KR19990085303A - Skin whitening material - Google Patents

Abstract

The present invention relates to a skin whitening agent that can be used as a medicine and cosmetics having a skin whitening effect, and in particular, it is safe and excellent skin whitening using Serena-4 (14), 7 (11) -diene-8-one as an active ingredient. It will have an effect.

Description

Skin Whitener

The present invention relates to a skin whitening agent that can be used as a medicine and cosmetics having a skin whitening effect, in particular, serena-4 (14), which is a kind of sesquiterpene excellent in improving melanin and freckles and inhibiting melanin production as a skin lightening agent. A skin whitening agent containing 7 (11) -diene-8-one.

In general, the skin color of a person is genetically determined by the concentration and distribution of melanin in the skin, but is also affected by environmental or physiological conditions such as ultraviolet rays, fatigue, stress, melanin is a type of amino acid tyrosine tyrosinase ( tyrosinase) acts as a dopa and a dopaquinone and then undergoes non-enzymatic oxidation.

As such, melanin production pathways are known, but the mechanisms that induce melanin synthesis, the previous stages of tyrosinase action, are still unknown.

Therefore, conventionally, a substance having tyrosinase inhibitory activity, such as hydroquinone, ascorbic acid, kojic acid, glutathione, and the like, is incorporated into ointments or cosmetics to improve skin whitening, blemishes, and freckles. Has been used.

However, such a skin lightening agent causes irritation to the skin or poor product stability, thereby limiting its use and having a weak effect.

Accordingly, the present invention is to solve the above problems, and has an object of providing a skin whitening agent having a strong melanin production inhibitory effect and less use problems.

The skin lightening agent of the present invention for achieving the above object is characterized in that it contains Cerina-4 (14), 7 (11) -diene-8-one of formula (1).

The serina-4 (14), 7 (11) -diene-8-one has an anti-inflammatory effect [Chem. Pharm. Bull., 27 (12), 2954, 1979] and anti-dementia effects (Japanese Patent Laid-Open No. JP09094452) have been reported, but are completely distinguished from the present invention.

Accordingly, the serena-4 (14), 7 (11) -diene-8-one is an organic compound having 15 carbon atoms, which is a known substance described in various literatures, and is present in essential oils such as microorganisms, plants, and animals. Can be used.

For example, it is possible to extract serena-4 (14), 7 (11) -diene-8-one contained in whitening, creation, extraction, roe deer, golden woo, sessin, liana, etc., and to use it as a skin lightening agent of the present invention. .

As described above, the present invention is to provide a skin whitening agent, which contains serena-4 (14), 7 (11) -diene-8-one, and the serena-4 (14), 7 (11). ) -Dien-8-one is a sesquiterpene, a natural organic compound that can be obtained from nature.

The serena-4 (14), 7 (11) -diene-8-one is particularly preferably extracted from plants such as baekrye, creation, extraction, hepatica, fern, sessin, wisteria, etc. It is not limited to kind.

Extraction of serena-4 (14), 7 (11) -diene-8-one from such plants can be carried out using a variety of known methods, for example, by using an organic solvent in a finely ground plant mill. 4 (14), 7 (11) -diene-8-one was extracted and dried, suspended in water, followed by hexane and the like, followed by liquid-liquid extraction, which was purified by column chromatography and high performance liquid chromatography. (14), 7 (11) -diene-8-one is obtained.

When the extracted serena-4 (14), 7 (11) -diene-8-one was treated to rat melanoma cells (B-16 melanoma cells), it showed a very strong melanin synthesis inhibitory effect. It is used in various cosmetics such as external skin ointments and lotions, and when applied to human skin, the skin whitening effect is very good.It does not cause any side effects, and it can be used as a safe and effective anti-freckle and skin whitening agent. And it was found.

The amount of serina-4 (14), 7 (11) -diene-8-one in the skin ointment or cosmetic preparation is preferably 0.000001-10.0% by weight in dry weight, but not more than 0.001% by weight. When contained, the skin whitening effect was not excellent, and when contained at 1.0 wt% or more, there was no apparent increase in effect with the increase of the content. Therefore, the content of Sena-4 (14), 7 (11) -diene-8-one It is more preferable to make the content 0.001-1.0% by weight.

Next, the present invention will be described in more detail based on Examples, Experimental Examples, and Preparation Examples, and the present invention is not limited only to this Example.

Example 1

Purified 100 g of the pulverized product was put in 500 ml of 100% n-hexane solvent, boiled for 3 hours in a reflux extractor equipped with a cooling capacitor, 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 matters. The mixture was concentrated under reduced pressure at 60 ° C. in a distillation apparatus equipped with a cooling condenser, suspended in 300 ml of purified water, and then shaken well with 300 ml of hexane. Hexane lysate was obtained. This hexane lysate was chromatographed on a silica gel column to obtain 450 mg of a fraction containing the active ingredient. This was further purified by high performance liquid chromatography to separate 210 mg of serena-4 (14), 7 (11) -diene-8-one.

The proto NMR spectra of the separated serina-4 (14), 7 (11) -diene-8-one are shown in Table 1 below, and the mass spectra are shown in Table 2 below.

Example 2

100 g of a pulverized product was purchased and 500 ml of 100% ethanol solvent was put in the same manner as in Example 1 to obtain 155 mg of serina-4 (14), 7 (11) -diene-8-one.

Example 3

100 g of a pulverized product was purchased and 100 ml of 100% chloroform solvent was put in the same manner as in Example 1 to obtain 175 mg of Serina-4 (14), 7 (11) -diene-8-one.

Example 4

Purified 100 g of crushed powder was put into 500 ml of 100% capric / caprylic triester, boiled for 3 hours in a reflux extractor equipped with a cooling condenser, filtered with 300 mesh filter paper, and then filter paper 2 times at room temperature. After removing the insoluble substance by filtration with Sera-4 (14), 7 (11) -diene-8-one using high-performance liquid chromatography, Serena-4 (14), 7 (11)- The content of diene-8-one was 280 mg per 100 g of milled product.

Example 5

100 g of the resulting pulverized product was put in 500 ml of n-hexane solvent, and the same procedure as in Example 1 was carried out to obtain 170 mg of serena-4 (14), 7 (11) -diene-8-one.

Example 6

100 g of the extracted pulverized product was put in 500 ml of n-hexane solvent, and the same procedure as in Example 1 was carried out to obtain 150 mg of serina-4 (14), 7 (11) -diene-8-one.

Example 7

100 g of pulverized pulverum was put in 500 ml of a n-hexane solvent, and was carried out in the same manner as in Example 1 to obtain 170 mg of serena-4 (14), 7 (11) -diene-8-one.

Example 8

100 g of sorghum pulverized product was put in 500 ml of n-hexane solvent, and the same procedure as in Example 1 was carried out to obtain 140 mg of serina-4 (14), 7 (11) -diene-8-one.

Example 9

100 g of sericin crushed product was put in 500 ml of n-hexane solvent, and it carried out by the same method as Example 1, and obtained 150 mg of serina-4 (14), 7 (11) -diene-8-one.

Example 10

100 g of the rattan crushed product was put in 500 ml of n-hexane solvent, and the same procedure as in Example 1 was carried out to obtain 165 mg of serina-4 (14), 7 (11) -diene-8-one.

Experimental Example 1

Serena-4 (14), 7 (11) -diene-8-one obtained according to Example 1 was added to the culture of mouse melanoma cells to test the whitening effect at the cellular level (Lotan R., Lotan D. Cancer Res. 40: 3345-3350, 1980).

First, serina-4 (14), 7 (11) -diene-8-one was brought to a final concentration of 1 μg / ml, 5 μg / ml, and 20 μg / ml, and the aqueous solution of B-16 melanoma cells with aqueous hydroquinone solution, respectively. After culturing for 3 days by adding to the culture medium, cells were trypsinized, separated from the culture vessel, centrifuged, and melanin was extracted. To this, 1 ml of sodium hydroxide solution (1N concentration) was added, boiled for 10 minutes to dissolve the melanin, and the absorbance was measured at 400 nm by using a spectrophotometer to measure the amount of melanin produced as the absorbance of 10 ⁶ cells. And, the melanin production relative to the control group was calculated as the inhibition rate (%) and the results are shown in Table 3 below. Here, serena-4 (14), 7 (11) -diene-8-one is designated as "AT-1", and is the result of three repeated experiments.

sample Melanin production % Inhibition Control 0.044 ± 0.004 - AT-1 (final concentration 1 μg / ml) 0.032 ± 0.001 28 AT-1 (final concentration 5 μg / ml) 0.019 ± 0.003 57 AT-1 (final concentration 20 μg / ml) 0.007 ± 0.001 85 Hydroquinone (final concentration 1 μg / ml) 0.025 ± 0.002 43

As can be seen from the results in Table 3, serena-4 (14), 7 (11) -diene-8-one obtained according to the embodiment is cultured mouse melanoma cells as compared to hydroquinone, a known whitening substance. It can be seen that there is a comparable inhibitor of melanogenesis. In addition, hydroquinone has strong melanin production inhibitory ability at low concentrations, but the cytotoxicity is so severe that it cannot be tested at 1 μg / ml or more, whereas serina-4 (14), 7 (11) -diene-8-one is 20 μg / It has a higher melanin inhibitory effect than hydroquinone without showing cytotoxicity in ml concentration.

The preparation example of the cosmetics containing serina-4 (14), 7 (11) -diene-8-one below is shown by the manufacture example.

Preparation Example 1 and Comparative Example 1

Examples of prescription external skin ointments containing serena-4 (14), 7 (11) -diene-8-one are shown in Table 4 below.

Composition water weight% Preparation Example 1 Comparative Example 1 Serena-4 (14), 7 (11) -Dien-8-on 0.01 - Diethyl sebacate 8 8 Prepayment 5 5 Polyoxyethylene Oleyl Ether Phosphate 6 6 Sodium benzoate Quantity Quantity vaseline to 100 to 100

Preparation Example 2 and Comparative Example 2

Formulation examples of the cream in the cosmetic containing serena-4 (14), 7 (11) -diene-8-one are shown in Table 5 below.

Composition water Preparation Example 1 (% by weight) Comparative Example 1 (% by weight) Serena-4 (14), 7 (11) -Dien-8-on 0.01 - 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

Preparation Example 3 and Comparative Example 3

Prescription examples of flexible cosmetics in cosmetics containing serena-4 (14), 7 (11) -diene-8-one are shown in Table 6 below.

Composition water weight% Preparation Example 1 Comparative Example 1 Serena-4 (14), 7 (11) -Dien-8-on 0.01 - ethanol 10.0 10.0 Polylauric acid polyoxyethylene sorbitan 1.0 1.0 Paraoxybenzoic Acid Methyl 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

Preparation Example 4 and Comparative Example 4

Prescription examples of essences in cosmetics containing serena-4 (14), 7 (11) -diene-8-one are shown in Table 7 below.

Composition water weight% Preparation Example 1 Comparative Example 1 Serena-4 (14), 7 (11) -Dien-8-on 0.01 - Propylene glycol 10.0 10.0 glycerin 10.0 10.0 Sodium hyaluronate aqueous solution (1%) 5.0 15.0 ethanol 5.0 5.0 Polyoxyethylene Cured Castor Oil 1.0 1.0 Paraoxybenzoic Acid Methyl 0.1 0.1 incense Quantity Quantity Purified water to 100 to 100

Preparation Example 5 and Comparative Example 5

Prescription examples of packs in cosmetics containing serena-4 (14), 7 (11) -diene-8-one are shown in Table 8 below.

Composition water weight% Preparation Example 1 Comparative Example 1 Serena-4 (14), 7 (11) -Dien-8-on 0.01 - Propylene glycol 4.0 4.0 glycerin 5.0 5.0 Polyvinyl alcohol 15.0 15.0 ethanol 8.0 8.0 Polyoxyethylene Oleethyl 1.0 1.0 Paraoxybenzoic Acid Methyl 0.2 0.2 incense Quantity Quantity Pigment Quantity Quantity Purified water to 100 to 100

Preparation Example 6 and Comparative Example 6

Prescription examples of nutrient cosmetics in cosmetics containing serena-4 (14), 7 (11) -diene-8-one are shown in Table 9 below.

Composition water weight% Preparation Example 1 Comparative Example 1 Serena-4 (14), 7 (11) -Dien-8-on 0.01 - Waselin 2.0 2.0 Sesquioleate sorbitan 0.8 0.8 Polyoxyethylene Oleethyl 1.2 1.2 Paraoxybenzoic Acid Methyl Quantity Quantity Propylene glycol 5.0 5.0 ethanol 3.2 3.2 Carboxy Vinyl Polymer 18.0 18.0 Calcium hydroxide 0.1 0.1 Pigment Quantity Quantity incense Quantity Quantity Purified water to 100 to 100

Experimental Example 2

Twenty healthy men and women were selected to attach aluminum foil in two rows of 6 holes with a diameter of 7 mm in the lower part of both arms, and 60mJ / cm ² light was irradiated using ORIEL solar simulator 1000W at a distance of 10 cm from the arm. . The irradiation site was washed well with 70% ethanol aqueous solution before irradiation. The bases prepared according to Preparation Example 1-6 and Comparative Example 1-6 were applied to the same line twice a day from 3 days before irradiation to 3 weeks after irradiation (pack prescription of Preparation Example 5 and Comparative Example 5). In case of application, it was removed after 15 minutes).

For each, the pigmentation degree of the preparation example and the comparative example were visually determined, and the degree to which the preparation example suppressed the pigmentation was evaluated in two stages of effective and no difference compared to the comparative example, and the results are shown in Table 10 below. .

Experimental substance Effective (persons) No difference (persons) Preparation Example 1 14 6 Preparation Example 2 12 8 Preparation Example 3 10 10 Preparation Example 4 11 9 Preparation Example 5 11 9 Preparation Example 6 12 8

As can be seen from the results in Table 10, ointments and cosmetics containing serena-4 (14), 7 (11) -diene-8-one prepared according to Preparation Example 1-6 were at least 10 out of 20 subjects. It showed whitening effect on more than one person. Especially, in Preparation Example 1, in which a large amount of serena-4 (14), 7 (11) -diene-8-one was applied, 70% showed pigmentation inhibitory effect, There are no side effects, suggesting that Serena-4 (14), 7 (11) -diene-8-one is a safe and highly effective blemish or freckles improver or skin whitening agent.

As described above, the skin whitening agent containing Serena-4 (14), 7 (11) -diene-8-one as an active ingredient according to the present invention has no side effects on the skin and is safe and has excellent blemishes and freckles, and skin whitening. It has an effect.

Claims (3)

A skin lightening agent containing Serena-4 (14), 7 (11) -diene-8-one as an active ingredient. The method of claim 1, wherein the serena-4 (14), 7 (11) -diene-8-one is extracted from one or more selected from the group consisting of bleeding, generating, extracting, hepatica, larvae, sessin, wisteria, and the like. Skin whitening agent, characterized in that. The skin lightening agent according to claim 1, wherein the serina-4 (14), 7 (11) -diene-8-one is contained in 0.000001% to 10%.