KR20140042489A - Composition for skin whitening containing compound of regulation for abh antigen - Google Patents

Abstract

The present invention relates to a skin whitening composition. The skin whitening composition according to the present invention contains a material regulating the expression of an ABH antigen as an effective component, and controls the generation of melanin, thereby having an excellent skin whitening effect of effectively treating or curing chloasma, freckles, spots, or skin pigmentation.

Description

TECHNICAL FIELD The present invention relates to a skin whitening composition containing a substance that regulates the expression of an ABH antigen.

The present invention relates to a composition for whitening skin.

Blood type antigen refers to a structure with specific antigenicity found in glycoproteins or glycolipids on the erythrocyte surface of blood. Typically, there are ABO blood type antigens (ABH antigens) and Lewis blood type antigens. Blood type is determined according to the glycosylation terminal structure of specific structure. ABO-type blood group antigens and Lewis-type blood group antigens are not only expressed in red blood cells but are found in various parts of the human body. In particular, ABO blood group type antigens are expressed in the epithelium of the esophagus, stomach, And is expressed in the granular layer of the epidermis in the skin.

The expression of the granules of the epidermis of the ABO type blood group antigen is closely related to skin-related diseases, particularly inflammatory diseases, because they appear on the outermost layer of the skin in anatomical location.

ABO blood group antigens are very important antigens that are responsible for rejection of transfusions and organ transplants, but since their discovery in 1900, there has been little research on physiological functions other than rejection.

The present inventors confirmed that a substance that regulates the expression of ABH antigen has a skin whitening effect, and completed the present invention.

Korean Patent Publication No. 10-2010-0082709

It is an object of the present invention to provide compositions that bring about skin whitening efficacy.

In order to achieve the above object, the present invention provides a skin whitening composition comprising a substance that regulates the expression of an ABH antigen as an active ingredient.

The composition according to the present invention contains a substance that regulates the expression of ABH antigen as an active ingredient and inhibits the production of melanin, so that it can have an excellent skin whitening effect, such as effectively improving and treating spots, freckles, dots or skin pigmentation .

Figure 1 shows the structure of ABH and Lewis blood type antigens.
FIG. 2 shows the results of confirming that the expression of B antigen is increased in HaCaT cell line by a substance that regulates the expression of ABH antigen.

In one aspect, the present invention relates to a skin whitening composition comprising, as an active ingredient, a substance that modulates the expression of an ABH antigen.

As used herein, the term "ABH antigen" refers to a structure having specific antigenicity expressed on the glycoprotein or glycolipids of the erythrocyte surface of blood. Typically, the ABH antigen is an ABH antigen represented by Figure 1, an ABH antigen such as Lewis- It is used in a sense to include all aggregates of analogs. An ABH antigen analogue is a substance to which a monosaccharide, an amino acid, or the like is further bound, and means a substance having the same function as the original function of the ABH antigen. FIG. 1 shows the structures of ABH and Lewis blood type antigens.

In the present specification, "skin whitening" is understood as a result of inhibition of the production of melanin, specifically, prevention of symptoms caused by the production of melanin, such as spots, freckles, skin aging, .

As used herein, the term " active ingredient "alone refers to an ingredient that exhibits the desired activity or that can exhibit activity with a carrier that is not itself active.

In the composition for skin whitening, which is one aspect of the present invention, the substance that regulates the expression of the ABH antigen includes a substance that increases the expression of the ABH antigen. The increased expression of ABH antigens may be due to increased expression of B antigen in the HaCaT cell line.

In the skin whitening composition according to one aspect of the present invention, the substance that regulates the expression of the ABH antigen is 1,3-dicaffeoylquinic acid, 1,5-dicaffeoylquinic acid 1,5-dicafeoylquinic acid, and amentoflavon, a derivative thereof, or a pharmaceutically acceptable salt thereof.

[Chemical Formula 1]

(2)

(3)

As used herein, the term "derivative" means any compound that can be substituted with another substituent at a substitutable position of the compound, and there is no limitation on the kind of such substituent.

As used herein, the term " pharmaceutically acceptable "refers to the approval of a government or equivalent regulatory agency that can be used on animals, and more specifically on humans, by avoiding significant toxic effects when used in conventional medicinal dosage Received, approved, or listed in pharmacopoeia or other general pharmacopoeia.

As used herein, "pharmaceutically acceptable salt" means a salt according to one aspect of the present invention which is pharmaceutically acceptable and has the desired pharmacological activity of the parent compound. The salt may be (1) formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like; (3-hydroxybenzoyl) benzoic acid, or an acetic acid, propionic acid, hexanoic acid, cyclopentenepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, Benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethane-disulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4- chlorobenzenesulfonic acid, 2- 4-methylbicyclo [2,2,2] -oct-2-en-1-carboxylic acid, glucoheptonic acid, 3-phenylpropionic acid, trimethylacetic acid, tert Acid addition salts formed with organic acids such as butylacetic acid, laurylsulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid; Or (2) salts formed when the acidic proton present in the parent compound is substituted.

In the composition for skin whitening, which is an aspect of the present invention, the composition may contain 0.001% to 20% by weight of a substance that controls the expression of an ABH antigen, based on the total weight of the composition.

When the substance that controls the expression of the ABH antigen is used within the above range, it is not only suitable for exhibiting the intended whitening effect of the present invention but also can satisfy both the stability and safety of the composition and is useful in terms of cost effectiveness . In view of the above, the composition of the present invention may contain 0.005 wt% to 19.5 wt%, 0.01 wt% to 19 wt%, 0.015 wt% to 18.5 wt%, 0.02 wt% of the substance that controls the expression of ABH antigen % To 18 wt%, 0.025 wt% to 17.5 wt%, 0.03 wt% to 17 wt%, 0.035 wt% to 16.5 wt%, 0.04 wt% to 16 wt% or 0.045 wt% to 15.5 wt% .

In the composition for skin whitening, which is one aspect of the present invention, the substance that regulates the expression of the ABH antigen can inhibit the production of melanin. Specifically, the composition for skin whitening, which is one aspect of the present invention, can inhibit or inhibit the conversion of tyrosine to dopa (DOPA) by inhibiting tyrosinase, and inhibit or inhibit the activity of dopaoxidase And inhibit or inhibit the conversion of dopa to Dopa-quinone, thereby inhibiting or inhibiting the production of melanin.

In one aspect of the invention, the composition may be a cosmetic composition.

The formulation of the cosmetic composition is not particularly limited and may be appropriately selected according to the purpose. For example, it can be applied to softeners (skin lotion and milk lotion), nutrition lotion, essence, nutrition cream, massage cream, pack, gel, essence, eye cream, eye essence, cleansing cream, cleansing foam, cleansing water, A body lotion, a body cream, a body oil, and a body essence, but the present invention is not limited thereto. In addition, the cosmetic composition may be used in the form of an external preparation for skin in the form of ointment, patch, or the like.

The cosmetic composition according to the present invention may be provided in all formulations suitable for topical application. For example, it may be provided as a solution, an emulsion obtained by dispersing an oil phase in an aqueous phase, an emulsion obtained by dispersing an oil phase in water, a suspension, a solid, a gel, a powder, a paste, a foam or an aerosol composition. Compositions of such formulations may be prepared according to conventional methods in the art.

The cosmetic composition according to the present invention may contain, in addition to the above-mentioned substances, other ingredients which can give a synergistic effect to the main effect, so long as they do not impair the main effect. The cosmetic composition according to the present invention may further comprise a moisturizing agent, an emollient agent, an ultraviolet absorber, an antiseptic, a bactericide, an antioxidant, a pH adjuster, an organic and inorganic pigment, a fragrance, a cold agent or a limiting agent. The compounding amount of the above components can be easily selected by those skilled in the art within a range not to impair the objects and effects of the present invention. The amount thereof may be 0.01 to 5% by weight, specifically 0.01 to 3% by weight, have.

In one aspect of the invention, the composition may be a pharmaceutical composition.

The formulation of the pharmaceutical composition according to the present invention may be a solution, a suspension, a milk, a gel, a drip agent, a suppository, a patch or a spray agent, but is not limited thereto. The formulations can be readily prepared according to conventional methods in the art and can be prepared by conventional means such as excipients, wetting agents, emulsifying accelerators, suspending agents, salts or buffers for controlling osmotic pressure, coloring agents, spices, stabilizers, preservatives, Adjuvants may be used as appropriate.

The effective ingredients of the pharmaceutical composition of the present invention will vary depending on the age, sex, weight, pathological condition and severity of the subject to be treated, administration route or judgment of the prescriber. Determination of the amount of application based on these factors is within the level of ordinary skill in the art and its daily dose is, for example, 0.000025 mg / g / day to 0.025 mg / g / day, more specifically 0.00025 mg / g / day. < / RTI >

The pharmaceutical composition of the present invention may be administered orally or transdermally, but is not limited thereto.

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 only for illustrating the present invention and that the scope of the present invention is not construed as being limited by these embodiments.

HaCaT  In cell line B antigen Effect

The effect of various kinds of compounds on the expression of ABH antigen was examined. For this, HaCaT cells were cultured in 10% FBS-DMEM in 35 mm dishes (provided by Prof. Dr. N. E. Fusenig, DKFZ Heidelberg, Germany) and starvation with 0% FBS-DMEM for 24 hours. The medium was replaced with 0% FBS-DMEM, and 1,3-dicaffeoylquinic acid, 1,5-dicafeoylquinic acid and a mentoflavone (amentoflavon) were respectively treated with HaCaT cells at a concentration of 2 ug / ml and then cultured for 48 hours (control group treated with DMSO). Proteins were extracted from the cells and the cell lysates were loaded in equal amounts and the expression of the B type antigen was examined by Western blot. Alpha-tubulin protein was used as a control.

As a result (FIG. 2), 1,3-dicaffeoylquinic acid, 1,5-dicafeoylquinic acid, and amentoflavon were found to have an effect of increasing the expression of B type antigen in HaCaT cells.

Assessment of Melanogenesis Inhibitory Effect

The inhibitory effect of 1,3-dicaffeoylquinic acid (1,5-dicafeoylquinic acid, amentoflavon), which increases the expression of ABH antigen, on melanin production was measured in comparison with kojisan, which is known to have an excellent skin whitening effect.

The degree of intracellular melanin production was measured by Dooley's method. The cell line was a Mel-Ab cell line (Falcon, USA) derived from a skin pigment of C57BL / 6. The culture was carried out in DMEM medium containing 10% fetal bovine serum, 100 nM 12-O-tetradecanoylphorbol-13-acetate and 1 nM cholera toxin at 37 ° C, 5 It was done under the condition of% CO _2. The cultured Mel-Ab cells were removed with 0.25% Trypsin-EDTA and inoculated again into the 24-well plate with the same number (1x10 ⁵ cells / well) The test substance was treated by replacing the medium with the medium containing the test compound. As test substances, 5 ppm, 10 ppm, 25 ppm and 50 ppm of koji, 25 ppm, 50 ppm and 100 ppm of DMSO (control group) of Examples 1 to 5 were used. After 5 days, the melanin contained in the cells was treated with 1N-NaOH, and the amount of melanin was measured by measuring the absorbance at 400 nm. The concentration (IC ₅₀ ) of the fermented product of the ash extract required to reduce the melanin production of the melanocyte in half was calculated, and the results are shown in the table below.

IC ₅₀ (ppm) Control group - 1,3-dicaffeoylquinic acid 23.5 1,5-dicafeoylquinic acid 23.5 amentoflavon 15.7 Kojic acid 39.36

As can be seen from the above results, it was confirmed that the substances that increase the expression of ABH antigen exhibited excellent melanin production inhibitory effect, and particularly had skin whitening effect superior to kojic acid, which is a conventional whitening agent.

Hereinafter, a formulation example of the composition according to the present invention will be described. However, the pharmaceutical composition and the cosmetic composition can be applied to various formulations, which are not intended to limit the present invention but merely to illustrate the present invention.

[Formulation Example 1] Lotion

Lotion is prepared according to a conventional method with the composition shown in the following table.

Content (% by weight) At least one member selected from the group consisting of 1,3-dicaffeoylquinic acid, 1,5-dicafeoylquinic acid and amentoflavon, compound 2.0 glycerin 3.0 Butylene glycol 2.0 Propylene glycol 2.0 Carboxyvinyl polymer 0.1 PEG 12 nonyl phenyl ether 0.2 Polysorbate 80 0.4 ethanol 10.0 Triethanolamine 0.1 Preservative, coloring, fragrance Suitable amount Purified water Balance

[Formulation Example 2] Nourishing cream

Nutritive creams are prepared according to the usual methods with the composition shown in the table below.

Content (% by weight) At least one member selected from the group consisting of 1,3-dicaffeoylquinic acid, 1,5-dicafeoylquinic acid and amentoflavon, compound 2.0 Polysorbate 60 1.5 Sorbitan sesquioleate 0.5 PEG 60 hardened castor oil 2.0 Liquid paraffin 10.0 Squalane 5.0 Caprylic / caproic triglyceride 5.0 glycerin 5.0 Butylene glycol 3.0 Propylene glycol 3.0 Triethanolamine 0.2 Preservative, coloring, fragrance Suitable amount Purified water Balance

[Formulation Example 3] Massage cream

A massage cream is prepared according to a conventional method with the composition shown in the following table.

Content (% by weight) At least one member selected from the group consisting of 1,3-dicaffeoylquinic acid, 1,5-dicafeoylquinic acid and amentoflavon, compound 1.0 Wax 10.0 Polysorbate 60 1.5 PEG 60 hardened castor oil 2.0 Sorbitan sesquioleate 0.8 Liquid paraffin 40.0 Squalane 5.0 Caprylic / capric triglyceride 4.0 glycerin 5.0 Butylene glycol 3.0 Propylene glycol 3.0 Triethanolamine 0.2 Preservative, coloring, fragrance Suitable amount Purified water Balance

[Formulation Example 4] Pack

A pack is prepared according to a conventional method with the composition shown in the following table.

Content (% by weight) At least one member selected from the group consisting of 1,3-dicaffeoylquinic acid, 1,5-dicafeoylquinic acid and amentoflavon, compound 1.0 Polyvinyl alcohol 13.0 Sodium carboxymethylcellulose 0.2 glycerin 5.0 Allantoin 0.1 ethanol 6.0 PEG 12 nonyl phenyl ether 0.3 Polysorbate 60 0.3 Preservative, coloring, fragrance Suitable amount Purified water Balance

[Formulation Example 5]

The gel is prepared according to a conventional method with the composition shown in the following table.

Content (% by weight) At least one member selected from the group consisting of 1,3-dicaffeoylquinic acid, 1,5-dicafeoylquinic acid and amentoflavon, compound 0.5 Ethylenediamine sodium acetate 0.05 glycerin 5.0 Carboxyvinyl polymer 0.3 ethanol 5.0 PEG 60 hardened castor oil 0.5 Triethanolamine 0.3 Preservative, coloring, fragrance Suitable amount Purified water Balance

[Formulation Example 6] ointment

Ointment was prepared by the conventional method with the composition shown in the following table.

Content (% by weight) At least one member selected from the group consisting of 1,3-dicaffeoylquinic acid, 1,5-dicafeoylquinic acid and amentoflavon, compound 0.1 glycerin 8.0 Butylene glycol 4.0 Liquid paraffin 15.0 Beta Glucan 7.0 Carbomer 0.1 Caprylic / capric triglyceride 3.0 Squalane 1.0 Cetearyl glucoside 1.5 Sorbitan stearate 0.4 Cetearyl alcohol 1.0 Wax 4.0 Preservative, coloring, fragrance Suitable amount Purified water Balance

[Formulation Example 1] Soft capsule

At least one member selected from the group consisting of 1,3-dicaffeoylquinic acid, 1,5-dicafeoylquinic acid and amentoflavon, 400 mg of each of the capsules was mixed with 0.0025 g of the compound, 0.0025 g of vitamin C, 50 mg of red ginseng extract, 2 mg of palm oil, 8 mg of palm kernel oil, 4 mg of yellow pigment and 6 mg of lecithin. .

[Formulation Example 2] Tablets

At least one member selected from the group consisting of 1,3-dicaffeoylquinic acid, 1,5-dicafeoylquinic acid and amentoflavon, 0.0025 g of the compound, 0.0025 g of vitamin C, 100 mg of glucose, 50 mg of red ginseng extract, 96 mg of starch and 4 mg of magnesium stearate were mixed and 40 mg of 30% ethanol was added thereto to form granules. And then the tablet was tableted.

[Formulation Example 3] Granules

At least one member selected from the group consisting of 1,3-dicaffeoylquinic acid, 1,5-dicafeoylquinic acid and amentoflavon, 150 mg of the compound, 150 mg of vitamin C, 100 mg of glucose, 50 mg of red ginseng extract and 600 mg of starch were mixed and 100 mg of 30% ethanol was added thereto to form granules, followed by drying at 60 ° C to form granules. Respectively. The final weight of the contents was 1 g.

[Formulation Example 4] Drinking agent

At least one member selected from the group consisting of 1,3-dicaffeoylquinic acid, 1,5-dicafeoylquinic acid and amentoflavon, 0.0025 g of the compound, 0.0025 g of vitamin C, 10 g of glucose, 50 mg of red ginseng extract, 2 g of citric acid and 187.8 g of purified water were mixed and filled in a bottle. The final volume of the contents was adjusted to 200 ml.

While the present invention has been particularly shown and described with reference to specific embodiments thereof, those skilled in the art will readily appreciate that many modifications are possible in the exemplary embodiments without materially departing from the novel teachings and advantages of this invention. something to do. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.

Claims (7)

A composition for skin whitening comprising as an active ingredient a substance that regulates the expression of an ABH antigen. The composition for skin whitening according to claim 1, wherein the substance that regulates the expression of the ABH antigen is a substance that increases the expression of the ABH antigen. The method according to claim 1,
The substances that regulate the expression of the ABH antigen include 1,3-dicaffeoylquinic acid, 1,5-dicafeoylquinic acid, and a mentoflavone amentoflavon), a derivative thereof, or a pharmaceutically acceptable salt thereof. The method according to claim 1,
Wherein the composition comprises from 0.001% to 20% by weight of a substance that controls the expression of an ABH antigen, relative to the total weight of the composition. The method according to claim 1,
Wherein the substance that regulates the expression of the ABH antigen inhibits the production of melanin. The skin whitening composition according to any one of claims 1 to 5, wherein the composition is a cosmetic composition. The skin whitening composition according to any one of claims 1 to 5, wherein the composition is a pharmaceutical composition.

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