KR102686600B1 - Cosmetic composition comprsing cross-linked hyaluronic acid and method for manufacturing the same - Google Patents

Abstract

The present invention relates to a method for producing cross-linked hyaluronic acid, a cosmetic composition containing the cross-linked hyaluronic acid, and a method for producing the same. When using the cross-linked hyaluronic acid according to the present invention, not only does it have superior moisturizing power and skin disease improvement effect compared to existing hyaluronic acid, but also has a clear outline effect.

Description

Cosmetic composition comprising cross-linked hyaluronic acid and method for manufacturing the same {Cosmetic composition comprsing cross-linked hyaluronic acid and method for manufacturing the same}

The present invention relates to a method for producing a cosmetic composition containing cross-linked hyaluronic acid and a cosmetic composition produced by the method. Specifically, it relates to a method for producing cross-linked hyaluronic acid, which has superior moisturizing power and moisture retention effect compared to existing hyaluronic acid, a method for producing a cosmetic composition containing the cross-linked hyaluronic acid, and a cosmetic composition prepared by the method.

Human skin contains components such as hyaluronic acid, collagen, and elistin, and the hyaluronic acid used in the present invention has excellent moisturizing power and has been developed into moisturizing creams, moisturizing serums, etc., and many products are currently sold on the market. It is becoming.

In particular, cross-linked hyaluronic acid, which is cross-linked hyaluronic acid, is currently used as a filler for wrinkles and contour correction of the skin by injecting it into specific areas of the skin.

Several patents have appeared on the manufacturing method of cross-linked hyaluronic acid used in the present invention.

In the hyaluronic acid filler manufacturing method, Patent Publication No. 10-2020-0006509 crosslinks the molecular weight of hyaluronic acid from 2.5 MDa to 3.5 MDa using sodium hydroxide and BDDE (1,4-Butandiol Diglycidyl ether), followed by sodium chloride and monohydrogen phosphate. Cross-linked hyaluronic acid was swelled by making a mixed buffer of sodium hydrate, sodium dihydrogen phosphate hydrate, and lidocaine hydrochloride, and by further preparation, a cross-linked hyaluronic acid filler was invented.

Publication Patent Publication No. 10-2018-0035032 is a hyaluronic acid of 1000 kDa, cross-linked using NaOH solution and BDDE, and then washed with pure water or saline solution to produce cross-linked hyaluronic acid with a concentration of 10 mg/ml. .

Publication Patent Publication No. 10-2020-0004503 crosslinks hyaluronic acid using an aqueous sodium hydroxide solution and BDDE, then dialyzes it into a PBS buffer using sodium dihydrogen phosphate hydrate, sodium monohydrogen phosphate hydrate, sodium chloride, etc. to reach pH 7.0. Cross-linked hyaluronic acid was made and cross-linked hyaluronic acid filler was prepared.

In this way, cross-linked hyaluronic acid is manufactured as a filler and is used for wrinkles and facial contours. Its applicability is that cross-linked hyaluronic acid is an elastic material, and when it is prepared as a cosmetic cream, lotion, or serum in addition to a filler, the elastic material itself generates particles like grains, making it useful for various purposes. There is a problem that makes it difficult to use.

Public Patent Publication No. 10-2020-0006509 Public Patent Publication No. 10-2018-0035032 Public Patent Publication No. 10-2020-0004503

In order to solve the above problems, the purpose of the present invention is to provide a water-soluble based moisturizing cosmetic composition and a method for manufacturing the same.

In addition, by manufacturing a water-soluble cosmetic composition by adjusting the elasticity and particle size, it has a superior moisturizing effect than existing hyaluronic acid cosmetics. When used on the face and body, it retains moisture longer than hyaluronic acid, making it a cross-linked hyaluronic acid that provides moisture and clear outlines to the face and body. The purpose of the present invention is to provide a cosmetic composition for moisturizing, whitening, improving wrinkles or improving skin diseases, and a method thereof.

In order to achieve the above object, the present invention provides a method for producing cross-linked hyaluronic acid using hyaluronic acid or a salt thereof, and a method for producing a cosmetic composition containing the cross-linked hyaluronic acid produced by the above method.

Additionally, a cosmetic composition containing cross-linked hyaluronic acid prepared by the cosmetic composition manufacturing method is provided.

The method for producing cross-linked hyaluronic acid according to the present invention includes the following steps:

(a) adding and stirring hyaluronic acid or a salt thereof and a cross-linking agent into an aqueous alkaline solution;

(b) dialyzing the aqueous solution stirred in step (a);

(c) pulverizing the cross-linked hyaluronic acid dialyzed in step (b); and

(d) Sterilizing the hyaluronic acid pulverized in (c) above.

The step (a) of adding hyaluronic acid and a cross-linking agent to an aqueous alkaline solution and stirring it is a step of adding hyaluronic acid and a cross-linking agent to an aqueous alkaline solution and stirring it.

The hyaluronic acid or its salt may include hyaluronic acid or an organic salt such as sodium hyaluronate, potassium hyaluronate, calcium hyaluronate, etc., but is not limited thereto.

The molecular weight of hyaluronic acid or its salt used to produce cross-linked hyaluronic acid can be 3.5 MDal or less. In this case, the molecular weight of hyaluronic acid or its salt is 0.1 MDal to 3.5 MDal, preferably 0.5 MDal to 0.5 MDal. It may be hyaluronic acid of 3.0 MDal, more preferably 0.5 MDal to 2.0 MDal. If the molecular weight of hyaluronic acid or its salt is less than the above range, it has the same problems as simply using hyaluronic acid in terms of moisturizing power. If the molecular weight is large, particles in the form of particles may be formed during preparation, and due to the large molecular weight, it is absorbed into the skin. There are problems that hinder this.

The aqueous alkaline solution used for crosslinking may be an aqueous alkali solution such as KOH, Ca(OH) ₂ , Mg(OH) ₂ , NH ₄ OH in addition to an aqueous NaOH solution, and the concentration of the aqueous alkaline solution is 0.01N to 1.0N. It may be a concentration of If the concentration exceeds the above concentration, cross-linked hyaluronic acid may be decomposed through a reversible reaction, which may reduce viscosity and elasticity when manufacturing the product.

Crosslinking agents include 1,4-Butandiol diglycidyl ether (BDDE), bisepoxypropoxyethylene (1,2-(bis(2,3-epoxypropoxy)ethylene), and propylene glycol die. Glycidyl ether (propylene glycol diglycidyl ether), polytetranethylene glycil diglycidyl ether, ethylene glycol diglycidyl ether (EGDGE), neopentyl glycol diglycidyl Ether (neopentyl glycoldiglydidiyl ether), polyglycerol polyglycidyl ether, diglycerol polyglycidyl ether, hexanediol diglycidyl ether (1.6-hexanediol diglycidyl ether), glycerol polyglycidyl ether Glycerol polyglycidyl ether, tri-methylpropane polyglycidyl ether, pentaerythritol polyglycidyl ether, sorbitol polyglycidyl ether ether), and preferably 1,4-butanediol diglycidyl ether, but is not limited thereto.

Step (b) is a step of dialyzing the aqueous solution stirred in step (a). Specifically, since the pH must be adjusted to 6.0 to 8.0 after removing the caustic soda or the cross-linking agent BDDE used as a cross-linking agent, a PBS buffer of monobasic or dibasic phosphate or a solution of NaCl can be used as a dialysate after cross-linking hyaluronic acid.

In addition, it can be used after simply using water for injection to remove caustic soda and BDDE in cross-linked hyaluronic acid through dialysis and adjusting the pH to between 6.0 and 8.0.

In dialysis to remove cross-linking agents and alkalis, it is preferable to use pure water alone, but NaCl solution or PBS solution can be additionally used.

At this time, BDDE (1,4-Butanediol diglycidyl ether) can be analyzed by GC (gas chromatography) to confirm 0 ppm.

Unlike existing cross-linked hyaluronic acid, the present invention may include cross-linked hyaluronic acid with a storage elasticity of 100 Pa or less. Alternatively, if it contains cross-linked hyaluronic acid with a storage elasticity of 100 Pa or more, it can be crushed and included.

Accordingly, the step (c) of pulverizing the dialyzed cross-linked hyaluronic acid may include pulverizing the dialyzed cross-linked hyaluronic acid to a particle size of 100 mesh to 1000 mesh, preferably 300 mesh to 500 mesh. If the particle size is less than the above particle size, dissolution may be difficult due to the large particles during preparation, and stirring for a long time may be required. If the particle size is exceeded, the mesh may be damaged due to the finely ground size.

In addition, in order to produce cross-linked hyaluronic acid with the above particle size, it can be finely ground using stirring grinding, mesh grinding, or using a MF (micro fluidizer), but is not limited thereto.

Cross-linked hyaluronic acid absorbs water and forms an elastic body when in contact with water, so it has the following problems when manufacturing cosmetic compositions (or products).

First, the aqueous solution and cross-linked hyaluronic acid are prepared at a certain concentration and then pulverized to form an elastic body when mixing the oil phase during production. When producing cosmetic cream or lotion, an elastic body is formed due to the oil component. Therefore, there is a problem that grain-like particles are caught when applied to the face or body, making it difficult to fundamentally solve the problem.

However, when only an aqueous solution is used, the elastic body is adjusted and pulverized, and when used, the elastic body itself absorbs moisture from the aqueous solution and is formed into a soft shape, showing a shape that shows a clear outline when applied to the face or body. The present invention uses cross-linked hyaluronic acid. The purpose was to crush and use it.

Second, the lower the molecular weight of hyaluronic acid, the easier it is to be absorbed, but the moisturizing power of the skin surface is lower than that of cross-linked hyaluronic acid, making it difficult to maintain moisture on the skin surface for a long time. The present invention prevents drying of the skin surface and uses The outer surface is cross-linked hyaluronic acid to increase moisture retention and minimize skin dryness.

In the present invention, hyaluronic acid of 0.1 Mdal or less can be used as food, but is generally not suitable for use in cosmetics considering foreign substances, moisturizing power, etc. In addition, hyaluronic acid of 3.5Mdal or more can be industrially produced, but it is expensive in terms of purchase price and it is difficult to use it in cosmetics due to the increase in manufacturing cost.

Thirdly, cross-linked hyaluronic acid is an elastic material that is not pulverized. When used, there are differences depending on the raw materials used in the preparation, but if raw materials with appropriate elasticity are not used, if the elasticity and particles are large, not only will it be difficult to dissolve, but it will also affect the skin texture when used (e.g. , skin absorption, feeling of being coated on the skin, etc.) may be low.

When pulverized to reduce the particle size, it is easily dissolved in aqueous solution, and is intended to harmonize with other components when preparing, and increases the feeling of use. If it is not pulverized, dissolution becomes more difficult as the amount of cross-linked hyaluronic acid used increases, and there is a problem that particles like elastic bodies are often formed when adding partial oil components.

Therefore, the cosmetic composition containing cross-linked hyaluronic acid prepared by the present invention is not limited, but is preferably based on an aqueous solution. Additionally, the cross-linked hyaluronic acid may contain 5 to 40 mg/ml, preferably 20 to 30 mg/ml.

The step (d) of sterilizing the divided hyaluronic acid is a step of preparing the cross-linked hyaluronic acid by adding pure water, pulverizing it, and sterilizing it. At this time, sterilization conditions may be performed at 120 to 130°C for 15 to 30 minutes, preferably at 121°C for 20 minutes. If the conditions are below the above conditions, sterilization does not work properly, and if the above conditions are exceeded, there is no difference in the sterilization effect and there is a risk that the components in the composition may change.

The storage elasticity of cross-linked hyaluronic acid prepared after sterilization may be 10 to 150 Pa, preferably 50 to 100 Pa. Additionally, the loss elasticity of the cross-linked hyaluronic acid may be 10 to 100 Pa, preferably 20 to 50 Pa.

When preparing a cosmetic composition using cross-linked hyaluronic acid according to the present invention, it contains 20 to 30 mg/ml of cross-linked hyaluronic acid or cross-linked hyaluronic acid elastomer, but 0.01% (w/w) to 15% (w/w). It can be prepared as an aqueous solution containing 0.1 to 5% (w/w), preferably.

The method for manufacturing a cosmetic composition containing cross-linked hyaluronic acid according to the present invention may further include a method of packaging the manufactured cosmetic composition in a container, ampoule, or pre-filling syringe.

In one embodiment of the present invention, when producing cross-linked hyaluronic acid, 10 to 20 g of 1.4 MDal hyaluronic acid is dissolved in 50 ml to 300 ml of 0.25 N NaOH solution at room temperature, and 1.5 g to 0.5 g of BDDE is added and incubated for 10 to 60 minutes. It is prepared by stirring for 10 minutes, leaving it for 10 to 15 hours, placing it in a dialysis net, and dialyzing 20 L of pure water 5 times.

At this time, the pH of the solution may be 6.0 to 8.0, preferably 7.5.

The cosmetic composition according to the present invention can be manufactured in various forms such as toner, mist, lotion, essence, ampoule, serum, cream, soap, cleansing foam, cleansing oil, cleansing water, shampoo, rinse, treatment, scalp cleanser, etc. It is not limited to this.

In addition, the cosmetic composition may additionally include additives such as solvents, carriers, excipients, diluents, thickeners, antioxidants, viscosity stabilizers, etc. commonly used in the art to manufacture cosmetics.

The cosmetic composition may be used for moisturizing, whitening, improving wrinkles, or improving skin diseases, but is not limited thereto.

The low-elasticity cross-linked hyaluronic acid according to the present invention can be contained by pulverizing it after production, and can be used not only as an excellent moisturizing serum but also as a functional cosmetic with whitening ingredients added. It can also be used as a one-time personal cosmetic serum by filling it into a prefilled syringe so that it can be used in high concentration.

In addition, the cross-linked hyaluronic acid according to the present invention is based on an aqueous solution, and the cosmetic composition containing the hyaluronic acid maximizes the utility of cross-linked hyaluronic acid through the effect of improving skin diseases and increasing the contour of the skin such as the face.

Figure 1 shows the effect of improving skin diseases by strengthening moisturizing power by applying cross-linked hyaluronic acid according to the present invention to the face.
Figure 2 shows the effect of improving skin diseases by strengthening moisturizing power by applying cross-linked hyaluronic acid according to the present invention to the neck and wrist.

Hereinafter, the present invention will be described in detail through examples and experimental examples.

However, the following examples and experimental examples only illustrate the present invention, and the content of the present invention is not limited to the following examples and experimental examples.

<Example 1> Preparation of cross-linked hyaluronic acid

15 g of 1.4 MDal hyaluronic acid was stirred in 300 ml of 0.25 N NaOH solution at room temperature at 250 rpm for 2 hours, then 0.5 g of BDDE, a cross-linking agent, was added and stirred for 30 minutes. After leaving at room temperature for 15 hours, add cross-linked hyaluronic acid to the dialysis net, dialyze 20L of pure water 5 times at room temperature to remove NaOH and BDDE, add pure water based on the hyaluronic acid content of 24 mg/ml, and spin at 1500 rpm. The cross-linked hyaluronic acid raw material was prepared by stirring for 10 minutes, grinding it, passing it through a 400 mesh mesh, and sterilizing it at 121°C for 20 minutes. The storage elasticity of the manufactured cross-linked hyaluronic acid was 80 Pa and the loss elasticity was 25 Pa.

<Example 2> Preparation of cross-linked hyaluronic acid

15 g of hyaluronic acid 2.4 MDal was stirred in 200 ml of 0.25 N NaOH solution at 250 rpm for 2 hours at room temperature, then 1.0 g of BDDE, a cross-linking agent, was added, stirred for 30 minutes, left at room temperature for 15 hours, placed in a dialysis net, and then added with 20 L of pure water. After removing NaOH and BDDE by dialysis at room temperature, pure water was added based on hyaluronic acid content of 24㎎/㎖, coarsely ground at 1500 rpm, dispersed through a micro fluidizer, finely ground, and sterilized at 121°C for 20 minutes to obtain a cosmetic serum raw material. Cross-linked hyaluronic acid was prepared.

<Example 3> Preparation of cosmetic serum using cross-linked hyaluronic acid

A cosmetic serum was prepared using the cross-linked hyaluronic acid prepared in Example 1 (storage elasticity of 80 Pa, loss elasticity of 25 Pa) according to the mixing ratio in Table 1 below. Water-based components and the composition and content (% by weight) shown in Table 1 below were used. The oil-based components were each heated and mixed at 75°C, cooled to room temperature, and then the water-based component and the oil-based component were stirred at a speed of 3,000 rpm at a temperature of 75°C for 25 minutes to homogenize. Ammonium acryloyl dimethyl taurate/VP copolymer was used as a thickener, and cross-linked hyaluronic acid was added to the aqueous component and stirred to homogenize. Polydeoxyribonucleotide (PDRN) and Centella Asia were added to the homogenized product. A serum-type cosmetic composition containing a mixture of PDRN, Centella asiatica quantitative extract, and natural products was prepared by adding and mixing a mixture of Tica quantitative extract and natural products and homogenizing them.

ingredient Cross-linked hyaluronic acid
1% mixing ratio Cross-linked hyaluronic acid
3% mixing ratio Usage% (w/w) Usage% (w/w) Awards Purified water 82,0 84.0 Cross-linked hyaluronic acid 1.0 3.0 Centella asiatica quantitative extract 0.01 0.01 1,2-Hexanediol 0.5 0.5 Allantoin 0.1 0.1 Betaine 0.1 0.1 D-Panthenol 0.05 0.05 ACRYLOYLDIMETHYLTAURATE/VP COPOLYMER 0.15 0.15 PDRN 0.02 0.02 Natural complex 1.0 1.0 Glycereth-26 3.0 3.0 Hydroxyethyl cellulose 0.04 0.04 Glycerine 2.0 2.0 EDTA-2NA 0.03 0.03 Glyceryl Polyacrylate 2.0 2.0 Ethanol 2.0 2.0 Dipropylene glycol 2.0 2.0 paid polyglyceryl-10 laurate 1.4 1.4 GLYCERYL CAPRYLATE 0.3 0.3 Spices 0.2 0.2 total 100% 100%

<Experimental Example 1> Evaluation of improvement in transepidermal water loss

To evaluate the improvement in transepidermal water loss of the cross-linked hyaluronic acid composition prepared according to the present invention, Table 2 shows that our product Queen's Queen AT Serum was used with 3% (w/w) hyaluronic acid, and Table 3 shows 1% (w/w) cross-linked hyaluronic acid. w) was applied using a Vapometer (Delfin Technologies Ltd., Finland). The same tester tested 10 subjects and measured transepidermal water loss by contacting the probe with the same pressure on the left cheek of all subjects. The Vapometer measures the amount of evaporation caused by an increase in relative humidity (RH) inside the chamber through a humidity sensor, and the unit of measurement is g/㎡/h. Compared to before using the test substance, the decrease in the measured value means that the amount of transepidermal water loss has improved.

The improvement rate in transepidermal water loss was calculated using the formula below, and instrumental measurements were made before and after two weeks of use of the composition. The results of the moisturizing power evaluation experiment are shown in Tables 2 to 4. Table 2 used only 3% (w/w) hyaluronic acid, Table 3 used 1.0% (w/w) cross-linked hyaluronic acid, and Table 4 used 3% (w/w) cross-linked hyaluronic acid.

Change in transepidermal water loss in comparative example (when using hyaluronic acid 3.0% (w/w)) person Before use After 2 weeks of use One 12 10 2 13 13 3 10 10 4 11 11 5 13 12 6 12 11 7 14 12 8 13 12 9 12 11 10 10 10 average 12 11.2

Transepidermal water loss improvement rate (%) in comparative example 　 After 2 weeks of use Improvement rate (%) 6.60%

Transepidermal water loss of the cross-linked hyaluronic acid composition according to the present invention (when using 1.0% (w/w) of cross-linked hyaluronic acid) person Before use After 2 weeks of use One 11 10.5 2 10 9.5 3 13 11.5 4 12 11 5 10 9 6 12 11 7 14 11 8 13 11 9 12 10.5 10 13 12 average 12 10.7

Transepidermal water loss improvement rate (%) of the cross-linked hyaluronic acid composition according to the present invention 　 After 2 weeks of use Improvement rate (%) 10.83%

Change in transepidermal water loss of the cross-linked hyaluronic acid composition according to the present invention (when using 3.0% (w/w) of cross-linked hyaluronic acid) person Before use After 2 weeks of use One 13 10 2 12 10.5 3 10 8 4 12 10.5 5 13 11 6 10 9 7 13 11 8 12 9 9 11 10 10 14 12 average 12 10.1

Transepidermal water loss improvement rate (%) of the cross-linked hyaluronic acid composition according to the present invention 　 After 2 weeks of use Improvement rate (%) 15.83%

As a result of the experiment, the improvement rate of transepidermal water loss of the cross-linked hyaluronic acid composition according to the present invention was more than two times higher than that of the comparative example, showing that it has excellent moisturizing power.

<Experimental Example 2> Evaluation of the effect of improving skin diseases by strengthening moisturizing power

Using Example 3, an experiment was conducted as follows to evaluate the effect of improving skin disease by strengthening moisturizing power. The results of evaluating the effect of improving skin disease by strengthening moisturizing power are shown in Figures 1 and 2.

To improve skin diseases, it was used after mixing 3% hyaluronic acid as the ingredient in Table 1. After applying it three times a day to improve inflammation due to strengthening moisturizing power, Figure 1 was photographed 10 days later, and Figure 2 was photographed 9 days later. The results showed that the skin was significantly improved due to the strengthening of moisturizing power. Therefore, the present invention showed that skin inflammation is improved by strengthening skin moisturization by using cross-linked hyaluronic acid.

Claims (13)

A method for producing cross-linked hyaluronic acid for a water-soluble cosmetic composition,
(a) adding and stirring hyaluronic acid or a salt thereof having a molecular weight of 0.5 to 2.0 Mdal and a cross-linking agent into an aqueous alkaline solution;
(b) dialyzing the aqueous solution stirred in step (a) to remove the cross-linking agent and adjusting the pH to 6.0 to 8.0;
(c) pulverizing the cross-linked hyaluronic acid dialyzed in step (b) to a particle size of 300 mesh to 500 mesh; and
(d) sterilizing the pulverized hyaluronic acid in (c);
Including,
A method of producing cross-linked hyaluronic acid for a water-soluble cosmetic composition, wherein the storage elasticity of the cross-linked hyaluronic acid after sterilization is 10 to 150 Pa, and the loss elasticity is 10 to 100 Pa.
delete The method of claim 1, wherein the crosslinking agent is butanediol diglycidyl ether (1,4-Butandiol Diglycidyl ether), bisepoxypropoxyethylene (1,2-(bis(2,3-epoxypropoxy)ethylene), and propylene glycol dily. Glycidyl ether (propylene glycol diglycidyl ether), polytetranethylene glycil diglycidyl ether, ethylene glycol diglycidyl ether (EGDGE), neopentyl glycol diglycidyl Ether (neopentyl glycoldiglydidiyl ether), polyglycerol polyglycidyl ether, diglycerol polyglycidyl ether, hexanediol diglycidyl ether (1.6-hexanediol diglycidyl ether), glycerol polyglycidyl ether glycerol polyglycidyl ether, tri-methylpropane polyglycidyl ether, pentaerythritol polyglycidyl ether, or sorbitol polyglycidyl ether. A method of producing cross-linked hyaluronic acid for a water-soluble cosmetic composition, characterized in that it is any one or more of ether).
The method of claim 1, wherein the aqueous alkaline solution is at least one selected from NaOH, KOH, Ca(OH) ₂ , Mg(OH) ₂ , and NH ₄ OH aqueous solution, and the aqueous alkaline solution has a concentration of 0.01N to 1.0N. A method for producing cross-linked hyaluronic acid for a water-soluble cosmetic composition.
delete The method of claim 1, wherein the sterilization in (d) is performed at 120 to 130°C for 15 to 30 minutes.
Cross-linked hyaluronic acid for a water-soluble cosmetic composition prepared according to claim 1.
delete A water-soluble cosmetic composition comprising the cross-linked hyaluronic acid of claim 7,
The cosmetic composition is a water-soluble cosmetic composition characterized in that it contains 0.01% (w/w) to 15% (w/w) of 10 to 40 mg/mL of cross-linked hyaluronic acid.
The water-soluble cosmetic composition of claim 9, wherein the water-soluble cosmetic composition is based on an aqueous solution.
The water-soluble cosmetic composition of claim 9, further comprising a solvent, carrier, excipient, diluent, thickener, antioxidant, and viscosity stabilizer.
The method of claim 9, wherein the water-soluble cosmetic composition is in the form of any one of toner, mist, lotion, essence, ampoule, serum, cream, soap, cleansing foam, cleansing oil, cleansing water, shampoo, rinse, treatment, and scalp cleanser. A water-soluble cosmetic composition characterized in that it is manufactured.
The water-soluble cosmetic composition according to claim 9, wherein the water-soluble cosmetic composition is used for moisturizing, whitening, improving wrinkles, or improving skin diseases.