KR100553157B1 - Composition containing stabilized resveratrol, alpha-lipoic acid or mixture thereof, preparation method for the same, and cosmetic composition containing the same - Google Patents

Abstract

Stabilization characterized in that the present invention comprises an active ingredient having at least one antioxidant activity selected from resveratrol and alpha-lipoic acid, at least one stabilizing agent selected from sulfur white extract and alternomonas ferment extract, and cyclodextrin as an inclusion agent. The present invention relates to a composition having antioxidant efficacy, a method for preparing the same, and a cosmetic composition comprising the same.

Compositions comprising resveratrol, alpha-lipoic acid or mixtures thereof stabilized according to the present invention not only provide excellent antioxidant effects but also improve the solubility of resveratrol and alpha-lipoic acid in polyols or ethanol, thus making it possible to Decreased feeling of use and skin irritation, crystal precipitation at low temperature, there is an effect to solve the problem of discoloration and discoloration in the sun.

Stabilized resveratrol, stabilized alpha-lipoic acid, clathrate, sulfur white extract, alteromonas ferment extract

Description

Composition containing stabilized resveratrol, alpha-lipoic acid or mixture especially, preparation method for the same, and cosmetic composition containing the same}

The present invention relates to compositions comprising stabilized resveratrol, alpha-lipoic acid or mixtures thereof, methods for their preparation, and cosmetic compositions containing them.

Alpha-lipoic acid used in the present invention has a strong antioxidant activity in itself, and also promotes the production of glutathione, another antioxidant in the body, or vitamin E and vitamin C. The function and regeneration of is known to play a role in strengthening the body's antioxidant activity. It is currently used in the treatment of diabetes, neurological disease, cataract, heart attack, atherosclerosis, etc. by using the efficacy of alpha-lipoic acid, and it is excellent in moisturizing by promoting ceramide production (see US Patent No. 5,472,698A) Effective in dermatitis, necrosis, tumors and allergies (see German Patent No. 441,708A), in allergic, irritating, tanning (see patent WO 9508564A), skin whitening and tyrosinase It is known to have an inhibitory effect (see Japanese Patent No. 6308315A), and to maintain and maintain the homeostasis of the body normally, thereby preventing and relieving acne (Korean Patent Publication No. 1999-025848). Due to the low dissolution of alpha-lipoic acid, deterioration of the feeling of use due to the use of excessive polyol, high odor due to sulfur component, and deodorization due to binding separation to thiol in sunlight I have a discoloration problem.

In addition, resveratrol, which has properties similar to alpha-lipoic acid, has a cis type and a trans type, and trans-resveratrol has anticancer properties (see Jang M., et al., Sci., 1997, 275: 218-220). As well as antithrombotic (Chung, ML et al., Planta Med., 58: 274-276, 1992; Frankel, ENet al., Lancet, 1993, 341: 1103-1104; Bertrilli, AAE et al., Int. J. Tissue React., 1995, 17: 1-3; Pae-Asciak, CR et al., Clin. Chim. Acta., 1995, 235: 207-219), anti-inflammatory (Kimura, Y. et al. , Biochim. Biophys.Acta., 1985, 834: 275-278) and hyperlipidemia (see Arichi, H., et al, chem .. Pharm. Bull., 1982, 30 (5): 1766-1770) It is well known as a bioactive substance. In particular, trans-resveratrol has been spotlighted as a phytoestrogen with the discovery of female hormone estrogen-like action (see Gehm, B.D. et al., Proc. Nasl. Acad. Sci., 1997, 94: 14138-14143). Moreover, as a patent regarding the cosmetic composition containing resveratrol, the cosmetic composition containing grape extract is disclosed by Japanese Patent Application No. 06336421, US Patent No. 5,683,683, 5,439,672 and 5,171,577, and international application number PCT / EP98 / 04223 discloses a cosmetic composition using resveratrol for inhibiting keratinocyte proliferation, inhibiting differentiation of keratinocytes, or controlling skin irritation caused by alpha-hydroxy acids. However, due to the low solubility of resveratrol itself in polyols and ethanols used as solvents in cosmetics, it is possible to solve the problem of decreased use and skin irritation, crystal precipitation at low temperatures, discoloration and discoloration in daylight due to excessive polyol or ethanol use. Is not reported.

Indeed, despite the excellent antioxidant effects of resveratrol, resveratrol is well soluble in polyols or ethanol, but when water is added to cosmetics, crystals are precipitated. Therefore, ethanol or polyol must be used in large amounts. For example, in view of the problem of crystallization, in order to contain resveratrol at 0.1% by weight, a solvent such as 10% by weight of polyol must be used. Therefore, resveratrol cannot be used in high content, and in order to use in high content, Although it is applicable to cosmetic formulations that do not use water, cosmetic compositions consisting only of ethanol or polyol solvents without water are rarely used due to severe irritation and deterioration of feeling, and for vitamin C, which is difficult to stabilize as a special composition, It is formulated and formulated as 'polyol in silicone' or 'silicone in olyol', but it is used only for very limited products due to poor feeling, difficult manufacturing process, and high manufacturing cost.

It is a first object of the present invention to provide a composition comprising stabilized resveratrol, alpha-lipoic acid or mixtures thereof.

It is a second object of the present invention to provide a process for preparing a composition comprising stabilized resveratrol, alpha-lipoic acid or mixtures thereof.

It is a third object of the present invention to provide a cosmetic composition containing a composition comprising stabilized resveratrol, alpha-lipoic acid or a mixture thereof.

A composition comprising stabilized resveratrol, alpha-lipoic acid or a mixture thereof according to the first object of the present invention is characterized in that it comprises an active ingredient having at least one antioxidant effect selected from resveratrol and alpha-lipoic acid and cyclodextrin as an inclusion agent. It is a composition having antioxidant efficacy.

Said cyclodextrin is preferably hydroxy propyl beta cyclodextrin.

The composition may further comprise at least one stabilizer selected from a yellowish white extract and an alteromonas ferment extract.

More specifically, the composition comprising the stabilized resveratrol, alpha-lipoic acid or a mixture thereof is 0.001 to 10.0% by weight, preferably 0.5 to 10.0% by weight of resveratrol, alpha-lipoic acid or a mixture thereof, and sulfur white extract and alter 0.01 to 15.0% by weight, preferably 1.0 to 15.0% by weight, and 0.1 to 50% by weight, preferably 10.0 to 50.0% by weight, of at least one stabilizer selected from the Lomonas ferment extract Dextrins.

In the composition comprising the stabilized resveratrol, alpha-lipoic acid or mixtures thereof, except for the active ingredients resveratrol and alpha-lipoic acid, clathrate and stabilizer, the solvent is composed of a polyol and a solvent comprising ethanol and water.

Resveratrol used as one of the active ingredients having an antioxidant effect in the present invention is trans-3,4,5-trihydroxycistilbene (trans-resveratrol) and cis isomers, each glycoside represented by the following formula (1): , And resveratrol containing extracts and powders obtained from any suitable plant species, including palm and dicotyledonous plants, in particular grapes and in particular grape husks, seeds, stems and grape leaves, in particular Vitis vinifera, Vitis rho Contained in large amounts in the tundifolia and Vitis larusca grapes, it is found in the extracts and powders of the wines and natural products mentioned above and also in many polygonum species (poly Also present in the roots of the Polygonaceae family, for example Polygonum cuspidatum and Polygonum multiflorum. It is also present in the free state in plants, but mostly in the form of glycosides associated with sugars (see Gorham, J., Prog. Phytochem., 1980, 6: 203-209). In addition, resveratrol has a cis type and a trans type, and is present in nature as a stable trans isomer (Trela, BC & Waterhouse, A, L., J. Agric. Food Chem., 1996, 44 (5): 1253-). 1257).

Alpha-lipoic acid used as another active ingredient having an antioxidant effect in the present invention is represented by the following formula (2), alpha-liponic acid (α-liponic acid), thioctic acid (Thioctic acid), thioctan (Thioctan), Co-factors, including 1,2-dithiolane-3-pentanoic acid, which are essential for energy metabolism and cellular respiration from microorganisms to humans Co-factor, which has been identified and identified in the 1950s and has been studied for its efficacy until now, has been recognized as a powerful antioxidant.

Alpha-lipoic acid is well dissolved in ethanol or polyol commonly used in cosmetics, but has a problem in use that causes problems of odor generation while being converted into dihydrolipoic acid represented by the following formula (3) in a solution.

Compositions comprising stabilized resveratrol, alpha-lipoic acid or mixtures thereof according to the invention contain from 0.001 to 10.0% by weight of resveratrol, alpha-lipoic acid or mixtures thereof, when the content of these active ingredients is less than 0.001% by weight. The desired antioxidant effect cannot be obtained, and when it is contained at 10.0% by weight or more, the improvement of the antioxidant effect and the like is insignificant compared to the cost increase due to the increase of these active ingredients.

As the solvent used in the present invention, solvents generally used in the cosmetic field, for example, ethanol, 1,3-butylene glycol, propylene glycol, dipropylene glycol, pentylene glycol, glycerin, etc. may be used. When a high content of silver generates a characteristic odor and strong irritation is generally used in about 10% by weight, it is rarely used in cosmetics for sensitive skin. In addition, the polyol remains sticky when used in a high content, so that the user's preference is low, and it is generally used at about 10% by weight.

The sulfur extract used as a stabilizer in the present invention is obtained by extracting sulfur white with ethanol or 1,3-butylene glycol solvent, and sulfur white as a bark of sulfur white, which is a plant of Unhyanghyeong (Phellodendron amurense Ruprecht or Rutaceae). Is cold, bitter and not poisonous. It mainly eliminates the heat, jaundice, and devices that have been found in the intestine and intestine. Diarrhea and dysentery, redness, swelling of food, killing insects, scabies and ringworms, fever and soreness due to fever in eyes, relieving pain in the mouth, and eliminating osteopenic fever. Antibacterial, anti-inflammatory, Although many antiviral effects have been known, there is no known function to alleviate discoloration and discoloration in products from daylight, ultraviolet rays, and the like. It was confirmed that it can be improved. The sulfur white extract is commercially available under the trade name 'Phellodendron Bark BG' from Koei of Japan.

Alteromonas Ferment Extract (Alteromonas Ferment Extract) which can be used as another stabilizer in the present invention is a fermentation of Alteromonas macleodii, a microorganism that lives in an extreme environment of about 3000m of ocean depth and about 300bar pressure. Dip acid composed of 11 glucosides, a polysaccharide product, has a molecular weight of 1.8 × 10 ⁶ Dalton and has been found to have an effect of relieving skin-induced irritation. Alteromonas Ferment Extract is commercially available under the trade name 'Abyssine 657' from Lanatech, France.

In the present invention, at least one stabilizing agent selected from sulfur white extract and alternomonas ferment extract is used in the range of 0.01 to 15.0% by weight based on the weight of the total stabilized mixture including resveratrol, alpha-lipoic acid or mixtures thereof. Can be. When used at more than 15% by weight, the effect of increased usage is minimal compared to the increase in cost.

Cyclodextrins used as inclusion agents in stabilized mixtures comprising resveratrol, alpha-lipoic acid or mixtures thereof of the present invention may be represented by the following formula, preferably hydroxy propyl beta cyclodextrin may be used.

The content of cyclodextrin should be used in the range of 0.1 to 50% by weight, based on the weight ratio of 5-20 times the active ingredient, or the total stabilized mixture including stabilized resveratrol, alpha-lipoic acid or mixtures thereof, If the weight ratio of the active ingredient is less than 5, the active ingredient is not completely encapsulated, so that undissolved crystals remain. If the weight ratio is more than 20, the cost and feeling of use may be impaired due to the excessive use of the inclusion agent.

Stabilized resveratrol, alpha-lipoic acid or mixtures thereof according to the first object of the present invention not only provide a superior antioxidant effect continuously but also the phase stability of discoloration, discoloration, crystal precipitation, etc. which may be present during the manufacturing process or storage of the product. It is effective in overcoming problems such as changes over time and reducing irritation to the skin.

According to a second object of the present invention, a method for preparing a composition comprising stabilized resveratrol, alpha-lipoic acid or a mixture thereof includes the following steps:

a) mixing the solvent and the inclusion agent;

b) adding resveratrol, alpha-lipoic acid or a mixture thereof to the mixture prepared in step a) and mixing; And

c) adding and mixing a stabilizer comprising a yellowish white extract, an alteromonas ferment extract or a mixture thereof to the mixture prepared in step b).

In the method for preparing a composition comprising the resveratrol, alpha-lipoic acid or a mixture thereof, the solvent may include polyol and ethanol and water.

The inclusion agent in step a) of the process for the preparation of a composition comprising said resveratrol, alpha-lipoic acid or mixtures thereof is cyclodextrin, preferably hydroxy propyl beta cyclodextrin.

The process for preparing a composition comprising the above resveratrol, alpha-lipoic acid or mixtures thereof is generally carried out at room temperature and atmospheric pressure, but may be heated as necessary.

A cosmetic composition comprising stabilized resveratrol, alpha-lipoic acid or a mixture thereof according to the third object of the present invention comprises a composition comprising the stabilized resveratrol, alpha-lipoic acid or a mixture thereof according to the first object of the present invention. It is included in the range of 1.0 to 50.0% by weight based on the weight of.

The cosmetic composition according to the third object of the present invention is not limited thereto, but all formulations which can be prepared by solubilizing, emulsifying or dispersing method, for example, skin, lotion, cream, essence, sunscreen, foam cleansing, cleansing cream or Pack formulation.

 In spite of excellent effects such as antioxidants, the inventors of the present invention found that yellow soybean extract and alteromonas ferment to solve the problems of low solubility of resveratrol and alpha-lipoic acid, discoloration, discoloration and crystal precipitation during long-term preservation. 0.01 to 15.0% by weight of one or more stabilizers selected from extracts, and 0.1 to 50% by weight of cyclodextrin stabilized as clathrate to determine the sustained effect over time of the effect over time of alpha-lipoic acid In the example, the radical scavenging ability was measured for the persistence of the antioxidant effect, and the patch test was performed on the skin of adult adults to confirm the skin safety and the skin irritation test was performed. The phase stability in the product was 40 ℃, 4 ℃ and daylight. Measurement of color change and precipitation over time W was OK.

Hereinafter, the present invention will be described in more detail with reference to the following Examples and Experimental Examples as follows, but the Examples and Experimental Examples of the present invention are not limited to the present invention only to help understanding of the present invention. .

Experimental Example 1

Preparation of Highly Concentrated Stabilizing Compositions

In order to examine the solubility and phase stability enhancing effects of resveratrol and alpha-lipoic acid, a stabilizing composition (Examples 1 to 5, Table 1a) and a comparative example (Table 1b) were prepared with the composition shown in Table 1 below. The composition manufacturing method of each Example and a comparative example is as follows.

First, the solvent containing the clathrates of Tables 1a and 1b is sufficiently stirred and kept transparent, and then the active ingredients (resveratrol and alpha-lipoic acid) parts are slowly added at room temperature and stirred for 30 to 60 minutes to completely dissolve. I was. After the active ingredient was completely dissolved, the stabilizer part was slowly added, followed by further mixing for about 10 to 20 minutes to complete the preparation of stabilized resveratrol and alpha-lipoic acid.

division Raw material name Example 1 Example 2 Example 3 Example 4 Example 5  Solvent 1. Purified water To 100 To 100 To 100 To 100 To 100 2. Hydroxypropyl Beta Cyclodextrin (Note 1) 10.0 20.0 30.0 50.0 50.0 3. 1,3-butylene glycol - - - - - 4. Ethanol - - - - - Active ingredient 5. Resveratrol 0.5 - 2.0 5.0 5.0 6. Alpha-Lipoic Acid - 2.0 3.0 5.0 5.0 Stabilizer 7. Yellow White Extract (Note 2) 1.0 3.0 5.0 10.0 10.0 8. Altero Monas Ferment Extract (Note 3) - 1.0 3.0 5.0 -

division Raw material name Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5 Solvent 1. Purified water To 100 To 100 To 100 To 100 To 100 2. Hydroxypropyl Beta Cyclodextrin (Note 1) 3.0 10.0 - 50.0 - 3. 1,3-butylene glycol - - 30.0 - 50.0 4. Ethanol - - 10.0 - 20.0 Active ingredient 5. Resveratrol 1.0 2.0 3.0 5.0 5.0 6. Alpha-Lipoic Acid - - - 5.0 5.0 Stabilizer 7. Yellow White Extract (Note 2) - - 3.0 - - 8. Altero Monas Ferment Extract (Note 3) - - 1.0 - -

Note 1) Product name: Celldex HP-β-CD (Japan Food Chemical Co., Ltd., JAPAN)

Note 2) Product name: Phellodendron Bark BG (Koei's, JAPAN)

Note 3) Trade name: Abyssine 657 (Lanatech, France)

Experimental Example 2

Solubility and Phase Stability Test

The solubility and phase stability of the stabilized resveratrol, alpha-lipoic acid or mixtures thereof according to the present invention are maintained in dissolution, discoloration and effectiveness during solubility and long-term storage compared to those dissolved in purified water, polyol and ethanol, which are conventional general solvents. In order to confirm whether the dissolution state and odor and color immediately after the preparation and after storage for a predetermined period of time was observed and shown in Table 2 and Table 3 below.

division Immediately after manufacture After 1 month Example 1 Completely dissolved Good Example 2 Completely dissolved Good Example 3 Completely dissolved Good Example 4 Completely dissolved Good Comparative Example 1 Unavailable (decision left) Crystal precipitation Comparative Example 2 Completely dissolved Good Comparative Example 3 Completely dissolved Crystal precipitation Comparative Example 4 Completely dissolved Good Comparative Example 5 Completely dissolved Crystal precipitation

As can be seen from the results of Table 2, the stabilized mixture according to the present invention is completely dissolved even when the concentration of the active ingredients (resveratrol and alpha-lipoic acid) mixture is 15% by weight, and crystals do not precipitate even after one month has elapsed. It can be seen that. In addition, the hydroxypropyl beta cyclodextrin, which is a clathrate, should be used in a weight ratio of 5 to 20 relative to the active ingredient, and if it is 5 or less by weight relative to the active ingredient, the inclusions will not be completely dissolved and crystals will remain (see Comparative Example 1). If the weight ratio is more than 20, it can be seen that an appropriate amount should be taken because it can increase the cost and impair the feeling of use due to the excessive use of the clathrate.

 Phase stability test result division 1 day later 1 month later 2 months later 3 months later Example 1 Room temperature ◎ ◎ ◎ ◎ 40 ℃ ◎ ◎ ◎ ○ 4 ℃ ◎ ◎ ◎ ◎ daylight ◎ ◎ ○ ○ Example 2 Room temperature ◎ ◎ ◎ ◎ 40 ℃ ◎ ◎ ○ ○ 4 ℃ ◎ ◎ ◎ ◎ daylight ◎ ◎ ○ ○ Example 3 Room temperature ◎ ◎ ◎ ◎ 40 ℃ ◎ ◎ ○ ○ 4 ℃ ◎ ◎ ◎ ◎ daylight ◎ ◎ ○ ○ Example 4 Room temperature ◎ ◎ ◎ ◎ 40 ℃ ◎ ◎ ○ ○ 4 ℃ ◎ ◎ ◎ ◎ daylight ◎ ◎ ○ ○ Comparative Example 2 Room temperature ◎ ◎ ◎ ○ 40 ℃ ◎ ○ ○ △ 4 ℃ ◎ ○ △ ★ daylight ○ △ ★ ★ Comparative Example 3 Room temperature ◎ ◎ ○ △ 40 ℃ ◎ ○ △ ★ 4 ℃ ◎ ○ △ ★ daylight ○ △ ★ ★ Comparative Example 4 Room temperature ◎ ◎ ○ △ 40 ℃ ◎ ○ △ ★ 4 ℃ ◎ ○ △ ★ daylight ○ △ ★ ★ Comparative Example 5 Room temperature ○ △ ★ ★ 40 ℃ ○ △ ★ ★ 4 ℃ ○ △ △ ★ daylight △ ★ ★ ★

(◎: No change, ○: Light discoloration, △: Many color change, Separation sign or suspension ★: Complete color change, Separation or precipitation)

As can be seen from Table 3, when hydroxypropyl beta cyclodextrin was not used as a solvent, crystal precipitation occurred at low temperatures in the case of resveratrol (see Comparative Examples 3 and 5). Odor was severely generated (see Comparative Example 5). At the same time, it was found that browning occurred more severely in daylight than when the stabilizer was not contained (see Comparative Example 4). This seems to be due to the sunscreen effect of the yellowish white extract used as a stabilizer. Although antibacterial, anti-inflammatory and antiviral effects on the skin of yellow-white skin have been well known, the function to alleviate the occurrence of discoloration and odor due to ultraviolet rays such as daylight is not known yet. It was confirmed that the phase stability of can be improved.

Experimental Example 3

Long-term retention test

In order to determine the long-term retention rate of the active ingredient of the stabilized mixture according to the present invention, the mixture of Example 4 and Comparative Example 5 was stored at room temperature and 40 ° C and 4 ° C for 3 months, followed by HPLC quantitative analysis of the active ingredient. The long-term preservation of the active ingredient was carried out to confirm the results of the long-term storage rate of resveratrol.

division Example 4 Comparative Example 5 Room temperature 40 ℃ 4 ℃ Room temperature 40 ℃ 4 ℃ Initial value 100 100 100 100 100 100 1 month later 98.01 97.50 98.50 85.20 80.46 75.46 3 months later 95.20 94.30 96.40 76.45 70.25 65.25

HPLC analysis conditions used in the long term retention test of resveratrol were as follows:

1) Analytical column: Inertsil C8, 120A, 5㎛, 4.6 X 150mm (GL science)

2) mobile phase: mobile phase 1; 25 mM NaH ₂ PO ₄ , Mobile phase 2; Acetonitrile

Minutes Mobile phase 1 Mobile phase 2 Rate (ml / min) 0.0 100 0 1.5 10.0 80 20 1.5 15.0 50 50 1.5 20.0 100 0 1.5 30.0 100 0 1.5

3) Column oven temperature: room temperature

4) Measurement wavelength: 310 nm

5) injection volume

As shown in Table 4, when resveratrol is dissolved in a general solvent (see Comparative Example 5), it can be seen that the long-term storage rate in the product is decreased due to crystal precipitation problems at low temperatures and instability at high temperatures. In the case of inclusion with beta cyclodextrin (see Example 4), it can be seen that the long-term retention rate is excellent.

The long-term retention rate of the alpha-lipoic acid test results are shown in Table 6 below.

division Example 4 Comparative Example 5 Room temperature 40 ℃ 4 ℃ Room temperature 40 ℃ 4 ℃ Initial value 100 100 100 100 100 100 1 month later 97.10 96.40 98.10 83.90 80.46 85.60 3 months later 94.50 94.60 98.50 76.20 70.50 80.20

HPLC analysis conditions used for long-term retention of alpha-lipoic acid were as follows:

1) Analytical column: Novapak C18, 120A, 5㎛, 4.6 X 150mm (GL science)

2) mobile phase: mobile phase 1; 0.1% trifluoroacetic acid, pH 2.4, mobile phase 2; Acetonitrile

Minutes Mobile phase 1 Mobile phase 2 Rate (ml / min) 0.0 100 0 1.0 3.0 100 0 1.0 8.0 50 50 1.0 13.0 50 50 1.0 20.0 100 0 1.0 25.0 100 0 1.0

3) column oven temperature; Room temperature

4) Measurement wavelength: 333nm

5) Injection amount: 20µl

As shown in Table 6, when alpha-lipoic acid is dissolved in a general solvent (see Comparative Example 5), it can be seen that the long-term storage rate in the product decreases due to phase instability in the mixture as the temperature is increased. In the case of inclusion with cyclodextrin (see Example 4), it can be seen that the long-term storage rate is excellent.

Experimental Example 4

Skin irritation test

In order to confirm the skin safety of the mixture according to the present invention, a patch test using skin of a normal person was performed on the mixture of Examples 4 and 5 and Comparative Examples 4 and 5, and the results are shown in Table 8 below. Indicated. In this experiment, 20 subjects were allowed to attach patches applied with the mixtures of the respective examples and comparative examples for 24 hours, and then the degree of stimulation was visually determined and the results are shown in the table below. In this experiment, the stimulus index was calculated by the following equation (1), 'minimum stimulus' when the stimulus index is 1.9 or less, 'mild stimulus' when 2.0 to 2.9, and 'normal stimulus' when 3.0 to 3.9. , And 4.0 or more were determined as 'severe stimulation'.

sample Stimulus index Stimulus Example 4 1.3 Minimal stimulation Example 5 2.1 Mild stimulation Comparative Example 4 3.0 Moderate irritation Comparative Example 5 4.5 Severe irritation

In Table 8, from the results of Example 4 and Comparative Example 5 was found to be safer to the skin when using the clathrate according to the present invention, comparing the results of Example 5 and Comparative Example 4 used as a stabilizer according to the present invention In the case of the yellowish white extract, the anti-inflammatory effect has been shown to be excellent stimulation effect, as is known. In addition, it was confirmed that the combination of Alteromonas ferment extract of one of the stabilizers to further alleviate the skin irritation (see Example 4, Example 5 and Comparative Example 4).

Experimental Example 5

Persistence test of antioxidant effect

In order to confirm the long-term sustainability of the stabilized composition according to the present invention, a free radical scavenging test was conducted on the persistence of the antioxidant effects of resveratrol and alpha-lipoic acid and the results are shown in Table 9.

The free radical scavenging force test was performed as follows. Samples of each mixture were taken after the initial, 1 and 3 months of preparation, and dissolved in ethanol at a concentration of 10 mg / ml for the mixtures of Examples 4 and 4 according to the invention in comparison and further as needed. Dilute with ethanol to prepare a sample solution, and 1 ml of the sample solution, 1 ml of a relatively stable blue-green DPPH (1,1-diphenyl-2-picryl-hydrzyl) radical solution at a concentration of about 0.1 mM dissolved in methanol prepared immediately before the experiment. Was added and vigorously stirred for about 10 minutes and then incubated at 37 ° C. for 30 minutes, and then the absorbance was measured. When DPPH radical scavenged, the solution turned from blue-blue to a clear solution and the absorbance decreased at a wavelength of 516 nm. The absorbance (ODexp.) Was measured using a spectrophotometer. For each mixture sample, the absorbance (ODcon.) Was measured using a sample containing no DPPH solution as a control sample, and the absorbance (ODstd.) Of the standard sample containing only DPPH without each mixture was also measured.

From each absorbance measurement value, the free radical scavenging ratio was calculated according to Equation 2 below, and the concentration at which the free radical scavenging ratio became 50%, that is, IC ₅₀ was calculated. Smaller IC ₅₀ values indicate better free radical scavenging ability.

division IC ₅₀ (μg / ml) Early 1 month later 3 months later Example 4 35 42 50 Comparative Example 4 40 80 > 100 Comparative Example 5 48 > 100 > 1000

As can be seen from the results of Table 9, the resveratrol and alpha-lipoic acid excellent in the antioxidant effect but relatively inferior in the long-term effect persistence using the inclusion agent and stabilizer according to the present invention is not the case Compared with Comparative Examples 4 and 5 it can be seen that the efficacy can be maintained for a long time.

Example 6

Preparation of the lotion

By the composition ratio shown in the following Table 10 1 to 3 paragraphs After the aqueous part and the alcohol parts of 4 to 8 each were sufficiently dissolved at room temperature with an azimixer, the alcohol parts were solubilized while gradually being added to the aqueous part. After all the alcohol parts were added and mixed for 10 to 20 minutes to prepare a lotion.

division Raw material name Example 6 Award part 1. The number of tablets To 100 2. Stabilized Composition (Example 4) 20 Paid Part 3. Ethanol 8.0 4. Hydroxy caster oil POE (60) 0.8 5. Incense Quantity 6. Preservative Quantity 7.Dimethicone Oil 0.2

Example 7

Lotion

By the composition ratio shown in the following table 11 1 to 5 paragraphs After dissolving the water phase parts and the oil phase parts of 6 to 12 to 75 ~ 80 ℃ completely dissolved, and slowly adding the oil phase parts to the water phase parts, and emulsified at 3000 rpm at 75 ~ 80 ℃ with a homomixer for 5 minutes. During the emulsification, the neutralizing agent of claim 13 was added and neutralized. After the first emulsification was cooled, the fragrance and additives of claim 14 were added at 50 to 55 ° C., and then emulsified at 3000 rpm for 3 minutes with a homomixer, and then cooled to 27 to 30 ° C. to prepare a lotion.

division Raw material name Example 7 Water Part 1. The number of tablets To 100 2. Stabilized Composition (Example 4) 30 3. Preservative Quantity 4. Carbomer 0.20 5. Xanthan Gum 0.05 Yu Sang Part 6. Cetostearyl Alcohol 1.0 7. Self-emulsifying glycerin monostearate 1.0 8. Sorbent monostearate (1) 0.5 9.Glyceryl Monostearate (POE40) (2) 1.0 10. Liquid paraffin 4.0 11.Squalane 4.0 12. Cetyl Octanoate 6.0 13. Vaseline 0.5 14. Beads wax 0.3 corrector 15. Triethanolamine 0.2 additive 16. Incense Quantity

          Note) (1) Product Name: Ar-60 (ICI, USA)

               (2) Product Name: My-52 (ICI, USA)

Example 8

Manufacture of cream

By the composition ratio shown in the following Table 12 1 to 5 paragraphs After dissolving the water phase parts and the oil phase parts of 6 to 14 to 75-80 ° C. to completely dissolve them, the oil phase parts were slowly added to the water phase parts and emulsified at 3000 rpm at 75 to 80 ° C. for 5 minutes. During the emulsification, the neutralizing agent of claim 15 was added and neutralized. After the first emulsification was cooled, the flavor and additives of claim 16 were added at 50 to 55 ° C and emulsified for 2 minutes at 3000 rpm with a homomixer for 2 minutes and then cooled to 27 to 30 ° C to prepare a cream.

division Raw material name Example 8 Water Part 1. The number of tablets To 100 2. Stabilized Composition (Example 4) 40 3. Preservative Quantity 4. Carbomer 0.30 5. Xanthan Gum 0.05  Yu Sang Part 6. Cetostearyl Alcohol 1.5 7. Self-emulsifying glycerin monostearate 2.0 8. Sorbent monostearate (1) 1.0 9.Glyceryl Monostearate (POE40) (2) 1.5 10. Liquid paraffin 6.0 11.Squalane 5.0 12. Cetyl Octanoate 5.0 13. Vaseline 0.5 14. Beads wax 1.6 corrector 15. Triethanolamine 0.3 additive 16. Incense Quantity

Example 9

Preparation of Essence

By the composition ratio shown in the following Table 13 1 to 5 paragraphs After completely dissolving the water phase parts and 6-10 oil phase parts to 75-80 ° C., the oil phase parts were slowly added to the water phase parts and emulsified at 3000 rpm at 75-80 ° C. for 5 minutes. During the emulsification, the neutralizing agent of claim 11 was added and neutralized. After completion of the first emulsification, the 12th fragrance and additives were added at 50 to 55 ° C, and then emulsified for 2 minutes at 3000 rpm with a homomixer for 3 minutes, and then cooled to 27 to 30 ° C to prepare an essence.

division Raw material name Example 9 Award part 1. Purified water To 100 2. Stabilized Composition (Example 4) 45 3. Preservative Quantity 4. Carbomer 0.40 5. Xanthan Gum 0.10 Paid parts 6. Cetostearyl Alcohol 1.20 7. Self-emulsifying glycerin monostearate 1.00 8. Hydroxy caster oil POE (60) 1.00 9. Cetyl Octanoate 5.00 10. Cyclomethicone 3.00 corrector 11.Triethanolamine 0.40 additive 12. Incense Quantity

As described above, according to the present invention, a high content of resveratrol or alpha-lipoic acid, which is a highly functional substance having excellent antioxidant effect, can be maintained for a long time. That is, the present invention may contain up to 15% by weight of resveratrol or alpha-lipoic acid in the cosmetic composition, and solves problems such as discoloration, discoloration phenomenon and crystal precipitation in the composition for a long time, and continuously excellent antioxidant for a long time. It can provide the effect and reduce the irritation to the skin.

Claims (6)

0.001 to 10.0% by weight of the active ingredient having at least one antioxidant activity selected from resveratrol and alpha-lipoic acid, 0.01 to 15% by weight of one or more stabilizers selected from the white and yellow extracts, and cyclodextrin as an inclusion agent. Cosmetic composition comprising 50% by weight and the residual solvent. The cosmetic composition according to claim 1, wherein the cyclodextrin is hydroxypropyl beta cyclodextrin. delete delete a) mixing the solvent and the inclusion agent; b) adding resveratrol, alpha-lipoic acid or a mixture thereof to the mixture prepared in step a) and mixing; And c) adding and mixing a stabilizer comprising a yellow white extract, an alteromonas ferment extract, or a mixture thereof to the mixture prepared in step b). A method of making a cosmetic composition according to claim 1. delete