WO2005048972A1

WO2005048972A1 - Skin whitening cosmetic composition

Info

Publication number: WO2005048972A1
Application number: PCT/KR2004/003004
Authority: WO
Inventors: Hee Kyung Ju; Hyun Jung Choi; Chang Hoon Park; Jae Sung Hwang; Sang Hoon Han; Han Kon Kim
Original assignee: Amorepacific Corporation
Priority date: 2003-11-19
Filing date: 2004-11-19
Publication date: 2005-06-02
Also published as: KR20050048259A; KR100921947B1

Abstract

The present invention relates to a skin whitening cosmetic composition, which has a skin-whitening effect by regulating melanin synthesis in a three (3)-stage, i.e. inhibiting of excessive formation of melanin, modulating of coloring of melanin and accelerating discharge of melanin. More particularly, the skin whitening cosmetic composition of the present invention comprises an EPS complex functioning as inhibitor of excessive formation of melanin and modulator of coloring of melanin, and a keratin remover as accelerator of discharge of melanin, and thus has an excellent skin-whitening effect.

Description

SKIN WHITENING COSMETIC COMPOSITION

BACKGROUD OF THE INVENTION

1. Field of the Invention The present invention relates to a skin whitening cosmetic composition, which regulates melanin synthesis in three stages, i.e. inhibiting excessive formation of melanin, modulating coloring of melanin and accelerating discharge of melanin. More particularly, the skin whitening cosmetic composition of the present invention comprises an EPS complex functioning as inhibitor of excessive formation of melanin as well as modulator of coloring of melanin, and a keratin remover as accelerator of discharge of melanin, and thus has an excellent skin-whitening effect.

2. Description of Prior Art When exposed to UV light, melanin determining the color of human skin is synthesized and released to induce hyperpigmentation such as melasma, freckles and spots, which are unfavorable results with regard to beauty. The process of the melanin synthesis is as follows: tyrosinase in cells acts on tyrosine to form dopaquinone, and melanin is produced therefrom. Thus, in order to prevent skin darkness, an approach to inhibit a part of the process of the melanin synthesis in order to reduce the melanin synthesis itself has been generally studied. Examples of such developed whitening agent are kojic acid, arbutine, vitamin A and vitamin C. Melanin plays important roles, in addition to that of determining skin color, such as protecting a gene from UV light by forming a hat-like structure around a nucleus, and protecting protein in the cell by eliminating free radicals. Thus, developing a novel type of whitening agent that does not excessively inhibit the synthesis of melanin is highly desired. Generally, melanin is composed of eumelanin, which is dark, and pheomelanin, which is pale, both of which are produced from dopaquinone. If cystein is acted on dopaquinone in the synthesis of melanin, cystenyldopa, which is the precursor of pheomelanin, is formed. The skin-darkening effect of melanin is caused by eumelanin, and there is a report that it is possible to obtain skin-whitening effect by converting eumelanin to pheomelanin, i.e. by modulating the coloring of melanin without reducing the quantity of melanin itself (Benathan M. et al; Cellular and Molecular Biology 1999; 45; 981 -990). Thus, it is possible to develop a skin-whitening agent modulating the coloring of melanin, which is even better and safer than a general skin- whitening agent inhibiting the melanin synthesis. The present inventors have conducted extensive studies in order to develop a skin- whitening agent having an excellent skin- whitening effect without any side effect, and found that compounds having -SH moiety in their structure such as cystein produce cystenyldopa, which is the precursor of pheomelanin, and have a skin-whitening effect, and that an EPS complex containing compounds with the general skin-whitening agent inhibiting the melanin synthesis has an excellent skin-whitening effect. In addition, the inventors found that when using a keratin remover in combination with the above EPS complex, the skin-whitening effect is promoted, and thereby completed the present invention. SUMMARY OF THE INVENTION

Thus, an object of the invention is to provide a new skin-whitening cosmetic composition, which produces an excellent skin- hitening effect without any side effect.

DETAILED DESCRIPTION OF THE INVENTION To attain the object of the present invention, there is provided a skin-whitening cosmetic composition, characterized in that it regulates melanin synthesis in three stages, i.e. inhibiting excessive formation of melanin, modulating coloring of melanin and accelerating discharge of melanin. The skin-whitening cosmetic composition according to the present invention is characterized in that it contains an EPS complex as an effective ingredient. The EPS complex of the present invention contains an inhibitor of melanin synthesis with a modulator of melanin coloring. Hereinafter, the present invention is described in more detail. Skin-whitening agents developed until the present date inhibit the activity of tyrosinase, which plays the most important role in melanin synthesis, and thereby reduce the quantity of melanin. However, such skin-whitening agents have a problem that their use amount is limited because of the side effect of inducing a skin irritation. Therefore, they cannot be used in sufficient amount so as to produce a satisfactory skin-whitening effect. However, according to the present invention, it is possible to obtain a satisfactory skin-whitening effect without any side effect by using an EPS complex containing both a skin-whitening agent converting eumelanin to pheomelanin, and an inhibitor of melanin synthesis in an appropriate amount so as not to produce a skin-irritation. Further, it is possible to produce an even better skin-whitening effect by further comprising a keratin remover, which can remove old keratin of skin in order to promote the discharge of melanin. The EPS complex of the present invention comprises an inhibitor of melanin synthesis and a modulator of melanin coloring. The inhibitor of melanin synthesis used in the EPS complex of the present invention, may include at least one selected from the group consisting of kojic acid, arbutine, vitamin A and its derivatives, vitamin C and its derivatives, hydroquinone, and licorice. The amount of the inhibitor is preferably 0.00001~2% by weight based on the total weight of the composition. If it exceeds 2% by weight, it may induce a skin irritation. The modulator of melanin coloring may include at least one substance having -SH moiety in its structure such as lipoic acid, dilinolylcystamine, glutathione, dipalmityl glutathione, S-lactyl glutathione or oxidized glutathione. The amount of the modulator is preferably 0.00001~10% by weight based on the total weight of the composition. If it is less than 0.00001% by weight, the skin- whitening effect by the modulation of melanin coloring cannot be obtained, and if it exceeds 10% by weight, the solubility of the substance in the composition may be decreased. The keratin remover, which can promote discharge of melanin in order to enhance the skin-whitening effect, may include one or more selected from protease, such as papain, and alpha-hydroxy acid. The amount of the keratin remover is preferably 0.01-10% by weight based on the total weight of the composition. If it is less than 0.01% by weight, the effect of removing keratin cannot be obtained, and if it exceeds 10% by weight, it may induce a side effect such as skin-irritation or change of smell. The skin-whitening cosmetic composition according to the present invention may be formulated into, but is not limited thereto, skin softener, nutrition water, massage cream, nutrition cream, pack, gel, essence, make-up base, foundation, lotion, ointment, gel, cream, patch or spray.

BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a photograph showing the effect of the EPS complex on the formation of melanin in the human melanoma cell. From the left are control group, the cell treated with licorice, and the cell treated with EPS complex I. Fig. 2 shows the effect of licorice, lipoic acid and EPS complex I on the formation of melanin in the melanoma cell. Fig. 3 shows the effect of ethyl ascorbate (EA), glutathione, and EPS complex II on the formation of melanin in the melanoma cell.

PREFERRED EMBODIMENT OF THE INVENTION

The present invention will be described in more detail by way of the following examples, comparative examples and experimental examples. However, these examples are provided for the purpose of illustration only and should not be construed as limiting the scope of the invention, which will be apparent to one skilled in the art.

[Preparation Example 1] EPS complexes I and II were prepared in accordance with the compositions in Table 1. In each complex, an inhibitor of melanin formation and a modulator of melanin coloring were mixed in a ratio of 1:1. For the inhibitor of melanin formation, licorice and ethyl ascorbate were used, and for the modulator of melanin coloring, lipoic acid and glutathione were used.

Experimental Example 1> Determination of the effect of inhibiting the formation of melanin HM3KO cells (Y. Funasaka, Department of Dermatology, Kobe University School of Medicine, 5-1 Kusunoki-cho 7-chrome, Chuo-ku, Kobe 650, Japan), which are the human melanoma cells, were placed in Minimum Essential Medium (MEM) containing 10% of bovine embryo serum and cultured at 37 ^°C, 5% C0₂. Cultured cells were spread on the bottoms of 75cm flasks with a cell number of 3 x lO⁵ per flask, and left overnight so that the cells were fully stuck on the walls of the flasks. After confirming that the cells were stuck on the wall, each medium was changed to a new one containing 10 ppm of the test samples described in Table 1. For the control group, a medium containing DMSO was used. In this way, each medium was changed to a new one containing test samples once every 2~3 days, untill the cells were cultured to fill the flask. When the cells were mature, the colors of the cells in the control group and those treated with the test samples were compared, and the result is shown in Fig. 1. The culture fluid was removed, washed with PBS, and dissolved with IN NaOH to measure optical density (OD) at 500 nm, and the rate of inhibiting the melanin formation was calculated in the following numerical formula I. The result was shown in Table 1.

[Numerical Formula 1 ] Rate of inhibiting the melanin formation (%) = 100 x [(OD of each test sample)/(OD of the control)]

[Table 1 ]

As can be seen in the result of Fig.1 and Table 1 , it was confirmed that a better skin-whitening effect was obtained when using the EPS complex than using each component of the complex.

Experimental Example 2>: Determination of the rate of the melanin formation in the melanoma cell To understand the melanin component, the optical density (OD) of the cells treated as in Experimental Example 1 was measured at 350 nm and 400 nm to obtain the amount of eumelanin and phemelanin, and the resultant amount was shown in Figs. 2 and 3. As can be seen in Figs. 2 and 3, it was confirmed that lipoic acid and glutathione increase the amount of pheomelanin and decrease the amount of eumelanin. In addition, it was confirmed that licorice and EA, a derivative of vitamin C, do not have an effect on the synthesis of the two melanin components. From the above results, it is considered that the function of modulating melanin coloring of EPS complex is caused by lipoic acid and glutathione contained in EPS complex, and it is assumed that a much better skin-whitening effect can be expected if such a modulator of melanin coloring is used together with an inhibitor of melanin formation.

[Examples 1~2 and Comparative Examples 1-2] Soluble formulations in the form of transparent gel were prepared according to the compositions in Table 2. The viscosity of the formulations was about 3,000 cps. The viscosity was measured at 30^°C , 12 rpm, using Brookfield (LVDVII+). [Table 2]

[Examples 3-4 and Comparative Examples 3-4] The formulations of Examples 3-4 and of Comparative Examples 3-4 were prepared according to the compositions in Table 3. Each oil phase and aqua phase was fully dissolved at 70 ^°C , then emulsified for 5 minutes at 7,000 rpm to prepare lotion in the form of turbid gel. The viscosity of the lotion was about 2,000 cps.

[Table 3]

Experimental Example 3>: Skin-whitening effect on human skin An opaque tape having 6 holes of diameter 1.5 cm was adhered to an upper-arm of each of twelve (12) healthy men, and UV beam (UVB) having strength 1.5 - 2 times the minimal erythema dose of each subject was radiated to induce melanization of the skin. The formulations of the examples and the comparative examples were then applied 2 times a day (in the morning and the evening), and after two (2) months the darkness of the skin was determined using chromameter. The effect was judged by way of the value "L" showing the lightness of the skin (The value "L" of the Korean people with no sun-burn is usually 50-70). In case there is any effect caused by application of the test sample, the value L is increased. The comparison was made between the test samples by the value ΔL (the final value of L - the value of L before the application of the test sample). The larger is the value ΔL, the greater is the skin-whitening effect. The values ΔL are shown in Table 4 below.

[Table 4]

From the results of Table 4, it was confirmed that the ΔL in Examples 1 and 3, which used EPS complex together with a keratin remover, were higher than those of Comparative Examples. As described in the above, it was confirmed that EPS complex consisting of an inhibitor of melanin formation and a modulator of melanin coloring has a superior skin-whitening effect compared with the prior skin-whitening agent. In addition, it was also confirmed that when the cosmetic composition further comprises a keratin remover, which can promote the discharge of melanin, an even more improved skin-whitening effect can be obtained. Therefore, the cosmetic composition comprising EPS complex as well as an accelerator of the discharge of melanin has a skin-whitening effect by a three stage process, and shows a much improved skin- whitening effect over the prior art. Although this invention has been described with respect to specific embodiments, the details of these embodiments are not to be construed as limitations. Various equivalents, changes and modifications may be made without departing from the spirit and scope of this invention, and it is understood that such equivalent embodiments are part of this invention.

Claims

1. A skin whitening cosmetic composition comprising an inhibitor of excessive formation of melanin and a modulator of coloring of melanin.

2. The composition according to Claim 1, further comprising an accelerator of discharge of melanin.

3. The composition according to Claim 1, wherein said inhibitor of excessive formation of melanin is at least one selected from the group consisting of kojic acid, arbutine, vitamin A, derivatives of vitamin A, vitamin C, derivatives of vitamin C, hydroquinone and licorice.

4. The composition according to Claim 1 , wherein said modulator of coloring of melanin converts eumelanin to pheomelanin, and is a substance containing -SH moiety.

5. The composition according to Claim 4,wherein said substance containing -SH moiety is at least one selected from the group consisting of lipoic acid, dilinolylcystamme, glutathione, dipalmityl glutathione, S-lactyl glutathione and oxidized glutathione.

6. The composition according to Claim 2, wherein said accelerator of discharge of melanin is at least one selected from the group consisting of protease and alpha-hydroxy acid.

7. The composition according to Claim 6, wherein said protease is papain.

8. The composition according to Claim 1, wherein the composition is formulated into skin softener, nutrition water, massage cream, nutrition cream, pack, gel, essence, make-up base, foundation, lotion, ointment, gel, cream, patch or spray.

9. A skin whitening cosmetic composition, characterized in that it regulates melanin synthesis in three stages comprising inhibiting excessive formation of melanin, modulating coloring of melanin and accelerating discharge of melanin.

1/2

FIG 1

control licorice EPS complex group

FIG 2

control licorice lipoic acid EPS group complex I 2/2

FIG 3

ffleumelanin El pheomelanin

control EA glutathione EPS complex group