KR100431271B1 - Composition for skin whitening containing Arecoline - Google Patents

Abstract

The present invention relates to a composition for skin whitening, the composition for skin whitening according to the present invention is characterized in that it contains Arecoline (Arecoline) as an active ingredient. The composition containing arecoline can be safely used without side effects on the skin, and also inhibits melanin production and is excellent in inhibiting pigmentation. Therefore, the composition containing these as active ingredients is very effective for improving blemishes and freckles and skin whitening. .

Description

Composition for skin whitening containing Arecoline}

The present invention relates to a composition for skin whitening, and more particularly, to a composition for skin whitening containing arecoline, which has excellent product stability and can be safely used without side effects on the skin, and inhibits melanin production and has excellent pigmentation inhibitory effect. It is about.

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 a type of amino acid tyrosine (tyrosinase) acts as an enzyme called tyrosinase (tyrosinase) is converted to dopa (DOPA), dopaquinone (dopaquinone) is produced through a non-enzymatic oxidation reaction. However, although the pathway by which melanin is made is known, it is still not clear what mechanisms induce melanin synthesis, the previous step in which tyrosinase works.

When such synthesis of melanin occurs excessively in the skin, it may darken the skin tone, and may 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, substances having inhibitory activity against tyrosinase such as hydroquinone, ascorbic acid, kojic acid, glutathione, and the like are applied to cosmetics such as skin ointments and essences. By blending, skin whitening was realized or skin hyperpigmentation such as blemishes and freckles was improved. However, hydroquinone exhibits a predetermined whitening effect, but has a problem of limiting the blending amount to a very small amount due to severe skin irritation. Kojic acid has the disadvantage of being unstable in solution, which complicates the manufacturing process of the cosmetic. In addition, thiol-based compounds such as glutathione and cysteine not only have a characteristic unpleasant odor, but also have problems with transdermal absorption, and glycosides and derivatives thereof have high polarity, making it difficult to use as a cosmetic ingredient. Placenta extract, on the other hand, has no irritation to the skin, but lacks a whitening effect.

Therefore, the technical problem to be achieved by the present invention is to solve the above problems to provide a composition for skin whitening excellent in product stability and safe use without side effects on the skin, as well as inhibiting melanin production to inhibit pigmentation. have.

In order to achieve the above technical problem, the present invention provides a composition for skin whitening containing Arecholine as an active ingredient.

In the composition for skin whitening according to the present invention, the content of arecholine is preferably 0.000001 to 10% by weight based on the total weight of the composition.

Arecoline contained in the composition for skin whitening according to the present invention is selected from the group consisting of lower alcohol, ethyl acetate, acetone, ether, benzene, chloroform, hexane, cyclohexane and petroleum ether having 1 to 4 carbon atoms from Areca catechu . It may be extracted with one or more selected solvents, and after heating and extracting with the solvent, it is more preferable to distill the pressure-reduced extract obtained by removing the insoluble substance and freeze drying or spray drying.

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

Arecholine (Arecoline; 1,2,5,6-Tetrahydro-1-methyl-3-pyridinecarboxylic acid methyl ester, hereinafter referred to as Arecoline) contained as an active ingredient in skin cosmetics according to the present invention is represented by the following general formula 1 Is displayed.

<Formula 1>

These are known to have effects such as alcoholism and anxiety treatment, obesity treatment, Parkin's disease treatment (WO200117966), heart attack treatment (US5977174), memory loss treatment (US5364629).

As such, although arecholine is known as a therapeutic agent for alcoholism, heart attack, etc., the present inventors can screen for a substance that inhibits melanin synthesis induction by using arecholine (B16 mouse). melanoma cells) have shown that they have very strong melanin production and whitening effects. Therefore, according to the present invention, when the arecholine is added to a cosmetic composition such as skin, lotion, cream, foundation, essence, gel, pack, foam cleansing, soap, or a pharmaceutical composition such as skin ointment, strong skin whitening without any side effects Can be effective.

Arecoline, an active ingredient of the skin whitening composition according to the present invention, is an organic compound having 8 carbon atoms (C ₈ H ₁₃ NO ₂ ), which can be obtained from essential oils such as microorganisms, plants, and animals. In particular, it can be extracted from Areca catechu , a kind of palm plant, but is not limited thereto. For example, the method of extracting arecholine from betel nut is as follows.

First of all, the medicinal herb, Daebokpi (Betel nut), which is commercially available, is pulverized and then pulverized. In an extractor equipped with a reflux condenser as a solvent, heat extraction at 50 ~ 100 ℃ 1-5 hours. The resultant was filtered with a filter cloth, and the residue was further extracted one or more times in the same manner. The extracts were combined, concentrated under reduced pressure, and lyophilized or spray dried to obtain a dry extract. The dried extract was suspended in water, followed by addition of the same volume of butanol, followed by liquid-liquid extraction to obtain a butanol fraction, which was then purified by column chromatography and high performance liquid chromatography (HPLC) filled with silica gel and activated alumina. do.

Arecoline obtained by the method described above may be used in various compositions such as skin external ointments or cosmetics. The content of arecholine contained in preparing the composition according to the present invention is preferably 0.000001 to 10% by weight, more preferably 0.0001 to 10.0% by weight, based on the total weight of the composition. If the content is less than 0.000001% by weight, it is difficult to expect a clear melanin production inhibitory effect and a whitening effect, and when the content is more than 10% by weight, a distinct effect is not expected.

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.

Arecoline extraction example

Extraction Example 1

Purchasing a commercially available betel powder was put 100g of pulverized crushed to 500ml 100% butanol, and extracted by boiling in a reflux extractor with a cooling capacitor for 3 hours. Subsequently, the resultant was filtered through a 300 mesh filter cloth, and the residue was extracted once more in the same manner. Each extract was combined and filtered using Whatman No. 2 filter paper at room temperature to remove insoluble materials, and then concentrated under reduced pressure at 60 ° C. in a distillation apparatus equipped with a cooling condenser and suspended in 300 ml of purified water. 300 ml of butanol was added thereto and shaken well to obtain a butanol melt. Subsequently, 450 ml of the fraction containing an active ingredient was obtained from this butanol lysate using silica gel column chromatography. This was further purified by high performance liquid chromatography to obtain 204 mg of arecoline. The structure was confirmed by mass spectrometry and nuclear magnetic resonance spectra.

Extraction Example 2

It was carried out in the same manner as in Extraction Example 1 except that 500ml of 100% ethanol instead of 500ml of 100% butanol to obtain 185 mg of Arecholine.

Extraction Example 3

Except that 500 ml of 100% chloroform instead of 500 ml of 100% butanol was carried out in the same manner as in Example 1 to obtain 155 mg of arecoline.

Extraction Example 4

Purchasing commercially available betel powder was added 100g of the pulverized crushed powder to 500ml of 100% Carrick / Caprylic Triester, and extracted by boiling in a reflux extractor with a cooling capacitor for 3 hours. Subsequently, the resultant was filtered with a 300 mesh filter cloth, and then filtered using Whatman No. 2 filter paper at room temperature to remove insoluble matter, and then purified by high performance liquid chromatography to obtain 166 mg of arecoline.

Experimental Examples 1-3

Aqueline and hydroquinone aqueous solutions obtained according to the extraction example 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). Arecholine obtained according to the extraction example was to have a final concentration of 1 μg / ml, 5 μg / ml and 20 μg / ml (Experimental Examples 1 to 3), and the final concentration of hydroquinone was 1 μg / ml, respectively. After incubation for 3 days by adding to -16 melanoma cells, the cells were trypsinized, separated from the culture vessel, centrifuged, and melanin was extracted.

1 ml of sodium hydroxide solution (1N concentration) was added thereto to boil for 10 minutes to dissolve the melanin, and the absorbance was measured at 400 nm using a spectrophotometer to indicate the amount of melanin produced per unit cell count (10 ⁶ cell). In addition, the relative melanin production relative to the control was calculated as the inhibition rate (%) and the results are shown in Table 1 below.

sample Melanin production % Inhibition Control group (no addition) 0.045 ± 0.004 - Experimental Example 1 (final concentration 1 μg / ml) 0.036 ± 0.001 20% Experimental Example 2 (final concentration 5 µg / ml) 0.024 ± 0.003 47% Experimental Example 3 (final concentration 20 µg / ml) 0.015 ± 0.001 67% Hydroquinone (final concentration 1 µg / ml) 0.025 ± 0.002 44%

* Repeat count = 3

Referring to Table 1, it can be seen that the Arecholine obtained according to the extraction example has a very strong melanin production inhibitory ability against the melanoma cells of the cultured mice compared to the control group (Experimental Examples 1 to 3), and Compared with hydroquinone, a known whitening substance, the effect is not inferior. In addition, hydroquinone has a strong melanin production inhibitory ability at low concentrations, it is not applicable to the cytotoxicity is more than 1 µg / ml or more. However, since arecholine does not exhibit cytotoxicity even at high concentrations of 20 µg / ml or more, it may exhibit a higher melanin production inhibitory effect (Experimental Examples 2 and 3) than hydroquinone.

Hereinafter, by adding Arecholine to an external skin ointment, cream, supple cosmetics, essences, packs and nutrient cosmetics to prepare a composition for skin whitening, to examine the pigmentation inhibitory effect appeared by prescribing them to the test subjects.

Example 1

Arecoline obtained according to the extraction example was added as an active ingredient, and an external skin ointment was prepared using the ingredients and contents shown in Table 2 below.

Comparative Example 1

The ophthalmic ointment was prepared using the ingredients and contents shown in Table 2 without adding arecholine.

Composition Example 1 (% by weight) Comparative Example 1 (% by weight) Arecoline 0.1 - Diethyl sebacate 8 8 Prepayment 5 5 Polyoxyethylene oleyl ether phosphate 6 6 Sodium benzoate Quantity Quantity vaseline to 100 to 100

Example 2

Arecoline obtained according to the extraction example was added as an active ingredient, and a cream was prepared with the ingredients and contents shown in Table 3 below.

Comparative Example 2

Cream was prepared with the ingredients and contents shown in Table 3 below without the addition of arecoline.

Composition Example 2 (% by weight) Comparative Example 2 (% by weight) Arecoline 0.1 - Stearic acid 15.0 15.0 Cetanol 1.0 1.0 Potassium hydroxide 0.7 0.7 glycerin 5.0 5.0 Propylene glycol 3.0 3.0 antiseptic Quantity Quantity incense Quantity Quantity Purified water to 100 to 100

Example 3

Arecholine obtained according to the extraction example was added as an active ingredient, and the flexible cosmetic water was prepared with the ingredients and contents shown in Table 4 below.

Comparative Example 3

Without adding arecholine, softening water was prepared with the ingredients and contents shown in Table 4 below.

Composition Example 3 (% by weight) Comparative Example 3 (wt%) Arecoline 0.1 - ethanol 10.0 10.0 Polylauric acid polyoxyethylene sorbitan 1.0 1.0 Methyl paraoxybenzoate 0.2 0.2 glycerin 5.0 5.0 1,3-butylene glycol 6.0 6.0 incense Quantity Quantity Pigment Quantity Quantity Purified water to 100 to 100

Example 4

Arecholine obtained according to the extraction example was added as an active ingredient, and an essence was prepared with the ingredients and contents shown in Table 5 below.

Comparative Example 4

Essence was prepared with the ingredients and contents shown in Table 5 below without the addition of arecoline.

Composition Example 4 (% by weight) Comparative Example 4 (wt%) Arecoline 0.1 - Propylene glycol 10.0 10.0 glycerin 10.0 10.0 Sodium hyaluronate aqueous solution (1%) 5.0 5.0 ethanol 5.0 5.0 Polyoxyethylene Cured Castor Oil 1.0 1.0 Methyl paraoxybenzoate 0.1 0.1 incense Quantity Quantity Purified water to 100 to 100

Example 5

Arecoline obtained according to the extraction example was added as an active ingredient, and a pack was prepared with the ingredients and contents shown in Table 6 below.

Comparative Example 5

Packs were prepared with the ingredients and contents shown in Table 6 below without the addition of arecoline.

Composition Example 5 (% by weight) Comparative Example 5 (wt%) Arecoline 0.1 - glycerin 5.0 5.0 Propylene glycol 4.0 4.0 Polyvinyl alcohol 15.0 15.0 ethanol 8.0 8.0 Polyoxyethylene oleylethyl 1.0 1.0 Methyl paraoxybenzoate 0.2 0.2 incense Quantity Quantity Pigment Quantity Quantity Purified water to 100 to 100

Example 6

Arecoline obtained according to the extraction example was added as an active ingredient, nutritional longevity was prepared by the ingredients and contents shown in Table 7 below.

Comparative Example 6

No nutrients were added, but the nutrient cosmetics were prepared using the ingredients and contents shown in Table 7 below.

Composition Example 6 (% by weight) Comparative Example 6 (wt%) Arecoline 0.1 - Waselin 2.0 2.0 Sesquioleate sorbitan 0.8 0.8 Polyoxyethylene oleylethyl 1.2 1.2 Methyl paraoxybenzoate Quantity Quantity Propylene glycol 5.0 5.0 ethanol 3.2 3.2 Carboxy Vinyl Polymer 18.0 18.0 Potassium hydroxide 0.1 0.1 Pigment Quantity Quantity incense Quantity Quantity Purified water to 100 to 100

The method used to verify the pigmentation inhibitory effect of 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. On the same line, a pair of the arecholine-containing compositions prepared according to Examples 1 to 6 and the bases not containing arecholine according to Comparative Examples 1 to 6 twice a day from 3 days before irradiation to 3 weeks after irradiation. Applied. Here, the pack agents of Example 5 and Comparative Example 5 were removed 15 minutes after the application.

After prescribing a composition according to each example and a comparative example according to the above method, the degree of pigmentation was visually determined, and the pigmentation inhibition degree of the composition according to each example and the composition according to the comparative example was effective. , And evaluated in two stages of no difference, and also examined the occurrence of skin side effects are shown in Table 8 below.

Experimental substance Effective (persons) No difference (persons) Side effects (persons) Example 1 11 9 0 Example 2 12 8 0 Example 3 13 7 0 Example 4 11 9 0 Example 5 10 10 0 Example 6 12 8 0

As shown in Table 8, the arecholine-containing compositions prepared according to Examples 1 to 6 showed a significant skin whitening effect on at least 10 or more of 20 subjects, and showed no side effects in the skin. Could.

As described above, the composition for skin whitening containing arecoline according to the present invention inhibits melanin production and inhibits pigmentation, and thus is effective for improving skin whitening or freckles and freckles. It can also be used safely because it does not show any side effects in the skin.

Claims (4)

A composition for skin whitening, characterized by containing Arecholine (Arecoline) represented by the following general formula (1) as an active ingredient. <Formula 1> The composition of claim 1, wherein the content of arecholine is 0.000001 to 10% by weight based on the total weight of the composition. The method of claim 1, wherein the arecholine is at least one solvent selected from the group consisting of lower alcohol, ethyl acetate, acetone, ether, benzene, chloroform, hexane, cyclohexane and petroleum ether having 1 to 4 carbon atoms from Areca catechu Skin whitening composition, characterized in that extracted with. According to claim 1, wherein the skin whitening composition is a skin whitening, characterized in that consisting of any one selected from the group consisting of skin, lotion, cream, foundation, essence, gel, pack, foam cleansing, soap and skin ointment. Composition.