Glabridin flexible lipidosome, glabridin flexible lipidosome mask liquid and preparation methods of glabridin flexible lipidosome and glabridin flexible lipidosome mask liquid

Abstract

The invention provides a glabridin flexible liposome, a glabridin flexible liposome mask liquid and a preparation method, and relates to the technical field of cosmetics. The glabridin flexible liposome provided by the invention comprises a flexible nano liposome and glabridin wrapped by the flexible nano liposome, the flexible nano liposome is a liposome modified by dipotassium glycyrrhizinate, and the liposome is formed by phospholipid and cholesterol. According to the invention, the dipotassium glycyrrhizinate is used as an edge active agent, and the glabridin is wrapped in the flexible liposome, so that the problems of poor solubility and poor stability of the glabridin are solved while the transdermal properties of the glabridin and the dipotassium glycyrrhizinate are improved. According to the glabridin flexible lipidosome mask liquid provided by the invention, the glabridin flexible lipidosome is uniformly dispersed in the mask liquid, and the obtained glabridin flexible lipidosome mask liquid has excellent stability and also has good moisturizing, soothing and whitening effects.

Description

Technical Field

[0001] The present invention relates to the technical field of cosmetics, in particular to a glabridin flexible liposome and a glabridin flexible liposome facial mask liquid and a preparation method thereof. Background Art

[0002] Licorice, a perennial herb in the Leguminosae family, is a traditional Chinese medicine widely used in modern medicine, food, and cosmetics. The chemical structures of the compounds discovered and determined in licorice include triterpenoid saponins (primarily glycyrrhizic acid and glycyrrhetinic acid), total flavonoids (liquiritin, isoliquiritin, liquiritigenin, licoricechalcone A, and glabridin), alkaloids, polysaccharides, and amino acids. The active ingredients in licorice have antioxidant, anti-allergic, anti-inflammatory, and anti-skin tumor properties, and are effective in removing skin pigmentation. They also prevent skin aging, effectively scavenge superoxide ions, and inhibit tyrosinase activity.

[0003] Glabridin, a major component of the active ingredients in glycyrrhizin flavonoids, possesses numerous physiological functions, including whitening, antioxidant, cardiovascular protection, estrogen-like effects, and anti-atherosclerosis. Glabridin holds significant development and application value in the cosmetics and pharmaceutical industries. Known as "whitening gold" in the cosmetics field, it achieves skin whitening through multiple pathways. However, due to its poor water solubility and low transdermal absorption rate, its inclusion in cosmetics is limited, hindering its effective skin care benefits. Summary of the Invention

[0004] In view of this, the purpose of the present invention is to provide a glabridin flexible liposome and a glabridin flexible liposome facial mask liquid and a preparation method thereof. The glabridin flexible liposome provided by the present invention has good solubility and transdermal absorption.

[0005] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0006] The invention provides a glabridin flexible liposome, comprising a flexible nano-liposome and glabridin wrapped by the flexible nano-liposome, wherein the flexible nano-liposome is a liposome modified with dipotassium glycyrrhizate and is formed by phospholipid and cholesterol; the mass percentages of phospholipid, dipotassium glycyrrhizate, cholesterol and glabridin in the glabridin flexible liposome are 50-75%, 10-30%, 1-20% and 0.5-10%, respectively.

[0007] Preferably, the phospholipid comprises soy lecithin.

[0008] Preferably, the particle size of the glabridin flexible liposome is 78 to 150 nm.

[0009] The application provides a preparation method of the glycyrrhizin flexible liposome in the above technical scheme, and comprises the following steps:

[0010] The phospholipid, the dipotassium glycyrrhizinate, the cholesterol, the glabridin and the organic solvent are mixed to obtain a mixed solution;

[0011] The solvent in the mixed solution is evaporated to obtain a film;

[0012] The film is hydrated to obtain the glabridin flexible liposome;

[0013] The mass percentage of the phospholipid, the dipotassium glycyrrhizinate, the cholesterol and the glabridin is 50-75%, 10-30%, 1-20% and 0.5-10% respectively based on the total mass of the phospholipid, the dipotassium glycyrrhizinate, the cholesterol and the glabridin.

[0014] Preferably, the temperature of the hydration is 40-45 DEG C, and the time is 40-120 min.

[0015] Preferably, after the hydration, the obtained emulsion is sequentially subjected to filtration and ultrasonic treatment, and the power of the ultrasonic treatment is 100-250 W, and the time is 10-30 min.

[0016] The application provides a glabridin flexible liposome mask liquid, which comprises the following components in mass percentage:

[0017] The 4-hydroxyacetophenone is 0.3-1%, the panthenol is 0.8-10%, the EDTA-2Na is 0.05-0.1%, the 1,2-hexanediol is 0.3-0.8%, the glycerol polyether is 0.8-4%, the first sodium hyaluronate is 0.1-0.6%, the second sodium hyaluronate is 0.05-0.5%, the third sodium hyaluronate is 0.1-0.2%, the xanthan gum is 0.05-0.5%, the glabridin flexible liposome is 1-2%, and the water is the balance.

[0018] The number average molecular weight of the first sodium hyaluronate is 200-400 thousand, the number average molecular weight of the second sodium hyaluronate is 130-160 thousand, the number average molecular weight of the third sodium hyaluronate is 180-200 thousand, and the glabridin flexible liposome is the glabridin flexible liposome in the above technical scheme or the glabridin flexible liposome prepared by the preparation method in the above technical scheme.

[0019] The application provides a preparation method of the glabridin flexible liposome mask liquid in the above technical scheme, and comprises the following steps:

[0020] Part of the water, the 4-hydroxyacetophenone, the panthenol, the EDTA-2Na, the 1,2-hexanediol and the glycerol polyether are mixed to obtain a first mixed solution;

[0021] performing a second mixing of the first mixed solution with the first sodium hyaluronate, the second sodium hyaluronate, the third sodium hyaluronate, and xanthan gum to obtain a second mixed solution;

[0022] The second mixed liquid, the glabridin flexible liposomes and the remaining part of water are mixed for a third time to obtain the glabridin flexible liposome facial mask liquid.

[0023] Preferably, the temperature of the first mixing is 40-50°C, the temperature of the second mixing is 55-70°C, and the temperature of the third mixing is 30-40°C.

[0024] Preferably, the first mixing, the second mixing and the third mixing are all stirred mixing.

[0025] The present invention provides a glabridin flexible liposome, comprising a flexible nanoliposome and glabridin encapsulated by the flexible nanoliposome. The flexible nanoliposome is a liposome modified with dipotassium glycyrrhizate and formed from phospholipids and cholesterol. The mass percentages of phospholipids, dipotassium glycyrrhizate, cholesterol, and glabridin in the glabridin flexible liposome are 50-75%, 10-30%, 1-20%, and 0.5-10%, respectively. The dipotassium glycyrrhizate described in the present invention is a skin conditioning agent and a multifunctional cosmetic ingredient with the functions of soothing sensitivity, repairing damage, resisting inflammation, and whitening the skin. It can increase the fluidity of the liposome bilayer membrane and, as a marginal active agent, can impart a high degree of deformability to the lipid membrane, thereby improving the permeability of the preparation. The present invention uses dipotassium glycyrrhizate as a marginal active agent and encapsulates glabridin in flexible liposomes, thereby increasing the transdermal permeability of glabridin and dipotassium glycyrrhizate while also improving the solubility and stability of glabridin, so that cosmetics containing glabridin can effectively exert skin care functions such as whitening and soothing.

[0026] In the examples of the present invention, the in vitro diffusion cell method was used to evaluate the transdermal effect of the glabridin flexible liposome product according to the "In Vitro Test Method for Skin Absorption of Chemicals" (using the mouse back skin as a model, the in vitro Franz diffusion cell method was used to measure the transdermal performance of the glabridin flexible liposome, and HPLC was used to measure the retention of glabridin in the skin). The results showed that the drug penetration and retention of the glabridin nano-flexible liposomes were much higher than those of free glabridin, reaching 3.9 times and 7 times the latter, respectively, significantly improving the bioavailability of glabridin.

[0027] The present invention provides a glabridin flexible liposome facial mask liquid, wherein the glabridin flexible liposomes can be uniformly dispersed in the facial mask liquid, and is combined with p-hydroxyacetophenone, panthenol, EDTA-2Na, 1,2-hexanediol, glycerol polyether, sodium hyaluronate and xanthan gum, so that the obtained glabridin flexible liposome facial mask liquid has excellent stability and good moisturizing, soothing and whitening effects.

[0028] The present invention provides a method for preparing the glabridin flexible liposome facial mask liquid described in the above technical solution, which has a simple process, easy-to-obtain ingredients, and is convenient for industrial promotion and application. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 The effect of the mass ratio of soybean lecithin and dipotassium glycyrrhizate on the particle size of glycyrrhizin flexible liposomes in Example 1 of the present invention is shown;

[0030] Figure 2 The effect of the mass ratio of soybean lecithin to cholesterol on the particle size of glycyrrhizin flexible liposomes in Example 1 of the present invention is shown;

[0031] Figure 3 The Tyndall effect of the glycyrrhizin flexible liposome preparation prepared by the optimal process in Example 1 of the present invention;

[0032] Figure 4 This is a transmission electron microscopy (TEM) image of the flexible liposomes added to the facial mask solution in an embodiment of the present invention;

[0033] Figure 5 The transdermal performance test results of glabridin flexible liposomes and free glabridin in the examples (glabridin cumulative transmittance);

[0034] Figure 6 The amount of glabridin retained in the skin after transdermal transdermal treatment using glabridin flexible liposomes and free glabridin in the examples;

[0035] Figure 7 The effect of glabridin flexible liposome mask on AQP3 in HaCaT cells in the example;

[0036] Figure 8 The effect of the glabridin flexible liposome mask solution on TNF-α in RAW.7 mouse cells in the example;

[0037] Figure 9 The effect of the glabridin flexible liposome mask on the melanin of B16F10 cells in the example;

[0038] Figure 10 The effect of the glabridin flexible liposome mask on tyrosinase in B16F10 cells in the example;

[0039] Figure 11 This is the sustained release curve of the glabridin flexible liposomes in the example. DETAILED DESCRIPTION

[0040] The invention provides a glabridin flexible liposome, comprising a flexible nano-liposome and glabridin wrapped by the flexible nano-liposome, wherein the flexible nano-liposome is a liposome modified with dipotassium glycyrrhizate and is formed by phospholipid and cholesterol; the mass percentages of phospholipid, dipotassium glycyrrhizate, cholesterol and glabridin in the glabridin flexible liposome are 50-75%, 10-30%, 1-20% and 0.5-10%, respectively.

[0041] In the present invention, the phospholipid preferably includes soybean lecithin.

[0042] In the present invention, the mass percentage of phospholipids in the glabridin flexible liposomes is 50-75%, which can be 50%, 55%, 60%, 65%, 67%, 70%, 71%, 72% or 75%, and is preferably 60-72%; the mass percentage of dipotassium glycyrrhizate in the glabridin flexible liposomes is 10-30%, which can be 14%, 15%, 16%, 17%, 19%, 19.5%, 20% or 25%, and is preferably 14-20%; the mass percentage of cholesterol in the glabridin flexible liposomes is 1-20%, which can be 5%, 10%, 13%, 15% or 20%, and is preferably 10-15%; the mass percentage of glabridin in the glabridin flexible liposomes is 0.5-10%, which can be 1%, 2%, 2.5%, 2.6%, 3%, 4% or 5%, and is preferably 2-4%.

[0043] Flexible nanoliposomes are a special type of nanoliposomes composed of phosphatidylcholine, cholesterol, and a surfactant called an edge activator. Edge activators influence the properties and functions of flexibility, imparting a high degree of deformability to the lipid membrane, forcing the vesicles to deform and enabling them to penetrate pores in the stratum corneum that are 1 / 10 smaller than their own particle size, resulting in enhanced permeability compared to liposomes. Edge activators occupy the combined space of phospholipid molecules and disrupt the orderly arrangement of the lipid bilayer, giving the transfersome a high degree of deformability. In addition to the deformability imparted by the surfactant, when flexible liposomes are evenly applied to the skin under non-enclosed conditions, the evaporation of water from the flexible liposomes forms an outside-in hydration osmotic gradient on the skin's surface, pulling fat-soluble ingredients along the pores into the skin and increasing transdermal absorption of active ingredients.

[0044] Dipotassium glycyrrhizate is a potassium salt of glycyrrhizic acid extracted from the root of licorice. The raw material is a white powder. It is a skin conditioner and a multifunctional cosmetic raw material with excellent biocompatibility, soothing sensitivity, repairing damage, anti-inflammatory and whitening functions. It can also increase the fluidity of the liposome bilayer membrane and act as a marginal surfactant to give the lipid membrane a high degree of deformation ability, effectively imparting flexibility and deformation ability to the liposome, improving the permeability of the preparation, overcoming the skin barrier, and achieving efficient transdermal delivery.

[0045] The present invention uses dipotassium glycyrrhizate as a marginal active agent in flexible liposomes, playing a key role primarily through its amphiphilic structure: its hydrophobic aglycone portion inserts into the phospholipid bilayer, disrupting the close arrangement of phospholipid molecules, increasing the molecular distance and weakening van der Waals interactions, thereby reducing membrane rigidity and significantly enhancing lipid membrane fluidity; at the same time, the larger hydrophilic uronic acid group forms a wedge-shaped structure, inducing local curvature defects in the membrane, making the liposome more deformable under mechanical stress or osmotic pressure. When acting synergistically with cholesterol, it can balance the fluidity and stability of the membrane, preventing liposome rupture caused by excessive flexibility. In addition, dipotassium glycyrrhizate also has unique natural active advantages: on the one hand, it has anti-inflammatory and anti-allergic effects, and on the other hand, it is gentle and safe when acting on the skin, reducing transdermal delivery irritation. This multiple mechanism of action not only effectively enhances the deformability of liposomes, but also gives the delivery system better biocompatibility.

[0046] Glabridin is a small molecule isoflavone substance with a molecular weight of 324.4g / mol, is hydrophobic, and has a low transdermal absorption rate. The present invention uses dipotassium glycyrrhizate as a marginal active agent, and wraps glabridin in a flexible liposome. While increasing the transdermal properties of glabridin and dipotassium glycyrrhizate, the characteristics of poor water solubility and low transdermal absorption rate of glabridin are solved, so that its cosmetics can efficiently play the role of skin care functions such as whitening and soothing. In addition, the glabridin flexible liposome has good compatibility with the cosmetic matrix liquid and can effectively maintain the stability of the active ingredient.

[0047] In the present invention, the particle size of the glabridin flexible liposomes is 78 to 150 nm. The small particle size of the glabridin flexible liposomes in the present invention enables them to have better transdermal efficiency. In the embodiments of the present invention, the glabridin flexible liposomes are also referred to as dipotassium glycyrrhizate-modified glabridin flexible liposomes.

[0048] The present invention provides a method for preparing the glabridin flexible liposomes described in the above technical solution, comprising the following steps:

[0049] mixing phospholipid, dipotassium glycyrrhizate, cholesterol, glabridin and an organic solvent to obtain a mixed solution;

[0050] Evaporating the mixed solution to remove the solvent to obtain a film;

[0051] hydrating the film to obtain the glabridin flexible liposome;

[0052] Based on the total mass of phospholipid, dipotassium glycyrrhizate, cholesterol and glabridin, the mass percentages of phospholipid, dipotassium glycyrrhizate, cholesterol and glabridin are 50-75%, 10-30%, 1-20% and 0.5-10% respectively.

[0053] In the present invention, unless otherwise specified, all raw materials involved are commercially available products well known in the art.

[0054] The invention mixes phospholipid, dipotassium glycyrrhizate, cholesterol, glabridin and an organic solvent to obtain a mixed solution.

[0055] In the present invention, based on the total mass of phospholipids, dipotassium glycyrrhizate, cholesterol and glabridin, the mass percentages of phospholipids, dipotassium glycyrrhizate, cholesterol and glabridin are 50-75%, 10-30%, 1-20% and 0.5-10%, respectively, preferably 60-72%, 14-20%, 10-15% and 2-4%, respectively; the mass ratio of the phospholipids, dipotassium glycyrrhizate, cholesterol and glabridin is preferably 25:5:4:0.8. The present invention controls the amount of phospholipids, dipotassium glycyrrhizate, cholesterol and glabridin within the above range, which can adapt to the particle size, high encapsulation efficiency and release characteristics (sustained release) of glabridin. In the present invention, the organic solvent is preferably an alcohol solvent, and the alcohol solvent is preferably ethanol. The present invention has no special requirements for the amount of the organic solvent, as long as it can fully dissolve the phospholipids, dipotassium glycyrrhizate, cholesterol and glabridin. In the present invention, the mixing of the phospholipid, dipotassium glycyrrhizate, cholesterol, glabridin and the organic solvent is preferably ultrasonically mixed.

[0056] After obtaining the mixed solution, the present invention evaporates the mixed solution to remove the solvent to obtain a film.

[0057] In the present invention, the evaporation is preferably rotary evaporation, specifically pouring the mixed liquid into a rotary evaporation flask for evaporation; the temperature of the rotary evaporation is preferably 40-50°C, and can be 40, 45 or 50°C, and the rotary evaporation time is until a uniform thin film appears on the wall of the rotary evaporation flask.

[0058] After obtaining the film, the present invention hydrates the film to obtain the glabridin flexible liposome.

[0059] In the present invention, the hydration temperature is preferably 40-45°C, and the time is preferably 40-120 minutes, which can be 40, 60, 100, or 120 minutes. The hydration is preferably rotary hydration. In the present invention, the specific operation of the hydration is preferably: adding pure water preheated to 40-45°C to the film, hydrating at 40-45°C to obtain a milky yellow emulsion, and then manually shaking with the aid of ultrasound until the film on the bottle wall is completely detached.

[0060] After the hydration, the present invention also preferably filters and ultrasonically treats the obtained emulsion in sequence; the power of the ultrasonic treatment is preferably 100-250W, which can be 150, 180 or 200W, and the time is preferably 10-30min, which can be 15 or 20min. The present invention makes the emulsion uniform and reduces the particle size of the preparation through the ultrasonic treatment.

[0061] The invention dissolves lecithin, cholesterol and glabridin in an organic solvent, and adds dipotassium glycyrrhizate, a key flexible additive, to form a lipid film through evaporation. In the hydration stage, an aqueous medium is added at a temperature higher than the phase transition temperature of the phospholipids, and the lipid film expands and peels off to form multilayer liposomes, which encapsulate the glabridin. The dipotassium glycyrrhizate, a flexible additive, is inserted into the phospholipid bilayer and modified by the dipotassium glycyrrhizate to increase the fluidity of the liposome lipid bilayer membrane and enhance its deformability.

[0062] The present invention provides a glabridin flexible liposome facial mask liquid, comprising the following components in percentage by weight:

[0063] p-Hydroxyacetophenone 0.3-1%, panthenol 0.8-10%, EDTA-2Na 0.05-0.1%, 1,2-hexanediol 0.3-0.8%, glycerol polyether 0.8-4%, first sodium hyaluronate 0.1-0.6%, second sodium hyaluronate 0.05-0.5%, third sodium hyaluronate 0.1-0.2%, xanthan gum 0.05-0.5%, glabridin flexible liposome 1-2%, balance water;

[0064] The number average molecular weight of the first sodium hyaluronate is 200,000 to 400,000, the number average molecular weight of the second sodium hyaluronate is 1.3 to 1.6 million, and the number average molecular weight of the third sodium hyaluronate is 1.8 to 2 million; the glabridin flexible liposomes are the glabridin flexible liposomes described in the above technical solution or the glabridin flexible liposomes prepared by the preparation method described in the above technical solution.

[0065] The glabridin flexible liposome facial mask provided by the present invention comprises 0.3-1% p-hydroxyacetophenone by mass percentage, which may be 0.3%, 0.5%, 0.6% or 0.8%. In the present invention, the p-hydroxyacetophenone has an antioxidant effect.

[0066] The glabridin flexible liposome facial mask provided by the present invention comprises 0.8-10% panthenol by weight, which may be 1%, 1.5%, 2%, 5% or 8%. In the present invention, the panthenol is preferably D-panthenol; the panthenol has a moisturizing and soothing effect.

[0067] The glabridin flexible liposome mask liquid provided by the present application contains 0.05-0.1% EDTA-2Na in terms of mass percentage, which can be 0.05%, 0.06%, 0.07%, 0.08%, 0.09% or 0.1%. In the present application, the EDTA-2Na is a chelating agent.

[0068] The glabridin flexible liposome mask liquid provided by the present application contains 0.3-0.8% 1,2-hexanediol in terms of mass percentage, which can be 0.5%, 0.6%, 0.7% or 0.8%. In the present application, the 1,2-hexanediol has a moisturizing effect.

[0069] The glabridin flexible liposome mask liquid provided by the present application contains 0.8-4% glycerol polyether in terms of mass percentage, which can be 1%, 2%, 3% or 4%. In the present application, the glycerol polyether is preferably glycerol polyether-26; the glycerol polyether is an emollient.

[0070] The glabridin flexible liposome mask liquid provided by the present application contains 0.1-0.6% first sodium hyaluronate in terms of mass percentage, which can be 0.2%, 0.3%, 0.4% or 0.5%. In the present application, the number average molecular weight of the first sodium hyaluronate is 200-400 thousand.

[0071] The glabridin flexible liposome mask liquid provided by the present application contains 0.05-0.5% second sodium hyaluronate in terms of mass percentage, which can be 0.1%, 0.2%, 0.3% or 0.4%. In the present application, the number average molecular weight of the second sodium hyaluronate is 1.3-1.6 million.

[0072] The glabridin flexible liposome mask liquid provided by the present application contains 0.1-0.2% third sodium hyaluronate in terms of mass percentage, which can be 0.1%, 0.15% or 0.2%. In the present application, the number average molecular weight of the third sodium hyaluronate is 1.8-2 million. In the present application, the sodium hyaluronate has a moisturizing and soothing effect; the present application adopts sodium hyaluronates with different molecular weights (i.e. the first sodium hyaluronate, the second sodium hyaluronate and the third sodium hyaluronate), among which the small-molecule sodium hyaluronate penetrates deep into the dermis to promote repair by taking advantage of small molecules, the medium-molecule sodium hyaluronate is mainly for water replenishment, densely replenishes water to make the skin elastic and moisturized, the large-molecule sodium hyaluronate has the hardest texture and has a crosslinking effect, which can form a water-locking film on the outer layer of the skin to protect the small and medium-molecule sodium hyaluronates, thereby playing a better effect.

[0073] The glabridin flexible liposome mask liquid provided by the present application contains 0.05-0.5% xanthan gum in terms of mass percentage, which can be 0.1%, 0.2%, 0.3% or 0.4%. In the present application, the xanthan gum is a thickening agent.

[0074] The glabridin flexible liposome facial mask provided by the present invention comprises 1-2% of glabridin flexible liposomes, which may be 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8% or 1.9%, in terms of mass percentage. The glabridin flexible liposomes are the glabridin flexible liposomes described in the above technical solution or the glabridin flexible liposomes prepared by the preparation method described in the above technical solution. In the present invention, the glabridin in the glabridin flexible liposomes has whitening and soothing effects, phospholipids are emulsifiers and have moisturizing effects, cholesterol is a skin conditioner and emollient, and dipotassium glycyrrhizate has moisturizing and soothing effects.

[0075] The glabridin flexible liposome facial mask provided by the present invention includes water as the remainder, calculated by weight percentage. In the present invention, the water is preferably pure water; the water serves as a solvent.

[0076] The glabridin flexible liposome facial mask provided by the present invention has excellent stability. When tested for heat resistance (40°C) and cold resistance (4°C), no adverse phenomena such as deterioration and stratification occurred. No oil-water separation and stratification occurred after centrifugation at 3000-5000 r / min. In the embodiment of the present invention, the glabridin flexible liposome facial mask was tested for whitening efficacy (using an Elisa kit to determine the tyrosinase inhibition rate and melanin inhibition rate after the flexible liposome facial mask was applied to B16F10 cells), moisturizing efficacy (using an Elisa kit to determine the AQP3 expression level after the flexible liposome facial mask was applied to HaCaT cells), and soothing efficacy (using LPS to stimulate macrophage modeling, and then using an Elisa kit to determine the inhibition rate of the inflammatory factor TNF-α after the flexible liposome facial mask was applied to macrophages). The results showed that the glabridin flexible liposome facial mask had good moisturizing, soothing and whitening efficacy.

[0077] The present invention successfully transforms pharmaceutical preparation technology into the facial mask category, achieving full-link optimization of "transdermal-retention-release", solving the dual pain points of "whitening irritation" and "insufficient efficacy" for people with sensitive skin, and achieving "instant soothing + long-lasting whitening" with a single use. The glabridin flexible liposome facial mask liquid provided by the present invention can achieve multifunctional skin care: it has the triple effects of whitening, soothing and moisturizing, which is in line with the current trend of "streamlined skin care" and reduces the burden on users of superimposed products. The present invention not only strengthens the whitening effect of glabridin, but also enhances the soothing and moisturizing functions through ingredients such as dipotassium glycyrrhizate, panthenol, and sodium hyaluronate, meeting consumers' dual needs for "whitening + repair".

[0078] The present invention provides a method for preparing the glabridin flexible liposome facial mask liquid described in the above technical solution, comprising the following steps:

[0079] Mixing a portion of water, p-hydroxyacetophenone, panthenol, EDTA-2Na, 1,2-hexanediol, and glycerol polyether to obtain a first mixed solution;

[0080] performing a second mixing of the first mixed solution with the first sodium hyaluronate, the second sodium hyaluronate, the third sodium hyaluronate, and xanthan gum to obtain a second mixed solution;

[0081] The second mixed liquid, the glabridin flexible liposomes and the remaining part of water are mixed for a third time to obtain the glabridin flexible liposome facial mask liquid.

[0082] In the present invention, part of water, p-hydroxyacetophenone, panthenol, EDTA-2Na, 1,2-hexanediol and glycerol polyether are first mixed to obtain a first mixed solution (referred to as phase A in the embodiment of the present invention).

[0083] In the present invention, the temperature of the first mixing is preferably 40-50°C, and can be 40, 45 or 50°C. In the present invention, water is preferably heated to 40-50°C, and then p-hydroxyacetophenone, panthenol, EDTA-2Na, 1,2-hexanediol and glycerol polyether are added in sequence, and each component is added while stirring. In the present invention, the first mixing is preferably stirring mixing, and the stirring mixing speed is preferably 1000-1800 rpm, and can be 1500 rpm. The time is preferably 2-4 hours, and can be 3 hours. The time of the first mixing is calculated from the completion of the addition of each component.

[0084] After obtaining the first mixed solution, the present invention performs a second mixing of the first mixed solution with the first sodium hyaluronate, the second sodium hyaluronate, the third sodium hyaluronate and xanthan gum to obtain a second mixed solution (referred to as phase B in the embodiment of the present invention).

[0085] In the present invention, the temperature of the second mixing is preferably 55-70°C, and can be 60, 65 or 70°C. In the present invention, the first mixed solution is preferably heated to 55-70°C, and the first sodium hyaluronate, the second sodium hyaluronate, the third sodium hyaluronate and xanthan gum are added in sequence, with each component being added while stirring. In the present invention, the second mixing is preferably stirring mixing, and the stirring mixing speed is preferably 1000-1800 rpm, and can be 1500 rpm, and the time is preferably 2-4 hours, and can be 3 hours.

[0086] After obtaining the second mixed liquid, the present invention performs a third mixing of the second mixed liquid, the glabridin flexible liposomes and the remaining water to obtain the glabridin flexible liposome facial mask liquid.

[0087] In the present invention, the temperature of the third mixing is preferably 30-40°C, and can be 35 or 40°C. The present invention preferably cools the second mixed liquid to 30-40°C, and then adds the glabridin flexible liposomes and the remaining water thereto. The glabridin flexible liposomes and the remaining water are added while stirring. In the present invention, the part of water and the remaining water constitute all the water in the glabridin flexible liposome mask liquid; when the glabridin flexible liposomes are prepared by the preparation method described in the above technical solution, the liposome emulsion formed by the glabridin flexible liposomes and water is obtained after hydration. The glabridin flexible liposomes and the remaining water can be directly added in the form of the liposome emulsion. In an embodiment of the present invention, the part of water accounts for 74.16% of the mass of the glabridin flexible liposome mask liquid.

[0088] In the present invention, the third mixing is preferably stirring mixing, the rotation speed of the stirring mixing is preferably 1500 rpm, and the time is preferably 30 minutes.

[0089] The present invention mixes the components according to the above mixing order, which is conducive to achieving uniform mixing of the components.

[0090] The preparation method of the glabridin flexible liposome facial mask liquid provided by the present invention has simple process, easy-to-obtain ingredients, and is convenient for industrial promotion and application.

[0091] To further illustrate the present invention, the glabridin flexible liposomes, glabridin flexible liposome facial mask liquid and preparation method provided by the present invention are described in detail below with reference to examples, but they should not be construed as limiting the scope of protection of the present invention.

[0092] Example 1

[0093] 1. Preparation and characterization of dipotassium glycyrrhizinate-modified glabridin flexible liposomes

[0094] The particle size of glabridin flexible liposomes was used as the evaluation index, and the effects of the mass ratio of soybean lecithin to dipotassium glycyrrhizate and the mass ratio of soybean lecithin to cholesterol on the particle size were investigated to determine their effects on glabridin flexible liposomes.

[0095] 1.1 Mass ratio of soybean lecithin and dipotassium glycyrrhizate

[0096] Take 10 mg of soy lecithin, 5 mg of cholesterol, and 0.4 mg of glycyrrhizin, accurately weigh them, and then weigh dipotassium glycyrrhizate according to the mass ratio of soy lecithin: dipotassium glycyrrhizate of 1:1, 2:1, 4:1, and 8:1, respectively, add them to an appropriate amount of ethanol and ultrasonically dissolve them, and rotary evaporate them at 45°C until a uniform film appears on the wall of the rotary evaporation flask; then add pure water preheated to 45°C to the film medium, and rotary hydrate at 45°C for 1 hour to obtain a milky yellow emulsion, which is then shaken by hand with the aid of ultrasound until the film on the wall of the cup completely falls off. After filtering the obtained emulsion, use a 180W probe to ultrasonically treat it for 15 minutes to ensure the uniformity of the solution to obtain a glycyrrhizin flexible liposome emulsion. The particle size of the glycyrrhizin flexible liposome emulsion was measured as follows Figure 1 As shown in Table 1, Figure 1 The 1:1, 2:1, 4:1, and 8:1 in the formula respectively indicate that the mass ratios of soybean lecithin to dipotassium glycyrrhizate are 1:1, 2:1, 4:1, and 8:1.

[0097] Table 1 Particle size of glabridin flexible liposomes obtained at different mass ratios of soybean lecithin and dipotassium glycyrrhizate

[0098] Soy Lecithin: Dipotassium Glycyrrhizate 1:1 2:1 4:1 8:1 Particle size 143nm 134nm 113nm 136nm

[0099] 1.2 Mass ratio of soybean lecithin and cholesterol

[0100] Take 10 mg of soy lecithin, 2.5 mg of dipotassium glycyrrhizate, and 0.4 mg of glycyrrhizin, accurately weigh them, and then weigh cholesterol according to the mass ratio of soy lecithin: cholesterol of 2:1, 5:1, 10:1, and 20:1, respectively, add them to an appropriate amount of ethanol and ultrasonically dissolve them, and rotary evaporate them at 45°C until a uniform film appears on the wall of the rotary evaporation flask; add pure water preheated to 45°C to the film medium, and rotary hydrate at 45°C for 1 hour to obtain a milky yellow emulsion, which is then shaken by hand with the aid of ultrasound until the film on the wall of the cup completely falls off. After filtering the obtained emulsion, use a 180W probe to ultrasonically treat it for 15 minutes to ensure the uniformity of the solution to obtain glycyrrhizin flexible liposome emulsion. The particle size of the glycyrrhizin flexible liposome emulsion was measured as follows Figure 2 As shown in Table 2, Figure 2 The 2:1, 5:1, 10:1, and 20:1 represent the mass ratios of soy lecithin and cholesterol.

[0101] Table 2 Particle size of glabridin flexible liposomes obtained at different mass ratios of soybean lecithin and cholesterol

[0102] Soy lecithin: cholesterol 2:1 5:1 10:1 20:1 Particle size 118nm 78nm 81nm 128nm

[0103] After comprehensive evaluation of the influence of various factors, it was determined that the minimum particle size was about 78nm when the ratio of soy lecithin: dipotassium glycyrrhizate: cholesterol mass: glycyrrhizin was 20:5:4:0.8, which was the optimal process prescription for the preparation.

[0104] 2.1 Characterization of dipotassium glycyrrhizinate-modified glabridin flexible liposomes

[0105] (1) The preparation prepared by the optimal formula, i.e., the glabridin flexible liposome modified with dipotassium glycyrrhizinate (transparent liquid), was diluted to 50 times with double distilled water, and its particle size and polydispersity index (PDI) were measured using a Malvern particle size analyzer, and its encapsulation efficiency (EE%) and drug loading were measured using HPLC. The results are shown in Table 3. The particle size was about 78 nm, the PDI was about 0.26, the encapsulation efficiency (EE%) was 89%, and the drug loading was 2.8%. Table 3 Particle size, polydispersity index (PDI), encapsulation efficiency (EE%) and drug loading of the glabridin flexible liposome modified with dipotassium glycyrrhizinate prepared by the optimal formula

[0106] PDI Particle size EE Drug loading 0.26 78nm 89％ 2.8％

[0107] The above characterization data demonstrate that dipotassium glycyrrhizinate-modified glabridin flexible liposome particles can be evenly dispersed in the dispersion medium and have excellent drug loading capacity. They also exhibit a relatively high drug encapsulation efficiency. With a particle size of 78 nm, these small particles offer improved transdermal efficiency compared to conventional emulsions. Their use as a new raw material in cosmetics could enhance the efficacy of active ingredients.

[0108] The above nanoformulations were illuminated by a laser pen and the Tyndall effect was observed to verify the light scattering properties of the particles. Figure 3 As shown, when irradiated with a laser pointer, there is a bright path, which proves that the preparation has a good Tyndall effect and forms good nanoparticles.

[0109] (2) The drug permeation experiment of isolated rat skin was conducted using the vertical Franz diffusion cell method. Figure 11 As shown, compared with the glabridin dispersion solution, the glabridin transfersome (i.e., glabridin flexible liposome) exhibited a more obvious sustained-release characteristic.

[0110] Example 2

[0111] Preparation and preparation process of glabridin flexible liposome facial mask liquid modified with dipotassium glycyrrhizinate

[0112] 1. Preparation of dipotassium glycyrrhizinate-modified glabridin flexible liposome facial mask

[0113] (1) The formula of the glabridin flexible liposome facial mask modified with dipotassium glycyrrhizate is shown in Table 4.

[0114] Table 4 Formulation composition of glycyrrhizin flexible liposome mask liquid

[0115]

[0116] (2) The preparation process of glycyrrhizin flexible liposome mask liquid modified by glycyrrhizic acid disodium is as follows:

[0117] Preparation of phase A: First, add 74.16% pure water, heat to 50°C in a water bath, then weigh 0.5% p-hydroxyacetophenone, 1.5% panthenol, 0.05% EDTA-2Na, 0.5% 1,2-hexanediol, and 1% glycerol polyether-26, add while stirring, and after adding all the materials, stir at 1500 rpm for 1 h to obtain a uniform translucent viscous liquid;

[0118] Preparation of phase B: Heat phase A to 70°C, then add 0.4% sodium hyaluronate (20-40 million), 0.1% sodium hyaluronate (130-160 million), 0.2% sodium hyaluronate (180-200 million), and 0.1% xanthan gum while stirring, with a stirring speed of 1500 rpm, and stir for 3 h;

[0119] Preparation of phase C (i.e. glycyrrhizin flexible liposome): Dissolve 0.04% glycyrrhizin, 1% soy lecithin, 0.2% cholesterol, and 0.25% glycyrrhizic acid disodium in 30 mL of ethanol, and after complete ultrasonic dissolution, pour into a rotary evaporation flask. Rotate and evaporate at 45°C until a uniform thin film appears on the wall of the rotary evaporation flask. Add 20% pure water preheated to 45°C to the thin film medium, and after rotating and hydrating at 45°C for 1 h, a milky yellow emulsion is obtained. Then shake by hand and assist with ultrasonic until the thin film on the cup wall completely falls off. Filter the obtained emulsion and optimize the particle size of the preparation by using an 180W probe for ultrasonic treatment for 15 min;

[0120] Cool phase B to 40°C, add phase C while stirring, with a stirring speed of 1500 rpm, and stir for 30 min. After cooling, make up to volume. Can, package.

[0121] 2. Physicochemical properties and stability of glycyrrhizin flexible liposome mask liquid modified by glycyrrhizic acid disodium

[0122] Use a transmission electron microscope (TEM) to observe the micro-morphology of the glycyrrhizin flexible liposome mask liquid. After adding the glycyrrhizin flexible liposome to the mask liquid, dilute 1 mL of the sample with ultrapure water, and then use a rubber dropper to drop a drop of the sample on a copper mesh. After natural air drying, drop another drop of 2% phosphotungstic acid solution for 1-2 min, absorb the excess liquid with filter paper, and then observe the morphology with a transmission electron microscope. The results are as follows: Figure 4As shown, the flexible liposomes are spherical vesicles and are evenly dispersed in the mask liquid.

[0123] The pH, appearance, odor, stability, etc. of the facial mask liquid were measured according to the facial mask implementation standard QBT2872-2017.

[0124] Cold and heat resistance test: 20 mL of the prepared dipotassium glycyrrhizinate-modified glabridin flexible liposome mask solution was placed in conical flasks. Five bottles were placed in a constant temperature incubator at (40±1)°C, and five bottles were placed in a 4°C refrigerator. After 24 hours, the flasks were removed and returned to room temperature. The remaining five bottles were placed in a constant humidity desiccator (room temperature) for 24 hours as a control group. The experimental groups were then visually compared with the control group before and after the experiment to see if there were any significant differences.

[0125] Stability test: Take three 25mL portions of homogeneous facial mask liquid and place them in 50mL centrifuge tubes. At room temperature, centrifuge them at 3000r / min, 3500r / min, 4000r / min, 4500r / min, and 5000r / min for 10min respectively. Then observe whether the samples in the centrifuge tubes show stratification.

[0126] The results showed that: after measurement, the pH value of the glycyrrhizin dipotassium modified flexible liposome mask liquid was about 6.8, the appearance was a white liquid, and the odor was odorless, which met the national mask implementation standard QBT2872-2017. When the mask was tested for heat and cold resistance, no adverse phenomena such as deterioration and stratification occurred. However, observation of its color revealed that the mask liquid can better maintain its original shape and odor in a 4°C environment. It is recommended to store it at room temperature or 4°C during use; when the mask was tested for stability, no oil-water separation and stratification occurred when the rotation speed was 3000r / min, 3500r / min, 4000r / min, 4500r / min, and 5000r / min, indicating that the formula of the glycyrrhizin dipotassium modified flexible liposome mask liquid is heat-resistant, cold-resistant, and relatively stable.

[0127] 3. Transdermal performance of dipotassium glycyrrhizinate-modified glabridin flexible liposomes and evaluation of their efficacy in facial mask solutions

[0128] 3.1 Evaluation of transdermal performance: The drug transdermal experiment of isolated mouse skin was carried out using the vertical Franz diffusion cell method. The abdominal skin of the mouse was fixed between the receiving chamber and the donor chamber of the diffusion cell with r=1 cm, and 0.5g of glabridin flexible liposomes and free glabridin release medium solution (i.e. Gla dispersion solution) were respectively taken in the donor chamber, and 2% Tween80-20% propylene glycol-normal saline was used as the receiving solution, and the mixture was stirred and diffused at 37°C and 300r / min. 0.5mL of the receiving solution was taken at 2h, 4h, 6h, 8h, 10h, 12h, and 24h, and an equal amount of constant temperature blank receiving solution was immediately added. The glabridin penetration at different times was measured by HPLC, and the cumulative penetration was calculated. The results are shown as follows. Figure 5 As shown, Figure 5 These are the transdermal performance test results of glabridin flexible liposomes and free glabridin (cumulative permeability of glabridin).

[0129] After 24 hours, the skin was removed, washed with ultrapure water to remove residual sample liquid, and then cut into pieces and transferred to a tissue homogenizer to fully grind into a homogenate. An appropriate amount of ethanol was added and transferred to a centrifuge tube. Ultrasonication was performed for 5 minutes, and centrifugation was performed at 5000 r / min for 10 minutes. The supernatant was analyzed by HPLC to calculate the retention amount of glycyrrhizin in the skin. The results are as follows: Figure 6 As shown, Figure 6 The skin retention amount of glabridin after transdermal transdermal administration of glabridin flexible liposomes and free glabridin.

[0130] Depend on Figure 5 and Figure 6 It can be seen that the cumulative permeation of each test sample per unit area of ​​skin in 24 hours is: Glabridin flexible liposome 180.3μg / cm 2 , free glabridin 45.9μg / cm 2 The 24-hour skin retention per unit area (calculated as glabridin) is: 135.3 μg / cm 2 , free glabridin 19.2μg / cm 2 The drug permeation and retention of visible-light glycyrrhizin nano-flexible liposomes were significantly higher than those of free glycyrrhizin, reaching 3.9 times and 7 times, respectively. This was attributed to the flexible nano-liposomes' strong deformability and small particle size, resulting in good skin permeability, high permeation and retention. The free glycyrrhizin solution group also showed some drug permeation and retention, but free glycyrrhizin has poor water solubility, making it difficult to effectively apply to various cosmetics.

[0131] 3.2 Evaluation of the efficacy of glabridin flexible liposome facial mask

[0132] Moisturizing effect

[0133] Determination of AQP3 expression in HaCaT cells: HaCaT cells were plated at 4 × 10 5 Cells were seeded at a density of 100 cells / mL in a 12-well cell culture plate and cultured in an incubator at 37°C and 5% CO2 for 24 hours. The culture medium was removed and a glabridin flexible liposome solution prepared in serum-free medium was added. A blank control group (control) was added with serum-free medium only and cultured for another 24 hours at 37°C and 5% CO2. The cultured cells and supernatant of each experimental group were collected and the AQP3 expression level in the cells was detected according to the instructions of the human AQP3 ELISA kit. The results are shown in Figure 2. Figure 7 As shown, Figure 7 Effects of glabridin flexible liposome mask on AQP3 in HaCaT cells.

[0134] In this experiment, the glabridin flexible liposome mask solution was applied to HaCaT cells to test the expression of AQP3 in the cell culture. The above indicators can be used to characterize the moisturizing effect of the glabridin flexible liposome mask solution. After treatment with the test substance, the higher the expression of AQP3 in the cells, the stronger the moisturizing activity of the test substance. Figure 7 It can be seen that compared with the control group (2.06 ng / mL), the glabridin flexible liposome mask liquid (5.36 ng / mL) can significantly upregulate the expression of cellular AQP3, indicating that the prepared glabridin flexible liposome mask liquid has excellent moisturizing effect.

[0135] Soothing effect

[0136] After culturing mouse macrophage RAW264.7 cells, they were centrifuged and mixed, and counted. Each well contained 3.2×10 4 The cells were plated in a 96-well plate and cultured in a 37°C, 5% CO2 incubator for 24 hours. After 24 hours, the culture medium was carefully aspirated and the culture medium solution containing the mask liquid was added and pretreated in a 37°C, 5% CO2 incubator for 2 hours. Normal culture medium was added to the blank control well; the cells were also pretreated in a 37°C, 5% CO2 incubator for 2 hours. After 2 hours of pretreatment, LPS with a final concentration of 10 μg / mL was added to each well except the blank control well for stimulation, and the cells were cultured in a 37°C, 5% CO2 incubator for another 24 hours. After 24 hours of incubation, 200 μL of cell culture supernatant was collected from each well in a sterile centrifuge tube and placed in a -80°C ultra-low temperature freezer for storage. The TNF-α content was detected according to the instructions of the ELISA detection kit. The results are as follows Figure 8 As shown, Figure 8 The effect of glabridin flexible liposome mask on TNF-α in RAW.7 mouse cells.

[0137] Lipopolysaccharide (LPS) is the main component of the cell wall of Gram-negative bacteria and is the main cause of sepsis caused by Gram-negative bacteria in clinical practice. The lipopolysaccharide-activated mouse RAW264.7 macrophage inflammation model is widely used to study inflammatory responses. Under the stimulation of lipopolysaccharide, macrophages can induce the rapid synthesis and release of various inflammatory factors such as TNF-α and IL-1, which are used here to characterize the soothing effect of the mask liquid. Figure 8 As shown in the results, the TNF-α content of mouse cells RAW264.7 was significantly increased under LPS stimulation, while the mask liquid group could significantly inhibit the production of TNF-α induced by LPS, indicating that the glabridin flexible liposome mask liquid has excellent soothing effect.

[0138] Whitening effect

[0139] B16F10 cells were plated at 8 × 10 5 The cells were inoculated at a density of 1000 cells / well in a 6-well cell culture plate and cultured in an incubator at 37°C and 5% CO2 for 24 h. The culture medium was removed and the glabridin flexible liposome mask prepared with serum-free medium was added. The blank control group was only added with serum-free medium and cultured at 37°C and 5% CO2 for 48 h. The cells were washed twice with PBS and 400 μL of 1.0 mol·L -1 Then add 100 μL of DMSO and incubate in a 75°C water bath for 1.5 hours to completely dissolve the melanin in the cells. 200 μL of each aspirate was transferred to a 96-well plate and the absorbance was measured at a wavelength of 450 nm. The inhibition rate of the sample on melanin synthesis in B16F10 cells was calculated according to the following formula 1. Figure 9 As shown, Figure 9 The effect of glabridin flexible liposome mask on melanin in B16F10 cells.

[0140]

[0141] B16F10 cell tyrosinase inhibition rate determination: B16F10 cells were plated at 8×10 5 The cells were inoculated into 6-well cell culture plates at a density of 100 cells / well and cultured in an incubator at 37°C and 5% CO2 for 24 hours. The culture medium was removed and a solution of glabridin flexible liposome mask prepared with serum-free culture medium was added. The blank control group was only added with serum-free culture medium and cultured at 37°C and 5% CO2 for 48 hours. The cells were then collected and the tyrosinase activity in the cells was detected according to the instructions of the tyrosinase activity detection kit, and the inhibition rate of the sample on the cell tyrosinase activity was calculated according to the following formula 2. The results are shown in Figure 2. Figure 10 As shown, Figure 10 The effect of glabridin flexible liposome mask on tyrosinase in B16F10 cells.

[0142]

[0143] The B16F10 cells were treated with glabridin flexible liposome mask and the melanin and tyrosinase inhibition rates of B16F10 cells were tested. The above indicators can be used to characterize the whitening effect of glabridin flexible liposome mask. The higher the cell melanin and tyrosinase inhibition rates, the stronger the whitening effect of the test substance. Figure 9 and Figure 10 It can be seen that the cell melanin inhibition rate is 50.53% and the tyrosinase inhibition rate is 42.1%, indicating that the glabridin flexible liposome mask liquid has a good whitening effect.

[0144] The above description is merely a preferred embodiment of the present invention and does not constitute any limitation thereto. It should be noted that those skilled in the art may make various improvements and modifications without departing from the principles of the present invention, and such improvements and modifications shall also be considered within the scope of protection of the present invention.

Claims

1. A glabridin flexible liposome, characterized in that: The invention comprises a flexible nano-liposome and glabridin wrapped by the flexible nano-liposome. The flexible nano-liposome is a liposome modified with dipotassium glycyrrhizate and is formed by phospholipid and cholesterol. The mass percentages of phospholipid, dipotassium glycyrrhizate, cholesterol and glabridin in the glabridin flexible liposome are 50-75%, 10-30%, 1-20% and 0.5-10% respectively.

2. The glabridin flexible liposome according to claim 1, characterized in that The phospholipids include soy lecithin.

3. The glabridin flexible liposome according to claim 1, characterized in that The particle size of the glabridin flexible liposome is 78-150 nm.

4. The method for preparing the glabridin flexible liposomes according to any one of claims 1 to 3, characterized in that: The following steps are involved: mixing phospholipid, dipotassium glycyrrhizate, cholesterol, glabridin and an organic solvent to obtain a mixed solution; Evaporating the mixed solution to remove the solvent to obtain a film; hydrating the film to obtain the glabridin flexible liposome; Based on the total mass of phospholipid, dipotassium glycyrrhizate, cholesterol and glabridin, the mass percentages of phospholipid, dipotassium glycyrrhizate, cholesterol and glabridin are 50-75%, 10-30%, 1-20% and 0.5-10% respectively.

5. The preparation method according to claim 4, characterized in that: The hydration temperature is 40-45° C., and the hydration time is 40-120 minutes.

6. The preparation method according to claim 4 or 5, characterized in that After the hydration, the obtained emulsion is filtered and ultrasonically treated in sequence, wherein the power of the ultrasonic treatment is 100 to 250 W and the time is 10 to 30 minutes.

7. A glabridin flexible liposome facial mask liquid, characterized in that: Includes the following components in percentage by mass: p-Hydroxyacetophenone 0.3-1%, panthenol 0.8-10%, EDTA-2Na 0.05-0.1%, 1,2-hexanediol 0.3-0.8%, glycerol polyether 0.8-4%, first sodium hyaluronate 0.1-0.6%, second sodium hyaluronate 0.05-0.5%, third sodium hyaluronate 0.1-0.2%, xanthan gum 0.05-0.5%, glabridin flexible liposome 1-2%, balance water; The number average molecular weight of the first sodium hyaluronate is 200,000 to 400,000, the number average molecular weight of the second sodium hyaluronate is 1.3 million to 1.6 million, and the number average molecular weight of the third sodium hyaluronate is 1.8 million to 2 million; the glabridin flexible liposomes are the glabridin flexible liposomes described in any one of claims 1 to 3 or the glabridin flexible liposomes prepared by the preparation method according to any one of claims 4 to 6.

8. The method for preparing the glabridin flexible liposome facial mask liquid according to claim 7, characterized in that: The following steps are involved: Mixing a portion of water, p-hydroxyacetophenone, panthenol, EDTA-2Na, 1,2-hexanediol, and glycerol polyether to obtain a first mixed solution; performing a second mixing of the first mixed solution with the first sodium hyaluronate, the second sodium hyaluronate, the third sodium hyaluronate, and xanthan gum to obtain a second mixed solution; The second mixed liquid, the glabridin flexible liposomes and the remaining part of water are mixed for a third time to obtain the glabridin flexible liposome facial mask liquid.

9. The preparation method according to claim 8, characterized in that The temperature of the first mixing is 40-50°C, the temperature of the second mixing is 55-70°C, and the temperature of the third mixing is 30-40°C.

10. The preparation method according to claim 8 or 9, characterized in that: The first mixing, the second mixing and the third mixing are all performed by stirring.

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