix | blended suitably as needed.

  Among the above optional ingredients, the oil component is branched from linear alcohols such as lauryl alcohol, cetyl alcohol, stearyl alcohol, myristyl alcohol, oleyl alcohol, monostearyl glycerin ether, lanolin alcohol, cholesterol, phytosterol, isostearyl alcohol, etc. Higher alcohols such as chain alcohols, higher fatty acids such as lauric acid, myristic acid, palmitic acid, stearic acid, waxes such as solid paraffin, bees wax, hydrogenated castor oil, carnauba wax, barico wax, beef tallow, pork fat, 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 triisoste Rate, 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 described as POP.) Synthetic oils such as pentaerythritol ether.

  Examples of surfactants include soap bases, fatty acid soaps such as sodium laurate and sodium palmitate, higher alkyl sulfates such as sodium lauryl sulfate and potassium lauryl sulfate, POE lauryl sulfate triethanolamine, and POE ralyl sulfate sodium. Alkyl ether sulfates, N-acyl sarcosine acids such as lauroyl sarcosine sodium, N-myristoyl-N-methyl taurine sodium, higher fatty acid amide sulfonic acids such as coconut oil fatty acid methyl tauride sodium, phosphorus such as POE stearyl ether phosphate Acid ester salts, sulfosuccinates such as monolauroyl monoethanolamide POE sodium sulfosuccinate, sodium lauryl polypropylene glycol sulfosuccinate, linear dodecyl Such as sodium benzenesulfonate, alkylbenzenesulfonate such as linear dodecylbenzenesulfonate triethanolamine, disodium N-stearoyl glutamate, N-acyl glutamate such as monosodium N-stearoyl glutamate, hardened coconut oil fatty acid sodium glycerine sulfate, etc. Higher fatty acid ester sulfate, sulfated oil such as funnel oil, POE alkyl ether carboxylic acid, POE alkyl allyl ether carboxylate, higher fatty acid ester sulfonate, secondary alcohol sulfate, higher fatty acid alkylolamide sulfate Salts, anionic surfactants such as sodium lauroyl monoethanolamide succinate, sodium caseinate; stearyltrimethylammonium chloride, lauryltrimethyl chloride Alkyltrimethylammonium salts such as ammonium, dialkyldimethylammonium salts such as distearyldimethylammonium chloride, alkylpyridinium salts such as cetylpyridinium chloride, alkyl quaternary ammonium salts, alkyldimethymethylbenzylammonium salts, alkylisoquinolinium salts, Cationic surfactants such as dialkyl morphonium salts, POE alkyl amines, alkyl amine salts, polyamine fatty acid derivatives, amyl alcohol fatty acid derivatives, benzalkonium chloride; 2-cocoyl-2-imidazolinium hydroxide-1-carboxyl Amphoteric surfactants such as imidazoline-based amphoteric surfactants such as ethyloxy disodium salt, betaine-based surfactants such as amide betaine and sulfobetaine; sorbitan monooleate, sorbi Sorbitan fatty acid esters such as tan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan trioleate, mono cottonseed oil fatty acid glycerin, glyceryl monostearate, glyceryl sesquioleate, glyceryl monostearate malate, etc. Lipophilic nonionic surfactants such as glycerin polyglycerin fatty acids, propylene glycol fatty acid esters such as propylene glycol monostearate, hydrogenated castor oil derivatives, glycerin alkyl ether, POE / methylpolysiloxane copolymer; POE sorbitan monoole POE sorbitan fatty acid esters such as POE sorbitan monostearate, POE sorbit monolaurate, POE sorbite monooleate, POE sorbitol POE sorbite fatty acid esters such as monostearate, POE glycerin monooleate, POE glycerin fatty acid esters such as POE glycerol distearate, POE monooleate, POE fatty acid esters such as POE distearate, POE monodiolate, POE lauryl ether, POE POE alkyl ethers such as oleyl ether and POE cholestanol ester, POE alkylphenyl ethers such as POE octylphenyl ether and POE nonylphenyl ether, pullaronic types such as pluronic, POE / POP monobutyl ether POE / POP alkyl ethers, P such as POE castor oil, POE hydrogenated castor oil, POE hydrogenated castor oil monoisostearate, POE hydrogenated castor oil maleic acid, etc. E castor oil hardened castor oil derivative, POE beeswax / lanolin derivative such as POE sorbite beeswax, alkanolamide such as coconut oil fatty acid diethanolamide, fatty acid isopropanolamide, POE propylene glycol fatty acid ester, POE fatty acid amide, POE alkylamine, sucrose fatty acid And hydrophilic nonionic surfactants such as esters and alkylethoxydimethylamine oxide.

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

  As thickeners, arabic gum, tragacanth gum, galactan, carob gum, guar gum, carrageenan, pectin, agar, starch (corn, wheat, potato, rice) and other vegetative polymers, dextran, pullulan and other microbial polymers, Starch polymers such as carboxymethyl starch and methylhydroxypropyl starch, animal polymers such as collagen, casein, gelatin, methylcellulose, nitrocellulose, ethylcellulose, hydroxyethylcellulose, sodium cellulose sulfate, hydroxypropylcellulose, carboxymethylcellulose, crystalline cellulose Cellulose polymers such as sodium alginate, alginic acid polymers such as propylene glycol alginate, polyvinyl methyl ether, Vinyl polymers such as ruxoxyvinyl polymer, POE polymers, POE / POP copolymer polymers, acrylic polymers such as sodium polyacrylate and polyacrylamide, polyethyleneimine, cationic polymers, bentonite, silica And water-soluble polymers such as inorganic water-soluble polymers such as aluminum magnesium oxide, laponite, hectorite, and silicic anhydride.

  Chelating agents include citramalic acid, agaric acid, glyceric acid, shikimic acid, hinokitiol, gallic acid, tannic acid, caffeic acid, ethylenediaminetetraacetic acid, ethyleneglycoldiaminetetraacetic acid, diethylenetriaminepentaacetic acid, phytic acid, polyphosphoric acid, metaphosphoric acid , As well as their analogs and their alkali metal salts and carboxylic acid esters.

  As active oxygen scavengers, superoxide dismutase, mannitol, catalase, β-carotene, baicalin, baicalein, hydroquinone derivatives, biryllin, cholesterol, tryptophan, histidine, quercetin, quercitrin, catechin, catechin derivatives, gallic acid, gallic acid derivatives , 2-O-ethylascorbic acid, proanthocyanidins, sesamin, episesamin, melissa extract, enamel extract, sage extract, rosemary extract, eleuterococcus extract, ginkgo biloba extract, clove extract, cucumber extract, hamamelis Examples include extract, Sakuhakuhi extract, Basil extract, Panax ginseng extract, Toki extract, Ogon extract, Senkyu extract and the like.

  Examples of UV absorbers include benzoic acid UV absorbers such as paraaminobenzoic acid; anthranilic acid UV absorbers such as methyl anthranilate; salicylic acid UV absorbers such as octyl salicylate; isopropyl paramethoxycinnamate and paramethoxysilicate. Examples thereof include cinnamic acid ultraviolet absorbers such as octyl cinnamate; benzophenone ultraviolet absorbers such as 2,4-dihydroxybenzophenone and 2-hydroxy-4-methoxybenzophenone; urocanic acid, ethyl urocanate and the like.

  As moisturizers, polyethylene glycol, propylene glycol, dipropylene glycol, 1,3-butylene glycol, glycerin, diglycerin, xylitol, maltitol, maltose, D-mannitol, glucose, fructose, sodium chondroitin sulfate, sodium hyaluronate , Sodium lactate, glucosamine, cyclodextrin and the like.

  As a medicinal component, vitamin A oil, retinol, retinol palmitate, pyridoxine hydrochloride, benzyl nicotinate, nicotinic acid amide, nicotinic acid dl-α-tocophenol, magnesium ascorbate phosphate, vitamin D2, dl-α-tocopherol, Vitamins such as pantothenic acid and biotin; anti-inflammatory agents such as azulene and glycyrrhizin; whitening agents such as arbutin; hormone agents such as estradiol; astringents such as zinc oxide and tannic acid; refreshing agents such as L-menthol and camphor; In addition, lysozyme chloride, pyridoxine hydrochloride, sulfur and the like can be blended. Furthermore, various extracts showing various medicinal effects can be blended. In other words, there are dokudami extract, apricot extract, licorice extract, peony extract, button pi extract, loofah extract, saxifrage extract, eucalyptus extract, clove extract, maronier extract, cornflower extract, seaweed extract, thyme extract and the like.

  Preservatives include paraoxybenzoates such as methylparaben, ethylparaben, and butylparaben, benzoic acid, salicylic acid, sorbic acid, parachlorometacresol, hexachlorophene, benzalkonium chloride, chlorhexidine chloride, trichlorocarbanilide, photosensitive Element, phenoxyethanol and the like.

  Examples of the neutralizing agent include 2-amino-2-methyl-1-propanol, 2-amino-2-methyl-1,3-propanediol, potassium hydroxide, potassium hydroxide, triethanolamine, sodium carbonate and the like. It is done.

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

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

  The said component is an illustration and is not limited to these. Further, these components can be appropriately combined and blended in accordance with a prescription according to a desired form.

  Further, the external preparation for skin of the present invention can be widely applied to cosmetics, pharmaceuticals, quasi-drugs, etc., particularly preferably cosmetics applied to the outer skin, and the dosage form is also applicable to the skin. Any dosage form is possible as long as it can be used, such as solution system, solubilization system, emulsification system, powder dispersion system, water-oil two-layer system, water-oil-powder three-layer system, ointment, gel, aerosol, etc. Applies.

  The use form of the external preparation for skin of the present invention is also arbitrary. For example, it may be used for makeup cosmetics, aromatic cosmetics, bath preparations, etc. in addition to facial cosmetics and foundations such as skin lotions, emulsions, creams and packs. it can. In addition, the form which the skin external preparation of this invention can take is not limited to said dosage form and usage form.

  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, gels, essences (beauty liquids), packs, masks, etc. Basic cosmetics; makeup cosmetics such as foundations and lipsticks; widely applicable to forms such as oral cosmetics, aromatic cosmetics, hair cosmetics and body cosmetics. In addition, the form which the said skin external preparation can take is not limited to these forms.

  Also, the dosage form can be a wide range of dosage forms such as aqueous solution, solubilization system, oil liquid system, gel system, ointment system, aerosol system, water-oil two-layer system, water-oil-powder three-layer system.

  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.

  EXAMPLES Next, an Example is given and this invention is demonstrated further in detail. The present invention is not limited thereby. Here, a compounding quantity is the mass%. Prior to the examples, the effect test of the wrinkle prevention / improving agent of the present invention will be described.

A. Preparation of plant extract Nepalese plants were used for the following plants.
(1) 50% ethanol aqueous extract of Elaeocarpus sphaericus
10.0 g of Elaeocarpus sphaericus fruit was immersed in 150 ml of 50% ethanol aqueous solution for one week at room temperature, the extract was filtered and the solvent was distilled off to obtain 3.3 g of 50% ethanol aqueous extract.

(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.

(3) Quercus lanata Sm. 70% ethanol aqueous extract
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.

(4) Ethanol extract of Pinus wallichiana ABJacks
51.1 g of Pinus wallichiana ABJacks bark was immersed 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.

(5) 80% ethanol aqueous extract of Dioscorea esculenta Burkill
10 g of bulb of Dioscorea esculenta Burkill was immersed in 100 ml of 80% ethanol aqueous solution for one week at room temperature, the extract was filtered and the solvent was distilled off to obtain 1.1 g of 80% ethanol aqueous extract.

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

(7) Coriaria nepalensis Wall. 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 for one week at room temperature, the extract is filtered, the solvent is distilled off, 50% 1,3 butylene glycol aqueous solution 1.72 g of extract was obtained.

(8) 30% 1,3-butylene glycol aqueous extract of Cinnamomum bejolghota
10.9 g of Cinnamomum bejolghota bark is immersed in 150 ml of 30% 1,3-butylene glycol aqueous solution for one week at room temperature, the extract is filtered, the solvent is distilled off, and 30% 1,3-butylene glycol aqueous solution extract is extracted. 1.23 g was obtained.

B. Screening for ADAM activity inhibitors First, HB-EGF-AP / HT-1080 (human fiber modified to forcibly express a fusion protein with the addition of thermostable alkaline phosphatase (AP) to the N-terminus of human HB-EGF) A compound having ADAM enzyme inhibitory activity was screened using sarcoma-derived cultured cells HT-1080). On the cell surface of the cell line HB-EGF-AP / HT-1080 used, the full-length HB-EGF molecule is expressed in a form fused with alkaline phosphatase. When this cell is stimulated with phorbol ester, the ADAM enzyme on the cell membrane surface is activated to cleave the HB-EGF molecule. Since alkaline phosphatase is bound to HB-EGF that has been cleaved to be free, the ADAM enzyme inhibitory activity of the compound can be indirectly measured by measuring the alkaline phosphatase activity in the culture supernatant.

Specifically, HB-EGF-AP / HT-1080, the number of cells of which was adjusted to 2.0 × 10 ⁵ cells / ml, was seeded in 0.2 ml / well on a 96-well culture microplate and incubated at 37 ° C. Cultured overnight. After removing the medium and washing with PBS (−), 0.1 ml / well of a medium containing the test substance was added and pretreated by incubation at 37 ° C. for 30 minutes. Thereafter, the culture supernatant is removed, and a medium containing the test substance and 60 nM TPA (phorbol ester: 12-o-Tetradecanoylphorbol-acetate; Sigma P8139) is added at a rate of 0.2 ml / well and further incubated for 60 minutes. Treated. The final concentration of each test substance was tested at both 10 μg / ml and 50 μg / ml.

  After completion of the treatment, 0.1 ml of the culture supernatant of each well was transferred to a well of a microplate for alkaline phosphatase activity measurement and incubated at 65 ° C. for 10 minutes to inactivate endogenous alkaline phosphatase. 1 mg / ml AP substrate (p-nitrophenylphosphate, Wako; 141-02341) was added to each well in an amount of 0.1 ml / well, and the absorbance at 405 nm of each well was immediately measured. After incubating at room temperature for 2 hours in the dark, the absorbance at 405 nm of each well was measured again. The absorbance of each well was obtained by subtracting the absorbance immediately after addition of AP substrate from the absorbance after incubation for 2 hours. The absorbance of the 0% inhibition control (medium containing only TPA) was A0, the absorbance of the 100% inhibition control (medium only) was A100, and the absorbance of the sample was AS, and the inhibition rate (%) was calculated by the following formula.

  Inhibition rate (%) = (A0−AS) / (A0−A100) × 100

  The results are shown in Table 1. Table 1 shows that Ellaeocarpus sphaericus of the family Astragalus, Quercus lineata Blume. Of the beech family, Quercus lanata Sm. Alston, Coriaria nepalensis Wall. Belonging to Cryceaeaceae, and Cinnamomum bejolghota belonging to Camphoraceae have high HB-EGF release inhibitory effects, suggesting that ADAM activity is inhibited.

C. Effect test of wrinkle improver (Measurement method of wrinkle improvement effect using barrier breaking wrinkle model)
The TEWL (measured using a water transpiration measuring device Meeco (Meeco, USA)) is 7-10 mg / cm ² / h on the left back of the hairless mouse (HR-1, male 6-week-old, Hoshino experimental animal) Tape stripping is performed 3 times a week for 4 weeks while adjusting. Immediately after tape stripping treatment, 100 μl each of 1% Cochlospermum religiosum (L.) Alston / ethanol solution or 1% Quercus lanata Sm./70% ethanol solution is used. Applied. The n number was 6 to 7.

  Four assessors scored the occurrence of wrinkles after 4 weeks by visual observation. The occurrence of wrinkles was “no wrinkles; 0”, “light wrinkles; 1”, “obvious wrinkles; 2”, “deep wrinkles; 3”, and scored in 0.5 increments. The larger the score, the deeper the wrinkle. The average value and standard deviation of each group were calculated and the effect of the drug is shown in FIG.

  In FIG. 1, “Vehicle” indicates no drug (ethanol solution or 70% ethanol aqueous solution). From FIG. 1, it can be seen that Cochlospermum religiosum (L.) Alston and Quercus lanata Sm. Show a significant wrinkle suppressing effect compared to Vehicle.

At the same time, transepidermal water loss (TEWL) was measured using a Vapometer (Delfin, Finland). TEWL is an index of rough skin, and the higher the value, the worse the skin condition. The ratio of the TEWL value (TS) of the left dorsal portion (= the portion where tape stripping is performed) to the TEWL value (NT) of the right back portion (= the portion where tape stripping is not performed) of the same individual is obtained, and the average value of each group And the standard deviation was calculated. The result is shown in FIG.
As shown in FIG. 2, TEWL increased about 1.5 times in the vehicle application group, but 1% Cochlospermum religiosum (L.) Alston / ethanol solution or 1% Quercus lanata Sm./70% ethanol aqueous solution group was applied. Then, it became clear that the increase in TEWL caused by tape stripping was significantly suppressed.

  These results revealed that Cochlospermum religiosum (L.) Alston and Quercus lanata Sm. Inhibit ADAM enzyme activity and prevent fine wrinkle formation by suppressing epidermal thickening associated with rough skin.

  The formulation example (formulation example) of the skin external preparation using the anti-wrinkle agent which concerns on this invention is shown below. All of the external preparations for skin had excellent wrinkle prevention and improvement effects.

Formulation Example 1: Wrinkle prevention / improvement cream ingredient content (% by mass)
Liquid paraffin 8
Vaseline 3
Dimethylpolysiloxane 2
Stearyl alcohol 3
Behenyl alcohol 2
Glycerin 5
Dipropylene glycol 4
Trehalose 1
Tetra-2-ethylhexanoic acid pentaerythrit 4
Polyisoethylene glyceryl monoisostearate 2
Polyoxyethylene glyceryl monostearate 1
Lipophilic glyceryl monostearate 2
Citric acid 0.05
Sodium citrate 0.05
Potassium hydroxide 0.015
Quercus lanata Sm. 70% ethanol extract 2.0
Elaeocarpus sphaericus 50% ethanol extract 0.001
Tocopherol acetate 0.1
P-Hydroxybenzoate appropriate amount phenoxyethanol appropriate amount dibutylhydroxytoluene appropriate amount edetate trisodium 0.05
4-t-butyl-4′-methoxydibenzoylmethane 0.01
2-Ethylhexyl paramethoxycinnamate 0.1
β-carotene 0.01
Polyvinyl alcohol 0.5
Hydroxyethyl cellulose 0.5
Carboxyvinyl polymer 0.05
Purified water Residual fragrance

Formulation Example 2: Wrinkle prevention / improvement cream component Amount (% by mass)
α-olefin oligomer 10
Vaseline 1
Microcrystalline wax 3
Decamethylcyclopentasiloxane 5
Glycerin 10
Dipropylene glycol 2
1,3-butylene glycol 2
Erythritol 2
Squalane 1
Glycerin fatty acid ester eicosannic acid condensate 0.1
Isostearic acid 1
Cetyl 2-ethylhexanoate 5
Sodium chloride 0.5
Sodium hexametaphosphate 0.05
Stearyl glycyrrhetinate 0.05
Koubo extract 0.1
L-ascorbyl magnesium phosphate 2
Tocopherol acetate 0.5
Cinnamomum bejolghota 30% 1,3-butylene glycol extract 1.0
Quercus lineata Blume. Ethanol extract 1
DL-pyrrolidonecarboxylate sodium 1
Edetate trisodium 0.1
Dimethyl distearyl ammonium hectorite 2
Sodium carboxymethylcellulose 0.1
Paraben Appropriate amount Purified water Residual perfume Appropriate amount

Formulation Example 3: Wrinkle prevention / improvement emulsion component content (% by mass)
Vaseline 5
Behenyl alcohol 0.5
Batyl alcohol 0.5
Glycerin 7
1,3-butylene glycol 7
1,2-pentanediol 1
Xylit 3
Polyethylene glycol 20000 2
Hardened oil 2
Jojoba oil 2
Squalane 5
Isostearic acid 0.5
Tetra-2-ethylhexanoic acid pentaerythlit 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 (L.) Alston ethanol extract 0.05
Arbutin 3
Yeast extract 0.1
Tocopherol acetate 0.1
Bengala appropriate amount quince seed extract 0.1
Carboxyvinyl polymer 0.2
Phenoxyethanol Suitable amount Purified water Residual

Formulation Example 4: Wrinkle prevention / improvement emulsion component content (% by mass)
Decamethylcyclopentasiloxane 15
Trimethylsiloxysilicic acid 5
Polyoxyethylene / methylpolysiloxane copolymer 5
Glycerin 5
1,3-butylene glycol 5
Maltitol solution 2
Macadamia nut oil 2
Squalane 2
Cholesteryl hydroxystearate 0.5
Cetyl 2-ethylhexanoate 2
Distearyldimethylammonium chloride 0.2
L-ascorbic acid sulfate disodium 0.1
α-tocopherol 2-L-ascorbic acid potassium phosphate diester 0.1
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 ABJacks ethanol extract 1.0
Edetate trisodium 0.05
Diparamethoxycinnamic acid mono-2-ethylhexanoate glyceryl 0.05
Aluminum magnesium silicate 0.3
Paraben Appropriate amount of purified water Residual

It is a figure which shows the measurement result of the generating condition of a wrinkle when the plant extract of this invention is used. It is a figure which shows the measurement result of the transepidermal water transpiration | evaporation amount (Transepidermal Water Loss; TEWL) at the time of using the plant extract of this invention.

Claims (2)

  Ellaocarpus sphaericus (Scientific name: Elaeocarpus sphaericus), Quercus linea bloom from the beech family. (Scientific name: Quercus lineata Blume.), Quercus lanata sm of the beech family. (Scientific name: Quercus lanata Sm.) Bee. Jacques (scientific name: Pinus wallichiana ABJacks), Dioscorea esculenta Burkill (scientific name: Dioscorea esculenta Burkill) of the genus Dioscorea, Kokolospermum religiosum (el.) Alston (scientific name: Cochlospermum religiosum (L. Characterized by containing one or more plants selected from the family Coralia nepalensis Wall (scientific name: Coriaria nepalensis Wall.), Cinnamomum bejolghota (scientific name: Cinnamomum bejolghota), or a solvent extract thereof Anti-wrinkle agent. Quercus lineata bloom from the beech family. (Scientific name: Quercus lineata Blume.), Quercus lanata sm of the beech family. (Scientific name: Quercus lanata Sm.) Bee. One or more kinds of plants selected from jacks (scientific name: Pinus wallichiana ABJacks), Dioscorea esculenta brukill (scientific name: Dioscorea esculenta Burkill), cinnamom bejorggota (scientific name: Cinnamomum bejolghota), or a solvent thereof An external preparation for skin characterized by comprising an extract.

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