CN1124841C - Cosmetic skin lightening product for topical application - Google Patents

Abstract

A cosmetic skin lightening product for topical application which contains components (A) cysteine and (B) glycyrrhizic extract or dicarboxyl of 7-30 carbon atom suitable to cosmetic carrier. The common components have a synergistic reaction in reduceing the generation of melanin.

Description

Cosmetic skin lightening product for topical application

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 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 when being 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.

United States Patent (USP) 5523077 has proposed a kind of skin whitening and has pressed down and shine compositions, wherein contains a kind of chemical compound, and this chemical compound does not contain the alkyl ether or the aralkyl ethers of glutathion and hydroquinone or hydroquinone.Preferred this chemical compound that does not contain glutathion that adopts is buthionine sulfoximine or Guang ammonia.

(Advances in Biology of skin.W.Motagna and F.Hu compile " skin progress biology ", Pergamon Press, Oxford, 1967,421-445 page or leaf) the sun-proof result of study shown in the 26th chapter comprises the catalog of depigmenting agent to normal chromatophorous usefulness.Under study for action, to black Carassius auratus subcutaneous injection concentration be 0.5% test compound.Report that the mercapto-amine derivant that comprises mercaptoethylmaine (MEA) and Guang ammonia can alleviate pigmentation.

We find some mercapto-amine derivant and two carboxylic acids or the shared energy of Radix Glycyrrhizae extract are promoted the inhibitory action that melanin is generated at present.Therefore the invention provides a kind of cosmetic skin lightening product for topical application, wherein comprise component (A) the half Guang ammonia that is present in the carrier that is applicable to cosmetics and (B) Radix Glycyrrhizae extract or contain two carboxylic acids of 7-30 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.

Component A is a cysteamine.The notion of cysteamine comprises 2-mercaptoethylmaine (2-MEA), that is, and and its alkali and hydrochloric acid mercaptoethylmaine.Most preferred component A is the 2-mercaptoethylmaine.

B component is two carboxylic acids, Radix Glycyrrhizae extract or its mixture that contains 7-30 carbon atom.Two carboxylic acids are the acid with HOOC-R-COOH structure.R is the saturated or undersaturated of straight or branched, and it can be substituted, for example can be through hydroxylating.Preferred R base is undersaturated, and contains 8-23 carbon atom, especially preferably contains 13-20 carbon atom.Therefore the contained the total number of carbon atoms of preferred acid is a 10-25 carbon atom, is in particular 15-22 carbon atom.The particularly preferred pair of carboxylic acid contains this chain length and carbochain is straight chain, is unsubstituted, and is to contain one, two or three unsaturated bonds.

Radix Glycyrrhizae extract for example can be prepared according to the described method of J02204495, for example adopts 10 parts of (volume) hexanes and 1-4 part (volume) acetone or 0.5-1.5 part (volume) ethanol mixed solvent extraction licorice or its water to carry residue also except that desolvating.Radix Glycyrrhizae extract is commercially available, for example available from MaruzenPharmaceutical Company, Japan.

The pH of preferred this product is 5-9, more preferably 6-8.

Component A and B component are 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.

The contained component A and the weight ratio of B component are 100: 1 to 1: 5000 in the preferred product, more preferably 10: 1 to 1: 500.

The consumption of cysteamine is preferably 0.001-10% (weight) in the product, more preferably 0.1-8% (weight), particularly 1-5% (weight).The consumption of B component is preferably 0.001-20% (weight) in the product, more preferably 0.1-15 (weight) 1-10% (weight) particularly.The mixing consumption of component A and B preferably accounts for the 0.1-25% (weight) of product, more preferably 1-15% (weight).

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 branch.Equally, the cysteamine derivant that can discharge cysteamine also can be used as component A.

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 2-4 month can occurring visible skin whitening effect, this will decide on component A and the consumption of B 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 is added with 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 MR5000) measures its absorbance under 540nm with microdroplet price fixing reader, and with the calibration of the absorbance reference value of fresh culture, 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 54nm 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.

Change in the eliminating minute titration dish melanin analysis with culture medium after, 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 2-mercaptoethylmaine and 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 two carboxylic acids 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.Mensuration shown in the Table A is C with two carboxylic acids ₁₈-two carboxylic acids.This pair carboxylic acid product is available from UnichemaNetherlands.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: 2-mercaptoethylmaine and two carboxylic acid

% suppresses percentage ratio	Dicarboxyl acid (mM)
					0	0.5	1
2-mercaptoethylmaine (mM)
				0	0	-9	39
0.01	1	-10	89
				0.02	9	-3	90
0.03	19	28	88

Table B:2-mercaptoethylmaine and Radix Glycyrrhizae extract

% suppresses percentage ratio	Radix Glycyrrhizae extract (ppm)
						0	1.8	3.5	7
2-mercaptoethylmaine (mM)
					0	0	16	25	72
0.01	7	24	30	89
					0.02	10	44	53	89
0.03	26	53	52	91

Table C:2-mercaptoethylmaine and nicotiamide (matched group)

% suppresses percentage ratio	Nicotiamide
						0	5	10	15
2-mercaptoethylmaine (mM)
					0	0	-23	-17	-14
0.01	36	-17	-10	-6
					0.02	48	-4	3	5
0.03	61	0	2	5

Table D: Radix Glycyrrhizae extract and citric acid (matched group)

% suppresses 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

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.

The above results shows that the cysteamine and the conjugate of two carboxylic acids or Radix Glycyrrhizae extract have synergism to suppressing the melanin generation.In contrast, the conjugate of cysteamine and commonly used skin whitening composition nicotiamide but shows and does not produce potentiation.It seems that these medicaments influence each other nocuously rather than strengthen each other effect mutually.Table D 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 GB2 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.

Chemical constituent full name or its CTFA name	Trade (brand) name	Weight %
			Radix Glycyrrhizae extract		3.0
The 2-mercaptoethylmaine		2.0
			The EDTA disodium	Sequestarene 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 18DEO	1.5
Petiolus Trachycarpi isooctadecanol ester	Protachem ISP	6.0
			Sad C 12-15Alcohol ester	Hetester FAO	3.0
Dimethyl polysiloxane	Silicone Fluid200(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
Palmic acid and flavol ester	Vitamin A Palmitate	0.06
			The 2-bisabolol	Alpha-bisabolol	0.2
Deionized water		Add to 100

Embodiment 2

In the compositions of embodiment 1, with 8.0% (C ₁₈, single-and two-unsaturated) alternative 3.0% Radix Glycyrrhizae extract of two carboxylic acids.

Claims (13)

1. human body skin is local with brightening cosmetics, wherein comprises component A cysteamine and B component Radix Glycyrrhizae extract that is present in the carrier that is applicable to cosmetics or the two carboxylic acids that contain 7-30 carbon atom.

2. the product of claim 1, wherein two carboxylic acids are to contain unsaturated pair of carboxylic acid of 10-25 carbon atom.

3. the product of claim 2, wherein two carboxylic acids are to contain unsaturated pair of carboxylic acid of 15-22 carbon atom.

4. arbitrary product of claim 1-3, the weight ratio of wherein contained component A and B component is 100: 1 to 1: 5000.

5. the product of claim 4, the weight ratio of wherein contained component A and B component is 10: 1 to 1: 500.

6. arbitrary product of claim 1-5 wherein comprises the cysteamine of 0.001-10% (weight).

7. the product of claim 6 wherein comprises the cysteamine of 0.1-8% (weight).

8. the product of claim 7 wherein comprises the cysteamine of 1-5% (weight).

9. arbitrary product of claim 1-8 wherein comprises the B component of 0.001-20% (weight).

10. the product of claim 9 wherein comprises the B component of 0.1-15% (weight).

11. the product of claim 10 wherein comprises the B component of 1-10% (weight).

12. the product of arbitrary claim among the claim 1-11 wherein contains sunscreen.

13. be used for the beauty method that human body skin brightens, wherein be product by arbitrary claim among the local coating claim 1-12 on skin.