WO2002053121A1

WO2002053121A1 - Cosmetic for skin whitening containing acyl substituted derivatives of glucose or sucrose

Info

Publication number: WO2002053121A1
Application number: PCT/KR2001/002269
Authority: WO
Inventors: Won-Chan Kim; Ho-Jeong Kim; Cheong-Taek Kim; Mu-Hyun Jin; Sang-Jin Kang
Original assignee: Lg Household & Healthcare Co., Ltd.
Priority date: 2000-12-30
Filing date: 2001-12-26
Publication date: 2002-07-11
Also published as: KR100479741B1; CN1531416A; KR20020059235A; JP2004517109A; CN1229107C

Abstract

The present invention relates to cosmetic for skin whitening containing glucose derivatives having 3≈5 of acyl groups and/or sucrose derivatives having 6≈8 of acyl groups as an effective component. Glucose acyl substituted derivatives and sucrose acyl substituted derivatives are easy to synthesize, have no side effects on skin, and have a superior effect to inhibit pigmentation on skin by restraining melanin from being generated. Accordingly, the cosmetic containing the same material is usefully used for skin whitening.

Description

COSMETIC FOR SKIN WHITENING CONTAINING ACYL SUBSTITUTED DERIVATIVES OF GLUCOSE OR SUCROSE

TECHNICAL FIELD

The present invention relates to cosmetic for skin whitening, and more

particularly, to cosmetic for skin whitening containing acyl substituted derivatives

of glucose or sucrose which are easy to synthesize, have 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 factor 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 hydroquinone shows a prescribed effect of whitening, the

mixture amount of the same should be restricted to 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, and 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.

On the other hand, it is reported that an plant extract such as licorice

extract or white mulberry extract(Fragrance.J., 6, 59 (1990)) has superior effect of

skin whitening. However, in case of using such a plant extract, it is difficult to

maintain the uniformity of products since the same considerably differs in its effect

according to the growing area of plant, plus the examination on skin irritativeness

and stability is not sufficient. In addition, in case of kazinol F extracted from paper

mulberry(Chem. Phar. Bull., 34(5) 1968 (1986), Cosmetics & Toiletries, 101 ,

51 (1995)), sucrose 4,7,8,1 1 ,12-pentaisovalerate(Kor. J. Pharmacogn. 21 (2) :

168-173 (2000)) extracted from Euphorbia lathyris , etc., it is difficult to

commercialize the same since the same is not easy to synthesize and has low

synthetic yield. DISCLOSURE OF THE INVENTION

Accordingly, an object of the present invention is to overcome the above- mentioned and to provide cosmetic for skin whitening, which is easy to synthesize, has no side effects on skin, and has a superior effect to inhibit pigmentation on skin by restraining melanin from being generated.

The detailed description about the cosmetic according to the present is provided hereinafter.

The present invention provides cosmetic for skin whitening containing an effective amount of one selected from a group comprising glucose acyl substituted derivatives represented by the following chemical formula 1 , sucrose acyl substituted derivatives represented by the following chemical formula 2, and mixtures of those. [Chemical Formula 1]

In the above chemical formula 1 , R means hydrogen atom or acyl group having the number of carbon of 3-6. The acyl group is linear chain type or branched chain type and the number of acyl group substituted is 3 to 5. [Chemical Formula 2]

In the above chemical formula 2, R means hydrogen atom or acyl group having the number of carbon of 3-6. The acyl group is linear chain type or branched chain type and the number of acyl group substituted is 6 to 8.

Such glucose acyl substituted derivatives or sucrose acyl substituted derivatives according to the present invention is easy to synthesize and have superior effect of restraining the generation of melanin and whitening skin without side effects on skin. Accordingly, when the same compound is added to cosmetic such as ointment for external use, essence, or cream, the high-potency of skin whitening without any special side effects can be obtained.

Glucose acyl substituted derivatives or sucrose acyl subustituted derivatives according to the present invention may be manufactured by using the conventionally known synthetic method according to the following reaction formula, respectively(Refer to Synthesis, 453 (1986)). [Reaction Formula 1]

acylation

In the above reaction formula 1 , R means hydrogen atom or acyl group having the number of carbon of 3-6. The acyl group is linear chain type or branched chain type and the number of acyl group substituted is 3 to 5. [Reaction Formula 2]

acylation

In the above reaction formula 2, R means hydrogen atom or acyl group

having the number of carbon of 3-6. The acyl group is linear chain type or

branched chain type and the number of acyl group substituted is 6 to 8.

Glucose and sucrose acyl substituted derivatives synthesized according to

the above reaction formulas have a different number of acyl group substituted

according to reaction temperature, reaction time, whether or not catalyst is used.

Glucose acyl substituted derivatives having 3-5 of acyl group substituted and

sucrose acyl substituted derivatives having 6-8 of acyl group substituted have

superior effect of restraining generation of melanin.

When the acylation reaction that glucose and sucrose acyl substituted

derivatives are synthesized is performed, DMF(dimethyl formamide), DMSO

(dimethyl sulfoxide), or pyridine may be used as a solvent and pyridine is preferable. In addition, as anhydrous acid used for acylation reaction, anhydrous

propionic aicd, anhydrous butylic acid, anhydrous isobutylic acid, anhydrous

valeric acid, anhydrous isovaleric acid, anhydrous 2-ethylbutyric acid, anhydrous

hexanoic acid, or anhydrous 2-methylvaleric acid may be used. Glucose acyl substituted derivatives synthesized according to the above

reaction formula 1 may be separated and refined into glucose 1 , 2,3,4, 6-penta-O-

isovalerate, glucose 1 ,2,3,4-tetra-O-isovalerate, glucose 1 ,2,4,6-tetra-O-

isovalerate, glucose 1 ,2,3,6-tetra-O-isovalerate, glucose 1 ,3,6-tri-O-isovalerate,

glucose 1 ,2, 3,4, 6-penta-O-isobutylate, glucose 1 ,2,3,4-tetra-O-isobutylate, glucose

1 ,2,4,6-tetra-O-isobutylate, glucose 1 ,2,3,6-tetra-O-isobutylate, glucose 1 ,3,6-tri-

O-isobutylate, etc. Among them, an α and β types of compound, glucose 1 ,2,3,4,6-

penta-O-isovalerate represented by the following chemical formula 3 has superior effect of skin whitening.

[Chemical Formula 3]

In the above chemical formula 3, R means

In addition, sucrose acyl substituted derivatives synthesized according to

the above reaction formula 2 may be separated and refined into sucrose

2,3,4,7,8,10,1 1 ,12-octa-O-isovalerate, sucrose 2,4,7,8,10,1 1 ,12-hepta-O-

isovalerate, sucrose 3,7,8,10,1 1 ,12-hexa-O-isovalerate, sucrose 2,3,4,7,8,10,11 , 12-octa-O-isobutylate, sucrose 2,4,7,8,10,1 1 ,12-hepta-O-isobutylate, sucrose 3,7,

8,10,1 1 ,12-hexa-O-isobutylate, etc.

Such glucose or sucrose acyl substituted derivatives may be used by

being mixed with various cosmetic such as ointment for external use, cream, softening lotion, essence, pack, nutritious lotion, etc. The content of glucose acyl

substituted derivatives and/or sucrose acyl substituted derivatives contained in the

cosmetic according to the present invention is preferably 0.0001 to 15 weight% on

the basis of total weight, and more preferably 0.001 to 10weight%.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

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 to be restricted to the embodiments described below. The embodiments of the

present invention are provided to more clearly and easily describe the present

invention to a person who has standard knowledge in this technical area.

Synthetic Example 1 (Synthetic example of glucose isovalerate derivative)

5g(27.8mmol) of glucose is put in a two-necked round bottom flask and

50ml of pyridine is added to dissolved completely in water bath. The solution

maintained at 0°C into which 5.5 equivalent weight of anhydrous isovaleric acid is

slowly dropped is agitated for 3 hours and then 5.5 equivalent weight of anhydrous isovaleric acid is additively dropped. Next, the reaction is performed for 30 hours

at the temperature raised up to 25°C. Then, the reaction is stopped by adding

150ml of methanol, the solvent is completely removed under reduced pressure,

and 300ml of chloroform is added. The product obtained above is washed twice respectively by adding 250ml of aqueous solution of 1 N hydrogen chloride and

250ml of saturated aqueous solution of sodium bicarbonate. A layer of chloroform

is dried under reduced pressure and then 13.5g of oil is obtained. The obtained oil

is separated and refined by using silica column chromatography

(ethylacetate/hexane 1 :5) and 4.5g(Rf=0.72, yield: 27.0%) of glucose 1 ,2,3,4,6- penta-O-isovalerate, 0.5g(Rf=0.60, yield: 3.5%) of glucose 1 ,2,3,4-tetra-O-

isovalerate, 2.3g(Rf=0.65, yield: 16.0%) of glucose 1 ,2,4,6-tetra-O-isovalerate,

0.6g(Rf=0.55, yield: 4.2%) of glucose 1 ,2,3,6-tetra-O-isovalerate, and 1 .2g

(Rf=0.43, yield: 10.0%) of glucose 1 ,3,6-tri-O-isovalerate is respectively obtained

thereby.

The above obtained glucose isovalerate derivatives are identified by the

Fast Atom Bombardment Mass Spectrometry(FAB-MS, hereinafter) and 300 MHz

NMR Spectrometry(¹H, ¹³C).

glucose 1 ,2,3 A6-penta-Q-isovalerate

FAB mass : 623.4 [M+Na]⁺

H-NMR(δ , CDCI3) : 6.36 (1 H, d, J 3.7 1-α -H), 5.72 (1 H, d, J 8.3 1-β -H),

5.50 (1 H, t, J 10.1 3-α -H), 5.28 (1H, t, J 9.5 3-β -H), 5.06-5.19 (4H, m, 2,4-α ,β -

H), 5.06 (2H, m, 2-α ,β -H) 4.13-4.17 (4H, m, 6-α ,β -H), 4.10 (1 H, m, 5-α -H),

3.82 (1 H, m, 5-β -H), 2.31-2.13 (20H, m, 5XCH₂CH(CH₃)₂) 2.13-2.03 (5H , m 5X

CH₂CH(CH₃)₂) 1.01-0.9 (60H , m, 4XCH₂CH(CH₃)₂)

glucose 1 ,2,3,4-tetra-O-isovalerate

FAB mass : 539 [M+Na] ⁺

H-NMR (δ , CDCI3) : 6.35 (1 H, d, J 3.6 1-H), 5.61 (1 H, t, J 9.5 3-H), 5.20- 5.06 (2H, m, 2,4-H), 3.91 (1 H, ddd, J 10, 4.5, 2, 5-H) 3.79-3.63 (2H, m, 6-H), 2.30-

2.13 (8H, m, 4XCH₂CH(CH₃)₂) 2.12-2.04.(4H, m, 4XCH₂CH(CH₃)₂) 1.01-0.9 (24H,

m, 4XCH₂CH(CH₃)₂)

glucose 1 ,2,3,6-tetra-O-isovalerate

FAB mass : 539 [M+Na] ⁺

H-NMR (δ , CDCI3) : 6.35 (1 H, d, J 3.6 1-H), 5.39 (1 H, t, J 10, 3-H), 5.12

(1 H, dd, J10 and 3.5, 2-H), 4.61-4.52 (2H, m, 6-H) 3.99 (1 H, ddd, J10,4 and 2.5, 5-

H), 3.60(1 H, t, J 10, 4-H) 2.32-2.14 (8H, m, 4XCH₂CH(CH₃)₂) 2.12-2.02.(4H , m, 4

XCH₂CH(CH₃)₂) 1.01-0.9 (24H , m, 4XCH₂CH(CH₃)₂)

glucose 1 ,2.4,6-tetra-O-isovalerate

FAB mass : 539 [M+Na] ⁺

H-NMR (δ , CDCI3) : 6.33 (1 H, d, J 3.6 1-H), 5.05-4.99 (2H, m, 2,4-H),

4.18 (1 H, dd, J10 and 3.5, 2-H), 4.61-4.52 (2H, m, 6-H) 3.99 (1 H, ddd, J10.4 and

2.5, 5-H), 3.60(1 H, t, J 10, 4-H) 2.32-2.14 (8H, m, 4xCH₂CH(CH₃)₂) 2.12-2.02.(4H ,

m, 4XCH₂CH(CH₃)₂) 1.01-0.9 (24H , m, 4XCH₂CH(CH₃)₂)

glucose 1 ,3,6-tri-O-isovalerate

FAB mass : 456 [M+Na] ⁺

H-NMR (δ , CDCI3) : 6.35 (1 H, d, J 3.6 1-H), 5.01 (1 H, t, J 9.8, 3-H), 4.53

(2H, m, 6-H), 3.98 (2H, ddd, , J9.8, 4 and 2.5, 5-H) 3.58 (1 H, m, 4-H), 3.60(1 H, t, J

9.8, 2-H) 2.30-2.13 (8H, m, 4XCH₂CH(CH₃)₂) 2.12-2.03.(3H, m, 3XCH₂CH(CH₃)₂)

1.00-0.89 (18H , m, 3XCH₂CH(CH₃)₂) Synthetic Example 2 (Synthetic example of glucose isobutylate derivative)

3.5g(Rf=0.80, yield: 27.5%) of glucose 1 ,2,3,4,6-penta-O-isobutylate,

0.4g(Rf=0.70, yield: 27.0%) of glucose 1 ,2,3,4-tetra-O-isobutylate, 2.7g(Rf=0.68,

yield: 23.0%) of glucose 1 ,2,4,6-tetra-O-isobutylate, 0.61 g(Rf=0.73, yield: 27.0%) of glucose 1 ,2,3,6-tetra-O-isobutylate and 0.59g(Rf=0.65, yield: 5.0%) of glucose

1 ,3,6-tri-O-isobutylate is respectively obtained by synthesizing, separating and

refining with the same method as that of the synthetic example 1 except that

anhydrous isobutylic acid instead of anhydrous isovaleric acid is used.

The above obtained glucose isobutylate derivatives are identified by using

the same spectrometry as that of the synthetic example 1.

glucose 1 ,2,3.4,6-penta-O-isobutylate

FAB mass : 558 [M+Na] ⁺

H-NMR (δ , CDCI3) : 6.33 (1 H, d, J 3.7 1-H), 5.49 (1 H, t, J 9.5 3-H), 5.13

(1 H, t, J 9.9 4-H ), 5.06 (1 H, dd, J 9.9 and 3.7, 2-H) 4.12 (2H, m, 6-H), 4.06 (1 H, m,

5-H), 2.75-2.42 (5H, m, 5XCH₂(CH₃)₂) 1.29-1.10 (30H , m, 5XCH(CH₃)₂)

glucose 1 ,2,3.4-tetra-O-isobutylate

FAB mass : 488 [M+Na] ⁺

H-NMR (δ , CDCI3) : 6.35 (1 H, d, J 3.6 1-H), 5.61 (1 H, t, J 9.5 3-H), 5.20-

5.06 (2H, m, 2,4-H), 3.91 (1 H, ddd, J 10, 4.5, 2, 5-H) 3.79-3.63 (2H, m, 6-H), 2.73-

2.40 (4H, m, 4XCH₂(CH₃)₂) 1.28-1.07 (24H , m, 4XCH(CH₃)₂)

glucose 1.2.3.6-tetra-O-isobutylate

FAB mass : 488 [M+Na] ⁺ H-NMR (δ , CDCI3) : 6.35 (1 H, d, J 3.6 1-H), 5.39 (1 H, t, J 10, 3-H), 5.12

(1 H, dd, J10 and 3.5, 2-H), 4.61-4.52 (2H, m, 6-H) 3.99 (1 H, ddd, J10.4 and 2.5, 5-

H), 3.60(1 H, t, J 10, 4-H) 2.76-2.40 (4H, m, 4xCH₂(CH₃)₂) 1.31-1.1 1 (24H , m, 4X

CH(CH₃)₂)

glucose 1 ,2,4,6-tetra-O-isobutylate

FAB mass : 488 [M+Na] ⁺

H-NMR (δ , CDCI3) : 6.33 (1 H, d, J 3.6 1-H), 5.05-4.99 (2H, m, 2,4-H),

2.5, 5-H), 3.60(1 H, t, J 10, 4-H) 2.32-2.14 (8H, m, 4XCH₂CH(CH₃)₂) 2.12-2.02 (4H ,

m, 4XCH₂CH(CH₃)₂) 1.01-0.9 (24H , m, 4xCH₂CH(CH₃)₂)

glucose 1 ,3,6-tri-O-isobutylate

FAB mass : 418 [M+Na] ⁺

H-NMR (δ , CDCI3) : 6.35 (1 H, d, J 3.6 1-H), 5.01 (1 H, t, J 9.8, 3-H), 4.53

(2H, , 6-H), 3.98 (2H, ddd, , J9.8, 4 and 2.5, 5-H) 3.58 (1 H, m, 4-H), 3.60(1 H, t, J

9.8, 2-H) 2.30-2.13 (6H, m, 3XCH₂CH(CH₃)₂) 2.12-2.03.(4H, m, 3XCH₂CH(CH₃)₂)

1.00-0.89 (18H, m, 3CH₂CH(CH₃)₂)

Synthetic Example 3 (Synthetic example of sucrose isovalerate derivative)

12.3g of oil is obtained by performing synthesis with the same method as

that of the synthetic example 1 except that sucrose instead of glucose is put and

the agitating temperature changes into 80°C. The obtained oil is separated and refined by using silica column chromatography(ethylacetate/hexane 1 :6) and

2.3g(Rf=0.83, yield: 15.8%) of sucrose 2,3,4,7, 8, 10,1 1 ,12-octa-O-isovalerate,

1 .8g(Rf=0.70, yield: 13.4%) of sucrose 2,4,7,8,10,1 1 ,12-hepta-O-isovalerate and 1.3g(Rf=0.62, yield: 10.6%) of sucrose 3,7,8,10,1 1 ,12-hexa-O-isovalerate is

respectively obtained thereby.

The above obtained sucrose isovalerate derivatives are identified by using

the same spectrometry as that of the synthetic example 1.

sucrose 2,3,4.7,8,10,11 ,12-octa-O-isovalerate

FAB mass : 1014 [M+Na] ⁺

H-NMR (δ , CDCI3) : 5.46 (1 H, m, 5-H), 5.42 (1 H, d, J 3.9, 7-H), 5.35 (1 H,

t, J 8, 8-H), 4.83 (1 H, t, J 9.9, 2-H), 4.80 (1 H, m, 4-H), 4.51 (1 H, t, J 9.9 3-H),

4.21 (2H, m, 12-H), 4.13 (1 H, m, 1-H), 4.10 (2H, m, 1 1-H), 4.06 (1 H, m, 9-H),

3.95 (1 H, m, 5-H), 2.19-2.10 (16H, m, 8XCH₂CH(CH₃)₂) 2.02-1.96(8H, m, 8X

CH₂CH(CH₃)₂, 0.90-0,7 (48H , m, 4XCH₂CH(CH₃)₂)

sucrose 2,4,7,8,10,1 1 ,12-hepta-O-isovalerate

FAB mass : 953 [M+Na] ⁺

H-NMR (δ , CDCI3) : 5.47 (1 H, m, 5-H), 5.43 (1 H, d, J 3.9, 7-H), 5.35 (1 H,

t, J 8, 8-H), 4.83 (1 H, t, J 9.9, 2-H), 4.83 (1 H, m, 4-H), 4.22 (2H, m, 12-H), 4.13

(1 H, m, 1-H), 4.12 (2H, m, 11-H), 4.08 (1 H, m, 9-H), 3.95 (2H, m, 10-H), 3.84

(1 H, t, J 9.9 3-H), 2.19-2.10 (14H, m, 4XCH₂CH(CH₃)₂) 2.02-1.96 (7H , m, 7X

CH₂CH(CH₃)₂) 0.91-0,75 (42H , m, 7XCH₂CH(CH₃)₂)

sucrose 3,7,8, 10,1 1 ,12-hexa-O-isovalerate FAB mass : 869 [M+Na] ⁺

H-NMR (δ , CDCI3) : 5.45-5.46 (2H, m, 5,7-H), 5.42 (1 H, t, J 9.9, 8-H),

5.00 (1 H, t, J 8, 3-H), 4.51 (1 H, m, 11-H), 4.37 (2H, m, 12-H), 4.36-4.21 (4H, m, 10,

11 , 12-H), 4.17 (1 H, m, 9-H), 4.05 (1 H, d, J3.8, 1-H), 3.57 (1 H, m, 4-H), 3.39 (1 H,

t, J9.9, 3-H), 2.19-2.10 (12H, m, 6XCH₂CH(CH₃)₂) 2.02-1 .96 (7H , m, 6X

CH₂CH(CH₃)₂) 0.91-0,75 (42H , m, 6xCH₂CH(CH₃)₂)

Synthetic Example 4 (Synthetic example of sucrose isobutylate

derivative)

-12.8g of oil is obtained by performing synthesis with the same method as that of the synthetic example 3 except that anhydrous isobutylic acid instead of anhydrous isovaleric acid is used. The obtained oil is separated and refined by

using silica column chromatography(ethylacetate/hexane 1 :6) and 2.0g(Rf=0.83,

yield: 16.8%) of sucrose 2,3,4,7,8,10,1 1 ,12-octa-O-isobutylate, 1.5g(Rf=0.70,

yield: 10.4%) of sucrose 2,4,7,8,10,1 1 ,12-hepta-O-isobutylate and 1.2g(Rf=0.62,

yield: 10.1 %) of sucrose 3,7,8,10,1 1 ,12-hexa-O-isobutylate is respectively

obtained thereby.

The above obtained sucrose isobutylate derivatives are identified by using

the same spectrometry as that of the synthetic example 1. sucrose 2.3,4,7,8,10,1 1 ,12-octa-O-isobutylate

FAB mass : 925 [M+Na] ⁺

H-NMR (δ , CDCI3) : 5.46 (1 H, m, 5-H), 5.39 (1 H, d, J 3.9, 7-H), 5.32 (1 H,

t, J 8, 8-H), 4.82 (1 H, t, J 9.8, 2-H), 4.81 (1 H, m, 4-H), 4.53 (1 H, t, J 9.8 3-H), 4.22 (2H, m, 12-H), 4.12 (1H, m, 1-H), 4.11 (2H, m, 11-H), 4.07 (1H, m, 9-H),

3.95 (1H, m, 5-H), 2.78-2.41 (8H, m, 8XCH₂(CH₃)₂) 1.20-1.08 (24H , m, 8X

CH(CH₃)₂)

sucrose 2,4,7,8,10,11 ,12-hepta-O-isobutylate

FAB mass : 855 [M+Na] ⁺

H-NMR (δ , CDCI3) : 5.49 (1H, m, 5-H), 5.44 (1H, d, J 3.9, 7-H), 5.34 (1H,

t, J 8, 8-H), 4.85 (1H, t, J 9.9, 2-H), 4.82 (1H, m, 4-H), 4.21 (2H, m, 12-H), 4.12

(1H, m, 1-H), 4.10 (2H, m, 11-H), 4.08 (1H, m, 9-H), 3.95 (2H, m, 10-H), 3.82 (1H,

t, J 9.93-H), 2.19-2.10 (14H, m, 7xCH₂CH(CH₃)₂) 2.76-2.40 (7H, m, 7XCH₂(CH₃)₂)

1.31-1.11 (42H, m, 7XCH(CH₃)₂)

sucrose 3,7,8,10,11,12-hexa-O-isobutylate

FAB mass: 785 [M+Na] ⁺

H-NMR (δ , CDCI3) : 5.45-5.46 (2H, m, 5,7-H), 5.42 (1H, t, J 9.9, 8-H),

5.00 (1H,t, 8, 3-H), 4.51 (1H, m, 11-H), 4.37 (2H, m, 12-H), 4.36-4.21 (4H, m, 10,

11, 12-H), 4.17 (1H, m, 9-H), 4.05 (1H, d, J3.8, 1-H), 3.57 (1H, m, 4-H), 3.39 (1H, t,

J9.9, 3-H), 2.76-2.40 (6H, m, 6XCH₂(CH₃)₂) 1.31-1.11 (36H, m, 6xCH(CH₃)₂)

Experimental Example

The whitening effect in a cellular level is tested by adding glucose acyl

substituted derivatives and sucrose acyl substituted derivatives compound

obtained according to the synthetic examples 1 to 4 and hydroquinone aqueous

solution to a culture fluid of B-16 mouse melanoma cell(Lotan R., Lotan D. Cancer Res. 40:3345-3350, 1980). The final concentrations of the mixture of synthesized

compound according to the synthetic examples 1 to 4, each compound separated

and refined, and hydroquinone are set according to the concentrations described in tables 1 to 4 and the mixture, each compound and hydroquinone are

respectively added to the culture medium of B-16 mouse melanoma cell and the

cells are cultured for 3 days. The cultured cells are treated by trypsin and

separated from the culture plate. Then, the cells are centrifuged to extract melanin.

1 ml of sodium hydroxide solution(1 N of concentration) is added to the above-mentioned extract and the mixture is boiled for 10 minutes to melt melanin.

Then, the absorbancy of melanin is measured at 400mn by a spectrophotometer

and the amount of generated melanin is indicated by the absorbancy per unit

number of cell(10⁶ cell). Further, the inhibition rate(%) is calculated by using the melanin generation amount of a comparative group is described in tables 1 to 4.

Each compound obtained by the separating and refining treatment

according to the synthesis examples 1 to 4 is described as follows.

glucose 1 ,2,3,4,6-penta-O-isovalerate : Glu-5-iV

glucose 1 ,2,3,4-tetra-O-isovalerate : Glu-4-iV-1

glucose 1 ,2,4,6-tetra-O-isovalerate : Glu-4-iV-2

glucose 1 ,2,3,6-tetra-O-isovalerate : Glu-4-iV-3

glucose 1 ,3,6-tri-O-isovalerate : Glu-3-iV

glucose 1 ,2, 3,4, 6-penta-O-isobutylate : Glu-5-iB

glucose 1 ,2,3,4-tetra-O-isobutylate : Glu-4-iB-1

glucose 1 ,2,4,6-tetra-O-isobutylate : Glu-4-iB-2

glucose 1 ,2,3,6-tetra-O-isobutylate : Glu-4-iB-3 glucose 1 ,3,6-tri-O-isobutylate : Glu-3-iB

sucrose 2,3,4,7,8,10,11 ,12-octa-O-isovalerate : Su-8-iV

sucrose 2,4,7,8, 10,11 ,12-hepta-O-isovalerate : Su-7-iV

sucrose 3,7,8,10,11 ,12-hexa-O-isovalerate : Su-6-iV

sucrose 2,3,4,7,8,10,11 ,12-octa-O-isobutylate : Su-8-iB

sucrose 2,4,7,8,10,11 ,12-hepta-O-isobutylate : Su-7-iB

sucrose 3,7,8,10,11 ,12-hexa-O-isobutylate : Su-6-iB

[Table 1]

[Table 2]

[Table 3]

[Table 4]

Referring to the tables 1 to 4, glucose acyl substituted derivatives and sucrose acyl substituted derivatives have a very high-potency of restraining the generation of melanin of the cultured mouse melanoma cells by comparison with those of the comparative group. Especially, glucose 1 ,2,3,4,6-penta-O-isovalerate has superior effect of restraining the generation of melanin. On the other hand, hydroquinone has a high-potency of restraining the generation of melanin, but the same has serious cytotoxicity when the concentration of the same is more than

1 μg/ml, so that the experiment is impossible. On the contrary, since glucose acyl

substituted derivatives and sucrose acyl substituted derivatives according to the

present invention have no cytotoxicity even when those concentrations are 20μg/m,

it is possible to make the same have a high-potency of restraining the generation of melanin.

Hereinafter, the effect of inhibiting pigmentation of cosmetic containing glucose acyl substituted derivatives and sucrose acyl derivatives is tested by applying cosmetic such as ointment for external use, cream, softening lotion, nutritious lotion, pack, or essence made by adding glucose acyl substituted derivatives and sucrose acyl substituted derivatives to testees. Embodiment 1 and comparative example 1

An ointment for external use is manufactured with components and

contents as described in table 5.

[Table 5]

Embodiment 2 and comparative example 2

A cream is manufactured with components and contents as described in

table 6.

[Table 6]

Embodiment 3 and comparative example 3

A softening lotion is manufactured with components and contents as

described in table 7.

[Table 7]

Embodiment 4 and comparative example 4

An essence is manufactured with components and contents as described

in table 8.

[Table 8]

Embodiment 5 and comparative example 5

A pack is manufactured with components and contents as described in

table 9.

[Table 9]

Embodiment 6 and comparative example 6

A nutritious lotion is manufactured with components and contents as

described in table 10. [Table 10]

A process for testing the effect thereof is as follows. First, an aluminium foil having two rows of six holes with 7mm of diameter is adhered to each forearm of twenty healthy men and women and 60mJ/cm² of light is irradiated at 10cm distance from arm by ORIEL solar simulator 1000W. The portion to be irradiated is washed by 70% of ethanol aqueous solution before irradiation. From 3 days before irradiation to 3 weeks after irradiation, the cosmetic according to the embodiments 1 to 6 and that according to the comparative examples 1 to 6 are respectively applied to two rows to be six pairs twice a day. The packs of the embodiment 5 and the comparative examples 5 are removed 15 minutes after application.

After applying the cosmetic according to each embodiment and comparative example as described above, the pigmentation degree is judged with the naked eye and the degrees of restraining pigmentation of the cosmetic according to each embodiment and that according to each comparative example are compared with each other. Then, the result classifying the degrees thereof into three steps: remarkably effective A, effective B, and no difference C is described in table 11. [Table 11]

As shown in table 11 , the cosmetics containing glucose acyl substituted derivatives or sucrose acyl substituted derivatives according to the embodiments 1 to 6 have superior effect of skin whitening in comparison with commonly used cosmetics and the cosmetics according to embodiments 1a to 6a containing glucose 1 ,2,3,4,6-penta-0-isovalerate(Glu-5-iV) have especially superior effect of skin whitening.

INDUSTRIAL APPLICABILITY

As described above, glucose acyl substituted derivatives and sucrose acyl substituted derivatives according to the present invention are easy to synthesize, have no side effects on skin, and have a superior effect to inhibit pigmentation on skin by restraining melanin from being generated. Accordingly, the cosmetic containing the same material is usefully used for skin whitening. While the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art will appreciate that various modifications and substitutions can be made thereto without departing from the spirit and scope of the present invention as set forth in the appended claims.

Claims

WHAT IS CLAIMED IS:

1. Cosmetic for skin whitening containing an effective amount of one selected from a group comprising glucose acyl substituted derivatives represented by the following chemical formula 1 , sucrose acyl substituted derivatives represented by the following chemical formula 2, and mixtures of those;

[Chemical Formula 1]

In the above chemical formula 1 , R means hydrogen atom or acyl group having the number of carbon of 3-6 and the number of the acyl group is 3 to 5; [Chemical Formula 2]

In the above chemical formula 2, R means hydrogen atom or acyl group having the number of carbon of 3-6 and the number of the acyl group is 6 to 8.

2. Cosmetic for skin whitening according to claim 1 , wherein said glucose acyl substituted derivative is glucose 1 ,2,3,4,6-penta-O-isovalerate.

3. Cosmetic for skin whitening according to claim 1 , wherein said glucose acyl substituted derivative is one selected from a group comprising glucose 1 ,2,3,4-tetra-O-isovalerate, glucose 1 ,2,4,6-tetra-O-isovalerate, glucose 1 ,2,3,6-tetra-O-isovalerate, glucose 1 ,3,6-tri-O-isovalerate, glucose 1 ,2,3,4,6- penta-O-isobutylate, glucose 1 ,2,3,4-tetra-O-isobutylate, glucose 1 ,2,4,6-tetra-O- isobutylate, glucose 1 ,2,3,6-tetra-O-isobutylate, glucose 1 ,3,6-tri-O-isobutylate, and mixtures of those.

4. Cosmetic for skin whitening according to claim 1 , wherein said sucrose acyl substituted derivative is one selected from a group comprising sucrose 2,3,4,7,8,10,11 ,12-octa-O-isovalerate, sucrose 2,4,7,8,10,11 ,12-hepta-O- isovalerate, sucrose 3,7,8,10,11 ,12-hexa-O-isovalerate, sucrose 2,3,4,7,8,10,11 , 12-octa-O-isobutylate, 2,4,7,8,10,11 ,12-hepta-O-isobutylate, sucrose 3,7,8,10,11 ,

12-hexa-O-isobutylate, and mixtures of those.

5. Cosmetic for skin whitening according to claim 1 , wherein the content of one selected from a group comprising said glucose acyl substituted

derivatives, sucrose acyl substituted derivatives, and mixtures of those is 0.0001

to 15 weight% on the basis of total weight of cosmetic.