KR100479741B1 - Cosmetic for skin whitening containing acyl substituted derivatives of glucose or sucrose - Google Patents

Abstract

The present invention relates to a cosmetic for skin whitening, comprising a glucose derivative having 3 to 5 acyl substituents and / or a sucrose derivative having 6 to 8 acyl substituents as an active ingredient. Glucose acylated derivatives and sucrose acylated derivatives are easy to synthesize and have no side effects on the skin, and also inhibit melanin production and have excellent pigmentation inhibitory effects on the skin. Thus, cosmetics containing the same may be useful for skin whitening. Can be.

Description

Cosmetic whitening agent containing glucose acylated derivative or sucrose acylated derivative {Cosmetic for skin whitening containing acyl substituted derivatives of glucose or sucrose}

The present invention relates to a cosmetic for skin whitening, and more particularly, skin whitening containing glucose or sucrose acylated derivatives that are easy to synthesize and have no side effects on the skin, inhibit melanin production, and have excellent pigmentation inhibitory effects on the skin. It is about cosmetics.

 It is everyone's constant desire to have white, fair skin. Human skin color is determined by the concentration and distribution of melanin in the skin. In addition to genetic factors, it is also influenced by environmental or physiological conditions such as ultraviolet rays, fatigue and stress. Melanin is made by tyrosine, an amino acid, called tyrosinase, which is converted into dopa or dopaquinone, followed by non-enzymatic oxidation. However, although the pathway by which melanin is made is known, the mechanisms that drive melanin synthesis, the previous step in which tyrosinase works, are still unknown.

When such synthesis of melanin occurs excessively in the skin, it may darken the skin tone, and may also cause spots and freckles. Therefore, by inhibiting the synthesis of melanin pigment in the skin, not only can brighten the skin tone to realize skin whitening, but also improve skin hyperpigmentation such as spots, freckles, etc. caused by ultraviolet rays, hormones and genetic causes. have.

Therefore, conventionally, a substance having an inhibitory activity against tyrosinase such as hydroquinone, ascorbic acid, kojic acid, glutathione, and the like is blended into a cosmetic such as skin ointment and essence. By doing so, we tried to realize skin whitening. However, hydroquinone exhibits a predetermined whitening effect, but there is a problem in that the amount of cosmetics is limited due to severe skin irritation, and ascorbic acid is easily oxidized, and thus the cosmetics containing it are discolored and discolored. And, Kojisan is unstable and there is a problem that the use is limited. In addition, thiol-based compounds such as glutathione and cysteine not only give a characteristic unpleasant odor but also have low transdermal absorption.

On the other hand, plant extracts such as licorice extract, lettuce extract (Fragrance. J., 6, 59 (1990)) and the like have been reported to exhibit excellent skin whitening effect. However, these plant extracts are not only difficult to maintain the homogeneity of the product due to the difference in potency depending on the origin of the plant, but also insufficient examination of skin irritation and stability. In addition, Kazinol F (Chem. Pharm. Bull., 34 (5) 1968 (1986), Cosmetics & Toiletries, 101, 51 (1995)) extracted from the mulberry, Sucrose 4,7,8,11 , 12-pentaisobalate (Kor. J. Pharmacogn. 31 (2): 168-173 (2000)), etc. are not easy to synthesize, but also difficult to commercialize due to low synthesis yield.

Accordingly, an object of the present invention is to solve the above problems, easy synthesis and no side effects on the skin, inhibit melanin production to provide a skin whitening cosmetics excellent in inhibiting pigmentation on the skin.

In order to achieve the above technical problem, the present invention contains any one selected from the group consisting of glucose acylation derivative represented by the following general formula (1), sucrose acylated derivative represented by the following general formula (2) and mixtures thereof as an active ingredient It provides a skin whitening cosmetics, characterized in that.

<Formula 1>

In Formula 1, R is a hydrogen atom or an acyl group having 3 to 6 carbon atoms, which may be linear or pulverized, and the number of substituted acyl groups is 3 to 5.

<Formula 2>

In Formula 2, R is a hydrogen atom or an acyl group having 3 to 6 carbon atoms, which may be linear or pulverized, with 6 to 8 substituted acyl groups.

These glucose acylation derivatives and sucrose acylation derivatives of the present invention are not only easy to synthesize, but also exhibit very strong melanin production inhibitory effect and skin lightening effect without side effects on the skin. Therefore, when these compounds are added to cosmetics such as skin ointments, essences, creams, etc., they can exhibit a strong skin whitening effect without any side effects.

Hereinafter, the cosmetic for skin whitening according to the present invention will be described in detail.

Glucose acylated derivatives or sucrose acylated derivatives according to the present invention can be prepared according to the following schemes, respectively, by applying a conventionally known synthetic method (see Synthesis, 453 (1986)).

<Scheme 1>

In Scheme 1, R is a hydrogen atom or an acyl group having 3 to 6 carbon atoms, which may be linear or pulverized, and the number of substituted acyl groups is 3 to 5.

<Scheme 2>

In Scheme 2, R is a hydrogen atom or an acyl group having 3 to 6 carbon atoms, which may be linear or pulverized, and the number of substituted acyl groups is 6 to 8

Glucose and sucrose acylated derivatives synthesized according to the above reaction schemes vary in the number of substituted acyl groups depending on reaction temperature, reaction time, catalyst use, and the like, and substituted glucose acylated derivatives having 3 to 5 substituted acyl groups. Sucrose acylated derivatives having 6 to 8 acyl groups exhibit excellent melanogenesis inhibitory effects.

In the acylation reaction for synthesizing glucose and sucrose acylated derivatives, dimethyl formamide, dimethyl sulfoxide, pyridine and the like may be used as a solvent, and among them, pyridine is preferable. . In addition, as the anhydride used in the acylation reaction, propionic anhydride, butyric anhydride, isobutyl anhydride, valeric anhydride, isovaleric anhydride, 2-ethylbutyric anhydride, hexanoic acid anhydride, 2-anhydride Methyl valeric acid and the like can be used.

Glucose acylated derivatives synthesized according to Scheme 1 include glucose 1,2,3,4,6-penta-o-isovalerate, glucose 1,2,3,4-tetra-o-isovalorate, glucose 1 , 2,4,6-tetra-o-isovalorate, glucose 1,2,3,6-tetra-o-isovalorate, glucose 1,3,6-tri-o-isovalorate, glucose 1, 2,3,4, 6-penta-o-isobutyrate, 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 the like can be separated and purified. Among them, the skin whitening effect of glucose 1,2,3,4,6-penta-o-isovalerate represented by the following general formula (3), which is a mixture of α- and β-types, is particularly excellent.

<Formula 3>

In Formula 3, R is to be.

In addition, the sucrose acylated derivatives synthesized according to Scheme 2 include sucrose 2,3,4,7,8,10,11,12-octa-o-isovalorate, sucrose 2,4,7,8,10, 11,12-hepta-o-isovalorate, sucrose 3,7,8,10,11,12-hexa-o-isovalorate, sucrose 2,3,4,7,8,10,11,12- Octa-o-isobutylate, sucrose 2,4,7,8,10,11,12-hepta-o-isobutylate, sucrose 3,7,8,10,11,12-hexa-o-isobutyl May be separated and purified at a rate or the like.

Such glucose or sucrose acylated derivatives may be used in combination with various cosmetics such as skin ointments, creams, soft cosmetics, essences, packs, nutrient cosmetics and the like. The content of the glucose acylated derivative and / or sucrose acylated derivative contained in the cosmetic according to the present invention is preferably 0.0001 to 15% by weight, more preferably 0.001 to 10% by weight based on the total weight of the cosmetic.

Hereinafter, the present invention will be described in detail with reference to Examples. However, embodiments according to the present invention can be modified in many different forms, the scope of the present invention should not be construed as limited to the embodiments described below. Embodiments of the present invention are provided to more completely explain the present invention to those skilled in the art.

Synthesis Example

Synthesis Example 1 (Synthesis example of glucose isovalerate derivative)

  5 g (27.8 mmol) of glucose was added to a round-necked flask, and then 50 ml of pyridine was added and completely dissolved in a water bath. Subsequently, 5.5 equivalents of isovaleric anhydride was slowly added dropwise to the solution maintained at 0 ° C. and stirred for 3 hours, followed by further dropping of 5.5 equivalents of isovaleric anhydride. Then, the reaction temperature was raised to 25 ° C. and reacted for 30 hours. Then, 150 ml of methanol was added to stop the reaction, the solvent was completely removed under reduced pressure, and then 300 ml of chloroform was added. Then, 250 ml of 1N aqueous hydrogen chloride solution and 250 ml of saturated sodium hydrogen carbonate aqueous solution were added thereto and washed twice, and the chloroform layer was dried under reduced pressure to give 13.5 g of oil. The obtained oil was separated and purified using silica column chromatography (ethyl acetate / hexane 1: 5), respectively, to obtain 4.5 g of glucose 1,2,3,4,6-penta-o-isovalorate (Rf = 0.72, Yield: 27.0%), glucose 1,2,3,4-tetra-o-isovalorate 0.5 g (Rf = 0.60, yield: 3.5%), glucose 1,2,4,6-tetra-o-isovaler Rate 2.3 g (Rf = 0.65, yield: 16.0%), glucose 1,2,3,6-tetra-o-isovalorate 0.6 g (Rf = 0.55, yield: 4.2%), glucose 1,3,6- 1.2 g (Rf = 0.43, yield: 10.0%) of tri-o-isovalates were obtained.

The obtained glucose isovalerate derivatives were identified using high-speed atom bombardment mass spectrometry (hereinafter FAB-MS) and 300 MHz NMR analysis ( ¹ H, ¹³ C).

Glucose 1,2,3,4,6-penta-o-isovalorate

FAB mass: 623.4 [M + Na] ⁺

H-NMR (δ, CDCl 3): 6.36 (1H, d, J 3.7 1-α-H), 5.72 (1H, d, J 8.3 1-β-H), 5.50 (1H, 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 (1H, m, 5-α-H), 3.82 (1H, m, 5-β-H), 2.31-2.13 (20H , m, 5 × CH ₂ CH (CH ₃ ) ₂ ) 2.13-2.03 (5H, m 5 × CH ₂ CH (CH ₃ ) ₂ ) 1.01-0.9 (60H, m, 4 × CH ₂ CH (CH ₃ ) ₂ )

Glucose 1,2,3,4-tetra-o-isovalorate

FAB mass: 539 [M + Na] ⁺

H-NMR (δ, CDCl 3): 6.35 (1H, d, J 3.6 1-H), 5.61 (1H, t, J 9.5 3-H), 5.20-5.06 (2H, m, 2,4-H), 3.91 (1H, ddd, J 10, 4.5, 2, 5-H) 3.79-3.63 (2H, m, 6-H), 2.30-2.13 (8H, m, 4 × CH ₂ CH (CH ₃ ) ₂ ) 2.12-2.04. (4H, m, 4 × CH ₂ CH (CH ₃ ) ₂ ) 1.01-0.9 (24H, m, 4 × CH ₂ CH (CH ₃ ) ₂ )

Glucose 1,2,3,6-tetra-o-isovalorate

FAB mass: 539 [M + Na] ⁺

H-NMR (δ, CDCl 3): 6.35 (1H, d, J 3.6 1-H), 5.39 (1H, t, J 10, 3-H), 5.12 (1H, dd, J10 and 3.5, 2-H) , 4.61-4.52 (2H, m, 6-H) 3.99 (1H, ddd, J10, 4 and 2.5, 5-H), 3.60 (1H, t, J 10, 4-H) 2.32-2.14 (8H, m , 4 × CH ₂ CH (CH ₃ ) ₂ ) 2.12-2.02. (4H, m, 4 × CH ₂ CH (CH ₃ ) ₂ ) 1.01-0.9 (24H, m, 4 × CH ₂ CH (CH ₃ ) ₂ )

Glucose 1,2,4,6-tetra-o-isovalorate

FAB mass: 539 [M + Na] ⁺

H-NMR (δ, CDCl 3): 6.33 (1H, d, J 3.6 1-H), 5.05-4.99 (2H, m, 2,4-H), 4.18 (1H, dd, J10 and 3.5, 2-H ), 4.61-4.52 (2H, m, 6-H) 3.99 (1H, ddd, J10, 4 and 2.5, 5-H), 3.60 (1H, t, J 10, 4-H) 2.32-2.14 (8H, m, 4 × CH ₂ CH (CH ₃ ) ₂ ) 2.12-2.02. (4H, m, 4 × CH ₂ CH (CH ₃ ) ₂ ) 1.01-0.9 (24H, m, 4 × CH ₂ CH (CH ₃ ) ₂ )

Glucose 1,3,6-tri-o-isovalorate

FAB mass: 456 [M + Na] ⁺

H-NMR (δ, CDCl 3): 6.35 (1H, d, J 3.6 1-H), 5.01 (1H, 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 (1H, m, 4-H), 3.60 (1H, t, J 9.8, 2-H) 2.30-2.13 (8H, m, 4 × CH ₂ CH (CH ₃ ) ₂ ) 2.12-2.03. (3H, m, 3 × CH ₂ CH (CH ₃ ) ₂ ) 1.00-0.89 (18H, m, 3 × CH ₂ CH (CH ₃ ) ₂ )

Synthesis Example 2 (Synthesis example of glucose isobutylate derivative)

Synthesis, separation, and purification were carried out in the same manner as in Synthesis Example 1, except that isobutylic anhydride was used instead of isovaleric anhydride, and 3.5 g of glucose 1,2,3,4,6-penta-o-isobutyrate ( Rf = 0.80, yield: 27.5%), glucose 1,2,3,4-tetra-o-isobutylate 0.4 g (Rf = 0.70, yield: 27.0%), glucose 1,2,4,6-tetra- 2.7 g of o-isobutylate (Rf = 0.68, yield: 23.0%), 0.61 g of glucose 1,2,3,6-tetra-o-isobutylate (Rf = 0.73, yield: 27.0%), glucose 1, 0.59 g (Rf = 0.65, yield: 5.0%) of 3,6-tri-o-isobutylate was obtained.

The obtained glucose isobutylate derivative was identified using the assay described in Synthesis Example 1.

Glucose 1,2,3,4,6-penta-o-isobutylate

FAB mass: 558 [M + Na] ⁺

H-NMR (δ, CDCl 3): 6.33 (1H, d, J 3.7 1-H), 5.49 (1H, t, J 9.5 3-H), 5.13 (1H, t, J 9.9 4-H), 5.06 ( 1H, dd, J 9.9 and 3.7, 2-H) 4.12 (2H, m, 6-H), 4.06 (1H, m, 5-H), 2.75-2.42 (5H, m, 5 x CH ₂ (CH ₃₎ ) ₂ ) 1.29-1.10 (30H, m, 5 × CH (CH ₃ ) ₂ )

Glucose 1,2,3,4-tetra-o-isobutyrate

FAB mass: 488 [M + Na] ⁺

H-NMR (δ, CDCl 3): 6.35 (1H, d, J 3.6 1-H), 5.61 (1H, t, J 9.5 3-H), 5.20-5.06 (2H, m, 2,4-H), 3.91 (1H, ddd, J 10, 4.5, 2, 5-H) 3.79-3.63 (2H, m, 6-H), 2.73-2.40 (4H, m, 4 × CH ₂ (CH ₃ ) ₂ ) 1.28-1.07 (24H, m, 4 × CH (CH ₃ ) ₂ )

Glucose 1,2,3,6-Tetra-o-isobutylate

FAB mass: 488 [M + Na] ⁺

H-NMR (δ, CDCl 3): 6.35 (1H, d, J 3.6 1-H), 5.39 (1H, t, J 10, 3-H), 5.12 (1H, dd, J10 and 3.5, 2-H) , 4.61-4.52 (2H, m, 6-H) 3.99 (1H, ddd, J10, 4 and 2.5, 5-H), 3.60 (1H, t, J 10, 4-H) 2.76-2.40 (4H, m , 4 × CH ₂ (CH ₃ ) ₂ ) 1.31-1.11 (24H, m, 4 × CH (CH ₃ ) ₂ )

Glucose 1,2,4,6-Tetra-o-isobutylate

FAB mass: 488 [M + Na] ⁺

H-NMR (δ, CDCl 3): 6.33 (1H, d, J 3.6 1-H), 5.05-4.99 (2H, m, 2,4-H), 4.18 (1H, dd, J10 and 3.5, 2-H ), 4.61-4.52 (2H, m, 6-H) 3.99 (1H, ddd, J10, 4 and 2.5, 5-H), 3.60 (1H, t, J 10, 4-H) 2.32-2.14 (8H, m, 4 × CH ₂ CH (CH ₃ ) ₂ ) 2.12-2.02 (4H, m, 4 × CH ₂ CH (CH ₃ ) ₂ ) 1.01-0.9 (24H, m, 4 × CH ₂ CH (CH ₃ ) ₂ )

Glucose 1,3,6-tri-o-isobutylate

FAB mass: 418 [M + Na] ⁺

H-NMR (δ, CDCl 3): 6.35 (1H, d, J 3.6 1-H), 5.01 (1H, 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 (1H, m, 4-H), 3.60 (1H, t, J 9.8, 2-H) 2.30-2.13 (6H, m, 3 × CH ₂ CH (CH ₃ ) ₂ ) 2.12-2.03. (4H, m, 3 × CH ₂ CH (CH ₃ ) ₂ ) 1.00-0.89 (18H, m, 3CH ₂ CH (CH ₃ ) ₂ )

Synthesis Example 3 (Synthesis example of sucrose isovalerate derivative)

Sucrose was added instead of glucose and synthesized in the same manner as in Synthesis Example 1, except that the stirring temperature was changed to 80 ° C., to obtain 12.3 g of oil. The oil thus obtained was separated and purified using a silica chromatography column (ethyl acetate / hexane 1: 6) to give sucrose 2,3,4,7,8,10,11,12-octa-o-isovalorate 2.3, respectively. g (Rf = 0.83, yield: 15.8%), sucrose 2,4,7,8,10,11,12-hepta-o-isovalorate 1.8 g (Rf = 0.70, yield: 13.4%), sucrose 3, 7,8,10,11,12-hexa-o-isovalorate 1.3g (Rf = 0.62, yield: 10.6%) was obtained.

The obtained sucrose isovalerate derivative was identified using the assay described in Synthesis Example 1.

Sucrose 2,3,4,7,8,10,11,12-octa-o-isovalorate

FAB mass: 1014 [M + Na] ⁺

H-NMR (δ, CDCl 3): 5.46 (1H, m, 5-H), 5.42 (1H, d, J 3.9, 7-H), 5.35 (1H, t, J 8, 8-H), 4.83 ( 1H, t, J 9.9, 2-H), 4.80 (1H, m, 4-H), 4.51 (1H, t, J 9.9 3-H), 4.21 (2H, m, 12-H), 4.13 (1H , m, 1-H), 4.10 (2H, m, 11-H), 4.06 (1H, m, 9-H), 3.95 (1H, m, 5-H), 2.19-2.10 (16H, m, 8 × CH ₂ CH (CH ₃ ) ₂ ) 2.02-1.96 (8H, m, 8 × CH ₂ CH (CH ₃ ) ₂ , 0.90-0,7 (48H, m, 4 × CH ₂ CH (CH ₃ ) ₂ )

Sucrose 2,4,7,8,10,11,12-hepta-o-isovalorate

FAB mass: 953 [M + Na] ⁺

H-NMR (δ, CDCl 3): 5.47 (1H, m, 5-H), 5.43 (1H, d, J 3.9, 7-H), 5.35 (1H, t, J 8, 8-H), 4.83 ( 1H, t, J 9.9, 2-H), 4.83 (1H, m, 4-H), 4.22 (2H, m, 12-H), 4.13 (1H, m, 1-H), 4.12 (2H, m , 11-H), 4.08 (1H, m, 9-H), 3.95 (2H, m, 10-H), 3.84 (1H, t, J 9.9 3-H), 2.19-2.10 (14H, m, 4 × CH ₂ CH (CH ₃ ) ₂ ) 2.02-1.96 (7H, m, 7 × CH ₂ CH (CH ₃ ) ₂ ) 0.91-0,75 (42H, m, 7 × CH ₂ CH (CH ₃ ) ₂ )

Sucrose 3,7,8,10,11,12-hexa-o-isovalorate

FAB mass: 869 [M + Na] ⁺

H-NMR (δ, CDCl 3): 5.45-5.46 (2H, m, 5,7-H), 5.42 (1H, t, J 9.9, 8-H), 5.00 (1H, t, J 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), 2.19-2.10 (12H, m , 6 × CH ₂ CH (CH ₃ ) ₂ ) 2.02-1.96 (7H, m, 6 × CH ₂ CH (CH ₃ ) ₂ ) 0.91-0,75 (42H, m, 6 × CH ₂ CH (CH ₃ ) ₂ )

Synthesis Example 4 (Synthesis example of sucrose isobutylate derivative)

Synthesis was carried out in the same manner as in Synthesis Example 3 except for using isobutylic anhydride instead of isovaleric anhydride to obtain 12.8 g of oil. Sucrose 2,3,4,7,8,10,11,12-octa-o-isobutyrate 2.0 by separating and purifying the obtained oil using a silica chromatography column (ethyl acetate / hexane 1: 6). g (Rf = 0.83, yield: 16.8%), sucrose 2,4,7,8,10,11,12-hepta-o-isobutyrate 1.5 g (Rf = 0.70, yield: 10.4%), sucrose 3, 1.2 g of 7,8,10,11,12-hexa-o-isobutylate (Rf = 0.62, yield: 10.1%) was obtained.

The obtained sucrose isobutylate derivative was identified using the assay described in Synthesis Example 1.

Sucrose 2,3,4,7,8,10,11,12-octa-o-isobutylate

FAB mass: 925 [M + Na] ⁺

H-NMR (δ, CDCl 3): 5.46 (1H, m, 5-H), 5.39 (1H, d, J 3.9, 7-H), 5.32 (1H, t, J 8, 8-H), 4.82 ( 1H, t, J 9.8, 2-H), 4.81 (1H, m, 4-H), 4.53 (1H, 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, 8 × CH ₂ (CH ₃ ) ₂ ) 1.20-1.08 (24H, m, 8 × CH (CH ₃ ) ₂ )

Sucrose 2,4,7,8,10,11,12-hepta-o-isobutylate

FAB mass: 855 [M + Na] ⁺

H-NMR (δ, CDCl 3): 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 9.9 3-H), 2.19-2.10 (14H, m, 7 × CH ₂ CH (CH ₃ ) ₂ ) 2.76-2.40 (7H, m, 7 × CH ₂ (CH ₃ ) ₂ ) 1.31-1.11 (42H, m, 7 × CH (CH ₃ ) ₂ )

Sucrose 3,7,8,10,11,12-hexa-o-isobutyrate

FAB mass: 785 [M + Na] ⁺

H-NMR (δ, CDCl 3): 5.45-5.46 (2H, m, 5,7-H), 5.42 (1H, t, J 9.9, 8-H), 5.00 (1H, t, J 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 , 6 × CH ₂ (CH ₃ ) ₂ ) 1.31-1.11 (36H, m, 6 × CH (CH ₃ ) ₂ )

Experimental Example

Glucose-acylated derivatives and sucrose acylated derivative compounds obtained in accordance with Synthesis Examples 1 to 4 and hydroquinone aqueous solution were added to the culture solution of mouse melanoma cells (B-16 mouse melanoma cells) to test the whitening effect at the cellular level. (Lotan R., Lotan D. Cancer Res. 40: 3345-3350, 1980). The final concentration of the mixture synthesized according to Synthesis Examples 1 to 4, each of the purified compounds, and hydroquinone was adjusted to the concentrations shown in Tables 1 to 4, and then added to the culture medium of B-16 melanoma cells, respectively, for 3 days. Incubated. The cultured cells were then trypsinized, removed from the culture vessel and centrifuged to extract melanin.

1 ml of sodium hydroxide solution (1N concentration) was added to the extract to dissolve melanin by boiling for 10 minutes, and then the absorbance at 400 nm was measured using a spectrophotometer to measure the amount of melanin produced per unit cell count (10 ⁶ cells). Represented. In addition, the relative melanin production relative to the control group was calculated as the inhibition rate (%) and the results are shown in the table.

Each of the compounds obtained by the separation and purification in Synthesis Examples 1 to 4 was expressed as follows.

Glucose 1,2,3,4,6-penta-o-isovalorate: Glu-5-iV

Glucose 1,2,3,4-tetra-o-isovalorate: Glu-4-iV-1

Glucose 1,2,4,6-tetra-o-isovalorate: Glu-4-iV-2

Glucose 1,2,3,6-tetra-o-isovalorate: Glu-4-iV-3

Glucose 1,3,6-tri-o-isovalate: 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-isovalorate: Su-8-iV

Sucrose 2,4,7,8,10,11,12-hepta-o-isovalorate: Su-7-iV

Sucrose 3,7,8,10,11,12-hexa-o-isovalorate: 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

sample Final concentration (㎍ / ㎖) Melanin production  % Inhibition Control 0 0.047 ± 0.004 - Hydroquinone One 0.025 ± 0.002 46 5 Death - Glucose Isovalate Mixture (Synthesis Example 1) One 0.035 ± 0.002 25 5 0.029 ± 0.003 38 20 0.026 ± 0.004 45 Glu-5-iV One 0.029 ± 0.002 38 5 0.026 ± 0.002 45 20 0.015 ± 0.002 68 Glu-4-iV-1 One 0.034 ± 0.002 28 5 0.029 ± 0.003 38 20 0.025 ± 0.004 47 Glu-4-iV-2 One 0.032 ± 0.002 32 5 0.024 ± 0.003 49 20 0.020 ± 0.002 57 Glu-4-iV-3 One 0.033 ± 0.002 30 5 0.026 ± 0.003 45 20 0.022 ± 0.002 53 Glu-3-iV One 0.035 ± 0.003 25 5 0.027 ± 0.002 46 20 0.024 ± 0.004 49

sample Final concentration (㎍ / ㎖) Melanin production  % Inhibition Control 0 0.047 ± 0.004 - Hydroquinone One 0.025 ± 0.002 46 5 Death - Glucose Isobutylate Mixture (Synthesis Example 2) One 0.039 ± 0.002 17 5 0.030 ± 0.002 36 20 0.023 ± 0.004 51 Glu-5-iB One 0.038 ± 0.003 19 5 0.030 ± 0.002 36 20 0.022 ± 0.002 53 Glu-4-iB-1 One 0.037 ± 0.002 21 5 0.029 ± 0.003 38 20 0.025 ± 0.002 47 Glu-4-iB-2 One 0.035 ± 0.003 25 5 0.030 ± 0.002 36 20 0.024 ± 0.002 49 Glu-4-iB-3 One 0.036 ± 0.003 23 5 0.029 ± 0.003 38 20 0.022 ± 0.002 53 Glu-3-iB One 0.038 ± 0.003 19 5 0.027 ± 0.002 43 20 0.023 ± 0.004 51

sample Final concentration (㎍ / ㎖) Melanin production  % Inhibition Control 0 0.047 ± 0.003 - Hydroquinone One 0.025 ± 0.002 46 5 Death - Sucrose isovalerate mixture (synthesis example 3) One 0.037 ± 0.003 21 5 0.030 ± 0.002 36 20 0.026 ± 0.004 45 Su-8-iV One 0.036 ± 0.002 23 5 0.028 ± 0.002 40 20 0.024 ± 0.002 49 Su-7-iV One 0.033 ± 0.002 30 5 0.026 ± 0.002 45 20 0.021 ± 0.002 55 Su-6-iV One 0.035 ± 0.002 25 5 0.028 ± 0.003 40 20 0.026 ± 0.002 45

sample Final concentration (㎍ / ㎖) Melanin production  % Inhibition Control 0 0.047 ± 0.003 - Hydroquinone One 0.025 ± 0.002 46 5 Death - Sucrose Isobutylate Mixture (Synthesis Example 4) One 0.038 ± 0.003 21 5 0.031 ± 0.002 34 20 0.025 ± 0.004 47 Su-8-iB One 0.036 ± 0.002 23 5 0.028 ± 0.002 40 20 0.024 ± 0.003 49 Su-7-iB One 0.037 ± 0.002 30 5 0.027 ± 0.004 45 20 0.023 ± 0.003 51 Su-6-iB One 0.035 ± 0.003 25 5 0.029 ± 0.002 38 20 0.027 ± 0.002 43

Referring to Tables 1 to 4, it can be seen that glucose acylation derivatives and sucrose acylation derivatives exhibit very strong melanin production inhibitory ability against cultured mouse melanoma cells. In particular, glucose 1,2,3,4,6-penta-o-isovalerate was found to be excellent in inhibiting melanogenesis. On the other hand, hydroquinone has a strong melanin production inhibitory ability, but the experiment was not possible because of the severe cytotoxicity above the concentration of 1 ㎍ / ㎖, glucose acylation derivatives and sucrose acylated derivatives according to the present invention concentration of 20 ㎍ / ㎖ In addition, because it does not exhibit cytotoxicity can have a higher melanin production inhibitory effect than hydroquinone.

Hereinafter, glucose acylation derivatives and sucrose acylated derivatives are added to an external skin ointment, cream, softening lotion, nourishing longevity, pack, and essence to prepare a cosmetic, and to prescribe them for the subjects, to prepare a glucose acylated derivative and sucrose. Examine the pigmentation inhibitory effect of the cosmetic containing an acylated derivative.

Example 1 and Comparative Example 1

To the skin ointment was prepared in the ingredients and contents shown in Table 5.

Composition (% by weight) Example 1 Comparative Example 1 a b c d e Glu-5-iV One - - - - - Glu-4-iV-2 - One - - - - Glu-5-iB - - One - - - Su-7-iV - - - One - - Su-7iB - - - - One - Diethyl sebacate 8 8 8 8 8 8 Prepayment 5 5 5 5 5 5 Polyoxyethylene oleyl ether phosphate 6 6 6 6 6 6 Sodium benzoate Quantity Quantity Quantity Quantity Quantity Quantity vaseline to 100 to 100 to 100 to 100 to 100 to 100

Example 2 and Comparative Example 2

To prepare a cream with the ingredients and contents shown in Table 6.

Composition (% by weight) Example 2 Comparative Example 2 a b c d e Glu-5-iV 0.1 - - - - - Glu-4-iV-2 - 0.1 - - - - Glu-5-iB - - 0.1 - - - Su-7-iV - - - 0.1 - - Su-7iB - - - - 0.1 - Stearic acid 1.0 1.0 1.0 1.0 1.0 1.0 Cetanol 2.0 2.0 2.0 2.0 2.0 2.0 Fiji-20 1.0 1.0 1.0 1.0 1.0 1.0 Sorbitan monostearate 1.0 1.0 1.0 1.0 1.0 1.0 Mineral oil 10.0 10.0 10.0 10.0 10.0 10.0 Trioctanoate 5.0 5.0 5.0 5.0 5.0 5.0 Triethanolamine 0.5 0.5 0.5 0.5 0.5 0.5 Carbomer 0.2 0.2 0.2 0.2 0.2 0.2 glycerin 5.0 5.0 5.0 5.0 5.0 5.0 Propylene glycol 3.0 3.0 3.0 3.0 3.0 3.0 antiseptic Quantity Quantity Quantity Quantity Quantity Quantity incense Quantity Quantity Quantity Quantity Quantity Quantity Purified water to 100 to 100 to 100 to 100 to 100 to 100

Example 3 and Comparative Example 3

To a flexible cosmetics was prepared in the ingredients and contents shown in Table 7.

Composition (% by weight) Example 3 Comparative Example 3 a b c d e Glu-5-iV 0.1 - - - - - Glu-4-iV-2 - 0.1 - - - - Glu-5-iB - - 0.1 - - - Su-7-iV - - - 0.1 - - Su-7iB - - - - 0.1 - ethanol 10.0 10.0 10.0 10.0 10.0 10.0 Polyoxyethylene Cured Castor Oil 1.0 1.0 1.0 1.0 1.0 1.0 Methyl paraoxybenzoate 0.2 0.2 0.2 0.2 0.2 0.2 glycerin 5.0 5.0 5.0 5.0 5.0 5.0 1,3-butylene glycol 6.0 6.0 6.0 6.0 6.0 6.0 incense Quantity Quantity Quantity Quantity Quantity Quantity Pigment Quantity Quantity Quantity Quantity Quantity Quantity Purified water to 100 to 100 to 100 to 100 to 100 to 100

Example 4 and Comparative Example 4

Essence was prepared with the ingredients and contents shown in Table 8 below.

Composition (% by weight) Example 4 Comparative Example 4 a b c d e Glu-5-iV 0.5 - - - - - Glu-4-iV-2 - 0.5 - - - - Glu-5-iB - - 0.5 - - - Su-7-iV - - - 0.5 - - Su-7iB - - - - 0.5 - Propylene glycol 10.0 10.0 10.0 10.0 10.0 10.0 glycerin 10.0 10.0 10.0 10.0 10.0 10.0 Sodium hyaluronate aqueous solution (1%) 5.0 5.0 5.0 5.0 5.0 5.0 ethanol 5.0 5.0 5.0 5.0 5.0 5.0 Polyoxyethylene Cured Castor Oil 1.0 1.0 1.0 1.0 1.0 1.0 Methyl paraoxybenzoate 0.1 0.1 0.1 0.1 0.1 0.1 Carbomer 0.4 0.4 0.4 0.4 0.4 0.4 incense Quantity Quantity Quantity Quantity Quantity Quantity Purified water to 100 to 100 to 100 to 100 to 100 to 100

Example 5 and Comparative Example 5

Packs were prepared with the ingredients and contents listed in Table 9 below.

Composition (% by weight) Example 5 Comparative Example 5 a b c d e Glu-5-iV 0.1 - - - - - Glu-4-iV-2 - 0.1 - - - - Glu-5-iB - - 0.1 - - - Su-7-iV - - - 0.1 - - Su-7iB - - - - 0.1 - glycerin 5.0 5.0 5.0 5.0 5.0 5.0 Propylene glycol 4.0 4.0 4.0 4.0 4.0 4.0 Polyvinyl alcohol 15.0 15.0 15.0 15.0 15.0 15.0 ethanol 8.0 8.0 8.0 8.0 8.0 8.0 Polyoxyethylene Cured Castor Oil 1.0 1.0 1.0 1.0 1.0 1.0 Polyoxyethylene oleyl ether phosphate 1.0 1.0 1.0 1.0 1.0 1.0 Methyl paraoxybenzoate 0.2 0.2 0.2 0.2 0.2 0.2 incense Quantity Quantity Quantity Quantity Quantity Quantity Pigment Quantity Quantity Quantity Quantity Quantity Quantity Purified water to 100 to 100 to 100 to 100 to 100 to 100

Example 6 and Comparative Example 6

To nutrient cosmetics was prepared with the ingredients and contents shown in Table 10 below.

Composition (% by weight) Example 6 Comparative Example 6 a b c d e Glu-5-iV 0.01 - - - - - Glu-4-iV-2 - 0.01 - - - - Glu-5-iB - - 0.01 - - - Su-7-iV - - - 0.01 - - Su-7iB - - - - 0.01 - Polyoxyethylene Cured Castor Oil 1.0 1.0 1.0 1.0 1.0 1.0 Methyl paraoxybenzoate Quantity Quantity Quantity Quantity Quantity Quantity glycerin 6.0 6.0 6.0 6.0 6.0 6.0 1,3-butylene glycol 5.0 5.0 5.0 5.0 5.0 5.0 Carbomer 0.2 0.2 0.2 0.2 0.2 0.2 Triethanolamine 0.3 0.3 0.3 0.3 0.3 0.3 Propylene glycol 5.0 5.0 5.0 5.0 5.0 5.0 ethanol 3.2 3.2 3.2 3.2 3.2 3.2 Carboxy Vinyl Polymer 0.1 0.1 0.1 0.1 0.1 0.1 Pigment Quantity Quantity Quantity Quantity Quantity Quantity incense Quantity Quantity Quantity Quantity Quantity Quantity Purified water to 100 to 100 to 100 to 100 to 100 to 100

The method used to verify the pigmentation inhibitory effect by the skin external ointment, cream, supple cosmetics, nutrient cosmetics, pack, essence prepared as described above is as follows.

First, select 20 healthy men and women and attach aluminum foil with two rows of 6 holes with a diameter of 7 mm in the lower part of both arms. Was investigated. The irradiation site was washed well with 70% ethanol aqueous solution before irradiation. The cosmetics of Examples 1-6 and the cosmetics of Comparative Examples 1-6 were applied to the same line twice a day from 3 days before irradiation to 3 weeks after irradiation. Here, the pack agents of Example 5 and Comparative Example 5 were removed 15 minutes after the application.

After prescribing the cosmetics according to the respective examples and the comparative example according to the above method, the degree of pigmentation was visually determined, and the effect of the pigmentation inhibition of the cosmetics according to each example and the cosmetics according to the comparative example was compared to the apparent effect. (A), the effect (B), no difference (C) evaluated in three stages, the results are shown in Table 11 below.

sample Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 A B C A B C A B C A B C A B C A B C a (Glu-5-iV) 5 9 6 5 8 7 6 9 5 7 9 4 5 9 6 6 8 6 b (Glu-4-iV-2) 2 8 10 3 9 8 6 6 8 3 8 9 3 6 11 3 8 9 c (Glu-5-iB) One 9 10 3 8 9 5 5 10 3 9 8 5 8 7 6 7 7 d (Su-7-iV) 3 5 12 5 8 7 5 7 8 3 8 9 4 8 8 4 7 9 e (Su-7-iB) 4 8 8 3 9 8 4 9 7 5 10 5 4 9 7 3 10 7

As shown in Table 11, the cosmetics of Examples 1 to 6 containing glucose acylated derivatives or sucrose acylated derivatives exhibited excellent skin whitening effects compared to conventional cosmetics, including glucose 1,2,3,4, The skin lightening effect of the cosmetics of Examples 1a to 6a containing 6-penta-o-isovalorate (Glu-5-iV) was particularly excellent.

As such, the glucose acylation derivatives and sucrose acylated derivatives of the present invention are easy to synthesize, have no side effects on the skin, and inhibit melanin production and have excellent pigmentation inhibition effects on the skin. Therefore, the cosmetic containing it may be usefully used for skin whitening.

Claims (5)

A cosmetic composition for skin whitening characterized in that it contains any one selected from the group consisting of glucose acylation derivatives represented by the following general formula (1), sucrose acylated derivatives represented by the following general formula (2), and mixtures thereof; <Formula 1> In Formula 1, R is a hydrogen atom or an acyl group having 3 to 6 carbon atoms, and the number of acyl groups is 3 to 5; <Formula 2> In Formula 2, R is a hydrogen atom or an acyl group having 3 to 6 carbon atoms, and the number of acyl groups is 6 to 8. The cosmetic for skin whitening according to claim 1, wherein the glucose acylated derivative is glucose 1,2,3,4,6-penta-o-isovalerate. The method of claim 1, wherein the glucose acylated derivative is glucose 1,2,3,4-tetra-o-isovalorate, glucose 1,2,4,6-tetra-o-isovalorate, glucose 1,2 , 3,6-tetra-o-isovalorate, glucose 1,3,6-tri-o-isovalorate, glucose 1,2,3,4,6-penta-o-isobutyrate, 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 any one selected from the group consisting of a mixture for skin whitening. The method of claim 1, wherein the sucrose acylated derivative is sucrose 2,3,4,7,8,10,11,12-octa-o-isovalorate, sucrose 2,4,7,8,10,11, 12-hepta-o-isovalorate, sucrose 3,7,8,10,11,12-hexa-o-isovalorate, sucrose 2,3,4,7,8,10,11,12-octa- O-isobutyrate, 2,4,7,8,10,11,12-hepta-o-isobutylate, sucrose 3,7,8,10,11,12-hexa-o-isobutyrate and these Skin whitening cosmetics, characterized in that any one selected from the group consisting of. The method of claim 1, wherein the content of the glucose acylation derivative represented by Formula 1, the sucrose acylated derivative represented by Formula 2 or a mixture thereof is 0.0001 to 15% by weight based on the total weight of the cosmetic Skin whitening cosmetics.