A glycyrrhetinic acid composition with anti-inflammatory function and its preparation method and application

Abstract

The application provides a glycyrrhetinic acid composition with redness-reducing and anti-inflammatory functions, and a preparation method and application thereof, and belongs to the technical field of cosmetics. Glycyrrhiza is subjected to enzymolysis, supercritical fluid extraction, and precipitation to obtain glycyrrhetinic acid, the glycyrrhetinic acid is coupled with allantoin to obtain a glycyrrhetinic acid-allantoin conjugate, the glycyrrhetinic acid is reacted with menthol to obtain glycyrrhetinic acid menthol ester, the glycyrrhetinic acid-allantoin conjugate, phospholipid and cholesterol are added into ethanol for dissolution, ethanol is removed by rotary evaporation under reduced pressure, a transparent film is obtained, an ethanol solution is added, ultrasonic treatment is carried out, and micro-porous membrane filtration is carried out to obtain the glycyrrhetinic acid composition with the redness-reducing and anti-inflammatory functions. The glycyrrhetinic acid composition with the redness-reducing and anti-inflammatory functions has the effects of redness reduction, anti-allergy, inflammation reduction, antibiosis, soothing, moisturizing and the like, effectively improves the transdermal penetration capacity of active ingredients, improves the water-solubility, greatly improves the bioavailability of the product, and thus expands the application range.

Description

Technical Field

[0001] This invention relates to the field of cosmetic technology, specifically to a glycyrrhizic acid composition with anti-inflammatory and redness-reducing functions, its preparation method, and its application. Background Technology

[0002] Glycyrrhetinic acid, also known as glycyrrhetinic acid or β-glycyrrhetinic acid, is a white crystalline or crystalline powder, odorless and tasteless. It is a natural compound extracted from licorice and possesses various pharmacological effects. It is a pentacyclic triterpenoid compound with multiple biological activities, including anti-inflammatory, anti-allergic, and antibacterial / viral activity. Glycyrrhetinic acid is widely used in the pharmaceutical and cosmetic industries, especially in cosmetics as a skin conditioning agent, serving as a soothing, anti-allergic, and whitening ingredient with good safety and efficacy. In addition, glycyrrhetinic acid also has antibacterial and antiviral effects, thus finding applications in the pharmaceutical field. In cosmetic formulations, the amount of glycyrrhetinic acid used is usually low, but it can effectively improve skin condition and reduce inflammation and allergic reactions. It can directly inhibit the production of inflammatory cytokines and inflammatory mediators through multiple targets, and can also indirectly exert its anti-inflammatory function through mechanisms such as enhancing the activity of steroid hormones.

[0003] Glycyrrhizic acid has a complex chemical structure, making its synthesis difficult, costly, and yielding, while also generating a large amount of waste. Alternatively, glycyrrhizic acid can be converted using concentrated sulfuric acid at 900°C, but this requires harsh reaction conditions and the product is extremely insoluble in water, oil, and most solubilizers. Furthermore, glycyrrhizic acid has low solubility and bioavailability, which limits its further clinical application. Summary of the Invention

[0004] The purpose of this invention is to propose a glycyrrhizic acid composition with anti-inflammatory and redness-reducing functions, its preparation method and application. It has the effects of reducing redness, anti-allergy, anti-inflammatory, antibacterial, soothing and moisturizing. It effectively improves the transdermal penetration ability of active ingredients, realizes the skin retention of active ingredients, and improves water solubility, which greatly improves the bioavailability of the product and thus expands its application scope.

[0005] The technical solution of this invention is implemented as follows: This invention provides a method for preparing a glycyrrhizic acid composition with anti-inflammatory and redness-reducing functions. The method involves enzymatically hydrolyzing licorice, supercritical fluid extraction, and precipitation to obtain glycyrrhizic acid. Glycyrrhizic acid is then coupled with allantoin to obtain a glycyrrhizic acid-allantoin conjugate. Glycyrrhizic acid is reacted with menthol to obtain glycyrrhizic acid-menthol ester. The glycyrrhizic acid-allantoin conjugate, phospholipids, and cholesterol are dissolved in ethanol, and the ethanol is removed by rotary evaporation under reduced pressure to obtain a transparent film. An ethanol solution is then added, followed by ultrasonication and filtration through a microporous membrane to obtain the glycyrrhizic acid composition with anti-inflammatory and redness-reducing functions.

[0006] As a further improvement to the present invention, the following steps are included: S1. Enzymatic hydrolysis: Grind licorice into powder, add water, add a compound enzyme for enzymatic hydrolysis, inactivate the enzyme, dry, and obtain the enzymatic hydrolysis complex; S2. Supercritical fluid extraction: The enzymatically hydrolyzed complex was subjected to supercritical fluid extraction to obtain an extract. The solvent was removed under reduced pressure, water was added, the extract was filtered, the solid was collected, washed, and dried to obtain glycyrrhetinic acid. S3. Preparation of glycyrrhetinic acid-allantoin conjugate: Glycyrrhetinic acid was dissolved in ethanol, EDC and NHS were added, the mixture was stirred and activated, allantoin was added, the mixture was stirred and reacted, acetone was added, the mixture was recrystallized, filtered, washed and dried to obtain glycyrrhetinic acid-allantoin conjugate. S4. Preparation of glycyrrhetinic acid menthol ester: Glycyrrhetinic acid and menthol were added to toluene, a catalyst was added, the mixture was heated under reflux and stirred, the product was washed successively with saturated brine, saturated sodium carbonate and water, the organic layer was dried, and the product was purified by column chromatography to obtain glycyrrhetinic acid menthol ester. S5. Preparation of glycyrrhetinic acid composition with anti-inflammatory and redness-reducing functions: Glycyrrhetinic acid-allantoin conjugate, glycyrrhetinic acid menthol ester, phospholipids and cholesterol are dissolved in ethanol, the ethanol is removed by rotary evaporation under reduced pressure to obtain a transparent film, an ethanol solution is added, ultrasonication is performed, and the film is filtered through a microporous membrane to obtain glycyrrhetinic acid composition with anti-inflammatory and redness-reducing functions.

[0007] As a further improvement of the present invention, the mass ratio of licorice and compound enzyme in step S1 is 10:0.5-1, the compound enzyme is cellulase and bromelain with a mass ratio of 5-7:2-3, and the enzymatic hydrolysis temperature is 35-40℃ and the time is 2-4h.

[0008] As a further improvement of the present invention, the supercritical fluid extraction conditions in step S2 are as follows: extraction pressure: 18-27 MPa, extraction temperature: 30-40℃, CO2 flow rate: 5-10 L / h, extraction time: 120-180 min, and the entrainer is ethanol, with an addition amount of 2-3 wt%.

[0009] As a further improvement of the present invention, the mass ratio of glycyrrhetinic acid, EDC, NHS and allantoin in step S3 is 4.5-5:1.4-1.6:1.0-1.2:1.3-1.6, the stirring activation temperature is 0-4℃, the time is 20-30 min, and the stirring reaction time is 10-14 h.

[0010] As a further improvement of the present invention, the mass ratio of glycyrrhetinic acid, menthol and catalyst in step S4 is 4.5-5:1.3-1.7:0.1-0.3, the catalyst is concentrated sulfuric acid, and the heating, reflux and stirring reaction time is 6-8 hours.

[0011] As a further improvement of the present invention, in step S5, the mass ratio of glycyrrhetinic acid-allantoin conjugate, glycyrrhetinic acid menthol ester, phospholipid, and cholesterol is 3-4:4-6:15-22:8-10, the concentration of the ethanol solution is 50-70wt%, the power of the ultrasound is 1000-1200W, the time is 10-20min, and the pore size of the microporous filter membrane is 0.22μm.

[0012] The present invention further protects a glycyrrhizic acid composition with anti-inflammatory and redness-reducing functions prepared by the above-mentioned preparation method.

[0013] This invention further protects the use of the above-mentioned glycyrrhizic acid composition with anti-inflammatory and redness-reducing functions in cosmetics.

[0014] As a further improvement of the present invention, the cosmetic has anti-inflammatory, redness-reducing, and soothing effects.

[0015] The present invention has the following beneficial effects: Glycyrrhetinic acid belongs to the pentacyclic triterpenoid class of compounds and possesses a wide range of pharmacological activities, especially its anti-inflammatory properties. These properties are related to the inhibition of superoxide radical production by neutrophils, which are the main mediators of inflammation. Furthermore, the steroid-like structure of glycyrrhetinic acid endows it with anti-inflammatory, anti-immune, repairing, and anti-allergic effects. However, due to its high logP (oil-water partition coefficient), glycyrrhetinic acid has difficulty penetrating the stratum corneum and has poor water solubility, limiting its application in cosmetics. This invention utilizes a composite enzymatic supercritical fluid extraction technology to extract glycyrrhetinic acid, resulting in a green and safe process with stable extraction rates and free from pesticide residues and other hazardous substances.

[0016] Allantoin can promote cell proliferation and extracellular matrix synthesis, accelerate wound healing, reduce the expression of inflammatory cytokines, alleviate inflammatory responses, and possess antioxidant properties, reducing oxidative stress and protecting cells. It can also bind with various substances to form complex salts, maintaining skin moisture and making it suitable for use in cosmetics to keep skin moisturized and soft. However, studies have found that long-term use may cause skin irritation, leading to redness, peeling, and allergies. Allantoin can also interact with other drugs, especially when mixed with other drugs containing allantoin, potentially causing overdose. This invention couples allantoin and glycyrrhetinic acid, avoiding the interactions that would occur when the two components are directly mixed, thus preventing reduced efficacy. The resulting conjugate has low skin irritation and exhibits anti-redness, anti-allergic, and anti-inflammatory effects. Simultaneously, allantoin promotes transdermal absorption, improving efficacy, reducing the dosage, and lowering costs.

[0017] The liposomes prepared in this invention are composed of phospholipids, polyols, and water, which can effectively improve the skin penetration efficiency of drugs. The addition of alcohol enhances the flexibility and extensibility of the structure, resulting in superior skin permeability compared to liposomes and stronger transdermal penetration. Encapsulating active ingredients in liposomes effectively improves their transdermal penetration, enabling skin retention and increasing water solubility, thus significantly improving the product's bioavailability and expanding its application scope.

[0018] The glycyrrhizic acid composition prepared by this invention has the functions of reducing redness and inflammation, including reducing redness, anti-allergy, anti-inflammatory, antibacterial, soothing and moisturizing. It effectively improves the transdermal penetration ability of active ingredients, enables active ingredients to remain on the skin, and improves water solubility, which greatly improves the bioavailability of the product and expands its application scope. Detailed Implementation

[0019] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0020] 1-Ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC), N-hydroxysuccinimide (NHS), commercially available. Cholesterol (Xi'an Yuanye Biotechnology Co., Ltd.); Phospholipids (phosphatidylcholine content: 88%, Shanghai Fubicheng Pharmaceutical Technology Co., Ltd.).

[0021] Cellulase, 10,000 U / g, and bromelain, 100,000 U / g, were both purchased from Nanning Dongheng Huadao Biotechnology Co., Ltd.

[0022] Example 1 This embodiment provides a method for preparing a glycyrrhizic acid composition with anti-inflammatory and redness-reducing functions, comprising the following steps: S1. Enzymatic hydrolysis: 10g of licorice was crushed, added to 200mL of water, 0.5g of compound enzyme was added, and enzymatic hydrolysis was carried out at 35℃ for 2h. The enzyme was then inactivated and dried to obtain the enzymatic hydrolysis complex. The composite enzyme is cellulase and bromelain in a mass ratio of 5:2. S2. Supercritical fluid extraction: The enzymatically hydrolyzed complex was extracted by supercritical fluid extraction to obtain an extract. The solvent was removed under reduced pressure. 10g of the product was added to 100mL of water, filtered, the solid was collected, washed, and dried to obtain glycyrrhetinic acid. The supercritical fluid extraction conditions are as follows: extraction pressure: 18 MPa, extraction temperature: 30℃, CO2 flow rate: 5 L / h, extraction time: 120 min, and the entrainer is ethanol, with an addition amount of 2 wt%. S3. Preparation of glycyrrhetinic acid-allantoin conjugate: 4.5 g glycyrrhetinic acid was dissolved in 500 mL ethanol, 1.4 g EDC and 1.0 g NHS were added, and the mixture was stirred and activated at 0 °C for 20 min. 1.3 g allantoin was added, and the mixture was stirred and reacted for 10 h. An equal volume of acetone was added, and the mixture was recrystallized, filtered, washed, and dried to obtain the glycyrrhetinic acid-allantoin conjugate. S4. Preparation of glycyrrhetinic acid menthol ester: 4.5 g glycyrrhetinic acid and 1.3 g menthol were added to 500 mL toluene, and 0.1 g concentrated sulfuric acid was added. The mixture was heated under reflux and stirred for 6 h. The product was washed successively with equal volumes of saturated brine, saturated sodium carbonate and water. The organic layer was dried and purified by column chromatography (ethyl acetate: petroleum ether volume ratio was 1:1) to obtain glycyrrhetinic acid menthol ester. S5. Preparation of glycyrrhetinic acid composition with anti-inflammatory and redness-reducing functions: 3 mg glycyrrhetinic acid-allantoin conjugate, 4 mg glycyrrhetinic acid menthol ester, 1 mg phospholipid, and 8 mg cholesterol were dissolved in 20 mL of ethanol. The ethanol was removed by rotary evaporation under reduced pressure to obtain a transparent film. 20 mL of 50 wt% ethanol solution was added, and the film was sonicated at 1000 W for 10 min. The film was then filtered through a 0.22 μm microporous membrane to obtain the glycyrrhetinic acid composition with anti-inflammatory and redness-reducing functions.

[0023] Example 2 This embodiment provides a method for preparing a glycyrrhizic acid composition with anti-inflammatory and redness-reducing functions, comprising the following steps: S1. Enzymatic hydrolysis: 10g of licorice was crushed, added to 200mL of water, 1g of compound enzyme was added, and enzymatic hydrolysis was carried out at 40℃ for 4h. The enzyme was then inactivated and dried to obtain the enzymatic hydrolysis complex. The complex enzyme is cellulase and bromelain in a mass ratio of 7:3. S2. Supercritical fluid extraction: The enzymatically hydrolyzed complex was extracted by supercritical fluid extraction to obtain an extract. The solvent was removed under reduced pressure. 10g of the product was added to 100mL of water, filtered, the solid was collected, washed, and dried to obtain glycyrrhetinic acid. The supercritical fluid extraction conditions are as follows: extraction pressure: 27 MPa, extraction temperature: 40℃, CO2 flow rate: 10 L / h, extraction time: 180 min, and the entrainer is ethanol, with an addition amount of 3 wt%. S3. Preparation of glycyrrhetinic acid-allantoin conjugate: 5g glycyrrhetinic acid was dissolved in 500mL ethanol, 1.6g EDC and 1.2g NHS were added, and the mixture was stirred and activated at 4℃ for 30min. 1.6g allantoin was added, and the mixture was stirred and reacted for 14h. An equal volume of acetone was added, and the mixture was recrystallized, filtered, washed, and dried to obtain the glycyrrhetinic acid-allantoin conjugate. S4. Preparation of glycyrrhetinic acid menthol ester: 5g glycyrrhetinic acid and 1.7g menthol were added to 500mL toluene, and 0.3g concentrated sulfuric acid was added. The mixture was heated under reflux and stirred for 8h. The product was washed successively with equal volumes of saturated brine, saturated sodium carbonate and water. The organic layer was dried and purified by column chromatography (ethyl acetate: petroleum ether volume ratio was 1:1) to obtain glycyrrhetinic acid menthol ester. S5. Preparation of glycyrrhetinic acid composition with anti-inflammatory and redness-reducing functions: 4 mg glycyrrhetinic acid-allantoin conjugate, 6 mg glycyrrhetinic acid menthol ester, 22 mg phospholipids, and 10 mg cholesterol were dissolved in 20 mL of ethanol. The ethanol was removed by rotary evaporation under reduced pressure to obtain a transparent film. 20 mL of 70 wt% ethanol solution was added, and the film was sonicated at 1200 W for 20 min. The film was then filtered through a 0.22 μm microporous membrane to obtain the glycyrrhetinic acid composition with anti-inflammatory and redness-reducing functions.

[0024] Example 3 This embodiment provides a method for preparing a glycyrrhizic acid composition with anti-inflammatory and redness-reducing functions, comprising the following steps: S1. Enzymatic hydrolysis: 10g of licorice was crushed, added to 200mL of water, 0.7g of compound enzyme was added, and enzymatic hydrolysis was carried out at 37℃ for 3h. The enzyme was then inactivated and dried to obtain the enzymatic hydrolysis complex. The complex enzyme is composed of cellulase and bromelain in a mass ratio of 6:2.5. S2. Supercritical fluid extraction: The enzymatically hydrolyzed complex was extracted by supercritical fluid extraction to obtain an extract. The solvent was removed under reduced pressure. 10g of the product was added to 100mL of water, filtered, the solid was collected, washed, and dried to obtain glycyrrhetinic acid. The supercritical fluid extraction conditions are as follows: extraction pressure: 22 MPa, extraction temperature: 35℃, CO2 flow rate: 7 L / h, extraction time: 150 min, and the entrainer is ethanol, with an addition amount of 2.5 wt%. S3. Preparation of glycyrrhetinic acid-allantoin conjugate: 4.7 g glycyrrhetinic acid was dissolved in 500 mL ethanol, 1.5 g EDC and 1.1 g NHS were added, and the mixture was stirred and activated at 2 °C for 25 min. 1.45 g allantoin was added, and the mixture was stirred and reacted for 12 h. An equal volume of acetone was added, and the mixture was recrystallized, filtered, washed, and dried to obtain the glycyrrhetinic acid-allantoin conjugate. S4. Preparation of glycyrrhetinic acid menthol ester: 4.7 g glycyrrhetinic acid and 1.5 g menthol were added to 500 mL toluene, and 0.2 g concentrated sulfuric acid was added. The mixture was heated under reflux and stirred for 7 h. The product was washed successively with equal volumes of saturated brine, saturated sodium carbonate and water. The organic layer was dried and purified by column chromatography (ethyl acetate: petroleum ether volume ratio was 1:1) to obtain glycyrrhetinic acid menthol ester. S5. Preparation of glycyrrhetinic acid composition with anti-inflammatory and redness-reducing functions: 3.5 mg glycyrrhetinic acid-allantoin conjugate, 5 mg glycyrrhetinic acid menthol ester, 19 mg phospholipid, and 9 mg cholesterol were dissolved in 20 mL of ethanol. The ethanol was removed by rotary evaporation under reduced pressure to obtain a transparent film. 20 mL of 60 wt% ethanol solution was added, and the film was sonicated at 1100 W for 15 min. The film was then filtered through a 0.22 μm microporous membrane to obtain the glycyrrhetinic acid composition with anti-inflammatory and redness-reducing functions.

[0025] Comparative Example 1 The difference from Example 3 is that step S1 was not performed.

[0026] Specifically as follows: S1. Supercritical fluid extraction: Licorice was pulverized and extracted by supercritical fluid to obtain an extract. The solvent was removed under reduced pressure. 10g of the product was added to 100mL of water, filtered, the solid was collected, washed, and dried to obtain glycyrrhetinic acid. The supercritical fluid extraction conditions are as follows: extraction pressure: 22 MPa, extraction temperature: 35℃, CO2 flow rate: 7 L / h, extraction time: 150 min, and the entrainer is ethanol, with an addition amount of 2.5 wt%. S2. Preparation of glycyrrhetinic acid-allantoin conjugate: 4.7 g glycyrrhetinic acid was dissolved in 500 mL ethanol, 1.5 g EDC and 1.1 g NHS were added, and the mixture was stirred and activated at 2 °C for 25 min. 1.45 g allantoin was added, and the mixture was stirred and reacted for 12 h. An equal volume of acetone was added, and the mixture was recrystallized, filtered, washed, and dried to obtain the glycyrrhetinic acid-allantoin conjugate. S3. Preparation of glycyrrhetinic acid menthol ester: 4.7 g glycyrrhetinic acid and 1.5 g menthol were added to 500 mL toluene, and 0.2 g concentrated sulfuric acid was added. The mixture was heated under reflux and stirred for 7 h. The product was washed successively with equal volumes of saturated brine, saturated sodium carbonate and water. The organic layer was dried and purified by column chromatography (ethyl acetate: petroleum ether volume ratio was 1:1) to obtain glycyrrhetinic acid menthol ester. S4. Preparation of glycyrrhetinic acid composition with anti-inflammatory and redness-reducing functions: 3.5 mg glycyrrhetinic acid-allantoin conjugate, 5 mg glycyrrhetinic acid menthol ester, 19 mg phospholipid, and 9 mg cholesterol were dissolved in 20 mL of ethanol. The ethanol was removed by rotary evaporation under reduced pressure to obtain a transparent film. 20 mL of 60 wt% ethanol solution was added, and the film was sonicated at 1100 W for 15 min. The film was then filtered through a 0.22 μm microporous membrane to obtain the glycyrrhetinic acid composition with anti-inflammatory and redness-reducing functions.

[0027] Comparative Example 2 The difference from Example 3 is that the supercritical fluid extraction in step S2 is replaced by ethanol solution extraction.

[0028] Specifically as follows: S2. Extraction: Add 50g of the enzymatically hydrolyzed complex to 500mL of 60wt% ethanol solution, heat to 60℃, extract for 2h, filter, dry the filtrate, add 10g of the product to 100mL of water, filter, collect the solid, wash, dry, and obtain glycyrrhetinic acid.

[0029] Comparative Example 3 The difference from Example 3 is that glycyrrhetinic acid-allantoin conjugate was not added in step S5.

[0030] Specifically as follows: S5. Preparation of glycyrrhetinic acid composition with anti-inflammatory and redness-reducing functions: 8.5 mg glycyrrhetinic acid menthol ester, 19 mg phospholipid and 9 mg cholesterol were dissolved in 20 mL ethanol, and the ethanol was removed by rotary evaporation under reduced pressure to obtain a transparent film. 20 mL of 60 wt% ethanol solution was added, and the film was sonicated at 1100 W for 15 min and filtered through a 0.22 μm microporous membrane to obtain glycyrrhetinic acid composition with anti-inflammatory and redness-reducing functions.

[0031] Comparative Example 4 Compared with Example 3, the difference is that in step S5, the glycyrrhetinic acid-allantoin conjugate is replaced by a mixture of glycyrrhetinic acid and allantoin in a mass ratio of 4.7:1.45.

[0032] Specifically as follows: S5. Preparation of glycyrrhetinic acid composition with anti-inflammatory and redness-reducing functions: 3.5 mg of a mixture (glycyrrhetinic acid and allantoin in a mass ratio of 4.7:1.45), 5 mg of glycyrrhetinic acid menthol ester, 19 mg of phospholipids, and 9 mg of cholesterol were dissolved in 20 mL of ethanol. The ethanol was removed by rotary evaporation under reduced pressure to obtain a transparent film. 20 mL of 60 wt% ethanol solution was added, and the film was sonicated at 1100 W for 15 min. The film was then filtered through a 0.22 μm microporous membrane to obtain the glycyrrhetinic acid composition with anti-inflammatory and redness-reducing functions.

[0033] Comparative Example 5 The difference from Example 3 is that menthol glycyrrhetinic acid was not added in step S5.

[0034] Specifically as follows: S5. Preparation of glycyrrhetinic acid composition with anti-inflammatory and redness-reducing functions: 8.5 mg glycyrrhetinic acid-allantoin conjugate, 19 mg phospholipids, and 9 mg cholesterol were dissolved in 20 mL of ethanol. The ethanol was removed by rotary evaporation under reduced pressure to obtain a transparent film. 20 mL of 60 wt% ethanol solution was added, and the film was sonicated at 1100 W for 15 min. The film was then filtered through a 0.22 μm microporous membrane to obtain the glycyrrhetinic acid composition with anti-inflammatory and redness-reducing functions.

[0035] Comparative Example 6 Compared with Example 3, the difference is that in step S5, glycyrrhetinic acid menthol ester is replaced by a mixture of glycyrrhetinic acid and menthol in a mass ratio of 4.7:1.5.

[0036] Specifically as follows: S5. Preparation of glycyrrhetinic acid composition with anti-inflammatory and redness-reducing functions: 3.5 mg glycyrrhetinic acid-allantoin conjugate, 5 mg mixture (glycyrrhetinic acid and menthol in a mass ratio of 4.7:1.5), 19 mg phospholipids, and 9 mg cholesterol were dissolved in 20 mL of ethanol. The ethanol was removed by rotary evaporation under reduced pressure to obtain a transparent film. 20 mL of 60 wt% ethanol solution was added, and the film was sonicated at 1100 W for 15 min. The film was then filtered through a 0.22 μm microporous membrane to obtain the glycyrrhetinic acid composition with anti-inflammatory and redness-reducing functions.

[0037] Comparative Example 7 The difference from Example 3 is that ethanol body embedding was not performed in step S5.

[0038] Specifically as follows: S5. Preparation of glycyrrhetinic acid composition with anti-inflammatory and redness-reducing functions: 3.5 mg glycyrrhetinic acid-allantoin conjugate and 5 mg glycyrrhetinic acid menthol ester were mixed for 10 min to obtain glycyrrhetinic acid composition with anti-inflammatory and redness-reducing functions.

[0039] Test Example 1 Fifty-five subjects were recruited to evaluate the rapid-acting soothing and repairing efficacy of the glycyrrhetinic acid compositions with redness-reducing and anti-inflammatory functions prepared in Examples 1-3 and Comparative Examples 1-7 (with deionized water as the control group).

[0040] Subject inclusion criteria are as follows: (1) 18-55 years old, healthy subjects, both male and female; (2) positive lactic acid sting test total score ≥3 points, those who are positive; (3) those who are prone to symptoms such as burning, stinging, itching and tightness on the face, and whose skin barrier is fragile; (4) those who have not used repair-related skin care products in the past month; (5) those who have no history of cosmetic or drug allergies; (6) those who are not allowed to participate in other facial tests during the testing period; those who cannot engage in prolonged sun exposure, outdoor sports, swimming, travel, etc.; (7) those who are informed about the project, are willing and able to comply with all testing requirements, accept skin examination, and agree to and accept a series of subsequent examinations.

[0041] Instructions for use: Subjects apply the test product to the test area. After cleansing, subjects apply 1 mL of the test product to the face. Use once daily for one week, followed by a test.

[0042] Evaluation method: Red zone area acquisition: Visia7 facial imaging tester; Image-Pro® Plus Chinese Version 7.0.1 image processing enhancement and analysis system; images were acquired at 0° frontal angle, 37° left side angle, and 37° right side angle, one acquisition and one analysis. The lower this value, the smaller the average red zone area within the test area. Unit: mm 2 .

[0043] Erythema Index (EI) value: Mexameter MX18 skin melanin and hemoglobin testing probe; average of 3 tests. The EI value represents the relative content of hemoglobin in the skin; the higher the value, the higher the relative content of hemoglobin in the skin. Unit: dimensionless.

[0044] Transdermal water loss: Tewameter™ Hex skin surface water loss test probe; 3 tests were performed and the average value was taken. The lower the value, the less transdermal water loss. Unit: g / (h·m) 2 ).

[0045] Test environment: temperature 22±2℃, relative humidity 55±5%.

[0046] The results are shown in Table 1.

[0047] Table 1

[0048] As can be seen from the table above, the glycyrrhizic acid compositions with redness-reducing and anti-inflammatory functions prepared in Examples 1-3 of the present invention have good redness-reducing, soothing, and moisturizing effects.

[0049] Meanwhile, data from each group of allergy sufferers were collected, and the results are shown in Table 2.

[0050] Table 2

[0051] As shown in the table above, the glycyrrhizic acid compositions with anti-inflammatory and redness-reducing functions prepared in Examples 1-3 of this invention have no allergic reactions and are safe with no side effects.

[0052] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing a glycyrrhizic acid composition with anti-inflammatory and redness-reducing functions, characterized in that, Licorice was enzymatically hydrolyzed, extracted by supercritical fluid, and precipitated to obtain glycyrrhetinic acid. Glycyrrhetinic acid was then reacted with allantoin to obtain glycyrrhetinic acid-allantoin conjugate. Glycyrrhetinic acid was then reacted with menthol to obtain glycyrrhetinic acid menthol ester. The glycyrrhetinic acid-allantoin conjugate, phospholipids, and cholesterol were dissolved in ethanol, and the ethanol was removed by rotary evaporation under reduced pressure to obtain a transparent film. An ethanol solution was added, and the film was sonicated and filtered through a microporous membrane to obtain a glycyrrhetinic acid composition with anti-inflammatory and redness-reducing functions. Includes the following steps: S1. Enzymatic hydrolysis: Grind licorice into powder, add water, add a compound enzyme for enzymatic hydrolysis, inactivate the enzyme, dry, and obtain the enzymatic hydrolysis complex; S2. Supercritical fluid extraction: The enzymatically hydrolyzed complex was subjected to supercritical fluid extraction to obtain an extract. The solvent was removed under reduced pressure, water was added, the extract was filtered, the solid was collected, washed, and dried to obtain glycyrrhetinic acid. S3. Preparation of glycyrrhetinic acid-allantoin conjugate: Glycyrrhetinic acid was dissolved in ethanol, EDC and NHS were added, the mixture was stirred and activated, allantoin was added, the mixture was stirred and reacted, acetone was added, the mixture was recrystallized, filtered, washed and dried to obtain glycyrrhetinic acid-allantoin conjugate. S4. Preparation of glycyrrhetinic acid menthol ester: Glycyrrhetinic acid and menthol were added to toluene, a catalyst was added, the mixture was heated under reflux and stirred, the product was washed successively with saturated brine, saturated sodium carbonate and water, the organic layer was dried, and the product was purified by column chromatography to obtain glycyrrhetinic acid menthol ester. S5. Preparation of glycyrrhetinic acid composition with anti-inflammatory and redness-reducing functions: Glycyrrhetinic acid-allantoin conjugate, glycyrrhetinic acid menthol ester, phospholipids and cholesterol are dissolved in ethanol, the ethanol is removed by rotary evaporation under reduced pressure to obtain a transparent film, an ethanol solution is added, ultrasonication is performed, and the film is filtered through a microporous membrane to obtain glycyrrhetinic acid composition with anti-inflammatory and redness-reducing functions.

2. The preparation method according to claim 1, characterized in that, In step S1, the mass ratio of licorice to compound enzyme is 10:0.5-1, the compound enzyme is cellulase and bromelain, and the mass ratio is 5-7:2-3. The enzymatic hydrolysis temperature is 35-40℃ and the time is 2-4h.

3. The preparation method according to claim 1, characterized in that, The supercritical fluid extraction conditions described in step S2 are as follows: extraction pressure: 18-27 MPa, extraction temperature: 30-40℃, CO2 flow rate: 5-10 L / h, extraction time: 120-180 min, the entrainer is ethanol, and the amount of entrainer added is 2-3 wt%.

4. The preparation method according to claim 1, characterized in that, In step S3, the mass ratio of glycyrrhetinic acid, EDC, NHS, and allantoin is 4.5-5:1.4-1.6:1.0-1.2:1.3-1.

6. The stirring activation temperature is 0-4℃, the time is 20-30 min, and the stirring reaction time is 10-14 h.

5. The preparation method according to claim 1, characterized in that, In step S4, the mass ratio of glycyrrhetinic acid, menthol, and catalyst is 4.5-5:1.3-1.7:0.1-0.3, the catalyst is concentrated sulfuric acid, and the heating, reflux, and stirring reaction time is 6-8 hours.

6. The preparation method according to claim 1, characterized in that, In step S5, the mass ratio of glycyrrhetinic acid-allantoin conjugate, glycyrrhetinic acid menthol ester, phospholipid, and cholesterol is 3-4:4-6:15-22:8-10, the concentration of the ethanol solution is 50-70 wt%, the ultrasonic power is 1000-1200 W, the time is 10-20 min, and the pore size of the microporous filter membrane is 0.22 μm.

7. A glycyrrhizic acid composition with anti-inflammatory and redness-reducing functions prepared by the preparation method according to any one of claims 1-6.

8. The use of a glycyrrhetinic acid composition with anti-inflammatory and redness-reducing functions as described in claim 7 in cosmetics.

9. The application according to claim 8, characterized in that, The cosmetic product has anti-inflammatory, redness-reducing, and soothing effects.

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