CN1191816C - Skin lightening composition - Google Patents
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- CN1191816C CN1191816C CN 96180451 CN96180451A CN1191816C CN 1191816 C CN1191816 C CN 1191816C CN 96180451 CN96180451 CN 96180451 CN 96180451 A CN96180451 A CN 96180451A CN 1191816 C CN1191816 C CN 1191816C
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Abstract
The present invention relates to a skin brightening composition which comprises a definitely safe and effective compound (a) of a type (I), a medially polar solvent (b), polyatomic alcohol (c), solid fatty alcohol (d), a non-ionic surfactant (e), water (f) and phosphatidyl choline (g), wherein Z is oxygen or sulphur, and at least one part of the components (a), (b), (c), (d), (e), (f) and (g) forms a liquid crystal.
Description
Technical field
The present invention relates to the skin Lightening field.More particularly, the present invention relates to contain a kind of energy and strengthen the new compositions of the hydroquinone derivatives of specific skin Lightening the liquid crystal of dermal osmosis effect.
Background of invention
Known is a kind of skin Lightening chemical compound suc as formula the specific hydroquinone shown in (I).See WO9523780.
Wherein Z is oxygen or sulfur.
Being combined among the WO9523780 of specific hydroquinone derivatives and penetration enhancers disclosed.
The penetration enhancers of WO9523780 narration is at Mahjour, M., B.Mauser, Z.Rashidbaigi and M.B.Fawzi, " egg yolk lecithin and the effect of the soybean lecithin that is purchased " (Effect of Egg Yolk Lecithins and CommercialSoybean Lecithins on to the vitro skin infiltration of medicine
In VitroSkin Permeation of Drugs "),
Sustained release is assorted Will, Vol.14 (1990), disclosed in the 243-252 page or leaf.This magazine discloses lecithin as a kind of penetration enhancers.Yet, do not have narration to contain the liquid crystal of specific hydroquinone derivatives and lecithin with infiltration potentiation.
An object of the present invention is to provide and be used for bright mammal skin, have good chemosmotic compositions, make specific have the active hydroquinone derivatives of skin Lightening and can more effectively permeate and more effectively work.
Summary of the invention
The present invention relates to a kind of skin Lightening composition, comprise
(a) the certain safety and formula (I) chemical compound of effective dose
[formula I]:
Wherein Z is oxygen or sulfur,
(b) a kind of average polar solvent,
(c) a kind of polyhydric alcohol,
(d) a kind of solid-state aliphatic alcohol,
(e) a kind of non-ionic surface active agent,
(f) water and
(g) lecithin
Wherein at least a portion said components (a) and (b), (c), (d), (e), (f) and (g) form a kind of liquid crystal.
Detailed Description Of The Invention
Formula (I) chemical compound has the effect of a kind of advantages of good skin light in mammal, but people still expect the osmosis of enhanced (I) chemical compound to mammal skin.Find beyond expectationly that now theme composition of the present invention has obtained the excellent permeability of formula (I) chemical compound in mammal skin.
As used in this, " local application " be meant and directly be applied to or spread on the crust.
As used in this, " skin Lightening " is meant melanic minimizing in skin, one or multinomial comprehensive light comprising skin key colour, alleviating of the damage of excessive chromogenesis, comprise senile plaque, melasma, moth patch, the pigment spot that the excessive chromogenesis or the sun bring out after freckle, the inflammation.
As used in this, " solid " is meant it is being that solid-state form and " liquid " are meant under 25 ℃ temperature it is liquid form under 25 ℃ the temperature.
As used in this, all percentage rate all are percetages by weight except as otherwise noted.
The representative example of formula (I) chemical compound is as follows.
4-[(tetrahydrochysene-2H-pyrans-2-yl) oxo] phenol (being called THPOP hereinafter).
4-[(tetrahydrochysene-2H-sulfo-pyrans-2-yl) oxo] phenol.
These chemical compounds are pressed the method preparation described in the WO9523780.
Skin Lightening composition of the present invention contains preferably from about 0.001% to about 10%, more preferably from about 0.01% to about 8%, being from about 0.1% to about 5% better, most preferably is that from about 0.5% to about 3% formula (I) chemical compound is as the activating agent the topical composition.
The theme composition that use contains the activating agent more than 3% for excessive chromogenesis damage alleviate and other zone of the light that needs are basic is preferred.
Average polar solvent
For dissolution type (I) chemical compound, because formula (I) chemical compound is all to be insoluble average polar molecules in intensive polar solvent and non-polar solven, formula (I) chemical compound is necessary to be dissolved in a kind of average polar solvent.The ratio (organic property/inorganic nature) that average polar solvent can preferably have organic property and inorganic nature is 0.2 to 3.6 solvent, more preferably is that organic property and inorganic nature ratio (organic property/inorganic nature) are 0.5 to 3.5 solvent.The ratio of organic property and inorganic nature (organic property/inorganic nature) is at medicine bulletin (Pharmaceutical Bulletin), and the 2nd rolls up, and No. 2,163 pages (1954); And chemical medicine field (The Field of Chemical (Kagaku no Ryoiki) the 11st volume, No. 10, narration to some extent in 10 months nineteen fifty-sevens.Average polar solvent comprises liquid triglyceride such as Oleum Ricini, olive oil and capric acid/Trivent OCG; Acceptable ester oil such as Palmic acid isopropyl esters, oleic acid oil base ester, tetradecanoic acid 2-octyl group dodecyl ester and two sad DOPCP on the cosmetics (commodity are called Cosmol 525, are made by Nisshin oil Mills LTD); Liquid fat alcohol is as oleyl alcohol, isooctadecanol, lanolin alcohol, hexadecanol, octyldodecanol, inferior oleyl alcohol, linolenyl alcohol, arachidic alcohol and 2-octyldodecanol; Liquid fatty acid such as oleic acid and isostearic acid; Cinnamic acid octyl group methoxyl group ester; Cinoxate; With right-dimethylaminobenzoic acid 2-ethyl phenyl ester.Following non-ionic surface active agent can be used as average polar solvent.Although following non-ionic surface active agent is used as average polar solvent, other non-ionic surface active agent of hereinafter mentioning (" non-ionic surface active agent " explains part in this manual) is absolutely necessary for purposes of the invention.Draw together ether such as polyoxypropylene 15 stearyl ether and polyoxypropylene ethylene glycol 14 butyl ethers of polyoxypropylene or polyoxyethylene and aliphatic alcohol, polyoxypropylene or polyoxyethylene castor oil or castor oil hydrogenated such as polyoxyethylene (3) Oleum Ricini and polyoxyethylene (5) castor oil hydrogenated as the ionic surfactant pack of average polar solvent; Polyoxypropylene or polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene (20) dehydrated sorbitol mono-fatty acid ester and sorbitan trioleate; Polyoxypropylene or polyoxyethylene sorbitol fatty acid ester such as polyoxyethylene (6) Sorbitol four oleates; Polynary glycerol or fatty acid glyceride such as single oleic acid two glyceride, glyceryl dioleate and single glyceryl isostearate; Polyoxypropylene or polyoxyethylene fatty acid glyceride such as polyoxyethylene (5) glyceryl monooleate; Polyoxypropylene or polyoxyethylene alkyl phenyl ether such as polyoxyethylene (2) nonylplenyl ether and polyoxyethylene (3) octyl phenyl ether.
In average polar solvent, liquid triglyceride or the acceptable ester oil of cosmetics are preferred, and capric acid/Trivent OCG or two sad DOPCP are preferred.The good penetration effect does not obtain by average polar solvent itself, but obtain by described liquid crystal.
The amount of average polar solvent depends on the amount of formula (I) chemical compound.Yet skin Lightening composition of the present invention contains preferably from 5% to 50% average polar solvent, more preferably from 10% to 25% average polar solvent.
A kind of or two kinds or multiple average polar solvent can be used among the present invention.
Polyhydric alcohol
Polyhydric alcohol comprises glycerol, two glycerol, triglycerin, polynary glycerol, polypropylene glycol, Polyethylene Glycol, ethylene glycol, diethylene glycol, 2,2'-ethylenedioxybis(ethanol)., propylene glycol, dipropylene glycol, hexanediol, 1,3-butanediol, 1,4-butanediol, ethylene glycol monoalkyl ether, diglycol monotertiary alkyl ether, glucose, maltose, sucrose, lactose, xylose, xylitol, Sorbitol, mannitol, maltose alcohol, malbit, pantothenylol, tetramethylolmethane and hyaluronic acid and salt thereof.
Skin Lightening composition of the present invention contains preferably from 0.1% to 10%, more preferably from 0.5% to 5% polyhydric alcohol.
One or both or multiple polyhydric alcohol can be used among the present invention.
Solid fatty alcohol
Solid fatty alcohol comprises hexadecanol, octadecanol, tadenan, tetradecanol, batilol, cholesterol and plant sterol.
In solid fatty alcohol, hexadecanol is preferred.
Skin Lightening composition of the present invention contains preferably from 0.1% to 10%, more preferably from 0.5% to 3% aliphatic alcohol.
One or both or multiple solid fatty alcohol can be used among the present invention.
Non-ionic surface active agent
Ionic surfactant pack is drawn together the poly-glycerine fatty acid ester, methyl glycol fatty acid ester, fatty acid glyceride, sorbitan fatty acid esters, sucrose fatty acid ester, polyoxyethylene sorbitan fatty acid esters, the polyoxyethylene sorbitol fatty acid ester, cithrol, the polyoxyethylene fatty acid glyceride, polyoxyethylene castor oil, the hardened Oleum Ricini of polyoxyethylene, polyoxyethylene alkyl ether, the polyoxyethylene plant sterol, polyoxyethylene polyoxy-propylene, polyoxyethylene alkyl phenyl ether, Wool wax alcohols,ethoxylated, polyoxyethylene lanolin alcohol, polyoxyethylene Cera Flava derivant, the polyoxyethylene fatty acid amide, polyether silicone derivant and polyoxyethylene fatty acid ester.
Non-ionic surface active agent preferably can be that the HLB value is 10 to 17 and is solid non-ionic surface active agent under room temperature (25 ℃).Preferred nonionic comprises polyoxyethylene (40) monostearate, polyoxyethylene (21) octadecyl ether and monostearate ten glyceride.
Skin Lightening composition of the present invention contains preferably from 0.1% to 5%, more preferably from 0.5% to 2% non-ionic surface active agent.
One or both or multiple non-ionic surface active agent can be used among the present invention.
Water
Skin Lightening composition of the present invention contains preferably from 40% to 90%, more preferably from 60% to 80% water.
Lecithin
Lecithin is a kind of natural product of deriving from Semen sojae atricolor or egg yolk and obtaining.
Skin Lightening composition of the present invention contains preferably from 0.5% to 5%, more preferably from 2% to 3% lecithin.
The active component of combination
A.
Sunscreen or sunlight screener
Tanning by the sun in the adjusting of the skin of the formed blackening of ultraviolet light to hold up the compositions of brightener and sunscreen or sunlight screener to reach by using active skin.The sunlight screener that is suitable for comprises, for example, and zinc oxide and titanium dioxide.
Ultraviolet light is a main cause that causes skin darkening.Therefore, for the purpose of skin Lightening, need be with skin lightener and a kind of UVA and/or the combination of UVB sunscreen.
Various conventional sunscreen are suitable for being used in combination with skin lightener.People such as Segarin,
Cosmetic science and technology (Cosmetics Science and Technology), chapter 8, place such as the 189th page discloses a large amount of sunscreen that are suitable for.The sunscreen of particularly suitable comprises, for example, and para-amino benzoic acid, and salt and its derivant (ethyl, isobutyl group, glyceryl ester; ESCAROL 507); O-aminobenzoa (that is o-aminobenzoa; Methyl, base, phenyl, benzyl, phenylethyl, linalyl, tyerpinyl and cyclohexenyl group ester); Salicylate (amyl group, phenyl, benzyl, base, glyceryl and dipropylene glycol ester); Cinnamic acid derivative ( base and benzyl ester, butyl cinnamoyl pyruvate); Dihydroxycinnamic acid derivant (umbelliferone, methylumbelliferone, methyl acetyl loose shape ketone); Trihydroxy cinnamic acid derivative (esculetin, methyl esculetin, daphnetin and glucoside, Esculin and daphnin); Hydrocarbon (diphenyl diethylene, stilbene); Dibenzalacetone and benzalacetophenone; Naphthol sulfonate (beta naphthal-3,6-sodium disulfonate and beta naphthal-6,8-disulfonic acid sodium salt); Dihydroxy naphthlene formic acid and salt thereof; Adjacent and to the hydroxy diphenyl disulfonate; Coumarin derivative (7-hydroxyl, 7-methyl, 3-phenyl); Diazole (2-acetyl group-3-bromo-indazole, benzene base benzoxazole, methyl naphtho-oxazole, various aryl benzothiazoles); 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 derivant thereof (for example Hexaethyl ether); (butyl carbotol) (6-propyl group piperonyl) ether; Hydroquinone; Benzophenone (oxybenzene, sulisobenzone, dioxybenzone, the benzo resorcinol, 2,2 ', 4,4 '-tetrahydroxybenzophenone, 2,2 '-dihydroxy-4,4 '-the dimethoxy benzophenone, octabenzone; 4-isopropyl diphenyl formyl methane; Butyl methoxydibenzoylmethise; Etocryene; With 4-isopropyl-dibenzoyl methane.
In these chemical compounds, 2-ethylhexyl p-methoxycinnamic acid ester, 4,4 '-tert-butyl group methoxy dibenzoyl methane, 2-hydroxyl-4-methoxy benzophenone, octyldimethyl-para-amino benzoic acid, two Galla Turcica (Galla Helepensis) acyl trioleates, 2,2-dihydroxy-4-methoxy benzophenone, ethyl-4-(two (hydroxypropyl)) Aminobenzoate, 2-ethylhexyl-2-cyano group-3,3-diphenylacrylate ester, the 2-Ethylhexyl salicylate, the glyceryl p-aminobenzoate, 3,3,5-trimethylcyclohexyl salicylate, the methyl o-aminobenzoa, ESCAROL 507 or Aminobenzoate, 2-ethylhexyl-right-dimethyl-Aminobenzoate, 2-Phenylbenzimidazole-5-sulfonic acid, the mixture of 2-(right-dimethylaminophenyl)-5-sulfo group benzoxazole acid (benzoxazoic acid) and these chemical compounds is preferred.
Be applicable to that the preferred sunscreen in the compositions of the present invention is 2-ethylhexyl-p-methoxycinnamic acid ester, butyl methoxydibenzoylmethise, 2-hydroxyl-4-methoxy benzophenone, octyldimethyl para-amino benzoic acid and their mixture.
The sunscreen that is specially adapted to equally in the compositions is to be presented to the United States Patent (USP) the 4th of Sabatelli in June 26 nineteen ninety, 937, No. 370 and the United States Patent (USP) the 4th that was presented to Sabatelli and Spirnak on March 12nd, 1991,999, disclosed those sunscreen in No. 186, these two pieces of patents merge as a reference at this.Have two different chromophore parts in this patent in the individual molecule of disclosed sunscreen, they demonstrate different ultraviolet radiation absorption spectrums.One in the chromophore mainly absorbs in the UVB radiation scope, and another absorbs consumingly in the UVA radiation scope.
The preferred member of this class sunscreen is 2, the 4-N of 4-dihydroxy benaophenonel, N-(2-ethylhexyl) methylamino benzoate; N, the ester of N-two-(2-ethylhexyl)-4-amino benzoic Acid and 4-hydroxy benzophenone acyl methane; 4-N, the ester of N-(2-ethylhexyl) methylamino benzoic acid and 4-hydroxy benzophenone acyl methane; 4-N, the ester of N-(2-ethylhexyl) methylamino benzoic acid and 2-hydroxyl-4-(2-hydroxyl-ethyoxyl) benzophenone; 4-N, the ester of N-(2-ethylhexyl) methylamino benzoic acid and 4-(2-hydroxyl-oxethyl) dibenzoyl methane; N, the ester of N-two (2-ethylhexyl)-4-amino benzoic Acid and 2-hydroxyl-4-(2-hydroxyl-oxethyl) benzophenone; And N, the ester of N-two (2-ethylhexyl)-4-amino benzoic Acid and 4-(2-hydroxyl-oxethyl) dibenzoyl methane and their mixture.
The sunscreen of certain safety and effective dose can be used in the compositions that the present invention is suitable for.Sunscreen must be compatible with skin lightener.Compositions preferably contains from about 1% to about 20%, more preferably from about 2% to about 10% sunscreen.Amount will depend on selected sunscreen and the needed sunlight protection factor (SPF) and change accurately.
A kind of reagent also be introduced in the present invention in the arbitrary composition that is suitable for to improve the skin substantivity of those compositionss, particularly strengthens their water-wash resistance or anti-wiping property.A kind of preferred reagent that this benefit can be provided is ethylene and acrylic acid copolymer.Be disclosed in the United States Patent (USP) 4,663,157 of the Brock that the compositions that contains this copolymer was issued on May 5th, 1987.
B.
Antiinflammatory
In being applicable to preferred skin Lightening composition of the present invention, antiinflammatory is contained in the compositions with skin lightener as a kind of active component.But the benefit that contains the skin Lightening of antiinflammatory enhancing composition.Antiinflammatory provides very strong protection (although it provides certain protection equally in the UVB scope) in the UVA radiation scope.Antiinflammatory partial application can reduce since long-term exposure in the skin darkening that ultraviolet produced.(see Bissett, Bush that on July 11st, 1989 issued and the United States Patent (USP) 4,847,071 of Chatterjee; And the United States Patent (USP) 4,847,069 of Bissett and Chatterjee, for referencial use in this merging.)
The certain safety and the antiinflammatory of effective dose be introduced in the present invention in the compositions that is suitable for, be preferably compositions about 0.1% to about 10%, more preferably be about 0.5% to about 5%.The accurate amount that joins the antiinflammatory in the compositions will depend on used specific antiinflammatory, because the effectiveness of these medicaments alters a great deal.
The steroid antiinflammatory, include but not limited to, corticosteroid such as hydrocortisone, the hydroxyl triamcinolone, the Alpha-Methyl dexamethasone, dexamethasone phosphate, beclomethasone dipropionate, the valeric acid Clobetasol, desonide, desoximetasone, Deseoxycortone, dexamethasone, dichlorisone, diflorasone diacetate, nerisona, fluadrenolone, the flucloronide, the fluorine hydrocortisone, the neopentanoic acid aniprime, fluocinolone acetonide, fluocinonide, fluocortin butyl, fluocortolone, fluprednylidene acetate, flurandrenolide, chlorine fluorine pine, hydrocortisone acetate, hydrocortisone butyrate, medrat, omcilon, cortisone, the deoxidation cortisone, fiucetonide, the fluorine hydrocortisone, two acetic acid difluorosone, fluradrenolone acetonide, 6, amcinafal, amcinafide, betamethasone and its ester trim thing, the chlorination prednisone, acetic acid chlorprednisone, Clocortolone, clescinolone, dichlorisone, difluprednate, the flucloronide, 9-removes the fluorine fluocinonide, flurandrenolide, fluperolone acetate, fluprednisolone, the valeric acid hydrocortisone, the cyclopentanepropanoiacid acid hydrocortisone, Hydrocortamate, the methyl prednisone, 6.alpha.-fluoro-16.alpha.-methylprednisolone, meticortelone, prednisone, beclomethasone dipropionate, triamcinolone and their mixture are operable.The preferred steroid antiinflammatory that is suitable for is a hydrocortisone.
Be applicable to that the second class antiinflammatory in the compositions comprises non-steroidal anti-inflammatory agents.The classes of compounds that this group comprised is well-known to those skilled in the art.More detailed open for the chemical constitution of non-steroidal anti-inflammatory agents, synthetic, side effect etc. can the reference standard textbook, comprises
Anti-inflammatory and wind resistance Wet medicine (Anti-inflammatory and Anti-Rheumatic Drugs), K.D.Rainsford, I-III volume, CRC publishing house, Boca Raton, (1985) and
Antiinflammatory, Chemistry and pharmacology(
Anti-inflammatory Agents, Chemistry and Pharmacology), 1, people such as R.A.Scherrer, academic press, New York (1974).
The specific non-steroidal anti-inflammatory agents that is applicable to the present composition includes, but are not limited to:
1) Oxicams such as piroxicam ， isoxicam, Tenoxicam, thiophene oxygen thiazine and CP-14,304;
2) salicylic acid, as aspirin, salsalate, benorylate, Choline magnesium trisalicylate, safapryn, probenecid, diflunisal and fendosal;
3) acetic acid derivative, as diclofenac, trichlorine (phenoxy) phenylacetic acid, indometacin, sulindac, tolmetin, oxygen acetic acid, Tiopinac, zidometacin, rantudil, Fentiazac, McN 2783-21-98, clidanac ， Oxepinac and felbinac;
4) fenamic acids is as mefenamic acid, meclofenamic acid, flufenamic acid, niflumic acid and clotame;
5) propanoic derivatives, as ibuprofen, naproxen benoxaprofen, flurbiprofen, ketone ibuprofen, fenoprofen, fenbufen, Indoprofen, Pirprofen, Carprofen Evil promazine, pranoprofen, miroprofen ， Tioxaprofen, sutoprofen see suprofen, alminoprofen and Artiflam;
6) pyrazoles is protected Qin Song as Phenylbutazone, Offitril, feprazone, azapropazone and front three.
The mixture of these non-steroidal anti-inflammatory agents also can be used for the present invention with their pharmaceutically acceptable salt is the same with ester.For example, etofenamate, a kind of flufenamic acid derivant is particularly useful for local the use.Ibuprofen in non-steroidal anti-inflammatory agents, naproxen, flufenamic acid, mefenamic acid, meclofenamic acid, piroxicam and felbinac are preferred; Ibuprofen, naproxen and flufenamic acid are most preferred.
Be applicable to that other class antiinflammatory in the compositions is a disclosed antiinflammatory in the people's such as Loomans that issue on November 24th, 1987 No. the 4th, 708,966, the United States Patent (USP).This patent disclosure one class non-steroidal anti-inflammatory compounds, they comprise the phenyl compound of replacement particularly, particularly replace 2, the 6-ditert-butyphynol derivative.For example, be selected from following chemical compound: 4-(4 '-pentyne-3 '-ketone)-2, the 6-DI-tert-butylphenol compounds; 4-(5 '-the hexin acyl group)-2, the 6-DI-tert-butylphenol compounds; 4-((S)-(-)-3 '-methyl-5 '-the hexin acyl group)-2, the 6-DI-tert-butylphenol compounds; 4-((R)-(+)-3 '-methyl-5 '-the hexin acyl group)-2, the 6-DI-tert-butylphenol compounds; And 4-(3 ', 3 '-the dimethoxy propiono)-2, the 6-DI-tert-butylphenol compounds is applicable in the method for the present invention; 4-(5 '-the hexin acyl group)-2, the 6-DI-tert-butylphenol compounds is most preferred.
Also have a class to be applicable to that antiinflammatory in the compositions is those disclosed antiinflammatory in No. the 4th, 912,248, the United States Patent (USP) of the Mueller that issues March 27 nineteen ninety.This patent disclosure specific ester compounds that contains the 2-naphthyl and non-enantiomer mixture thereof, particularly have the naproxen ester and the Naproxol ester compounds of two or more chiral centres.For example, be selected from (S)-naproxen-(S)-2-butyl ester, (S)-naproxen-(R)-the 2-butyl ester, (S)-Naproxol-(R)-the 2-Methyl Butyric Acid ester, (S)-chemical compound of Naproxol-(S)-2-Methyl Butyric Acid ester, (S)-naproxen-(S)-2-butyl ester and (S)-naproxen-(R)-non-enantiomer mixture of 2-butyl ester and (S)-Naproxol-(R)-2-Methyl Butyric Acid ester and (S)-Naproxol-(S)-non-enantiomer mixture of 2-Methyl Butyric Acid ester is applicable to the present invention.
At last, so-called " natural " antiinflammatory is applicable in the method for the present invention.For example, candelilla wax, α-bisabolol, Aloe, Manjistha, (rubia belongs to, particularly the extract of Arisaema balansae Engl. platymiscium) and Guggal (bdellium, the particularly extract of guggal resin plant) can be used for the present invention.
Be applicable to that other preferred compositions of the present invention contains skin lightener, sunscreen and antiinflammatory and is used for skin Lightening jointly, their amount is as disclosed in each component hereinbefore.
C.
Antioxidant/free radical scavenger
In being applicable to preferred skin Lightening composition of the present invention, antioxidant/free radical scavenger is included in the compositions with skin lightener as a kind of active component.Containing antioxidant/free radical scavenger can increase the benefit of compositions skin Lightening.
The certain safety and the antioxidant/free radical scavenger of effective dose be introduced into and be applicable in the compositions of the present invention, be preferably compositions about 0.1% to about 10%, more preferably be about 1% to about 5%.
Antioxidant/free radical scavenger such 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 (commercially available) with the Trolox trade mark, gallate and its Arrcostab, propyl gallate particularly, uric acid and its salt and Arrcostab, sorbic acid and its salt, the acid ascorbyl ester of fatty acid, amine (for example, N, N-diethyl hydroxylamine, amino-guanidine), sulfhydryl compound (for example glutathion) and Dihydroxyfumaric acid and its salt can use.
In being applicable to preferred compositions of the present invention, that compositions contains is a kind of, the sunscreen of any two or all three kinds, antiinflammatory, and/or antioxidant/free radical scavenger is included in the compositions with skin lightener as active component.These reagent that contain two or all three kinds with skin lightener can increase the skin Lightening benefit of compositions.
D.
Chelating agen
In the preferred compositions of Shi Yonging, chelating agen is contained in the compositions with skin lightener as a kind of active component in the present invention.Be meant and from an individual system, remove a metal ion species by forming a kind of complex as " chelating agen " used in this literary composition, so metal ion is difficult for a kind of activating agent of participation or catalyzed chemical reaction.Including a kind of chelating agen can increase the benefit of the skin Lightening of compositions.
The certain safety and the chelating agen of effective dose be introduced in the present invention in the compositions that is suitable for, be preferably compositions about 0.1% to about 10%, more preferably be about 1% to about 5%.The chelating agen that is suitable in compositions is in U.S. Patent Application Serial Number 619,805, Bissett, Bush and Chatterjee, file an application (continuation application that it is the U.S. Patent Application Serial Number 251,910 of submission on October 4th, 1988) November 27 nineteen ninety; Bush that submit to April 26 nineteen ninety and the U.S. Patent Application Serial Number 514,892 of Bissett; Bush with on February 25th, 1991 submitted to is disclosed in the U.S. Patent Application Serial Number 657,847 of Bissett and Chatterjee, and these patent applications are for referencial use in this merging.The preferred chelating agen that is suitable in compositions of the present invention is furil-dioxime and its derivant.
In the preferred compositions of Shi Yonging, compositions includes a kind of, any two kinds, any three kinds or whole four kinds sunscreen, antiinflammatory, antioxidant/free radical scavenger and/or chelating agen and skin lighteners as activating agent in the present invention.Contain the skin Lightening benefit that two kinds, three kinds or whole four kinds of these reagent can increase compositions with skin lightener.
E.
Retinoic acid-like
In the present invention in the preferred compositions of Shi Yonging, retinoic acid-like (retinoid), preferably tretinoin is contained in the compositions with skin lightener as a kind of activating agent.But the skin Lightening benefit that includes the retinoic acid-like enhancing composition.The certain safety and the retinoic acid-like of effective dose be introduced in the present invention in the compositions that is suitable for, be preferably compositions about 0.001% to about 2%, more preferably be 0.01% to about 1%.Comprise vitamin A analog all natural and/or synthetic or retinol similar compound as " retinoic acid-like " used in this literary composition, the same with the geometric isomer and the stereoisomer of these chemical compounds, these chemical compounds have the biological activity of vitamin A in skin, as all-trans retinoic acid and 13-suitable-tretinoin.
In the present invention in the preferred compositions of Shi Yonging, also contain a kind of, any two kinds, any three kinds, any four kinds with skin lightener as active ingredient compositions, and/or whole five kinds sunscreen, antiinflammatory, antioxidant/free radical scavenger, chelating agen and/or retinoic acid-like.But contain the skin Lightening benefit of two kinds, three kinds, four kinds or whole five kinds of these reagent enhancing composition with skin lightener.
Other optional component
Other optional component comprises thickening agent such as CVP Carbopol ETD2050, antiseptic, lipoidis, vitamin, nutrient and the skin conditioning agent of liquid and mastic pigment, astringent, pH buffer agent, spice, infrared ray screening agent, amphoteric and solid amorphous.
The skin conditioning agent that is suitable for is the elastin fiber of β-Radix Glycyrrhizae thujic acid and its derivant, vegetation extract, alantin (alantoin), collagen protein, extract and processing.
Be applicable to that topical composition of the present invention can make emulsion type products.These include, but are not limited to emulsion, emulsifiable paste and ointment.
Emulsion type products contains a kind of chemical compound that comprises formula (I), the liquid crystal of average polar solvent, polyhydric alcohol, aliphatic alcohol, non-ionic surface active agent, water and lecithin.
Usually contain acceptable aqueous solution on a kind of cosmetics or as organic solvent and a kind of lipoid or the oil of ethanol, isopropyl alcohol, sorbitol ester and their mixture according to emulsion of the present invention.Lipoid and oil can be derived from animal, plant or oil and can is natural or synthetic (promptly synthetical).
Emulsion also can contain defoamer so that make foam minimum on being used in skin the time.Defoamer comprises other material of knowing for this usage in high-molecular weight siloxanes and this area.
Emulsion preferably contains a kind of siloxanes that is used to transmit a kind of preferred dermal sensation.Common this siloxanes has lower molecular weight.The siloxanes that is suitable for comprises cyclomethicone, and polydimethylsiloxane and mixture such as Dow Corning 200 fluids (particularly 10cs) and Dow CorningQ2-1401, this class siloxanes are from Midland, and the Dow Corning company of MI can be purchased.
Skin Lightening composition of the present invention can contain the acceptable emollient of a kind of topical cosmetic.Be meant except that protection as " emollient " used in this literary composition and also be used to prevent or alleviate exsiccant material the skin.Various suitable emollient are known and can be used among the present invention.Sagarin, cosmetics, Science and Technology, second edition, the 1st rolls up, and 32-43 page or leaf (1972) is for referencial use in this merging, contains the example of the material that is suitable for use as emollient in a large number.Skin Lightening cosmetics of the present invention contain typically from about 5% to about 50%, preferably from about 10% to about 25% emollient.
The method of mammal skin light
The present invention also relates to the method for skin Lightening in the mammal, comprise local application skin Lightening composition of the present invention.The amount of activating agent and frequency of administration alter a great deal with the speed of already present skin color in the subjects, the further melanism of skin and the degree of required light.
Usually the certain safety and the skin lightener of effective dose are to about 10 gram per centimeters from about 1 gram in each topical composition that uses
2Skin preferably restrains to about 8 gram per centimeters from about 2
2Skin more preferably is to about 7 gram per centimeters from about 3 grams
2Skin preferably restrains to about 5 gram per centimeters from about 4
2Skin.Preferably the scope of access times be from about one day four times to about one all secondaries, more preferably be from about one day three times to approximately every once a day, preferably from approximately once a day to about one day secondary.At least need to use the effect that just can see the lower animal skin Lightening in 5 days.At least need to use the skin Lightening effect that just can see the people in one month.After obtaining skin Lightening, the frequency of use and dosage can reduce to the level of keeping as required.This keeping according to the personal considerations changes, and still, preferably from about 1/10 to about 1/2, more preferably is from about 1/5 to about 1/3 original dosage and/or frequency according to needed.
The method that preferably is used for the mammal skin light of the present invention comprises that use further contains one or more the skin Lightening composition of the present invention of sunscreen, antiinflammatory, antioxidant/free radical scavenger, chelating agen and/or retinoic acid-like of certain safety and effective dose.The amount of used sunscreen is preferably from about 0.01 milligram to about 0.1 milligram/centimetre
2Skin; The amount of used antiinflammatory is preferably from about 0.005 milligram to about 0.5 milligram, is from about 0.01 milligram to about 0.1 milligram/centimetre better
2Skin; The amount of used antioxidant/free radical scavenger is preferably from about 0.001 milligram to about 1.0 milligrams, is from about 0.05 milligram to about 0.5 milligram/centimetre better
2Skin; The amount of used chelating agen is preferably from about 0.01 milligram to about 1.0 milligrams, more preferably is from 0.01 milligram to about 0.5 milligram, preferably from about 0.05 milligram to about 0.1 milligram/centimetre
2Skin; The amount of used retinoic acid-like is preferably from about 0.001 milligram to about 0.5 milligram/centimetre
2Skin is more preferably from about 0.005 milligram to about 0.1 milligram/centimetre
2Skin; The amount of used skin lightener is preferably extremely made an appointment with for about 0.001 milligram from each use
2Milligram/centimetre
2Skin is from each use about 0.01 milligram to about 1 milligram/centimetre better
2Skin.
The preparation method of skin Lightening composition of the present invention
For example, the skin Lightening composition that contains liquid crystal of the present invention can make through the following steps:
(i) under 60 ℃ to 100 ℃ temperature with a kind of formula (I) chemical compound of certain safety and effective dose, a kind of average polar solvent, a kind of aliphatic alcohol, a kind of non-ionic surface active agent and lecithin mixed mixture 1 and
(ii) a kind of polynary alcohol and water is mixed mutually with mixture 1, simultaneous temperature remains on 45 ℃ to 100 ℃.Will be as above step (i) and the mixture that (ii) makes be cooled to room temperature usually.
Other component can be mixed in a conventional manner, yet common oil-soluble component can add in above-mentioned (i) step and water miscible component added in the above-mentioned (ii) step.
Liquid crystal can detect by the shape of a polarized light microscope observing liquid crystal.
Embodiment
Embodiment is within the scope of the present invention further narrated and illustrated to the following example.Embodiment only is used for illustrative purposes, and should not be counted as limitation of the present invention, because their many variants may not exceed the spirit and scope of the present invention.
Test implementation example 1
The preparation method of reference composition
THPOP is dissolved in polypropylene glycol (14) butyl ether (THPOP phase-1).Individually polyoxyethylene (21) octadecanol, polyoxyethylene (2) octadecanol, hexadecanol, octadecanol, cyclomethicone and hexadecanoic acid acid ascorbyl ester are dissolved down and fully stir at 70 ℃.Adding THPOP phase-1 then mixes (THPOP mutually-2) with continuing.
In another container, other component of all except that said components is in 70 ℃ of dissolvings (water).
THPOP phase-2 and water fully mixed and be cooled to obtain O/w emulsion (O/W emulsion).The component of reference composition sees Table 1.
The preparation method of No. 1 test composition
THPOP, capric acid/Trivent OCG (Migyol 812), hexadecanol, polyoxyethylene (40) monostearate and lecithin are mixed together and are heated to 70 ℃.Then, under agitation add deionized water and glycerol and with emulsifying mixture.Then under agitation emulsive mixture is cooled to room temperature, obtains having the emulsion of liquid crystal.To have the emulsion of liquid crystal and all other components except that said components is mixed together and obtains compositions No. 1.The component of No. 1 compositions sees Table 2.
The preparation method of No. 2 test composition
THPOP, two sad DOPCP (Cosmol 525), hexadecanol, polyoxyethylene (40) monostearate and lecithin are mixed together and are heated to 70 ℃.Then, under agitation add deionized water and glycerol and with emulsifying mixture.Then, under agitation emulsive mixture is cooled to room temperature, obtains a kind of emulsion with liquid crystal.To have the emulsion of liquid crystal and all other components except that said components is mixed together and obtains compositions No. 2.The component of No. 2 compositions sees Table 3.
Table 1
Contrast (O/w emulsion)
Group component (weight %)
Deionized water 75.70
IN hydrochloric acid 2.30
Triethanolamine 1.40
Magnesium ascorbyl phosphate 0.10
Sodium metabisulfite 0.05
EDTA disodium salt 0.05
Polyoxyethylene (21) stearyl alcohol (21) 2.00
Polyoxyethylene (2) stearyl alcohol (2) 1.00
Polypropylene glycol (14) butyl ether 7.50
Hexadecanol 3.00
Stearyl alcohol 1.50
Cyclomethicone 1.00
Ascorbic palmitate 0.10
THPOP 3.00
Butanediol 1.00
Glydant?Plus 0.30
(" Glydant Plus " is dihydroxymethyl-5, the 5-dimethyl hydantoin (with) the iodo propinyl butyl carbamate)
Table 2
No. 1 compositions
Group component (weight %)
Lecithin 3.00
Polyoxyethylene (40) monostearate 1.00
(Myrj?52)
Hexadecanol 1.00
Capric acid/Trivent OCG 15.00
(Migyol?812)
D-Δ tocopherol 0.10
Glycerol 5.00
Propyl parabene 0.10
Nipagin 0.20
THPOP 3.00
Deionized water 69.13
Sodium metabisulfite 0.08
Sodium sulfite 0.20
Sodium hydroxide 0.59
CVP Carbopol ETD2050 1.00
(Carbopol?980)
Benzyl alcohol 0.60
Table 3
No. 2 compositions
Group component (weight %)
Lecithin 3.00
Polyoxyethylene (40) monostearate 1.00
(Myrj?52)
Hexadecanol 1.00
Two sad DOPCP 21.00
(Cosmol?525)
D-Δ tocopherol 0.10
Glycerol 5.00
Propyl parabene 0.10
Nipagin 0.20
THPOP 3.00
Deionized water 63.13
Sodium metabisulfite 0.08
Sodium sulfite 0.20
Sodium hydroxide 0.59
CVP Carbopol ETD2050 1.00
(Carbopol?980)
Benzyl alcohol 0.60
Method of testing
(1)
Device
Use the diffusion liquid bath of no jacket layer.The area of section of infiltration is 0.79 centimetre
2
This design by E.W.Merritt and E.R.Cooper at " sustained release magazine ", 1 (2), narration to some extent among the 161-162.The low glass top of acceptable dose solution evaporation is used for this research.
To spread liquid bath and remain on 37 ℃ body temperature at the aluminium part that places an agitating heating assembly (Peirce Chemical Co.).Each aluminium part can be placed six liquid baths.Assembly is controlled temperature and stirring motor is provided for the diffusion liquid bath.
(2)
Buffer solution
Used normal saline solution is from Wako Pure ChemicalIndustries LTD in this preparation, the saline of the Dulbeco ' s phosphate-buffered that does not contain calcium chloride and sodium bicarbonate that CAM7276 obtains (hereinafter claiming " PBS ").PBS regenerates with distilled water by label explanation and adds 0.002% (S/V) Hydrazoic acid,sodium salt (Wako Pure Chemical Industries LTD is KCE6293) to slow down microbial growth.PBS solution is maintained in one 37 ℃ the water-bath so that the solution degassing in whole experiment.It also is acceptable under agitation solution being evacuated 15 minutes with a getter.
(3)
People's corpse skin of excision
(OH) thickness that can obtain freezing excision is 0.25 millimeter fell (wash and cut hair after) for Shriners Burns Institute, Cincinnati from Ohio Valley skin and organization center.Skin is placed the solution bath 24 hours of broad ectrum antibiotic, and the glycerite with 10% is handled, with the gauze parcel and place the aseptic paper tinsel bag of sealing.Skin is cut into～1.2 * 1.2 centimetres with a dissecting knife (Keisei MedicalIndustrial Co.4# handle, 21# blade)
2The receptor compartment that the glass diffusion liquid bath of PBS solution (4-5 milliliter) is housed remains on 37 ℃ in aluminium part.Skin chunk flatly is placed on the liquid bath, and horny layer is towards donor compartment, and corium contacts with receptor compartment.The glass top of Zu Saiing is not placed on the liquid bath and clamps securely in position.Aluminium parts is put back in the assembly and little magnetic stirring bar is put into the receptor compartment of liquid bath, continuous stirring in whole experiment.
(4)
Experimental technique
Contact with PBS solution and horny layer is exposed under the airborne situation skin-balance is spent the night at corium, or balance 16 hours at least.The basic computer program is used to the randomization group and each spreads correspondingly labelling of liquid bath quilt.After balance and before the medication, new PBS solution is outwelled and reloaded to the solution in the receptor compartment.This step comprises the solution of pouring out in the receptor compartment, with the fresh PBS solution rinsing of 2-3 milliliter with reload fresh PBS solution.When pouring out solution, prevent that with a hands of possessing the band glove of Magnet little stirring rod is poured out.By holding the glass liquid bath at a certain angle and rapping and remove the air bubble of assembling at the skin surface of fell.Observe the temperature of solution in receptor compartment randomly and adjusted SATOPAC-9400 thermocouple thermometer of use in whole experiment in case of necessity.
(5)
Dosed administration and sampling method
With a pipette test composition and reference composition are applied on the horny layer (donor compartment).If apply the material of smaller size smaller, this material is evenly distributed on the skin with the imbibition tip.Occlusion if desired can be sealed film with a fritter immediately and be sealed the glass top behind dosed administration.The collection in 6 and 24 hours behind dosed administration usually of receptor compartment sample.The collection sample comprises to be poured the solution in the receptor compartment in the phial into, pours in the phial PBS solution of packing into fresh then into the PBS solution rinsing of 2-3 milliliter with this rinsing liquid.Blank sample (just PBS solution) is collected all after dates at each and is obtained and be used for background measuring.Simulation dosed administration solution aliquot is weighed to join in the flicker phial and is used for efficient liquid phase chromatographic analysis so that calculate the used mean dose of each liquid bath.A kind of solution of test substances of preparation and alcoholic acid aliquot also will be carried out efficient liquid phase chromatographic analysis, so that result standardization and set up conversion factor for data analysis.
(6)
Clean method
When experiment finishes, the liquid bath demolition is got off and washing in strong detergent solution (Alconox), with the distilled water rinsing with at air drying.Skin with paper tinsel wrap with incineration process before be stored in the refrigerator.Lacking under the cremation facilities situation, can use dense H
2SO
4Solution dissolving skin.With the stirring rod rinsing be placed on one and fill in the alcoholic acid beaker and spend the night.Clamping plate are with the distilled water rinsing and wash with Alconox solution once in a while.
(7)
Efficient liquid phase chromatographic analysis
The aliquot of infiltration sample and dosed administration solution and standard solution is then analyzed THPOP% with high performance liquid chromatography (using the Shimazu LC-9A of JSPHERE ODS M80 post).
Osmotic value calculates with following formula
Test result sees Table 4.
Table 4
The osmotic value of each time of test composition (%)
6 hours 24 hours
No. 1 compositions 5.20 18.07
No. 2 compositions 6.47 23.92
Contrast 2.94 6.54
As shown in the table 4 in the above, can obtain the excellent permeation reinforced effects by No. 1 compositions of the present invention and No. 2 compositions.
Claims (19)
1. skin Lightening composition, said composition contains
(a) certain safety, a kind of formula (I) chemical compound of effective dose
[formula (I)]:
Wherein Z is oxygen or sulfur,
(b) a kind of average polar solvent,
(c) a kind of polyhydric alcohol,
(d) a kind of solid fatty alcohol,
(e) a kind of non-ionic surface active agent
(f) water and
(g) lecithin,
Wherein at least a portion said components (a) and (b), (c), (d), (e) (f) and (g) form a kind of liquid crystal.
2. skin Lightening composition, said composition contains by whole composition weight meter
(a) chemical compound of a kind of formula (I) of 0.001-10%
[formula (I)]:
Wherein Z is oxygen or sulfur,
(b) a kind of average polar solvent of 5-50%,
(c) a kind of polyhydric alcohol of 0.1-10%,
(d) a kind of solid fatty alcohol of 0.1-10%,
(e) a kind of non-ionic surface active agent of 0.1-5%,
(f) water of 40-90% and
(g) lecithin of 0.5-5%.
Wherein at least a portion said components (a) and (b), (c), (d), (e), (f) and (g) form a kind of liquid crystal.
3. the compositions of claim 2, wherein Z is an oxygen.
4. the compositions of claim 2, wherein Z is a sulfur.
5. the compositions of claim 2, the compound dissolution of its Chinese style (I) is in a kind of average polar solvent.
6. the compositions of claim 2, wherein the organic property and the inorganic nature ratio of average polar solvent are 0.2 to 3.6.
7. the compositions of claim 2, wherein average polar solvent is a kind of liquid triglycerides.
8. the compositions of claim 2, wherein average polar solvent is an acceptable ester oil on a kind of cosmetics.
9. the compositions of claim 2, wherein average polar solvent is capric acid/Trivent OCG.
10. the compositions of claim 2, wherein average polar solvent is two sad DOPCP.
11. the compositions of claim 2, wherein polyhydric alcohol is a glycerol.
12. the compositions of claim 2, wherein solid fatty alcohol is a hexadecanol.
13. the compositions of claim 2, wherein the HLB of non-ionic surface active agent is 2 to 20.
14. the compositions of claim 2, wherein non-ionic surface active agent is polyoxyethylene (a 40) monostearate.
15. the compositions of claim 2, wherein compositions is a kind of topical composition.
16. an emulsion compositions, said composition contain the said liquid crystal of with good grounds claim 2.
17. a paste composition, said composition contain the said liquid crystal of with good grounds claim 2.
18. one kind is used for mammalian skin light method, this method comprises the local skin Lightening composition that uses according to claim 1.
19. a method for preparing the skin Lightening composition that contains liquid crystal, this method comprises the following steps:
(i) press whole composition weight meter 60 ℃ of-100 ℃ of mixing
(a) a kind of formula (I) chemical compound of 0.001-10%
[formula (I)]:
Wherein Z is oxygen or sulfur,
(b) a kind of average polar solvent of 5-50%,
(c) a kind of solid fatty alcohol of 0.1-10%,
(d) a kind of non-ionic surface active agent of 0.1-5% and
(e) lecithin of 0.5-5%
With obtain mixture 1 and
(ii) following component is mixed with mixture 1 by whole composition weight meter
(f) a kind of polyhydric alcohol of 0.1-10% and
(g) water of 40-90%
And remain on 45 ℃-100 ℃ temperature.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 96180451 CN1191816C (en) | 1996-08-21 | 1996-08-21 | Skin lightening composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 96180451 CN1191816C (en) | 1996-08-21 | 1996-08-21 | Skin lightening composition |
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| Publication Number | Publication Date |
|---|---|
| CN1229354A CN1229354A (en) | 1999-09-22 |
| CN1191816C true CN1191816C (en) | 2005-03-09 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 96180451 Expired - Fee Related CN1191816C (en) | 1996-08-21 | 1996-08-21 | Skin lightening composition |
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| CN104274340A (en) * | 2013-07-09 | 2015-01-14 | 苏州元素集化学工业有限公司 | Composition with stable liquid crystal structure and application of composition |
| CN107308019A (en) * | 2017-06-12 | 2017-11-03 | 上海应用技术大学 | A kind of improved emulsifying agent and preparation method thereof |
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