KR20090039008A - Cosmetic compositions for skin whitening containing plant extracts - Google Patents

Abstract

A whitening cosmetic composition having the herbal medicine extract is provided to achieve synergy effect of whitening by effects of radical remove inside cell, melanogenesis inhibition, inhibition of melanosome migration. A whitening cosmetic composition comprises 0.001-10.0% of Draconis Sanguis extract, Saussurea involucrate extract, Glycyrrhiza radix extract and nicotinamide. Draconis Sanguis extract, Saussurea involucrate extract, and Glycyrrhiza radix extract are extracted by using water, anhydrous or hydrous low alcohol which contains 1~4 carbons, acetone, ethylacetate, butylacetate or 1,3-buthylene glycole. The cosmetic composition is used in forms of liquid, suspension, emulsion, paste, gel, cream, lotion, powder, soap, cleansing containing surfactant, oil, powder foundation, emulsion foundation, wax foundation, or spray.

Description

Cosmetic composition for skin whitening containing plant extracts

The present invention is to suppress the oxidative stress generated in the skin by external stress factors such as ultraviolet irradiation, to suppress the excessive production of melanin in melanocytes, and also to inhibit the migration of melanin produced in the skin keratin The present invention relates to a skin whitening cosmetic composition having a whitening effect.

In general, the pigmentation phenomenon on the skin is a combination of a number of external factors such as ultraviolet rays, medications, pollutants, external irritant skin, and internal factors such as hormonal imbalance, inflammatory response factors, cytokines, etc. What is important is exposure to ultraviolet light. When the skin is exposed to ultraviolet rays, the activity of an enzyme called tyrosinase in the melanocytes in the basement layer increases, and this enzyme acts on tyrosine, a type of amino acid present in skin tissue. It acts to produce DOPA, which in turn turns into Dopaquinone, which automatically triggers a complex, multi-step reaction that forms melanin, which causes skin pigmentation. Meanwhile, the melanin pigment thus produced is widely distributed to the surrounding keratinocytes through dendrite of melanocytes, thereby changing the color of the skin.

Recently, the possibility of controlling pigmentation has been sought by understanding the interaction with keratinocytes and the delivery of melanosomes rather than melanocytes alone. The melanosomal transfer from melanocytes to keratinocytes has recently been called phagocytosis by the activity of protease activated receptor-2 (PAR-2). Inhibition of melanosome transfer results in skin lightening, J. Invest Dermatol., 115, 162-167, 2000. However, the biological understanding of melanin formation is still unclear, and further studies on pigmentation disorders such as blemishes and blotch, pigmentation caused by ultraviolet rays, and the action of hormones related to pigmentation should be studied.

Such hyperpigmentation often acts as a serious mental burden from the point of view of skin cosmetology and may adversely affect normal social activities. Therefore, as the main causes and mechanisms of skin hyperpigmentation as described above are revealed to some extent, in addition to blocking ultraviolet rays to prevent pigmentation, dermatologically related substances that can inhibit the activity of tyrosinase By combining with cosmetics, many studies are actively conducted to improve or prevent pigmentation phenomenon such as blemishes and freckles. In particular, Asians, such as Korea, Japan, and China, who consider having white skin as a measure of beauty, are very interested in skin whitening cosmetics, and the desire to expect a substantial skin improvement effect from such whitening cosmetics is very high. strong. However, as described above, melanin production in the skin is induced through various pathways, and is produced from melanocyte-forming cells, and the path through which the generated melanin affects skin color also goes through a complex route. Therefore, the whitening agent that only affects some processes such as tyrosinase is difficult to lead to the actual whitening effect.

Therefore, it is thought that it is possible to develop a whitening agent that is more effective than the whitening agent until now by complexly inhibiting the process of melanin production and migration, including the fundamental blocking of melanin production factors, not the simple effect of melanin production inhibition.

Therefore, the object of the present invention is not a simple effect by the melanin production inhibitory, including the fundamental blocking of melanin production factors, by inhibiting the complex process of melanin production and migration, the efficacy is superior to the whitening agent so far, whitening effect in clinical It is to provide a whitening cosmetic composition having a synergistic whitening effect by the combination. In addition, another object of the present invention is to provide a whitening cosmetic composition that has little irritation to the skin and does not have problems such as stability for cosmetic formulations.

In order to achieve the above object, the skin whitening cosmetic composition of the present invention can suppress the oxidative stress generated from ultraviolet rays by adjusting the melanin synthesis path, and inhibit the excessive production of melanin by inhibiting the melanin biosynthesis process, The melanin produced is characterized in that whitening action in three steps to inhibit the migration to the skin keratin. The skin whitening cosmetic composition according to the present invention is characterized in that it contains a complex consisting of red blood extract, sulcus extract, licorice extract and nicotine amide as an active ingredient.

In order to develop a whitening cosmetic having a complex inhibitory effect on melanocyte migration from melanogenesis to melanocytes in melanin producing cells in the skin, the present inventors have suggested that intracellular antioxidant activity and intracellular tyrosinase activity are inhibited. The present invention has been developed a cosmetic composition of the present invention having an effect, the inhibitory effect on melanogenesis and the inhibitory effect on the migration of melanocytes from melanocytes to keratinocytes, and for another object of the present invention is almost no irritation to the skin and cosmetic formulation As a result of efforts to solve the problems such as stability, the present invention was completed by confirming that the mixed composition of red blood extract, suol extract, licorice extract and nicotine amide has an excellent effect in solving the problem.

As described above, the present invention provides a cosmetic composition for skin whitening comprising red blood extract, sorrel extract, licorice extract and nicotine amide as active ingredients. The cosmetic composition of the present invention by using the red blood extract, the extract of smelt extract, licorice extract and nicotine amide as an active ingredient, the effect of intracellular radical scavenging effect by the blood and extract of smelt extract, the effect of inhibiting the melanin production of the red blood extract and licorice extract, In addition, the effect of inhibiting melanoma migration by nicotine amide is combined to achieve a synergistic whitening effect by combining the whitening effect in the clinic, and to reduce cosmetic skin irritation by the excellent formulation safety and nicotine amide for skin whitening. It can be usefully used as a cosmetic composition.

Hereinafter, the present invention will be described in more detail.

Draconis Sanguis is a red lump made by heating and squeezing resin from the fruit of a plant belonging to the Damonorops, which is called Giraffal (Draconis Sanguis). Do not break up. In oriental medicine, various spears, scabies and ringworms are lowered and used to injure iron.

Sasusurea involucrata is a potted plant with the main effects of atopic dermatitis, menopausal disorders, cold diseases such as women's diseases, and anticancer.

Licorice (Glycyrrhiza radix) is the root or stem of Glycyrrhiza glabra L. of legumes (Leguminosae). To keep your skin healthy.

The present invention is conventionally used to extract the active ingredients of red blood, snow, licorice having such pharmacological efficacy is prepared by a method well known to those skilled in the art. For example, water, anhydrous or hydrous lower alcohol, acetone, ethyl acetate or diethyl ether having 1 to 3 carbon atoms are added to the medicinal herb powder in an amount of 1 to 15 parts by volume based on the dry weight of the powder, and then the cooling capacitor It is extracted by heating for 5 to 24 hours at a temperature of 50 ~ 100 ℃ in the extractor attached; Water, anhydrous or hydrous lower alcohol, acetone, ethyl acetate or diethyl ether having 1 to 3 carbon atoms are added to the ground product in an amount of 1 to 15 parts by volume based on the dry weight of the ground product, and then the temperature is 4 to 25 ° C. Immersion for 3-20 days to obtain an extract; After adding an appropriate amount of water to anhydrous or hydrous ethanol or methanol extract, the resulting precipitate is filtered off and added to it with ethyl acetate, butanol or diethyl ether, mixed well, left to separate the layers, and the upper layer separated. After that, the extract is obtained in the extractor to which the cooling capacitor is attached. Such herbal extracts have excellent safety on the skin. Meanwhile, the extract filtrate of the herbal medicine extract extracted by the above method is concentrated under reduced pressure, dried, and then blended into a cosmetic.

Until now, the developed whitening agent reduced the amount of melanin by inhibiting the activity of tyrosinase, an essential and most important enzyme in melanin biosynthesis, and the whitening agents are used by side effects that cause skin irritation. A limited amount could not be used enough to produce a satisfactory whitening effect. In this regard, the herbal medicines that do not cause skin irritation are selected and the main route of the process from melanogenesis to keratinocytes is intracellular antioxidant activity, melanogenesis inhibition, and melanoma to keratinocytes. By using herbal combinations in three stages to inhibit migration, a clear whitening effect can be obtained without causing any side effects.

In order to achieve the desired effect in the present invention, one or more herbal medicine extracts selected from the group consisting of red blood, snow lily and licorice are contained in an amount of 0.0001 to 20% by weight, preferably 0.01% to 5% by weight, based on the total weight of the composition. do.

In addition, according to a preferred embodiment of the present invention, the content of red blood extract, sulcus extract, herbal extract of licorice extract and nicotine amide are 0.002 to 10.0% by weight and 0.03 to 5.0% by weight relative to the total weight of the cosmetic composition, more preferably Preferably 1.0 to 6.0% by weight and 0.1 to 2.0% by weight, respectively.

At this time, if the content of red blood extract, sullen extract and licorice extract in the cosmetic composition of the present invention is less than 0.002% by weight, there is a problem that can not expect the anti-oxidant effect, melanin production inhibitory effect, when the content exceeds 10.0% by weight There is no increase in the apparent effect with the increase of and there is a problem in the stability of the formulation. In addition, when the content of nicotinamide in the cosmetic composition of the present invention is less than 0.03% by weight, there is a problem that can not be expected to inhibit the melanosome movement by synergistic effect with the extract of sulphide, and when the content exceeds 5.0% by weight There is no apparent increase in effect and there is a problem in the stability of the formulation.

In addition, the present invention, the whitening cosmetic composition is characterized in that the red blood extract, characterized in that selected from the formulation of the lotion, gel, water-soluble liquid, cream, essence, oil-in-water (O / W) type and water-in-oil (W / O) type, Provided is a skin whitening cosmetic composition containing sulphur extract, licorice extract and nicotine amide as main active ingredients.

Whitening combinations including red blood extract, soda extract, licorice extract and nicotine amide as active ingredients can be formulated into pharmaceutical compositions such as capsules, liquids, ointments, patch or sustained-release agent using a pharmaceutically acceptable carrier. , Pharmacologically acceptable bases, carriers, excipients, binders (e.g. starch, tragacanth gum, gelatin, molasses, polyvinyl alcohol, polyvinylether, polyvinyl pyrrolidone, hydroxypropyl cellulose, methyl cellulose, Ethyl cellulose and carboxymethyl cellulose), grinding agents (e.g., agar, starch, vellatin powder, sodium carboxymethyl cellulose, carboxymethyl cellulose calcium, crystalline cellulose, calcium carbonate, sodium bicarbonate and sodium alginate), lubricants (e.g. stearic acid) Magnesium, talc, hydrogenated vegetable oil), colorants and the like. The carriers and excipients include lactose, glucose, sucrose, mannitol, potato starch, corn starch, calcium carbonate, calcium phosphate and cellulose.

In addition to the above, additives such as adjuvants such as stabilizers, dissolution aids, transdermal absorption accelerators, and preservatives may be further added.

The pharmaceutical composition prepared as described above may be applied to the skin once or several times a day depending on the symptoms and may adjust the application according to the degree of improvement of the symptoms.

Hereinafter, the present invention will be described in more detail with reference to Examples. However, these Examples are only illustrative description of the present invention and the scope of the present invention is not limited to these Examples.

Production Example  One: Herbal medicine  Extract manufacturer

After shaving, the dried red blood, snow, and licorice were each refluxed three times for 5 hours with an aqueous 95% (V / V) ethanol solution, cooled down, and filtered through Whatman # 5 filter paper. The filtered extracts were concentrated under reduced pressure and freeze-dried at 50 ° C. or lower, and then, using the at least one solvent selected from purified water, ethanol, butylene glycol, and propylene glycol so as to contain 0.001 to 30.0 wt% of the reduced pressure concentrate and the lyophilized product, Sullyol, licorice extract was prepared.

Test Example  One: Intracellular  Free radical scavenging effect

EGCG with comparative sample to see the inhibitory effect of the generation of active oxygen generated in the cell by ultraviolet rays of red blood, sorrel, licorice extract and nicotine amide obtained in Preparation Example 1, ie, free radical scavenging effect, and using fluorescent material The experiment was carried out as follows.

The cell line used in the experiment was a human keratinocytes HaCaT cell line distributed by Dr. Fusenig of the German Cancer Research Center, which was used per well in a 96-well black plate for fluorescence measurement. Incubate at 2.0 × 104 cells and incubate for 1 day at 37 ° C and 5% CO2 using DMEM (Dulbeccos Modification of Eagles Medium, FBS 10%, Gibco, USA) medium supplemented with penicillin / streptomycin The sample was processed.

Test sample was added and cultured for 24 hours, and then washed with HCSS (HEPES-buffered control salt solution) to remove the remaining medium, and DCFH-DA (2 ', 7'-dichlorodihydro-fluorescein diacetate, Molecular Probes prepared with 20 μM in HCSS). , USA) was added thereto, incubated for 20 minutes at 37 ° C. and 5% CO 2, followed by washing with HCSS. Thereafter, 100 μl of the treated HCSS was added to each concentration, and the fluorescence of DCF (dichlorofluorescein) oxidized with active oxygen was measured with a fluorescence plater (Ex; 485 nm, Em; 530 nm). After UVB (20mJ / cm2) was irradiated and the fluorescence was measured by a fluorescent plate reader (Ex; 485 nm, Em; 530nm) after sample treatment.

As can be seen from Table 1, the red blood extract and the fusiform extract showed an active oxygen scavenging effect. When the red blood extract and the fusiform extract were used at the same time, the free radical scavenging effect was significantly increased compared to the case where they were used respectively, and they were used as a comparative sample. It was found that there was an active oxygen scavenging effect superior to EGCG.

Sample Name Free radical scavenging effect (%) 0.01% by weight red blood extract 51 0.01% by weight of extract 48 0.01% by weight licorice extract 9 Nicotinamide 0.01% by weight 8 Blood Brown Extract 0.01% by weight + Sulfur Extract 0.01% by weight 79 EGCG 61

Test Example  2: melanin production inhibitory effect measurement

Melanin synthesis inhibitory effect on B16F10 melanocytes was measured in order to confirm the whitening effect of red blood, sorrel, licorice extract and nicotine amide obtained in Preparation Example 1. The melanin synthesis inhibitory effect of B16F10 melanocytes was measured as follows. B16F10 melanocytes were dispensed in 6-well plates at a concentration of 2 × 10 6 per well, and the cells were attached and incubated for 72 hours by treating the samples at a concentration that does not cause toxicity. After 72 hours of incubation, the cells were detached with trypsin-EDTA, the cell number was measured, and the cells were recovered by centrifugation. Quantification of intracellular melanin was performed by slightly modifying the method of Rotan ( Cancer Res. , 40: 3345-3350, 1980). The cell pellet was washed once with PBS, and then 1 ml of homogenization buffer (50 mM sodium phosphate, pH 6.8, 1% Triton X-100, 2 mM PMSF) was added to vortex for 5 minutes to disrupt the cells. Melt the extracted melanin by adding 1N NaOH (10% DMSO) to the cell filtrate obtained by centrifugation (3,000 rpm, 10 minutes), and measure the absorbance of melanin at 405 nm with a microplate reader. Percent inhibition of production was measured. Melanin inhibition rate (%) of B16F10 melanocytes was calculated by the equation (1).

% Inhibition = [(A-B) / A] x 100

A: Melanin amount in wells without sample

B: Melanin amount in the wells to which the sample was added

As a result of testing the melanin production inhibitory effect of B16F10 melanocytes, blood and licorice extract showed melanin production inhibitory effect, and when blood brown extract and licorice extract were used at the same time, melanin production inhibitory effect was significantly increased. , It was confirmed that the melanin production inhibitory effect than the arbutin is a comparative sample (Table 2).

Sample Name Melanin production inhibition rate (%) 0.01% by weight red blood extract 15.4 0.01% by weight of extract 7.18 0.01% by weight licorice extract 20.37 Nicotinamide 0.01% by weight 3.49 Blood Brown Extract 0.01% by weight + Licorice Extract 0.01% by weight 39.3 Arbutin 35.8

Test Example  3: Melanosome  Measurement of the inhibitory effect on migration to keratinocytes

Melanosite to keratinocytes through co-culture of melanocytes and keratinocytes in order to confirm the inhibitory effect on the migration of the reddish brown, vulgaris, licorice extract and nicotine amide to the keratinocytes obtained in Preparation Example 1 Some migration was tested (Minwalla L, Zhao Y, Cornelius J et al. Inhibition of melanosome transfer from melanocytes to kerationcytes by lectins and neoglycoproteins in an in vitro model system.Pigment Cell Res. 2001, 14, 185-194). Briefly, melanocytes were co-cultured with keratinocytes by labeling them with the carboxyl fluorescein diacetate succinimidyl ester (CFDA SE) (molecular Probes, OR, USA). Fresh media treated with co-cultured cells are exchanged every 24 hours. Cells were fixed with 4% paraformaldehyde, permeated and washed using flow cytometer permeation solution (FACS perm, Becton Dickinson, CA, USA). These cells were treated with a monoclonal mouse anticytokeratin primary antibody (1: 300), washed off, and reacted with a 1:10 goat antimouse IgG conjugated with phycoerythrin (PE) (Caltag, Burlingame, CA, USA). . Cells were fixed in 1% paraformaldehyde and the amount of melanosomes transferred was determined by evaluating CFDA fluorescence values in PE-positive keratinocytes with and without inhibitor using EPICS XL flow cytometer (Coulter Cytometry, Coulter). Experimental results were analyzed using COULTER XL software.

As a result of testing the melanocyte migration inhibition effect using co-culture, blood extract and licorice extract did not show melanocyte migration inhibition effect, but sule extract and nicotine amide showed 12% and 29% inhibition effects, respectively. In each case, the inhibitory effect was increased by showing a movement inhibitory effect to 39% than when used alone (Table 3).

Sample Name Melanin move inhibition rate (%) 0.01% by weight red blood extract 0 0.01% by weight of extract 12.4 0.01% by weight licorice extract 0 Nicotinamide 0.01% by weight 29.5 Nicotinamide 0.01% by weight + Sulfur Extract 0.01% by weight 39.1

Test Example  4: whitening effect test on human skin

Emulsion Example 1 containing all of red blood, sulchu, licorice extract and nicotine amide obtained in Preparation Example 1 and Comparative Examples 1 to 4 containing each extract and nicotinamide alone, and each extract and nicotinamide Comparative Examples 5 to 8 containing three selected from the group consisting of prepared as shown in Table 4 was subjected to the whitening effect test on the human skin.

The whitening effect test on human skin was carried out by attaching an opaque tape with six holes of 1.5cm in diameter to the inside of the upper arm of 20 healthy women, and then applying 1.5 ~ 2 times the minimum erythema of each subject. (UVB) was irradiated to induce skin blackening. Example 1 and Comparative Examples 1 to 8 prepared above were applied twice daily, and after 2 months, the contrast of the skin was measured using a chromameter (Minolta CR300). The determination of the effect was determined by obtaining a "L" value representing the contrast of the skin (unburned Korean skin color generally shows a value of 50-70). When the test material is applied, the L value gradually increases, and the comparison between the test materials is expressed as the change in brightness (ΔL) value of the color (final L value-the value before application of the test material). The larger the ΔL value, the greater the whitening effect. The ΔL values according to the experimental results are summarized in Table 5 below.

Ingredient (% by weight) Example 1 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5 Comparative Example 6 Comparative Example 7 Comparative Example 8 Stearyl alcohol 8 8 8 8 8 8 8 8 8 Stearic acid 2 2 2 2 2 2 2 2 2 Stearic Acid Cholesterol 2 2 2 2 2 2 2 2 2 Squalane 4 4 4 4 4 4 4 4 4 2-octyldodecyl alcohol 6 6 6 6 6 6 6 6 6 Polyoxyethylene Alcohol Ester 3 3 3 3 3 3 3 3 3 Glyceromonostearic acid ester 2 2 2 2 2 2 2 2 2 Purified water To 100 To 100 To 100 To 100 To 100 To 100 To 100 To 100 To 100 Blood Extract One One - - - - One One One Sulfur Extract One - One - - One - One One Licorice Extract One - - One - One One - One Nicotinamide 2 - - - 2 2 2 2 -

division Example 1 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5 Comparative Example 6 Comparative Example 7 Comparative Example 8 ΔL value 4.57 2.81 2.69 2.89 2.42 3.49 3.61 3.74 3.22

From the results of Table 5, it was confirmed that the ΔL value of Example 1, which shows the whitening effect of 3 steps containing all of the red blood extract, the sulcus extract, licorice extract and nicotine amide, showed a higher value than the other comparative examples.

Test Example  5: Skin irritation effect test

In order to test the skin irritation of each of the cosmetics of Examples 1 and Comparative Examples 1 to 8 prepared above, a patch test was conducted on 20 healthy men and women. After applying the pin chamber (Finn chamber, 100 × 10, EPITEST, Finland) containing the sample of Examples 1 and 8 in the inner part of the arm, the patch was removed after 24 hours and 48 hours. -150, DAZOR, USA) was observed according to the regulations of the International Contact Dermatitis Research Association, and the average value of 20 subjects was calculated. The results are shown in Table 6 below.

(Evaluation Criteria and Score of Skin Response)

6: cannon formation

3: severe erythema and vesicle formation

2: pronounced erythema, papules and vesicles

1: borderline but weak erythema, edema and papules

0.5: faint or light erythema

0: no response, normal skin

division Example 1 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5 Comparative Example 6 Comparative Example 7 Comparative Example 8 24 hours 0.38 0.06 0.02 0.17 0.73 0.50 0.41 0.21 0.19 48 hours 0.09 0.04 0.01 0.06 0.59 0.32 0.26 0.10 0.08

As shown in Table 6, the degree of skin irritation in Example 1 containing all of the red blood extract, sulcus extract, licorice extract and nicotine amide used in the present invention was compared with the case of using only nicotinamide as in Comparative Example 4. Very low.

Claims (4)

A cosmetic composition for skin whitening containing red blood extract, sorrel extract, licorice extract and nicotine amide as active ingredients. The method of claim 1, wherein the red blood extract, sorrel extract, and licorice extract is selected from the group consisting of water, anhydrous or hydrous lower alcohol having 1 to 4 carbon atoms, acetone, ethyl acetate, butyl acetate and 1,3-butylene glycol Cosmetic composition for skin whitening, characterized in that extracted using the extraction solvent. The cosmetic composition for skin whitening according to claim 1, wherein the reddish brown extract, the soybean extract, the oil-soluble licorice extract and nicotine amide are included in the cosmetic composition in an amount of 0.001 · 10.0 wt% based on the total weight. The method of claim 1, wherein the cosmetic composition is composed of a solution, a suspension, an emulsion, a paste, a gel, a cream, a lotion, a powder, a soap, a surfactant-containing cleansing, an oil, a powder foundation, an emulsion foundation, a wax foundation and a spray Cosmetic composition for skin whitening, characterized in that it has a formulation selected from the group.