KR102339804B1 - Manufacturing method for more enhancing stability by encapsulating active ingredients in a liposome structure formed as a multilayer in a molecular clustering state, and a cosmetic composition containing the same - Google Patents

Abstract

The present invention relates to a liposome, which is formed in multiple layers by injecting carbon dioxide into a mixture containing hydrogenated phosphatidylcholine, hydrogenated phosphatidylinositol, hydrogenated sucrose dystearate, and potassium phosphate and dissolving the mixture in a molecular clustering state, and a cosmetic composition containing the same. Through this, the present invention forms a stable multilayer liposome, manufactures the cosmetic composition containing the liposome for stably encapsulating various encapsulated components, and provides excellent skin percutaneous absorption, a skin moisturizing effect, and antioxidant ability and skin elasticity improving effects by securing long-term stability.

Description

A manufacturing method for further enhancing stability by encapsulating an active ingredient in a multilayered liposome structure in a molecular clustering state, and a cosmetic composition containing the same, and a cosmetic composition containing the same. clustering state, and a cosmetic composition containing the same}

The present invention relates to a manufacturing method in which a liposome structure is formed as a multilayer in a molecular clustering state, and an active ingredient (a component to be encapsulated) is encapsulated therein to increase stability, and a cosmetic composition containing the same, and more specifically to a hydrogenated By injecting carbon dioxide into a mixture containing phosphatidylcholine, hydrogenated phosphatidylinositol, hydrogenated sucrose distearate, and potassium phosphate, it is dissolved in a molecular clustering state to form a multi-layered liposome and a cosmetic composition containing the same. .

In traditional liposomes, phospholipids are placed in an organic solvent and dissolved by heating, then the active ingredient is added and encapsulated, and heated to a high temperature in the process of removing the organic solvent by heating. there will be no In addition, the complete removal of organic solvents corresponding to poisons has also been a stumbling block.

In addition, lipid components such as cholesterol and egg yolk lecithin obtained from egg yolk have been used as surfactants for forming conventional liposomes. Many studies are known. Since these formulations have to use a high-temperature process, they are also thermodynamically unstable, and their potency drops a lot over time, which may cause unexpected side effects on the skin.

On the other hand, the technology for forming liposomes using the molecular clustering method has not been studied much, and it is difficult to find a technology for forming a multi-layered lamellar endoplasmic reticulum by injecting carbon dioxide gas without any organic solvent to create a molecular clustering state. , further research is needed.

Republic of Korea Patent Registration No. 10-1321346 (Registration date: October 17, 2013) relates to a cosmetic composition containing a low-temperature process liposome containing a human stem cell culture medium extract, and a carbon dioxide supercritical state by mixing lecithin and water. It is described about low-temperature process liposomes that form reverse mile cells and stabilize human-derived stem cell culture extracts. Republic of Korea Patent No. 10-2177196 (registration date: 2020.11.04.) is a multi-layered lamellar niosome formed by nano-particle formation and formed as giant niosomes in a supercritical state, and a cosmetic composition containing the same to enhance percutaneous absorption And to a method for producing the same, after dissolving a complex nonionic surfactant in a supercritical state and adding an active ingredient, a large multi-layered niosome formed in a subcritical state coexisting with carbon dioxide is continuously applied to a high-pressure microfluidizer It passes through to prepare a nano-multilayer lamellar niosome, and it is described with respect to a cosmetic composition with improved percutaneous absorption including this.

The present invention relates to a liposome formed into a multilayer by dissolving in a molecular clustering state by injecting carbon dioxide into a mixture containing hydrogenated phosphatidylcholine, hydrogenated phosphatidylinositol, hydrogenated sucrose distearate, and potassium phosphate, and a cosmetic composition containing the same develop and provide. That is, without using a toxic organic solvent, carbon dioxide gas is injected at a low temperature to form a multi-layered liposome in a molecular clustering state, and various encapsulation target components are encapsulated to make a more stable liposome.

In the present invention, by injecting carbon dioxide into a mixture containing all of hydrogenated phosphatidylcholine, hydrogenated phosphatidylinositol, hydrogenated sucrose distearate, and potassium phosphate, the molecular clustering state in which the mixture is dissolved in carbon dioxide in a molecular state is obtained dissolving so as to (a); After dissolving the step (a), after adding the component to be encapsulated, stirring step (b); After the step (b), dispersing in a hydrophilic solvent to form a multi-layered liposome (c); And after the step (c), passing through a high-pressure microfluidizer to form a multi-layered nano-liposome (d); provides a method for producing a multi-layered nano-liposome comprising the.

On the other hand, in the method for producing a multilayer nanoliposome of the present invention, the component to be encapsulated in step (b) is, for example, ethyl ascorbic acid, ascorbic acid and its derivatives, tocopherol. (tocopherol) and its derivatives, retinol and its derivatives, adenosine, cordycepin, niacinamide, idebenone, alpha lipoic acid, catechin , kinetin, allantoin, dipotassium glycyrrhizate, carnitine, centella asiatica extract, lutein, astaxanthin ( astaxanthine), coenzyme Q10, ursolic acid, hot spring water, and deep sea water may be encapsulated together with any one or two or more.

On the other hand, in the manufacturing method of the multilayer nano-liposome of the present invention, the hydrophilic solvent of step (c) is preferably any one or more selected from purified water, glycerol, butylene glycol, and dipropylene glycol. .

On the other hand, in the method for producing a multi-layered nano-liposome of the present invention, the method for producing the multi-layered nano-liposome may be to remove carbon dioxide, preferably between steps (c) and (d).

On the other hand, in the method for producing a multilayer nanoliposome of the present invention, the high-pressure microfluidizer of step (d) is preferably at a temperature of -10 to 30° C., a pressure of 10 to 5,000 bar, and the number of passes 1 to 10 times. It may have a driving condition.

In the present invention, carbon dioxide is injected into a mixture containing hydrogenated phosphatidylcholine, hydrogenated phosphatidylinositol, hydrogenated sucrose distearate, and potassium phosphate to dissolve in molecular clustering state to form a more stable multi-layered liposome. In addition, it is possible to prepare a cosmetic composition containing a liposome that more stably encapsulates various components to be encapsulated, and by securing its long-term stability, excellent skin percutaneous absorption, skin moisturizing effect, antioxidant ability and skin elasticity improvement effect can be exhibited. .

1 is a picture (a) showing the molecular structure of the components of the mixture of the present invention (a) and a picture (b) showing the finished mixture.
Figure 2 is a schematic diagram showing the stable formation of a multi-layered liposome vesicles in a molecular clustering state.
3 is a schematic diagram showing that the mixture is dissolved in a molecular clustering state to form a compound to form a liposome endoplasmic reticulum.
Figure 4 is a schematic diagram showing the phenomenon that the lipophilic active ingredient and the hydrophilic active ingredient is encapsulated in the multi-layered liposome vesicles in a molecular clustering state.
Figure 5 is a diagram showing the path through which the multi-layered liposome vesicles prepared in the present invention penetrate into the skin.
6 is a photograph showing the appearance of an example of the multilayer liposome of the present invention in which the component to be encapsulated is stably encapsulated.
7 is a photograph showing an example of the multilayered liposome of the present invention through analysis with an electron microscope, Cryo-TEM.
8 is a graph showing the results of a comparative experiment on the long-term stability of the multilayer liposome of the present invention and the general liposome.
9 is a graph showing the results of a comparative experiment on the percutaneous absorption capacity of the multilayer liposome of the present invention and the general liposome.
10 is a graph showing the results of a comparative experiment on the skin moisturizing effect of the multilayer liposome of the present invention and the general liposome.
11 is a graph showing the results of a comparative experiment on the antioxidant efficacy of the ABTS method of the multilayer liposome of the present invention and the general liposome.
12 is a graph showing the results of a comparative experiment on skin elasticity between the multilayer liposome and the general liposome of the present invention.

Traditional liposomes use phospholipids and put them in an organic solvent to dissolve them by heating, then put the active ingredients and encapsulate them, and then heat them to a high temperature in the process of removing the organic solvent by heating. In this case, the active ingredient is destroyed or decomposed by high temperature, so that its efficacy cannot be properly exhibited, and it is difficult to completely remove the organic solvent corresponding to the poison. In addition, it is known to use lipid components such as cholesterol and egg yolk lecithin obtained from egg yolk as a surfactant for forming liposomes, or lecithin extracted from soybeans and their derivatives. There is a problem that it becomes thermodynamically unstable, such as causing odor, and its potency drops a lot over time, which can cause unexpected side effects on the skin.

On the other hand, until now, there have not been many studies on the technology of forming liposomes using the molecular clustering method, and the technology of forming a multi-layered lamellar endoplasmic reticulum by injecting carbon dioxide gas without any organic solvent to create a molecular clustering state. It is difficult to see, and further research is needed. Therefore, in the present invention, diligent efforts were made to solve the problems of existing liposome-making technologies, and problems such as destruction of active ingredients due to high temperature and instability of liposomes were solved by using carbon dioxide gas without using toxic organic solvents. , it was possible to prepare a multi-layered liposome that more stably encapsulates the component to be encapsulated.

The present inventor further improved stability by using hydrogenated (hydrogenated) vegetable phospholipids in order to have technological differentiation from the previous Patent No. 10-2177196 (registration date: 2020.11.04), and the molecular clustering state It is designed to be easy to make. Therefore, it can be said that it is an important key point of the present invention to use the main surfactant by hydrogenating it.

Specifically, in the previous patent, the name niosome was used because it forms a similar liposome rather than a liposome by using only a nonionic surfactant. By preventing discoloration and acid waste of the mixed surfactant through hydrogenation and forming more stable, clean multi-layered liposomes in a low-temperature molecular clustering state, a unique technology different from previous patents was devised.

In order to help the understanding of the present invention, a mechanistic explanation of how a stable vegetable mixed surfactant capable of forming liposomes in molecular clustering conditions forms multi-layered liposomes. First, hydrogenated phosphatidylcholine and hydrogenated phosphatidyl inositol were developed to make multi-layered liposomes. This component made by hydrogenation (hydrogenation) has the characteristic of being stably maintained even in the presence of _{oxygen (O 2} ), carbon dioxide (CO _{2 ), and hydroxyl groups (OH-).} Specifically, looking at the molecular structure of these components, it was found that molecules in which choline or inositol-type molecules are bound to the tail group with two alkyl chains spontaneously form a multi-layered structure when dispersed in water or glycerol. . Here, by mixing hydrogenated sucrose distearate, it was packed into a multi-layered membrane to further enhance stability. In addition, a mixture containing potassium phosphate was found to have a function of further strengthening the bonding of the mixed surfactant by packing it into a multilayer wall film, and based on this result, a mixed surfactant containing all of these components was developed. Here, 'molecular clustering state' means that the mixed surfactant is dissolved in a molecular state by injecting carbon dioxide, and an encapsulation active material (component to be encapsulated) is added thereto and encapsulated in a molecular clustering state to form a multi-layered liposome structure. can do.

Accordingly, the present invention injects carbon dioxide into a mixture containing all of hydrogenated phosphatidylcholine, hydrogenated phosphatidylinositol, hydrogenated sucrose distearate, and potassium phosphate, and the mixture is molecular clustering in which it is dissolved in carbon dioxide. dissolving to a state (a); After dissolving the step (a), after adding the component to be encapsulated, stirring step (b); After the step (b), dispersing in a hydrophilic solvent to form a multi-layered liposome (c); And after the step (c), passing through a high-pressure microfluidizer to form a multi-layered nano-liposome (d); provides a method for producing a multi-layered nano-liposome comprising the.

On the other hand, in step (a) of the present invention, the mixture is preferably a mixture of hydrogenated phosphatidylcholine and hydrogenated phosphatidylinositol in a ratio of 2:1, more preferably 46 to 60% by weight of hydrogenate. Tied phosphatidylcholine, 23 to 30% by weight of hydrogenated phosphatidylinositol, 8 to 21% by weight of hydrogenated sucrose distearate, and 2 to 10% by weight of potassium phosphate are mixed and used. By mixing and using the composition as described above, a more stable liposome formulation in the molecular clustering state could be completed in the present invention.

On the other hand, in step (a) of the present invention, the mixing temperature in the molecular clustering state dissolution tank is preferably -10 to 30° C., the pressure 50 to 700 bar (more preferably 100 to 300 bar), and the stirring speed in the reaction tank is 10 It is recommended to stir at ~5,000 rpm. Through this, an irregular state with a particle size distribution of 0.1 to 50 μm is formed in the molecular clustering state.

Hydrogenated phosphatidylcholine is a raw material obtained by additional hydrogenation of phosphatidylcholine, and is widely used as a skin conditioning agent. In addition, hydrogenated phosphatidylinositol is a raw material obtained by further hydrogenating phosphatidylinositol. In addition, hydrogenated sucrose distearate is a raw material obtained by further hydrogenating sucrose distearate, and sucrose distearate is also widely used as a skin conditioning agent. In addition, potassium phosphate is another name for potassium phosphate, and is often used as a pH adjuster due to its basicity. In the present invention, hydrogenated phosphatidylcholine and hydrogenated phosphatidylinositol are used as surfactants for forming stable liposomes, and hydrogenated sucrose dithearate and potassium phosphate are used as liposome-forming auxiliary components to prepare a more stable liposome formulation. completed. The characteristic of this mixture is that when carbon dioxide is injected into the mixer, it is easily dissolved to create a molecular clustering state. It is an important point to dissolve to form multi-layered liposomes without a separate heating process.

On the other hand, in step (b) of the present invention, the component to be encapsulated is, for example, ethyl ascorbic acid, ascorbic acid and its derivatives, tocopherol and its derivatives, retinol (retinol) and its derivatives, adenosine, cordycepin, niacinamide, idebenone, alpha lipoic acid, catechin, kinetin, Allantoin, dipotassium glycyrrhizate, carnitine, centella asiatica extract, lutein, astaxanthine, coenzyme Q10 , ursolic acid, hot spring water, and deep sea water may be encapsulated together with any one or two or more.

On the other hand, in step (c) of the present invention, the hydrophilic solvent is preferably purified water, ethanol, glycerol, butylene glycol, dipropylene glycol, pentylene glycol, propylene glycol, methyl propane diol, It is preferable that at least one selected from methylgluceth-20, and more preferably at least one selected from purified water, ethanol, glycerol, butylene glycol, and dipropylene glycol.

On the other hand, in the method for producing a multi-layered nano-liposome of the present invention, the method for producing the multi-layered nano-liposome may be to remove carbon dioxide, preferably between steps (c) and (d). At this time, a method for removing carbon dioxide is not limited as long as it is known in the art, but a method for removing carbon dioxide by removing pressure was used.

On the other hand, in step (d) of the present invention, the high-pressure microfluidizer may preferably have a temperature of -10 to 30° C., a pressure of 10 to 2,000 bar, and operating conditions of 1 to 10 passages, More preferably, it is good to have a temperature of -5 to 25° C., a pressure of 50 to 300 bar, and operating conditions of 2 to 6 passages. Through this, it can be prepared homogeneously into nanoliposomes of 30 to 1200 nm in an irregular state with a particle size distribution of 0.1 to 50 μm. Finally, after completing the nano-multilayered liposome, it is obtained, and any method used in the art may be used.

On the other hand, according to the following experiment, the multilayer liposome prepared in the present invention was superior in long-term stability compared to when using the liposome prepared by the general method using the conventional phospholipid base, appearance, purity, transdermal absorption, skin moisturizing, antioxidant The efficacy and elasticity were excellent. In addition, the present invention was able to prepare multi-layered liposomes stably encapsulating various components to be encapsulated. Therefore, the present invention can make liposomes without a high-temperature process, thereby improving the stability of thermodynamically unstable ingredients to be encapsulated, and producing multi-layered liposomes with excellent skin functionality without using toxic organic solvents, thereby providing various cosmetic industries and dermatological sciences. It is considered to be able to contribute to the research.

Hereinafter, the content of the present invention will be described in more detail through the following Examples and Experimental Examples. However, the scope of the present invention is not limited only to the following examples, and includes modifications of technical ideas equivalent thereto.

[Examples 1 to 15: Preparation of multi-layered liposomes formed in molecular clustering state]

In this example, multi-layered liposomes formed in molecular clustering were prepared.

1) Preparation of a composition of a mixed surfactant comprising the mixture of the present invention

In Examples 1 to 3, instead of the general phospholipid base, hydrogenated phosphatidylcholine, hydrogenated phosphatidylinositol, hydrogenated sucrose distearate, and potassium phosphate were mixed and used based on 100% by weight of the total weight. Figure 1a shows the molecular structure of the components used. Looking at their structures, it can be seen that two alkyl chains are bonded to the hydrophilic head group, and only potassium phosphate has phosphoric acid bonded to the potassium ion. Looking at these structures, the components of hydrogenated phosphatidylcholine and hydrogenated phosphatidylinositol were selected as phospholipid components for forming liposome vesicles, so that stable liposomes can be formed in a molecular clustering state. Here, the hydrogenated sucrose distearate-formed liposome wall membrane further stably strengthened, and potassium phosphate crosslinked the multi-layered membrane wall membrane to further improve stability. Specific compositions are shown in Table 1, and Comparative Examples 1 to 3, which are general phospholipid bases, were prepared for comparison. Figure 1b is a photograph showing the finished mixture.

division Ingredient name Example (wt%) One 2 3 One Hydrogenated Phosphatidylcholine 46 50 60 2 Hydrogenated phosphatidylinositol 23 25 30 3 Hydrogenated Sucrose Distearate 21 20 8 4 potassium phosphate 10 5 2 sub Total 100 100 100 Exterior pale yellow pale yellow pale yellow appearance flake flake flake surface activity Good Good Good HLB 12.5 13.8 14.2

division Ingredient name Comparative example (wt%) One 2 3 One yolk phospholipid 10 60 100 2 animal-derived cholesterol 5 30 50 sub Total 15 90 150 Exterior pale yellow pale yellow pale yellow appearance powder powder powder

2) Preparation of multi-layered liposomes in molecular clustering state

The mixture of Example 2 was added and dissolved in carbon dioxide in a molecular clustering state. After that, the encapsulation target component to be added was added and stirred to form liposomes. Thereafter, the formed liposomes were dispersed in a hydrophilic solvent and passed through a high-pressure microfluidizer to prepare multi-layered nano-liposomes. The basic composition was shown in Table 3.

division Ingredient name Example (wt%) 4 5 6 7 8 One Example 2 0.1 One 3 5 10 2 glycerol 10 10 30 - 20 3 Butylene Glycol 10 20 - 10 10 4 dipropylene glycol 10 - - 20 10 5 Purified water 69.9 69 67 65 50 sub Total 100 100 100 100 100 Exterior milk white milk white milk white milk white milk white appearance liquid emulsion liquid emulsion liquid emulsion cream emulsion cream emulsion Formation of liposomes △ ○ ◎ ○ ○

Specifically, as the component to be encapsulated, ethyl ascorbic acid, ascorbic acid and its derivatives, tocopherol and its derivatives, retinol and its derivatives, adenosine ), cordycepin, niacinamide, idebenone, alpha lipoic acid, catechin, kinetin, allantoin, dipotassium glycyrrhizide hedge Dipotassium glycyrrhizate, carnitine, centella asiatica extract, lutein, astaxanthine, coenzyme Q10, ursolic acid, hot spring water One or two or more of hot spring water) and deep sea water were selected and used.

In addition, when the mixing temperature in the molecular clustering dissolution tank was 20° C., the pressure 180 bar, and the stirring speed in the reaction tank was 2,000 rpm, molecular clustering was achieved and irregular liposomes with a particle size distribution of 12 μm were formed. Thereafter, a 235 nm nano-liposome structure was formed by passing it through a high-pressure microfluidizer three times.

Figure 2 is a schematic diagram showing the stable formation of a multi-layered liposome endoplasmic reticulum in a molecular clustering state. It can be seen that the surfactant is mixed to form a multilayer.

3 is a schematic diagram showing that the mixture is dissolved in a molecular clustering state to form a compound to form a liposome endoplasmic reticulum. As in the schematic diagram, when the surfactant is left standing without stirring in the molecular clustering state, a linear multi-layer structure is formed, and when it is stirred under the same conditions as above, a multi-layered endoplasmic reticulum is made like a spherical micellar.

Figure 4 is a schematic diagram showing the phenomenon that the lipophilic active ingredient and the hydrophilic active ingredient is encapsulated in the multi-layered liposome vesicles in a molecular clustering state. 5 is a diagram showing the path through which the multi-layered liposome vesicles prepared in the present invention penetrate into the skin, and skin absorption is made in this way.

3) Check the solubility of the mixture

An experiment was performed to confirm the solubility of the mixtures of Examples 1 to 3, and the results are shown in Table 4 below. For comparison, Comparative Examples 1 to 3 were also tested. At this time, the experiment was performed at a carbon dioxide injection pressure of 50 to 200 bar.

division Ingredient name Example (wt%) Comparative example (wt%) 9 10 11 4 5 6 One CO2 gas injection pressure (bar) 50 150 200 50 150 200 2 [Example 1] 10g - - - - - 3 [Example 2] - 10g - - - - 4 [Example 3] - - 10g - - - 5 [Comparative Example 1] - - - 10g - - 6 [Comparative Example 2] - - - - 10g - 7 [Comparative Example 3] - - - - - 10g stirring time 90 minutes 90 minutes 90 minutes 90 minutes 90 minutes 90 minutes result insoluble dissolved dissolved insoluble insoluble insoluble

4) Preparation of multi-layered liposomes in molecular clustering state and confirmation of their formation (C0 ₂ gas injection pressure condition change)

Additionally, by varying the carbon dioxide gas injection pressure to 100 to 500 bar, it was confirmed whether multi-layered liposomes were formed using Example 2, and detailed compositions and results are shown in Table 5 below.

division Ingredient name Example (wt%) Comparative Example 7 (wt%) 12 13 14 15 Comparative Example 4 One [Example 2] One 2 3 5 - 2 [Comparative Example 3] - - - - 2 3 glycerol 30 30 30 30 30 4 Butylene Glycol 5 - 5 5 - 5 dipropylene glycol 7 - 7 7 - 6 Purified water 57 68 55 53 68 sub Total 100 100 100 100 100 set temperature 0~25℃ 0~25℃ 0~25℃ 0~25℃ 98℃ CO ₂ gas injection pressure (bar) 100 150 200 500 - Whether multi-layered liposomes are formed formed formed formed formed formed stability stability stability stability stability Instability

As a result, it was confirmed that Examples 12 to 15 in which 1 to 5% by weight of the mixed surfactant was used were well formed in multi-layered liposomes, and it was confirmed that there was stability unlike Comparative Example 7 in which a general phospholipid base was used.

[Examples 16 to 24: Preparation of a composition containing a multi-layered liposome encapsulating a component to be encapsulated using Example 2]

In this example, a composition containing a multi-layered liposome encapsulating an active ingredient was prepared by using the mixed surfactant of Example 2 prepared above. Detailed composition and results are It is shown in Tables 6 and 7 below.

division Ingredient name Example
(weight%) 16 17 18 19 20 21 22 23 One [Example 2] 2 2 2 3 3 3 5 10 2 glycerol 30 30 30 30 30 30 30 30 3 Purified water 60 49 64.5 64 64.5 62 58.2 47.1 4 Genistein 3 - - - - - One - 5 Daidzein 2 - - - - - 0.1 - 6 Quercetin 3 - - - - One - - 7 pure retinol - 5 - - - - - - 8 Ethyl Ascorbic Acid - 5 - - - - - One 9 Ascorbic Acid - 5 - - - - - 3 10 tocopherol - 2 - - - - 0.5 One 11 fisetin - 2 - - - One One One 12 Adenosine or Cordycepin - - 0.5 - - - One One 13 Nicinamide - - 2 - - - One One 14 Idebenone or Alpha Lipoic Acid - - One - - - - One 15 Centella asiatica quantitative extract - - - 2 - - One One 16 lutein or biotin - - - One - - - One 17 astaxanthin - - - - 0.5 - One One 18 Coenzyme Q10 - - - - One - 0.2 0.2 19 ursolic acid - - - - One - - 0.5 20 Salicylic Acid - - - - - 2 - 0.1 21 menthol or panthenol - - - - - One - 0.1 sub Total 100 100 100 100 100 100 100 100 CO ₂ gas injection pressure (bar) 120 150 200 300 400 500 600 700 Temperature (℃) 0-25 0-25 0-25 0-25 0-25 0-25 0-25 0-25 Formation of liposomes formed formed formed formed formed formed formed formed stability Good Good Good Good Good Good Good Good

division Ingredient name Example (wt%) Comparative example (wt%) 24 8 One [Example 2] 2 - 2 [Comparative Example 3] - 2 3 retinol One One 4 Genistein One One 5 glycerol 10 10 6 Butylene Glycol 5 5 7 dipropylene glycol One One 8 Purified water 80 80 sub Total 100 100 CO ₂ gas injection pressure (bar) 150 - Temperature (℃) 0-25 90-98 Formation of liposomes formed formed particle size distribution 320 nm 580 cm pH 6.3 7.2 appearance Liquid Liquid

As a result, as shown in Table 6, it was confirmed that the multi-layered liposomes encapsulated in various encapsulation target components in Examples 16 to 23 were stably well formed. In addition, compared with Comparative Example 8 of the general phospholipid base in Table 7, it was confirmed that in Example 24, 320 nm liposomes were stably well formed. 6 is a view showing the appearance of the final product in which the active ingredient of Example 24 is stably encapsulated, and although it looks like a milky white color, it has a blue color when spread out on a plate, so it can be seen that the particles are small in size. 7 is a photograph of Example 24 analyzed by an electron microscope, Cryo-TEM, and it was confirmed that a multi-layered liposome vesicle was stably formed.

[Examples 25 to 27: Preparation of a cosmetic composition (skin essence) containing the multi-layered liposome of the present invention]

In this example, a cosmetic composition containing the multi-layered liposome composition (Examples 16 to 18) prepared above was prepared. As an example, skin essence was prepared and the detailed composition was shown in Table 8 below.

division Ingredient name Example 25
(wt%) Example 26
(wt%) Example 27
(wt%) Awards dipropylene glycol 2 2 2 glycerin 3 3 3 1,3-butylene glycol 5 5 5 1,2-Hexanediol 2 2 2 Ethylhexylglycerin 0.1 0.1 0.1 betaine One One One Ilantoin 0.1 0.1 0.1 EDTA-2Na 0.1 0.1 0.1 transparent xanthan gum `0.5 0.5 0.5 Purified water 81.83 79.83 79.83 solubilization Polyglyceryl-10 Oleate 0.5 0.5 0.5 Spices 0.05 0.05 0.05 adding Sodium Hyaluronate 0.02 0.02 0.02 [Example 16] 3 - - [Example 17] - 5 - [Example 18] - - 5 xanthan gum 0.1 0.1 0.1 Centella asiatica leaf extract 0.1 0.1 0.1 Aloe Vera Leaf Extract 0.3 0.3 0.3 green tea extract 0.2 0.2 0.2 sodium citrate 0.1 0.1 0.1 sub Total 100 100 100

[Examples 28 to 29: Preparation of a cosmetic composition (emulsifying cream) containing the multi-layered liposome of the present invention]

In this example, a cosmetic composition containing the multi-layered liposome composition (Examples 20 and 23) prepared above was prepared. As an example, an emulsified cream was prepared and the detailed composition was shown in Table 9 below.

division Ingredient name Example 28
(wt%) Example 29
(wt%) Awards Methyl glucose-20 3 3 glycerin 5 5 1,3-butylene glycol 3 3 Ethylhexylglycerin 0.1 0.1 1,2-Hexanediol 2 2 Carbomer 0.4 0.4 xanthan gum 0.2 0.2 EDTA-2Na 5 5 Purified water 53 52.85 paid ceteyl alcohol 3 3 Stearic Acid 2 2 beeswax 2 2 Polyglyceryl-10 Oleate/Polyglyceryl-10 Stearate 3 3 organic argan oil 3 3 organic macadamia oil 2 2 organic grapeseed oil 2 2 Cetylethylhexanoate 2 2 triethylhexanoin 3 3 natural tocopherol 0.1 0.1 neutralization L-Arginine 0.5 0.5 adding Centella asiatica leaf extract 0.3 0.3 [Example 20] 5 - [Example 23] - 5 cucumber extract 0.1 0.1 Red Ginseng Extract 0.2 0.2 Purslane Extract 0.1 0.2 Spices 0.05 0.05 sub Total 100 100

[Experimental Example 1: Long-term stability test of multi-layered liposomes prepared in molecular clustering state of the present invention]

In this experimental example, the long-term stability of the multilayer liposome prepared in molecular clustering state using a surfactant-containing mixture (Example 24) and the liposome prepared by the general method using a phospholipid base (Comparative Example 8) was compared.

As a result, the liposome prepared by the general method using a phospholipid base (Comparative Example 8) had a strong odor, and the base was corroded due to a brown change phenomenon and was unstable, but the multilayer prepared in the molecular clustering state of the present invention In the liposome (Example 24), it was confirmed that the content of the main component was 98% or more, so that it was significantly stable in terms of odor, discoloration, etc. (FIG. 8). It can be considered that the reason for this is that the formation of liposomes in the molecular clustering state at a low temperature and the invention of a hydrogenated mixed surfactant were the main factors, and it can be considered that more stable liposomes were made by using this.

[Experimental Example 2: Transdermal absorption test of multi-layered liposomes prepared in molecular clustering state of the present invention]

In this experimental example, the percutaneous absorption capacity of the multilayer liposome prepared in molecular clustering state using a surfactant-containing mixture (Example 24) and the liposome prepared by the general method using a phospholipid base (Comparative Example 8) was compared.

As a result, the transdermal absorption of the multi-layered liposome (Example 24) prepared in the molecular clustering state of the present invention is significantly superior to that of the liposome prepared by the general method using a phospholipid base as shown in FIG. 9 (Comparative Example 8) could confirm that

[Experimental Example 3: Evaluation of skin moisturizing, antioxidant efficacy and skin elasticity of multi-layered liposomes prepared in molecular clustering state of the present invention]

In this experimental example, the skin moisturizing, antioxidant and skin elasticity of the multilayer liposome (Example 24) prepared in molecular clustering state using a surfactant-containing mixture and the liposome prepared by the general method using a phospholipid base (Comparative Example 8) were compared.

1) Evaluation of skin moisturizing effect

The skin moisturizing efficacy of the multi-layered liposome (Example 24) prepared in molecular clustering state using a surfactant-containing mixture and the liposome prepared by the general method using a phospholipid base (Comparative Example 8) was compared. As a result, the multilayer liposome (Example 24) prepared in the molecular clustering state of the present invention compared to the liposome prepared by the general method (Comparative Example 8) using a phospholipid base as shown in FIG. Significantly, it was confirmed that the skin moisturizing effect was excellent.

2) Antioxidant efficacy evaluation

The antioxidant efficacy of multilayer liposomes prepared in molecular clustering state using a surfactant-containing mixture (Example 24) and liposomes prepared by a general method using a phospholipid base (Comparative Example 8) were compared. As a result, as shown in FIG. 11, the multi-layered liposome (Example 24) prepared in the molecular clustering state of the present invention compared to the liposome prepared by a general method using a phospholipid base (Comparative Example 8) was encapsulated with retinol, a component, In all genistein, it was confirmed that the antioxidant effect was significantly significantly superior with the passage of time.

3) Evaluation of skin elasticity

The skin elasticity of the multi-layered liposome (Example 24) prepared in molecular clustering state using a surfactant-containing mixture and the liposome prepared by the general method using a phospholipid base (Comparative Example 8) was compared. As a result, the multilayer liposome (Example 24) prepared in the molecular clustering state of the present invention compared to the liposome prepared by the general method (Comparative Example 8) using a phospholipid base as shown in FIG. 12 has significantly superior skin elasticity was able to confirm

Claims (5)

By injecting carbon dioxide into a mixture containing all of the hydrogenated phosphatidylcholine, hydrogenated phosphatidylinositol, hydrogenated sucrose distearate, and potassium phosphate, the mixture is dissolved in a molecular clustering state in which it is dissolved in carbon dioxide step (a);
After dissolving the step (a), after adding the component to be encapsulated, stirring step (b);
After the step (b), dispersing in a hydrophilic solvent to form a multi-layered liposome (c); and
After the step (c), passing through a high-pressure microfluidizer to form a multi-layered nano-liposome (d);
According to claim 1,
The component to be encapsulated in step (b) is,
Ethyl ascorbic acid, ascorbic acid and its derivatives, tocopherol and its derivatives, retinol and its derivatives, adenosine, cordycepin, niacinamide (niacinamide), idebenone, alpha lipoic acid, catechin, kinetin, allantoin, dipotassium glycyrrhizate, carnitine , centella asiatica extract, lutein, astaxanthine, coenzyme Q10, ursolic acid, hot spring water, deep sea water water), any one or two or more selected from the manufacturing method of multi-layered nano-liposomes, characterized in that encapsulated together.
According to claim 1,
The hydrophilic solvent of step (c) is,
Purified water, glycerol, butylene glycol, a method for producing a multi-layered liposome, characterized in that at least one selected from dipropylene glycol.
According to claim 1,
The method for preparing the multi-layered nano liposome is,
Between the steps (c) and (d), a method for producing a multi-layered nano-liposome, characterized in that carbon dioxide is removed.
According to claim 1,
The high-pressure microfluidizer of step (d),
A method for producing multi-layered liposomes, characterized in that the operating conditions are a temperature of -10 to 30° C., a pressure of 10 to 5,000 bar, and 1 to 10 passages.

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