CN118161418B - Moisturizing and whitening liposome essence and preparation method thereof - Google Patents

Abstract

The invention provides a moisturizing and whitening liposome essence and a preparation method thereof, and relates to the field of cosmetics. The invention provides a moisturizing and whitening liposome essence, which comprises the following components: acid-modified liposome solutions and salt-modified liposome solutions; acid-modified liposomes include cationic liposomes and acids electrostatically adsorbed onto the cationic liposomes; salt-modified liposomes include anionic liposomes and salts electrostatically adsorbed onto the anionic liposomes; according to the invention, the acid modified cationic liposome and the salt modified anionic liposome are respectively prepared according to the electrostatic adsorption principle, wherein the active ingredients with whitening and moisturizing effects are encapsulated in the liposome, and the active ingredients and the salt modified cationic liposome are stored independently without generating gas, can realize gas release under specific conditions only when being mixed for use, can promote the permeation of the active ingredients to the deep layer of the skin under the pushing of bubbles, and are simple and efficient.

Description

Moisturizing and whitening liposome essence and preparation method thereof

Technical Field

The invention relates to the field of cosmetics, in particular to a moisturizing and whitening liposome essence and a preparation method thereof.

Background technique

The existence of the stratum corneum can provide a strong barrier to external damage to the skin, but it also blocks the percutaneous absorption of many effective ingredients. How to overcome the barrier function of the stratum corneum to increase the percutaneous absorption of skin care ingredients has become a research hotspot in the field of medical cosmetology. To this end, people have made many efforts, such as using chemical penetration enhancers such as azone and adding small molecule transdermal peptides, but the amount of these ingredients added is limited, and the transdermal effect is also limited. Other methods, such as using physical means such as ultrasound, radio frequency, and electroporation, can create tiny gaps on the skin surface in a short time to promote the efficiency of effective ingredients entering the skin, but they are limited to short-term and low-frequency use, and the operation is complicated, requiring special equipment and technology, which does not meet people's daily skin care needs.

Liposome technology was first used in the pharmaceutical industry, and then widely used in the cosmetics industry, such as liposome lotion, beauty serum, moisturizing cream, etc. Due to the high efficiency of liposomes and the characteristics of carrying both water-soluble and fat-soluble active ingredients and nutrients, more and more beauty products use liposome technology to promote the penetration and absorption of beauty ingredients, so as to achieve the desired beauty effect. Cosmetics containing liposomes can have different effects on the skin than ordinary cosmetics: first, liposomes have a strong affinity with the skin, so that the skin has a better absorption capacity for liposome-containing cosmetics; second, due to the special bimolecular membrane structure, the skin has a good acceptance of the substances contained in the liposomes; third, due to its encapsulation effect, some substances that are difficult for the skin to absorb can be brought into the deep layers of the skin, thereby reducing the irritation of certain contents. At the same time, for some chemically active substances that are beneficial to the skin, liposomes play the role of protective carriers.

Compared with skin care products such as toner and lotion, essences have a richer variety of active ingredients, higher concentrations, and more comprehensive functions. However, if the active ingredients exist alone, they are easily affected by pH, oxidation, interactions, etc., resulting in their inability to exert their full effects and reduced effectiveness. CN 113208968 B provides an essence with whitening and freckle removing functions, which contains a variety of whitening ingredients: 3-6 parts by weight of glycerin, 3-8 parts by weight of 1,3-propylene glycol, 60-80 parts by weight of deionized water, 0.5-1 parts by weight of gamma polyglutamic acid, 0.2-1 parts by weight of carbomer, 10-30 parts by weight of water-soluble fullerene, 1-3 parts by weight of ascorbyl glucoside, 0.1-1 parts by weight of p-hydroxyacetophenone, 0.5-4 parts by weight of dipotassium glycyrrhizinate, 0.1-1 parts by weight of sodium hyaluronate, 0.5-2 parts by weight of 1,2-pentanediol, 0.5-2 parts by weight of niacinamide, 1-10 parts by weight of plant essence extract, and 0.1-5 parts by weight of skin conditioner. The final form of the product is a simple mixture of the above active ingredients, and it is difficult to ensure the stability and effectiveness of the multiple whitening ingredients. CN 115531276 A provides a moisturizing essence, which contains 10-20 parts by weight of glycerin, 0.3-0.5 parts by weight of sodium hyaluronate, 1-2 parts by weight of castor oil, 0.5-5 parts by weight of betaine, 0.1-1 parts by weight of p-hydroxyacetophenone, 0.1-0.3 parts by weight of xanthan gum, 0.2-0.4 parts by weight of allantoin, 0.02-0.05 parts by weight of disodium EDTA and 1-3 parts by weight of Glycyrrhiza inflata extract. The essence uses multiple moisturizing factors to exert moisturizing effect, but lacks the assistance of penetration-promoting technology and has a large room for improvement in skin permeability.

As one of the entry-level means of medical cosmetology, small bubble beauty is widely welcomed by consumers. By using instruments and equipment to generate bubbles, the effective ingredients can be pushed deep into the skin. Its main disadvantage is that it is not suitable for daily skin care. CN202130877311.7 and CN202130838577.0 designed different small bubble beauty instruments and obtained authorization to promote the penetration of beauty ingredients into the skin, further proving the practicality of small bubbles in the field of beauty and skin care. However, the existing technical means have certain requirements for equipment and operation, which are not enough for daily use. In short, although the cosmetics market is huge, the quality of cosmetics on the market is uneven, and the effect of use is often unsatisfactory. Therefore, it is urgent to develop a high-end cosmetic with significant efficacy, gentleness and safety.

In view of this, the present invention is proposed.

Summary of the invention

The first purpose of the present invention is to provide a moisturizing and whitening liposome essence, which can spontaneously generate bubbles without the aid of special equipment, and combines physical means and biological means to double promote penetration, which is simple and efficient to solve the above problems.

The second object of the present invention is to provide a method for preparing the above-mentioned moisturizing and whitening liposome essence.

In order to achieve the above objectives, the following technical solutions are proposed:

In a first aspect, the present invention provides a moisturizing and whitening liposome essence, comprising: an acid-modified liposome solution and a salt-modified liposome solution;

The acid-modified liposomes include cationic liposomes and acids electrostatically adsorbed on the cationic liposomes; the cationic liposomes include soybean lecithin, cationic lipids and cholesterol;

The salt-modified liposomes include anionic liposomes and salts electrostatically adsorbed on the anionic liposomes; the anionic liposomes include soybean lecithin, anionic lipids and cholesterol;

The acid and the salt react to generate a gas;

The acid-modified liposomes and the salt-modified liposomes independently encapsulate whitening active ingredients and/or moisturizing active ingredients.

As a further technical solution, the acid includes at least one of citric acid, fruit acid, salicylic acid, ferulic acid, ascorbic acid, niacin, folic acid, tartaric acid, lauric acid, alginic acid, ursolic acid, maleic acid, rosmarinic acid, cinnamic acid, carnosic acid, mandelic acid, ellagic acid, gallic acid or madecassoic acid;

and/or, the salt comprises at least one of sodium bicarbonate, ammonium bicarbonate, calcium carbonate or sodium carbonate;

and/or, the cationic lipid comprises at least one of octadecylamine, (1,2-dioleyloxypropyl)trimethylammonium chloride (DOTAP) or dioleoylphosphatidylethanolamine (DOPE);

and/or, the anionic lipid comprises at least one of phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidic acid (PA) or phosphatidylglycerol (PG);

and/or, the whitening active ingredient comprises at least one of niacinamide, vitamin C and its derivatives, α-arbutin, 4-butylresorcinol, idebenone, resveratrol or ferulic acid;

And/or, the moisturizing active ingredient includes at least one of ergothioneine, ectoine, avocado oil, vitamin E or olive oil.

As a further technical solution, in the cationic liposomes, the mass ratio of soybean lecithin to cholesterol is 5:1-20:1, the mass ratio of soybean lecithin to cationic lipid is 10:1-30:1, and the mass ratio of soybean lecithin to whitening active ingredients and/or moisturizing ingredients is 8:1-40:1.

As a further technical solution, in the anionic liposomes, the mass ratio of soybean lecithin to cholesterol is 5:1-20:1, the mass ratio of soybean lecithin to anionic lipid is 10:1-30:1, and the mass ratio of soybean lecithin to whitening active ingredients and/or moisturizing ingredients is 8:1-40:1.

As a further technical solution, the acid-modified liposome solution and the salt-modified liposome solution also independently include at least one of glycerol, sodium hyaluronate, 1,3-butanediol, betaine or allantoin.

In a second aspect, the present invention provides a method for preparing the above-mentioned moisturizing and whitening liposome essence, comprising the following steps:

a. mixing the cationic liposomes with an acid to obtain an acid-modified liposome solution;

b. mixing the anionic liposomes with the salt to obtain a salt-modified liposome solution;

c. The acid-modified liposome solution and the salt-modified liposome solution are respectively homogenized under high pressure to prepare a moisturizing and whitening liposome essence.

As a further technical solution, the cationic liposomes and anionic lipids are independently prepared by a thin film dispersion method.

As a further technical solution, in step a, the method of the mixing reaction is: under stirring conditions, the cationic liposome solution is added dropwise to the acid solution to carry out a mixing reaction;

The stirring speed is 100-300 rpm, the reaction temperature is 25-37°C, the reaction time is 20 min-2 h, and the concentration of the acid solution is 0.1-1 mg/mL.

As a further technical solution, in step b, the method of the mixing reaction is: under stirring conditions, the anionic liposome solution is added dropwise to the salt solution to carry out a mixing reaction;

The stirring speed is 100-300 rpm, the reaction temperature is 25-37°C, the reaction time is 20 min-2 h, and the salt solution concentration is 0.3-3 mg/mL.

As a further technical solution, the pressure of the high-pressure homogenization is 500-2500 bar, and the number of times is 5-20 times.

Compared with the prior art, the moisturizing and whitening liposome essence provided by the present invention has the following beneficial effects:

1. According to the principle of electrostatic adsorption, the present invention prepares acid-modified cationic liposomes and salt-modified anionic liposomes respectively, wherein the liposomes encapsulate active ingredients with whitening and moisturizing effects. The two will not produce gas when stored separately, and only when they are mixed will the gas release under specific conditions be achieved, which can promote the penetration of the active ingredients into the deep layers of the skin under the promotion of bubbles.

2. Existing cosmetics often add abundant active ingredients to achieve multiple functions, but in most cases, such products are simply a mixture of multiple ingredients, lacking efficient means of permeation promotion, and most of the active ingredients remain on the skin surface and cannot enter the deep layer of the skin, and thus cannot fundamentally improve the skin condition. The present invention encapsulates the active ingredients with a liposome nanosystem with bubble propulsion, which can increase the solubility of poorly soluble ingredients, achieve multiple delivery of active ingredients, and take full effect. It can also protect the active ingredients, and the nanostructured carrier helps promote the penetration of active ingredients into the deep layer of the skin, restoring skin regeneration from the cellular level.

3. The skin can be divided into stratum corneum, epidermis and dermis from top to bottom. According to the different skin care effects, the skin penetration depth requirements are different. The present invention can adjust the composition of liposomes as needed to achieve the controllability of its skin penetration. Whitening cosmetics mainly target the epidermis, anti-aging cosmetics mainly act on the dermis, moisturizing cosmetics can act on different skin layers at the same time, and skin care products with different effects can be used in combination as needed.

4. Generally, cationic liposomes or anionic liposomes will have certain cytotoxicity when used alone. The present invention uses the two liposomes after surface modification respectively. On the one hand, the advantages of the two liposomes are retained. On the other hand, the charge is neutralized after the combined use, avoiding the toxicity problem that may exist in the individual application, which is safe and efficient.

BRIEF DESCRIPTION OF THE DRAWINGS

In order to more clearly illustrate the specific implementation methods of the present invention or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

Figure 1 shows the product appearance (left) and the morphology of citric acid-modified whitening liposomes characterized by transmission electron microscopy (right);

Figure 2 is a characterization of the gas production effect;

FIG3 is a Franz diffusion cell method for characterizing the transdermal absorption effect of carriers with different compositions;

FIG4 is a characterization of the transdermal absorption effect of carriers with different compositions using an inverted fluorescence microscope;

Figure 5 shows the changes in skin moisture of the subjects 10 minutes after topical application of liposome moisturizing and whitening essence;

Figure 6 shows the changes in skin oil content 10 minutes after the subjects were topically applied with liposome moisturizing and whitening essence;

Figure 7 shows the changes in skin moisture within 8 hours after the subjects were topically applied with liposome moisturizing and whitening essence.

Detailed ways

The embodiments of the present invention will be described in detail below in conjunction with the embodiments and examples, but it will be appreciated by those skilled in the art that the following embodiments and examples are only used to illustrate the present invention and should not be considered as limiting the scope of the present invention. Based on the embodiments in the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative work are within the scope of protection of the present invention. If specific conditions are not specified, proceed according to normal conditions or the conditions recommended by the manufacturer. If the manufacturer is not specified for the reagents or instruments used, they are all conventional products that can be purchased commercially.

In a first aspect, the present invention provides a moisturizing and whitening liposome essence, comprising: an acid-modified liposome solution and a salt-modified liposome solution;

The acid-modified liposomes include cationic liposomes and acids electrostatically adsorbed on the cationic liposomes; the cationic liposomes include soybean lecithin, cationic lipids and cholesterol;

The salt-modified liposomes include anionic liposomes and salts electrostatically adsorbed on the anionic liposomes; the anionic liposomes include soybean lecithin, anionic lipids and cholesterol;

The acid and the salt react to generate a gas; the gas is carbon dioxide;

The acid-modified liposomes and the salt-modified liposomes independently encapsulate whitening active ingredients and/or moisturizing active ingredients.

The present invention utilizes the principle of electrostatic adsorption to prepare acid-modified cationic liposomes and salt-modified anionic liposomes respectively, wherein the liposomes encapsulate active ingredients with whitening and moisturizing effects. The two will not produce gas when stored separately, and only when they are mixed will gas release under specific conditions be achieved, which can promote the penetration of the active ingredients into the deep layers of the skin under the promotion of bubbles.

In some optional embodiments, the acid includes but is not limited to at least one of citric acid, fruit acid, salicylic acid, ferulic acid, ascorbic acid, niacin, folic acid, tartaric acid, lauric acid, alginic acid, ursolic acid, maleic acid, rosmarinic acid, cinnamic acid, carnosic acid, mandelic acid, ellagic acid, gallic acid or madecassic acid;

and/or, the salt includes but is not limited to at least one of sodium bicarbonate, ammonium bicarbonate, calcium carbonate or sodium carbonate;

And/or, the cationic lipid includes but is not limited to octadecylamine, (1,2-dioleyloxypropyl)trimethylammonium chloride or dioleoylphosphatidylethanolamine, or other cationic lipids well known to those skilled in the art;

In some optional embodiments, the anionic lipid includes but is not limited to phosphatidylserine, phosphatidylinositol, phosphatidic acid or phosphatidylglycerol, or other anionic lipids well known to those skilled in the art;

In some optional embodiments, the whitening active ingredients include but are not limited to niacinamide, vitamin C and its derivatives (ascorbyl palmitate, ascorbyl glucoside, 2-o-ethyl ascorbic acid, aminopropanol ascorbyl phosphate), α-arbutin, 4-butylresorcinol, idebenone, resveratrol or ferulic acid, or other active ingredients with whitening effects known to those skilled in the art;

In some optional embodiments, the moisturizing active ingredients include but are not limited to ergothioneine, ectoine, avocado oil, vitamin E, olive oil, or other active ingredients with moisturizing effects known to those skilled in the art.

In some optional embodiments, in the cationic liposomes, the mass ratio of soybean lecithin to cholesterol can be, for example, but not limited to 5:1, 10:1, 15:1 or 20:1, the mass ratio of soybean lecithin to cationic lipid can be, for example, but not limited to 10:1, 20:1 or 30:1, and the mass ratio of soybean lecithin to whitening active ingredients and/or moisturizing ingredients can be, for example, but not limited to 8:1, 16:1, 24:1, 32:1 or 40:1.

In some optional embodiments, in the anionic liposomes, the mass ratio of soybean lecithin to cholesterol can be, for example, but not limited to 5:1, 10:1, 15:1 or 20:1, the mass ratio of soybean lecithin to anionic lipid can be, for example, but not limited to 10:1, 20:1 or 30:1, and the mass ratio of soybean lecithin to whitening active ingredients and/or moisturizing ingredients can be, for example, but not limited to 8:1, 16:1, 24:1, 32:1 or 40:1.

In some optional embodiments, the acid-modified liposome solution and the salt-modified liposome solution also independently include at least one of glycerol, sodium hyaluronate, 1,3-butanediol, betaine or allantoin, which mainly plays a moisturizing role.

In some optional embodiments, the acid-modified liposome solution and the salt-modified liposome solution further independently include a preservative;

The preservative includes, but is not limited to, at least one of phenoxyethanol, methylparaben, or DMDM hydantoin.

In a second aspect, the present invention provides a method for preparing the above-mentioned moisturizing and whitening liposome essence, comprising the following steps:

a. mixing the cationic liposomes with an acid to obtain an acid-modified liposome solution;

b. mixing the anionic liposomes with the salt to obtain a salt-modified liposome solution;

c. The acid-modified liposome solution and the salt-modified liposome solution are respectively homogenized under high pressure to prepare a moisturizing and whitening liposome essence.

The preparation method is simple, and the prepared moisturizing and whitening liposome essence has uniform liposome particle size and good stability.

In some optional embodiments, the cationic liposomes and anionic lipids are each independently prepared by a thin film dispersion method.

In some optional embodiments, in step a, the method of the mixing reaction is: under stirring conditions, the cationic liposome solution is added dropwise to the acid solution to carry out the mixing reaction;

The stirring speed may be, for example, but not limited to 100 rpm, 200 rpm or 300 rpm, the reaction temperature may be, for example, but not limited to 25°C, 30°C, 35°C or 37°C, the reaction time may be, for example, but not limited to 20 min, 40 min, 1 h or 2 h, and the concentration of the acid solution may be, for example, but not limited to 0.1 mg/mL, 0.2 mg/mL, 0.4 mg/mL, 0.6 mg/mL, 0.8 mg/mL or 1 mg/mL.

In some optional embodiments, in step b, the method of the mixing reaction is: under stirring conditions, the anionic liposome solution is added dropwise to the salt solution to carry out the mixing reaction;

The stirring speed may be, for example, but not limited to, 100 rpm, 200 rpm or 300 rpm, the reaction temperature may be, for example, but not limited to, 25°C, 30°C, 35°C or 37°C, the reaction time may be, for example, but not limited to, 20 min, 40 min, 1 h or 2 h, and the concentration of the salt solution may be, for example, but not limited to, 0.3 mg/mL, 0.5 mg/mL, 1 mg/mL, 2 mg/mL or 3 mg/mL.

In some optional embodiments, the pressure of the high-pressure homogenization may be, for example, but not limited to, 500 bar, 1000 bar, 1500 bar, 2000 bar or 2500 bar, and the number of times is 5-20 times.

The present invention is further described below by specific examples and comparative examples. However, it should be understood that these examples are only used for more detailed description and should not be construed as limiting the present invention in any form.

In the following examples and comparative examples, human keratinocytes (HaCaT) and fibroblasts (HSF), mouse melanoma cells (B16) were purchased from Shanghai ATCC cell bank; soybean lecithin, cholesterol, anionic lipids, and cationic lipids were all purchased from Shanghai Avite Pharmaceutical Technology Co., Ltd.; niacinamide, vitamin C derivatives (ascorbyl palmitate, ascorbyl glucoside, 2-o-ethyl ascorbic acid, aminopropanol ascorbyl phosphate), α-arbutin, 4-butylresorcinol , idebenone, resveratrol, ferulic acid, glycerin, 1,3-butylene glycol, methylparaben, phenoxyethanol, DMDM hydantoin, sodium hyaluronate, betaine, allantoin, citric acid, fruit acid, salicylic acid, ferulic acid, ascorbic acid, niacin, folic acid, tartaric acid, lauric acid, alginic acid, ursolic acid, maleic acid, rosmarinic acid, cinnamic acid, carnosic acid, mandelic acid, ellagic acid, gallic acid, madecassic acid, sodium bicarbonate, ammonium bicarbonate, calcium carbonate, and sodium carbonate were all purchased from Guangzhou Baiyu Biotechnology Co., Ltd.

Other reagents and raw materials are commercially available.

Example 1

Preparation of a moisturizing and whitening liposome essence with gas motor propulsion

(1) Preparation of whitening liposomes: 100 mg of soybean lecithin, 5 mg of cholesterol, 5 mg of octadecylamine, and 10 mg of ascorbyl palmitate were weighed into a 250 mL eggplant-shaped bottle, 10 mL of anhydrous ethanol was added and ultrasonically dissolved, and vacuum-dried at 25°C for 10 min to obtain a dry lipid film, which was vacuum-dried overnight to remove excess organic solvent, and 10 mL of phosphate buffer (PBS, pH 6.6) was added to hydrate for 20 min. The free whitening components that were not encapsulated were removed by dialysis bag to obtain a liposome solution encapsulating the whitening components, which was stored at 4°C for future use.

(2) Preparation of citric acid modified whitening liposomes: The liposome solution prepared in step (1) was added dropwise into a 0.1 mg/mL citric acid solution under low-speed stirring at 100 rpm, and the reaction was carried out at 25°C for 20 min to obtain a citric acid modified liposome solution, which was then stored at 4°C for later use.

(3) Preparation of hydrating and moisturizing liposomes: Weigh 100 mg of soybean lecithin, 5 mg of cholesterol, 5 mg of phosphatidylserine (PS), and 10 mg of olive oil in a 250 mL eggplant-shaped bottle, add 20 mL of anhydrous ethanol and ultrasonically dissolve, dry under vacuum at 25°C for 10 min to obtain a dry lipid film, vacuum dry overnight to remove excess organic solvent, add 10 mL of phosphate buffered saline (PBS, pH 6.6) to hydrate for 20 min, remove unencapsulated free components through a dialysis bag, and obtain a liposome solution encapsulating moisturizing components, which is stored at 4°C for later use.

(4) Preparation of sodium bicarbonate modified hydrating liposomes: The liposome solution prepared in step (3) was added dropwise into a 0.3 mg/mL sodium bicarbonate solution under stirring at 100 rpm, and the mixture was reacted at 25° C. for 20 min to obtain a sodium bicarbonate modified liposome solution, which was then stored at 4° C. for later use.

(5) Preparation of liposome whitening and moisturizing essence with gas motor propulsion: Take the whitening liposome solution in step (2), add 0.3g glycerol, 2g 1,3-butylene glycol, 0.1g betaine, 0.1g allantoin, and 0.1g phenoxyethanol, and stir to mix. Take the moisturizing liposome solution in step (4), add 0.3g glycerol, 2g 1,3-butylene glycol, 0.1g betaine, 0.1g allantoin, and 0.1g phenoxyethanol, and stir to mix. The liposome solutions obtained above are subjected to high-pressure homogenization (500 bar, 5 times) to obtain liposome essences with uniform particle size and store them separately. Mix them before use to generate bubbles.

Example 2

Preparation of a moisturizing and whitening liposome essence with gas motor propulsion

(1) Preparation of whitening liposomes: 500 mg of soybean lecithin, 50 mg of cholesterol, 50 mg of octadecylamine, and 62.5 mg of vitamin C were weighed into a 250 mL eggplant-shaped bottle, 20 mL of anhydrous ethanol was added and ultrasonically dissolved, and the solution was dried under vacuum at 25°C for 10 min to obtain a dry lipid film. The solution was vacuum dried overnight to remove excess organic solvent, and 20 mL of phosphate buffer (PBS, pH 6.6) was added to hydrate the solution for 20 min. The free whitening components that were not encapsulated were removed through a dialysis bag to obtain a liposome solution encapsulating the whitening components, which was stored at 4°C for future use.

(2) Preparation of salicylic acid modified whitening liposomes: The liposome solution prepared in step (1) was added dropwise into a 0.2 mg/mL salicylic acid solution under low-speed stirring at 200 rpm, and the reaction was carried out at 25° C. for 40 min to obtain a salicylic acid modified liposome solution, which was then stored at 4° C. for later use.

(3) Preparation of hydrating and moisturizing liposomes: 500 mg of soybean lecithin, 50 mg of cholesterol, 50 mg of phosphatidylinositol (PI), and 62.5 mg of avocado oil were weighed into a 250 mL eggplant-shaped bottle, 20 mL of anhydrous ethanol was added and ultrasonically dissolved, and the mixture was dried under vacuum at 25°C for 10 min to obtain a dry lipid film. The mixture was vacuum dried overnight to remove excess organic solvent, and 20 mL of phosphate buffered saline (PBS, pH 6.6) was added to hydrate the mixture for 20 min. The free components not encapsulated were removed by dialysis bag to obtain a liposome solution encapsulating moisturizing components, which was stored at 4°C for future use.

(4) Preparation of sodium bicarbonate modified hydrating liposomes: The liposome solution prepared in step (3) was added dropwise into a 0.6 mg/mL sodium bicarbonate solution under stirring at 200 rpm, and the mixture was reacted at 25° C. for 40 min to obtain a sodium bicarbonate modified liposome solution, which was then stored at 4° C. for later use.

(5) Preparation of liposome whitening and moisturizing essence with gas motor propulsion: Take the whitening liposome solution in step (2), add 0.5g glycerol, 2.5g 1,3-butylene glycol, 0.5g betaine, 0.5g allantoin, and 0.2g phenoxyethanol, and stir to mix. Take the moisturizing liposome solution in step (4), add 0.5g glycerol, 2.5g 1,3-butylene glycol, 0.5g betaine, 0.5g allantoin, and 0.2g phenoxyethanol, and stir to mix. The liposome solutions obtained above are subjected to high-pressure homogenization (500 bar, 15 times) to obtain liposome essences with uniform particle size and store them separately. Mix them before use to generate bubbles.

Example 3

Preparation of a moisturizing and whitening liposome essence with gas motor propulsion

(1) Preparation of whitening liposomes: Weigh 1 g of soybean lecithin, 100 mg of cholesterol, 25 mg of dioleoylphosphatidylethanolamine (DOPE), 25 mg of (1,2-dioleyloxypropyl)trimethylammonium chloride (DOTAP), and 25 mg of idebenone into a 500-mL eggplant-shaped bottle, add 20 mL of anhydrous ethanol and ultrasonically dissolve, dry under vacuum at 25°C for 10 min to obtain a dry lipid film, vacuum dry overnight to remove excess organic solvent, add 20 mL of phosphate buffer (PBS, pH 6.6) to hydrate for 20 min, remove unencapsulated free whitening components through a dialysis bag, and obtain a liposome solution encapsulating the whitening components, which is stored at 4°C for later use.

(2) Preparation of whitening liposomes modified with fruit acid and ursolic acid: The liposome solution prepared in step (1) was added dropwise to a solution containing 0.25 mg/mL of fruit acid and ursolic acid respectively under low-speed stirring at 300 rpm, and the mixture was reacted at 37°C for 30 min to obtain a liposome solution modified with fruit acid and ursolic acid, which was then stored at 4°C for later use.

(3) Preparation of hydrating and moisturizing liposomes: 1 g of soybean lecithin, 100 mg of cholesterol, and 50 mg of phosphatidylserine (PS) were weighed into a 500 mL eggplant-shaped bottle, 20 mL of anhydrous ethanol was added for ultrasonic dissolution, and vacuum-dried at 25° C. for 10 min to obtain a dry lipid film, which was vacuum-dried overnight to remove excess organic solvent, and 10 mL of phosphate buffered saline (PBS, pH 6.6) containing 25 mg of ergothioneine was added for hydration for 20 min. The free components not encapsulated were removed by dialysis bag to obtain a liposome solution encapsulating the moisturizing components, which was stored at 4° C. for future use.

(4) Preparation of sodium carbonate modified hydrating liposomes: The liposome solution prepared in step (3) was added dropwise into a 1.5 mg/mL sodium carbonate solution under stirring at 300 rpm and reacted at 37° C. for 30 min to obtain a sodium carbonate modified liposome solution, which was stored at 4° C. for later use.

(5) Preparation of liposome whitening and moisturizing essence with gas motor propulsion: Take the whitening liposome solution in step (2), add 1g glycerol, 5g 1,3-butylene glycol, 0.2g betaine, 0.3g allantoin, and 0.2g phenoxyethanol, and stir to mix. Take the moisturizing liposome solution in step (4), add 1g glycerol, 5g 1,3-butylene glycol, 0.2g betaine, 0.3g allantoin, and 0.2g phenoxyethanol, and stir to mix. The liposome solutions obtained above are subjected to high-pressure homogenization (1000 bar, 10 times) to obtain liposome essences with uniform particle size and store them separately. Mix them before use to generate bubbles.

Example 4

Preparation of a moisturizing and whitening liposome essence with gas motor propulsion

(1) Preparation of whitening liposomes: 4 g of soybean lecithin, 800 mg of cholesterol, 133 mg of octadecylamine, 100 mg of ascorbyl glucoside and 100 mg of 2-o-ethyl ascorbic acid were weighed into a 500 mL eggplant-shaped bottle, 20 mL of anhydrous ethanol was added and ultrasonically dissolved, and vacuum dried at 25°C for 10 min to obtain a dry lipid film, which was vacuum dried overnight to remove excess organic solvent, and 20 mL of phosphate buffer (PBS, pH 6.6) was added to hydrate for 20 min. The free whitening components that were not encapsulated were removed by dialysis bag to obtain a liposome solution encapsulating the whitening components, which was stored at 4°C for future use.

(2) Preparation of ascorbic acid and maleic acid modified whitening liposomes: The liposome solution prepared in step (1) was added dropwise into a 1 mg/mL ascorbic acid and maleic acid solution under low-speed stirring at 300 rpm, and the reaction was carried out at 25°C for 1 h to obtain the ascorbic acid and maleic acid modified liposome solution, which was stored at 4°C for later use.

(3) Preparation of hydrating and moisturizing liposomes: Weigh 4 g of soybean lecithin, 800 mg of cholesterol, and 133 mg of phosphatidylglycerol (PG) in a 500 mL eggplant-shaped bottle, add 20 mL of anhydrous ethanol and ultrasonically dissolve, dry under vacuum at 25 °C for 10 min to obtain a dry lipid film, vacuum dry overnight to remove excess organic solvent, add 20 mL of phosphate buffer (PBS, pH 6.6) containing 100 mg of ectoine and 100 mg of ergothioneine and hydrate for 20 min, remove the unencapsulated free components through a dialysis bag, and obtain a liposome solution encapsulating the moisturizing components, which is stored at 4 °C for later use.

(4) Preparation of calcium carbonate modified hydrating liposomes: The liposome solution prepared in step (3) was added dropwise into a 3 mg/mL calcium carbonate solution under stirring at 100 rpm, and the mixture was reacted at 25° C. for 1 h to obtain a calcium carbonate modified liposome solution, which was then stored at 4° C. for later use.

(5) Preparation of liposome whitening and moisturizing essence with gas motor propulsion: Take the whitening liposome solution in step (2), add 1g of α-arbutin, 5g of glycerol, 5g of 1,3-butylene glycol, 0.5g of betaine, 0.5g of allantoin, and 0.25g of phenoxyethanol, and stir to mix. Take the moisturizing liposome solution in step (4), add 5g of glycerol, 5g of 1,3-butylene glycol, 0.5g of betaine, 0.5g of allantoin, and 0.25g of phenoxyethanol, and stir to mix. The liposome solutions obtained above are subjected to high-pressure homogenization (1500 bar, 15 times) to obtain liposome essences with uniform particle size and store them separately. Mix them before use to generate bubbles.

Example 5

Preparation of a moisturizing and whitening liposome essence with gas motor propulsion

(1) Preparation of whitening liposomes: Weigh 5 g of soybean lecithin, 500 mg of cholesterol, 50 mg of dioleoylphosphatidylethanolamine (DOPE), 200 mg of (1,2-dioleyloxypropyl)trimethylammonium chloride (DOTAP), 25 mg of aminopropanol ascorbyl phosphate, and 600 mg of ascorbyl palmitate in a 500 mL eggplant-shaped bottle, add 25 mL of anhydrous ethanol and ultrasonically dissolve, dry under vacuum at 25 °C for 10 min to obtain a dry lipid film, vacuum dry overnight to remove excess organic solvent, add 25 mL of phosphate buffer (PBS, pH 6.6) and hydrate for 20 min, remove the unencapsulated free whitening components through a dialysis bag, and obtain a liposome solution containing whitening components, which is stored at 4 °C for later use.

(2) Preparation of ferulic acid, niacin, folic acid and tartaric acid modified whitening liposomes: The liposome solution prepared in step (1) was added dropwise into a solution containing 0.25 mg/mL of ferulic acid, niacin, folic acid and tartaric acid respectively under low speed stirring at 300 rpm, and the mixture was reacted at 25°C for 2 h to obtain a liposome solution modified with ferulic acid, niacin, folic acid and tartaric acid, which was then stored at 4°C for later use.

(3) Preparation of hydrating and moisturizing liposomes: Weigh 5 g of soybean lecithin, 500 mg of cholesterol, 250 mg of phosphatidylserine (PS), and 200 mg of vitamin E, put them in a 500 mL eggplant-shaped bottle, add 25 mL of anhydrous ethanol and ultrasonically dissolve them, dry them under vacuum at 25°C for 10 min to obtain a dry lipid film, vacuum dry it overnight to remove excess organic solvent, add 25 mL of phosphate buffer (PBS, pH 6.6) containing 200 mg of ectoine and 225 mg of ergothioneine, hydrate them for 20 min, remove the free components that are not encapsulated by the dialysis bag, and obtain a liposome solution encapsulating the moisturizing components, which is stored at 4°C for future use.

(4) Preparation of sodium bicarbonate modified hydrating liposomes: The liposome solution prepared in step (3) was added dropwise into a 1 mg/mL sodium bicarbonate solution under stirring at 300 rpm, and the mixture was reacted at 25° C. for 2 h to obtain a sodium bicarbonate modified liposome solution, which was then stored at 4° C. for later use.

(5) Preparation of liposome whitening and moisturizing essence with gas motor propulsion: Take the whitening liposome solution in step (2), add 4.375g niacinamide, 4g glycerol, 8g 1,3-butylene glycol, 0.09g betaine, 0.09g allantoin, and 0.25g phenoxyethanol, and stir to mix. Take the moisturizing liposome solution in step (4), add 4g glycerol, 8g 1,3-butylene glycol, 0.09g betaine, 0.09g allantoin, and 0.25g phenoxyethanol, and stir to mix. The liposome solutions obtained above are subjected to high-pressure homogenization (2500 bar, 20 times) to obtain liposome essences with uniform particle size and store them separately. Mix them before use to generate bubbles.

Example 6

Preparation of a moisturizing and whitening liposome essence with gas motor propulsion

(1) Preparation of whitening liposomes: 2 g of soybean lecithin, 200 mg of cholesterol, 100 mg of octadecylamine, 150 mg of ascorbyl palmitate, and 50 mg of idebenone were weighed into a 500 mL eggplant-shaped bottle, and 20 mL of anhydrous ethanol was added for ultrasonic dissolution. The solution was dried under vacuum at 25°C for 10 min to obtain a dry lipid film. The solution was vacuum dried overnight to remove excess organic solvent. 20 mL of phosphate buffer (PBS, pH 6.6) was added for hydration for 20 min. The free whitening components that were not encapsulated were removed by dialysis bag to obtain a liposome solution encapsulating the whitening components. The solution was stored at 4°C for future use.

(2) Preparation of whitening liposomes modified with rosmarinic acid, cinnamic acid and lauric acid: The liposome solution prepared in step (1) was added dropwise into a solution containing 0.33 mg/mL of rosmarinic acid, cinnamic acid and lauric acid respectively under low-speed stirring at 300 rpm, and the mixture was reacted at 37°C for 40 min to obtain a liposome solution modified with rosmarinic acid, cinnamic acid and lauric acid, which was then stored at 4°C for later use.

(3) Preparation of hydrating and moisturizing liposomes: 2 g of soybean lecithin, 200 mg of cholesterol, 30 mg of phosphatidylserine (PS), 36 mg of phosphatidylinositol (PI), and 100 mg of olive oil were weighed into a 250 mL eggplant-shaped bottle, 20 mL of anhydrous ethanol was added for ultrasonic dissolution, and vacuum-dried at 25° C. for 10 min to obtain a dry lipid film, which was vacuum-dried overnight to remove excess organic solvent, and 20 mL of phosphate buffer (PBS, pH 6.6) containing 50 mg of ergothioneine was added for hydration for 20 min. The free components not encapsulated were removed by dialysis bag to obtain a liposome solution encapsulating moisturizing components, which was stored at 4° C. for future use.

(4) Preparation of calcium carbonate modified hydrating liposomes: The liposome solution prepared in step (3) was added dropwise into a 3 mg/mL calcium carbonate solution under stirring at 300 rpm, and the mixture was reacted at 37° C. for 40 min to obtain a calcium carbonate modified liposome solution, which was then stored at 4° C. for later use.

(5) Preparation of liposome whitening and moisturizing essence with gas motor propulsion: Take the whitening liposome solution in step (2), add niacinamide 3g, glycerol 0.5g, 1,3-butylene glycol 5.5g, betaine 0.2g, allantoin 0.3g, methylparaben 0.25g, and stir to mix. Take the moisturizing liposome solution in step (4), add glycerol 0.5g, 1,3-butylene glycol 5.5g, betaine 0.2g, allantoin 0.3g, methylparaben 0.25g, and stir to mix. The liposome solutions obtained above are respectively subjected to high pressure homogenization (1500bar, 20 times) to obtain liposome essences with uniform particle size and stored separately. Mix well before use to generate bubbles.

Example 7

Preparation of a moisturizing and whitening liposome essence with gas motor propulsion

(1) Preparation of whitening liposomes: 2 g of soybean lecithin, 200 mg of cholesterol, 100 mg of octadecylamine, and 200 mg of 4-butylresorcinol were weighed into a 500 mL eggplant-shaped bottle, and 20 mL of anhydrous ethanol was added for ultrasonic dissolution. The solution was dried under vacuum at 25° C. for 10 min to obtain a dry lipid film. The solution was vacuum dried overnight to remove excess organic solvent. 20 mL of phosphate buffer (PBS, pH 6.6) was added for hydration for 20 min. The free whitening components that were not encapsulated were removed by dialysis bag to obtain a liposome solution encapsulating the whitening components. The solution was stored at 4° C. for future use.

(2) Preparation of whitening liposomes modified with alginate, carnosic acid, mandelic acid and ellagic acid: The liposome solution prepared in step (1) was added dropwise into a solution containing 0.25 mg/mL of alginate, carnosic acid, mandelic acid and ellagic acid respectively under low-speed stirring at 300 rpm, and the mixture was reacted at 37°C for 40 min to obtain a liposome solution modified with alginate, carnosic acid, mandelic acid and ellagic acid, which was then stored at 4°C for later use.

(3) Preparation of hydrating and moisturizing liposomes: 2 g of soybean lecithin, 200 mg of cholesterol, and 66 mg of phosphatidylserine (PS) were weighed into a 250 mL eggplant-shaped bottle, 20 mL of anhydrous ethanol was added for ultrasonic dissolution, and vacuum-dried at 25° C. for 10 min to obtain a dry lipid film, which was vacuum-dried overnight to remove excess organic solvent, and 20 mL of phosphate buffer (PBS, pH 6.6) containing 100 mg of ergothioneine was added for hydration for 20 min. The free components not encapsulated were removed by dialysis bag to obtain a liposome solution encapsulating the moisturizing components, which was stored at 4° C. for future use.

(4) Preparation of ammonium bicarbonate modified hydrating liposomes: The liposome solution prepared in step (3) was added dropwise into a 3 mg/mL ammonium bicarbonate solution under stirring at 300 rpm, and the mixture was reacted at 37° C. for 40 min to obtain an ammonium bicarbonate modified liposome solution, which was then stored at 4° C. for later use.

(5) Preparation of liposome whitening and moisturizing essence with gas motor propulsion: Take the whitening liposome solution in step (2), add 2g of ferulic acid, 2g of resveratrol, 0.5g of glycerol, 5.5g of 1,3-butylene glycol, 0.2g of betaine, 0.3g of allantoin, and 0.25g of phenoxyethanol, and stir to mix. Take the moisturizing liposome solution in step (4), add 0.5g of glycerol, 5.5g of 1,3-butylene glycol, 0.2g of betaine, 0.3g of allantoin, and 0.25g of phenoxyethanol, and stir to mix. The liposome solutions obtained above are subjected to high-pressure homogenization (1500 bar, 20 times) to obtain liposome essences with uniform particle size and store them separately. Mix them before use to generate bubbles.

Example 8

Preparation of a moisturizing and whitening liposome essence with gas motor propulsion

(1) Preparation of whitening liposomes: Weigh 1 g of soybean lecithin, 100 mg of cholesterol, 50 mg of octadecylamine, and 100 mg of ascorbyl palmitate in a 250 mL eggplant-shaped bottle, add 20 mL of anhydrous ethanol, and ultrasonically dissolve the mixture. Dry the mixture under vacuum at 25°C for 10 min to obtain a dry lipid film. Vacuum dry the mixture overnight to remove excess organic solvent, add 20 mL of phosphate buffer (PBS, pH 6.6) to hydrate the mixture for 20 min, remove the unencapsulated free whitening components through a dialysis bag, and obtain a liposome solution encapsulating the whitening components. Store the solution at 4°C for later use.

(2) Preparation of citric acid modified whitening liposomes: The liposome solution prepared in step (1) was added dropwise into a 1 mg/mL citric acid solution under low-speed stirring at 300 rpm, and the reaction was carried out at 37°C for 40 min to obtain a citric acid modified liposome solution, which was then stored at 4°C for later use.

(3) Preparation of hydrating and moisturizing liposomes: Weigh 2 g of soybean lecithin, 200 mg of cholesterol, and 100 mg of phosphatidylinositol (PI) in a 250 mL eggplant-shaped bottle, add 20 mL of anhydrous ethanol and ultrasonically dissolve, dry under vacuum at 25°C for 10 min to obtain a dry lipid film, vacuum dry overnight to remove excess organic solvent, add 20 mL of phosphate buffer (PBS, pH 6.6) containing 50 mg of ectoine and hydrate for 20 min, remove unencapsulated free components through a dialysis bag, and obtain a liposome solution encapsulating the moisturizing components, which is stored at 4°C for later use.

(4) Preparation of sodium bicarbonate modified hydrating liposomes: The liposome solution prepared in step (3) was added dropwise into a 3 mg/mL sodium bicarbonate solution under stirring at 300 rpm, and the mixture was reacted at 37° C. for 40 min to obtain a sodium bicarbonate modified liposome solution, which was then stored at 4° C. for later use.

(5) Preparation of liposome whitening and moisturizing essence with gas motor propulsion: Take the whitening liposome solution in step (2), add 1g of ferulic acid, 1g of resveratrol, 2g of niacinamide, 0.5g of glycerol, 5.5g of 1,3-butylene glycol, 0.2g of betaine, 0.3g of allantoin, and 0.25g of DMDM hydantoin, and stir to mix. Take the moisturizing liposome solution in step (4), add 0.5g of glycerol, 5.5g of 1,3-butylene glycol, 0.2g of betaine, 0.3g of allantoin, and 0.25g of DMDM hydantoin, and stir to mix. The liposome solutions obtained above are subjected to high-pressure homogenization (1500 bar, 20 times) to obtain liposome essences with uniform particle size and are stored separately, as shown in Figure 1. Mix well before use to generate bubbles (as shown in Figure 2, the left figure is the result after 5 minutes of mixing, and the right figure is the result after 10 minutes of mixing).

Example 9

Preparation of a moisturizing and whitening liposome essence with gas motor propulsion

(1) Preparation of whitening liposomes: 2 g of soybean lecithin, 200 mg of cholesterol, 100 mg of octadecylamine, and 200 mg of 4-butylresorcinol were weighed into a 500 mL eggplant-shaped bottle, and 20 mL of anhydrous ethanol was added for ultrasonic dissolution. The solution was dried under vacuum at 25° C. for 10 min to obtain a dry lipid film. The solution was vacuum dried overnight to remove excess organic solvent. 20 mL of phosphate buffer (PBS, pH 6.6) was added for hydration for 20 min. The free whitening components that were not encapsulated were removed by dialysis bag to obtain a liposome solution encapsulating the whitening components. The solution was stored at 4° C. for future use.

(2) Preparation of gallic acid modified whitening liposomes: The liposome solution prepared in step (1) was added dropwise into a solution containing 1 mg/mL gallic acid under low-speed stirring at 300 rpm, and the reaction was carried out at 37°C for 40 min to obtain a gallic acid modified liposome solution, which was then stored at 4°C for later use.

(3) Preparation of hydrating and moisturizing liposomes: 2 g of soybean lecithin, 200 mg of cholesterol, and 66 mg of phosphatidylserine (PS) were weighed into a 250 mL eggplant-shaped bottle, 20 mL of anhydrous ethanol was added for ultrasonic dissolution, and vacuum-dried at 25° C. for 10 min to obtain a dry lipid film, which was vacuum-dried overnight to remove excess organic solvent, and 20 mL of phosphate buffer (PBS, pH 6.6) containing 100 mg of ergothioneine was added for hydration for 20 min. The free components not encapsulated were removed by dialysis bag to obtain a liposome solution encapsulating the moisturizing components, which was stored at 4° C. for future use.

(4) Preparation of ammonium bicarbonate modified hydrating liposomes: The liposome solution prepared in step (3) was added dropwise into a 3 mg/mL ammonium bicarbonate solution under stirring at 300 rpm, and the mixture was reacted at 37° C. for 40 min to obtain an ammonium bicarbonate modified liposome solution, which was then stored at 4° C. for later use.

(5) Preparation of liposome whitening and moisturizing essence with gas motor propulsion: Take the whitening liposome solution in step (2), add 2g of ferulic acid, 2g of resveratrol, 0.5g of glycerol, 5.5g of 1,3-butylene glycol, 0.2g of betaine, 0.3g of allantoin, and 0.25g of phenoxyethanol, and stir to mix. Take the moisturizing liposome solution in step (4), add 0.5g of glycerol, 5.5g of 1,3-butylene glycol, 0.2g of betaine, 0.3g of allantoin, and 0.25g of phenoxyethanol, and stir to mix. The liposome solutions obtained above are subjected to high-pressure homogenization (1500 bar, 20 times) to obtain liposome essences with uniform particle size and store them separately. Mix them before use to generate bubbles.

Example 10

Preparation of a moisturizing and whitening liposome essence with gas motor propulsion

(1) Preparation of whitening liposomes: Weigh 5 g of soybean lecithin, 500 mg of cholesterol, 50 mg of dioleoylphosphatidylethanolamine (DOPE), 200 mg of (1,2-dioleyloxypropyl)trimethylammonium chloride (DOTAP), 25 mg of aminopropanol ascorbyl phosphate, and 600 mg of ascorbyl palmitate in a 500 mL eggplant-shaped bottle, add 25 mL of anhydrous ethanol and ultrasonically dissolve, dry under vacuum at 25 °C for 10 min to obtain a dry lipid film, vacuum dry overnight to remove excess organic solvent, add 25 mL of phosphate buffer (PBS, pH 6.6) and hydrate for 20 min, remove the unencapsulated free whitening components through a dialysis bag, and obtain a liposome solution containing whitening components, which is stored at 4 °C for later use.

(2) Preparation of madecassoic acid modified whitening liposomes: The liposome solution prepared in step (1) was added dropwise into a solution containing 1 mg/mL madecassoic acid under low-speed stirring at 300 rpm, and the mixture was reacted at 25° C. for 2 h to obtain a madecassoic acid modified liposome solution, which was then stored at 4° C. for later use.

(3) Preparation of hydrating and moisturizing liposomes: Weigh 5 g of soybean lecithin, 500 mg of cholesterol, 250 mg of phosphatidylserine (PS), and 200 mg of vitamin E, put them in a 500 mL eggplant-shaped bottle, add 25 mL of anhydrous ethanol and ultrasonically dissolve them, dry them under vacuum at 25°C for 10 min to obtain a dry lipid film, vacuum dry it overnight to remove excess organic solvent, add 25 mL of phosphate buffer (PBS, pH 6.6) containing 200 mg of ectoine and 225 mg of ergothioneine, hydrate them for 20 min, remove the free components that are not encapsulated by the dialysis bag, and obtain a liposome solution encapsulating the moisturizing components, which is stored at 4°C for future use.

(4) Preparation of sodium carbonate modified hydrating liposomes: The liposome solution prepared in step (3) was added dropwise into a 1 mg/mL sodium carbonate solution under stirring at 300 rpm, and the mixture was reacted at 25° C. for 2 h to obtain a sodium carbonate modified liposome solution, which was then stored at 4° C. for later use.

(5) Preparation of liposome whitening and moisturizing essence with gas motor propulsion: Take the whitening liposome solution in step (2), add 4.375g niacinamide, 4g glycerol, 8g 1,3-butylene glycol, 0.09g betaine, 0.09g allantoin, and 0.25g phenoxyethanol, and stir to mix. Take the moisturizing liposome solution in step (4), add 4g glycerol, 8g 1,3-butylene glycol, 0.09g betaine, 0.09g allantoin, and 0.25g phenoxyethanol, and stir to mix. The liposome solutions obtained above are subjected to high-pressure homogenization (2500 bar, 20 times) to obtain liposome essences with uniform particle size and store them separately. Mix them before use to generate bubbles.

Comparative Example 1

A moisturizing and whitening liposome essence, which differs from Example 8 in that it does not include the acid and salt modification steps, and the specific steps are as follows:

(1) Preparation of whitening liposomes: Weigh 1 g of soybean lecithin, 100 mg of cholesterol, 50 mg of octadecylamine, and 100 mg of ascorbyl palmitate in a 250 mL eggplant-shaped bottle, add 20 mL of anhydrous ethanol and ultrasonically dissolve, dry under vacuum at 25°C for 10 min to obtain a dry lipid film, vacuum dry overnight to remove excess organic solvent, add 20 mL of phosphate buffer (PBS, pH 6.6) to hydrate for 20 min, remove unencapsulated free whitening components through a dialysis bag, and obtain a liposome solution encapsulating the whitening components, which is stored at 4°C for later use.

(2) Preparation of hydrating and moisturizing liposomes: Weigh 2 g of soybean lecithin, 200 mg of cholesterol, and 100 mg of phosphatidylinositol (PI) in a 250 mL eggplant-shaped bottle, add 20 mL of anhydrous ethanol and ultrasonically dissolve, dry under vacuum at 25 °C for 10 min to obtain a dry lipid film, vacuum dry overnight to remove excess organic solvent, add 20 mL of phosphate buffered saline (PBS, pH 6.6) containing 50 mg of ectoine and hydrate for 20 min, remove unencapsulated free components through a dialysis bag, and obtain a liposome solution encapsulating moisturizing components, which is stored at 4 °C for later use.

(3) Preparation of liposome whitening and moisturizing essence: Take the whitening liposome solution in step (1), add 1g of ferulic acid, 1g of resveratrol, 2g of niacinamide, 0.5g of glycerol, 5.5g of 1,3-butylene glycol, 0.2g of betaine, 0.3g of allantoin, and 0.25g of DMDM hydantoin, and stir to mix. Take the moisturizing liposome solution in step (2), add 0.5g of glycerol, 5.5g of 1,3-butylene glycol, 0.2g of betaine, 0.3g of allantoin, and 0.25g of DMDM hydantoin, and stir to mix. The liposome solutions obtained above are subjected to high-pressure homogenization (1500 bar, 20 times) to obtain liposome essences with uniform particle size and stored separately, and mixed before use.

Test Example 1

Experimental animals: 20 male ICR mice (20±2 g) were purchased from Nanjing Qinglongshan Animal Farm.

In this study, the skin-whitening ingredient ascorbyl palmitate was used as a model drug, and the Franz diffusion cell method was used to study the in vitro transdermal effects of liposomes with different compositions.

Mice were anesthetized with chloral hydrate (concentration 2%), and the abdominal hair was removed. After being killed by cervical dislocation, the abdominal skin was peeled off, excess fat was removed, and stored at -20°C for later use. The following 4 groups were set up, with 4 mouse skins in each group.

Experimental group 1: ascorbyl palmitate liposome solution group with gas motor propulsion (prepared by the method of step (5) of Example 8);

Experimental group 2: a physical mixture of ascorbyl palmitate and phospholipids (the same amount of ascorbyl palmitate and phospholipids as in step (1) of Example 8 were weighed and simply physically stirred and mixed, and the solvent composition was the other components in step (5) of Example 8 except liposomes);

Experimental group 3: an ascorbyl palmitate liposome solution group without gas motor propulsion (prepared by the method of step (3) of comparative example 1);

Blank control group: free ascorbyl palmitate solution group (weigh an amount of ascorbyl palmitate equal to that in step (1) of Example 8, and the solvent composition is the other components except liposomes in step (5) of Example 8);

Positive control group (containing 2% azone, the solvent composition is the other components except liposomes in step (5) of Example 8);

The mouse skin was thawed at room temperature, and the stratum corneum was fixed to a diffusion cell (1 cm in diameter) with a clamp with the stratum corneum facing upward. 8 mL of PBS was added to the receiving chamber, and 1 g of each group of preparations was added to the supply chamber. In vitro transdermal experiments were performed at 37 °C and 250 rpm. 0.2 mL of samples were taken at 0, 2, 4, 6, 8, 10, 12, and 24 h after administration, and fresh PBS of equal volume and temperature was immediately added to measure the cumulative permeation per unit area (Q ₂₄ ) for 24 h. The calculation formula is as follows:

;

Where, _Cn is the drug concentration at the nth sampling point (μg/mL), Ci _is the drug concentration at the ith sampling point (μg/mL), A is the effective drug delivery area (3.14 ^cm2 ), and V is the volume of the receiving solution (mL). The Qt curve was plotted (Figure 3), and the slope was the transdermal absorption rate _Jss . The results are shown in Table 1.

Table 1 Transdermal penetration parameters of different groups

.

As can be seen from Table 1, the cumulative permeation per unit area of the liposomes with gas motor propulsion prepared by the present invention within 24 hours is not much different from that of the positive control azone, which proves that the whitening ingredients can effectively penetrate deep into the skin under the promotion of the gas motor. At the same time, the use of liposomes is safe and non-irritating, while azone has skin irritation and irreversible skin damage. The liposomes without gas motor propulsion (i.e., Comparative Example 1) have limited penetration effect in the skin. Therefore, the preparation of the present invention is expected to safely promote the efficient absorption of the active ingredients in the skin without the additional addition of a penetration enhancer.

In addition, the inventors also conducted experiments on Examples 1-7, 9-10 with reference to the above experimental methods. The results showed that the cumulative permeation per unit area of the liposomes with gas motor propulsion provided by the present invention within 24 hours was significantly higher than that of the control group, and was not much different from the positive control azone, indicating that the liposomes with gas motor propulsion provided by the present invention can promote the efficient absorption of active ingredients in the skin.

Test Example 2

In this test example, an inverted fluorescence microscope was used to study the in vivo transdermal absorption effect of the liposome cosmetic preparation of the present invention.

Twelve healthy male ICR mice with intact skin were selected, and their abdominal hair was removed under 2% chloral hydrate anesthesia, with the hair removal area of 1 cm×1 cm. The following groups all used FITC as a model drug (i.e., FITC was used instead of the active ingredient ascorbyl palmitate in Example 8 to facilitate observation of penetration under a fluorescence microscope), and the required carriers for each group were prepared according to the method of Example 8, and the following 3 groups were set up, with 4 mice in each group.

Experimental group 1: liposome solution group propelled by a gas motor (using the method of step (5) of Example 8, wherein FITC is substituted for ascorbyl palmitate, and the liposome whitening and moisturizing essence with gas motor propulsion is prepared in the same manner);

Experimental group 2: whitening component-loaded liposome solution group (using the method of step (1) of Example 8, wherein FITC replaces ascorbyl palmitate, and the liposome solution is prepared in the same manner);

Experimental group 3: free whitening ingredient ascorbyl palmitate group (FITC with the same mass of ascorbyl palmitate as that in step (1) of Example 8 was weighed and dissolved in PBS);

Take 0.5 g of each preparation and apply it to the administration site. After 8 hours, wipe the skin surface with warm water, cut and remove excess fat, prepare skin slices with a thickness of 7 μm by freezing microtome, and observe the penetration of model drugs in mouse skin of different groups by inverted fluorescence microscope (Figure 4). The free whitening component group (experimental group 3) is almost difficult to enter the skin. After encapsulating the free whitening component in liposomes (experimental group 2), a certain amount of fluorescence accumulation is observed in the surface layer of the skin, especially in the stratum corneum, but it is still not ideal. When combined with the gas motor (experimental group 1), fluorescence distribution is also observed in the deep layer of the skin, proving that gas molecules help to enhance the penetration of liposomes in the deep layer of the skin.

Test Example 3

Human keratinocytes (HaCaT), human fibroblasts (HSF), and mouse melanoma cells (B16 F10) were purchased from Shanghai ATCC Cell Bank; L-dopa was purchased from Shanghai Yuanye Biotechnology Co., Ltd.

In this test example, human keratinocytes, human fibroblasts, mouse B16 F10 melanoma cells and the liposome whitening and moisturizing essence with gas motor propulsion prepared in Example 8 were used as research objects. The proliferation of human keratinocytes and human fibroblasts, the tyrosinase activity of mouse melanoma cells, and the amount of melanin synthesis were used as indicators to evaluate the whitening effect of the moisturizing and whitening liposome essence with gas motor propulsion at the in vitro level.

(1) The MTT method was used to determine the effect of the moisturizing and whitening liposome essence with gas motor propulsion on the survival rate of human keratinocytes and fibroblasts. The experimental steps are as follows:

(a) Seeding: Cells in the logarithmic phase were seeded at a cell density of 7 × 10 ³ cells/well in a 96-well plate. 100 μL of DMEM high-glucose medium (containing 10% fetal bovine serum) was added to each well. Five replicate wells were set up for each group. The plates were cultured in a cell culture incubator containing 5% CO ₂ and 37°C for 24 h.

(b) Administration: The culture medium was aspirated and 100 μL of the whitening liposome essence solution containing different concentrations of drugs (0, 200, 400, 800, 1000, 1500 μg/mL) was added to each well (the solvent was DMEM culture medium). A control group (i.e., a full-living group without drugs, the solvent was DMEM culture medium) and a zeroing group (i.e., a zeroing well without cells and culture medium, the solvent was PBS) were set up. The cells were cultured for 24 h at 5% _CO2 and 37°C.

(c) Detection: The culture medium was aspirated and 120 μL of DMEM culture medium solution containing 0.5 mg/mL MTT was added to each well. After culturing for 4 h, the supernatant was aspirated and 150 μL of DMSO solution was added to each well. The cells were shaken at 500 rpm for 10 min, and the absorbance of each well was measured at 490 nm using a microplate reader (A).

The survival rate of each group of cells was calculated according to the following formula:

Survival rate (%) = (A _{preparation group} - A _{zeroing group} ) / (A _{control group} - A _{zeroing group} );

The measurement results are shown in Table 2.

Table 2 Effects of moisturizing and whitening liposome essence with gas motor propulsion on the proliferation rate of human keratinocytes and fibroblasts

.

As shown in Table 2, the moisturizing and whitening liposome essence with gas motor propulsion has no effect on the proliferation rate of human keratinocytes and fibroblasts, which proves the safety of the carrier.

(2) Tyrosinase activity inhibition experiment:

(a) Seed plate: B16F10 cells grown to the logarithmic phase were collected and seeded into 96-well plates at a cell density of 7000 cells/well. 100 μL of DMEM high-glucose medium (containing 10% fetal bovine serum) was added to each well, and 5 replicate wells were set up. The cells were cultured in a cell culture incubator containing 5% _CO2 and 37°C for 24 h.

(b) Administration: The culture medium was removed and 100 μL of liposome essence (solvent: DMEM medium) containing different concentrations of drugs (0, 200, 400, 800, 1000, 1500 μg/mL) was added. A control group (i.e., a full-living group without drugs, solvent: DMEM medium) was set up and cultured in a cell culture incubator containing 5% _CO2 and 37°C for 24 h.

(c) Determination: After 24 h of drug treatment, the supernatant was discarded, 90 μL of PBS buffer containing 1% TritonX-100 and 10 μL of 1 mg/mL L-dopa were added to each well, and the wells were placed in a 30°C constant temperature water bath for 30 min after ultrasonic treatment for 30 seconds. The absorbance (A) at 475 nm was measured and calculated as follows:

Tyrosinase activity (%) = A _{experimental group} /A _{control group} × 100%;

The measurement results are shown in Table 3.

Table 3 Effects of moisturizing and whitening liposome essence with gas motor propulsion on tyrosinase activity of mouse melanoma cells

.

Tyrosinase is one of the key enzymes for intracellular melanin synthesis, and its activity has a direct impact on the synthesis of melanin. As shown in Table 3, the moisturizing and whitening liposome essence with gas motor propulsion has a certain dose-dependent effect on the inhibition of tyrosinase activity in mouse melanoma cells. Combined with the cell proliferation experiment, it is shown that the present invention can downregulate tyrosinase activity without affecting cell viability, and the reduction of enzyme activity leads to a reduction in melanin synthesis.

(3) Determination of melanin synthesis

(a) Seed plate: B16F10 cells grown to the logarithmic phase were collected and inoculated into 6-well plates, each well containing 2 mL of complete medium, and 4 replicate wells were set up. The plates were cultured at 5% _CO2 and 37°C for 24 h.

(b) Administration: The culture medium was removed and 100 μL of liposome essence (solvent was DMEM culture medium) containing different concentrations of drugs (0, 200, 400, 800, 1000, 1500 μg/mL) was added. A control group (i.e., a cell-alive group without drugs and solvent was culture medium) was set up and cultured for 24 h at 5% _CO2 and 37°C.

(c) Determination: After 24 h of drug treatment, the supernatant was discarded, the cells were washed twice with PBS solution, collected in a centrifuge tube, centrifuged at 1500 rpm for 10 min, the supernatant was discarded, 2 mL of PBS was added for resuspending, and then 500 μL of ethanol-ether (1:1, v/v) was added, and the cells were placed at room temperature for 30 min, centrifuged at 3000 rpm for 5 min, and 1 mL of 1 mol/L NaOH solution containing 10% DMSO was added. The cells were incubated at 85°C for 45 min, and the absorbance (A) at 405 nm was measured. The calculation formula is as follows:

Melanin synthesis amount (%) = A _{experimental group} /A _{control group} × 100%.

The measurement results are shown in Table 4.

Table 4 Effect of moisturizing and whitening liposome essence with gas motor propulsion on melanin synthesis in mouse melanoma cells

.

It can be seen from Table 4 that the moisturizing and whitening liposome essence with gas motor propulsion prepared in the present invention can inhibit the formation of melanin within a certain concentration range, indicating that the preparation of the present invention has a good application prospect in whitening and removing spots.

Test Example 4

A commercially available skin moisture meter was used to measure the immediate and long-term moisturizing effects of the subjects after using the liposome essence prepared in Example 8 of the present invention.

20 subjects were randomly selected. Before the test, the volunteers were asked to clean their faces and dry them with a towel. 2 mL of liposome essence was evenly applied to the face and massaged until absorbed. The skin water content at the same location at different times after use was measured to obtain the immediate moisturizing results (Figure 5 and Figure 6, measured immediately after 10 minutes of use) and the long-term moisturizing effect (Figure 7, measured within 8 hours of use). The test results show that the product can achieve an immediate hydrating effect after application, and the skin water content can still be maintained within 8 hours, proving that the product can better meet people's daily hydration and moisturizing needs.

Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or replace some or all of the technical features therein by equivalents. However, these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims (7)

1. A moisturizing and whitening liposome essence, characterized by comprising: an acid-modified liposome solution and a salt-modified liposome solution; The acid-modified liposomes include cationic liposomes and acids electrostatically adsorbed on the cationic liposomes; the cationic liposomes include soybean lecithin, cationic lipids and cholesterol; The salt-modified liposomes include anionic liposomes and salts electrostatically adsorbed on the anionic liposomes; the anionic liposomes include soybean lecithin, anionic lipids and cholesterol; The acid and the salt react to generate a gas; The acid-modified liposomes and salt-modified liposomes independently encapsulate whitening active ingredients and/or moisturizing active ingredients; The acid is citric acid; The salt is at least one of sodium bicarbonate, ammonium bicarbonate, calcium carbonate or sodium carbonate; The cationic lipid is at least one of octadecylamine, (1,2-dioleyloxypropyl)trimethylammonium chloride or dioleoylphosphatidylethanolamine; The anionic lipid is at least one of phosphatidylserine, phosphatidylinositol, phosphatidic acid or phosphatidylglycerol; The whitening active ingredient is at least one of niacinamide, vitamin C and its derivatives, α-arbutin, 4-butylresorcinol, idebenone, resveratrol or ferulic acid; The moisturizing active ingredient is at least one of ergothioneine, ectoine, avocado oil, vitamin E or olive oil; In the cationic liposomes, the mass ratio of soybean lecithin to cholesterol is 5:1-20:1, the mass ratio of soybean lecithin to cationic lipid is 10:1-30:1, and the mass ratio of soybean lecithin to whitening active ingredients and/or moisturizing ingredients is 8:1-40:1; In the anionic liposomes, the mass ratio of soybean lecithin to cholesterol is 5:1-20:1, the mass ratio of soybean lecithin to anionic lipid is 10:1-30:1, and the mass ratio of soybean lecithin to whitening active ingredients and/or moisturizing ingredients is 8:1-40:1. 2. The moisturizing and whitening liposome essence according to claim 1, characterized in that the acid-modified liposome solution and the salt-modified liposome solution also independently include at least one of glycerol, sodium hyaluronate, 1,3-butylene glycol, betaine or allantoin. 3. The method for preparing the moisturizing and whitening liposome essence according to claim 1 or 2, characterized in that it comprises the following steps: a. mixing the cationic liposomes with an acid to obtain an acid-modified liposome solution; b. mixing the anionic liposomes with the salt to obtain a salt-modified liposome solution; c. The acid-modified liposome solution and the salt-modified liposome solution are respectively homogenized under high pressure to prepare a moisturizing and whitening liposome essence. 4. The preparation method according to claim 3, characterized in that the cationic liposomes and anionic lipids are independently prepared by a thin film dispersion method. 5. The preparation method according to claim 3, characterized in that in step a, the mixing reaction method is: under stirring conditions, the cationic liposome solution is added dropwise to the acid solution to carry out a mixing reaction; The stirring speed is 100-300 rpm, the reaction temperature is 25-37°C, the reaction time is 20 min-2 h, and the concentration of the acid solution is 0.1-1 mg/mL. 6. The preparation method according to claim 3, characterized in that in step b, the mixing reaction method is: under stirring conditions, the anionic liposome solution is added dropwise to the salt solution to carry out the mixing reaction; The stirring speed is 100-300 rpm, the reaction temperature is 25-37°C, the reaction time is 20 min-2 h, and the salt solution concentration is 0.3-3 mg/mL. 7. The preparation method according to claim 3 is characterized in that the pressure of the high-pressure homogenization is 500-2500 bar and the number of times is 5-20 times.