Glycyrrhetinic acid entrapped cosurfactant-free microemulsion as well as preparation method and application thereof

Abstract

The invention discloses a co-surfactant-free microemulsion entrapped with glycyrrhetinic acid as well as a preparation method and application of the co-surfactant-free microemulsion entrapped with glycyrrhetinic acid. The co-surfactant-free microemulsion entrapped with glycyrrhetinic acid comprises carvacrol / thymol, fatty acid, a nonionic surfactant and water, wherein the glycyrrhetinic acid accounts for 0.1-5% by mass of the raw materials, the carvacrol / thymol accounts for 0.1-5% by mass of the raw materials, the fatty acid accounts for 0.1-10% by mass of the raw materials, the nonionic surfactant accounts for 1-30% by mass of the raw materials, and the balance is water. The cosurfactant-free microemulsion loaded with glycyrrhetinic acid prepared by the invention contains glycyrrhetinic acid and carvacrol / thymol, the carvacrol / thymol not only increases the solubility of glycyrrhetinic acid, but also promotes percutaneous absorption of glycyrrhetinic acid, and the cosurfactant-free microemulsion loaded with glycyrrhetinic acid is a cosmetic composite efficacy composition with antioxidant, anti-inflammatory and antibacterial effects.

Description

Technical Field

[0001] The invention belongs to the technical field of cosmetics, and in particular relates to a surfactant-free microemulsion encapsulating glycyrrhetinic acid and a preparation method and application thereof. Background Art

[0002] Glycyrrhetinic acid (GA), also known as glycyrrhetinic acid, is a pentacyclic triterpenoid compound extracted from licorice. It is used in cosmetics and other fields due to its antioxidant, whitening, and soothing effects. However, GA has extremely poor water solubility, with a solubility in water of only 6.32 mg / L, which greatly limits its application. At the same time, although the molecular weight of GA is less than 500 Da, the logP value of GA is 6.574, which seriously hinders the transdermal penetration of GA.

[0003] Therefore, there is an urgent need for some suitable carrier systems that can encapsulate and transport GA, improve its transdermal penetration effect and bioavailability, and enable it to fully exert its skin care function.

[0004] For many years, microemulsions, as thermodynamically and kinetically stable systems, have been attracting much attention in the encapsulation and delivery of active substances and drugs. However, in the preparation process of microemulsions, a large amount of surfactants and co-surfactants are usually required to stabilize the system, and most of the co-surfactants are short-chain alcohols and short-chain acids, which may damage the stratum corneum of the skin and cause skin sensitivity, inflammation, etc. Therefore, how to prepare co-surfactant-free microemulsions is a difficult problem to be solved in the field of cosmetics; at the same time, how to choose a suitable solvent to dissolve poorly soluble active substances and increase the loading of active substances in microemulsions is another major problem in the preparation of microemulsions.

[0005] At present, studies have shown that deep eutectic solvents (DES) can significantly increase the solubility of poorly soluble drugs and promote transdermal absorption of drugs. However, there is no report on the preparation of deep eutectic solvents using glycyrrhetinic acid as a hydrogen bond donor or acceptor and their application in microemulsions. Summary of the invention

[0006] The purpose of this section is to summarize some aspects of embodiments of the present invention and briefly introduce some preferred embodiments. Some simplifications or omissions may be made in this section and the specification abstract and the invention title of this application to avoid blurring the purpose of this section, the specification abstract and the invention title, and such simplifications or omissions cannot be used to limit the scope of the present invention.

[0007] In view of the above problems and / or the problems existing in the prior art, the present invention is proposed.

[0008] Therefore, the purpose of the present invention is to overcome the deficiencies in the prior art and provide a surfactant-free microemulsion encapsulating glycyrrhetinic acid.

[0009] In order to solve the above technical problems, the present invention provides the following technical solutions: a surfactant-free microemulsion encapsulating glycyrrhetinic acid, comprising carvacrol / thymol, fatty acid, nonionic surfactant and water;

[0010] Wherein, in terms of percentage by mass of raw materials, the glycyrrhetinic acid is 0.1-5%, the carvacrol / thymol is 0.1-5%, the fatty acid is 0.1-10%, the nonionic surfactant is 1-30%, and the remainder is supplemented to 100% with water.

[0011] As a preferred embodiment of the surfactant-free microemulsion of the present invention, the fatty acid includes at least one of caprylic acid, nonanoic acid, capric acid and oleic acid.

[0012] As a preferred embodiment of the surfactant-free microemulsion of the present invention, the nonionic surfactant includes at least one of Tween 40, Tween 60, Tween 80, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 60, and polyoxyethylene castor oil.

[0013] As a preferred embodiment of the surfactant-free microemulsion of the present invention, the non-ionic surfactant comprises polyoxyethylene hydrogenated castor oil 40.

[0014] As a preferred embodiment of the surfactant-free microemulsion of the present invention, the average particle size of the surfactant-free microemulsion containing glycyrrhetinic acid is 17-20 nm, and the particle size distribution index PDI of the surfactant-free microemulsion containing glycyrrhetinic acid is 0.01-0.1.

[0015] Another object of the present invention is to overcome the deficiencies in the prior art and provide a method for preparing a surfactant-free microemulsion, comprising:

[0016] The oil phase is prepared by mixing carvacrol / thymol with fatty acids;

[0017] dissolving glycyrrhetinic acid in the oil phase to prepare an oil phase mixture;

[0018] The oil phase mixture and the nonionic surfactant are uniformly mixed to prepare a mixture;

[0019] Water was added dropwise to the mixture in a water bath, and after mixing well, it was added dropwise to prepare a microemulsion.

[0020] As a preferred embodiment of the method for preparing the surfactant-free microemulsion of the present invention, the temperature of the water bath is 25-45°C.

[0021] Another object of the present invention is to overcome the deficiencies in the prior art and provide an application of a surfactant-free microemulsion in the preparation of daily cosmetics.

[0022] As a preferred embodiment of the application of the present invention, the daily cosmetics include facial cream and facial cleanser.

[0023] Beneficial effects of the present invention:

[0024] (1) The present invention provides a surfactant-free microemulsion encapsulating glycyrrhetinic acid, which is prepared by using carvacrol or thymol and a fatty acid mixture as an oil phase and a non-ionic surfactant as a surfactant. On the one hand, the low eutectic solvent formed between carvacrol or thymol and glycyrrhetinic acid can effectively solubilize glycyrrhetinic acid and increase the loading capacity of glycyrrhetinic acid in the microemulsion; on the other hand, the formation of the low eutectic solvent can effectively promote the penetration of glycyrrhetinic acid in the skin, thereby exerting the multiple functions of glycyrrhetinic acid.

[0025] (2) The surfactant-free microemulsion loaded with glycyrrhetinic acid prepared by the present invention is a transparent liquid, which is a thermodynamically stable oil-water mixture dispersion system. It remains transparent after being infinitely diluted with water and can be applied to cosmetics of various dosage forms.

[0026] (3) The surfactant-free microemulsion loaded with glycyrrhetinic acid prepared by the present invention contains glycyrrhetinic acid and carvacrol / thymol. Carvacrol / thymol not only increases the solubility of glycyrrhetinic acid, but also promotes the percutaneous absorption of glycyrrhetinic acid. It is a cosmetic composite composition with antioxidant, anti-inflammatory and antibacterial effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following briefly introduces the drawings required for describing the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative labor. Among them:

[0028] Figure 1 This is the appearance of the mixed samples with different mass ratios of GA and carvacrol in the examples of the present invention after being kept at -20°C for 48 hours.

[0029] Figure 2 1. The infrared spectra of GA and carvacrol in different mass ratios in the embodiments of the present invention (a) and the diagram of the interaction mechanism between GA and carvacrol (b).

[0030] Figure 3 The DSC spectra of GA and carvacrol in different mass ratios in the examples of the present invention are shown in FIG.

[0031] Figure 4 These are the appearance pictures of GA microemulsion stored at 45° C. on the 0th and 30th days in the examples of the present invention.

[0032] Figure 5 Graph showing the changes in particle size, PDI (a) and retention rate (b) of the GA microemulsion when stored at 4°C, 25°C and 45°C in an example of the present invention.

[0033] Figure 6 This is a diagram of an irritation evaluation experiment in an embodiment of the present invention.

[0034] Figure 7 Graph showing the cumulative content and total amount of GA in the stratum corneum, epidermis and dermis in different samples in the examples of the present invention. DETAILED DESCRIPTION

[0035] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the specific implementation methods of the present invention are described in detail below in conjunction with the embodiments of the specification.

[0036] In the following description, many specific details are set forth to facilitate a full understanding of the present invention, but the present invention may also be implemented in other ways different from those described herein, and those skilled in the art may make similar generalizations without violating the connotation of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed below.

[0037] Secondly, the term "one embodiment" or "embodiment" as used herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The term "in one embodiment" that appears in different places in this specification does not necessarily refer to the same embodiment, nor does it refer to a separate or selective embodiment that is mutually exclusive with other embodiments.

[0038] The raw materials or reagents used in the following examples and comparative examples are commercially available products.

[0039] Examples 1 to 20

[0040] The embodiment of the surfactant-free microemulsion loaded with glycyrrhetinic acid of the present invention comprises glycyrrhetinic acid, carvacrol, caprylic acid, an emulsifier and water, and the mass percentage of each component is shown in Table 1.

[0041] Table 1

[0042]

[0043]

[0044] The preparation method of the surfactant-free microemulsion loaded with glycyrrhetinic acid comprises the following steps:

[0045] (1) mixing carvacrol and fatty acids to prepare an oil phase;

[0046] (2) dissolving glycyrrhetinic acid in the oil phase in step (1);

[0047] (3) mixing the oil phase and the nonionic surfactant uniformly;

[0048] (4) Add water droplets to the mixture in step (3) in a water bath, mix well, and then add dropwise to prepare a microemulsion.

[0049] As a preferred embodiment of the present invention, in step (4), the water bath temperature is 30°C.

[0050] Examples 21 to 24

[0051] Examples 21 to 24 respectively provide surfactant-free microemulsions loaded with glycyrrhetinic acid and preparation methods thereof. The difference between Examples 21 to 24 and Example 8 is that:

[0052] In step (3) of Example 21, the surfactant is polyoxyethylene-60-hydrogenated castor oil;

[0053] In step (3) of Example 22, the surfactant is Tween 60;

[0054] In step (3) of Example 23, the surfactant is Tween 80;

[0055] In step (3) of Example 24, the surfactant is polyoxyethylene castor oil EL.

[0056] Examples 25 to 27

[0057] Examples 25 to 27 respectively provide surfactant-free microemulsions loaded with glycyrrhetinic acid and preparation methods thereof. The difference between Examples 25 to 27 and Example 8 is that:

[0058] In step (1) of Example 25, the fatty acid is nonanoic acid;

[0059] In step (1) of Example 26, the fatty acid is capric acid;

[0060] In step (1) of Example 27, the fatty acid is oleic acid.

[0061] Comparative Example 1

[0062] This comparative example provides a method for preparing glycyrrhetinic acid microemulsion. The difference between this comparative example and Example 8 is that:

[0063] The nonionic surfactant is replaced by a mixture of a nonionic surfactant and diethylene glycol monoethyl ether, wherein the mass fractions of the nonionic surfactant and diethylene glycol monoethyl ether are 12% and 12% respectively;

[0064] When preparing the microemulsion, firstly, a nonionic surfactant and diethylene glycol monoethyl ether are mixed, and then an oil phase containing glycyrrhetinic acid is added to obtain a uniform mixture, and then deionized water is added dropwise to prepare the microemulsion.

[0065] Comparative Example 2

[0066] This comparative example prepares a glycyrrhetinic acid suspension, and the difference between this comparative example and Example 7 is that:

[0067] Replace water with caprylic / capric triglyceride.

[0068] Effect Example 1

[0069] The products obtained in the above embodiments and comparative examples were used as samples and the following tests were performed:

[0070] (1) Place each sample in a transparent glass sample bottle and observe its appearance.

[0071] (2) Each sample was sealed and stored at 42°C for 7 days, and the content of glycyrrhetinic acid in each sample was tested. The specific test steps were as follows: a certain amount of sample was taken and centrifuged at 13,000 rpm for 20 min, the supernatant was taken and demulsified with methanol, the volume was fixed, and then filtered through an organic membrane (pore size 220 nm). The content of glycyrrhetinic acid in the supernatant was determined by high performance liquid chromatography as W2, and the content of glycyrrhetinic acid added when preparing the sample was W1.

[0072] Retention rate (%) = W2 / W1×100%

[0073] (3) The average particle size of each sample was measured using a Brookhaven nanoparticle size analyzer. Each sample was placed in a transparent sample bottle, sealed, and stored at 42° C. for 7 days. The average particle size of each sample was then measured using a Brookhaven nanoparticle size analyzer.

[0074] The test results are shown in Table 2.

[0075] Table 2

[0076]

[0077]

[0078] As can be seen from Table 2, the loading capacity of the glycyrrhetinic acid microemulsion prepared by using caprylic acid and carvacrol as the oil phase in the present invention is 0.5%, which is higher than the loading capacity of the microemulsion prepared by using only caprylic acid or other combinations as the oil phase. The loading capacity of glycyrrhetinic acid is also related to the types of surfactant and oil phase. The loading capacity of the microemulsion prepared by using polyoxyethylene-40-hydrogenated castor oil as the surfactant is significantly higher than that of other surfactants. The best formula is caprylic acid content 4%, thymol content 2%, polyoxyethylene-40-hydrogenated castor oil content 24%, glycyrrhetinic acid content 0.5%. The prepared glycyrrhetinic acid microemulsion has a clear and transparent appearance, a retention rate of 97.79%, and a particle size of 17.44 nm.

[0079] Effect Example 2

[0080] Glycyrrhetinic acid and carvacrol were mixed evenly in mass ratios of 1:10, 2:10, 3:10, 4:10 and 5:10, and then kept at -20°C for 48 hours, and the appearance was recorded.

[0081] like Figure 1 As shown, carvacrol was completely frozen after being placed at -20°C for 48 hours, while the mixture of GA and carvacrol was still a clear liquid after being placed at -20°C for 48 hours. It can be seen that the addition of GA significantly lowered the freezing point of carvacrol.

[0082] Effect Example 3

[0083] Samples with glycyrrhetinic acid:carvacrol ratios of 1:10, 2:10, 3:10 and 4:10 (mass ratio) were dripped onto the ZnSe ATR crystal of a total reflection-Fourier transform infrared spectrometer at 650-4000 cm -1 FTIR spectra were collected in the range.

[0084] like Figure 2 As shown, the -OH stretching vibration peak of GA is at 3432.13 cm -1 A sharp peak appears at 1700.39 cm -1 The -OH stretching vibration peak of carvacrol is at 3357.74 cm -1 In the mixture, the -OH peaks of GA and carvacrol overlapped, and no new peak shape was observed, indicating that no new substances were produced. When the mass ratio of GA to carvacrol was 1:10, the -C=O stretching vibration peak of the mixture increased from 1700.39 cm -1 Redshift to 1709.09 cm -1 ,This change indicates that hydrogen bonding interaction is formed between GA and carvacrol.With the increase of GA content, the displacement of -C=O stretching vibration peak gradually decreases.

[0085] Effect Example 4

[0086] Carvacrol and its mixture (the mass ratio of GA to carvacrol was 1:10, 2:10, 3:10 and 4:10, respectively) were placed in an aluminum pot and covered with a lid, with a mass of about 6 to 9 mg.

[0087] Differential scanning calorimetry analysis was performed using a NETZSCH DSC 204F1. High-purity indium and tin standard substances were used to calibrate the DSC temperature, and the melting temperature was determined with an accuracy of ±0.5°C. The temperature range of carvacrol was -20 to 30°C, and the temperature range of the mixture was -80 to 40°C at a heating rate of 5°C / min.

[0088] Figure 3 GA is a white solid powder at room temperature with a melting point of about 300°C, and the melting point of carvacrol is 4°C. After carvacrol and GA are mixed, the mixture has no obvious melting point when the mass ratio of GA to carvacrol is 1:10 and 2:10. However, when the mass ratio is 3:10 and 4:10, the glass transition temperature is observed to be -46.76°C and -42.32°C, respectively. Therefore, it is speculated that GA and carvacrol may form a low eutectic solvent.

[0089] Figure 4 These are the appearance pictures of the glycyrrhetinic acid microemulsion prepared in Example 8 after being sealed and stored at 45°C on the 0th day and the 30th day. As can be seen from the figure, the microemulsion remains clear and transparent after being stored at 45°C for 1 month, and no glycyrrhetinic acid is precipitated, indicating that the carrier is very stable.

[0090] Figure 5 The particle size and retention rate of the glycyrrhetinic acid microemulsion prepared in Example 8 after being stored at different temperatures for 1 month. After the microemulsion was stored at 4°C, 25°C and 45°C for 1 month, the appearance was still clear and transparent, the particle size remained at about 17nm, the PDI remained below 0.1, and the glycyrrhetinic acid retention rate was above 95%.

[0091] Effect Example 5

[0092] The irritation of glycyrrhetinic acid microemulsion was studied by chicken embryo chorioallantoic membrane test (HET-CAM test). 100 μL of Example 8 and Comparative Example 1 were respectively dripped onto the surface of the chorioallantoic membrane, and the bleeding, coagulation and hemolysis within 5 min were observed and recorded. The irritation was evaluated by the average value of the irritation score (IS) of the experimental results.

[0093]

[0094] Among them, T h T is the time of bleeding onset, l T is the time of vascular thawing. c The time for blood clotting.

[0095] Figure 6 Table 3 is the chicken embryo chorioallantoic membrane result diagram of Example 8 and Comparative Example 1. It can be seen from the figure that diethylene glycol monoethyl ether is very irritating to the chicken embryo chorioallantoic membrane, and the prepared alcohol-free microemulsion is obviously less irritating to the chicken embryo chorioallantoic membrane than the alcohol microemulsion.

[0096] Table 3 Evaluation of irritation of microemulsion

[0097]

[0098] Effect Example 6

[0099] Example 7, Example 12 and Comparative Example 2 were applied to transdermal absorption.

[0100] The pig skin was placed between the supply pool and the receiving pool of the Franz diffusion cell, 1 ml of sample was added to the supply pool and placed in the transdermal diffusion tester for 12 hours. After the reaction, the content of glycyrrhetinic acid in the stratum corneum was determined by the tape stripping method:

[0101] Use 3M tape to stick the stratum corneum of the pig skin, discard the first layer, and continue to stick 20 layers;

[0102] The extracts were collected in centrifuge tubes, and an extractant was added for extraction. The content of glycyrrhetinic acid was determined by high performance liquid chromatography, which is the content of glycyrrhetinic acid in the stratum corneum.

[0103] The remaining pig skin after removing the stratum corneum by pasting 21 layers of 3M tape was cut into pieces and collected in a centrifuge tube. The extractant was added for extraction, and the content of glycyrrhetinic acid was determined by high performance liquid chromatography, which is the content of glycyrrhetinic acid in the dermis.

[0104] Figure 7 The results of Example 7, Example 12, and Comparative Example 2 of the present invention applied to transdermal absorption show that the transdermal effect of the glycyrrhetinic acid suspension is significantly lower than that of the other two groups. Example 12 is to encapsulate glycyrrhetinic acid in a microemulsion with only caprylic acid as the oil phase. It can be seen from the figure that the content of glycyrrhetinic acid in the dermis is higher than that in the stratum corneum, and higher than that in the glycyrrhetinic acid suspension group, which indicates that the microemulsion as a carrier can effectively deliver glycyrrhetinic acid into the deep layer of the skin, which is beneficial to the transdermal absorption of glycyrrhetinic acid. At the same time, when another oil phase, carvacrol, is added to the microemulsion, the content of glycyrrhetinic acid in the stratum corneum and dermis is significantly increased, which indicates that the low eutectic solvent formed by hydrogen bonding between carvacrol and glycyrrhetinic acid is not only beneficial to increase the loading capacity of glycyrrhetinic acid, but also effectively promotes its transdermal absorption.

[0105] Effect Example 7

[0106] The ability of Examples 6, 8 and 12 to remove ·OH free radicals was determined by using the Fenton reaction: H2O2+Fe2+=·OH+H2O+Fe3+ to generate ·OH. Salicylic acid reacts with ·OH to generate 2,3-dihydroxybenzoic acid with special absorption at 510nm. If a test substance with the function of removing ·OH is added to the reaction system, the generation of ·OH will be reduced, thereby reducing the colored compounds and achieving the purpose of removing ·OH. 9mmol / L ethanol-salicylic acid solution, 9mmol / LFeSO4 solution and 8.8mmol / LH2O2 solution were prepared for the reaction. The reaction solution was prepared as shown in Table 4. After mixing, it was reacted in a 37°C water bath for 15 minutes. The absorbance of the reaction solution at 510nm was detected by an enzyme marker. The OH free radical inhibition rate was calculated as follows:

[0107]

[0108] Where Ax is the absorbance of the sample group; A0 is the absorbance of the blank control group; AX0 is the absorbance without adding H2O2

[0109] Table 4 Experimental method for removing OH

[0110]

[0111] The test results are shown in Table 5.

[0112] Table 5

[0113] sample OH removal rate Example 8 (93.739±1.89)％ Example 12 (56.036±0.91)％ Example 6 (53.950±1.38)％

[0114] As shown in Table 5, Example 12 is the ·OH scavenging rate of the microemulsion with only caprylic acid as the oil phase for glycyrrhetinic acid, which is (56.036±0.91)%, Example 6 is the ·OH scavenging rate of the blank microemulsion without glycyrrhetinic acid, which is (53.950±1.38)%, and Example 8 is the ·OH scavenging rate of the glycyrrhetinic acid-caprylic acid / carvacrol microemulsion, which is (93.739±1.89)%. It can be seen that microemulsion co-loading carvacrol and glycyrrhetinic acid can simultaneously exert the antioxidant capacity of both.

[0115] In the present invention, glycyrrhetinic acid and carvacrol / thymol have a eutectic phenomenon, which has not been reported so far. Carvacrol / thymol can solubilize glycyrrhetinic acid in large quantities and promote the percutaneous absorption of glycyrrhetinic acid. Carvacrol / thymol has biological activities such as antioxidant, antibacterial, and anti-inflammatory activities, and glycyrrhetinic acid also has these activities. Encapsulating these two effective ingredients together can achieve double the effect.

[0116] 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 preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention can be modified or replaced by equivalents without departing from the spirit and scope of the technical solutions of the present invention, which should all be included in the scope of the present invention.

Claims

1. A surfactant-free microemulsion containing glycyrrhetinic acid, characterized in that: include, Glycyrrhetinic acid, carvacrol / thymol, fatty acids, nonionic surfactants, and water; Wherein, in terms of percentage by mass of raw materials, the glycyrrhetinic acid is 0.1-5%, the carvacrol / thymol is 0.1-5%, the fatty acid is 0.1-10%, the nonionic surfactant is 1-30%, and the remainder is supplemented to 100% with water.

2. The surfactant-free microemulsion according to claim 1, characterized in that: The fatty acid includes at least one of caprylic acid, nonanoic acid, capric acid and oleic acid.

3. The surfactant-free microemulsion according to claim 1 or 2, characterized in that: The nonionic surfactant includes at least one of Tween 40, Tween 60, Tween 80, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 60, and polyoxyethylene castor oil.

4. The surfactant-free microemulsion according to claim 3, characterized in that: The nonionic surfactant includes polyoxyethylene hydrogenated castor oil 40.

5. The surfactant-free microemulsion according to any one of claims 1, 2 or 4, characterized in that: The average particle size of the surfactant-free microemulsion containing glycyrrhetinic acid is 17-20 nm.

6. The surfactant-free microemulsion according to claim 5, characterized in that: The particle size distribution index PDI of the surfactant-free microemulsion containing glycyrrhetinic acid is 0.01-0.

1.

7. The method for preparing a surfactant-free microemulsion according to any one of claims 1 to 6, characterized in that: include, The oil phase is prepared by mixing carvacrol / thymol with fatty acids; dissolving glycyrrhetinic acid in the oil phase to prepare an oil phase mixture; The oil phase mixture and the nonionic surfactant are uniformly mixed to prepare a mixture; Water was added dropwise to the mixture in a water bath, and after mixing well, it was added dropwise to prepare a microemulsion.

8. The preparation method according to claim 7, characterized in that: The temperature of the water bath is 25-45°C.

9. Use of the surfactant-free microemulsion according to any one of claims 1 to 6 in the preparation of daily cosmetics.

10. The use according to claim 9, characterized in that: The daily cosmetics include facial cream and facial cleanser.

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