KR101534523B1 - Cosmetic Composition for Skin Whitening Comprising 1,2,3,4-Tetrahydro-6-methoxy-1-oxo-beta-carboline - Google Patents

Abstract

The present invention provides a cosmetic composition for skin whitening comprising 1,2,3,4-tetrahydro-6-methoxy-1-oxo-beta-carboline. The cosmetic composition according to the present invention inhibits the production of a protein called myosin Va, which is a carrier of the organelles called melanosomes in the melanin-producing cells, inhibits the movement of melanin and ultimately inhibits the migration to keratinocytes, .

Description

TECHNICAL FIELD The present invention relates to a cosmetic composition for skin whitening comprising 1,2,3,4-tetrahydro-6-methoxy-1-oxo-beta-carboline -methoxy-1-oxo-beta-carboline < / RTI >

The present invention relates to a cosmetic composition for skin whitening comprising 1,2,3,4-tetrahydro-6-methoxy-1-oxo-beta-carboline.

The chemical action of melanin production, which determines skin color, is now well known. The melanocyte, melanocyte, is a melanocyte called melanosome, And the melanosomes migrate to keratinocytes through melanocyte dendrites. Melanin transferred to the keratinocyte is interpreted as an important factor in determining skin color.

Three constituents are involved primarily in transferring melanomas to dendrites of melanin-producing cells. Rab27a is composed of three proteins, Melanophilin and Myosin Va. Rab27a is a carrier that binds to the melanosome membrane and allows melanophilin to recognize and transport the melanosomes. In order to move to the end, it is necessary to meet the myosin Va protein, which is a cytoskeleton of the cell. In the middle, it is a protein which is a linker for recognizing and linking these two proteins. That is, a protein called melanophilin to be. When these three constituents meet and form a tripartite complex, it is possible to move the melanoma normally to the dendritic tips and eventually to the keratinocytes. If any one of these three constituents is abnormal, there is no problem in the production of melanin, but there is a problem in the movement of the melanosome, which eventually results in a lightening of the skin color.

Therefore, there is a desperate need to develop a substance capable of suppressing the movement of melanin to exhibit skin whitening effect.

1,2,3,4-Tetrahydro-6-methoxy-1-oxo-beta-carboline (1,2,3,4-Tetrahydro- Lt; / RTI > of formula (I) with OMe at the R < 1 >

[Chemical Formula 1]

Carboline compounds have been studied as inhibitors of MAPKAP K2, and many studies have been conducted in this regard (References: Bioorganic & Medicinal Chemistry Letters Volume 17, Issue 16, 4664-4669, 2007). As a reverse transcriptase inhibitor of HIV virus using such 1,2,3,4-tetrahydro-6-methoxy-1-oxo-beta-carboline, 0216746, but there have not yet been developed whitening substances or verified the effectiveness of whitening.

Korean Patent No. 10-0356720 discloses a cosmetic for inhibiting melanin production and skin whitening containing petroleum ether extract and fraction (mixture of ginseng alkaloid) of ginseng as a main component and containing an ordinary excipient. One of the ginseng alkaloids 1-Carboethoxy-beta-Carboline of the following formula (2) is described.

(2)

Korean Patent No. 10-0482695 discloses a composition for skin whitening comprising a beta-carboline derivative represented by the following formula (3) as an active ingredient. Such a skin whitening composition exhibits a whitening effect by inhibiting the production of melanin .

 (3)

In this formula,

R represents hydrogen or an alkoxy group having 1 to 5 carbon atoms.

However, the beta-carboline derivatives are known to inhibit the production of melanin, but the effect of inhibiting melanin migration is not mentioned.

U.S. Published Patent Application No. 2010/0216746 Korean Patent No. 10-0356720 Korean Patent No. 10-0482695

The inventors of the present invention have conducted intensive research to develop a cosmetic composition that exhibits skin whitening effect by inhibiting the movement of melanin. As a result, 1,2,3,4-tetrahydro-6-methoxy-1-oxo-beta-carboline The present inventors have found that melanogenesis inhibits the movement of melanosomes by inhibiting the production of carrier protein responsible for the transfer of melanosomes in melanin-producing cells, thereby resulting in an excellent whitening effect despite normal melanogenesis. .

Accordingly, an object of the present invention is to provide a cosmetic composition for skin whitening comprising 1,2,3,4-tetrahydro-6-methoxy-1-oxo-beta-carboline.

The present invention relates to a cosmetic composition for skin whitening comprising 1,2,3,4-tetrahydro-6-methoxy-1-oxo-beta-carboline represented by the following formula (1).

[Chemical Formula 1]

The 1,2,3,4-tetrahydro-6-methoxy-1-oxo-beta-carboline synthesizes a protein called myosin Va, which is a carrier protein responsible for the transfer of melanosomes in melanin- To inhibit the binding of melanophilin and myosin Va, thereby inhibiting the transfer of melanosomes, thereby providing a whitening effect even though the melanin synthesis function is normal.

The cosmetic composition of the present invention specifically contains 0.0001 to 10.0% by weight, more specifically 0.001 to 10.0% by weight, of 1,2,3,4-tetrahydro-6-methoxy-1-oxo- . If the content is less than 0.0001% by weight, the effect can not be expected. If the content is more than 10% by weight, the composition stability and formulation stability are difficult. The content of the active ingredient may be appropriately determined depending on the intended use thereof.

The cosmetic composition of the present invention may contain, in addition to 1,2,3,4-tetrahydro-6-methoxy-1-oxo-beta-carboline as an active ingredient, components commonly used in cosmetic compositions such as antioxidants, Stabilizers, solubilizers, vitamins, customary adjuvants such as pigments and perfumes, and carriers.

The cosmetic composition of the present invention may be prepared in any form conventionally used in the art and may be formulated into, for example, solutions, suspensions, emulsions, pastes, gels, creams, powders, sprays and the like.

When the formulation of the present invention is a paste, cream or gel, an animal oil, a vegetable oil, a wax, a paraffin, a starch, a tracer, a cellulose derivative, polyethylene glycol, silicon, bentonite, silica, talc, .

When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, polyamide powder and the like may be used as a carrier component. In particular, Propane / butane or dimethyl ether.

When the formulation of the present invention is a solution or an emulsion, a solvent, a solubilizer or an emulsifier such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 3-butyl glycol oil, glycerol fatty acid ester, polyethylene glycol, fatty acid esters of sorbitan, and the like.

When the formulation of the present invention is a suspension, a carrier such as water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester or polyoxyethylene sorbitan ester, Cellulose, aluminum metahydroxide, bentonite, agar, tracant and the like may be used.

The cosmetic composition of the present invention can be applied to cosmetics such as skin, lotion, cream, pack, color cosmetic, sunscreen, two way cake, face powder, compact, makeup base, skin cover, eye shadow, lipstick, lip gloss, lip fix, Can be applied.

The cosmetic composition according to the present invention contains 1,2,3,4-tetrahydro-6-methoxy-1-oxo-beta-carboline as an active ingredient, and thereby produces myosin Va as a carrier of the organelles called melanosomes in melanin- , Inhibits the movement of melanin, and ultimately inhibits the migration to keratinocytes, thereby exhibiting an excellent whitening effect.

1 is a graph showing the distribution of melanosomes in cells treated with 1,2,3,4-tetrahydro-6-methoxy-1-oxo-beta-carboline and untreated cells (control) Lt; / RTI >
FIG. 2 is a graph showing the number of melanin migration inhibitory cells in cells treated with 1,2,3,4-tetrahydro-6-methoxy-1-oxo-beta-carboline and untreated cells (control group).
Figure 3 shows the number of melanin migration inhibitory cells in cells treated with 1,2,3,4-tetrahydro-6-methoxy-1-oxo-beta-carboline, untreated cells (control) Graph.
Figure 4 shows that Rab27a, melanopyrin (Mlph) and myosin Va (DMSO) in cells treated with 1,2,3,4-tetrahydro-6-methoxy-1-oxo- And Western blot results indicating the amount of protein expression.

Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these embodiments are for illustrative purpose only and that the scope of the present invention is not limited to these embodiments.

Example 1: Confirmation of melanosomal migration inhibitory effect

Culture of melanin-producing cells

Melan-a cells, which are immortalized melanocytes of mice, were cultured in RPMI 1640 medium containing 10% fetal bovine serum for 90% confluency, until you see the the cells were cultured at 10% CO ₂ incubator.

Confirmation and quantification of melanin migration inhibition in melanin-producing cells by 1,2,3,4-tetrahydro-6-methoxy-1-oxo-beta-carboline

The melan-a cells cultured in the above manner were removed with 0.25% Trypsin-EDTA, and the same number (4 × 10 ⁵ cells / well) was added to the wells of the 6- Were cultured for 24 hours. Then, 1,2,3,4-tetrahydro-6-methoxy-1-oxo-beta-carboline was treated at three concentrations, and after 2 days, the cell shape was observed through an optical microscope. 1.

As can be seen in FIG. 1, it was observed that melanosomes were darker than 1,2,3,4-tetrahydro-6-methoxy-1-oxo-beta-carboline, In the cells treated with 3,4-tetrahydro-6-methoxy-1-oxo-beta-carboline, it was confirmed that melanosomes were not distributed throughout the cells but distributed around the nucleus.

Then, a cell photograph in which melanin migration observed through a microscope was inhibited is shown in Table 1 and FIG. 2, in which the number of cells in which melanin migration was inhibited under the same area is counted.

Control group 1,2,3,4-Tetrahydro-6-methoxy-1-oxo-beta-carboline density 23uM 11.5 uM 4.6 uM Melanin
Inhibition of movement
Cell number Primary 0 58 50 12 Secondary 0 33 45 3 Third 0 53 48 8 Average 0 48 47.7 7.7 Standard Deviation 0 13.2 2.5 4.5

As can be seen in Table 1 and FIG. 2, cells treated with 1,2,3,4-tetrahydro-6-methoxy-1-oxo-beta-carboline inhibited melanin migration I can confirm that there are more numbers.

Confirmation and quantification of melanin migration inhibition in melanin-producing cells by 1,2,3,4-tetrahydro-6-methoxy-1-oxo-beta-carboline and conventional beta-carboline derivatives

1,2,3,4-tetrahydro-6-methoxy-1-oxo-beta-carboline and the comparative compound 1-Carboethoxy-beta-Carboline 4-Methoxy-1-vinyl-beta-Carboline (R is hydrogen), and 4,8-dimethoxy-1-vinyl -Beta-carboline (compound of formula (III) wherein R is methoxy) was treated at a concentration of 10 uM each, and after 2 days, the cell shape was observed through an optical microscope The number of cells in which melanin migration was inhibited under the same area was counted in Table 2 and FIG. 3, in which a cell photograph in which melanin migration observed through a microscope was inhibited is counted.

　
　 Control group 1,2,3,4-Tetrahydro-6-methoxy-1-oxo-beta-carboline 1-Carbethoxy-beta-carboline 4-Methoxy-1-vinyl-beta-carbolin 4,8-dimethoxy-1-vinyl-beta-carboline density 10uM 10uM 10uM 10uM Melanin
Inhibition of movement
Cell number Primary 0 50 3 4 2 Secondary 0 45 2 2 5 Third 0 48 0 One 7 Average 0 47.7 1.7 2.3 4.7 Standard Deviation 0 2.5 1.5 1.5 2.5

As can be seen in Table 2 and FIG. 3, cells treated with 1,2,3,4-tetrahydro-6-methoxy-1-oxo-beta-carboline showed significantly higher levels of melanin It was confirmed that the number of movement inhibited was significant.

Example 2: Determination of Expression Level of Rab27a, Melanopyrin and Myosin Va Protein

After melan-a cells were treated with 1,2,3,4-tetrahydro-6-methoxy-1-oxo-beta-carboline for 3 days, lysis buffer (RIPA buffer , Protease inhibitor cocktail, 1 mM PMSF). After centrifugation at 13,000 rpm, the supernatant was taken, electrophoresed using NuPage® 10% Bis-Tris gel, and transferred to PVDF membrane for 18 hours. PVDF membranes were incubated in skim milk for 1 hour and incubated with Rab27a (Santa Cruz, 1: 500), Melanophilin (ProteinTech Group, Inc, 1: 600), Myosin Va , 1: 1000), and reacted overnight. After the reaction, the cells were washed three times with 1 × TBS-T solution containing 0.1% Tween 20 and reacted using a secondary antibody (Bethyl, 1: 5000) with HRP (Horseradish peroxidase) Respectively. This was analyzed by photoluminescence using an X-ray film. The results are shown in Fig.

Western blotting revealed that the expression of Myosin Va protein, one of the three proteins involved in the transfer of melanomas, was reduced.

Claims (3)

1. A cosmetic composition for skin whitening comprising 1,2,3,4-tetrahydro-6-methoxy-1-oxo-beta-carboline represented by the following formula 1 as an active ingredient:
[Chemical Formula 1]

The cosmetic composition for skin whitening according to claim 1, wherein 1,2,3,4-tetrahydro-6-methoxy-1-oxo-beta-carboline is contained in an amount of 0.0001 to 10% . The cosmetic composition for skin whitening according to claim 1 or 2, which is formulated into a solution, a suspension, an emulsion, a paste, a gel, a cream, a powder or a spray.

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