Glycyrrhizic acid composition with functions of removing redness and resisting inflammation as well as preparation method and application of glycyrrhizic acid composition

Abstract

The invention provides a glycyrrhizic acid composition with functions of removing redness and resisting inflammation as well as a preparation method and application of the glycyrrhizic acid composition, and belongs to the technical field of cosmetics. The preparation method comprises the following steps: carrying out enzymolysis, supercritical fluid extraction and precipitation on liquorice to prepare glycyrrhizic acid, coupling glycyrrhizic acid with allantoin to prepare a glycyrrhizic acid-alkaloid conjugate, reacting glycyrrhizic acid with menthol to prepare glycyrrhizic acid menthol ester, adding glycyrrhizic acid menthol ester, the glycyrrhizic acid-alkaloid conjugate, phospholipid and cholesterol into ethanol for dissolving, and carrying out reduced pressure rotary evaporation to remove ethanol, so as to obtain the glycyrrhizic acid menthol ester. Adding an ethanol solution, performing ultrasonic treatment, and filtering with a microfiltration membrane, so as to obtain the glycyrrhizic acid composition with the redness-removing and anti-inflammatory functions. The glycyrrhizic acid composition with the functions of removing redness and resisting inflammation has the effects of removing redness, resisting allergy, diminishing inflammation, resisting bacteria, relieving, moisturizing and the like, the percutaneous infiltration capacity of active ingredients is effectively improved, the water-soluble capacity is improved, the bioavailability of a product is greatly improved, and therefore the application range of the glycyrrhizic acid composition is widened.

Description

Technical Field

[0001] The present invention relates to the technical field of cosmetics, and in particular to a glycyrrhetinic acid composition with redness-removing and anti-inflammatory functions, a preparation method and application thereof. Background Art

[0002] Glycyrrhetinic acid, also known as glycyrrhetinic acid or β-glycyrrhetinic acid, is a white crystal or crystalline powder, odorless and tasteless. It is a natural compound extracted from licorice with multiple pharmacological effects. It is a pentacyclic triterpenoid compound with multiple biological activities such as anti-inflammatory, anti-allergic, and antibacterial and antiviral. Glycyrrhetinic acid is widely used in the pharmaceutical and cosmetic industries, especially as a skin conditioner in cosmetics, used as a soothing, anti-allergic and whitening ingredient, with good safety and effectiveness. In addition, glycyrrhetinic acid also has the effects of inhibiting bacterial reproduction and antiviral, so it is also used in the medical field. In cosmetic formulas, the amount of glycyrrhetinic acid used is usually low, but it can effectively improve skin conditions 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] The chemical structure of glycyrrhizic acid is complex, the chemical synthesis process is difficult, the chemical synthesis cost is high, the yield is low, and a large amount of waste is generated. Alternatively, glycyrrhizic acid is converted in concentrated sulfuric acid at a high temperature of 900°C, the reaction conditions are harsh, and the product is extremely difficult to dissolve in water, oil, and most solubilizers. In addition, the solubility and bioavailability of glycyrrhizic acid are low, which limits its further clinical application. Summary of the invention

[0004] The purpose of the present invention is to provide a glycyrrhetinic acid composition with redness-removing and anti-inflammatory functions, as well as a preparation method and application thereof, which has the effects of redness-removing, anti-allergic, anti-inflammatory, antibacterial, soothing, moisturizing, etc., effectively improves the transdermal penetration ability of active ingredients, realizes the skin residence of active ingredients, and improves the water solubility, greatly improves the bioavailability of the product, thereby expanding its application surface.

[0005] The technical solution of the present invention is achieved in this way:

[0006] The invention provides a preparation method of a glycyrrhetinic acid composition with redness-removing and anti-inflammatory functions. The method comprises the following steps: subjecting licorice to enzymolysis, supercritical fluid extraction and precipitation to obtain glycyrrhetinic acid; coupling glycyrrhetinic acid with allantoin to obtain a glycyrrhetinic acid-alkaloid conjugate; reacting glycyrrhetinic acid with menthol to obtain glycyrrhetinic acid menthol ester; adding the glycyrrhetinic acid-alkaloid conjugate, phospholipid and cholesterol into ethanol for dissolution; removing ethanol by vacuum rotary evaporation to obtain a transparent film; adding an ethanol solution, ultrasonicating and filtering with a microporous filter membrane to obtain the glycyrrhetinic acid composition with redness-removing and anti-inflammatory functions.

[0007] As a further improvement of the present invention, the following steps are included:

[0008] S1. Enzymatic hydrolysis: crush licorice, add to water, add complex enzyme for enzymatic hydrolysis, inactivate the enzyme, dry, and obtain an enzymatic complex;

[0009] S2. Supercritical fluid extraction: The enzymatic complex is subjected to supercritical fluid extraction to obtain an extract, the solvent is removed under reduced pressure, added to water, filtered, the solid is collected, washed, and dried to obtain glycyrrhetinic acid;

[0010] S3. Preparation of glycyrrhetinic acid-alkaloid conjugate: dissolving glycyrrhetinic acid in ethanol, adding EDC and NHS, stirring to activate, adding allantoin, stirring to react, adding acetone, recrystallizing, filtering, washing, and drying to obtain glycyrrhetinic acid-alkaloid conjugate;

[0011] S4. Preparation of glycyrrhetinic acid menthol ester: glycyrrhetinic acid and menthol were added to toluene, a catalyst was added, the reaction was heated to reflux with stirring, the product was washed with saturated brine, saturated sodium carbonate and water, the organic layer was dried, and separated and purified by column chromatography to obtain glycyrrhetinic acid menthol ester;

[0012] S5. Preparation of a glycyrrhetinic acid composition with redness-removing and anti-inflammatory functions: add glycyrrhetinic acid-alkaloid conjugate, glycyrrhetinic acid menthol ester, phospholipids, and cholesterol to ethanol for dissolution, remove ethanol by vacuum rotary evaporation to obtain a transparent film, add ethanol solution, perform ultrasound, and filter with a microporous membrane to obtain a glycyrrhetinic acid composition with redness-removing and anti-inflammatory functions.

[0013] As a further improvement of the present invention, in step S1, the mass ratio of licorice and compound enzyme is 10:0.5-1, the compound enzyme is cellulase and bromelain, the mass ratio is 5-7:2-3, the temperature of the enzymolysis is 35-40°C, and the time is 2-4h.

[0014] As a further improvement of the present invention, the supercritical fluid extraction conditions in step S2 are: extraction pressure: 18-27MPa, extraction temperature: 30-40°C, CO2 flow rate: 5-10L / h, extraction time: 120-180min, the entrainer is ethanol, and the entrainer addition amount is 2-3wt%.

[0015] 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°C, the time is 20-30min, and the stirring reaction time is 10-14h.

[0016] As a further improvement of the present invention, 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 stirring reaction time is 6-8h.

[0017] As a further improvement of the present invention, the mass ratio of glycyrrhetinic acid-alkaloid conjugate, glycyrrhetinic acid menthyl ester, phospholipid and cholesterol in step S5 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.

[0018] The present invention further protects a glycyrrhetinic acid composition with redness-removing and anti-inflammatory functions obtained by the above-mentioned preparation method.

[0019] The present invention further protects the use of the glycyrrhetinic acid composition having redness-removing and anti-inflammatory functions in cosmetics.

[0020] As a further improvement of the present invention, the cosmetic has the effects of anti-inflammatory, reducing redness and soothing.

[0021] The present invention has the following beneficial effects:

[0022] Glycyrrhetinic acid belongs to pentacyclic triterpenoid compounds and has a wide range of pharmacological activities, especially its anti-inflammatory properties, which are related to the inhibition of superoxide radical production by neutrophils, which are the main mediators of inflammation. In addition, the steroid-like structure of glycyrrhetinic acid gives it anti-inflammatory and anti-immune, repair and anti-allergic effects. However, due to the high logP (oil-water partition coefficient) of glycyrrhetinic acid, it is difficult to penetrate the stratum corneum of the skin, and its water solubility is very poor, which limits its application in cosmetics. The present invention uses a composite enzyme supercritical fluid extraction technology to extract glycyrrhetinic acid, which is green and safe, has a stable extraction rate, and does not contain risk substances such as pesticide residues.

[0023] Borneol has a wide range of pharmacological effects such as analgesia, anti-inflammatory, and antibacterial. It can not only be used as a transdermal drug, but also is a good transdermal enhancer. However, long-term clinical findings show that borneol is easy to sublimate and has certain toxic and side effects, thereby limiting its application in cosmetics. The present invention reacts glycyrrhetinic acid with borneol to obtain an ester, which complements each other and has a synergistic effect. The product has low irritation and has a strong transdermal absorption effect, thereby greatly improving the efficacy, reducing the amount of drug used, and reducing the cost.

[0024] Allantoin can promote cell proliferation and extracellular matrix synthesis, accelerate wound healing process, reduce the expression of inflammatory cytokines, alleviate inflammatory response, have antioxidant properties, can reduce oxidative stress reaction, protect cells, can also combine multiple substances to form complex salts, keep skin moisture, used in cosmetics, keep skin moisturized and soft. However, studies have found that long-term use may cause skin irritation, leading to phenomena such as redness, peeling, allergies, and allantoin can also interact with other drugs, especially when mixed with other drugs containing allantoin, may cause drug overdose. The present invention couples allantoin and glycyrrhetinic acid, avoids the interaction that will occur when two components are directly mixed and reduces drug efficacy, and the obtained conjugate is less irritating to the skin, has the effect of de-reddening, anti-allergy, and anti-inflammatory. Meanwhile, allantoin also has the effect of promoting skin transdermal absorption, improves drug efficacy, reduces the usage amount of medicine, and reduces cost.

[0025] The ethosome prepared by the present invention is composed of phospholipids, polyols and water, and can effectively improve the skin penetration efficiency of drugs. Due to the addition of alcohol, the flexibility and ductility of the structure are improved, the skin penetration performance is better than that of liposomes, and the transdermal property is stronger. After the active ingredient is wrapped by the ethosome, the transdermal penetration ability of the active ingredient can be effectively improved, the active ingredient can be retained in the skin, and the water solubility is improved, which greatly improves the bioavailability of the product, thereby expanding its application area.

[0026] The glycyrrhetinic acid composition with redness-removing and anti-inflammatory functions prepared by the present invention has the effects of redness-removing, anti-allergic, anti-inflammatory, antibacterial, soothing, moisturizing and the like, effectively improves the transdermal penetration ability of the active ingredients, realizes the skin residence of the active ingredients, and improves the water solubility, greatly improves the bioavailability of the product, thereby expanding its application range. DETAILED DESCRIPTION

[0027] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0028] 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.).

[0029] Cellulase, 10,000 U / g, and bromelain, 100,000 U / g, were purchased from Nanning Dongheng Huadao Biotechnology Co., Ltd.

[0030] Example 1

[0031] This embodiment provides a method for preparing a glycyrrhetinic acid composition having redness-removing and anti-inflammatory functions, comprising the following steps:

[0032] S1. Enzymatic hydrolysis: 10 g of licorice was crushed, added to 200 mL of water, 0.5 g of complex enzyme was added, and enzymatic hydrolysis was carried out at 35 ° C for 2 h, the enzyme was inactivated, and dried to obtain an enzymatic complex;

[0033] The complex enzyme is cellulase and bromelain, with a mass ratio of 5:2;

[0034] S2. Supercritical fluid extraction: The enzymatic complex was subjected to supercritical fluid extraction to obtain an extract, the solvent was removed under reduced pressure, 10 g of the product was added to 100 mL of water, filtered, the solid was collected, washed, and dried to obtain glycyrrhetinic acid;

[0035] The supercritical fluid extraction conditions are: extraction pressure: 18 MPa, extraction temperature: 30°C, CO2 flow rate: 5 L / h, extraction time: 120 min, the entrainer is ethanol, and the entrainer addition amount is 2 wt%;

[0036] S3. Preparation of glycyrrhetinic acid-alkaloid conjugate: 4.5 g of glycyrrhetinic acid was dissolved in 500 mL of ethanol, 1.4 g of EDC and 1.0 g of NHS were added, and the mixture was stirred and activated at 0°C for 20 min, 1.3 g of allantoin was added, and the mixture was stirred and reacted for 10 h, and an equal volume of acetone was added, and the mixture was recrystallized, filtered, washed, and dried to obtain glycyrrhetinic acid-alkaloid conjugate;

[0037] S4. Preparation of glycyrrhetinic acid menthol ester: 4.5 g of glycyrrhetinic acid and 1.3 g of menthol were added to 500 mL of toluene, 0.1 g of concentrated sulfuric acid was added, and the mixture was stirred under reflux for 6 h. The product was washed with equal volumes of saturated saline, saturated sodium carbonate and water, and the organic layer was dried and separated and purified by column chromatography (ethyl acetate: petroleum ether volume ratio of 1:1) to obtain glycyrrhetinic acid menthol ester;

[0038] S5. Preparation of a glycyrrhetinic acid composition with redness-removing and anti-inflammatory functions: 3 mg of glycyrrhetinic acid-alkaloid conjugate, 4 mg of glycyrrhetinic acid menthol ester, 1 mg of phospholipids, and 8 mg of cholesterol were added to 20 mL of ethanol and dissolved, and the ethanol was removed by vacuum rotary evaporation to obtain a transparent film, 20 mL of 50 wt% ethanol solution was added, and ultrasound was performed at 1000 W for 10 min, and filtered through a 0.22 μm microporous filter membrane to obtain a glycyrrhetinic acid composition with redness-removing and anti-inflammatory functions.

[0039] Example 2

[0040] This embodiment provides a method for preparing a glycyrrhetinic acid composition having redness-removing and anti-inflammatory functions, comprising the following steps:

[0041] S1. Enzymatic hydrolysis: 10 g of licorice was crushed, added to 200 mL of water, 1 g of complex enzyme was added, and enzymatic hydrolysis was carried out at 40 ° C for 4 h, the enzyme was inactivated, and dried to obtain an enzymatic complex;

[0042] The complex enzyme is cellulase and bromelain, with a mass ratio of 7:3;

[0043] S2. Supercritical fluid extraction: The enzymatic complex was subjected to supercritical fluid extraction to obtain an extract, the solvent was removed under reduced pressure, 10 g of the product was added to 100 mL of water, filtered, the solid was collected, washed, and dried to obtain glycyrrhetinic acid;

[0044] The supercritical fluid extraction conditions are: extraction pressure: 27MPa, extraction temperature: 40°C, CO2 flow rate: 10L / h, extraction time: 180min, the entrainer is ethanol, and the entrainer addition amount is 3wt%;

[0045] S3. Preparation of glycyrrhetinic acid-alkaloid conjugate: 5 g of glycyrrhetinic acid was dissolved in 500 mL of ethanol, 1.6 g of EDC and 1.2 g of NHS were added, and the mixture was stirred and activated at 4°C for 30 min, 1.6 g of allantoin was added, and the mixture was stirred and reacted for 14 h, and an equal volume of acetone was added, and the mixture was recrystallized, filtered, washed, and dried to obtain glycyrrhetinic acid-alkaloid conjugate;

[0046] S4. Preparation of glycyrrhetinic acid menthol ester: 5 g of glycyrrhetinic acid and 1.7 g of menthol were added to 500 mL of toluene, 0.3 g of concentrated sulfuric acid was added, and the mixture was stirred under reflux for 8 h. The product was washed with equal volumes of saturated saline, saturated sodium carbonate and water, and the organic layer was dried and separated and purified by column chromatography (ethyl acetate: petroleum ether volume ratio of 1:1) to obtain glycyrrhetinic acid menthol ester;

[0047] S5. Preparation of a glycyrrhetinic acid composition with redness-removing and anti-inflammatory functions: 4 mg of glycyrrhetinic acid-alkaloid conjugate, 6 mg of glycyrrhetinic acid menthol ester, 22 mg of phospholipids, and 10 mg of cholesterol were added to 20 mL of ethanol and dissolved, and the ethanol was removed by vacuum rotary evaporation to obtain a transparent film, 20 mL of 70 wt% ethanol solution was added, and ultrasound was performed at 1200 W for 20 min, and filtered through a 0.22 μm microporous filter membrane to obtain a glycyrrhetinic acid composition with redness-removing and anti-inflammatory functions.

[0048] Example 3

[0049] This embodiment provides a method for preparing a glycyrrhetinic acid composition having redness-removing and anti-inflammatory functions, comprising the following steps:

[0050] S1. Enzymatic hydrolysis: 10 g of licorice was crushed, added to 200 mL of water, 0.7 g of complex enzyme was added, and enzymatic hydrolysis was carried out at 37 ° C for 3 h, the enzyme was inactivated, and dried to obtain an enzymatic complex;

[0051] The complex enzyme is cellulase and bromelain, with a mass ratio of 6:2.5;

[0052] S2. Supercritical fluid extraction: The enzymatic complex was subjected to supercritical fluid extraction to obtain an extract, the solvent was removed under reduced pressure, 10 g of the product was added to 100 mL of water, filtered, the solid was collected, washed, and dried to obtain glycyrrhetinic acid;

[0053] The supercritical fluid extraction conditions are: extraction pressure: 22MPa, extraction temperature: 35°C, CO2 flow rate: 7L / h, extraction time: 150min, the entrainer is ethanol, and the entrainer addition amount is 2.5wt%;

[0054] S3. Preparation of glycyrrhetinic acid-alkaloid conjugate: 4.7 g of glycyrrhetinic acid was dissolved in 500 mL of ethanol, 1.5 g of EDC and 1.1 g of NHS were added, and the mixture was stirred and activated at 2°C for 25 min, 1.45 g of allantoin was added, and the mixture was stirred and reacted for 12 h, and an equal volume of acetone was added, and the mixture was recrystallized, filtered, washed, and dried to obtain glycyrrhetinic acid-alkaloid conjugate;

[0055] S4. Preparation of glycyrrhetinic acid menthol ester: 4.7 g of glycyrrhetinic acid and 1.5 g of menthol were added to 500 mL of toluene, 0.2 g of concentrated sulfuric acid was added, and the mixture was stirred under reflux for 7 h. The product was washed with equal volumes of saturated saline, saturated sodium carbonate and water, and the organic layer was dried and separated and purified by column chromatography (ethyl acetate: petroleum ether volume ratio of 1:1) to obtain glycyrrhetinic acid menthol ester;

[0056] S5. Preparation of a glycyrrhetinic acid composition with redness-removing and anti-inflammatory functions: 3.5 mg of glycyrrhetinic acid-alkaloid conjugate, 5 mg of glycyrrhetinic acid menthyl ester, 19 mg of phospholipids, and 9 mg of cholesterol were added to 20 mL of ethanol and dissolved, and the ethanol was removed by vacuum rotary evaporation to obtain a transparent film, 20 mL of 60 wt% ethanol solution was added, and ultrasound was applied at 1100 W for 15 min, and filtered through a 0.22 μm microporous filter membrane to obtain a glycyrrhetinic acid composition with redness-removing and anti-inflammatory functions.

[0057] Comparative Example 1

[0058] Compared with Example 3, the difference is that step S1 is not performed.

[0059] The details are as follows:

[0060] S1. Supercritical fluid extraction: Grind licorice, extract it with supercritical fluid, remove the solvent under reduced pressure, add 10 g of the product to 100 mL of water, filter, collect the solid, wash and dry to obtain glycyrrhetinic acid;

[0061] The supercritical fluid extraction conditions are: extraction pressure: 22MPa, extraction temperature: 35°C, CO2 flow rate: 7L / h, extraction time: 150min, the entrainer is ethanol, and the entrainer addition amount is 2.5wt%;

[0062] S2. Preparation of glycyrrhetinic acid-alkaloid conjugate: 4.7 g of glycyrrhetinic acid was dissolved in 500 mL of ethanol, 1.5 g of EDC and 1.1 g of NHS were added, and the mixture was stirred and activated at 2°C for 25 min, 1.45 g of allantoin was added, and the mixture was stirred and reacted for 12 h, and an equal volume of acetone was added, and the mixture was recrystallized, filtered, washed, and dried to obtain glycyrrhetinic acid-alkaloid conjugate;

[0063] S3. Preparation of glycyrrhetinic acid menthol ester: 4.7 g of glycyrrhetinic acid and 1.5 g of menthol were added to 500 mL of toluene, 0.2 g of concentrated sulfuric acid was added, and the mixture was stirred under reflux for 7 h. The product was washed with equal volumes of saturated saline, saturated sodium carbonate and water, and the organic layer was dried and separated and purified by column chromatography (ethyl acetate: petroleum ether volume ratio of 1:1) to obtain glycyrrhetinic acid menthol ester;

[0064] S4. Preparation of a glycyrrhetinic acid composition with redness-removing and anti-inflammatory functions: 3.5 mg of glycyrrhetinic acid-alkaloid conjugate, 5 mg of glycyrrhetinic acid menthyl ester, 19 mg of phospholipids, and 9 mg of cholesterol were added to 20 mL of ethanol and dissolved, and the ethanol was removed by vacuum rotary evaporation to obtain a transparent film, 20 mL of 60 wt% ethanol solution was added, and ultrasound was applied at 1100 W for 15 min, and filtered through a 0.22 μm microporous filter membrane to obtain a glycyrrhetinic acid composition with redness-removing and anti-inflammatory functions.

[0065] Comparative Example 2

[0066] Compared with Example 3, the difference is that the supercritical fluid extraction in step S2 is replaced by ethanol solution extraction.

[0067] The details are as follows:

[0068] S2. Extraction: Add 50 g of the enzymatic complex to 500 mL of 60 wt% ethanol solution, heat to 60°C, extract for 2 h, filter, dry the filtrate, add 10 g of the product to 100 mL of water, filter, collect the solid, wash, and dry to obtain glycyrrhetinic acid.

[0069] Comparative Example 3

[0070] Compared with Example 3, the difference is that no glycyrrhetinic acid-alkaloid conjugate is added in step S5.

[0071] The details are as follows:

[0072] S5. Preparation of a glycyrrhetinic acid composition with redness-removing and anti-inflammatory functions: 8.5 mg of glycyrrhetinic acid menthol ester, 19 mg of phospholipids, and 9 mg of cholesterol were added to 20 mL of ethanol and dissolved, and the ethanol was removed by vacuum rotary evaporation to obtain a transparent film, 20 mL of 60 wt% ethanol solution was added, and ultrasound was performed at 1100 W for 15 min, and filtered through a 0.22 μm microporous filter membrane to obtain a glycyrrhetinic acid composition with redness-removing and anti-inflammatory functions.

[0073] Comparative Example 4

[0074] Compared with Example 3, the difference is that in step S5, the glycyrrhetinic acid-alkaloid conjugate is replaced by a mixture of glycyrrhetinic acid and allantoin in a mass ratio of 4.7:1.45.

[0075] The details are as follows:

[0076] S5. Preparation of a glycyrrhetinic acid composition with redness-removing and anti-inflammatory 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 added to 20 mL of ethanol and dissolved, 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 ultrasound was performed at 1100 W for 15 min, and filtered through a 0.22 μm microporous filter membrane to obtain a glycyrrhetinic acid composition with redness-removing and anti-inflammatory functions.

[0077] Comparative Example 5

[0078] Compared with Example 3, the difference is that glycyrrhetinic acid menthyl ester is not added in step S5.

[0079] The details are as follows:

[0080] S5. Preparation of a glycyrrhetinic acid composition with redness-removing and anti-inflammatory functions: 8.5 mg of glycyrrhetinic acid-alkaloid conjugate, 19 mg of phospholipid, and 9 mg of cholesterol were added to 20 mL of ethanol and dissolved, and the ethanol was removed by vacuum rotary evaporation to obtain a transparent film, 20 mL of 60 wt% ethanol solution was added, and ultrasound was applied at 1100 W for 15 min, and filtered through a 0.22 μm microporous filter membrane to obtain a glycyrrhetinic acid composition with redness-removing and anti-inflammatory functions.

[0081] Comparative Example 6

[0082] Compared with Example 3, the difference is that in step S5, glycyrrhetinic acid menthyl ester is replaced by a mixture of glycyrrhetinic acid and menthol in a mass ratio of 4.7:1.5.

[0083] The details are as follows:

[0084] S5. Preparation of a glycyrrhetinic acid composition with redness-removing and anti-inflammatory functions: 3.5 mg of glycyrrhetinic acid-alkaloid conjugate, 5 mg of a mixture (glycyrrhetinic acid and menthol in a mass ratio of 4.7:1.5), 19 mg of phospholipids, and 9 mg of cholesterol were added to 20 mL of ethanol and dissolved, 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 ultrasound was performed at 1100 W for 15 min, and filtered through a 0.22 μm microporous filter membrane to obtain a glycyrrhetinic acid composition with redness-removing and anti-inflammatory functions.

[0085] Comparative Example 7

[0086] Compared with Example 3, the difference is that no ethosome embedding is performed in step S5.

[0087] The details are as follows:

[0088] S5. Preparation of a glycyrrhetinic acid composition having redness-removing and anti-inflammatory functions: 3.5 mg of glycyrrhetinic acid-alkaloid conjugate and 5 mg of glycyrrhetinic acid menthol ester were mixed for 10 minutes to prepare a glycyrrhetinic acid composition having redness-removing and anti-inflammatory functions.

[0089] Test Example 1

[0090] 55 subjects were recruited to evaluate the rapid soothing and repairing efficacy of the glycyrrhetinic acid compositions with redness-removing and anti-inflammatory functions prepared in Examples 1-3 and Comparative Examples 1-7 (with deionized water as the control group).

[0091] The criteria for subject selection are as follows:

[0092] (1) 18-55 years old, healthy subjects, both men and women; (2) positive lactic acid sting test total score ≥ 3 points, positive; (3) prone to facial symptoms such as burning, stinging, itching and tightness, and fragile skin barrier; (4) no repair-related skin care products have been used in the past month; (5) no history of cosmetic or drug allergy; (6) no other facial tests during the test period; no long-term sun exposure, outdoor sports, swimming, travel, etc.; (7) informed of the project, willing and able to comply with all test requirements, accept skin examinations, and agree to and accept a series of subsequent examinations.

[0093] Usage: The subject uses the test product on the test area. After cleansing, the subject applies 1 mL of the test product to the face. The frequency of use is once a day, and the test is conducted after 1 week of continuous use.

[0094] Evaluation method:

[0095] Red zone area collection: Visia7 facial imaging tester; Plus Chinese Version 7.0.1 image processing enhanced analysis system; front 0°, left 37°, right 37° image acquisition, 1 acquisition, 1 analysis. The lower the value, the smaller the average red area in the test area. Unit: mm 2 .

[0096] Skin erythema index EI value: MexameterMX18 skin melanin and hemoglobin test probe; test 3 times and take the average value. 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.

[0097] Transepidermal water loss: Tewameter TM Hex skin surface water loss test probe; test 3 times and take the average value. The lower the value, the less transepidermal water loss. Unit: g / (h·m 2 ).

[0098] Test environment: temperature 22±2℃, relative humidity 55±5%.

[0099] The results are shown in Table 1.

[0100] Table 1

[0101]

[0102] It can be seen from the above table that the glycyrrhetinic acid compositions with redness-removing and anti-inflammatory functions prepared in Examples 1-3 of the present invention have good redness-removing, soothing and moisturizing effects.

[0103] At the same time, data of allergic people in each group were collected, and the results are shown in Table 2.

[0104] Table 2

[0105] Group Number of people with allergies (persons) Example 1 0 Example 2 0 Example 3 0 Comparative Example 1 0 Comparative Example 2 0 Comparative Example 3 0 Comparative Example 4 0 Comparative Example 5 0 Comparative Example 6 0 Comparative Example 7 0

[0106] It can be seen from the above table that the glycyrrhetinic acid compositions with redness-removing and anti-inflammatory functions prepared in Examples 1-3 of the present invention have no allergic reaction and are safe and have no side effects.

[0107] 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 principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing a glycyrrhetinic acid composition having redness-removing and anti-inflammatory functions, characterized in that: Licorice is subjected to enzymatic hydrolysis, supercritical fluid extraction, and precipitation to obtain glycyrrhetinic acid, which is then coupled with allantoin to obtain a glycyrrhetinic acid-alkaloid conjugate, and glycyrrhetinic acid is reacted with menthol to obtain glycyrrhetinic acid menthol ester, which is added with ethanol to dissolve the glycyrrhetinic acid-alkaloid conjugate, phospholipids, and cholesterol, and the ethanol is removed by vacuum rotary evaporation to obtain a transparent film, which is then added with an ethanol solution, subjected to ultrasound, and filtered through a microporous membrane to obtain a glycyrrhetinic acid composition with redness-removing and anti-inflammatory functions.

2. The preparation method according to claim 1, characterized in that: The following steps are involved: S1. Enzymatic hydrolysis: crush licorice, add to water, add complex enzyme for enzymatic hydrolysis, inactivate the enzyme, dry, and obtain an enzymatic complex; S2. Supercritical fluid extraction: The enzymatic complex is subjected to supercritical fluid extraction to obtain an extract, the solvent is removed under reduced pressure, added to water, filtered, the solid is collected, washed, and dried to obtain glycyrrhetinic acid; S3. Preparation of glycyrrhetinic acid-alkaloid conjugate: dissolving glycyrrhetinic acid in ethanol, adding EDC and NHS, stirring to activate, adding allantoin, stirring to react, adding acetone, recrystallizing, filtering, washing, and drying to obtain glycyrrhetinic acid-alkaloid conjugate; S4. Preparation of glycyrrhetinic acid menthol ester: glycyrrhetinic acid and menthol were added to toluene, a catalyst was added, the reaction was heated to reflux with stirring, the product was washed with saturated brine, saturated sodium carbonate and water, the organic layer was dried, and separated and purified by column chromatography to obtain glycyrrhetinic acid menthol ester; S5. Preparation of a glycyrrhetinic acid composition with redness-removing and anti-inflammatory functions: add glycyrrhetinic acid-alkaloid conjugate, glycyrrhetinic acid menthol ester, phospholipids, and cholesterol to ethanol for dissolution, remove ethanol by vacuum rotary evaporation to obtain a transparent film, add ethanol solution, perform ultrasound, and filter with a microporous membrane to obtain a glycyrrhetinic acid composition with redness-removing and anti-inflammatory functions.

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

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

5. The preparation method according to claim 2, 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°C, the time is 20-30min, and the stirring reaction time is 10-14h.

6. The preparation method according to claim 2, 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 stirring reaction time is 6-8h.

7. The preparation method according to claim 2, characterized in that: In step S5, the mass ratio of glycyrrhetinic acid-alkaloid conjugate, glycyrrhetinic acid menthyl 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.

8. A glycyrrhetinic acid composition having redness-removing and anti-inflammatory functions obtained by the preparation method according to any one of claims 1 to 7.

9. Use of the glycyrrhetinic acid composition having redness-removing and anti-inflammatory functions as claimed in claim 8 in cosmetics.

10. The use according to claim 9, characterized in that: The cosmetic has the effects of anti-inflammation, reducing redness and soothing.

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