CN1224345A - Skin lightening compositions - Google Patents
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- CN1224345A CN1224345A CN 96180386 CN96180386A CN1224345A CN 1224345 A CN1224345 A CN 1224345A CN 96180386 CN96180386 CN 96180386 CN 96180386 A CN96180386 A CN 96180386A CN 1224345 A CN1224345 A CN 1224345A
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Abstract
The subject invention relates to a water-in-silicone gel composition for skin lightening comprising: a) a safe and effective amount of a compound of formula (I), wherein Z is oxygen or sulfur; b) a mixture of dimethicone copolyol surfactant and cyclomethicone; and c) a cosmetically-acceptable carrier for said compound of formula (I) and said mixture.
Description
Technical background
The present invention relates to the skin whitening field.Especially, the present invention relates to new polysiloxanes bag hydrogel composition, said composition can strengthen the dermal osmosis effect of the specific hydroquinone derivatives that is used for skin whitening.
Background of invention
Specific hydroquinone shown in formula I is known as the skin whitening chemical compound, with reference to WO9523780.
Formula I
Wherein Z is oxygen or sulfur.
The specific hydroquinone derivatives and the combination of penetration enhancers are disclosed among the WO 9523780.
Describe among the WO9523780, penetration enhancers is disclosed in US4, and 537,776, Cooper, authorizing day is on August 27th, 1985, US4,552,872, people such as Cooper, authorizing day is December in 1985 12 days, US4,557,934, Cooper, authorizing day is December in 1985 10 days, US4,130,667, Smith, authorizing day is December in 1978 19 days, US3,989,816, Rhaadhyaksha, authorizing day is on November 2nd, 1976, US4,017,641, DiGiulio, authorizing day is on April 12nd, 1977 and US4,954,487, Cooper, Loomans﹠amp; Wickett, authorizing day is nineteen ninety JIUYUE 4 days, other penetration enhancers is disclosed in Cooper, E.R. in Zhu " decyl methyl sulfoxide is to the effect of dermal osmosis ", the solution behavior of surfactant, the 2nd volume (Mittal and Fendler edit), Plenum Publishing company publishes, 1982, PP.1505-1516, Mahjour, M., B.Mauser, in " Ovum Gallus domesticus Flavus lecithin and industrial soybean lecithin are to the effect of external drug penetration through skin " of Z.Rashidbaigi and M.B.Fawzi work, controlled release magazine (Journal of Controlled Release), the 14th volume (1990), pp.243-252, Wong, O., J.Huntington, R.Konishi, " the unsaturated ring urea as new nontoxic biological degradable transdermal penetration reinforcing agent I: synthetic " of J.H.Rytting and T.Higuchi work, pharmaceutical science magazine, the 77th volume, No.11 (in November, 1998), pp.967-971, Willams, " enhanced terpene of dermal osmosis and fat-albumen is separated theoretical " of A.C. and B.W.Barry work, drug research, the 8th volume, No.1 (1991), PP.17-24 and Wong, O., J.Huntington, " the new N, the alkyl glycinate hydrochloride that the N-dialkyl group replaces is as the transdermal penetration reinforcing agent " of T.Nishihata and J.H.Rytting work, drug research, the 6th volume, No.4 (1989), PP.286-295.
Polysiloxanes bag water composition is disclosed among GB patent publication No. 2079300A and the US5216033A, but the not description of the specific hydroquinone derivatives shown in formula I and the combination of polysiloxanes bag water composition, this combination can strengthen infiltration.
An object of the present invention is to provide the compositions that is used to brighten mammal skin, said composition has the good penetration effect, so that can effectively permeate and work effectively as the specific hydroquinone derivatives of skin whitening activating agent.
Summary of the invention
The present invention relates to a kind of polysiloxanes bag hydrogel composition that is used for skin whitening, said composition comprises:
(a) a kind of safety and the chemical compound shown in formula I of effective dose,
Formula I:
Wherein Z is oxygen or sulfur,
(b) a kind of dimethicone is total to the mixture of polyol surfactant and SILIBIONE OIL 70047 V20 DC-21330 DC21330,
(c) a kind of cosmetic gone up the acceptable chemical compound of described formula I and the carrier of described mixture of being used for.
Detailed Description Of The Invention
The chemical compound of formula I has the good skin whitening effect to mammal, but also need strengthen the osmosis of the chemical compound of formula I to mammal skin.Make us unexpectedly finding that the present composition has obtained the good osmosis of chemical compound shown in the formula I on mammalian skin.
In order to obtain good osmosis, the present composition must form the gel of a kind of polysiloxanes Bao Shui.
" local application " used herein refers to directly and is coated on the skin appearance.
" skin whitening " used herein is meant the melanocyte that reduces in the skin, comprise in the following situation one or more: the integral body of skin key colour brightens, and the infringement that reduces hyperpigmentation is as comprising: the pigmentation speckle of hyperpigmentation or sunlight-induced after senile plaque, melasma, moth patch, freckle and the inflammation.
All percents used herein, except as otherwise noted all by weight.
" dimethicone polyol " used herein refers to " polymer with dimethyl siloxane of polyoxyethylene and/or polyoxy propylidene side chain ".
" SILIBIONE OIL 70047 V20 DC-21330 DC21330 " used herein refers to " cyclic dimethyl polysiloxane ".
The chemical compound of described formula I: the mixture of dimethicone polyol surfactant and SILIBIONE OIL 70047 V20 DC-21330 DC21330: the weight rate of acceptable carrier should be 0.001-10 on the cosmetics: 10-30: 89.999-60.
The typical example of the chemical compound of formula I is as follows.4-[(tetrahydrochysene-2H-pyrans-2-yl) oxygen] phenol (hereinafter claiming THPOP) 4-[(tetrahydrochysene-2H-thiapyran-2-yl) oxygen] these chemical compounds of phenol are to produce according to the method described among the WO9523780.
Skin whitening composition of the present invention preferably is contained in the formula I chemical compound of about 0.001% in the topical composition to about 10%, more preferably from about 0.01% to about 8%, especially more preferably 0.1% to about 5%, most preferably is about 0.5% to about 3% formula I chemical compound.
Use contains infringement and other zone that need obviously brighten that the present composition that surpasses 3% activating agent is preferred for brightening hyperpigmentation.The mixture of dimethicone polyol surfactant and SILIBIONE OIL 70047 V20 DC-21330 DC21330
The weight rate of dimethicone polyol surfactant and SILIBIONE OIL 70047 V20 DC-21330 DC21330 is generally 5: 95 to 25: 75, is preferably 5: 95 to 15: 85, more preferably 5: 95 to 10: 90.
Skin feel has good effect to this mixture for giving preferably.This class polysiloxanes in the usual hybridization has lower molecular weight.The suitable mixture of dimethicone polyol surfactant and SILIBIONE OIL 70047 V20 DC-21330 DC21330 comprises Dow Corning Q2-3225C, and this mixture can obtain from the Dow Corning Corporation that is positioned at Midland city, U.S. MI. state.
Skin whitening composition of the present invention preferably comprises 10% to about 30%, more preferably from about 15% to about 20% the dimethicone polyol surfactant and the mixture of SILIBIONE OIL 70047 V20 DC-21330 DC21330.Be used for acceptable carrier on the cosmetics of the chemical compound of formula I and described mixture
Term used herein " acceptable carrier on the cosmetics " refers to one or more compatible solids or liquid filling agent, diluent, extender etc., and they are acceptable on the cosmetics as herein defined.Term used herein " compatible " refers to the component of the present composition can be mixed mutually with main activating agent of the present invention, and does not have under usual conditions to cause that the significantly reduced interaction of compositions efficient takes place.The type of the carrier of Shi Yonging depends on required product type in the present invention.The topical compositions of Shi Yonging can be made a variety of product types in the present invention.These product types comprise, but not as limit, astringent, gel, propellant, ointment and mousse.These product types can comprise several bearer types, comprise, but not as limit, solution, aerosol and gel.
Solution according to the present invention generally includes water or organic solvent acceptable on the cosmetics, that main activating agent is dispersed or dissolved therein.Because the formula I chemical compound is the molecule (its " solubility parameter " is about 9.5) of middle polarity, it both had been insoluble in the very polar solvent and also had been insoluble in the nonpolar solvent, in order to dissolve the chemical compound of formula I, just it must be dissolved in the solvent of middle polarity.It is 7 to 11 solvent that the solvent of middle polarity is preferably those solubility parameters, and more preferably those solubility parameters are 8 to 10 solvent.The solvent of middle polarity comprises water soluble clycol ether, rudimentary single pure ether such as polyoxy propylidene 15 stearyl ethers and polypropylene glycol-14 butyl ether as ethanol, polyhydroxy-alcohol, triglyceride such as capric acid/Trivent OCG, hot pentanediol dicaprylate (commodity are called Cosmol, and Nisshin Oil Mills LTD company produces), octyl methoxycinnamate and polyoxy propylidene or polyoxyethylene and aliphatic alcohol.
Its characteristics of above-mentioned water soluble clycol ether are for having general formula: R
1-O-[(CH
2)
mO]
nH, wherein R
1Be a kind of alkyl with 1 to 6 carbon atom, m is about 2 to about 3, and n is about 1 to about 2.The example of alkylidene/two alkylidene groups comprises ethylidene, propylidene and diethylidene group.Alkyl R
1Example comprise methyl, ethyl, propyl group, butyl, hexyl.Having the diethylidene group is diethylene glycol monoethyl ether as alkylidene group and ethyl group as alkyl structure glycol ethers partly, its CTFA called after ethoxydiglycol.One of most preferred is the product of the commodity Transcutol by name that can obtain from the Gattefosse of France.
The example of above-mentioned polyhydroxy-alcohol comprises glycerol, two glycerol, triglycerin, Polyethylene Glycol, ethylene glycol, diethylene glycol, propylene glycol, dipropylene glycol, hexanediol, 1,3-butanediol, 1,4-butanediol, glucose, maltose, sucrose, xylose, sorbitol, maltol, malbit, panthenol, hyaluronic acid and salt thereof, with and composition thereof.
Any material all preferably is used as lytic agent so that the formula I chemical compound is remained on aqueous phase in the combining of diethylene glycol monoethyl ether (Transcutol) or diethylene glycol monoethyl ether (Transcutol) and ethanol and propylene glycol, and dimethicone polyol surfactant can be used as continuous phase to form stable clear gel.
The good penetration effect can not be obtained by the solvent of middle polarity, but is obtained by the gel of polysiloxanes Bao Shui.
The consumption of the solvent of middle polarity depends on the consumption of formula I chemical compound.
Other carrier beyond the solvent of above-mentioned middle polarity comprises water.
Comprising aerosol composition of the present invention can obtain by add propellant in above-mentioned solution.The propellant of illustrative comprises the fluorizated low molecular weight hydrocarbon of chloro-.Here operable other propellant is described in the Sagarin work, cosmetic science and technology, and second edition, second volume, PP.443-465 (1972) is incorporated herein by reference here.Aerosol is used for skin as ejecting product usually.
Skin whitening composition of the present invention preferably include about 60% to about 89.999%, more preferably from about 72% to about 84.99% the cosmetics acceptable carrier.
Preferred compositions of the present invention has high viscosity, and about 10,000 to about 300,000 centipoises, and more preferably from about 20,000 to about 200,000 centipoises, most preferably from about 50,000 to about 150,000 centipoises.
Except main activating agent, comprise single carrier base material or water-solubility carrier that ointment compositions of the present invention comprises hydrocarbon, for example the water-soluble solution carrier.Ointment can contain a kind of thickening agent in addition, as outstanding at Sagarin, and cosmetic science and technology, second edition, second volume, the thickening agent that PP.72-73 (1972) describes, this paper is incorporated herein by reference, and/or carrier.For example, a kind of ointment can comprise about 2% to about 10% carrier, about 0.1% to about 2% thickening agent and the main activating agent of above-mentioned consumption.
It is 8 or higher that the present composition preferably is re-dubbed pH.The pH value of these compositionss is preferably about 8 to about 9, more preferably about 8 to about 8.5, most preferably is about 8.2 to about 8.5.Greater than about 8 compositions, pH value is in the less stable of about compositions of 4.5 to 8.0 with respect to pH value.Agent is shone in surfactant composition A. sunscreen and screening
Regulate because of being exposed to the skin darkening that produces under the ultraviolet light and can realize by using skin whitening active agent and sunscreen or hiding the mixture that shines agent.Operable screening is shone agent and is comprised as zinc oxide and titanium dioxide.
Ultraviolet light is the principal element that causes skin darkening.Therefore, for making skin whitening, it is required that skin whitener is combined with UVA and/or UVB sunscreen.
The wide variety of conventional sunscreen is fit to be used in combination with skin whitener.People such as Segarin are in the cosmetic science technology, the VIII chapter, and the 189th page discloses many suitable reagent later on.Concrete suitable sunscreen for example comprises para-amino benzoic acid, its salt and derivant (ethyl, isobutyl group, glyceryl ester, ESCAROL 507), ammonia Fructus Foeniculi acid esters (being o-aminobenzoa, methyl, Gallate base, phenyl, benzyl, phenylethyl, linalyl, tyerpinyl and cyclohexenyl group ester); Salicylate (amyl group, phenyl, benzyl, Gallate base, glyceryl and dipropylene glycol ester); Cinnamic acid derivative (Gallate base and benzyl ester, α-phenyl cinnamonitrile; Butyl cinnamoyl pyruvate); Dihydroxycinnamic acid derivant (umbelliferone, methylumbelliferone, methyl acetyl umbelliferone); Trihydroxy cinnamic acid derivative (esculetin, methyl esculetin, daphnetin and glucoside, Esculin and daphnin); Hydro carbons (diphenyl diethylene, stilbene); Dibenzalacetone and benzalacetophenone; Naphthol sulfonate (beta naphthal-3,6-disulfonic acid and beta naphthal-6, the sodium salt of 8-disulfonic acid); Dihydroxy naphthlene formic acid and its salt; Neighbour and parazon base disulfonate; Coumarin derivative (7-hydroxyl, 7-methyl, 3-phenyl); Diazole (2-acetyl group-3-bromo-indazole, Ben base benzoxazole, Jia Ji naphthoxazole, various aryl benzothiazole); Quinine salt (disulfate, sulfate, chloride, oleate and tannate); Quinoline (oxinate, 2-phenylchinoline); The benzophenone that hydroxyl or methoxyl group replace; Uric acid and vilouric acid; Tannin and its derivant (for example Hexaethyl ether); (butyl carbotol) (6-propyl group piperonyl) ether; Hydroquinone; Benzophenone (oxybenzene, sulisobenzone, two oxybenzone, benzo resorcinol, 2,2 ', 4,4 '-tetrahydroxybenzophenone, 2,2 '-dihydroxy-4,4 '-dimethoxy benzophenone, octabenzone; 4-isopropyl-dibenzoyl methane; Butyl methoxy benzoylmethane; Etocrylene; With 4-isopropyl-dibenzoyl methane.
Wherein, p-methoxycinnamic acid 2-ethyl hexyl ester; 4; 4 '-tert-butyl group methoxy dibenzoyl methylmethane; 2-hydroxyl-4-methoxyl group benzophenone; octyldimethyl-para-amino benzoic acid; two galloyl trioleates; 2; 2-dihydroxy-4-methoxyl group benzophenone; 4-(two (hydroxypropyl)) amino benzoic Acid ethyl ester; 2-cyano group-3; 3-diphenylacrylate 2-ethyl hexyl ester; salicylic acid 2-ethyl hexyl ester; para-amino benzoic acid glyceride; salicylic acid 3; 3, the 5-trimethylcyclohexyl; ammonia anisic acid methyl ester; ESCAROL 507 or Aminobenzoate; ESCAROL 507 2-ethyl hexyl ester; 2-Phenylbenzimidazole-5-sulfonic acid; the mixture of 2-(to the dimethylamino phenyl)-5-sulfo group benzoxazole acid (benzoxazoic acid) and these chemical compounds is preferred.
The preferred sunscreen that can be used in the compositions of the present invention is 2-ethylhexyl-p-methoxycinnamic acid ester, PAROSOL 1789,2-hydroxyl-4-methoxyl group benzophenone, octyldimethyl-para-amino benzoic acid and composition thereof.
Be particularly suitable for equally in the present composition is the US4 that authorizes Sabatelli on (for example) June nineteen ninety 26,937, authorized the US4 of Sabatelli and Spirnak on March 12nd, 370 and 1991, those disclosed sunscreen in 999,186 (all the introducing) here as reference.Wherein disclosed sunscreen has two different chromophore parts that show different ultraviolet radiation absorption spectras in a molecule.One of them chromophore part mainly absorbs in the UVB radiation scope, and another chromophore part mainly absorbs in the UVA radiation scope.
In this class sunscreen preferably 2; the 4-N of 4-dihydroxy benzophenone; N-(2-ethylhexyl) methylamino benzoate; the N of 4-hydroxy benzophenone acyl group methane; N-two-(2-ethylhexyl)-4-Aminobenzoate; the 4-N of 4-hydroxy benzophenone acyl group methane; N-(2-ethylhexyl) methylamino benzoate; the 4-N of 2-hydroxyl-4-(2-hydroxyl-oxethyl) benzophenone; N-(2-ethylhexyl) methylamino benzoate; the 4-N of 4-(2-ethoxy) dibenzoyl methane; N-(2-ethylhexyl) methylamino benzoate; the N of 2-hydroxyl-4-(2-hydroxyl-oxethyl) benzophenone; N-two-(2-ethylhexyl)-4-Aminobenzoate; and the N of 4-(2-hydroxyl-oxethyl) dibenzoyl methane, N-two-(2-ethylhexyl)-4-Aminobenzoate and composition thereof.
The sunscreen of safety and effective dose can be used among the present invention.This sunscreen must be compatible with skin whitener.Compositions preferably includes about 1% to about 20%, more preferably from about 2% to about 10% sunscreen.Consumption will change according to sunscreen of choosing and required SPF (sun protection factor) (SPF) accurately.
A kind of reagent can also be added and be used for any compositions of the present invention, particularly strengthen it and anti-ly water-washed away or wiped performance to improve the affinity of these compositionss to skin.The preferred reagent that this effect can be provided is ethylene and acrylic acid copolymer.The compositions that comprises this copolymer is disclosed in the US4 that authorized Brock on May 5th, 1987, in 663,157 (the introducing as reference here).B. antiinflammatory
Be used for preferred skin whitening composition of the present invention, comprising with the antiinflammatory of skin whitener as active component.The antiinflammatory that adds has strengthened the skin whitening effect of compositions.Antiinflammatory plays strong protective effect (although it also provides some UVB protections) in the UVA radiation scope.The local antiinflammatory that uses has reduced the skin darkening that causes because of long term exposure under the UV radiation.(referring to the US4 that authorized Bissett, Bush and Chatterjee on July 11st, 1989,847,071, introduce as reference here; With the US4 that authorized Bissett and Chatterjee on July 11st, 1989,847,069, introduce as reference here.)
The antiinflammatory of safety and effective dose can be added and be used for compositions of the present invention, the consumption of antiinflammatory be preferably compositions about 0.1% to about 10%, more preferably from about 0.5% to about 5%.The accurate amount of the antiinflammatory that uses in the compositions will depend on specific antiinflammatory, because the effect of these antiinflammatories can extensively change.
Operable steroid antiinflammatory includes but not limited to: corticosteroid such as hydrocortisone, hydroxyl fluorine hydroxyl dehydrogenation cortex (steroid) alcohol, the Alpha-Methyl dexamethasone, dexamethasone phosphate, beclomethasone dipropionate, the valeric acid Clobetasol, the acetone hydroxyl meticortelone that contracts, fluorine dihydroxy methyl pregnen diethylene diketone, Deseoxycortone, dexamethasone, dichloro deoxidation prednisone, diflorasone diacetate, nerisona, fluadrenolone, flucloronide's acetonide, fludrocortisone, the trimethylace tonitric flumetasone, the fluosinolone acetonide, lidex, aniprime (flucortine) butyl ester, fluocortolone, acetic acid fluorine prednisone, the acetone fluorine hydroxyl dragon that contracts, halcinonide, hydrocortisone acetate, hydrocortisone butyrate, medrat, the triamcinolone acetonide, cortisone, can hold in the palm pine more, flucetonide, hydrogen fluorine cortisone, difluorosone diacetate, the acetone fluorine hydroxyl dragon acetonide that contracts, medrysone, amcinafal, amcinafide, the ester of betamethasone and its surplus, the chlorine prednisone, acetic acid chlorine prednisone, clocortolone, clescinolone, the pine of dichloro deoxidation, difluprednate, the flucloronide, 9-removes the fluorine fluocinonide, flumetasone, fluperolone acetate, fluprednisolone, the valeric acid hydrocortisone, the hydrocortisone cipionate, hydrocortamate, meprednisone, paramethasone, andrographolide, prednisone, Beclomethasone, triamcinolone and its mixture.The preferred steroid antiinflammatory that uses is hydroxyl-cortisone.
Can be used for the second class antiinflammatory of the present invention and comprise non-steroidal anti-inflammatory agents.The chemical compound that this class antiinflammatory comprises is that those skilled in the art are known.Open in detail for the chemical constitution of non-steroidal anti-inflammatory agents, synthetic, side effect etc., can comprise with reference to authoritative works: antiinflammatory and antirheumatic, K.D.Rainsford, Vol. I-III, CRC publishing house, Boca Raton, (1985), with antiinflammatory, chemistry and materia medica 1, people such as R.A.Scherrer, publishing house of institute, New York (1974)
The concrete non-steroidal anti-inflammatory agents that is used for the present composition includes but not limited to:
1) oxicams such as piroxicam, isoxicam, tenoxicam, sudoxicam and CP-14,304;
2) salicylic acid esters such as aspirin, salicyl salicylate (salsalate), benorylate, trilistate, safaprin, solprin, diflunisal and fendosal;
3) acetogenin such as diclofenac, fragrant fluoric acid, indometacin, sulindac, tolmetin, Isoxepac, ethyl dihydro and furan acetic acid, tiopinac cycloheptatriene acetic acid, zidometacin, acemetacin, fentiazac, zomepirac, clidanac, Oxepinac and felbinac;
4) fenamic acids such as mefenamic acid, meclofenamic acid, flufenamic acid, niflumic acid and tolfenamic acid;
5) propanoic derivatives such as ibuprofen, naprosyn, benoxaprofen, flurbiprofen, ketone propanoic acid, fenoprofen, fenbufen, indoprofen, pirprofen, carprofen, Evil third Qin, pranoprofen, miroprofen, tioxaprofen, suprofen, alminoprofen and tiaprofenic acid.
6) pyrazoles such as bute, oxyphenbutazone, feprazone, I third and front three protects Qin Song.
Can also use the mixture of these non-steroidal anti-inflammatory agents and the ester of pharmaceutically acceptable salt and these reagent thereof.For example etofenamate (derivant of flufenamic acid) is specially adapted to local coating.In these non-steroidal anti-inflammatory agents, ibuprofen, naprosyn, flufenamic acid, mefenamic acid, meclofenamic acid, piroxicam and felbinac are preferred; Ibuprofen, naprosyn and felbinac are most preferred.
The another kind of antiinflammatory that can be used in the compositions is to be disclosed in the US4 that authorized people such as Loomans on November 24th, 1987, those antiinflammatories in 708 966.This patent disclosure comprise the phenyl compound of special replacement, particularly replace 2, a class non-steroidal anti-inflammatory compounds of 6-ditert-butyphynol derivative.For example be selected from 4-(4 '-pentynyl-3 '-ketone)-2, the 6-DI-tert-butylphenol compounds; 4-(5 '-hexin acyl group-2, the 6-DI-tert-butylphenol compounds; 4-((S)-(-)-3 '-methyl-5 '-hexin acyl group-2, the 6-DI-tert-butylphenol compounds; 4-((R)-(+)-3 '-methyl-5 '-hexin acyl group-2, the 6-DI-tert-butylphenol compounds; And 4-(3 ', 3 '-the dimethoxy propiono)-2, the chemical compound of 6-DI-tert-butylphenol compounds can be used in the inventive method; 4-(5 '-hexin acyl group-2, the 6-DI-tert-butylphenol compounds is most preferred.
A class antiinflammatory again that can be used in the compositions is to be disclosed in the US4 that authorizes Muller March 27 nineteen ninety, those antiinflammatories in 912,248.This patent disclosure have the carboxylate, particularly naproxen ester of specific 2-naphthyl of containing of two or more chiral centres and the chemical compound or a non-enantiomer mixture of naproxol ester compounds.For example be selected from (S)-naproxen-(S)-2-butyl ester, (S)-naproxen-(R)-2-butyl ester, (S)-naproxol-(R)-2-Methyl Butyric Acid ester, (S)-naproxol-(S)-2-Methyl Butyric Acid ester, (S)-naproxen-(S)-2-butyl ester with (S)-non-enantiomer mixture of naproxen-(R)-2-butyl ester and (S)-naproxol-(R)-2-Methyl Butyric Acid ester with (S)-chemical compound of the non-enantiomer mixture of naproxol-(S)-2-Methyl Butyric Acid ester can be used among the present invention.
In addition, so-called " natural " antiinflammatory can be used in the inventive method.For example can use candelilla wax, α bisabolol, Lu Yun, Manjistha (, particularly extracting in the Rubia Cordifolia platymiscium) and Guggal (, particularly extracting in the CommiphoraMukul platymiscium) from Commiphora from Rubia.
Be used for another kind of preferred composition of the present invention and comprise above disclosed respectively skin whitener, sunscreen and the antiinflammatory that makes the consumption of skin whitening simultaneously.C. antioxidant/free radical scavenger
Be used for preferred skin whitening composition of the present invention, comprising with the antioxidant/free radical scavenger of skin whitener as active component.Antioxidant/the free radical scavenger that adds has increased the effect of the skin whitening of compositions.
The antioxidant of safety and effective dose/free radical scavenger can be added in the present composition, its consumption be preferably compositions about 0.1% to about 10%, more preferably from about 1% to about 5%.
The example of operable antioxidant/free radical scavenger is as ascorbic acid (vitamin C) and its salt, tocopherol (vitamin E), tocopherol sorbic acid ester, other ester of tocopherol, butylated hydroxy benzoic acid and their salt, 6-hydroxyl-2,5,7,8-tetramethyl benzo dihydropyran-2-carboxylic acid (can be commercial) by trade name Trolox , gallate and its Arrcostab (particularly propyl gallate), uric acid and its salt and Arrcostab, sorbic acid and its salt, the ascorbyl ester of fatty acid, amine (N for example, N-diethyl hydroxylamine, amino-guanidine), sulfhydryl compound (for example glutathion) and Dihydroxyfumaric acid and its salt.
Be used for preferred composition of the present invention, compositions comprise a kind of, any two kinds or all three kinds in sunscreen, antiinflammatory and/or the antioxidant/free radical scavenger with the skin whitener that comprises as active component.In these reagent that add two kinds or all three kinds increase the skin whitening effect of compositions with skin whitener.D. chelating agen
Be used for preferred composition of the present invention, add chelating agen with skin whitener as active component." chelating agen " used herein is meant and can removes the activating agent of metal ion by forming coordination compound, and metal ion can not easily participate in or catalyzed chemical reaction like this.The chelating agen that adds has improved the skin whitening effect of compositions.
The chelating agen of safety and effective dose can be added and be used for the present composition, its consumption be preferably compositions about 0.1% to about 10%, more preferably from about 1% to about 5%.The chelating agen that is used for the present composition is disclosed in the U.S. Patent application serial number 619 that Bissett, Bush and Chatterjee apply on November nineteen ninety 27,805 (it is the subsequent application of the U.S. Patent application serial number 251,910 of application on October 4th, 1988); The U.S. Patent application serial number 514,892 that Bush and Bissett1990 applied at April 26; In the U.S. Patent application serial number of February 25 applying for Bush, Bissett and Chatterjee1991 657,847; All these applications are all introduced as reference here.The preferred sequestrant that is used for the present composition is furil-dioxime and its derivant.
Be used for preferred composition of the present invention, compositions comprise in sunscreen, antiinflammatory, antioxidant/free radical scavenger and/or the chelating agen any, any two kinds, any three kinds or all four kinds with the skin whitener that comprises as active component.In these reagent that add two kinds, three kinds or all four kinds increase the skin whitening effect of compositions with skin whitener.E. retinoid
Be used for preferred composition of the present invention, add retinoid (preferred tretinoin) with skin whitener as active component.The retinoid that adds increases the skin whitening effect of compositions.The retinoid of safety and effective dose can be added and be used for the present composition, its consumption be preferably compositions about 0.001% to about 2%, more preferably from about 0.01% to about 1%." retinoid " used herein comprises the analog of all natural and/or synthetic vitamin A or have the retinoid chemical compound of physiologically active of vitamin A and the geometric isomer and the stereoisomer of these chemical compounds in skin, as all trans retinoic acids and 13-cis-retinoic acid.
Be used for preferred composition of the present invention, compositions comprise in sunscreen, antiinflammatory, antioxidant/free radical scavenger, chelating agen and/or the retinoid any, any two kinds, any three kinds, any four kinds and/or all five kinds with the skin whitener that comprises as active component.In these reagent that add two kinds, three kinds, four kinds or all five kinds increase the skin whitening effect of compositions with skin whitener.Brighten the method for mammal skin
The present invention relates to brighten the method for mammal skin.Such method comprises safe in utilization and skin whitener effective dose.According to speed and the desirable degree that brightens of using subject's skin color, skin darkening, the consumption of activating agent and frequency of administration have bigger variation.
Safe in utilization and skin whitener effective dose, in topical compositions is generally each about 1g to about 10g/cm
2Skin is preferably each about 2g to about 8g/cm
2Skin, more preferably about at every turn 3g is to about 7g/cm
2Skin also is preferably each about 4g to about 5g/cm
2Skin.Frequency of administration is preferably approximately every day 4 times to approximately biweekly, and more preferably about every day 3 times is to approximately every one day 1 time, is preferably approximately once a day to twice of every day approximately again.For rudimentary animal, need use and to see the skin whitening effect at least 5 days.For the people, need at least one month can see the skin whitening effect.After skin obtained brightening, frequency of administration and amount of application can be reduced to the consumption of keeping as required.This consumption of keeping is according to individual different and different, but is preferably about 1/10 as required to about 1/2, more preferably about 1/5 to about 1/3 initial content and/or frequency.
Being used for the preferred method of the present invention that mammal skin brightens relates to and uses safety simultaneously on skin and the skin whitener of effective dose and safety and one or more sunscreen, anti-inflammatory agent, antioxidant/free radical scavenger, chelating agen and/or the retinoid of effective dose." using simultaneously " used herein or " simultaneously " refer in about while and use these materials on the skins of the same area of object.Though this can realize by these materials are administered on the skin respectively, preferably a kind of compositions that comprises all these materials is administered on the skin.The amount of the sunscreen of using is preferably about 0.01mg to about 0.1mg/cm
2Skin.The amount of the anti-inflammatory agent of using is preferably about 0.005mg to about 0.5mg/cm
2Skin, more preferably about 0.01mg is to about 0.1mg/cm
2Skin.The amount of antioxidant/free radical scavenger of using is preferably about 0.01mg to about 1.0mg/cm
2Skin, more preferably about 0.05mg is to about 0.5mg/cm
2Skin.The amount of the chelating agen of using is preferably about 0.001mg to about 1.0mg/cm
2Skin, more preferably about 0.01mg is to about 0.5mg/cm
2Skin is preferably about 0.05mg again to about 0.1mg/cm
2Skin.The amount of the retinoid of using is preferably about 0.001mg to about 0.5mg/cm
2Skin, more preferably about 0.005mg is to about 0.1mg/cm
2Skin.The amount of the skin whitener of using is preferably each about 0.001mg to about 2mg/cm
2Skin, more preferably about at every turn 0.01mg is to about 1mg/cm
2Skin.The step for preparing polysiloxanes bag hydrogel composition of the present invention
For example, polysiloxanes bag hydrogel composition of the present invention can prepare by following steps:
(ⅰ) with formula I compound dissolution (activating agent phase-1) in the solvent of middle polarity;
(ⅱ) in another container with water soluble ingredient intermingling (water);
(ⅲ) after above-mentioned two kinds of mixture clarification, water is mixed in activating agent phase-1, mixture is fully stirred (activating agent phase-2);
(ⅳ) in another container, the mixture that activating agent phase-2 and dimethicone polyol surfactant and SILIBIONE OIL 70047 V20 DC-21330 DC21330 are formed slowly mixes under constant speed stirs, to form the gel combination of polysiloxanes Bao Shui of the present invention.
Embodiment
Following embodiment further describes and has illustrated embodiment within the scope of the invention.These embodiment do not become restriction of the present invention only for illustrative purposes, because under the situation of not violating spirit and scope of the invention, have the change example of a lot of these embodiment.
Test implementation example 1
The step of preparation reference composition
THPOP is dissolved in polypropylene glycol (14) butyl ether (THPOP phase-1).In addition, polyoxyethylene (21) stearyl alcohol, polyoxyethylene (2) stearyl alcohol, hexadecanol, stearyl alcohol, SILIBIONE OIL 70047 V20 DC-21330 DC21330 and ascorbic palmitate are dissolved under 70 ℃ of conditions, and fully stir.Add THPOP phase-1, and continue mixing (THPOP phase-2).
In another container, other composition that mentioned component is outer dissolves (water) under 70 ℃ of conditions.
THPOP phase-2 and water are fully mixed, and cooling is to obtain O/w emulsion (o/w emulsion).The component of reference composition is listed in table 1.
The step of preparation test composition No.1
THPOP is dissolved in (THPOP mutually-1) in diethylene glycol monoethyl ether, propylene glycol and the alcoholic acid mixture.In an other container, deionized water, sodium sulfite, sodium sulfite, glycerol and benzyl alcohol are mixed (water).
After above-mentioned two kinds of mixture clarification, water is mixed in THPOP phase-1, and fully stir (THPOP phase-2).
In another beaker, under constant speed stirs, DC Q2-3225C is slowly stirred mutually-2 with THPOP.Form a stable polysiloxanes bag hydrogel.The component of compositions No.1 is listed in table 2.
Table 1 reference composition (O/w emulsion)
Group component (% by weight) deionized water 75.70 hydrochloric acid 1N 2.30 triethanolamines 1.40 magnesium ascorbyl phosphate 0.10 sodium metabisulfite 0.05EDTA disodium 0.05 polyoxyethylene (21) stearyl alcohol (21) 2.00 polyoxyethylene (2) stearyl alcohols (2) 1.00 polypropylene glycol (14) butyl ethers 7.50 hexadecanols 3.00 stearyl alcohols 1.50 SILIBIONE OIL 70047 V20s 1.00 ascorbyl palmitate 0.10THPOP 3.00 butanediol 1.00Glydant Plus 0.30 (" Glydant Plus " is dimethanol-5, the 5-dimethyl hydantoin (with) iodine propinyl butyl carbamate)
Table 2 compositions No.1 (polysiloxanes bag hydrogel)
Group component (weight %) deionized water 30.20THPOP 3.00 diethylene glycol monoethyl ether 20.00 (transcutol) propylene glycol 15.00 ethanol 10.00 sodium sulfite (NaHSO
3) 0.20 sodium sulfite (Na
2SO
3) (2% diformazan gathers silicon to 0.50 benzyl alcohol, 0.60 glycerol 0.50DC Q2-3225C 20.00
Oxygen alkane polyol and
18% SILIBIONE OIL 70047 V20 DC-21330 DC21330) (" DC Q2-3225C " is the mixture of the dimethicone polyol of 90% SILIBIONE OIL 70047 V20 DC-21330 DC21330 and 10%) method of testing (1) experimental facilities
Use the spreading grooves of no chuck.The cross-sectional area of infiltration is 0.79cm
2
According to E.W.Merritt and E.R.Cooper at controlled release magazine (J.ControlledRelease), 1 (2), the description on the 161-162 designs.
Low glass top allows the liquid medicine evaporation, and this device will be used for this research.
Spreading grooves is kept in the device of an aluminum under 37 ℃ body temperature condition, and this device is placed in the module of a band stirrings-heating (from Peirce Chemical Co. company acquisition).Each aluminum device can be adorned six spreading grooves.This module temperature controllable, and provide stirring power for spreading grooves.(2) buffer solution
The normal saline solution that uses in this preparation process is the Dulbeco phosphate buffered saline (PBS), does not contain calcium chloride and sodium bicarbonate (hereinafter claiming " pbs "), obtains CAM7276 from Wako Pure ChemicalIndustries LTD..According to the indication of institute target, allocate pbs again with distilled water, and the Hydrazoic acid,sodium salt that adds 0.002% (s/v) (obtains from Wako Pure ChemicalIndustries LTD., KCE6293) to suppress growth of microorganism.Pbs solution remains in 37 ℃ the water-bath, so that solution is outgased in whole experiment.Also can under stirring condition, use asepwirator pump to make the solution degassing 15 minutes.(3) the human body corpse skin of Qie Xiaing
It is 0.25mm (after cleaning and unhairing processing) that refrigerated human body skin is cut into thickness, obtains (Shriners Burns academy, Cincinnati, Ohio) from Ohio Valley skin and organization center.Skin was soaked 24 hours in the wide spectrum biocides, and handle, wrap in the measurement instrument, put into the aseptic paillon foil assembly of a sealing then with 10% glycerite.(from Keisei Medical Industrial Co., handle#4 balde#21) is cut into skin about 1.2 * 1.2cm to use dissecting knife
2In the aluminum device, the receptor chamber that the glass spreading grooves of pbs solution (4-5ml) will be housed remains on 37 ℃.Square skin is horizontally fixed on the permeable tank, makes horny layer face toward the cell of application of sample, corium contacts with the receptor cell.Be contained in the glass end that does not seal on the spreading grooves and fix.The aluminum device is put back in the module, the receptor that little shape magnetic stirring bar is put into spreading grooves is indoor, in whole experiment, ceaselessly to stir.(4) experimental technique
Skin-balance is spent the night, or at least 16 hours, corium is contacted with pbs solution, and horny layer is exposed in the air.The program of using a computer is come the randomization group, and each spreading grooves has all correspondingly been done labelling.After balance and before the adding medicine, discard the indoor solution of receptor, fill again with fresh pbs solution.This step comprises that the solution that receptor is indoor outwells, and uses the fresh pbs solution rinsing of 2-3 milliliter then, fills with fresh pbs solution then again.When pouring soln, use magnetic force cover hands to drop out to prevent little shape magnetic bar.The glass spreading grooves is fixed at one jiao, and attack is to remove the bubble at the corium surface aggregation of skin gently.In whole experiment, with the temperature of SATO PAC-9400 thermocouple thermometer random observation receptor indoor solution, if necessary and adjust.(5) step of application of sample and sampling
With pipet test composition and Comparative composition are added on the horny layer (sample addition zone).If the application of sample amount is little, just sample is evenly distributed on the skin with the pipettor top.Stop up if desired, just and then behind the application of sample, a fritter parafilm is placed on the glass top.Usually, behind the application of sample 3,6,24 hours, collect the sample of receptor cell.Sampling comprises pours solution the bottle into from the receptor cell, cleans with 2-3ml pbs solution, and cleanout fluid is poured in the bottle, refills full cell with fresh pbs solution then.After each sampling, obtain blank sample (pure pbs solution) and be used for determining background concn.The aliquot of the sample introduction solution of sample is weighed in scintillation vial and is used for the HPLC analysis, to calculate the average sample size in each groove.The aliquot of the solution of being made up of test substances and ethanol is also carried out HPLC and is analyzed, with the standardization result with set up the conversion factor of data analysis.(6) cleaning step
Last what test, groove is pulled down and in powerful wash solution (Alconox), cleaned, use the distilled water rinsing, then air drying.Skin is packaged in the paillon foil and before burning disposal is stored in the fridge.If there is not burning facility, can uses concentrated sulphuric acid to soak and dissolve skin.Place with the stirring rod rinsing and in containing alcoholic acid beaker and to spend the night.Rinsing clamping plate in distilled water also clean in Alconox solution sometimes.(7) HPLC analyzes
With the aliquot of infiltration sample, sample size and the percentage composition of standard solution HPLC (high performance liquid chromatography-Shimazu LC-9A is used JSPHEREODS M80 post) analysis THPOP.Calculate osmotic value by following formula.
Test result is listed in table 3.
Table 3 testing combination is at the osmotic value (%) of each time point
3 hours 6 hours 24 hours compositions No.1 2.6 6.8 39 Comparative composition 2.0 2.8 7.7 test implementation examples 2
The enhanced osmosis of the following example explanation institute is not obtained by solvent, but by the polysiloxanes bag hydrogel formulation acquisition of forming as the chemical compound of formula I.Preparation compositions No.2
THPOP is dissolved in (THPOP phase-1) in the diethylene glycol monoethyl ether.In another container, deionized water, sodium sulfite, triethanolamine, glycerol, benzyl alcohol and sodium citrate are mixed together (water).After above-mentioned two kinds of mixture clarification, water is mixed in THPOP phase-1 and fully stirring (THPOP phase-2).
In another beaker, DC Q2-3225C under stirring, constant speed is slowly mixed mutually-2 with THPOP.Just made stable polysiloxanes bag hydrogel.
The component of compositions No.2 is listed in the step of table 4 preparation Comparative composition No.1
THPOP is dissolved in (THPOP phase-1) in the diethylene glycol monoethyl ether.In another container, deionized water, sodium sulfite, triethanolamine, benzyl alcohol, sodium citrate and hydroxyethyl-cellulose are mixed together (water).After above-mentioned two kinds of mixture clarification, water is mixed and fully stirring in mutually at THPOP, just obtained a kind of hydrogel (not being polysiloxanes bag hydrogel).The component of Comparative composition No.1 is listed in table 4.
Table 4
Components composition No.2 Comparative composition No.1
(polysiloxanes bag hydrogel) (hydrogel)
Content (% by weight) content (% by weight) THPOP 3.00 3.00Transcutol 35.00 35.00 (diethylene glycol monoethyl ether) phenmethylols 0.60 0.60 sodium hydrogensulfite 0.08 0.20 triethanolamine 0.14 0.35 natrium citricum 0.31 0.80 glycerine 3.00-hydroxyethylcellulose-0.75DC Q2-3225C 20-
(2% dimethicone copolymerization
Polyhydric alcohol and the poly-silicon of 18% ring first
Oxygen alkane) deionized water 37.87 59.30 (" DC Q2-3225C " is the mixture of the dimethicone polyol of 90% SILIBIONE OIL 70047 V20 DC-21330 DC21330 and 10%) method of testing
With with embodiment 1 in identical method of testing.
The activating agent osmotic value of above-mentioned prescription is listed in table 5.
Table 5
Testing combination is at the osmotic value (%) of each time point
3 hours 6 hours 24 hours compositions No.2 0.65 1.51 26.40 Comparative composition (O/W emulsion) (identical) Comparative composition No.1 0.40 0.71 8.80 Comparative composition (O/W emulsion) (identical) with real 1.19 2.19 8.90 Comparative composition of executing in the example 1 of test with real 2.00 2.78 6.53 Comparative composition of executing in the example 1 of test
Claims (16)
1. polysiloxanes bag hydrogel composition that is used for skin whitening, said composition comprises:
(a) safety and the chemical compound shown in formula I of effective dose,
Formula I:
Wherein Z is oxygen or sulfur,
(b) a kind of dimethicone is total to the mixture of polyol surfactant and SILIBIONE OIL 70047 V20 DC-21330 DC21330,
(c) a kind of cosmetic gone up the acceptable chemical compound of described formula I and the carrier of described mixture of being used for.
2. the compositions of claim 1, wherein Z is an oxygen.
3. the compositions of claim 1, wherein Z is a sulfur.
4. the compositions of claim 1 comprises a kind of solvent of middle polarity in addition.
5. the compositions of claim 1 comprises the solvent of water soluble clycol ether as a kind of middle polarity in addition.
6. the compositions of claim 4, the compound dissolution shown in the wherein said formula I is in described solvent.
7. the compositions of claim 1 comprises a kind of solvent in addition, and its solvent degree parameter is 7 to 11.
8. the compositions of claim 7, wherein said compound dissolution shown in formula I is in described solvent.
9. the compositions of claim 6, wherein said solvent is a diethylene glycol monoethyl ether, this solvent is as a kind of solvent of middle polarity.
10. the compositions of claim 6, wherein said solvent is the mixture of diethylene glycol monoethyl ether, ethanol and propylene glycol, this solvent is as a kind of solvent of middle polarity.
11. the compositions of claim 1, wherein compositions is a kind of topical composition.
12. a gel combination, said composition comprise the polysiloxanes bag hydrogel composition according to claim 1.
13. an astringent compositions, said composition comprise the polysiloxanes bag hydrogel composition according to claim 1.
14. an aerosol combination, said composition comprise the polysiloxanes bag hydrogel composition according to claim 1.
15. a method for preparing polysiloxanes bag water composition, this method may further comprise the steps:
(ⅰ) the formula I compound dissolution is obtained mixture 1 in the solvent of middle polarity; Formula I:
Wherein Z is oxygen or sulfur
(ⅱ) with the water soluble ingredient intermingling, obtain mixture 2;
(ⅲ) mixture 1 and mixture 2 are mixed, obtain mixture 3;
(ⅳ) mixture that mixture 3 and dimethicone polyol surfactant and SILIBIONE OIL 70047 V20 DC-21330 DC21330 are formed mixes.
16. one kind is used for the method that mammal skin brightens, this method comprises the polysiloxanes bag hydrogel composition of local application according to claim 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 96180386 CN1233637C (en) | 1996-07-02 | 1996-07-02 | Skin lightening compositions |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 96180386 CN1233637C (en) | 1996-07-02 | 1996-07-02 | Skin lightening compositions |
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| Publication Number | Publication Date |
|---|---|
| CN1224345A true CN1224345A (en) | 1999-07-28 |
| CN1233637C CN1233637C (en) | 2005-12-28 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 96180386 Expired - Fee Related CN1233637C (en) | 1996-07-02 | 1996-07-02 | Skin lightening compositions |
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| Country | Link |
|---|---|
| CN (1) | CN1233637C (en) |
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1996
- 1996-07-02 CN CN 96180386 patent/CN1233637C/en not_active Expired - Fee Related
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