CN-122011079-A - Glycyrrhetinic acid-tromethamine eutectic crystal and preparation method and application thereof in skin care

Abstract

The invention discloses a glycyrrhetinic acid-tromethamine eutectic crystal, a preparation method thereof and application thereof in skin care, and belongs to the technical field of biological medicines. The molecular formula of the glycyrrhetinic acid-tromethamine eutectic is [ C 4 H 11 NO 3 ·2C 30 H 46 O 4 ], the precise structure of the eutectic is characterized by single crystal X-ray diffraction, and the eutectic is a basic structural unit formed by two glycyrrhetinic acid molecules and one tromethamine molecule. The preparation method of the eutectic comprises the steps of mixing glycyrrhetinic acid and tromethamine according to a molar ratio of 3:1-1:3, adding organic solvents such as methanol, ethanol, acetonitrile or isopropanol, stirring and dissolving at 40-60 ℃, then evaporating the solvents under reduced pressure at 40-50 ℃, and vacuum drying to obtain white eutectic solid. The method has simple process and is suitable for large-scale production. The prepared eutectic obviously improves the water solubility of glycyrrhetinic acid, solves the core problems of easy delamination and precipitation in an aqueous system, and expands the application range and effect of the glycyrrhetinic acid.

Inventors

• YU YUEMING
• GUO KEYING
• ZHANG LIYUAN
• LIU LU
• CHEN XIANGZHU
• JIANG FEI
• ZHANG ZENGTAO
• ZHANG CHUN

Assignees

• 临沂大学

Dates

Publication Date

20260512

Application Date

20260127

Claims (8)

1. 1. The glycyrrhetinic acid-amino tributyl alcohol eutectic crystal is characterized in that a molecular formula of the eutectic crystal is [ C 4 H 11 NO 3 ·2C 30 H 46 O 4 ], a basic structural unit is formed by two glycyrrhetinic acid molecules and one amino butanetriol molecule, the eutectic space group is C1 21, and unit cell parameters are a= 30.891 (11) a, b= 30.891 (11) a, c= 30.891 (11) a, a=90.00 DEG, beta= 92.910 (11) DEGand gamma=90.00 deg.
2. 2. The glycyrrhetinic acid-aminotributol co-crystal of claim 1, wherein the co-crystal powder X-ray diffraction signature diffraction peak is at 6.6 °,9.06 °,12.08 °,13.12 °,14.72 °,16.08 °.
3. 3. A method of preparing the glycyrrhetinic acid-aminotributol co-crystal of claim 1 or 2, comprising the steps of: 1) Weighing glycyrrhetinic acid and tromethamine according to a molar ratio, and placing the glycyrrhetinic acid and the tromethamine in a reaction container; 2) Adding an organic solvent into the container, stirring and dissolving for 0.5-2 hours at the temperature of 40-60 ℃ to form a clear solution; 3) And (3) placing the solution in a rotary evaporator, evaporating the solvent at 40-50 ℃ under reduced pressure to obtain a white solid crude product, and then placing the white solid crude product in a vacuum drying oven, and drying at 40 ℃ for 12-24 hours to obtain the white solid crude product.
4. 4. The method for preparing a glycyrrhetinic acid-aminotributol eutectic crystal according to claim 3, wherein the molar ratio of glycyrrhetinic acid to tromethamine in the step (1) is 3:1-1:3.
5. 5. The method for preparing a glycyrrhetinic acid-aminotributol eutectic crystal according to claim 3, wherein the organic solvent is one or a mixed solvent of more than two of methanol, ethanol, acetonitrile and isopropanol.
6. 6. The method for preparing a glycyrrhetinic acid-aminotributol eutectic crystal according to claim 3, wherein the solid-to-liquid ratio of the mixture powder to the organic solvent is 100 mg (8-15) mL.
7. 7. Use of the glycyrrhetinic acid-aminotriabutanol co-crystal of claim 1 or 2 in skin care.
8. 8. The use according to claim 7, wherein the skin care comprises moisturization, anti-aging, antioxidant, whitening, anti-wrinkle or repair.

Description

Glycyrrhetinic acid-tromethamine eutectic crystal and preparation method and application thereof in skin care Technical Field The invention relates to a glycyrrhetinic acid-tromethamine eutectic crystal, a preparation method thereof and application thereof in skin care, and belongs to the technical field of biological medicine. Background Glycyrrhetinic acid (GLYCYRRHETINIC ACID, GA) is one of core active ingredients of liquorice, belongs to pentacyclic triterpene compounds, has excellent effects of resisting inflammation, relieving, reducing melanin generation, repairing skin barrier, resisting oxidation and the like, and is a natural active raw material with great value in the cosmetic field. However, the physicochemical defects of glycyrrhetinic acid cause a plurality of bottlenecks in the application of cosmetics, which severely limit the wide application and efficacy exertion in cosmetics, and the specific problems are as follows: 1. The glycyrrhetinic acid is a typical fat-soluble compound, and has extremely low solubility in water. The modern cosmetics mainly use a water-based system (such as essence, emulsion, face cream, facial mask and the like), fat-soluble glycyrrhetinic acid is difficult to uniformly disperse in the water-based system, and problems such as layering, precipitation, granular feel and the like are easy to occur, so that the appearance and the texture of the cosmetics are influenced, the use experience is also influenced, the active ingredients are unevenly distributed, and the effects cannot be fully exerted. 2. The skin absorption efficiency is low, the efficacy conversion is poor, the stratum corneum of the surface layer of the skin is a lipophilic barrier, but the conduction capability of the aqueous environment inside the skin on the fat-soluble components is weak. The glycyrrhetinic acid is difficult to penetrate through the stratum corneum into the deep layer of the skin due to insufficient water solubility, and most of the glycyrrhetinic acid stays on the surface of the skin, so that the effects of anti-inflammatory and relieving, barrier repairing and the like cannot be effectively exerted, the expected effect can be achieved only by adding a higher dose, the cost of raw materials is increased, and the skin irritation risk can be caused by overhigh local concentration. 3. The preparation has poor stability, affects the shelf life of the product, and is easy to destabilize due to crystal form transformation and particle aggregation in the conventional production process (such as emulsification, homogenization and sterilization) of cosmetics, thus not only leading to rough product quality and efficacy attenuation, but also possibly causing unstable system (such as layering and precipitation) and shortening the shelf life of the cosmetics. In order to improve the application defects of glycyrrhetinic acid in cosmetics, the prior art has obvious defects that ① is prepared into glycyrrhetinic acid sodium salt and glycyrrhetinic acid potassium salt, although the water solubility is slightly improved, the salts are sensitive to the pH of a cosmetic system, free glycyrrhetinic acid is easy to separate out in a slightly acidic cosmetic formula, salt components can increase the sticky feel of the product and influence the use experience, ② adopts a cyclodextrin inclusion technology, the dispersibility can be improved, the drug loading rate of the inclusion compound is lower, the formula redundancy components can be increased, the inclusion process is complex, the production cost is higher, ③ adopts a nano dispersion technology, the solubility can be improved, nano particles are easy to agglomerate in the cosmetic system, the storage stability is poor, and the industrial production difficulty is high, so that the method is not suitable for being applied to the cosmetic industry on a large scale. Co-crystallization technology is a novel technique for improving physicochemical properties of poorly soluble active ingredients in recent years, and forms a eutectic crystal having a specific crystal structure by non-covalent bond interactions (hydrogen bonds, pi-pi stacking, van der Waals forces, etc.) between active ingredient molecules and molecules of the eutectic formation. The technology does not need to change the covalent structure of the active ingredient, can obviously improve the properties of water solubility, dispersibility, stability and the like on the basis of keeping the original efficacy of the active ingredient, has simple preparation process and is suitable for industrial production of cosmetics. Tromethamine (Tris (hydroxymethyl) aminomethane, tris for short) is an organic compound containing polyhydroxy and amino, has excellent biocompatibility and skin tolerance, contains a plurality of sites (hydroxy and amino) capable of forming hydrogen bonds in a molecular structure, and can form stable eutectic with glycyrrhetinic acid. Meanwhile, the tromethamine has certain pH a