KR20050117958A - Topical nano liposome formulation including extracted purified herbal mixture and whitening cosmetics using this formulation - Google Patents

Abstract

The present invention relates to a nano liposome composition containing the herbal herbal extract extract, and a cosmetic for skin whitening using the same, more specifically, the herbal herbal extract obtained by mixing and extracting cheonhwabun, haechocho and gastric acid at an appropriate ratio as an active ingredient By adding a certain amount of hydrogenated lecithin, glycerin, capric and capric triglycerides, cholesterol and purified water to obtain nano-sized liposomes, long-term storage stability, transdermal absorption, moisturizing persistence of active ingredients, as well as small amounts of extracts are effective. The present invention relates to a nano liposome composition applicable to cosmetics for skin whitening which is excellent in whitening improvement effect, antioxidant effect, and anti-irritant effect even when contained as a component.

Description

Topical nano liposome formulation including extracted purified herbal mixture and whitening cosmetics using this formulation

The present invention relates to a nano liposome composition containing the herbal herbal extract extract, and a cosmetic for skin whitening using the same, more specifically, the herbal herbal extract obtained by mixing and extracting cheonhwabun, haechocho and gastric acid at an appropriate ratio as an active ingredient By adding a certain amount of hydrogenated lecithin, glycerin, capric and capric triglycerides, cholesterol and purified water to obtain nano-sized liposomes, long-term storage stability, transdermal absorption, moisturizing persistence of active ingredients, as well as small amounts of extracts are effective. The present invention relates to a nano liposome composition applicable to cosmetics for skin whitening which is excellent in whitening improvement effect, antioxidant effect, and anti-irritant effect even when contained as a component.

The skin of modern people is damaged by exposure to various harmful environments and stresses such as ultraviolet rays, environmental pollution, etc., and the physiological activity of the skin decreases with aging, which slows down the recovery of damaged skin, resulting in drying, decreased elasticity, wrinkle formation, and skin sensitization. Experience various skin aging phenomena. In addition, overexposure to ultraviolet rays due to destruction of the ozone layer results in blemishes and freckles due to skin pigmentation. Among these aging phenomena, especially in Asian women, the expectation of the whitening effect is very high, and in order to make the skin clear and white through the improvement of the skin pigmentation, the melanin formed or the production itself should be suppressed. Therefore, various cosmetics have been developed to improve aging and skin pigmentation, but most of them are concentrated on products that inhibit melanin formation by mono-drugs or existing synthetic whitening materials, and even when whitening agents are applied to the formulation. Whitening effects such as discoloration, odor, and instability of the formulation could not be maximized.

In particular, conventional synthetic whitening agents, such as kojic acid, absorb copper ions present in the active sites of tyrosinase and inhibit enzymatic activity, whereas there are problems of instability and skin side effects when formulated in cosmetics, vitamin-C and derivatives thereof. Because of its high oxidation instability, it is difficult to use as a raw material for cosmetics. Hydroquinone has excellent skin whitening effect, but has high skin irritation such as allergic properties, toxicity to melanocytes, and permanent depigmentation to the skin. Although only a limited concentration is allowed in each country, arbutin is a derivative of hydroquinone combined with glucopyranoside, which acts to inhibit the synthesis of melanin pigments with little side effects when using hydroquinone and without toxicity to the human body. It is used as a therapeutic agent for skin diseases in which melanin pigmentation is increased. But the possibility is presented, there is a disadvantage that some degradation by skin enzymes,

Therefore, in recent years, a lot of research has been conducted on the method of extracting the herbal ingredients of plants and using the extract as a whitening cosmetic, and using whitening cosmetics (Japanese Patent Publication No. 55-44375) and licorice using In addition to whitening cosmetics [Japanese Patent Laid-Open No. 60-214721], whitening cosmetics using a number of herbal ingredients, such as red ginseng, green tea, bilberry leaf, cornus oil, have been known.

However, the whitening cosmetics using the conventional plant extracts are effective to be used at a high concentration even in the case of single extracts or complex extracts, and there are problems such as discoloration and discoloration during long-term storage.

On the other hand, drug delivery and stabilization technology of the active ingredient using liposomes have been studied as a delivery medium of physiological substances in the pharmaceutical field as well as in the cosmetic field. However, even though these liposomes have similar characteristics to biological membranes, they are limited to be absorbed through keratinocytes unless the particles are ultrafine in cosmetics, which are mainly composed of external coating formulations. It was difficult to maximize the percutaneous absorption because the route is common.

Lipids that form liposomes are aliphatic hydrocarbon chains and are represented by fatty acids, glycerides, long chain alcohols, sphingolipids, phospholipids, glycolipids, sterols, and the like. It is well known as a cosmetic compounding ingredient, and researches on application of skin affinity, safety improvement, and effectiveness by biofunctional membranes are being conducted, but practical applications are few. It is necessary to ensure the stability of the formulation in order to show the effectiveness of the lipid-specific, constituents phospholipids, sterols, sphingolipids, ceramides, etc. It is not easy to mix stably in aqueous solution, even if stabilized by a special emulsification machine This is because it is difficult to make a nano form, such as weakened stability.

The advantage of liposomes composed of this lipid as a cosmetic preparation is that it can contain both water-soluble and oil-soluble active ingredients inside the membrane, low biocompatibility and low irritation with bio-derived ingredients, high percutaneous absorption, and long lasting moisturizing effect. In spite of the many advantages, the expansion of the application area was insignificant due to the limited amount of active ingredients and the instability of the formulation.

Therefore, the phospholipid (lecithin), a membrane component of liposomes, has various limitations in terms of application due to the following limitations. That is, the peroxide value or acid value of phospholipid is low, the nitrogen substitution is sufficient, the initial pH is set to 6-7, the sugar or polyhydric alcohol is used as an isotonic agent, and the long-term preservation stability of the phospholipid in a liposome preparation Affected by purity and fatty acid composition of phosphatidylcholine component, phospholipid alone is susceptible to breakdown of interfacial membranes by salt or charged components, hydrolyzed by microorganisms under heat and pH conditions, fatty acids constituting phospholipids In the presence of unsaturated bonds, lipids have good fluidity and can easily penetrate the gaps between keratinocytes, but they have weak lipid stability and low stability of double bonds in phospholipids. The phospholipids derived from saturated fatty acids (hydrogenated lecithin) are known to have excellent physicochemical stability. Liposomes prepared with lecithin have good oxidative stability during manufacture and storage, but the melting point of the fatty acid chain of hydrogenated saturated hydrocarbon is higher than room temperature, so it is not easy to be absorbed transdermally by fusion with stratum corneum lipids due to lipid rigidity. It is difficult to make stable liposomes in general storage conditions and use environment of cosmetics because of the disadvantages of phase change in lipid bilayers and release of inclusions and coagulation of liposomes themselves. In particular, in solubilization-based transparent products such as skins or low-viscosity liquid products, there is a risk of precipitation by combining with the charged materials in the formulation, and the problem of color change caused by physical factors such as external ultraviolet rays. There was also.

Therefore, the present invention was stabilized by the use of nano liposome technology of the herbal medicine extract, overcoming weaknesses such as discoloration, malodor, deactivation of the active ingredient by applying the nano liposome composition to cosmetics inhibit melanin production, antioxidant, UV The suitability of complex skin whitening mechanism including irritation reduction by In addition, to improve the percutaneous absorption of the active ingredient to improve the efficacy with only a small amount of extracts

In the present invention, among the various components exhibiting complex whitening mechanisms, the extracts of cheonhwamin, hachicho, and gastrointestinal medicinal herbs are not only excellent in tyrosinase inhibitory activity such as arbutin, but also antioxidant activity such as vitamin C and stimulating alleviation effect such as licorice From exposure to melanin formation stage, it was confirmed that it is a substance having various complex effects required for whitening.

Accordingly, the present inventors have studied the stabilization problem of liposomes, and as a result, providing nano liposomes suitable for containing the herbal extract, the skin irritation and excellent transdermal absorption of the active ingredient, but also excellent stability of the contained components nano The present invention has been completed by developing a liposome-containing skin whitening cosmetic.

Accordingly, the present invention provides a skin whitening cosmetic that is excellent in percutaneous absorption while having excellent skin whitening effect, antioxidant effect, and irritation-reducing effect by ultraviolet light using nano liposomes containing the herbal medicine extracts of cheonhwa flour, haechocho, and stomach cancer. The purpose is.

The present invention is characterized by nanoliposomes containing 0.01 to 20.0% by weight of the herbal extracts of cheonhwabun, Hagocho and gastric glands.

In addition, the skin whitening cosmetics containing the nano liposomes is another feature.

Hereinafter, the present invention will be described in detail.

The present invention contains a medicinal herb extract obtained by mixing and extracting cheonhwa flour, haejucho, and gastrointestinal tract at an appropriate ratio, and by adding a certain amount of hydrogenated lecithin, glycerin, capric and capric triglyceride, cholesterol and purified water, etc. By obtaining the size of liposome, long-term storage stability, transdermal absorption, moisturizing persistence of the active ingredient as well as a small amount of extract as an active ingredient, whitening improvement effect, antioxidant effect, anti-irritant effect by UV rays, and very stable skin whitening It relates to a nano liposome composition applicable to a cosmetic for cosmetic.

First, the herbal extract (Trichosanthes kirilowii Var) used as a herbal extract is a toxic herb that has been used to clean the roots of perennial vine herb Hanultari in the fall and to clean the outer shells, cut them into proper lengths, and use them as sun-dried herbs as medicines. The most widely known components are Trichosanthin, a protein, and the other amino acids include Arginin and Citrulline. Palmitic acid and Linoleic acid are fatty acids. Known. Recently, stenols such as bronolic acid, cucurbitacin, and alpha-spinasterol have been identified, and in oriental medicine, it is possible to stop small sputum, boil, bruises, skin eczema, wound disinfection. It is effective in drainage, detoxification, and antipyretic effect. It is used for drainage, detoxification and antipyretic activity [Korea Research Institute of Plant Resources, Korea Research Institute of Chemical Technology, 1988]

Prunella vulgaris Linne is an orchard of perennial herbaceous plants and is collected in summer as fruit trees of horticulture and horticulture plants. When it is half withered, it is collected in the sun and used as a medicinal herb. The components of the vinegar include saponins such as oleanolic acid and ursolic acid, carotene, vitamin C, vitamin K, tannin, and caffeic acid. acid), Chlorogenic acid, Rosmarinic acid, etc., have been used in Korean medicine for chronic boils, pulp, acute mastitis and lymphatic tuberculosis. 1988, Research on Hagocho Ingredients Lee, Jak-pyung and 3 others, Journal of Beijing Medical Science, 1991, Chinese Medicine Dictionary].

Clematis chinensis Osbeck refers to the roots of the plant of the creeper and the Buttercup family. It is a non-toxic herbal medicine that has been harvested in the fall and chopped and dried in the sun as a medicinal herb. So far known ingredients include saponins such as crematin, cremontanoside, crematoside, etc. In addition, anemonin, anemonol, and sterol ), Sugars (Glucose), lactone (Lactone), amino acid (Amino acid), etc. are known, and the application of the oriental medicine has been widely used for diseases with infectious liver disease, conjunctivitis, tonsillitis [Korea useful plant resources General Research, Korea Research Institute of Chemical Technology, 1988, Dohae Hyangjeomsa Dictionary-Younglim, 1990].

In addition, the present invention by using a certain ratio of the cheonhwabun, Hagocho and gastric glands to prepare a herbal extract of the herbal medicine and nano liposomes containing the same as follows.

It is preferable to mix cheonhwabun, hagocho and yeongseonseon at a weight ratio of 0.5-2.0: 0.5-1.5: 1, because the skin whitening effect, antioxidant effect, and anti-irritant effect of the herbal medicine extract are maximized. to be.

In extracting the herbal medicine extract, the extraction solvent is extracted with water or an alcoholic aqueous solution, and the filtrate obtained in the extraction step is separated by layer addition by adding the same amount of saturated n-butanol, and then concentrated only under reduced pressure by collecting only n-butanol layers. After the addition of the same amount of water is suspended and lyophilized to prepare a final extract. Alternatively, the same extraction step may be made by adding the same amount of ethanol to separate the ethanol layer and then collecting only the ethanol layer to prepare a final extract.

In order to protect and stabilize the active ingredient of the herbal medicine extract as described above, it is embedded in the nano liposome to facilitate skin penetration.

The herbal herbal extract is preferably contained in an amount of 0.01 to 20.0% by weight based on the total weight of the nano liposomes. At this time, if the content of the herbal herbal extract is less than 0.01% by weight it is difficult to expect the effect when the formulation is applied, and when it exceeds 20.0% by weight there is a drawback that does not appear a clear increase in effect when the skin is applied.

The nano liposomes containing the herbal extracts prepared by the above method are 10-15 wt% of hydrogenated lecithin, 10-50 wt% of glycerin, and 10-40 wt% of caprylic capric triglyceride, based on the total weight of liposome composition. Nanoporous liposomes are prepared by several passes through a high pressure micro homogenizer, including 0.3 to 2.0% by weight of cholesterol and 3 to 70% by weight of purified water. In this case, when the content of hydrogenated lecithin is less than 10% by weight, there is a problem that the percutaneous absorption is reduced because the particles become more than 100 nanosizes, and when the content exceeds 15% by weight, the problem of increasing skin irritation is not reduced. have. In addition, when the content of glycerin is low, the solubility of the extract is low, which may cause precipitation, and the content thereof is not preferable because it may cause irritation to the skin. In addition, the content of caprylic capric triglyceride is a content to give a role as a co-former of the nano liposomes and skin absorption and safety, when used less than 10% by weight, there is a problem in the solubility of the complex herbal extract, If it exceeds 40% by weight, there is a problem that the nanoparticles are large. In addition, when the content of cholesterol is less than 0.3% by weight, there is a problem in that it does not act as an interfacial film strengthening agent, and when it exceeds 2.0% by weight, there is a problem in that the activity of the herbal medicine extract is lowered because the heating temperature must be increased during the manufacturing process. If the content of purified water is less than 3% by weight, there is a problem in the solubility of the herbal medicine extract, and if it exceeds 70% by weight, there is a problem in that the stability over time changes due to particle aggregation after the production of nanoliposomes.

The nano liposomes prepared above have a particle size of 20 to 100 nm, preferably 30 to 50 nm, and can contain an excess of water-soluble or polyol-soluble, semi-soluble herbal herbal extracts, while maintaining long-term storage stability, transdermal absorption, It can be used as a skin whitening cosmetic because it improves moisturizing persistence and contains a small amount of extract as an active ingredient.

Therefore, when applying the liposome containing the herbal medicine extract in cosmetics, various formulations such as softening longevity, astringent longevity, lotion, essence, cream, gel, pack, soap, essence sheet, hydrogel patch or mask, sunscreen products Applicable to, especially to liquid or transparent cosmetics. In addition, the nano liposome is preferably blended 0.01 to 20% by weight based on the total cosmetic composition.

Hereinafter, the present invention will be described in more detail based on the following examples, but the present invention is not limited thereto.

Example 1: Preparation of Herbal Herb Extract

In order to develop natural whitening agent suitable for skin mechanism by using cheonhwa flour, haechocho, and yeongyeongseon, 150 g of each herbal medicine is finely chopped and shaded and put into a round flask attached with a reflux cooler, which is equivalent to 10 times the weight of the herbal medicine. Water, ethanol, butanol, ethyl acetate and chloroform solvent were added, and the extracts were heated at 80 ± 5 ° C for 6 to 8 hours in a water bath. The whitening efficacy test was preliminarily tested by the mushroom tyrosinase activity method as shown in the yield [Table 1] and Experimental Example 1 for each extract obtained by filtration and concentration under reduced pressure. The whitening efficacy of Example 2 and Example 3, which is a method for preparing an extract, was shown in Table 2 below.

Example 2 Preparation of Herbal Herbal Extracts (1)

Wash the dried liquor line with tap water to dry 100 g, 200 g of chopped chunks of 1 ~ 2 cm, 100 g of fruit tree part collected in late summer, add 4 L of water and stir well After the extraction, the mixture was heated and extracted at 80 ± 5 ° C. for 6 to 8 hours to collect the filtrates, and the mixture was heated and extracted for about 3 hours by adding 3 L of water to the residue. The same amount of ethanol was added to the mixture, followed by centrifugation to collect the supernatant, and concentrated under reduced pressure until the herbal extract was dried at 55 to 60 ° C. to obtain 21 g of extract. As a result of analyzing the obtained extract by liquid chromatography, the content of each indicator component was 0.62% of oleanoic acid and 0.08% of rosmarinic acid.

Example 3: Preparation of Herbal Herbal Extracts (2)

Wash the dried gastric glands with water to remove any deposits. 300 g, 600 g of chopped chunks cut into 1.0 to 2.0 cm, mix the leaves of the vinegar and 300 g of fruit trees collected in late summer, and then add 12 L of water. The mixture was heated and extracted at 80 ± 5 ° C. for 6 to 8 hours with stirring to collect the filtrates, and 5 liters of water was added to the residue. The same amount of saturated n-butanol was added thereto, and the layers were separated three times. Then, only the n-butanol layer was collected and concentrated under reduced pressure until the herbal extract was dried at 55 to 60 ° C. g extracts were obtained. As a result of analyzing the obtained extract by gas chromatography, the amount of residual n-butanol was 136 ppm, and when analyzed by liquid chromatography, the content of the indicator component was 6.18% of oleanoic acid and 0.43% of rosmarinic acid.

Experimental Example 1: Whitening effect experiment by inhibiting mushroom tyrosinase activity

Into each well of a 96 well plate, add 40 μl of test substance and positive control substance by concentration, and add 20 μl of 100 μl of 0.1 M potassium phosphate buffer (pH 6.5) and 2000 units / ml of mushroom tyrosinase to each well. 40 μl of mM L-tyrosine was added. After reacting for 10 minutes in a 37 ° C incubator, the absorbance was measured at 490 nm using an ELISA reader (VERSAmax). After correcting the Balnk absorbance of each test substance and negative control group, the inhibition rate of tyrosinase activity (%) was calculated by the following equation 1 based on the negative control group, and the concentration of each substance that inhibits 50% of the obtained tyrosinase activity inhibition rate is IC. _It is shown as ₅₀ . The results are shown in Table 2 below.

As: O.D. of test substance. value

Asb: O.D value of test substance Balnk

Anc: O.D value of negative control

Ancb: O.D value of negative control Balnk

Yield (wt%) of each extract Extraction solvent Natural flower Hagocho A lieutenant ship Flower pot: Gochocho: Maternity line (2: 1: 1) water 16.6 29.3 19.6 22.3 ethanol 5.9 13.7 6.8 8.2 Butanol 1.4 1.9 1.3 1.6 Ethyl acetate 1.7 3.4 2.1 2.5 chloroform 1.3 2.6 1.9 1.8 Example 2 - - - 5.2 Example 3 - - - 2.3

division IC ₅₀ (ppm) Negative Control (No Sample) - Vitamin c 95.9 Arbutin 531.9 Soluble Licorice Extract 54.3 Lettuce extract 214.1 Green tea extract 1000 < Cheonhwahwa hot water extract 245.2 Cheonhwahwa ethanol extract 86.7 Natural Flower Butanol Extract 98.9 Cheonhwabun Ethyl Acetate Extract 102.4 Natural Flower Powder Chloroform Extract 114.3 Higocho hot water extract 356.2 Higocho ethanol extract 241.8 Hagocho Butanol Extract 172.0 Higocho ethyl acetate extract 188.7 Higocho chloroform extract 212.6 Gastric Hydrothermal Extract 298.3 Gastric Ethanol Extract 162.5 Gastric Butanol Extract 152.0 Gastric Ethyl Acetate Extract 196.7 Gastric chloroform extract 231.1 Example 2 Extract 68.0 Example 3 Extract 87.9

In this experimental example, one of the causes of skin pigmentation, the melanogenesis inhibitory effect was demonstrated through the inhibition rate of mushroom tyrosinase activity, the herbal extracts of Examples 2 and 3 were somewhat more potent than the useful control extract of licorice. Except for this weakness, it was slightly higher in efficacy than vitamin C, and it was found to be more effective than arbutin, and as a single extract, ethanol extract of ethanol was more effective than vitamin C and arbutin. Irrespective of the medicinal herb extracts of the medicinal herb extracts of the medicinal herb extracts or the mixed extracts of the medicinal herb extracts, the effect of tyrosinase activity on the material extracted with the extracting solvent was high.

Experimental Example 2: Whitening efficacy test using B16 / F10 melanin producing cells

① MTT analysis

In each well of a 96-well plate, B16 melanin-producing cells obtained from the Korea Cell Line Bank were added at 2.5 × 10 ³ cells / well (Final volume 200 μl) and placed at 37 ° C. in a 5% CO ₂ incubator (MCO-20AIC, Sanyo). After incubation, the medium of each well was removed and replaced with new DMEM (Dulbecco's modified eagle's medium). To each well, the sample extracted above and 2 µl of the existing whitening material were added, followed by incubation for 72 hours, and 20 µl of MTT solution (5 mg / ml in DMEM) was added to each well 3 hours before the end of the incubation. At the end of the incubation, remove the culture solution from each well and add 150 μl of DMSO solution to it. Absorbance was measured at 570 nm using an ELISA reader, and cell viability (%) was calculated by the following equation 2 based on the negative control group treated with DMSO instead of the sample.

② Determination of tyrosinase activity inhibition

B16 / F10 melanin-producing cells were added to each well of a 6-well plate, incubated in 1 × 10 ⁵ cells / well (Final volume 3 ml) for 24 hours at 37 ° C. in a 5% CO ₂ incubator, and then the medium was removed from each well. Changed to new DMEM. As a result of MTT analysis, 30 μl of a test substance having a non-toxic concentration was added to each well, and incubated in an incubator for 24 hours. To each well, add 1 ml of Lysis buffer (100 mM Sodium phosphate buffer (pH 6.8) containing 1% Triton X-100 and 1% 0.1mM PMSF) and leave at -70 ° C for 2 hours and thaw at room temperature. Cells from each well were removed with a cell scraper and transferred to each 1.5 ml tube and centrifuged at 4 ° C. and 13000 rpm for 30 minutes to transfer the supernatant to a new 1.5 ml tube. Total protein analysis was performed to dilute the protein to 0.3 mg / ml and use it as an assay sample. 50 μl of 100 mM sodium phosphate buffer (pH 6.8) was added to each well of a 96 well plate followed by 100 μl of the sample and 50 μl of 100 mM Pyrocatechol in each well. Absorbance was measured at 405 nm for 60 minutes at 37 ° C. for 10 minutes using an ELISA reader. The inhibition rate of tyrosinase activity (%) based on the negative control group was calculated by the following equation (3). The negative control group was used as a sample treated with DMSO instead of a sample.

③ Measurement of melanin production inhibitory effect

B16 / F10 melanin-producing cells were added to each well of a 6 well plate at 1 × 10 ⁵ cells / well (Final volum 3 ml), incubated for 24 hours in a 37 ° C., 5% CO ₂ incubator, and then the medium was removed from each well. Changed to new DMEM. Add 30 μl of non-toxic test substance to each well as the MTT assay result, incubate for 72 hours in an incubator, remove the culture medium, add 1 ml of PBS and scrape each well with a cell scraper to remove cells. Take out and transfer to each 1.5 ml tube. Subsequently, the supernatant was removed by centrifugation at 4 ° C. and 13000 rpm for 30 minutes, and the cell pellets were collected, dried at 60 ° C. for 3 hours, and then 1 ml of 1N NaOH added with 10% DMSO was added thereto at 60 ° C. for 1 hour. I dissolved my melanin. Synthetic melanin (Sigma) was diluted to prepare a standard solution. 150 μl of the supernatant and standard solution dissolved in each well of a 96 well plate were measured at 405 nm using an ELISA reader (VERSA). Negative controls were treated with DMSO instead of samples. The amount of melanin was calculated from the standard curve prepared using synthetic melanin, and the inhibition rate of melanin production based on the negative control group was calculated by the following Equation 4.

A: the amount of melanin in the control group

B: melanin content of test substance

Example 2 and Example 3, the best inhibition of mushroom tyrosinase activity among the extracts of Table 1 were evaluated by the method of Experiment 2 with the following synthetic whitening raw material in the B16 melanin-producing cells, each sample cell In consideration of the survival rate, the experiment was performed at the maximum concentration, and the results are shown in Table 3 and FIG. 1.

division Maximum concentration (ppm) % Tyrosinase activity inhibition Melanin formation inhibition rate (%) Negative Control (Sample-Free) DMSO 1% - - Vitamin c 100 58.4 74.1 Arbutin 500 71.2 67.3 Soluble Licorice Extract 12.5 52.4 58.6 Green tea extract 50 36.9 27.8 Lettuce extract 50 13.4 3.7 Example 2 Extract 50 84.8 73.2 Example 3 Extract 50 72.4 81.8

At the concentration considering the maximum cell viability in the tyrosinase activity inhibition and melanin formation inhibition experiment using B16 melanin-producing cells of Experimental Example 2, the herbal extracts of Examples 2 and 3 were slightly higher in effect than vitamin C, a positive control group. Or, it showed a slightly lower effect, but showed a better effect than arbutin, green tea, and lettuce extract showed sufficient potential as a natural whitening agent.

Experimental Example 3: Antioxidant Effect Test by DPPH Radical Scavenging Activity

To measure the antioxidant activity of the extract of Table 1, 100 μl of the test substance was added to each well (triplicate / sample) of the 96 well plate, and 100 μl of DMSO was added to the control group. In each well, 100 μl of 0.2 mM DPPH (2,2-Diphenyl-1-picrylhydrazyl, Sigma) solution was added. However, 100 μl of methanol stock solution was added to the blank wells of the control and test substance. The series was diluted to an appropriate concentration to obtain IC ₅₀ to the raw liquid in the case of the liquid stock solution (Stock solution), a high concentration (ppm units) to a stock solution, if the test substance in solid phase is by measuring the solubility in the solvent DMSO (Step 5) was prepared and applied to the test. The test material was reacted for 20 minutes in a 37 ℃ incubator and the absorbance was measured at 517 nm using an ELISA reader. After correcting the blank absorbance values of each test substance and control group, the antioxidant ability was expressed as an electron donating ability (EDA%) for DPPH radicals based on the blank test group [Equation 5]. The concentration of each substance that inhibits 50% of the obtained EDA level is expressed as IC ₅₀ . The results are shown in Table 4 and FIG. 2.

As: O.D value of sample material

Asb: O.D value of sample material blank

Ac: O.D value of control group

Acb: O.D value of control blank

division IC ₅₀ (ppm) Negative Control (No Sample) - Vitamin c 13.2 BHT 17.4 Soluble Licorice Extract 103.6 Routine 24.8 Lettuce extract 956.0 Green tea extract 512.0 Cheonhwahwa hot water extract 121.1 Cheonhwahwa ethanol extract 66.3 Natural Flower Butanol Extract 18.2 Cheonhwabun Ethyl Acetate Extract 102.6 Natural Flower Powder Chloroform Extract 111.3 Higocho hot water extract 52.2 Higocho ethanol extract 11.3 Hagocho Butanol Extract 7.2 Higocho ethyl acetate extract 19.7 Higocho chloroform extract 20.6 Gastric Hydrothermal Extract 94.3 Gastric Ethanol Extract 22.1 Gastric Butanol Extract 32.0 Gastric Ethyl Acetate Extract 66.7 Gastric chloroform extract 91.1 Example 2 Extract 22.4 Example 3 Extract 10.5

As a result of the antioxidant effect test using DPPH radical scavenging ability, ethanol, butanol extract, and gastric ethanol extract of hachocho, extracts of botanical herb extracts of Examples 2 and 3 showed similar or equivalent effects than conventional whitening raw materials. It can be seen that the herbal herbal extracts are excellent antioxidant effect.

Example 4 Preparation of Liposome Herbal Extract-Containing Nanoliposomes (1)

10 g of the herbal extract extracted in Example 2, 40 g of glycerin, and 9.00 g of purified water were mixed and warmed and dissolved at 55 ° C., and then 10 g of hydrogenated lecithin, caprylic and carbohydrate, which was previously dissolved at 55 ° C. Ultrafine emulsion on semi-transparent gel made of nano liposomes by adding 30 g of fructriglycerides and 0.6 g of cholesterol and cooling by recirculating five times at 600 bar using a high-pressure microfluidizer (Microfluidizer, model M110F, MICROFUIDICS, USA). The particle size of the particle size distribution using the particle size analyzer (ZETASIZER 3000H, MALVERN, UK) is shown in FIG. 3 and the particle size of the high-resolution transmission electron microscope FF-TEM (JEM1010, JEOL, Japan). .

Example 5 Preparation of Liposome Herbal Extract-Containing Nanoliposomes (2)

10 g of the herbal extract extracted in Example 3, 40 g of glycerin, and 9.00 g of purified water were mixed and warmed and dissolved at 55 ° C., and then 10 g of hydrogenated lecithin and caprylic / ca were previously dissolved at 55 ° C. 30 g of fructriglycerides and 0.6 g of cholesterol were added and cooled with 5 recycles at 600 bar using a high-pressure microfluidizer to obtain ultrafine emulsions on translucent gels made of nano liposomes.

Comparative Example 1

Except for not adding 0.6 g of cholesterol in Example 4 and replacing the remaining amount with purified water is the same as the manufacturing method of Example 4.

Comparative Example 2

In Example 4, the same method as in Preparation Example 4 was repeated except that 10 g of the herbal extract of bovine herb extract was replaced with purified water.

Division (weight%) Example 4 Example 5 Comparative Example 1 Comparative Example 2 Example 2 Extract 10.0 - 10.0 - Example 3 Extract - 10.0 - - Concentrated glycerin 40.0 40.0 40.0 40.0 Purified water Remaining amount Remaining amount Remaining amount Remaining amount Hydrogenated Lecithin 10.0 10.0 10.0 10.0 Caprylic & Capric Triglycerides 30.0 30.0 -30.0 30.0 cholesterol 0.60 0.60 - 0.60

The nano liposomes collected from the herbal herbal extracts prepared in Examples 4 and 5 have different physicochemical properties from conventional emulsions such as stability, rheological properties, uniformity, and high interfacial area.

Prescription Examples 1-2 and Comparative Prescription Examples 1-2

Prescription examples of the lotion in the cosmetic preparations containing the nanoliposomes of Example 4, 5 and Comparative Example 1 of the present invention and the extract of Example 2 are as follows.

Division (weight%) Prescription Example 1 Prescription Example 2 Comparative Prescription 1 Comparative Prescription 2 Example 4 Nanoliposomes 5.00 - - - Example 5 Nanoliposomes - 5.00 - - Comparative Example 1 Nanoliposomes - - 5.00 - Example 2 Extract - - - 0.50 Purified water Remaining amount Remaining amount Remaining amount Remaining amount 1,3-butylene glycol 6.00 6.00 6.00 6.00 Hydroxypropyl cellulose 0.05 0.05 0.05 0.05 Fiji-Fiji 18/4 copolymer 1.00 1.00 1.00 1.00 Disodium ID 0.02 0.02 0.02 0.02 Fiji-26-butes-26 / fiji-40 hardening castor oil 0.03 0.03 0.03 0.03 Methylparaben 0.15 0.15 0.15 0.15 ethanol 8.00 8.00 8.00 8.00 incense Quantity Quantity Quantity Quantity

Prescription Examples 3-4 and Comparative Prescription Examples 3-5

Cream compositions containing nanoliposomes of Examples 4 and 5 (prescription examples 3 to 4), cream compositions to which nanoliposomes of comparative example 2 were added and extracts of comparative example 2 (comparative prescription example 3), extracts of example 3 Only the cream composition (Comparative Example 4) added and the control cream composition (Comparative Example 5) to which nothing was added were prepared, respectively.

Division (weight%) Prescription Example 3 Prescription Example 4 Comparative Prescription 3 Comparative Prescription 4 Comparative Prescription 5 Example 4 Nanoliposomes 5.00 - - - - Example 5 Nanoliposomes - 5.00 - - - Example 3 Extract - - 0.50 0.50 - Comparative Example 2 Nanoliposomes - - 4.50 - - Arachidyl alcohol / bihenyl alcohol / arachidyl glucoside 1.00 1.00 1.00 1.00 1.00 Cetearyl Alcohol / Cetearyl Glucoside 1.00 1.00 1.00 1.00 1.00 Cetearyl Alcohol 3.50 3.50 3.50 3.50 3.50 Phytosqualene 2.00 2.00 2.00 2.00 2.00 Shea Butter 2.00 2.00 2.00 2.00 2.00 Emu oil 3.00 3.00 3.00 3.00 3.00 Safflower Seed Oil 1.00 1.00 1.00 1.00 1.00 Macadamia oil 3.00 3.00 3.00 3.00 3.00 Pyromethicone 2.00 2.00 2.00 2.00 2.00 1,3-butylene glycol 6.00 6.00 6.00 6.00 6.00 Xanthan Gum 0.05 0.05 0.05 0.05 0.05 Disodium ID 0.02 0.02 0.02 0.02 0.02 Beta Glucan (0.4%) 5.00 5.00 5.00 5.00 5.00 antiseptic Quantity Quantity Quantity Quantity Quantity incense Quantity Quantity Quantity Quantity Quantity Purified water Remaining amount Remaining amount Remaining amount Remaining amount Remaining amount all 100 100 100 100 100

Experimental Example 4: Comparative Test of Stability of Nanoliposomes

The stability of Formulations 1-2 and Comparative Formulations 1-2 of the cosmetic preparations containing the nanoliposomes which stabilized the herbal extracts of hwahwabun, hagocho, and gastrointestinal tract according to the present invention were measured by the following method. This is because, in the case of selecting a cosmetic lotion, it is possible to visually determine the stability such as layer separation and discoloration in a relatively short period of time.

Samples 1 to 2 and Comparative Examples 1 to 2 were stored in a transparent glass container for 3 months in a 45 ° C. thermostatic chamber, stored for 3 months at 4 ° C., and stored in transparent glass for 3 months under shading conditions, at room temperature. The color change and separation of the samples stored in the transparent candle for 3 months were measured and shown in the following Table 6.

Stability test of nano liposomes applied to lotion Sample storage temperature Separation / discoloration degree of each sample Prescription Example 1 Prescription Example 2 Comparative Prescription 1 Comparative Prescription 2 4 ℃ 0 0 0 One Room temperature 0 0 0 One 45 ℃ 0 0 One 2  Separation strength: The higher the precipitation strength or the amount of suspended oil, the higher the value.

As shown in Table 6, the nano liposome composition added to the lotion of Formulations 1 and 2 was very stable without discoloration or separation phenomenon, the nano liposome composition without addition of cholesterol added to the lotion of Comparative Example 1 At a high temperature storage condition of 45 ℃, the degree of discoloration and a very small separation band was formed in the upper layer of the container, Example 2 Comparative lotion of Example 2 with the addition of the extract and nano liposomes separated and discolored at room temperature and 45 ℃ The storage conditions were unstable enough to reveal the naked eye. This is because hydrogenated lecithin (saturated fatty acid-derived phospholipid) forming nano liposomes causes a phase change in the lipid bimolecular film in the gel-liquid phase transition temperature region, resulting in the removal of the extract or particle uniformity of nano liposomes. It is caused by Ostwald lifeening, which is absorbed and fused to large particles, and it is necessary to add cholesterol for the purpose of suppressing it, and the interaction of the minority period is weakened below the phase transition temperature, and the stability of the inner membrane is improved above the lipid phase transition temperature. The gel-phase transition temperature disappears, suggesting the formation of highly stable nano liposomes. In addition, nano liposome stabilized using hydrogenated lecithin and cholesterol in a certain ratio has the advantage of not only improve the stability over time, such as color, odor, pH lowering, but also does not have to consider the HLB value of the sulfide.

Experimental Example 5: Evaluation of the retention rate of oleanoic acid of nano liposomes applied to the lotion

To determine the relationship between the effect of adding cholesterol and the stability on the stability of nano liposomes, based on the oleanoic acid content retention rate, which is one of the index components of the herbal medicine extracts of Example 2, based on Formulation Example 1, Comparative Formulation Examples 1 and 2 The stability of the active ingredient was evaluated. Stability was measured by absorbance at 213 nm oleanolic acid titer immediately after the preparation and oleanolic acid titer after 45 ℃, 1, 3 months and the results are shown in Table 7 below.

Variation of Oleanoic Acid Titer of Nanoliposomes Applied to Facial Skin division Oleanoic acid titer of each sample (45 ° C) Immediately after manufacture 1 month after manufacture 4 months after manufacture Prescription Example 1 98.2% 96.4% 95.5% Comparative Prescription 1 97.3% 89.1% 83.3% Comparative Prescription 2 96.7% 76.3% 60.8%

As shown in Table 7, the nano liposomes containing cholesterol while containing the extract of Example 2 in the lotion of Formulation Example 1 were stable because the titer retention rate of oleanoic acid was very good even after 45 ° C and 3 months. The comparative lotion of Comparative Example 1 containing the extract of Example 2 contained in the nano liposome was relatively stable, whereas the lotion of Comparative Formula 2 to which the extract of Example 1 was added was significantly reduced in the titer of oleanolic acid over time. Could know. It can be seen that a suitable ratio (10: 0.60) between hydrogenated lecithin and cholesterol, which acts as an endothelial membrane enhancer, significantly affects stability in order to make nanoliposomes containing stable herbal extracts. When the extract is separately added to the cosmetic formulation, it can be seen that the retention rate of the active ingredient such as oleanoic acid is weakened.

Experimental Example 6: Test for Transdermal Absorption in Hairless Mice

The transdermal absorption test was performed using the cream manufactured by the prescription example 4 and comparative prescription examples 3-4. For percutaneous permeation, skin layer was extracted from hairless mouse of 4 weeks old, then skin was removed from the fat layer of dermis layer, cut into square area of 1 cm ² , and it was installed in permeation cell of 0.9 cm in diameter. And clamped. 0.5 ml of the cosmetic composition (the creams prepared in Prescription Examples 4 and Comparative Examples 3 to 4) was applied to one side of the skin, and the other side was brought into contact with a solvent of 0.025M phosphate buffer solution. The experiment temperature was stirred at 600 rpm using a magnetic stirrer while maintaining the actual skin temperature of 32 ㅁ 0.5 ℃, and the permeated components were collected at a predetermined time interval after application for quantification. The phosphate buffer solution was filled again. The collected phosphate buffer solution was measured by oleanoic acid, which is an indicator component of the herbal medicine extract, and quantitatively analyzed by HPLC at absorbance of 213 nm. The results are shown in Table 8 and FIG.

time Example 1 Oleanoic Acid Permeation (μg / mL) in Extracts Prescription Example 4 Comparative Prescription 3 Comparative Prescription 4 0 0 0 0 4 9.2 2.3 1.4 8 20.4 5.1 2.6 12 34.8 8.5 3.8

Considering that the makeup duration of the average person is within 8 hours, Formula 4 using nano liposomes containing the herbal herbal extracts (oleanoic acid index component) as shown in Table 8 is separately added nano liposomes and herbal herbal extracts It can be seen that the transdermal absorption increased by 4 to 8 times or more compared to Comparative Prescription Example 4 in which only the Comparative Prescription Example 3 and the Example 3 extract were added, and the drug release pattern was sustained release.

Experimental Example 7: Whitening Effect Test on Brown Guinea Pig Skin

The whitening effect of the cosmetic of the present invention was evaluated using a color difference meter (Chromameter CR-300, Minolta). As an evaluation method, xenon lamps (wavelengths 290-290-2) in which a hole of 2.5 x 2.5 cm was pierced in the skin from which hairs of brown guinea pigs, which are pigmented due to ultraviolet rays and allergic reactions, were removed, such as human skin. 400 nm) was irradiated at 1.50 mW / cm ² for 5 minutes, once a day for 3 days to induce pigmentation. Sample application time was applied after 2 weeks of the highest pigmentation after UV irradiation to determine the improvement effect, the number of times was applied once a day for 30 days continuously. Determination of skin pigmentation degree was measured using the L value (Lightness) of the colorimeter as an index, and the average value was repeated three times or more at one site. The difference in skin color (ΔL value) between the start time and the completion time of application was calculated according to Equation 6 below to compare the dissipation rate of pigmentation [Table 9].

division Whitening effect L value (%) Prescription 3 Cream 86 Prescription 4 Cream 80 Comparative Example 3 Cream 78 Comparative Example 4 Cream 72 Comparative Example 5 Cream 16

Through Table 9, it can be seen that the nanoliposomes containing the herbal herbal extracts of Example 2 had an excellent whitening effect compared to the control of Comparative Formula 5, and also the herbal herbal extracts were simplified through Comparative Formulas 3 and 4. It was found that the whitening effect was relatively higher in the nanoliposomes than the cream composition.

Experimental Example 8: Suppression Effect of Ultraviolet Rays

Thirty subjects with UV-sensitive skin were tested for the anti-irritant effect against UV rays on the herbal extracts extracted from the present invention and nanoliposomes stabilized therefrom. The samples used in this experiment were prepared by dissolving 0.5% of each herbal powder, haejucho, single stomach extract, and herbal extracts of Examples 2-3 in 1.3-butylene glycol and 5.0% of nanoliposomes of Examples 4-5. -A patch for patch containing only 1.3-butylene glycol and a solution dispersed in butylene glycol, after patching on the upper left side with the same final concentration of the extract, remove it after 24 hours and remove it with a marking pen. The test site was marked and irradiated with 2MED (minimum erythema dose) ultraviolet rays after 1 hour, and after 24 hours, irritation such as erythema was observed. In addition, the cream composition of Formulation Examples 3-4 and Comparative Formulations 3-5 was tested in the same manner in the upper right upper part in order to examine the effect of inhibiting the irritation by ultraviolet rays when the formulation was applied. In this experiment, the stimulation degree was classified into 5 grades according to the ICDRG criterion, and the average value was calculated according to the following equation (7). Table 10 shows.

Respondents: People with erythema

Response intensity: stimulus value determined according to stimulus grade

Peak response intensity: highest value at the stimulus level

Average skin responsiveness criteria Criteria (Grade) medium Stimulus type No irritation (grade 1) 0.00-0.75 Non-irritating Unstimulated (Level 2) 0.76-1.50 Faint erythema Light Stimulation (Level 3) 1.51-2.50 Weak erythema, edema and papules Medium stimulus (grade 4) 2.51-4.00 Pronounced erythema, papules and vesicles Strong stimulus (grade 5) 4.00 or more Severe erythema, alveolus, crust

 The stimulation inhibition rates shown in the following Tables 11 to 12 and FIG. 6 are expressed as percentages of the relative decrease in sample application based on each case of the untreated herbal herbal extract and the negative control group of the untreated herbal herbal extract in the cream formulation. .

division medium Stimulation inhibition rate (%) Negative Control (No Sample) 4.09 - Cheonhwahwa hot water extract 2.65 35.21 Cheonhwahwa ethanol extract 2.43 40.59 Natural Flower Butanol Extract 2.54 37.90 Cheonhwabun Ethyl Acetate Extract 2.62 35.94 Natural Flower Powder Chloroform Extract 2.87 29.83 Higocho hot water extract 2.76 32.52 Higocho ethanol extract 2.31 43.52 Hagocho Butanol Extract 2.48 39.36 Higocho ethyl acetate extract 2.56 37.41 Higocho chloroform extract 2.72 33.50 Gastric Hydrothermal Extract 2.32 43.28 Gastric Ethanol Extract 1.81 55.75 Gastric Butanol Extract 1.63 60.15 Gastric Ethyl Acetate Extract 2.13 47.92 Gastric chloroform extract 2.43 40.59 Example 2 Botanical Herbal Medicine Extract 2.28 44.25 Example 3 Botanical Herbal Extracts 2.02 50.61 Example 4 Nanoliposomes 1.47 64.06 Example 5 Nanoliposomes 1.32 67.73

division medium Stimulation inhibition rate (%) Comparative Prescription 5 (without extract) 3.61 - Comparative Prescription 4 1.88 47.92 Comparative Prescription 3 1.64 54.58 Prescription Example 3 1.22 66.20 Prescription Example 4 1.09 69.81

Through the experimental example 8, the ethanol and butanol extracts of the gastric glands were the most excellent in reducing the irritation effect by UV rays compared to the untreated negative control group. Nanoliposomes of Example 5 had a better stimulation-reducing effect than the negative control group without the extract. On the other hand, compared with Comparative Formula 5 of the formulation negative control group, the nano liposomes and Formulas 3 to 4 of Examples 4 to 5 have a higher anti-irritant effect. Due to the sustained sustained release effect of the nano liposomes containing the same, it can be seen that the effect is further enhanced when nano liposomes are formed.

Experimental Example 9: Whitening Effect Through Clinical Trials

Experimental Example of the present invention is applied to the cream composition of the nano liposome of Example 4 containing the medicinal herb extract of Example 2 to the cream composition and the cream of Comparative Example 5 which is a cream containing no natural products on the face The subjects of 30 healthy females (mean age: 38.4 years old) who had pigmentation and pigmentation were evaluated for the improvement effect of left and right facial application for 8 weeks. It was.

① Whitening effect by device evaluation after artificial pigment deposition

 Select the artificial pigmentation site inside the lower arm of the arm (1.5 × 1.5 cm) and increase the amount of ultraviolet light sequentially using the UV irradiation device equipped with UV-B lamp (TL20W / 01RS). ) Was repeatedly irradiated 2-3 times depending on the blackening state. After pigmentation, before using the product, and after 4 and 8 weeks of using the product, the lens was acclimated for 20 minutes in a constant temperature and humidity condition using a spectrophotometer CM 2600D. The average value was obtained.

Skin color improvement effect after artificial color deposition division Prescription example 3 cream (test group) Comparative Example 5 Cream (Control) Average skin color before blackening 66.81 66.74 Average value after using the product after blackening 59.81 59.83 Average value after 4 weeks of product use 64.13 60.94 Average value after 8 weeks of product use 68.26 62.32 △ L (after blackening-before blackening) average value -7.00 -6.91 △ L (4 weeks-0 weeks) mean value 4.32 1.11 △ L (8 weeks-0 weeks) mean value 8.45 2.49

The cream of Formulation Example 3 was applied to the right side of the cream of Comparative Formula 5 as a control on the left side to observe the change in skin color according to use. As a result, the cream of Formulation Example 3 significantly increased the brightness of the skin color at 4 weeks (brightness: 3.8 times higher than the control) and after 8 weeks (brightness: 3.4 times higher than the control) compared to before the product. The cream of Comparative Example 5 had a slight increase in skin color brightness over time compared with the use of the product after blackening.

① Whitening effect through usability test

For the same subject and the same sample, a cream of Comparative Example 5 was applied on the face left side and a comparative prescription example 5 on the face right side for 8 weeks, and the whitening effect by the user questionnaire was evaluated. Self-evaluation was conducted by filling out a questionnaire about the whitening effect, skin safety and usability of the product at 4 and 8 weeks after using the test product. The results are summarized in the following Tables 14-16.

division Comparative Prescription 5 (Control) Prescription Example 3 (Test Group) Number of people % Number of people % Whitening effect 4 weeks after product use 2 6.67 19 63.33 After 8 weeks of product use 3 10.00 23 76.67

division Comparative Prescription 5 (Control) Prescription Example 3 (Test Group) Number of people % Number of people % Skin irritation 4 weeks after product use 3 10.00 0 0.00 After 8 weeks of product use 3 10.00 One 3.33

division Comparative Prescription 5 (Control) Prescription Example 3 (Test Group) Number of people % Number of people % incense 4 weeks after product use 18 60.00 18 60.00 After 8 weeks of product use 20 66.67 21 70.00 Feeling 4 weeks after product use 21 70.00 23 76.67 After 8 weeks of product use 21 70.00 22 73.33 Absorbency 4 weeks after product use 22 73.33 24 80.00 After 8 weeks of product use 21 70.00 23 76.67 Skin compatibility 4 weeks after product use 23 76.67 25 83.33 After 8 weeks of product use 23 76.67 25 83.33 Moisturizing 4 weeks after product use 19 63.33 24 80.00 After 8 weeks of product use 20 66.67 26 86.67

The results of the experiment showed that the liposomes containing the herbal extracts of botanical herb extracts showed excellent whitening effect, and the moisturizing retention was particularly good among the usability test items, which is the biocompatible substance of hydrogenated lecithin. In particular, in the skin safety evaluation, the cream of the test group is superior to the cream of the control group because the herbal medicine extract itself has an irritating effect and is stabilized with nano liposomes, and thus has a sustained release effect of sustained release.

As described above, the present invention relates to a nano liposome composition containing a medicinal herb extract of cheonhwabun, hagocho, and stomach cancer as an active ingredient, and a cosmetic for skin whitening using the same, the medicinal herb extract encapsulated stably with nanoparticles. The active ingredient of the skin provides a skin whitening cosmetic having the effect of promoting transdermal absorption, whitening effect, antioxidant effect, and anti-irritant effect by ultraviolet rays.

Claims (5)

Nano liposome composition, characterized in that 0.01 to 20.0% by weight of the herbal medicine extracts of cheonhwabun, Hagocho, and gastrointestinal tract as an active ingredient. The method according to claim 1, wherein 10-15 wt% of hydrogenated lecithin, 10-50 wt% of glycerin, 10-40 wt% of capric and capric triglycerides, 0.3-2.0 wt% of cholesterol, and purified water, based on the total nanoliposome composition. Nano liposome composition, characterized in that containing -70% by weight. The nanoliposome composition according to claim 1, wherein the herbal extract of the botanical herb extract is obtained by mixing at a weight ratio of 0.5-2: 0.5-1. The nano liposome composition according to claim 1, wherein the particle size of the nano liposome is 20 to 100 nm. Cosmetics for skin whitening, characterized in that the formulation of the nano-liposomal composition of any one of claims 1 to 4.