CN104994831A - Use of a resveratrol derivative for skin whitening - Google Patents
Use of a resveratrol derivative for skin whitening Download PDFInfo
- Publication number
- CN104994831A CN104994831A CN201480005704.6A CN201480005704A CN104994831A CN 104994831 A CN104994831 A CN 104994831A CN 201480005704 A CN201480005704 A CN 201480005704A CN 104994831 A CN104994831 A CN 104994831A
- Authority
- CN
- China
- Prior art keywords
- resveratrol
- skin
- mentioned
- derivatives
- whitening
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 0 CC(*c1cc(OC(C)=O)c(C=Cc2cc(OC(C)=O)cc(OC(C)=O)c2)cc1)=O Chemical compound CC(*c1cc(OC(C)=O)c(C=Cc2cc(OC(C)=O)cc(OC(C)=O)c2)cc1)=O 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/37—Esters of carboxylic acids
- A61K8/375—Esters of carboxylic acids the alcohol moiety containing more than one hydroxy group
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Dermatology (AREA)
- Epidemiology (AREA)
- Birds (AREA)
- Emergency Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Cosmetics (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention relates to a use of a resveratrol derivative for skin whitening, and more specifically, to: a cosmetic composition containing an acetylated derivative of resveratrol or a hydroxy derivative thereof, or a cosmetically acceptable salt thereof as an active ingredient; a cosmetic product containing the cosmetic composition; a skin whitening pharmaceutical composition containing an acetylated derivative of resveratrol or a hydroxy derivative thereof, or a pharmaceutically acceptable salt thereof as an active ingredient; a skin preparation for external use, containing the skin whitening pharmaceutical composition; a skin whitening method in which an acetylated derivative of resveratrol or a hydroxy derivative thereof, or a pharmaceutically acceptable salt thereof is administered to an individual; and a novel resveratrol derivative compound having a skin whitening effect.
Description
Technical field
The present invention relates to the skin-whitening purposes of Verakanol derivative, in more detail, relate to as effective ingredient contain resveratrol or its hydroxy derivatives, acetyl derivatives or its cosmeceutical allow the cosmetic combination that uses; Cosmetics containing above-mentioned cosmetic combination; As effective ingredient contain resveratrol or its hydroxy derivatives, acetyl derivatives or its skin-whitening pharmaceutical compositions pharmaceutically allowing the salt used; Skin preparations for extenal use containing above-mentioned skin-whitening pharmaceutical compositions; By resveratrol or its hydroxy derivatives, acetyl derivatives or its salt used that pharmaceutically allows drops into the skin-whitening method of individuality; And there is the Verakanol derivative compound of novelty of skin whitening effects.
Background technology
Melanin (melanin) is the pigment be seen everywhere at nature, is present in most organism, is the general designation being mainly present in the black of tissue such as the skin of animal or eyes or the pigment of brown.Mainly exist with the melanoprotein matter form forming strong bond with globulin (globuline), water insoluble, but be dissolved in alkaline solution or high-concentration acidic wastewater solution.Melanin possesses the ultraviolet function of blocking more than scheduled volume, keeps the body temperature of skin, thus protection skin is not by uv damage.Such as, absorb and can bring out maligna and swell and the ultraviolet of skin carcinoma, convert thereof into harmless heat.The colour of skin is decided by this melanic amount.That is, as the important elements of the colour of skin of the decision mankind, do not exist only in skin, in hair, eyes, ear, even brain, all there is melanin.The melanin of skin is generated by melanocyte, but according to the difference of ethnic group, it is different that melanin generates gene, decides the colour of skin by regulating the amount of melanocyte.Few or the non-existent albinism (albino) of melanocyte has been found in Some Animals or people.Melanin is multiple micromolecular aggregations, of a great variety, such as pheomelanin (pheomelanin) and eumelanin (eumelanin) are found in skin and the hair of people, and based on eumelanin, the deficiency of above-mentioned eumelanin causes albinic main cause.
The appropriate melanin be present in skin can absorb ultraviolet, has and makes people healthy and have the good effects such as glamour, but melanism, skin can be made to seem dim, cause appearance plain.In addition, melanic surplus generates melanism or the pigmentosa dermatosis such as speckle, freckle that also can cause skin.Usually, the mistake pigementation of skin is that the external essential factor such as inherent essential factor and/or excessive ultraviolet radiation of hormone exception, hereditary etc. causes.
As everyone knows, in pigementation in the process of skin, the ferment being called as tryrosinase (tyrosinase) is had an effect, and by a series of oxidizing process, generates excessive melanin polymer, is accumulated in skin.Tryrosinase is generating the polymeric intermediate material of melanin, i.e. DOPA (DOPA using converting to as amino acid whose a kind of tyrosine (tyrosine), 3,4-dihydroxy phenylalanine), very important ferment in the melanin generative process of DOPA quinone (DOPA-quinone).In addition, the activity of the ferment generated by the generation or suppression suppressing above-mentioned tryrosinase, can regulate melanin to generate.
From object cosmetically or the object for the treatment of dermatosis, unremitting effort the composition with skin whitening effects is studied, as one of method wherein, make great efforts in a sustained way to excavate the material of the activity of the generation that can suppress to relate to major enzyme, i.e. tryrosinase that melanin generates or the tryrosinase generated.Given this situation, resveratrol and oxidized resveratrol are as the composition extracted from natural materials, little to harm, check melanin generate excellent effect, as skin-whitening compositions candidate and extensively know.But the chemical stability of these compounds is not guaranteed, be difficult to cosmetics or the pharmaceutical compositions dosage form as more than some months can be preserved.In order to solve this problem, attempt the effort such as the new dosage form of exploitation, but currently all also do not realize reliable complete countermeasure.
Summary of the invention
Technical problem
The present inventor in order to find out harmless as resveratrol or oxidized resveratrol and there is excellent white-skinned face function, chemical stability increases, the material that can take care of for a long time after dosage form; that carries out furtheing investigate found that; the compound that these compound acetyl are obtained; demonstrate above-mentioned effect, thus complete the present invention.
Technological means
One object of the present invention is, provides a kind of cosmetic combination, wherein, as effective ingredient, containing resveratrol or its hydroxy derivatives, acetyl derivatives or its cosmeceutical allow the salt that uses.
Another object of the present invention is to, a kind of cosmetics containing above-mentioned cosmetic combination are provided.
Another object of the present invention is to, a kind of skin-whitening pharmaceutical compositions is provided, wherein, as effective ingredient, containing resveratrol or its hydroxy derivatives, acetyl derivatives or its salt pharmaceutically allowing to use.
Another object of the present invention is to, a kind of skin preparations for extenal use containing above-mentioned skin-whitening pharmaceutical compositions is provided.
Another object of the present invention is to, a kind of skin-whitening method is provided, comprises such step: by resveratrol or its hydroxy derivatives, acetyl derivatives or its salt pharmaceutically allowing to use, drop into the individuality needing it.
Another object of the present invention is to, a kind of tetra-acetylated oxidized resveratrol compound possessing skin whitening effects is provided.
Technique effect
Based on triacetyl resveratrol of the present invention and tetra-acetylated oxidized resveratrol; compared to compound, the i.e. resveratrol before its acetylation and tetra-acetylated oxidized resveratrol; while the whitening effect of quite level can be kept; chemical stability is more excellent, can use as whitening cosmetic preparation and pharmaceutical compositions.
Accompanying drawing explanation
Fig. 1 illustrates the reaction equation from preparing triacetyl resveratrol (III) and tetra-acetylated oxidized resveratrol (IV) respectively based on resveratrol of the present invention (I) or oxidized resveratrol (II).
Fig. 2 illustrates the HPLC chromatogram of resveratrol (I), oxidized resveratrol (II), triacetyl resveratrol (III) and tetra-acetylated oxidized resveratrol (IV).
Fig. 3 illustrates the UV absorption spectra of resveratrol (I), oxidized resveratrol (II), triacetyl resveratrol (III) and tetra-acetylated oxidized resveratrol (IV).
Fig. 4 (a) illustrates resveratrol (I)
1hNMR composes, and Fig. 4 (b) illustrates oxidized resveratrol (II)
1hNMR composes, and Fig. 4 (c) illustrates triacetyl resveratrol (III)
1hNMR composes, and Fig. 4 (d) illustrates tetra-acetylated oxidized resveratrol (IV)
1hNMR composes.
Fig. 5 (a) illustrates resveratrol (I)
13cNMR composes, and Fig. 5 (b) illustrates oxidized resveratrol (II)
13cNMR composes, and Fig. 5 (c) illustrates triacetyl resveratrol (III)
13cNMR composes, and Fig. 5 (d) illustrates tetra-acetylated oxidized resveratrol (IV)
13cNMR composes.
Fig. 6 (a) illustrates the quality analysis results of resveratrol (I); Fig. 6 (b) illustrates the quality analysis results of oxidized resveratrol (II); Fig. 6 (c) illustrates the quality analysis results of triacetyl resveratrol (III), and Fig. 6 (d) illustrates the quality analysis results of tetra-acetylated oxidized resveratrol (IV).
Fig. 7 illustrates the result carrying out processing rear mensuration cell survival for B16/F10 cell (A) and HEMs cell (B) respectively according to each concentration of resveratrol, oxidized resveratrol, triacetyl resveratrol and tetra-acetylated oxidized resveratrol.
Fig. 8 is the result carrying out processing rear mensuration melanin amount for B16/F10 cell (A) and HEMs cell (B) respectively according to each concentration of resveratrol, oxidized resveratrol, triacetyl resveratrol and tetra-acetylated oxidized resveratrol.
Detailed description of the invention
As a kind of mode for realizing above-mentioned purpose, the invention provides a kind of cosmetic combination, as effective ingredient contain resveratrol or its hydroxy derivatives, acetyl derivatives or its cosmeceutical allow the salt that uses.
Above-mentioned cosmetic combination has skin whitening effects.Term of the present invention " whitening " refers to, even if continuous skin is by ultraviolet radiation, melanocyte increases, and melanin also can be prevented exceedingly to be deposited in skin, or make settled melanin thinning.Thereby, it is possible to suppress the generation of speckle or the freckle caused by excessive melanic precipitation.
Based on above-mentioned acetyl derivatives of the present invention compared to the reactant before acetylation, chemical stability increases, even if so at high temperature take care of for a long time, also can not variable color, and the content of effective ingredient remains constant.
Resveratrol (Resveratrol) is that IUPAC is called 5-[2-(4-hydroxyphenyl) vinyl] benzene-1,3-glycol (5-[2-(4-hydroxyphenyl) ethenyl] benzene-1, compound 3-diol), above-claimed cpd can also represent with following another name.3,5,4'-trihydroxy-trans-stilbene (3,5,4'-trihydroxy-trans-stilbene); Trans-3,5,4'-resveratrols (trans-3,5,4'-Trihydroxystilbene); 3,4', 5-resvertrol (3,4', 5-Stilbenetriol); Trans-res-veratrol (trans-Resveratrol); (E)-5-(p-hydroxystyrene based) Benzodiazepines ((E)-5-(p-Hydroxystyryl) resorcinol); (E)-5-(4-Vinyl phenol base) benzene-1,3-glycol ((E)-5-(4-hydroxystyryl) benzene-1,3-diol).
Above-mentioned resveratrol can, to the pathogen such as antibacterium or mycete, be by the spontaneous phytoalexin of various plants (phytoalexin), is one, the i.e. stilbene compound (stilbenoid) that are present in natural phenols.Above-mentioned stilbene compound chemically aspect is the hydroxylation derivative (hydroxylated derivatives) of stilbene (stilbene), from the viewpoint of biology, it is the compound belonging to the Phenylpropanoid Glycosides (phenylpropanoids) relevant with utilizing the most Biosynthetic pathway of chalcone derivative (chalcone).Contain in a large number in the peel and other fruit of Radix seu Herba Tetrastigmatis Hypoglauci, can extract from them, or the microorganism utilizing chemical or metabolism to be conditioned, synthesized by life sciences method and use.
Current, the multi-effect produced on humans and animals for resveratrol is studied.Known effect is improved the life-span, but this is still had to the leeway of discussion.By the experiment to Mouse and rat, also confirm anticancer, antiinflammatory, blood sugar lowering and other useful relate to cardiovascular effect.But, to the effect that people produces, although it is useful for can understanding substantially, clear and definite not enough.Such as, with improve organism synthesize resveratrol prepared by object with very high consumption (3 to 5g) administration time, confirm significant blood glucose and reduce effect.Further, also know that it has anti-aging effects, but still lack scientific evidence.Research for resveratrol is also in introduction stage, does not also know its long-term effect to the mankind.
The hydroxy derivatives preferential oxidation resveratrol (Oxyresveratrol) of above-mentioned resveratrol.Above-mentioned oxidized resveratrol is that IUPAC is called 4-[(E)-2-(3,5-dihydroxyphenyl) vinyl] benzene-1,3-glycol (4-[(E)-2-(3,5-dihydroxyphenyl) ethenyl] benzene-1, compound 3-diol), above-claimed cpd also can represent with another name below.2,3 ', 4,5 '-tetrahydroxy-trans-stilbene (2,3 ', 4,5 '-Tetrahydroxy-trans-stilbene); 2,3 ', 4,5 '-tetrahydroxystilbene (2,3 ', 4,5 '-Tetrahydroxystilbene); 4-[(E)-2-(3,5-dihydroxyphenyl) vinyl] Benzodiazepines (4-[(E)-2-(3,5-dihydroxyphenyl) vinyl] resorcinol); Tetrahydroxystilbene (tetrahydroxystilbene).
Above-mentioned oxidized resveratrol is a kind of stilbene compound of the heartwood (heartwood) being present in Yunnan Fructus Artocarpi Heterophylli (Artocarpus lakoocha), is the raw material of traditional medicine " Puag-Haad ".Further, be the aglycon (aglycone) setting compound, the i.e. Mulberroside A (mulberrosideA) existed in (whitemulberry) known mulberry (Morusalba) as Morus alba.Oxidized resveratrol can extract from natural materials or adopt chemical method synthesis and use.Its tyrosinase inhibitor as potentiality and extensively being known.
In the present invention; although above-mentioned resveratrol or its hydroxy derivatives have skin whitening effects; but make to be difficult to use as skin-whitening compositions because of its distinctive chemical instability; the present invention is conceived to this, in order to realize can keeping or increase skin whitening effects, gives stability simultaneously; in fact can use as skin-whitening compositions; that carries out furtheing investigate found that, if be formed as acetyl derivatives, then can meet above-mentioned condition.And; when containing the acetyl derivatives of the acetyl derivatives of above-mentioned resveratrol or the hydroxy derivatives of resveratrol as effective ingredient; in order to can actually use; be prepared into cosmetic combination or skin-whitening pharmaceutical compositions described below, thus can effectively utilize.
The preferred triacetyl resveratrol (Triacetylresveratrol) of acetyl derivatives of above-mentioned resveratrol.Above-mentioned triacetyl resveratrol can be represented as again trans-triacetyl resveratrol (trans-Triacetylresveratrol); Acetyl group-resveratrol (Acetyl-resveratrol); Acetyl group-trans-res-veratrol (Acetyl-trans-resveratrol); Trans-res-veratrol triacetate (trans-resveratroltriacetate); 5-[(1E)-2-[4-(acetoxyl group) phenyl] vinyl]-1,3-Benzenediol-1,3-diacetin (5-[(1E)-2-[4-(Acetyloxy) phenyl] ethenyl]-1,3-benzenediol-1,3-diacetate); 4-[(E)-2-(3,5-diacetoxy phenyl) vinyl] phenyl acetate salt (4-[(E)-2-(3,5-Diacetoxphenyl) vinyl] phenylacetate); Resveratrol 3,5,4'-triacetate (Resveratrol3,5,4'-triacetate); 3,5,4'-tri--O-acetylation resveratrol (3,5,4'-Tri-O-acetylresveratrol); 3,5,4'-triacetoxyl group-trans-stilbene (3,5,4'-triacetoxy-trans-stilbene; With trans-3,5,4'-triacetoxyl group stilbene (trans-3,5,4'-Triacetoxystilbene), can also represent with the structural formula of following chemical formula 1.
[chemical formula 1]
In addition, the acetyl derivatives of the hydroxy derivatives of above-mentioned resveratrol is preferably tetra-acetylated oxidized resveratrol (tetraacetyl oxyresveratrol).Above-mentioned tetra-acetylated oxidized resveratrol also can be called as acetyl group-oxidized resveratrol (acetyl-oxyresveratrol); Trans-tetra-acetylated oxidized resveratrol (trans-Tetraacetyloxyresveratrol); Acetyl group-trans-oxidized resveratrol (acetyl-trans-oxyresveratrol); Trans-oxidized resveratrol tetraacetate (trans-oxyresveratroltetraacetate); 4-[(E)-2-(3,5-diacetoxy phenyl) vinyl] benzene-1,3-diacetin (4-[(E)-2-(3,5-diacetoxyphenyl) ethenyl] benzene-1,3-diacetate); 2,3 ', 4,5 '-tetrem acetoxy-trans-stilbene (2,3 ', 4,5 '-Tetraacetoxy-trans-stilbene); 2,3 ', 4,5 '-four acetoxyl group stilbene (2,3 ', 4,5 '-Tetraacetoxystilbene); And four acetoxyl group stilbenes (tetraacetoxystilbene) etc., can also represent with the structural formula of following chemical formula 2.
[chemical formula 2]
According to a particular embodiment of the invention; triacetyl resveratrol and tetra-acetylated oxidized resveratrol are from dosage form; chemical stability than the compound before acetylation, i.e. resveratrol and oxidized resveratrol more excellent; even if at high temperature preserve for a long time, also can not variable color, under the state keeping certain content; when being applicable to human body; decomposed by ester amylase (esterase), be converted into resveratrol and oxidized resveratrol respectively, demonstrate whitening active.In addition, in disposable developmental tube, carry out test cell line, confirm cytotoxicity low, be applicable to human body, harmless, demonstrate excellent white-skinned face function, be judged as to use as skin-whitening cosmetic preparation and pharmaceutical compositions.
As the effective ingredient of compositions of the present invention, above-mentioned resveratrol or its hydroxy derivatives, acetyl derivatives can use its cosmeceutical to allow the form of the salt used.As salt, the sour additional salt formed by allowing the free acid (freeacid) of use on cosmeceutical is useful.Acid additional salt can adopt usual way to prepare: such as, by compound dissolution in excessive aqueous acid, utilize water-soluble organic solvent, such as this salt precipitates by methanol, ethanol, acetone or acetonitrile, thus preparation.By the acid in the compound of same molar and water or alcohol (such as, glycol monoethyl ether) heating, then by said mixture evaporation drying, or suction filtration is carried out to the salt of separating out.Now, as free acid, organic acid and mineral acid can be used, as mineral acid, hydrochloric acid can be used, phosphoric acid, sulphuric acid, nitric acid, tartaric acid etc., as organic acid, methanesulfonic acid can be used, p-toluenesulfonic acid, acetic acid, trifluoroacetic acid, maleic acid (maleic acid), succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid (fumaricacid), mandelic acid, propanoic acid (propionic acid), citric acid (citric acid), lactic acid (lacticacid), glycolic (glycollic acid), gluconic acid (gluconic acid), galacturonic acid (
galacturonic acid), glutamic acid (glutamic acid), glutaric acid (glutaric acid), glucuronic acid (glucuronic acid), aspartic acid, vitamin C, carbonic acid, vanillic acid (Vanillicacid), hydroiodic acid (hydroiodic acid) etc., but to be not limited thereto.
Further, alkali can be utilized to be prepared in slaine cosmeceutical allowing use.Alkali metal or alkali salt are usually as under type obtains: such as, by compound dissolution in excessive alkali metal hydroxide or alkaline earth metal hydroxide solution, after non-dissolved compound salt is filtered, filtrate is evaporated, carry out drying, thus obtain alkali metal or alkali salt.Silver salt is correspondingly by being undertaken reacting by alkali metal or alkali salt and appropriate silver salt (such as, silver nitrate) and obtain.
For above-mentioned resveratrol or its hydroxy derivatives, the salt allowing to use on cosmeceutical of acetyl derivatives; in case of no particular description, the salt of acidity in the most acetyl derivatives that can be present in resveratrol or its hydroxy derivatives or alkalescence is comprised.Such as, cosmeceutical allows the salt used, comprises the sodium of hydroxyl, calcium and potassium salt etc.; As amino other from pharmaceutically allow use salt, comprise hydrobromate, sulfate, disulfate, phosphate, hydrophosphate, dihydric phosphate, acetate, succinate, citrate, tartrate (tartrate), lactate (lactate), mandelate (mandelate), mesylate (methanesulphonate), methoxide (methylate) and p-toluene fulfonate (toluenesulfonate) etc., can by well known to a person skilled in the art prepared by the preparation method of salt.
In cosmetic combination of the present invention, relative to whole compositions, the content of above-mentioned effective ingredient is 0.001 to 5 % by weight, is preferably 0.01 to 5 % by weight.
Based on cosmetic combination of the present invention, cosmetic preparation excipient can also be contained.In the scope not damaging effect of the present invention, i.e. skin whitening effects, as auxiliary element, can containing the known composition used in common cosmetics, such as wetting agent, powdered ingredients, UV absorbent, oxidant, Cosmetic Ingredient, glycolipid matter, plant extraction liquid, antiseptic, spice, pH adjusting agent, pigment, viscosity modifier or gellant etc.
As the not limiting example of wetting agent, can be propylene glycol, Isopropanediol, 1, the reduzate of the di-alcoholss such as 2-heptandiol, 1,3 butylene glycol, dipropylene glycol, hexanediol, Polyethylene Glycol glycerol, glycerol, two polyglycereol, three polyglycereol, polyglycerol, neopentyl glycol, Sorbitol, erythritol, tetramethylolmethane, glucose, galactose, fructose, sucrose, maltose, xylose, 1,4-.beta.-Xylobiose, oligosaccharide, protein, mucopolysaccharide, collagen protein, elastin laminin, keratin or triethanolamine etc.
As the not limiting example of powdered ingredients, it can be titanium oxide, silicon process titanium oxide, the white inorganic pigment such as zinc oxide and barium sulfate, ferrum oxide, carbon black, the colored inorganic pigment such as titanium titanium oxide sinter and ultramarine, Talcum, silicon process Talcum, white mica, Kaolin, carborundum, bentonite, Montmorillonitum (smectite), anhydrous silicic acid, aluminium oxide, magnesium oxide, zirconium oxide, kieselguhr, calcium silicates, barium silicate, magnesium silicate, calcium carbonate, magnesium carbonate, the white body constitution powder body such as hydroxyapatite and boron nitride, coated by titanium dioxide Muscovitum, ferrum oxide mica titanium, silicon process mica titanium, guanin, polythylene resin, fluorine-type resin, the organic polymer resin powder body such as cellulosic resin and silicone resin, the organic low molecular powder body such as zinc stearate and N-acyl-lysine (acyl lysine), starch, natural organic powder such as silk powder and cellulose powder etc., red No. 201, red No. 202, orange No. 203, orange No. 204, the organic pigment powder body such as No. 404, cyan and No. 401, yellow, red No. 3, red No. 104, red No. 106, orange No. 205, yellow No. 4, Sunset Yellow FCF, the zirconiums such as No. 3, green and No. 1, cyan, the organic powder pigment in barium or aluminum color lake etc., mica powder (mica), the native gold powder body such as bronze, and the composite granule etc. such as micropartical titanium oxide coated mica titanium.
As the not limiting example of UV absorbent, can be benzophenone (benzophenone) derivant, para-amino benzoic acid derivant, methoxycinnamate acid derivative, the acid of urine Canis familiaris L. etc.
As the not limiting example of oxidant, can be BHT, BHA, vitamin c class, vitamin E class, their derivant and their salt etc.
As the not limiting example of Cosmetic Ingredient, can be comprise the vitamins of said vitamin, their derivant and their salt, antiinflammatory and former medicine etc.
As the not limiting example of glycolipid matter, can be sphingol glycolipid matter etc.
As the not limiting example of plant extraction liquid, it can be the extract of aloe vera, Hamamelis virginiana (witchhazel), Radix Hamamelidis Mollis (Hamamelis), Fructus Cucumidis sativi, Fructus Citri Limoniae, lavandula angustifolia (lavender) and Flos Rosae Rugosae etc.
As the not limiting example of antiseptic, can be methyl parahydroxybenzoate, ethylparaben, butyl p-hydroxybenzoate, propyl p-hydroxybenzoate, phenyl phenol and ethanol etc.
As the not limiting example of spice, can be Oleum Camphora, Oleum Citri tangerinae, Oleum menthae, jasmin quintessence oil (jasminumabsolute), Oleum Pini, lime oil, Essential lavender oil, Oleum Rosae Rugosae and Moschus wet goods.
As the not limiting example of pH adjusting agent, can be edetic acid, edetate sodium, sodium chloride, citric acid, sodium citrate, sodium hydroxide, potassium hydroxide and triethanolamine etc.
As the not limiting example of pigment, can be No. 1, cyan, No. 204, cyan, No. 3, redness and No. 201, yellow etc.
As the not limiting example of viscosity modifier, can be polyvinyl alcohol (PVA), methylcellulose (MC), ethyl cellulose, hydroxypropyl emthylcellulose, Cellulose ethyl hydroxypropyl ether, in addition cellulose derivative, polyvinylpyrrolidone (PVP), carboxymethyl cellulose, xanthan gum, alginic acid or its salt, carrageenin (carrageenan), WENBO kind (Quince Ceed), Alcaligenes polysaccharide, CVP Carbopol ETD2050, acrylates, acrylate copolymer (chain type, cross-linking type) and acrylic arid methacrylic acid copolymer etc.
As the not limiting example of gellant, can be (behenic acid/20 acid) glyceride and (behenic acid/20 acid) Natrulon H-10, fatty acid metal salts, hydroxy stearic acid, dextrin fatty acid ester, inulin fatty acid ester, white sugar fatty acid ester, acetyl fibre two candy (acylationcellubiose), dibenzyl sorbitol, amino acids gellant, anhydrous silicic acid, organically-modified viscosity mineral, smoke-like silicon dioxide, aluminium oxide, cross-linking type organopolysiloxane, the hydrocarbon wax such as Tissuemat E or paraffin, the vegetalitas waxes such as Brazil wax (CarnaubaWax) or candelilla wax (CandelillaWax), cold sky and gel etc.
Any dosage form preparation that cosmetic combination of the present invention can be prepared usually with this area, dosage form can turn to such as solution, suspension, emulsion, mud (paste), condensation, frost, emulsion (lotion), loose powder (powder), soap, the cleansing milk containing surfactant, oil, powder foundations, emulsion foundation cream, wax foundation and spraying etc., but be not limited thereto.In more detail, can with the preparation of the dosage form of flexible astringent, nutrition astringent, frost, nourishing cream, massage cream, essence, eye cream, cleansing cream, cleaning foam, makeup remover, facial film, spraying or loose powder.
In addition, cosmetic combination of the present invention can containing more than the a kind usual carrier allowing to use on cosmeceutical mixed in skin cosmetic, as common composition, suitably can mix oil content, water, surfactant, wetting agent, lower alcohol, thickening agent, chelating agen (chelateagent), pigment, antiseptic, spice etc., but be not limited thereto.
The carrier allowing to use on cosmeceutical comprised in cosmetic combination of the present invention is different according to dosage form.When dosage form of the present invention is mud, frost or condensation, as carrier components, animality oil, plant oil, wax (wax), paraffin (paraffin), starch, tragacanth (tragacanth), cellulose derivative, macrogol, silicon, bentonite, silicon dioxide, Talcum or zinc oxide etc. can be used.
When dosage form of the present invention be powder (powder) or spraying, as carrier components, lactose, Talcum, silicon dioxide, aluminium hydroxide, calcium silicates or polyamide powder can be used, especially, when spraying, Chlorofluorocarbons (CFCs), propyl group/promoter such as butyl or dimethyl ether can also be comprised further.
And, when dosage form of the present invention be solution or emulsion, as carrier components, utilize solvent, solvation or demulsifier, can use such as water, ethanol, isopropyl alcohol, ethyl carbonate ester, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3 butylene glycol, oil, especially, Oleum Gossypii semen, Oleum Arachidis hypogaeae semen, Fructus Maydis oil, olive oil, Oleum Ricini and Oleum sesami, fatty glyceride, macrogol or sorbitan fatty acid ester etc.
And, when dosage form of the present invention is suspension, as carrier components, the diluent of the liquid phases such as water, ethanol or propylene glycol can be used, the suspensions such as ethoxylated isostearyl alcohols (ethoxylationIsostearylAlcohol), polyoxyethylene sorbitol ester and polyoxyethylene sorbitan esters, micro-crystalline cellulose, partially aluminium hydroxide (aluminum metahydroxide), bentonite, agar (agar) or tragacanth etc.
And, when dosage form of the present invention is the cleansing milk containing surfactant, as carrier components, aliphatic alcohol sulfate can be used, fatty alcohol ether sulphate, sulfosuccinic acid monoesters (sulfosuccineic acid mono ester), isethionate, imidazolidine derivatives, N-methyltaurine, sarcosinate (sarcosinate), fatty acid amidogen ether sulfuric ester, alkyl amido betaine (alkylamidobetaine), aliphatic alcohol, fatty glyceride, fatty acid diethanolamine, plant oil, lanolin derivative or ethoxylated glycerol fatty acid ester etc.
Alternatively, the invention provides a kind of cosmetics containing above-mentioned cosmetic combination.
The term " cosmetics " of the invention described above is defined as, and by human body clean, beautifies and makes it more charming, making appearance brighter, or in order to can keep or improve skin, hair health and to human body use product, slight to the effect of human body.
Being preferably based on cosmetics of the present invention is the functional cosmetics with skin whitening effects.Above-mentioned " functional cosmetics " is the cosmetics that given efficacy and effect are strengthened, be contribute to skin-whitening product, improve wrinkle of skin product, make the U.S. black or protection skin of skin by the product of uv damage.
Confirm the effect demonstrating skin-whitening based on cosmetics of the present invention when being applicable to human body, so from needless to say belonging to functional cosmetics.
Cosmetics based on the invention described above dosage form can turn to skin lotion (skinlotion), toner/smoothing toner (skinsoftener), cosmetic water (skintoner), firming lotion (astringent), emulsion, moisturizer (milklotion), moisturizing emulsion (moisturelotion), nutritional emulsions, massage cream, nourishing cream, moisturiser, hand cream, essence, nutrition essence, facial film, fancy soap, shampoo, facial cleansing foam, facial milk cleanser liquid, cleansing cream, body lotion, bath foam, emulsion, press-powder (press powder), loose powder (loose powder) or eye shadow.
Alternatively, the invention provides a kind of acetyl derivatives or its skin-whitening pharmaceutical compositions pharmaceutically allowing the salt used that contain resveratrol or its hydroxy derivatives as effective ingredient.
For above-mentioned effective ingredient; as mentioned above; the hydroxy derivatives of preferred resveratrol is oxidized resveratrol; the acetyl derivatives of above-mentioned resveratrol can be triacetyl resveratrol, and the acetyl derivatives of the hydroxy derivatives of above-mentioned resveratrol can be tetra-acetylated oxidized resveratrol.
The definition of above-mentioned each compound is same as described above.
As the effective ingredient of compositions of the present invention, the acetyl derivatives of above-mentioned resveratrol or its hydroxy derivatives can use with its form of the salt used that pharmaceutically allows.The above-mentioned form of the salt used that pharmaceutically allows is identical with for illustrating of the salt allowing as cosmeceutical to use with preparation method.
In pharmaceutical compositions of the present invention, above-mentioned effective ingredient is relative to whole compositions, and its content is 0.001 to 10 % by weight, is preferably 0.01 to 10 % by weight, is more preferably 0.1 to 10 % by weight.
Pharmaceutical compositions of the present invention can also be included in the excipient pharmaceutically allowing to use.Term of the present invention " pharmaceutically allows to use " and refers to that the cell or people demonstrated being exposed to above-mentioned composition does not have virose characteristic.Above-mentioned carrier can use buffer agent, preservative agent, painless agent, solubilizing agent, isotonic agent, stabilizing agent, base, excipient, lubricant etc., as long as well known in the art, just can use ad lib.And, pharmaceutical compositions of the present invention can turn to the oral class dosage forms such as powder, granule, lozenge, capsule, suspension, Emulsion, syrup, spray (aerosol) according to each usual way dosage form, also can dosage form turn to external preparation, suppository and sterilizing injecting solution form use.In addition, also can use with the form of the skin preparations for extenal use of the form of ointment, emulsion agent, spray, patch, cream, powder, suspension, condensation agent or gel.The carrier that can comprise in compositions of the present invention, excipient and diluent, can use lactose, glucose, sucrose, Sorbitol, mannitol, xylitol, erythritol, maltose alcohol, starch, Radix Acaciae senegalis, alginate, gel, calcium phosphate, calcium silicates, cellulose, methylcellulose, microcrystalline Cellulose, polyvinyl pyrrolidone, water, methyl hydroxybenzoate, nipasol, Talcum, magnesium stearate and mineral oil.When formulation, the diluent such as normally used filler, extender, bonding agent, wetting agent, disintegrating agent, surfactant or excipient is used to regulate.When for oral solid preparation, comprise lozenge, pill, powder, granule, capsule etc., this solid preparation by add in above-mentioned Medulla Tetrapanacis extract at least more than one excipient, such as starch, calcium carbonate (calcium carbonate), sucrose (sucrose) or lactose (lactose), gel etc. and prepare.In addition, except simple excipient, the lubricant such as magnesium citrate, Talcum can also be used.As for oral liquid phase preparation, suspension, interior liquor, Emulsion, syrup etc. can be used, except often use simple diluent, i.e. water, except liquid paraffin, various excipient can also be used, comprise such as wetting agent, sweetener, aromatic, preservative agent etc.For parenteral preparation, comprise sterile water solution, non-aqueous solvent, suspension, Emulsion, freeze-dried preparation, suppository.As non-aqueous solvent, suspension, propylene glycol (propylene glycol), macrogol, Fructus Canarii albi wet goods plant oil can be used, the ester etc. that ethanol ester (ethylate) etc. can be injected.As the bodying agent of suppository, can use dimension too element (witepsol), Polyethylene Glycol (Macrogol), tween (tween) 61, cocoa butter, trilaurin (
laurinum), glycerin gelatine (glycerogelatin) etc.
Alternatively, the invention provides a kind of skin preparations for extenal use containing above-mentioned skin-whitening pharmaceutical compositions.
Term of the present invention " skin preparations for extenal use " refers to the concept comprising the total material being generally used for external preparation for skin, as the not limiting example of dosage form comprising above-mentioned pharmaceutical compositions, can be unguentum (PLASTERS), emulsion agent (LPTIONS), liniment (LINIMENTS), liquor (LIQUIDSANDSOLUTIONS), spray (AEROSOLS), concentrating agents (EXTRACTS), ointment (OINTMENTS), fluid extract (FLUIDEXTRACTS), Emulsion (EMULSIONS), suspension (SUSPESIONS), capsule (CAPSULES), cream (CREAMS), soft or hard capsules, patch, westernization preparation.
Based on skin preparations for extenal use of the present invention, conventional inorganic or organic carrier, excipient and diluent and formulation with form that is semi-solid or liquid phase can be added, by parenteral input.As above-mentioned oral formulations, can be the non-oral dosage forms selected from the group be made up of a drop, ointment, emulsion, condensation, frost, patch, spraying, suspension and Emulsion, but be not limited thereto.
The carrier that above-mentioned external preparation can comprise, excipient and diluent can be lactose, glucose, sucrose, oligosaccharide, Sorbitol, mannitol, xylitol, erythritol, maltose alcohol, starch, Radix Acaciae senegalis, alginate, gel, calcium phosphate, calcium silicates, cellulose, methylcellulose, microcrystalline Cellulose, polyvinyl pyrrolidone, water, methyl hydroxybenzoate, nipasol, Talcum, magnesium stearate and mineral oil.
In the Dermatologic preparation composition based on each dosage form, those skilled in the art easily can select other compositions outside above-mentioned compositions of the present invention to mix according to the dosage form of other skin preparations for extenal use or application target etc., when using with other raw materials simultaneously, likely produce and promote effect.
And, based on compositions of the present invention when using as pharmaceutical compositions, antiseptic, stabilizing agent, wettable powder or emulsification promoter can be contained further, for regulating pharmacy adjuvant and other materials useful in treatment such as salt or buffer agent of osmotic pressure, according to usual way, can with parenteral form dosage form.
It is to be appreciated that the actual input amount of effective ingredient, decide according to age of the serious symptom degree of symptom, selected input path, object, sex, the multiple correlation factors such as body weight and health status.
Usually, the input amount of effective ingredient at 0.001 μ g/kg/ days to roughly 2000 μ g/kg/ days.Preferred input amount be 0.5 μ g/kg/ days to 2.5 μ g/kg/ days.External drops into can once a day, or point drop into several times.
Alternatively, the invention provides a kind of skin-whitening method, comprise by resveratrol or its hydroxy derivatives, acetyl derivatives or its salt used that pharmaceutically allows puts into the step of its individuality of needs.
In the present invention, above-mentioned resveratrol or its hydroxy derivatives, acetyl derivatives or its salt used that pharmaceutically allows demonstrates skin whitening efficacy, so can provide the skin-whitening method of the compositions that make use of containing above-claimed cpd.
Further, according to skin whitening efficacy of the present invention, can prevent or improve the pigementation on skin, can alleviate or eliminate the symptom caused by pigementation.The symptom caused by above-mentioned pigementation comprises macula lutea, freckle, seborrheic keratosis (senile black speck, senile plaque) and inflammation, post-stimulatory pigementation excessively etc.
In the present invention, term " individuality " refers to all animals comprising the mankind needing skin-whitening as above, more particularly, chromogenesis precipitation or can chromogenesis precipitation or occurred symptom by above-mentioned pigementation or likely occurred that the mankind of symptom are at interior all animals is included on skin.And, above-claimed cpd of the present invention or the compositions that comprises this compound are put into individuality, thus effectively can realize skin whitening effects, can prevent or improve the pigementation on skin, or the symptom caused by pigementation can be alleviated or eliminate.Pharmaceutical compositions of the present invention can use together with existing skin-whitening pharmaceutical compositions.
In the present invention, term " input " refers to and provides predetermined material by method suitable arbitrarily to individuality, and above-mentioned input path can be dropped into by any common path that can arrive skin as object.Above-mentioned input can be oral or parenteral, and preferred parenteral input, is more preferably applied to the mode of skin.
In the present invention, method suitable arbitrarily that term " coating " refers to employing makes, based on any means of compositions of the present invention with individual contact skin, to penetrate into for the purpose of skin inside to be made correspondent composition by the method.
As a kind of mode, the invention provides a kind of compound possessing skin whitening effects represented with following chemical formula 2.
[chemical formula 2]
The compound possessing skin whitening effects represented by above-mentioned chemical formula 2 is tetra-acetylated oxidized resveratrol, can be prepared by the acetylization reaction of oxidized resveratrol or esterification.
Term of the present invention " acetylation (acetylation) reaction "; being the reaction being called that acetylation (ethanoylation) is reacted according to IUPAC nomenclature, is the reaction introducing acetyl group functional group (acetyl functional group) in compound.Its result, acetyl group replaces active hydrogen atom, thus prepares the compound that acetoxyl group (acetoxygroup) replaces.Representatively property example, comprises the reaction etc. from salicylic acid synthesis aspirin.Especially, when the reaction of the hydrogen atom of acetyl group substituted hydroxy, generate the acetas of specific form as product.As the acetylizing agent with hydroxyl reaction, can anhydrous acetic acid be used, but be not limited thereto.Above-mentioned acetylization reaction can use method well known in the art, is not particularly limited.
Term of the present invention " esterification (esterification) reaction " refers to and such as carboxylic acid (RCOOH) and alcohol (R'OH) is heated under an acid catalysis and carry out reacting and generate ester (RCOOR') and water (H
2o) reaction.As above-mentioned acid catalyst, concentrated sulphuric acid, hydrochloric acid or p-toluenesulfonic acid (p-toluenesulfonicacids) etc. can be used, also can use dry hydrogen chloride gas, but be not limited thereto.Usually, esterification is comparatively slow, and is reversible reaction, so react by continuing to remove other products, thus suppressing back reaction, improving productive rate.Or, at the ester as product than as the alcohol of reactant and carboxylic, in low-boiling situation, can adopt and collect product by distilling and continue the method for carrying out reacting.Above-mentioned esterification can use method well known in the art, is not particularly limited.
According to a particular embodiment of the invention; the resveratrol and the oxidized resveratrol that make to comprise the hydroxyl reacted of 3 or 4 react with anhydrous acetic acid under pyridine exists; the hydrogen atom of 3 or 4 hydroxyls is all replaced by acetyl group; and generate triacetyl resveratrol and tetra-acetylated oxidized resveratrol (Fig. 1, embodiment 1 and 2).
Detailed description of the invention
Below, in further detail the present invention is described by embodiment.These embodiments, just in further detail the present invention being described, are not to limit the scope of the present invention to these embodiments.
Embodiment 1: triacetyl resveratrol (triacetyl resveratrol; III) preparation
By the resveratrol (resveratrol of 20g; I), after being dissolved in the mixture of pyridine (pyridine) 100g and Glacial acetic acid (aceticanhydride) 200g, 24 hours have been stirred at normal temperatures.The water slowly adding 700g in said mixture mixes, and reactant is precipitated.Filter it, by above-mentioned recycling precipitate, with water cleaning, then heating for dissolving in ethanol 2000g, is placed in room temperature, induced crystallization.Again it is filtered, crystallization is reclaimed, carries out drying, obtain the triacetyl resveratrol (triacetylresveratrol of 22g; III).
Embodiment 2: tetra-acetylated oxidized resveratrol (tetraacetyl oxyreveratrol; IV) preparation
By 20g oxidized resveratrol (oxyresveratrol; II), after being dissolved in the mixture of pyridine (pyridine) 200g and Glacial acetic acid (aceticanhydride) 50g, at 50 DEG C, 3 hours have been stirred.The water slowly adding 750g in said mixture mixes, and reactant is precipitated.Filter it, by above-mentioned recycling precipitate, with water cleaning, then heating for dissolving in ethanol 200g, slowly adds 100g water, is placed in room temperature, induced crystallization.Again it is filtered, crystallization is reclaimed, carries out drying, obtain tetra-acetylated oxidized resveratrol (the tetraacetyl oxyresveratrol of 24g; IV).
Analyze example 1: prepared triacetyl resveratrol and the analysis of tetra-acetylated oxidized resveratrol
In order to confirm the triacetyl resveratrol of preparation in above-described embodiment 1 and 2 and tetra-acetylated oxidized resveratrol, HPLC, UV and NMR is utilized to analyze
1-1:HPLC analyzes
By the analysis that HPLC carries out, make use of the gloomy HPLC system (GilsonInc., Middleton, WI, USA) of the gill being provided with UV/VIS151 detector.Immobile phase employs 5 μm of Hector-MC18 chromatographic column (Hector-MC18 posts; 4.6mm × 250mm; RS tech co., land for growing field crops, Korea S).As mobile phase, employ 0.5% formic acid (formicacid; And acetonitrile (acetonitrile A); B) mixed solution, through 50 minutes, is increased to 100% from 30% with certain slope by the content of B.Flow velocity is 0.8ml per minute, and the determined wavelength of UV detection machine is set as 280nm.By concentration adjustment to 1mM, employ test portion
HPLC analysis result is shown in Fig. 2.Confirm each compound and demonstrate peak value in special retention time (retention time).
1-2: spectrophotometric analysis
The test portion of preparation is dissolved in ethanol, by Shimadzu UV-1650PC spectrophotometer (Shimadzu Corporation, capital of a country, Japan) record UV absorption spectra.
Measurement result is shown in Fig. 3.Each compound demonstrates special absorption spectra, and acetyl derivatives is compared to the reactant before acetylation, and wavelength is more or less short, confirms absorption spectra and is moved.
1-3:NMR analyzes
Prepared test portion is dissolved in acetone-d6, utilizes 500MHz Varian Unity INOVA 500FT-NMR (VarianInc., PaloAlto, CA, USA), obtain
1h-and
13c-NMR composes.With tetramethylsilane (tetramethylsilane) for benchmark, have recorded chemical shift (chemicalshift; δ ppm).Its result is shown in Figure 4 and 5.
1-4:MS analyzes
Utilize Agilent 5975CGC/MSD quality spectrophotometer, measure DIP/MS spectrum, the results are shown in Fig. 6.
Embodiment 3: the white-skinned face function evaluation of triacetyl resveratrol and tetra-acetylated oxidized resveratrol in other developmental tube of cell grade
In order to know the triacetyl resveratrol of preparation and the skin whitening effects of tetra-acetylated oxidized resveratrol in above-described embodiment 1 and 2, confirm to hinder activity and the impact of cell survival and the melanin (melanin) of cell to generate inhibition on tryrosinase (tyrosinase).
In order to confirm the effect of above-claimed cpd in cell rank, buy mice black kind B16F10 cell use from American Type Culture Collecti (American Type Culture Collection) (ATCC).Cell is with containing 10% hyclone (fetal bovine serum; FBS), the DMEM culture medium of 100U/ml penicillin (penicillin) and 0.1mg/ml streptomycin (streptomycin), at the 5%CO of 37 DEG C
2cultivate in incubator.
3-1: in developmental tube, tyrosinase activity hinders effect
Cultured cells is regained, adds cytolysate (10mM Tris-Cl, pH 7.4,120mMNaCl, 25mM KCl, 2mM EGTA, 1mM EDTA, 0.5%Triton X-100, proteolytic enzyme/inhibitor mixture), be placed in and place 45 minutes on ice, after cytoclasis, at 4 DEG C, with 14,000 × g carries out the centrifugalize of 15 minutes, takes out upper liquid, for measuring enzyme activity.
In 96-orifice plate microplate reader, add 0.1M phosphate buffered solutions (pH6.8), as the cytolysate 20 μ g/ml of tryrosinase, 0.5mML-tyrosine (tyrosin), the substances of 1 μM of L-3,4 dihydroxyphenylalanine (DOPA) and various concentration, makes the load of reactant liquor reach altogether
60 minutes have been reacted at 37 DEG C.Utilize microplate reader reader, under absorbing wavelength, the i.e. 490nm of the dopachrome (DOPA chrome) as product, measure OD (optical density (optical density)), have rated enzyme activity.Tyrosinase activity obstruction rate is calculated by following formula.
Tyrosinase activity obstruction rate (%)
=[(OD
contrast/
tryrosinase -OD
experiment/
tryrosinase )/(OD
contrast/
tryrosinase -OD
contrast)] × 100
OD
contrast; Only containing measured value time excipient (vehicle)
OD
contrast/
tryrosinase ; Containing measured value when excipient and tryrosinase
OD
experiment/
tryrosinase ; Containing measured value when test portion and tryrosinase
Result of calculation is shown in following table 1.As shown in table 1, the triacetyl resveratrol prepared by embodiment 1 and 2 and tetra-acetylated oxidized resveratrol, compared to resveratrol and oxidized resveratrol, can hinder the activity of tryrosinase more effectively.Specifically; triacetyl resveratrol and tetra-acetylated oxidized resveratrol are converted to resveratrol and oxidized resveratrol respectively by the ester amylase contained in cytolysate; demonstrating tryrosinase hinders active, and after confirming acetylation, tryrosinase hinders activity to increase further.
On the other hand, in the developmental tube confirming oxidized resveratrol and tetra-acetylated oxidized resveratrol tryrosinase hinder specific activity resveratrol and triacetyl resveratrol higher.
Table 1 [table 1]
Active obstruction rate (%) of tyrosinase
3-2: on the impact of cell survival
Cell survival is measured by trypan exclusion stain (trypan blue exclusion assay).Specifically, utilize B16/F10 melanoma cells and people's epidermal melanocytes (humanepidermal melanocytes of mice, HEMs), to each cell, respectively with after each substances process 3 to 100 μMs, by insulin process, cell is reclaimed, carried out the centrifugalize of 3 minutes with 1200rpm speed.Make cell swim in culture medium, mix according to the ratio of 1:1 with 0.1% trypan blue solution (Sigma-Aldrich).Under the microscope, count by the quantity of hemocytometer (hemocytometer) to the cell be in the dust colored and the cell lived be not colored.
Result is shown in Fig. 7, confirms entirety and does not all possess cytotoxicity at low concentrations.First; to the experimental result of B16/F10 cell; oxidized resveratrol is compared to resveratrol; convenient excellent in cells survival rate; triacetyl resveratrol is compared to resveratrol; tetra-acetylated oxidized resveratrol, compared to oxidized resveratrol, all confirms cytotoxicity lower (A of Fig. 7).And; to the experimental result of HEMs cell; concentration below 30 μMs, the cytotoxicity of triacetyl resveratrol is lower than resveratrol, confirms the cells survival rate (B of Fig. 7) that tetra-acetylated oxidized resveratrol demonstrates the rank similar with oxidized resveratrol.By these results, above-mentioned acetyl derivatives can be known compared to the compound before acetylation, there is excellent stability in cells survival rate.
3-3: the melanin of cell generates inhibition
Utilize the B16/F10 melanoma cells of mice and people's epidermal melanocytes (HEMs) to determine intracellular melanin to generate.For B16/F10 cell, after substances has been managed process in 60 minutes according to concentration other places, 48 hours are have stimulated with the α-MSH of 100nM.For HEMs cell, after substances having been managed 60 minutes according to concentration other places, 48 hours are have stimulated with the TYR of 1.0mM.Replaced medium, carries out 3 above-mentioned steps repeatedly.The melanin 0.1MNaOH generated in cell is extracted 60 minutes in 60 DEG C, measures melanic absorbing wavelength, i.e. 490nm absorbance, carry out quantitatively, by albumen quality standardization.Albumen quality utilizes Bio-Rad DC assay.
Result is shown in Fig. 8, and triacetyl resveratrol and the melanin of tetra-acetylated oxidized resveratrol generate inhibition entirety and compares with oxidized resveratrol with the compound before acetylation, i.e. resveratrol, maintain similar level.Specifically; from the experimental result for B16/F10 cell, resveratrol, oxidized resveratrol, triacetyl resveratrol and tetra-acetylated oxidized resveratrol all can hinder the intracellular melanin amount (A of Fig. 8) increased because of α-MSH effectively.Further, from the experimental result for HEMs cell, resveratrol, oxidized resveratrol, triacetyl resveratrol and tetra-acetylated oxidized resveratrol all can hinder the melanin amount (B of Fig. 8) increased because of TYR effectively.Infer thus and arrive, being directed in cell based on triacetyl resveratrol of the present invention and tetra-acetylated oxidized resveratrol, by being present in intracellular ester amylase, being converted to resveratrol and oxidized resveratrol respectively, can generate by check melanin.
And; as shown in Table 1 above; hinder in effect at tyrosinase activity; confirming oxidized resveratrol and tetra-acetylated oxidized resveratrol has than resveratrol and the stronger obstruction effect of triacetyl resveratrol; but as depicted in figure 8; generate in inhibition at melanin, resveratrol and triacetyl resveratrol demonstrate more remarkable effect compared to oxidized resveratrol and tetra-acetylated oxidized resveratrol.These difference implies that in the process generated at the melanin of T suppression cell, other factors outside tryrosinase participate in some extent.And the white-skinned face function of these materials needs finally to be evaluated by human trial.
Preparation example 1: the preparation of skin-whitening cosmetic combination
Prepare and contained cosmetic combination based on triacetyl resveratrol of the present invention and/or tetra-acetylated oxidized resveratrol as effective ingredient.As comparable group, prepare and contained resveratrol or oxidized resveratrol as effective ingredient or do not use containing the cosmetic combination of mentioned component.Following table 2 shows the content ratio of each composition of prepared cosmetic combination.Experimental group 1 and 2 is prepared containing the triacetyl resveratrol of 0.5% or the cosmetic combination of tetra-acetylated oxidized resveratrol respectively; experimental group 3 and 4 is prepared containing the triacetyl resveratrol of 2.0% or the cosmetic combination of tetra-acetylated oxidized resveratrol respectively, and experimental example 5 prepares the cosmetic combination containing the triacetyl resveratrol of 2.0% and the tetra-acetylated oxidized resveratrol of 2.0%.Comparable group preparation respectively containing 2.0% resveratrol or oxidized resveratrol or not containing the cosmetic combination of any effective ingredient.Employ other compositions with certain content, the content difference of the effective ingredient of above-mentioned use regulates according to the content of the pure water in compositions, to meet total 100%.
Table 2 [table 2]
The composition ratio of cosmetic combination
Embodiment 4: dosage form stability analysis
In order to test the dosage form stability of the cosmetic combination of experimental group 1 to the 5 and comparable group 1 to 3 prepared by above-mentioned preparation example, each compositions is put in cosmetics containers, in 60 DEG C of baking box keepings, every 30 days, quantitative analysis is carried out to effective ingredient, confirm the content of residual effective ingredient, and be with the naked eye confirmed whether variable color.
The quantitative analysis of effective ingredient utilizes the instruments and methods identical with the method recorded in above-mentioned analysis example 1 to carry out.As test portion, by each cosmetic preparation test portion methanol dilution of being prepared by above-mentioned preparation example 1 to 1/100, get
as test portion.
Result is shown in following table 3.The cosmetic combination, the i.e. comparable group 1 and 2 that contain resveratrol or oxidized resveratrol as effective ingredient started variable color occurs after 1 month, and the content of effective ingredient reduces, and reduces to residual quantity lower than 50% after confirming 5 months.On the other hand, contain cosmetic combination, the i.e. experimental group 1 to 5 of triacetyl resveratrol and/or tetra-acetylated oxidized resveratrol as effective ingredient, had not yet to see variable color through 6 months, the content confirming effective ingredient also maintenance to a certain extent.By above dosage form stability analysis result, combine with white-skinned face function evaluation result in other developmental tube of cell grade implemented in above-described embodiment 3, triacetyl resveratrol of the present invention or four acetoxyl group resveratrols are compared with resveratrol or oxidized resveratrol (pyrocatechol dimethyl ether. (veratrole)), the whitening effect of similar degree can be demonstrated in cell rank, can expect, be prepared into cosmetic combination, when high temperature keeping, variable color or content minimizing can not be there is because taking care of for a long time, when being applicable to skin, demonstrate excellent whitening effect.
Table 3 [table 3]
Effective ingredient in cosmetic composition residual quantity in time and whether variable color
Embodiment 5: be applicable to stability test during human body skin
5-1: skin irritation is tested
In order to confirm the human body zest of each cosmetic combination of experimental group and the comparable group prepared by above-mentioned preparation example 1, an irritant test is carried out to human body skin.The cosmetic combination of comparable group 1 and 2 likely be harmful to because of rotten, does not adopt so be suitable in experiment at human body, only with not containing resveratrol and/or oxidized resveratrol and stable comparable group 3 is tested.
Above-mentioned human body is suitable for experiment, with the men and women of health totally 30 objects by name, get appropriate amount (
) each cosmetic combination be positioned over patch test IQ chamber, on back paste 48 hours, then chamber is removed.After removal through the moment of 30 minutes and 24 hours, with the naked eye sentence the change of readding skin condition.The metewand of dermoreaction and corresponding scores are shown in following table 4.
Table 4 [table 4]
Skin irritant test metewand and mark
| Mark | Metewand |
| 0 | Reactionless |
| 1 | There is an erythema |
| 2 | The uniform erythema of intermediate degree |
| 3 | Obvious erythema and edema |
| 4 | Obvious erythema, edema and vesicle |
Remove patch, carry out 1 time after 30 minutes and judge, after 24 hours, carry out secondary judgement, according to following formulae discovery degree of reaction.Stimulation degree for human body skin is represented with the average response degree that 1 time and 2 times judge, is arranged in following table 5.
Stimulation degree
=[(fraction reacted × reaction number)/{ maximum fraction reacted (4) × overall test number (n) }] × 100 × 1/2
Table 5 [table 5]
Based on skin irritant test result of cosmetic combination
As shown in Table 5 above, the average response degree confirming the cosmetic combination of experimental group 1 to 5 and comparable group 3 belongs to low field stimulation in human body skin once stimulates, and all not producing skin stimulates.
5-2: the white-skinned face function for human body skin is tested
Utilize and to confirm when being applied to human body not each experimental group of Diazolidinyl Urea and the cosmetic combination of comparable group 3 by the test of above-mentioned skin irritation, test the white-skinned face function to human body skin, the results are shown in following table 6.
Skin whitening efficacy test carry out in the following way: using the adult men and women of health totally 20 as object, at the both sides inner forearm of subject, stickup comprises the hyaline membrane in the hole of 4 1.5cm × 1.5cm sizes, irradiate the ultraviolet (UVB) of about 2 times of the minimal erythema dose (MED) of each subject, guide the artificial color precipitation of skin.The cosmetic combination of the experimental group 1 to 5 prepared according to above-mentioned preparation example 1 and comparable group 3 is sooner or later coated test position for totally 2 times at pigementation position and continued 8 weeks respectively on the 1st.Evaluation for result is before cosmetic combination uses and after using 8 weeks, utilizes skinanalysis apparatus (Mexameter) and spectrophotometer (spectrophotometer) to have rated the melanin exponential sum colour of skin.The melanin index measured utilizing skinanalysis apparatus is shown in table 6.The melanin index measured before the melanin index measured after using is than use is little, and can be judged as possessing whitening effect, their difference is larger, can be judged as that effect is more excellent.And the cosmetic combination based on experimental group 1 to 5 of the present invention shows remarkable skin whitening effects compared to comparable group 3, and the content confirming effective ingredient is higher, and effect is better.
Table 6 [table 6]
Based on the melanin index that the skin whitening effects of cosmetic combination is tested
For the colour of skin change effect, utilize following formula, by use spectrophotometric determination to L
*, a
*and b
*value calculates ITA ° of (Individual Typological Angle, the individual type angle) value of having reacted the pale degree of skin and evaluates.The value calculated is shown in following table 7, and ITA ° of value is larger, is evaluated as whitening effect more excellent.
ITA°＝arctg[(L
*-50)/b
*]×(180/π)
L
*: luminance factor: bright
B
*: the color factor; Green-yellow
Table 7 [table 7]
Skin whitening efficacy ITA ° of value of cosmetic combination
As shown in Table 7 above, confirm in colour of skin change, the cosmetic combination of experimental group 1 to 5 has the skin whitening effects more excellent than the cosmetic combination of comparable group 3.Especially, confirm the high experimental group 3 and 4 of the content of effective ingredient and experimental group 5 all high for the content of these 2 effective ingredient shown remarkable whitening effect.
Preparation example 2: the skin-whitening preparation of pharmacy Dermatologic preparation composition
Prepare a kind of skin-whitening pharmaceutical compositions, wherein, as effective ingredient, containing the triacetyl resveratrol prepared by embodiments of the invention 1 or 2 and/or tetra-acetylated oxidized resveratrol.The content of above-mentioned effective ingredient and other compositions is shown in following table 8.Adopt the stable dosage forms prepared in this way, be suitable for human body.
Table 8 [table 8]
The skin-whitening composition ratio of pharmacy Dermatologic preparation composition
Claims (20)
1. a cosmetic combination, wherein, as effective ingredient, containing resveratrol or its hydroxy derivatives, acetyl derivatives or its cosmeceutical allow the salt that uses.
2. cosmetic combination according to claim 1, is characterized in that, above-mentioned composition has skin whitening effects.
3. cosmetic combination according to claim 1, is characterized in that, above-mentioned acetyl derivatives is compared to the reactant before acetylation, and chemical stabilization increases.
4. cosmetic combination according to claim 1, is characterized in that, the hydroxy derivatives of above-mentioned resveratrol is oxidized resveratrol.
5. cosmetic combination according to claim 1, is characterized in that, the acetyl derivatives of above-mentioned resveratrol is triacetyl resveratrol.
6. cosmetic combination according to claim 1, is characterized in that, the acetyl derivatives of the hydroxy derivatives of above-mentioned resveratrol is tetra-acetylated oxidized resveratrol.
7. cosmetic combination according to claim 1, is characterized in that, containing the above-mentioned effective ingredient of 0.01 to 5 % by weight.
8. cosmetic combination according to claim 1, is characterized in that, also comprises cosmetic preparation excipient.
9. cosmetics, containing the cosmetic combination described in any one in claim 1-8.
10. a skin-whitening pharmaceutical compositions, wherein, as effective ingredient, containing resveratrol or its hydroxy derivatives, acetyl derivatives or its salt pharmaceutically allowing to use.
11. pharmaceutical compositions according to claim 10, is characterized in that, the hydroxy derivatives of above-mentioned resveratrol is oxidized resveratrol.
12. pharmaceutical compositions according to claim 10, is characterized in that, the acetyl derivatives of above-mentioned resveratrol is triacetyl resveratrol.
13. pharmaceutical compositions according to claim 10, is characterized in that, the acetyl derivatives of the hydroxy derivatives of above-mentioned resveratrol is tetra-acetylated oxidized resveratrol.
14. pharmaceutical compositions according to claim 10, is characterized in that, containing the above-mentioned effective ingredient of 0.1 to 10 % by weight.
15. pharmaceutical compositions according to claim 10, is characterized in that, are also included in the excipient pharmaceutically allowing to use.
16. 1 kinds of skin preparations for extenal use, the skin-whitening pharmaceutical compositions described in any one containing claim 10-15.
17. 1 kinds of skin-whitening methods, comprise such step: by resveratrol or its hydroxy derivatives, acetyl derivatives or its salt pharmaceutically allowing to use, drop into the individuality needing it.
18. skin-whitening methods according to claim 17, above-mentioned input is applied to skin.
19. 1 kinds of compounds with skin whitening effects, are represented by following chemical formula 2,
20. want the compound described in 19 according to right, and above-claimed cpd is prepared by the acetylization reaction of oxidized resveratrol or esterification.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR20130007171A KR101480600B1 (en) | 2013-01-22 | 2013-01-22 | A use for skin whitening of resveratrol derivatives |
| KR10-2013-0007171 | 2013-01-22 | ||
| PCT/KR2014/000619 WO2014116022A1 (en) | 2013-01-22 | 2014-01-22 | Use of resveratrol derivative for skin whitening |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104994831A true CN104994831A (en) | 2015-10-21 |
Family
ID=51227766
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201480005704.6A Pending CN104994831A (en) | 2013-01-22 | 2014-01-22 | Use of a resveratrol derivative for skin whitening |
Country Status (4)
| Country | Link |
|---|---|
| JP (1) | JP6219410B2 (en) |
| KR (1) | KR101480600B1 (en) |
| CN (1) | CN104994831A (en) |
| WO (1) | WO2014116022A1 (en) |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106265488A (en) * | 2016-09-19 | 2017-01-04 | 乐山职业技术学院 | Resveratrol external-use gel and preparation method thereof |
| CN107802559A (en) * | 2017-12-14 | 2018-03-16 | 广州市科能化妆品科研有限公司 | Lightening compositions and its production and use |
| CN108159027A (en) * | 2018-03-05 | 2018-06-15 | 天津中医药大学 | It is a kind of to cooperate with composition for inhibiting MITF and TRP1 and application thereof |
| CN109071389A (en) * | 2016-03-07 | 2018-12-21 | Elc 管理有限责任公司 | Resveratrol ethyl glycolate and tartrate derivative and its synthetic method |
| US10188590B2 (en) | 2015-06-16 | 2019-01-29 | Hong Kong Baptist University | Skin-protection composition containing Dendrobium-based ingredients |
| CN109464296A (en) * | 2018-11-19 | 2019-03-15 | 拉芳家化股份有限公司 | A kind of reparation cream of the triacetate containing resveratrol |
| CN109890383A (en) * | 2016-08-24 | 2019-06-14 | 株式会社爱茉莉太平洋 | Include the chloro- N- of 3- [trans- -4-(methylamino) cyclohexyl]-N- [[3-(4- pyridyl group) phenyl] methyl] composition for whitening skin of benzo [b] thiophene-2-carboxamide derivatives |
| CN109937029A (en) * | 2017-04-24 | 2019-06-25 | 汤姆凯特国际有限公司 | The combination and method of anti-aging sign |
| TWI732967B (en) * | 2016-11-15 | 2021-07-11 | 香港浸會大學 | Skin-protection composition containing dendrobium-based ingredients |
| CN113580797A (en) * | 2021-07-16 | 2021-11-02 | 硕包科技(扬州)有限公司 | Film multilayer three-dimensional pattern anti-counterfeiting printing process with prism refraction function |
| CN114748399A (en) * | 2022-03-28 | 2022-07-15 | 深圳润邦之家生物科技有限公司 | Plant anti-wrinkle cosmetic cream and preparation method thereof |
| CN114886825A (en) * | 2022-04-29 | 2022-08-12 | 深圳润邦之家生物科技有限公司 | Sun-screening wrinkle-removing beauty cream and preparation method thereof |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102325943B1 (en) * | 2014-08-07 | 2021-11-12 | (주)주환바이오.셀 | Composition having improved light stability of peanut sprout extract |
| KR101971767B1 (en) * | 2015-09-30 | 2019-04-23 | 경북대학교 산학협력단 | Use of resveratrol derivatives for preventing the skin aging |
| US11219222B2 (en) | 2016-01-21 | 2022-01-11 | Penta 5 USA, LLC | Topical mosquito control product |
| US11045414B2 (en) | 2016-01-21 | 2021-06-29 | Penta 5 USA, LLC | Topical mosquito control product |
| WO2017127799A1 (en) * | 2016-01-21 | 2017-07-27 | Penta 5 USA, LLC | Topical mosquito control product |
| US10851042B2 (en) | 2016-03-07 | 2020-12-01 | Elc Management Llc | Solubization of resveratrol glycolate and tartrate derivatives |
| WO2018118059A1 (en) * | 2016-12-22 | 2018-06-28 | Muhammed Majeed | Novel method for extraction of oxyresveratrol from artocarpus hirsutus |
| US11103465B2 (en) * | 2017-11-22 | 2021-08-31 | Ted's Brain Science, Inc. | Trans-resveratrol topical medication for the treatment of pain and method of manufacture thereof |
| AU2019282691A1 (en) | 2018-06-05 | 2020-12-24 | Flagship Pioneering Innovations V, Inc. | Active agents and methods of their use for the treatment of metabolic disorders and nonalcoholic fatty liver disease |
| JP6757012B1 (en) * | 2020-03-03 | 2020-09-16 | マイスターバイオ株式会社 | Bisel containing a compound having a rigid chemical structure and an external composition containing it |
| JPWO2023008218A1 (en) * | 2021-07-28 | 2023-02-02 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1794967A (en) * | 2003-05-26 | 2006-06-28 | 安普拉尼株式会社 | Whitening and antioxidative cosmetic composition containing resveratrol and method for preparing the same |
| CN101264069A (en) * | 2007-03-14 | 2008-09-17 | 中南大学 | Application of resveratrol derivative in preparing medicine for treating disease relative to immune |
| CN103086884A (en) * | 2012-12-14 | 2013-05-08 | 湖南科源生物制品有限公司 | Method for semi-synthesis of resveratrol |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2502318B2 (en) * | 1987-07-31 | 1996-05-29 | ポーラ化成工業株式会社 | Whitening cosmetics |
| FR2766176B1 (en) * | 1997-07-15 | 1999-10-29 | Caudalie | COMPOSITIONS BASED ON RESVERATROL DERIVATIVES |
| US6270780B1 (en) * | 1997-07-25 | 2001-08-07 | Chesebrough-Pond's Usa Co., Division Of Conopco | Cosmetic compositions containing resveratrol |
| DE102004047118A1 (en) * | 2004-09-27 | 2006-04-06 | Celanese Emulsions Gmbh | Polymer dispersions with fungicidal activity and their use |
| FR2887251B1 (en) * | 2005-06-17 | 2008-02-01 | Rhodia Chimie Sa | BIOPRECURSEUR BASED ON POLYPHENOL |
| BRPI0705319A2 (en) * | 2007-07-23 | 2009-07-21 | Uniao Brasileira De Educacao Manedora Da Pucrs | process for obtaining a soluble resveratrol complex and / or derivatives thereof; resveratrol complex and / or derivatives thereof; nutraceutical composition |
| ES2685094T3 (en) * | 2007-07-31 | 2018-10-05 | Elc Management Llc | Cosmetic compositions containing resveratrol |
| US20090047309A1 (en) * | 2007-08-13 | 2009-02-19 | Maes Daniel H | Cosmetic methods and compositions for repairing human skin |
| KR100971631B1 (en) | 2008-03-31 | 2010-07-22 | 코스맥스 주식회사 | Lipophilic nanocapsulepowder containing Dihydroquercetin and its cosmetic compositions |
| US20110229536A1 (en) * | 2008-05-12 | 2011-09-22 | Tagra Biotechnologies Ltd. | Compositions for topical application comprising microencapsulated colorants |
| BRPI0900400B1 (en) * | 2009-02-10 | 2017-12-19 | União Brasileira De Educação E Assistência | COMPOSITION UNDERSTANDING VEGETABLE OIL AND RESVERATROL AND PROCESS FOR PRODUCING THEM |
-
2013
- 2013-01-22 KR KR20130007171A patent/KR101480600B1/en active IP Right Grant
-
2014
- 2014-01-22 JP JP2015555096A patent/JP6219410B2/en active Active
- 2014-01-22 CN CN201480005704.6A patent/CN104994831A/en active Pending
- 2014-01-22 WO PCT/KR2014/000619 patent/WO2014116022A1/en active Application Filing
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1794967A (en) * | 2003-05-26 | 2006-06-28 | 安普拉尼株式会社 | Whitening and antioxidative cosmetic composition containing resveratrol and method for preparing the same |
| CN101264069A (en) * | 2007-03-14 | 2008-09-17 | 中南大学 | Application of resveratrol derivative in preparing medicine for treating disease relative to immune |
| CN103086884A (en) * | 2012-12-14 | 2013-05-08 | 湖南科源生物制品有限公司 | Method for semi-synthesis of resveratrol |
Non-Patent Citations (1)
| Title |
|---|
| 伍春: "《西南大学硕士学位论文》", 2 June 2012 * |
Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10188590B2 (en) | 2015-06-16 | 2019-01-29 | Hong Kong Baptist University | Skin-protection composition containing Dendrobium-based ingredients |
| CN109071389A (en) * | 2016-03-07 | 2018-12-21 | Elc 管理有限责任公司 | Resveratrol ethyl glycolate and tartrate derivative and its synthetic method |
| CN109890383A (en) * | 2016-08-24 | 2019-06-14 | 株式会社爱茉莉太平洋 | Include the chloro- N- of 3- [trans- -4-(methylamino) cyclohexyl]-N- [[3-(4- pyridyl group) phenyl] methyl] composition for whitening skin of benzo [b] thiophene-2-carboxamide derivatives |
| CN109890383B (en) * | 2016-08-24 | 2022-06-07 | 株式会社爱茉莉太平洋 | Composition for skin whitening |
| CN106265488A (en) * | 2016-09-19 | 2017-01-04 | 乐山职业技术学院 | Resveratrol external-use gel and preparation method thereof |
| TWI732967B (en) * | 2016-11-15 | 2021-07-11 | 香港浸會大學 | Skin-protection composition containing dendrobium-based ingredients |
| CN109937029A (en) * | 2017-04-24 | 2019-06-25 | 汤姆凯特国际有限公司 | The combination and method of anti-aging sign |
| CN107802559A (en) * | 2017-12-14 | 2018-03-16 | 广州市科能化妆品科研有限公司 | Lightening compositions and its production and use |
| CN108159027A (en) * | 2018-03-05 | 2018-06-15 | 天津中医药大学 | It is a kind of to cooperate with composition for inhibiting MITF and TRP1 and application thereof |
| CN109464296A (en) * | 2018-11-19 | 2019-03-15 | 拉芳家化股份有限公司 | A kind of reparation cream of the triacetate containing resveratrol |
| CN113580797A (en) * | 2021-07-16 | 2021-11-02 | 硕包科技(扬州)有限公司 | Film multilayer three-dimensional pattern anti-counterfeiting printing process with prism refraction function |
| CN113580797B (en) * | 2021-07-16 | 2023-03-07 | 硕包科技(扬州)有限公司 | Film multilayer three-dimensional pattern anti-counterfeiting printing process with prism refraction function |
| CN114748399A (en) * | 2022-03-28 | 2022-07-15 | 深圳润邦之家生物科技有限公司 | Plant anti-wrinkle cosmetic cream and preparation method thereof |
| CN114886825A (en) * | 2022-04-29 | 2022-08-12 | 深圳润邦之家生物科技有限公司 | Sun-screening wrinkle-removing beauty cream and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2014116022A1 (en) | 2014-07-31 |
| JP6219410B2 (en) | 2017-10-25 |
| KR101480600B1 (en) | 2015-01-08 |
| JP2016506925A (en) | 2016-03-07 |
| KR20140094394A (en) | 2014-07-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104994831A (en) | Use of a resveratrol derivative for skin whitening | |
| CN100484509C (en) | Use of C-glycosides for depigmenting skin | |
| WO2009122046A1 (en) | Crocus sativus depigmenting composition | |
| KR101071414B1 (en) | Composition for Whitening Containing Extract of Annona muricata as an active ingredient | |
| JPH0930954A (en) | Beautifying and whitening dermal preparation for external use | |
| JP2010100554A (en) | Melanin formation inhibitor | |
| KR100602684B1 (en) | Cosmetic composition comprising extract of erigeron breviscapus for whitening | |
| KR101299024B1 (en) | Cosmetics composition for skin lightening color, antioxidantsand and method for preparing the same | |
| KR101289813B1 (en) | Composition for anti-wrinkle comprising an extract of Sophora japonica L., Leguminosae | |
| JP2010047497A (en) | Elastin production promoting agent | |
| JP5463667B2 (en) | Topical skin preparation | |
| WO2018053706A1 (en) | Composition comprising paeoniflorin or albiflorin analogue, method of preparation thereof | |
| KR100894714B1 (en) | Extract of humata tyermanni moore having skin whitening and anti-oxidative activation | |
| KR100865071B1 (en) | Composition comprising the saururus chinensis extract or compound isolated therefrom for skin whitening | |
| JPH0812566A (en) | Inhibitor of tyrosinase activity | |
| JP2007106675A (en) | Skin whitening agent | |
| CN101027041B (en) | Skin whitening agent | |
| JPH0987164A (en) | Skin preparation for external use | |
| JP2009184997A (en) | Collagen production promoter | |
| CN102438641B (en) | Elastase inhibitor | |
| JPH0812561A (en) | Beautifying and whitening skin preparation for external use | |
| JPH0930949A (en) | Beautifying and whitening dermal preparation for external use | |
| JP2011157319A (en) | Melanin production inhibitor | |
| KR102289135B1 (en) | Herbal medicine mixed extract and uses therof | |
| JPH0987135A (en) | Dermal preparation for external use |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20151021 |