KR101923966B1 - Composition containing ly294002 for skin whitening - Google Patents

Abstract

The present invention provides a skin whitening composition comprising LY294002 as an active ingredient. According to the skin whitening composition containing LY294002 of the present invention as an active ingredient, skin whitening occurs due to reduction of melanin production, suppression of tyrosinase activity and decrease of expression of melanin-related genes and proteins, Stability, and therefore can be widely applied to external preparations for skin, cosmetic compositions and pharmaceutical compositions.

Description

COMPOSITION CONTAINING LY294002 FOR SKIN WHITENING COMPOSITION CONTAINING LY294002

The present invention relates to a skin whitening composition containing LY294002, and more particularly, to a composition which contains LY294002 as an active ingredient to enable skin whitening due to reduction of melanin production, inhibition of tyrosinase activity and decrease of expression of melanin-related protein .

Melanin is a pigment that determines the skin color of a person. Skin color is determined by the amount and distribution of melanin. Cells that make melanin are made from a cell called melanocyte underneath the epidermis and move to the surface of the skin with the metabolism of the skin. Regardless of skin color, the number of melanin-forming cells is almost the same. Only melanin is produced in different amounts, because of the kind and distribution of skin color is different.

In the skin, tyrosine is converted to dopa (DOPA) by a human enzyme called tyrosinase, and a series of subsequent oxidation steps finally produce a dark brown polymer, melanin.

Since the melanin formation process is an oxidation process, it is further promoted by active oxygen in the body, which is an oxidation promoting substance, or active oxygen generated by ultraviolet rays. Therefore, antioxidants (vitamin A / E, flavonoids, tannins, etc.) can inhibit excessive production even if they do not inhibit the direct production of melanin.

LY294002, on the other hand, is known to act as an inhibitor of the PI3K-Akt pathway. However, there was no known skin whitening efficacy of LY294002.

Korea Patent Publication No. 10-2008-0020029

In order to solve the above problems, it is an object of the present invention to provide a composition having excellent skin whitening effect by containing LY294002 as an active ingredient.

In order to solve the above-mentioned problems, the present invention provides a skin whitening composition comprising LY294002 as an active ingredient.

In one embodiment of the present invention, the LY294002 may have a concentration of 0.1 to 1000 μM.

In one embodiment of the present invention, the composition may be to whiten the skin by reducing the production of melanin.

In one embodiment of the present invention, the composition may be to whiten skin by inhibiting the activity of tyrosinase.

In one embodiment of the invention, the composition may be to whiten the skin by reducing the expression of a melanogenesis-related protein.

In one embodiment of the present invention, the melanogenesis-related protein may be at least one selected from the group consisting of MITF, tyrosinase, TYRP1 and DCT.

In one embodiment of the present invention, the composition may be a cosmetic composition or a pharmaceutical composition.

According to the skin whitening composition containing LY294002 of the present invention as an active ingredient, skin whitening occurs due to reduction of melanin production, suppression of tyrosinase activity and decrease of expression of melanin-related genes and proteins, Stability, and therefore can be widely applied to external preparations for skin, cosmetic compositions and pharmaceutical compositions.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a photograph showing the amount of melanin produced in a skin whitening composition according to an embodiment of the present invention. FIG.
FIG. 2 is a graph illustrating the effect of reducing the melanin production of a skin whitening composition according to an embodiment of the present invention.
FIG. 3 is a graph showing an effect of inhibiting tyrosinase activity of a skin whitening composition according to an embodiment of the present invention.
4 is a photograph showing changes in cellular morphology of a skin whitening composition according to an embodiment of the present invention.
FIG. 5 is a graph showing the expression level of the melanin-related gene of the composition for skin whitening according to an embodiment of the present invention.
FIG. 6 is a graph showing the amount of melanin-related protein expressed in a skin whitening composition according to an embodiment of the present invention.

Hereinafter, preferred embodiments of the present invention will be described in detail in order to facilitate the present invention by those skilled in the art.

The present invention provides a skin whitening composition comprising LY294002 as an active ingredient.

LY294002 is a morpholine derivative of quercetin known as a PI3K inhibitor. LY294002 is represented by the following formula (1).

[Chemical Formula 1]

Conventional LY294002 has been known to be effective against allergic airways diseases, but no skin-related effects have been studied at all. The present invention confirms that LY294002 has excellent efficacy in skin whitening, and has incorporated it into the skin whitening composition as an effective ingredient.

In the present invention, LY294002 may be a concentration of 0.1 to 1000 μM. Preferably 10 to 800 μM, more preferably 300 to 700 μM. Most preferably 500 [mu] M. When the concentration of LY294002 is less than 0.1 mu M, the whitening effect is not sufficiently exhibited, and when it is more than 1000 mu M, a problem of skin stability may occur.

According to the invention The skin whitening composition containing LY294002 as an active ingredient has excellent skin whitening effect.

The composition according to the present invention may be to whiten the skin by reducing the production of melanin. This can be confirmed in Experimental Example 1 to be described later.

In addition, the composition according to the present invention may be one which whitens skin by inhibiting the activity of tyrosinase. This can be confirmed in Experimental Example 2 to be described later. Tyrosinase is converted to tyrosine (DOPA) by the human enzyme in the skin, and melanin, which is a dark brown polymer, is finally produced through a series of oxidation steps. Therefore, when the activity of tyrosinase decreases, As a result, a skin whitening effect appears.

In addition, the composition according to the present invention may be that the composition whitens the skin by reducing the expression of a melanogenesis-related protein. This is due to decreased expression of the melanin-forming gene. This can be confirmed in Experimental Example 4 to be described later.

The melanogenesis-related protein is not particularly limited as long as it is a protein involved in melanogenesis, but is preferably selected from the group consisting of MITF, tyrosinase, tyrosinase-related protein 1 (TYRP1) and DCT (also referred to as TRP2) It can be one or more selected.

In the present invention, the composition may be a cosmetic composition or a pharmaceutical composition.

The formulation of the cosmetic composition is not particularly limited and may be appropriately selected according to the purpose. For example, skin lotion, skin softener, skin toner, astringent, lotion, milky lotion, moisturizing lotion, nutrition lotion, massage cream, nutritional cream, moisturizing cream, hand cream, foundation, essence, nutrition essence, pack, soap, cleansing But the present invention is not limited thereto, and may be manufactured by any one or more formulations selected from the group consisting of a foam, a cleansing lotion, a cleansing cream, a body lotion and a body cleanser.

When the formulation of the present invention is a paste, cream or gel, animal fiber, plant fiber, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as the carrier component .

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

In the case of the solution or emulsion of the present invention, a solvent, a solvent or an emulsifier is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, , 3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan fatty acid esters.

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 and polyoxyethylene sorbitan ester, Cellulose, aluminum metahydroxide, bentonite, agar or tracant, etc. may be used.

When the formulation of the present invention is an interfacial active agent-containing cleansing, the carrier component may include aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty acid amide Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, linolenic derivatives or ethoxylated glycerol fatty acid esters.

The content of the active ingredient is not particularly limited, but may be in the range of 0.001 to 20% by weight based on the total weight of the composition. When the active ingredient satisfies the above content, it can exhibit excellent efficacy without side effects.

The above-mentioned cosmetic composition may further contain the components included in the functional additive and the general cosmetic composition in addition to the above. The functional additives may include water-soluble vitamins, oil-soluble vitamins, polymer peptides, polymeric polysaccharides, sphingolipids and seaweed extracts.

The cosmetic composition of the present invention may further contain, in addition to the above-described functional additive, components contained in a general cosmetic composition as required. Examples of the other ingredients that can be included in the composition include humectants, emollients, surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbents, preservatives, bactericides, antioxidants, plant extracts, pH adjusters, alcohols, Accelerators, coolants, antiperspirants, purified water, and the like.

The pharmaceutical composition may further contain a preservative, a stabilizer, a wetting agent or an emulsifying accelerator, a pharmaceutical adjuvant such as a salt and / or a buffer for controlling osmotic pressure, and other therapeutically useful substances, May be formulated into oral administration forms. Parenteral dosage forms, and may be, for example, but not limited to lotions, ointments, gels, creams, patches or spray formulations.

The dosage of the active ingredient is within the level of those skilled in the art, and the daily dose of the drug depends on various factors such as the degree of progress of the subject to be administered, the age of onset, age, health condition, As a standard, it is generally possible to administer the composition at a dose of 1 / / kg to 200 mg / kg, preferably 50 / / kg to 50 mg / kg, once or twice a day, Are not intended to limit the scope of the present invention.

Further, the present invention relates to an external preparation for skin comprising the composition, wherein the external preparation for skin is a generic term that may be applied to any external skin, and cosmetics and medicines of various formulations may be included.

The present invention will be described in more detail through the following examples. However, the examples are for illustrating the present invention, and the scope of the present invention is not limited thereto.

[Experimental Example 1] Melanin measurement experiment

1-1. After lysing 500 μM LY294002 for 2 days in MNT-1 cells (human melanoma cell line, Lonza, SWISS) with excessive melanogenesis, the cell lysate was centrifuged (eppendorf, centrifuge 5415R, Germany) Respectively. (Con) and mock treated with only DMSO as a solvent were observed together. This is shown in FIG. As shown in FIG. 1, it was confirmed that 500 μM LY294002 decreased melanin production.

1-2. The contents of the pellet were dissolved with sodium hydroxide, absorbance was measured at an OD490 specific to the melanin pigment and corrected to the total amount of protein. This is shown in FIG. As can be seen in Figure 2, a decrease in the amount of melanin was observed in 500 [mu] M LY294002.

[Experimental Example 2] Tyrosinase activity inhibition test

DOPA (dihydroxyphenylalanine) was added to cell lysate to determine the amount of dopachrome produced by the action of tyrosinase, a key enzyme of melanin synthesis, to compare the absorbance of OD490 to inhibit enzyme activity Were measured. (Con) and mock treated with only DMSO as a solvent were observed together. This is shown in FIG. As shown in FIG. 3, it was confirmed that the activity of tyrosinase was reduced in 500 μM LY294002.

[Experimental Example 3] Cell morphology observation

MNT-1 cells treated with 500 μM LY294002 for 2 days were photographed using a DP70 camera of a microscope (Olympus IX71, Japan). As a control group, no control was observed. This is shown in FIG. As can be seen in FIG. 4, the production of melanin was remarkably decreased in 500 μM LY294002, and no significant change in cell morphology was observed. That is, it can be seen that LY294002 does not have a large adverse effect on the cells at the concentration showing the whitening effect.

[Experimental Example 4] Gene / Protein expression

4-1. 500 μM LY294002 was treated with MNT-1 cells (human melanoma cell line, Lonza, SWISS) for two days. CDNA was synthesized from the isolated RNA and the changes of mRNA levels were measured by Q-PCR (Applied biosystems, 7500 Fast) using primers of MITF, tyrosinase, TYRP1 and DCT. (Con) and mock treated with only DMSO as a solvent were observed together. This is shown in FIG.

4-2. In addition, 500 μM LY294002 was treated with MNT-1 cells (human melanoma cell line, Lonza, SWISS) for two days. Twenty micrograms of the cell lysate was loaded, and the amount of protein expression of MITF, tyrosinase, TYRP1 and DCT was confirmed by Western blotting. GAPdh was used as a control. This is shown in Fig.

As shown in FIG. 5 and FIG. 6, the expression of MITF, tyrosinase, TYRP1 and DCT was decreased, and the expression of GAPdh was not changed. Thus, melanogenesis-related protein expression by LY294002 expression of melanin is thought to be due to a decrease in MITF, tyrosinase, TYRP1, and DCT by LY294002 treatment.

Claims (8)

As a skin whitening composition,
Wherein said composition contains LY294002 of formula (1) as an active ingredient,
The LY294002 has a concentration of 300 to 700 [mu] M,
Wherein the composition is a cosmetic composition.
[Chemical Formula 1]

delete The method according to claim 1,
Wherein the composition whitens the skin by reducing the production of melanin. The method according to claim 1,
Wherein the composition whitens the skin by inhibiting activity of tyrosinase. The method according to claim 1,
Wherein the composition whitening the skin by reducing the expression of a melanogenesis-related protein. 6. The method of claim 5,
Wherein the melanin formation-related protein is at least one selected from the group consisting of microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein 1 (TYRP1), and DCT (dopachrome tautomerase). delete delete

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