Cosurfactant-free microemulsion encapsulating glycyrrhetinic acid, preparation method therefor, and use thereof

Abstract

Provided are a cosurfactant-free microemulsion encapsulating glycyrrhetinic acid, a preparation method therefor, and use thereof. The cosurfactant-free microemulsion comprises carvacrol / thymol, a fatty acid, a nonionic surfactant, and water. Based on the mass percentage of the raw materials, the glycyrrhetinic acid accounts for 0.1-5%, the carvacrol / thymol accounts for 0.1-5%, the fatty acid accounts for 0.1-10%, the nonionic surfactant accounts for 1-30%, and the balance is made up to 100% with water. Carvacrol / thymol not only increases the solubility of glycyrrhetinic acid, but also promotes the transdermal absorption of glycyrrhetinic acid, and is a cosmetic composite efficacy composition having antioxidant, anti-inflammatory, and antibacterial effects.

Description

A glycyrrhetinic acid-loaded unhelpful surfactant microemulsion, its preparation method and application Technical Field

[0001] This invention belongs to the field of cosmetic technology, specifically relating to a microemulsion of glycyrrhetinic acid-coated non-adjuvant surfactant, its preparation method, and its application. Background Technology

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

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

[0004] For many years, microemulsions, as thermodynamically and kinetically stable systems, have attracted much attention for their application in the encapsulation and delivery of active ingredients and drugs. However, the preparation of microemulsions usually requires the use of large amounts of surfactants and co-surfactants to stabilize the system, and most of the co-surfactants are short-chain alcohols and short-chain acids. These substances may damage the stratum corneum of the skin, causing skin sensitivity, inflammation, and other phenomena. Therefore, how to prepare surfactant-free microemulsions is a pressing problem to be solved in the cosmetics field. At the same time, how to select a suitable solvent to dissolve poorly soluble active ingredients and increase the loading of active ingredients in microemulsions is another major challenge in microemulsion preparation.

[0005] Current research indicates that deep eutectic solvents (DES) can significantly increase the solubility of poorly soluble drugs and promote transdermal absorption. However, there are currently no reports 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 outline some aspects of embodiments of the present invention and to briefly describe some preferred embodiments. Simplifications or omissions may be made in this section, as well as in the abstract and title of this application, to avoid obscuring the purpose of these documents; however, such simplifications or omissions should not be construed as limiting the scope of the invention.

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

[0008] Therefore, the purpose of this invention is to overcome the shortcomings of the prior art and provide a microemulsion of glycyrrhetinic acid-coated non-adjuvant surfactant.

[0009] To solve the above-mentioned technical problems, the present invention provides the following technical solution: a microemulsion of glycyrrhetinic acid-loaded unhelpful surfactant, comprising carvacrol / thymol, fatty acid, nonionic surfactant and water;

[0010] The composition, by weight percentage of raw materials, includes 0.1-5% glycyrrhetinic acid, 0.1-5% carvacrol / thymol, 0.1-10% fatty acids, 1-30% nonionic surfactant, and the remainder is made up to 100% with water.

[0011] As a preferred embodiment of the non-adjuvant surfactant microemulsion of the present invention, the fatty acid includes at least one of octanoic acid, nonanoic acid, decanoic acid, and oleic acid.

[0012] As a preferred embodiment of the non-ionic surfactant microemulsion described in this 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 non-ionic surfactant microemulsion of the present invention, the nonionic surfactant comprises polyoxyethylene hydrogenated castor oil 40.

[0014] As a preferred embodiment of the unhelpful surfactant microemulsion of the present invention, wherein: the average particle size of the unhelpful surfactant microemulsion loaded with glycyrrhetinic acid is 17-20 nm, and the particle size distribution index (PDI) of the unhelpful surfactant microemulsion loaded with glycyrrhetinic acid is 0.01-0.1.

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

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

[0017] Glycyrrhetinic acid was dissolved in the oil phase to prepare an oil phase mixture;

[0018] The oil phase mixture is mixed evenly with a nonionic surfactant to obtain a mixture;

[0019] Water droplets are added to the mixture in a water bath, and after thorough mixing, water is added droplets to prepare a microemulsion.

[0020] In a preferred embodiment of the method for preparing unhelpful surfactant microemulsions according to the present invention, the temperature of the water bath is 25–45°C.

[0021] Another objective of this invention is to overcome the shortcomings of the prior art and provide an application of a non-adjuvant surfactant microemulsion in the preparation of daily cosmetics.

[0022] As a preferred embodiment of the application described in this invention, the daily cosmetic product includes face cream and facial cleanser.

[0023] Beneficial effects of this invention:

[0024] (1) This invention provides a glycyrrhetinic acid-loaded unhelpful surfactant microemulsion, which is prepared by using a mixture of carvacrol or thymol and fatty acids as the oil phase and a nonionic surfactant as the surfactant. On the one hand, the eutectic solvent formed between carvacrol or thymol and glycyrrhetinic acid can effectively solubilize glycyrrhetinic acid and increase the loading of glycyrrhetinic acid in the microemulsion. On the other hand, the formation of the eutectic solvent can effectively promote the penetration of glycyrrhetinic acid into the skin, thereby exerting the multiple effects of glycyrrhetinic acid.

[0025] (2) The glycyrrhetinic acid-loaded non-adjuvant surfactant microemulsion prepared in this invention is a transparent liquid and a thermodynamically stable oil-water mixture dispersion system. It remains transparent even after infinite dilution with water and can be applied to cosmetics of various dosage forms.

[0026] (3) The glycyrrhetinic acid-loaded unhelpful surfactant microemulsion prepared in this invention contains glycyrrhetinic acid and carvacrol / thymol. Carvacrol / thymol increases the solubility of glycyrrhetinic acid and promotes its transdermal absorption. It is a cosmetic compound composition with antioxidant, anti-inflammatory and antibacterial effects. Attached Figure Description

[0027] To more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings used in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort. Wherein:

[0028] Figure 1 shows the appearance of samples with different mass ratios of GA and carvacrol in the embodiments of the present invention after being kept at -20℃ for 48 hours.

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

[0030] Figure 3 shows the DSC spectra of GA and carvacrol at different mass ratios in the embodiments of the present invention.

[0031] Figure 4 shows the appearance of the GA microemulsion stored at 45°C on day 0 and day 30 in an embodiment of the present invention.

[0032] Figure 5 shows the changes in particle size, PDI (a), and retention rate (b) of GA microemulsions stored at 4℃, 25℃, and 45℃ in the embodiments of the present invention.

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

[0034] Figure 7 shows the cumulative content and total amount of GA in the stratum corneum, epidermis and dermis of different samples in the embodiments of the present invention. Detailed Implementation

[0035] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, the specific embodiments of the present invention will be described in detail below with reference to the examples in the specification.

[0036] Many specific details are set forth in the following description in order to provide a full understanding of the invention. However, the invention may also be practiced in other ways different from those described herein, and those skilled in the art can make similar extensions without departing from the spirit of the invention. Therefore, the 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 phrase "in one embodiment" appearing in different places in this specification does not necessarily refer to the same embodiment, nor is it a single 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 1-20

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

[0041] Table 1

[0042] A method for preparing a glycyrrhetinic acid-loaded unsupported surfactant microemulsion includes the following steps:

[0043] (1) Prepare an oil phase by mixing carvacrol with fatty acids;

[0044] (2) Dissolve glycyrrhetinic acid in the oil phase of step (1);

[0045] (3) Mix the oil phase and the nonionic surfactant evenly;

[0046] (4) Add water droplets to the mixture in step (3) in a water bath, mix evenly, and then add water droplets to prepare a microemulsion.

[0047] In a preferred embodiment of the present invention, the water bath temperature in step (4) is 30°C.

[0048] Examples 21-24

[0049] Examples 21-24 respectively provide glycyrrhetinic acid-loaded unsupported surfactant microemulsions and their preparation methods. The difference between Examples 21-24 and Example 8 is as follows:

[0050] In step (3) of Example 21, the surfactant is polyoxyethylene-60-hydrogenated castor oil;

[0051] In step (3) of Example 22, the surfactant is Tween 60;

[0052] In step (3) of Example 23, the surfactant is Tween 80;

[0053] In step (3) of Example 24, the surfactant is polyoxyethylene castor oil EL.

[0054] Examples 25-27

[0055] Examples 25-27 respectively provide glycyrrhetinic acid-loaded unsupported surfactant microemulsions and their preparation methods. The difference between Examples 25-27 and Example 8 is as follows:

[0056] In step (1) of Example 25, the fatty acid is nonanoic acid;

[0057] In step (1) of Example 26, the fatty acid is decanoic acid;

[0058] In step (1) of Example 27, the fatty acid is oleic acid.

[0059] Comparative Example 1

[0060] This comparative example provides a method for preparing glycyrrhetinic acid microemulsion. The difference between this comparative example and Example 8 is that:

[0061] The nonionic surfactant is replaced with a mixture of nonionic surfactant and diethylene glycol monoethyl ether, wherein the mass fractions of nonionic surfactant and diethylene glycol monoethyl ether are 12% and 12%, respectively.

[0062] To prepare this microemulsion, a nonionic surfactant is first mixed with diethylene glycol monoethyl ether, and then an oil phase containing glycyrrhetinic acid is added to obtain a homogeneous mixture. Finally, deionized water is added dropwise to prepare the microemulsion.

[0063] Comparative Example 2

[0064] This comparative example prepared a glycyrrhetinic acid suspension. The difference between this comparative example and Example 7 is that:

[0065] Replace water with caprylic / capric triglyceride.

[0066] Example 1

[0067] Using the products obtained from the above embodiments and comparative examples as samples, the following tests were conducted:

[0068] (1) Place each sample in a transparent glass sample bottle and observe its appearance.

[0069] (2) After sealing each sample, store it at 42℃ for 7 days. The glycyrrhetinic acid content in each sample was then tested. The specific testing steps were as follows: A certain amount of sample was centrifuged at 13000 rpm for 20 min. The supernatant was demulsified with methanol, diluted to a final volume, and then filtered through an organic membrane (pore size 220 nm). The glycyrrhetinic acid content in the supernatant was determined by high-performance liquid chromatography (HPLC) as W2. The amount of glycyrrhetinic acid added during sample preparation was W1. Retention rate (%) = W2 / W1 × 100%

[0070] (3) The average particle size of each sample was determined 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 determined using a Brookhaven nanoparticle size analyzer.

[0071] The test results are shown in Table 2.

[0072] Table 2

[0073] As shown in Table 2, the glycyrrhetinic acid microemulsion prepared by the present invention using octanoic acid and carvacrol as the oil phase has a loading of 0.5%, which is higher than that of microemulsions prepared using only octanoic acid or other combinations as the oil phase. The loading of glycyrrhetinic acid is also related to the type of surfactant and oil phase. The microemulsion prepared using polyoxyethylene-40-hydrogenated castor oil as the surfactant has a significantly higher loading than other surfactants. The optimal formulation is 4% octanoic acid, 2% thymol, 24% polyoxyethylene-40-hydrogenated castor oil, and 0.5% glycyrrhetinic acid. The prepared glycyrrhetinic acid microemulsion is clear and transparent in appearance, with a retention rate of 97.79% and a particle size of 17.44 nm.

[0074] Example 2

[0075] Glycyrrhetinic acid and carvacrol were mixed evenly at mass ratios of 1:10, 2:10, 3:10, 4:10 and 5:10 and then kept at -20℃ for 48 hours before recording their appearance.

[0076] As shown in Figure 1, carvacrol completely froze after being placed at -20℃ for 48 hours, while the mixture of GA and carvacrol remained a clear and transparent liquid after being placed at -20℃ for 48 hours. This indicates that the addition of GA significantly lowered the freezing point of carvacrol.

[0077] Example 3

[0078] Samples with glycyrrhetinic acid:carvacrol ratios of 1:10, 2:10, 3:10, and 4:10 (mass ratio) were dropped onto a ZnSe ATR crystal in a total reflectance-Fourier transform infrared spectrometer, and analyzed at 650–4000 cm⁻¹. -1 FTIR spectra were collected within the range.

[0079] As shown in Figure 2, the -OH stretching vibration peak of GA is at 3432.13 cm⁻¹. -1 A sharp peak appears at 1700.39 cm⁻¹, with the C=O peak located at 1700.39 cm⁻¹. -1 The peak of the -OH stretching vibration of carvacrol is at 3357.74 cm⁻¹. -1 A relatively broad peak appeared. In the mixture, the -OH peaks of GA and carvacrol overlapped, and no new peak shape was observed, indicating that no new substances were formed. When the mass ratio of GA to carvacrol was 1:10, the -C=O stretching vibration peak of the mixture changed from 1700.39 cm⁻¹. -1 The redshift reached 1709.09 cm. -1 This change indicates the formation of hydrogen bonds between GA and carvacrol. As the GA content increases, the shift of the -C=O stretching vibration peak gradually decreases.

[0080] Example of effect 4

[0081] Carvacrol and its mixtures (GA to carvacrol in mass ratios of 1:10, 2:10, 3:10 and 4:10, respectively) were placed in an aluminum pot, covered, and the mass was approximately 6 to 9 mg.

[0082] Differential scanning calorimetry (DSC) was performed using a NETZSCH DSC 204F1. The DSC was calibrated for temperature using high-purity indium and tin standards, achieving an accuracy of ±0.5 °C for melting temperature determination. Measurements were taken at a heating rate of 5 °C / min. The temperature range for carvacrol was -20 to 30 °C, and for mixtures, it was -80 to 40 °C.

[0083] In Figure 3, GA is a white solid powder at room temperature with a melting point of approximately 300°C, while carvacrol has a melting point of 4°C. When carvacrol and GA are mixed, no obvious melting point is observed in the mixture at mass ratios of GA:10 and 2:10. However, at mass ratios of 3:10 and 4:10, glass transition temperatures of -46.76°C and -42.32°C, respectively, are observed. Therefore, it is speculated that GA and carvacrol may form a eutectic solvent.

[0084] Figure 4 shows the appearance of the glycyrrhetinic acid microemulsion prepared in Example 8 after sealing and storage at 45°C on day 0 and day 30. As can be seen from the figure, the microemulsion remained clear and transparent after being stored at 45°C for one month, and no glycyrrhetinic acid was precipitated, indicating that the carrier is very stable.

[0085] Figure 5 shows the particle size and retention rate of the glycyrrhetinic acid microemulsion prepared in Example 8 after storage at different temperatures for one month. After storage at 4°C, 25°C, and 45°C for one month, the microemulsions remained clear and transparent, with a particle size of approximately 17 nm, a PDI of less than 0.1, and a glycyrrhetinic acid retention rate of over 95%.

[0086] Example 5

[0087] The irritant properties of glycyrrhetinic acid microemulsion were studied using the chicken embryo chorioallantoic membrane assay (HET-CAM assay). 100 μL of each of Example 8 and Comparative Example 1 was dropped onto the surface of the allantoic membrane. Bleeding, coagulation, and hemolysis within 5 minutes were observed and recorded. The irritant properties were evaluated using the average value of the Irritation Score (IS).

[0088] Among them, T h The time of onset of bleeding, T l T is the time for blood vessel dissolution. c This refers to the time it takes for the blood to clot.

[0089] Figure 6 and Table 3 show the results of chicken embryo allantoic membranes in Example 8 and Comparative Example 1. As can be seen from the figures, diethylene glycol monoethyl ether is highly irritating to chicken embryo allantoic membranes, and the alcohol-free microemulsions prepared are significantly less irritating to chicken embryo allantoic membranes than the alcohol-containing microemulsions.

[0090] Table 3. Evaluation of Microemulsion Irritation

[0091] Example 6

[0092] Examples 7, 12, and 2 were applied to transdermal absorption.

[0093] Pigskin was placed between the supply and receiving cells of a Franz diffusion cell. 1 ml of sample was added to the supply cell, and the cell was placed in a transdermal diffusion apparatus for 12 hours. After the reaction, the glycyrrhetinic acid content in the stratum corneum was determined using the tape stripping method.

[0094] Use 3M tape to adhere the keratin layer of the pigskin, discarding the first layer and continuing to adhere 20 more layers;

[0095] Collected in centrifuge tubes, extracted with an extractant, and the content of glycyrrhetinic acid was determined by high performance liquid chromatography, which is the content of glycyrrhetinic acid in the stratum corneum.

[0096] The remaining pigskin after removing the stratum corneum by attaching 21 layers with 3M tape was cut into pieces and collected in centrifuge tubes. Extraction was performed by adding an extractant, and the content of glycyrrhetinic acid was determined by high performance liquid chromatography, which is the content of glycyrrhetinic acid in the dermis.

[0097] Figure 7 shows the results of transdermal absorption of Examples 7, 12, and 2 of the present invention. It can be seen that the transdermal effect of the glycyrrhetinic acid suspension is significantly lower than the other two groups. Example 12 involves encapsulating glycyrrhetinic acid in a microemulsion with caprylic acid as the oil phase only. The figure shows that the content of glycyrrhetinic acid in the dermis is higher than in the stratum corneum and also higher than in the glycyrrhetinic acid suspension group. This indicates that the microemulsion carrier can effectively deliver glycyrrhetinic acid into the deep layers of the skin, which is beneficial for its transdermal absorption. Simultaneously, the addition of another oil phase, carvacrol, to the microemulsion significantly increases the content of glycyrrhetinic acid in both the stratum corneum and dermis. This indicates that the eutectic solvent formed by hydrogen bonding between carvacrol and glycyrrhetinic acid not only increases the loading capacity of glycyrrhetinic acid but also effectively promotes its transdermal absorption.

[0098] Example 7

[0099] The ability of Examples 6, 8, and 12 to scavenge ·OH radicals was determined using the Fenton reaction: H₂O₂ + Fe²⁺ = ·OH + H₂O + Fe³⁺ to generate ·OH. Salicylic acid reacts with ·OH to generate 2,3-dihydroxybenzoic acid, which has a specific absorption at 510 nm. Adding an analyte with ·OH scavenging function to the reaction system reduces the generation of ·OH, thereby reducing the amount of colored compounds and achieving the purpose of ·OH scavenging. A 9 mmol / L ethanol-salicylic acid solution, a 9 mmol / L FeSO₄ solution, and an 8.8 mmol / L H₂O₂ solution were prepared for the reaction according to Table 4. After mixing, the reaction was carried out in a 37°C water bath for 15 min. The absorbance of the reaction solution at 510 nm was then measured using a microplate reader. The OH radical inhibition rate was calculated using the following formula:

[0100] Where Ax is the absorbance of the sample group; A0 is the absorbance of the blank control group; and AX0 is the absorbance without H2O2.

[0101] Table 4 Experimental methods for removing ·OH

[0102] The test results are shown in Table 5.

[0103] Table 5

[0104] As shown in Table 5, the ·OH scavenging rate of the microemulsion with only octanoic acid as the oil phase in Example 12 was (56.036±0.91)%, the ·OH scavenging rate of the blank microemulsion without glycyrrhetinic acid in Example 6 was (53.950±1.38)%, and the ·OH scavenging rate of the glycyrrhetinic acid-octanoic acid / carvacrol microemulsion in Example 8 was (93.739±1.89)%. It can be seen that microemulsions co-loaded with carvacrol and glycyrrhetinic acid can exert the antioxidant capacity of both simultaneously.

[0105] In this invention, glycyrrhetinic acid exhibits a eutectic phenomenon with carvacrol / thymol, which is unprecedented. Carvacrol / thymol significantly solubilizes glycyrrhetinic acid and promotes its transdermal absorption. Carvacrol / thymol possesses antioxidant, antibacterial, and anti-inflammatory bioactivities, which glycyrrhetinic acid also exhibits. Encapsulating these two active ingredients together achieves double the effect.

[0106] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, and all such modifications or substitutions should be covered within the scope of the present invention.

Claims

1. A microemulsion of an unhelpful surfactant loaded with glycyrrhetinic acid, characterized in that: include, Glycyrrhetinic acid, carvacrol / thymol, fatty acids, nonionic surfactants, and water; The composition, by weight percentage of raw materials, includes 0.1-5% glycyrrhetinic acid, 0.1-5% carvacrol / thymol, 0.1-10% fatty acids, 1-30% nonionic surfactant, and the remainder is made up to 100% with water.

2. The non-adjuvant surfactant microemulsion as described in claim 1, characterized in that: The fatty acids include at least one of caprylic acid, nonanoic acid, capric acid, and oleic acid.

3. The non-adjuvant surfactant microemulsion as described in 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 non-adjuvant surfactant microemulsion as described in claim 3, characterized in that: The nonionic surfactant includes polyoxyethylene hydrogenated castor oil 40.

5. The unhelpful surfactant microemulsion as described in any one of claims 1, 2, or 4, characterized in that: The average particle size of the unhelpful surfactant microemulsion loaded with glycyrrhetinic acid is 17–20 nm.

6. The unhelpful surfactant microemulsion as described in claim 5, characterized in that: The particle size distribution index (PDI) of the glycyrrhetinic acid-loaded unhelpful surfactant microemulsion is 0.01 to 0.

1.

7. The method for preparing the unassisted surfactant microemulsion according to any one of claims 1 to 6, characterized in that: include, The oil phase was prepared by mixing carvacrol / thymol with fatty acids; Glycyrrhetinic acid was dissolved in the oil phase to prepare an oil phase mixture; The oil phase mixture is mixed evenly with a nonionic surfactant to obtain a mixture; Water droplets are added to the mixture in a water bath, and after thorough mixing, water is added droplets 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. The use of the non-adjuvant surfactant microemulsion according to any one of claims 1 to 6 in the preparation of daily cosmetics.

10. The application as described in claim 9, characterized in that: The daily cosmetics mentioned include face cream and facial cleanser.

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