WO2004089328A1

WO2004089328A1 - Composition for skin whitening containing machilin-a

Info

Publication number: WO2004089328A1
Application number: PCT/KR2003/000738
Authority: WO
Inventors: Won-Chan Kim; Ho-Jeong Kim; Cheong-Taek Kim; Mu-Hyun Jin; Sang-Jin Kang; Seung-Ho Lee; Hyeun-Wook Chang; Jong-Keun Son
Original assignee: Lg Household & Healthcare Co., Ltd.
Priority date: 2003-04-12
Filing date: 2003-04-12
Publication date: 2004-10-21
Also published as: AU2003225373A1

Abstract

Disclosed is composition for skin whitening containing machilin-A as an effective component. Machilin-A shows no side effect on skin, and has a superior effect to inhibit pigmentation on skin by restraining melanin from being generated. Thus, the composition containing the same is effectively used for skin whitening.

Description

COMPOSITION FOR SKIN WHITENING CONTAINING MACHILIN-A

TECHNICAL FIELD ^' The present invention relates to composition for skin whitening, and more particularly to composition for skin whitening that has excellent stability with giving no side effects on skin, and have a superior effect to inhibit pigmentation on skin by restraining melanin from being generated.

BACKGROUND ART Most people want to have white and fine skin. The color of human skin is determined by the density and the distribution of melanin inside skin and affected by the environmental or physiological factors such as ultraviolet rays of the sun, fatigue, or stress as well as the genetic factor. Melanin is made through the following steps: first, enzyme tyrosinase affects on a kind of amino acid, tyrosine, to change the same into DOPA or dopaquinone and then the same goes through non-enzymatic oxidation reaction. However, the mechanism that derives melanin synthesis, which is a step before tyrosinase affects, is not clarified in detail though the process through which melanin is made is disclosed.

When the melanin synthesis is excessively performed inside skin, the tone of skin darkens, and chloasma and freckles can be generated. Accordingly, when the melanin synthesis inside skin is inhibited, the skin whitening is possible, plus hyperpigmentation such as chloasma, freckles, etc. due to ultraviolet rays or hormonic and genetic factors can be improved. Conventionally, the skin whitening is tried by mixing material having inhibition function against tyrosinase such as hydroquinone, ascorbic acid, kojic acid, or glutathione with cosmetic such as essence or ointment for external use. However, although hydroqumone shows a prescribed effect of whitening, the mixture amount of the same should be restricted to the minimum since the same seriously irritates skin. In case of ascorbic acid, since the same is easy to be oxidized, cosmetic mixed with the same has problems of discoloration and change of scent. In addition, in case of kojic acid, the same is restricted to be used since the same is unstable. Further, thiol compound such as glutathione or cysteine has a peculiar bad smell and low absorptiveness to skin.

DISCLOSURE OF THE INVENTION

Accordingly, the present invention is designed to solve the problems of the prior art, and an object of the present invention is to provide composition for skin whitening that has excellent stability with giving no side effects on skin, and has a superior effect to inhibit pigmentation on skin by restraining melanin from being generated.

In order to accomplish the object, the present invention provides composition for skin whitening containing machilin-A expressed by the following Chemical Formula 1 as an effective component.

Chemical Formula 1

At this time, the content of the machilin-A is preferably 0.000001 to 10 weight% on the basis of total weight of the composition, more particularly 0.0001 to 10 weight% on the basis of total weight of the composition.

Preferably, the machilin-A is extracted from Areca catechu by means of at least one solvent selected from the group consisting of low alcohol having 1 to 4 carbon atoms, ethyl acetate, acetone, ether, benzene, chloroform, hexane, cyclohexane and petroleum ether. In addition, the composition for skin whitening may have one form selected from the group consisting of skin, lotion, cream, foundation, essence, gel, pack, foam cleansing, soup and ointment for external use.

DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, composition for skin whitening according to the present invention will be described in detail.

The composition for skin whitening according to the present invention contains machilin-A (machilin-A; CAS No. 110269-50-6 5,5'[(2R,3S)-dimethyl-l,4- butanediyl]bis-l, 3-bezodioxole), which is expressed by the following chemical formula 1, as an effective component for skin whitening. Chemical Formula 1

It was reported that machilin-A is a machilin derivative different from nor- dihydroguaiaretic acid, and may be used as an antioxidant (Chem. Pharm. (1990), 21(4), 270-3).

Though machilin-A is known as an antioxidant, the inventors have found that machilin-A show very strong inhibitory effect on formation of melanin and show excellent skin whitening effect as a result from the experiment on B16 mouse melanoma cell which can screen even the material which restrains induction of melanin synthesis itself. Therefore, if machilin-A is added and mixed into the composition for skin whitening such as skin lotion, cream, foundation, essence, gel, pack, foam cleansing, soap and ointment for external use according to the present invention, the high-potency of skin whitening without any special side effect can be obtained.

Machilin-A, an effective whitening component of the composition for skin whitening according to the present invention, is an organic compound having 20 carbon atoms, and may be obtained from essential oil of a microbe, a plant or an animal. In particular, machilin-A may be extracted from peel or root of Area catechu, but not limitedly. An extraction method of machilin-A from Areca catechu will be explained below as an example.

At first, after purchasing and pulverizing peel or root of Areca catechu which is sold in the market as a crude material, the pulverized peel or root is heat-extracted at 50 to 100°C for 1 to 5 hours in an extractor having a spill cooler by means of a coolant such as low alcohol having 1 to 4 carbon atoms, ethyl acetate, acetone, ether, benzene, chloroform, hexane, cyclohexane or petroleum ether. The extract is filtered by a filter cloth, and the residue is then extracted once more in the same way and added to the extract liquid, and then vacuum-concentrated, and freeze-dried or spray-dried to obtain a dried extract. The dried extract is suspended in water, adding ethyl acetate of the same amount thereto, thereby obtaining ethyl acetate fraction by liquid-liquid extraction.

The fraction is then purified by HPLC (High Performance Liquid Chromatography) or column chromatography filled with silica gel or activated alumina.

Machilin-A obtained by the above mentioned method can be added into various skin whitening compositions such as ointment for external use or cosmetic. The content of machilin-A contained in the skin whitening composition of the present invention is preferably 0.000001 to 10 weight% based on the total weight of the composition in consideration of whitening effect and economic efficiency, more preferably 0.0001 to 10 weight%.

The detailed description of the present invention referring to the embodiments is provided hereinafter. However, the embodiments according to the present invention can be modified in various ways and should not be understood that the present invention is restricted to the embodiments described below. The embodiments of the present invention are provided for illustration purpose only to a person having ordinary skill in the art.

Embodiments Extraction Examples of Machilin-A

Extraction Example 1

After purchasing a peel of Areca catechu in the market and then pulverizing it, lOOg of the pulverized peel was put into 500ml of 100% ethyl acetate, and then boiled in a spill extractor having a cooling condenser for 3 hours for the purpose of extraction. Subsequently, the extract was filtered by a 300-mesh filter cloth, and the residue was extracted once more in the same way. The extract liquids were mixed and filtered by Whatman No.2 filter paper at a room temperature to remove insoluble materials, and then vacuum-concentrated at 60°C in a distiller having a cooling condenser and suspended in 300ml of a purified water. 300ml of ethyl acetate was added thereto, and well stirred to obtain an ethyl acetate solution. Subsequently, 450ml of fraction containing an effective component was obtained from the ethyl acetate by using the silica gel column chromatography. It was again purified by HPLC to obtain 200mg of machilin-A. The structure of the machilin-A was validated using mass-spectroscopy and NMR spectroscopy.

Extraction Example 2

105mg of machilin-A was obtained using substantially the same way as the extraction example 1, except that 500ml of 100% ethanol was used instead of 500ml of 100% ethyl acetate.

Extraction Example 3

208mg of machilin-A was obtained using substantially the same way as the extraction example 1, except that 500ml of 100% chloroform was used instead of 500ml of 100% ethyl acetate.

Extraction Example 4

A peel of Areca catechu was purchased in the market and then pulverized, and then lOOg of the pulverized peel was put into 500ml of 100% capric/caprilic triester and then boiled in a spill extractor having a cooling condenser for 3 hours for the purpose of extraction. Subsequently, the extract was filtered by a 300-mesh filter cloth, and then filtered by Whatman No.2 filter paper at a room temperature to remove insoluble materials, and then purified by HPLC to obtain 150mg of machilin-A.

Extraction Example 5

208mg of machilin-A was obtained using substantially the same way as the extraction example 1, except that a pulverized root was put instead of the pulverized peel of Areca catechu and 500ml of n-hexane was used instead of 500ml of 100% ethyl acetate.

Extraction Example 6

208mg of machilin-A was obtained using substantially the same way as the extraction example 1, except that 500ml of n-hexane was used instead of 500ml of 100% ethyl acetate.

Experimental Examples 1 to 3 The whitening effect in a cellular level was tested by adding aqueous solutions of hydroqumone and machilin-A obtained according to the above extraction examples to a culture medium of B-16 mouse melanoma cell (Lotan R., Lotan D. Cancer Res. 40:3345-3350, 1980). The final concentrations of machilin-A were prepared to be 1 μg/ml, 5μg/ml and 20 μg/ml respectively (Experimental Examples 1 to 3) and the final concentration of hydroquinone was prepared to be 1 μg/ml, and each was added to the culture medium of B-16 mouse melanoma cell, and then cultured for 3 days. Next, the cultured cells were treated with trypsin, and separated from the culture plate, and then centrifuged to extract melanin. lml of sodium hydroxide solution (IN of concentration) was added to each of above obtained extracts and the mixtures were boiled for 10 minutes for melanin to melt.

Then, the light absorbency at 400mn was measured by spectrophotometer and the amount of generated melanin was indicated as the light absorbency per unit number of cells (10⁶ cells). Then, the inhibition ratio (%) was obtained by calculating the amount of generated melanin relative to the control group, and the results are described in Table 1.

Table 1

* number of replication = 3

Referring to Table 1, it is found that machilin-A has a very high-potency of

restraining the generation of melanin of the cultured mouse melanoma cells, when

compared with that of the control group (see Experimental Examples 1 to 3), and it may also be understood that its effect is not behind hydroquinone, which is a well-known

whitening material. In addition, hydroquinone cannot be applied at a concentration of

1 μg/ml or above due to its toxicity though it shows very strong potency of restraining

the generation of melanin at a low concentration. However, machilin-A is not showing

cell toxicity even at a high concentration of 20 μg/ml or above, so it may give excellent

effects in restraining the generation of melanin rather then hydroquinone.

Hereinafter, the composition for skin whitening was prepared by adding

machilin-A to the cosmetics such as ointment for external use, cream, softening lotion,

essence, pack, and nutritious lotion, and then the effect of inhibiting pigmentation was

tested by applying it to the testees. Embodiment 1

Machilin-A obtained according to the extraction example was added as an effective component, and then ointments for external use were manufactured with the components and contents as described in Table 2.

Comparative Example 1

Ointments for external use were manufactured with the components and contents as described in Table 2 without adding machilin-A.

Table 2

Embodiment 2

Machilin-A obtained according to the extraction example was added as an effective component, and then creams were manufactured with the components and contents as described in Table 3.

Comparative Example 2

Creams were manufactured with the components and contents as described in Table 3 without adding machilin-A.

Table 3

Embodiment 3

Machilin-A obtained according to the extraction example was added as an effective component, and then softening lotions were manufactured with the components and contents as described in Table 4.

Comparative Example 3

Softening lotions were manufactured with the components and contents as described in Table 4 without adding machilin-A.

Table 4

Embodiment 4

Machilin-A obtained according to the extraction example was added as an effective component, and then essences were manufactured with the components and contents as described in Table 5.

Comparative Example 4

Essences were manufactured with the components and contents as described in Table 5 without adding machilin-A.

Table 5

Embodiment 5 Machilin-A obtained according to the extraction example was added as an effective component, and then packs were manufactured with the components and contents as described in Table 6.

Comparative Example 5

Packs were manufactured with the components and contents as described in Table 6 without adding machilin-A.

Table 6

Embodiment 6

Machilin-A obtained according to the extraction example was added as an effective component, and then nutritious lotions were manufactured with the components and contents as described in Table 7. Comparative Example 6

Nutritious lotions were manufactured with the components and contents as described in Table 7 without adding machilin-A.

Table 7

The process for testing the pigmentation inhibitory effect by the ointment for external use, cream, softening lotion, essence, pack, and nutritious lotion manufactured as described above is as follows. First, an aluminum foil having two rows of six holes of 7mm diameter was adhered to each forearm of twenty healthy men and women, and 60 mJ/cm² of light was irradiated at 10cm distance from the arm by ORIEL solar simulator 1000W. Before the irradiation, the portion to be irradiated was washed with 70% aqueous ethanol solution. From 3 days before the irradiation to 3 weeks after the irradiation, the cosmetic compositions containing machilin-A according to the embodiments 1 to 6 and the cosmetic compositions not containing machilin-A according to the comparative examples 1 to 6 were applied to the same row respectively in pairs twice a day. The packs of the embodiment 5 and the comparative examples 5 were removed 15 minutes after the application.

After applying the cosmetic compositions according to each embodiment and comparative example to the testees as described above, the pigmentation degree is determined with an naked eye. Then, the degrees of restraining pigmentation of the cosmetic compositions according to the embodiments were compared with those of the comparative examples respectively, and the result was evaluated into two stages, i.e., effective and no-difference, and was depicted in the following Table 8 along with the result of side effect occurrence.

Table 8

As shown in Table 8, at least 13 persons of 20 testees to whom the cosmetic compositions containing machilin-A according to ihe embodiments 1 to 6 show superior skin whitening effect without no side effect.

INDUSTRIAL APPLICABILITY As described above, the composition for skin whitening containing machilin-A according to the present invention shows a superior effect to inhibit pigmentation on skin by restraining melanin from being generated, so it is very effective to eliminate chloasma and freckles. In addition, the composition of the present invention may be used safely since it shows no side effects on skin.

The present invention has been described in detail. However, it should be understood that the detailed description and specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.

Claims

WHAT IS CLAIMED IS:

1. Composition for skin whitening containing machilin-A expressed by the following Chemical Formula 1 as an effective component.

Chemical Formula 1

2. Composition for skin whitening according to claim 1, wherein the content of the machilin-A is 0.000001 to 10 weight% on the basis of total weight of the composition.

3. Composition for skin whitening according to claim 2, wherein the content of the machilin-A is 0.0001 to 10 weight% on the basis of total weight of the composition.

4. Composition for skin whitening according to claim 1, wherein the machilin-A is extracted from Areca catechu by means of at least one solvent selected from the group consisting of low alcohol having 1 to 4 carbon atoms, ethyl acetate, acetone, ether, benzene, chloroform, hexane, cyclohexane and petroleum ether.

5. Composition for skin whitening according to claim 1, wherein the composition for skin whitening has one form selected from the group consisting of skin, lotion, cream, foundation, essence, gel, pack, foam cleansing, soup and ointment for external use.