CN1214241A - Cosmetic skin lightening product for topical application - Google Patents
Cosmetic skin lightening product for topical application Download PDFInfo
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- CN1214241A CN1214241A CN 98120560 CN98120560A CN1214241A CN 1214241 A CN1214241 A CN 1214241A CN 98120560 CN98120560 CN 98120560 CN 98120560 A CN98120560 A CN 98120560A CN 1214241 A CN1214241 A CN 1214241A
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- ferulic acid
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- skin
- radix glycyrrhizae
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Abstract
A cosmetic skin lightening product for topical application which contains components (A) a dicarboxylic acids contains HOOC-R-COOH structure, wherein R is alkyl or alkenyl of 5-13 carbon atoms, B ferulic acid, ferulic acidic ester or licorice extract. The common components have a synergistic reaction in reduceing the generation of melanin.
Description
It is local with the method that brightens cosmetics and human body skin is brightened to the present invention relates to a kind of human body skin.
Many people worry some the pigementation phenomenon on their skin.For example there are the people of senile plaque or wrinkle to wish that these mottles can become not too obvious.Other people then wish to reduce the skin melanism that causes because of Exposure to Sunlight, and its natural colour of skin is shoaled.For satisfying these requirements, attempt having developed and manyly can reduce pigmentogenic product in the melanocyte.But these materials of finding all have disadvantageous side effect, for example skin irritation at present.Therefore these materials are not suitable for cosmetics, perhaps only can be used for local coating and its skin whitening effect is lower than desired effect with finite concentration.It is believed that the shared meeting of various skin whitening materials is reduced side effect, but the main trouble of doing like this is: since the competition effect of each material, this shared skin whitening effect reduction that also can make.Therefore need improve the usefulness of skin whitening cosmetics.
British patent discloses and discloses a kind of skin whitening cosmetic formulation in 2287405, wherein contains the plant extract of Glycyrrhiza glabra L. extract or corresponding kind, and 'alpha '-hydroxy acids, beta-hydroxy acid or keto acid, or its amide, salt or ester.This mixture allegedly has coordinate repression to tryrosinase, thereby can suppress melanic formation.
International patent application discloses 94/07462 disclosed compositions and particularly contains retinol or derivatives thereof and a kind of pair of carboxylic acid in the skin whitening composition.
International patent application discloses 94/09756 and propose to adopt retinol or derivatives thereof and a kind of selected skin whitener to be common to reach to comprise some purpose that alleviates the colour of skin.Preferred skin whitener is a hydroquinone, but also mentions some other composition, comprises Radix Glycyrrhizae extract.
Comprise kojic acid in the skin whitening product that United States Patent (USP) 4990330 is described, it and other composition are shared, and these compositions are selected from certain limit, comprise Azelaic Acid.Report that this shared inhibition melanin is synthesized has synergism.
JP63284119 (Derwent digest) proposes a kind of preparation for external application to skin with anti-ultraviolet and whitening effect, wherein comprises Hesperetic acid or its salt, and a kind of organic acid or its salt.
J06199646 (Derwent digest) has described a kind of skin-whitening cosmetic, wherein comprises plant extract, urea and urea stabilizing agent.Extract can be selected from widely, and plant comprises licorice (root of Radix Glycyrrhizae).The urea stabilizing agent also is selected from thing group widely, comprises aliphatic dicarboxylic acid.
Find that so far the said goods is not extensively to be suitable for, also need this field is proceeded to improve.
We find some two carboxylic acid and ferulic acid or its ester or the shared inhibitory action that can promote the melanin generation of Radix Glycyrrhizae extract at present.Therefore the invention provides a kind of cosmetic skin lightening product for topical application, wherein comprise two carboxylic acids and ferulic acid, ferulic acid ester or Radix Glycyrrhizae extract, wherein two carboxylic acids contain the HOOC-R-COOH structure, and wherein R is the alkyl or alkenyl that contains 5-13 carbon atom.
The present invention includes a kind of beauty method that human body skin brightens that is used for, this method is by the product of the present invention of local coating on skin.
The R base of preferred two carboxylic acids is the alkyl that contain 6-10 carbon atom.Most preferred pair of carboxylic acid is Azelaic Acid [HOOC-(CH
2)
7-COOH].
Ferulic acid is the structure such as the formula I of 3-methoxyl group-4-hydroxycinnamic acid:
Two carboxylic acids, ferulic acid and ferulic acid ester all are commercially available.
Ferulic acid ester can be used for substituting ferulic acid or can be shared with ferulic acid.Esterified group preferably contains 1-30 carbon atom, more preferably comprises 2-20 carbon atom.This group can be saturated or unsaturated, straight or branched, and can be substituted, for example by hydroxylating.In a preferred embodiment of the invention, ferulic acid is compared with ferulic acid ester, preferably adopts ferulic acid itself.
Radix Glycyrrhizae extract for example can be prepared according to the described method of J02204495, for example adopts 10 parts of (volume) hexanes and 4 parts of (volume) acetone or 0.5-1.5 part (volume) ethanol mixed solvent to extract licorices or its water and carries residue and remove and desolvate.Radix Glycyrrhizae extract is commercially available, for example available from MaruzenPharmaceutical Company, Japan.
The pH of preferred this product is 5-9,6-8 more preferably, particularly about 7.
The active component that is suitable for is added in the carrier that is applicable to cosmetics to make this cosmetics.Carrier can comprise the composition that is usually used in skin care item, for example water, liquid or solid skin protectant, silicone oil, emulsifying agent, solvent, wetting agent, thickening agent, dusting, spray agent etc.Skin effective active composition that other is special such as sunscreen and hydroxy acid also can add in the carrier.Add sunscreen particularly preferably in product of the present invention, particularly when product is used for general skin whitening rather than mottle nursing.Also can comprise adjuvant such as essence, antioxidant, antiseptic, coloring agent and buffer agent in the carrier.Suitable skin care item dosage form commonly used such as cream frost or the emulsion etc. made of this product.This product also can be the product that is called as " eccysis formula product ", for example bathe and use gel, wherein may comprise the active component induction system, can promote in the rinse cycle skin to the absorption of active component, but preferably this product is disposable product, need not careful rinsing after promptly being coated on the skin so that the product of removing substantially from skin.Can adopt the same procedure that is usually used in preparing skin care item to prepare this product.Suitable earlier active component being dissolved or dispersed in a part of water or other solvent or liquid of compositions.
Can adopt conventional method with the product splendid attire in container such as canister, bottle for example.
Two carboxylic acid parts are 1: 10 to 5000: 1 with the ferulic acid composition of another part or the weight ratio of Radix Glycyrrhizae extract in the preferred product, more preferably 1: 1 to 500: 1.Therefore, if adopt ferulic acid, preferably its consumption is by the relative weight of above-mentioned pair of carboxylic acid.Only do not adopt ferulic acid ester if do not adopt ferulic acid, or it is shared, preferably its consumption by the weight of esterified group and, thereby limit is determined the consumption of ferulic acid group or ferulic acid part according to above-mentioned weight ratio.
The consumption of two carboxylic acids is preferably 0.001-20% (weight) in the product, more preferably 0.1-15% (weight), particularly 1-10% (weight).The consumption of the ferulic acid in the product and/or its ester (in ferulic acid partly) or Radix Glycyrrhizae extract is preferably 0.001-10% (weight), more preferably 0.1-8 (weight), particularly 1-5% (weight).The mixing consumption of active component preferably accounts for the 0.1-20% (weight) of product, more preferably 1-15% (weight), particularly 3-10% (weight).For Radix Glycyrrhizae extract, its consumption is with the dry weight basis of extract.
Preferably in product, adopt ferulic acid (ester) or Radix Glycyrrhizae extract, but both should be not shared.We find that ferulic acid and Radix Glycyrrhizae extract have retroaction each other, can reduce the inhibitory action that melanin is generated.
If necessary, two carboxylic acids can its salt or the form of ester add in the product of the present invention, it can be in product or on the skin or skin discharge acid inner the decomposition.Equally, ferulic acid also can be used by its salt form.Like this, should adopt the phase application quantity.But the present invention preferably adopts two carboxylic acids and ferulic acid itself.
In a preferred embodiment of the invention, ferulic acid and/or its ester are used for product with the plant extract form.Certain plants comprises a large amount of ferulic acids or its ester.For example content of ferulic acid is stated to be 13000ppm in Resina Ferulae (Ferula ass-foetida) quintessence oil.Contain the ferulic acid that is higher than 2000ppm in the seed of salvia miltiorrhiza (Salvia sp.), comprise the 200-800ppm ferulic acid in the Fructus Ananadis comosi (Ananas comosus).Plant extract can be provided for all or part of ferulic acid and/or the ferulic acid ester of product of the present invention.
Can this product be coated on the skin according to the similar coating method of conventional skin care item.For example can be coated on the skin (for example face and/or hand or arm) its every day for 1-3 time.For mottle, the user for example can select this product only is coated in site of action.Generally through the 2-3 month can occurring visible skin whitening effect, this will decide on the concentration of active component and the consumption and the coating frequency of product in the situation of skin, the product.Product of the present invention is specially adapted to general skin whitening, when product is used for wherein also can specifically comprising sunscreen when daily.Assay method * cell is kept
Under 37 ℃, moisture-saturated, 5% carbon dioxide existence condition, with B16-F1 mouse black-in tumor cell (American Type Culture Collection, Maryland, USA) 75 square centimeters contain RPMI1640 culture medium (ICN-Flow, classification number 12-60-54) keeps in the culture bottle, additionally added L-glycosamine (4mM) and 10% hyclone (FBS) in the culture medium.Cell is weekly through passage 2 times.* pigmentation test
The 3rd generation of little fusion and the inoculum density of the B16 cell between the 25th generation reach 5 * 10
5Gathered in 72 hours behind cell/75 square centimeter.The pair cell counting, through centrifugal (60 gram) balling-up, and resuspending is in the DMEM that adds L-glycosamine (4mM) and 10%FBS (ICN-Flow classification number 16-427-54).Cell is inoculated in the round bottom hole of the microtiter plates that contains 100 μ lDMEM, and inoculum density is 5 * 10
3Cells/well.Inoculation dish overnight incubation.After about 24 hours, remove culture medium and be replaced with the fresh culture that 200 μ l contain or do not contain measured object immediately through preheating.Every processing procedure repeats 4 times.The media transfer that 180 μ l are painted is in clean flat microtiter plates, in every hole, charge into the normal octane steam to remove bubble, (Dynatech MR 5000) measures its absorbance under 540nm with microdroplet price fixing reader, and send out reference value with the extinction of fresh culture and calibrate, thereby determine the melanin amount that produces in every hole after about 120 hours.The absorbance of calibration is directly proportional with melanin concentration, and the pigmentation percentage ratio of tested skin whitening composition can be calculated as follows: pigmentation percentage ratio=(under the 540nm under measured object optical density/540nm object of reference optical density) * 100% wherein 540nm down and under measured object optical density and the 540nm object of reference optical density be the absorbance meansigma methods of culture medium that contains the culture medium of measured object in the finger-hole and do not contain measured object through calibrating.The inhibition percentage ratio that measured object produces is pigmentation percentage ratio.* cell survival rate test
Can reduce the melanin generation by suppressing the melanin generative process, cytotoxicity and cell proliferation are also influential to melanic generation.Whether exist for measuring this, measure cell survival rate by the absorbance of neutral orchil.Dimethyl diaminophenazine chloride is a water-soluble dye, can be through complete cytoplasmic membrane and in the inner enrichment of the lysosome of intact cell.The absorbtivity of dimethyl diaminophenazine chloride dyestuff is directly proportional with viable count in the culture.
After changing the culture medium of melanin analysis usefulness in the eliminating minute titration dish, the 200 μ l that immediately 200 μ l contained the dimethyl diaminophenazine chloride that concentration is 25 μ l/ml (available from Sigma, UK, classification number 2889) add in the cell through the fresh culture of preheating, cultivate 3 hours to keep cell.Inversion titration dish is also patted in absorbent paper and can be removed the cell that does not have absorbing dye.With 200 μ lPBS washed cells, and then remove PBS.Add 100 μ l solvents (50% water, 49% ethanol, 1% acetic acid).At room temperature left standstill 20 minutes, and with the microtiter plates agitator each titration dish was vibrated for 5 seconds then.Measure absorbance as stated above.In the mensuration to following tested skin whitening composition, the survival rate of measured object pair cell does not also make significant difference.Measure
Shown in the following table is the mensuration and the consumption thereof of the skin whitening composition and composition thereof to tested.The consumption of all the components is all in mmol, but the consumption of Radix Glycyrrhizae extract is in 1,000,000/weight portion (ppm).Tested composition causes that melanin generates inhibition percentage ratio and also lists in the table.In the test, measured object is taken from the aqueous base fluid of citric acid.At first Radix Glycyrrhizae extract is dissolved in DMSO.Make that DMSO concentration is 0.5% (weight) in every hole.When adopting DMSO, should guarantee that the consumption (0.5%) of DMSO in the every hole of matched group is also identical.Earlier ferulic acid and two carboxylic acid are dissolved in the 1N sodium hydroxide.PH regulator to 8.0 to 9.0, is further diluted this solution, the base fluid that obtains being suitable for then.Its pH is 7.4.C is adopted in the matched group test
18-two carboxylic acids.This pair carboxylic acid product is available from Unichema Netherlands.It mainly by the list that has the straight chain that contains 18 carbon atoms-and two-unsaturated pair carboxylic acids constitute, as the R base band 16 carbon atoms are arranged.
Table A: ferulic acid and Azelaic Acid
Table B: ferulic acid and citric acid (matched group)
Table C: Radix Glycyrrhizae extract and Azelaic Acid
Table D: the two carboxylic acids (matched group) of Radix Glycyrrhizae extract and C18-
Table E: Radix Glycyrrhizae extract and citric acid (matched group)
If two kinds of skin whitening compositions do not react to each other each other, pigmentation ratio sum when using separately that the pigmentation ratio (pigmentation percentage ratio/100) when shared can predicted it should be it.Can calculate shared thus and do not have inhibition percentage ratio when reacting to each other.
| Suppress percentage ratio | Ferulic acid (mM) | ||
| ????0 | ????0.001 | ????0.01 | |
| Azelaic Acid (mM) | |||
| ????0 | ????0 | ????5 | ????16 |
| ????0.5 | ????12 | ????0 | ????37 |
| ????1 | ????13 | ????-1 | ????73 |
| ????2 | ????36 | ????39 | ????75 |
| Suppress percentage ratio | Ferulic acid (mM) | ||
| ????0 | ????0.001 | ????0.01 | |
| Citric acid (mM) | |||
| ????0 | ????0 | ????0 | ????19 |
| ????0.5 | ????5 | ????6 | ????28 |
| ????1 | ????8 | ????8 | ????27 |
| ????5 | ????28 | ????24 | ????25 |
| Suppress percentage ratio | Radix Glycyrrhizae extract (ppm) | ||
| ????0 | ????1.8 | ????3.5 | |
| Azelaic Acid (mM) | |||
| ????0 | ????0 | ????-2 | ????36 |
| ????0.5 | ????-1 | ????5 | ????47 |
| ????1 | ????-3 | ????20 | ????73 |
| ????2 | ????0 | ????23 | ????73 |
| Suppress percentage ratio | Radix Glycyrrhizae extract (ppm) | ||
| ????0 | ????1.8 | ????3.5 | |
| The two carboxylic acids (mM) of C18 | |||
| ????0 | ????0 | ????2 | ????15 |
| ????0.5 | ????1 | ????3 | ????8 |
| ????1 | ????0 | ????-7 | ????10 |
| ????1.5 | ????11 | ????13 | ????19 |
| Suppress percentage ratio | Radix Glycyrrhizae extract (ppm) | ||
| ????0 | ????1.8 | ????3.5 | |
| Citric acid (mM) | |||
| ????0 | ????0 | ????13 | ????69 |
| ????0.5 | ????4 | ????2 | ????58 |
| ????1 | ????7 | ????1 | ????57 |
| ????5 | ????16 | ????4 | ????58 |
The above results shows that the combination of Azelaic Acid and ferulic acid or Radix Glycyrrhizae extract has synergism to suppressing the melanin generation.On the contrary, the combination of ferulic acid and citric acid or Radix Glycyrrhizae extract and C
18The combination of-two carboxylic acids or citric acid there is no synergism.As if two compositions interact opposite rather than produce potentiation.Table E shows and there is no interaction with Radix Glycyrrhizae extract and citric acid (a kind of 'alpha '-hydroxy acids) are shared, although should have synergism according to the content of the open GB 2 287 405 of British patent.Adding citric acid also can have a negative impact to the melanin generation inhibitory action of Radix Glycyrrhizae extract.
Embodiment 1
What following compositions was described is cream frost emulsified body of the present invention.
Embodiment 2
| Chemical constituent full name or its CTFA name | Trade (brand) name | Weight % |
| Azelaic Acid | ????7.0????? | |
| Ferulic acid | ????2.0 | |
| The EDTA disodium | ????Sequesterene?Na2 | ????0.05 |
| Magnesiumaluminumsilicate | ????Veegum?Ultra | ????0.6 |
| Nipagin | ????Methyl?Paraben | ????0.15 |
| The monomethyl polysiloxanes | ??DC?Antifoam?Emulsion | ????0.01 |
| 1,3-butanediol | ??Butylene?Glycol?1,3 | ????3.0 |
| Hydroxyethyl-cellulose | ????Natrosol?250HHR | ????0.5 |
| Glycerol (American Pharmacopeia) | ????Glycerine?USP | ????2.0 |
| Xanthan gum | ????Keltrol?1000 | ????0.2 |
| Triethanolamine | ??Triethanolamine(99％) | ????1.2 |
| Stearic acid | ????Pristerene?4911 | ????3.0 |
| Propyl parabene NF | ????Propylparaben?NF | ????0.1 |
| The hydrogenation tristerin | ????Naturechem?GMHS | ????1.5 |
| Stearyl alcohol | ????Lanette?18?DEO | ????1.5 |
| Palmic acid isooctadecanol ester | ????Protachem?ISP | ????6.0 |
| Sad C 12-15Alcohol ester | ????Hetester?FAO | ????3.0 |
| Dimethyl polysiloxane | Silicone?Fluid?200(50cts) | ????1.0 |
| Cholesterol NF | ????Cholesterol?NF | ????0.5 |
| Sorbitan monostearate | ????Sorbitan?Stearate | ????1.0 |
| Butylated hydroxyl toluene | ????Embanox?BHT | ????0.05 |
| Tocopherol acetate ester | ??Vitamin?E?Acetate | ????0.1 |
| The PEG-100 stearate | ????Myrj?59 | ????2.0 |
| Sodium stearoyl lactate | ????Pationic?SSL | ????0.5 |
| Hydroxycaprylic acid | Hydroxycaprylic?Acid | ????0.1 |
| Retinyl palmitate | Vitamin?A?Palmitate | ????0.06 |
| α-bisabolol | ????Alpha-bisabolol | ????0.2 |
| Deionized water | Add to 100 |
In the compositions of embodiment 1, substitute ferulic acid with 2.0% Radix Glycyrrhizae extract.
Claims (9)
1. human body skin is local with brightening cosmetics, wherein comprises:
A. the two carboxylic acids that contain the HOOC-R-COOH structure, wherein R is the alkyl or alkenyl that contains 5-13 carbon atom, and
B. ferulic acid, ferulic acid ester or Radix Glycyrrhizae extract.
2. the product of claim 1, wherein R is the alkyl that contains 6-10 carbon atom.
3. the product of claim 2, two carboxylic acids wherein are Azelaic Acids.
4. the product of arbitrary claim among the claim 1-3, wherein two carboxylic acids parts are 1: 10 to 5000: 1 with the ferulic acid composition of another part or the weight ratio of Radix Glycyrrhizae extract, more preferably 1: 1 to 500: 1.
5. the product of arbitrary claim among the claim 1-4 wherein comprises the two carboxylic acids of component of 0.001-20% (weight), preferred 0.1-15% (weight).
6. the product of arbitrary claim among the claim 1-5 wherein comprises ferulic acid composition or the Radix Glycyrrhizae extract of 0.001-10% (weight).
7. the product of arbitrary claim among the claim 1-6, ferulic acid wherein and/or ferulic acid ester are used with the form of plant extract.
8. the product of arbitrary claim among the claim 1-7 wherein contains sunscreen.
9. being used for the beauty method that human body skin brightens, wherein is the product by arbitrary claim among the local coating claim 1-8 on skin.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9721097.5 | 1997-10-03 | ||
| GBGB9721097.5A GB9721097D0 (en) | 1997-10-03 | 1997-10-03 | Cosmetic skin lightening product for topical application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1214241A true CN1214241A (en) | 1999-04-21 |
| CN1135966C CN1135966C (en) | 2004-01-28 |
Family
ID=10820062
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB981205607A Expired - Fee Related CN1135966C (en) | 1997-10-03 | 1998-10-03 | Cosmetic skin lightening product for topical application |
Country Status (4)
| Country | Link |
|---|---|
| CN (1) | CN1135966C (en) |
| GB (1) | GB9721097D0 (en) |
| ID (1) | ID21648A (en) |
| IN (1) | IN190682B (en) |
-
1997
- 1997-10-03 GB GBGB9721097.5A patent/GB9721097D0/en not_active Ceased
-
1998
- 1998-09-18 IN IN597BO1998 patent/IN190682B/en unknown
- 1998-09-21 ID IDP981267D patent/ID21648A/en unknown
- 1998-10-03 CN CNB981205607A patent/CN1135966C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| ID21648A (en) | 1999-07-08 |
| IN190682B (en) | 2003-08-16 |
| GB9721097D0 (en) | 1997-12-03 |
| CN1135966C (en) | 2004-01-28 |
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