Preparation method and application of high-water-solubility zinc glycyrrhizinate

Abstract

The invention relates to the technical field of fine chemical engineering and daily chemicals, and particularly discloses a preparation method and application of high-water-solubility zinc glycyrrhizinate, the high-water-solubility zinc glycyrrhizinate is prepared from natural indissolvable zinc glycyrrhizinate through three steps of precursor synthesis, ligand exchange and recrystallization refining in combination with optimization of organic ligands, and the high-water-solubility zinc glycyrrhizinate is prepared into the high-water-solubility zinc glycyrrhizinate. The zinc glycyrrhizinate is converted into high-water-solubility zinc glycyrrhizinate with a specific crystalline structure, and the application of the zinc glycyrrhizinate in the field of personal care is further expanded.

Description

A method for preparing highly water-soluble zinc glycyrrhizate and its application Technical Field

[0001] This invention belongs to the field of fine chemical and daily chemical products technology, specifically relating to a method for preparing highly water-soluble zinc glycyrrhizate and its application. Background Technology

[0002] Glycyrrhizic acid is a natural organic tricarboxylic acid extracted from licorice, possessing excellent anti-inflammatory, anti-allergic, and antibacterial biological activities. However, glycyrrhizic acid itself is only slightly soluble in hot water, and while its common salts (such as ammonium, sodium, and potassium salts) are readily soluble in water, their stability and specific efficacy are limited. Furthermore, salts formed by glycyrrhizic acid and high-valence cations, such as zinc glycyrrhizate, can form poorly soluble precipitates due to chelation, which significantly limits its application in water-based personal care products.

[0003] In the prior art, the insolubility of zinc glycyrrhizate is mainly attributed to two aspects: first, the purity of the raw material glycyrrhizic acid (especially the 18β configuration) is insufficient, containing a large number of structural analogs; second, as a multivalent anion, glycyrrhizic acid has disordered binding sites with high-valent cations, which easily forms amorphous or non-crystalline chelate precipitates, resulting in poor solubility and low bioavailability.

[0004] To improve the utilization rate of zinc glycyrrhizate in related products, technicians have adjusted the preparation process of zinc glycyrrhizate. For example, patent CN105541956A discloses a method for preparing zinc glycyrrhizate by directly reacting glycyrrhizic acid with zinc acetate. The main steps include: dissolving zinc acetate, reacting glycyrrhizic acid at a temperature adjusted by ammonia water, filtering with a titanium rod to remove impurities, adding zinc acetate to react, centrifuging, washing, drying, pulverizing, inspection, and packaging. This process is relatively simple, but it does not mention the control of the zinc ion complexation state, which may affect the structural consistency of zinc glycyrrhizate. Another example is patent CN104530177B, which discloses a process for synthesizing zinc glycyrrhizate from glycyrrhizic acid as a raw material. The process involves dissolving glycyrrhizic acid with an ice-water mixture, adjusting the pH to a jelly-like state, freezing and thawing at low temperature, centrifuging and washing with ice water, adding zinc sulfate to react, and post-treatment. This process does not require the separation of the intermediate triammonium salt, which simplifies the process, and the raw material is inexpensive. However, the jelly-like form is difficult to standardize, which may affect the reproducibility of the process.

[0005] Therefore, given the problems of difficult process control and poor crystal stability in existing technologies, there is an urgent need in the market for a preparation process of zinc glycyrrhizate that can achieve good water solubility and a stable crystal structure. Summary of the Invention

[0006] To overcome the shortcomings of the prior art, this invention provides a process-controllable method for preparing zinc glycyrrhizate. By using an optimized organic ligand to replace traditional citric acid, it helps to induce the formation of highly water-soluble zinc glycyrrhizate with a specific crystalline structure, further expanding the application of zinc glycyrrhizate in the field of personal care.

[0007] To achieve the above objectives, the technical solution adopted by the present invention is as follows: The present invention provides a method for preparing highly water-soluble zinc glycyrrhizate, comprising the following steps: S1, preparing an aqueous solution of glycyrrhizic acid / glycyrrhizate with a concentration of 15-20% (w / v) and an aqueous solution of zinc salt with a concentration of 5-15% (w / v); [The following steps are described:] [The solution is prepared at] 300-500 rpm and 50-60 [rpm]. o Under conditions C, the zinc salt aqueous solution is added to the glycyrrhizic acid / glycyrrhizate aqueous solution over 30–60 min, and stirred at this temperature for 30–60 min. The mixture is then cooled to room temperature and allowed to stand for 10–15 h. The filter cake is separated by suction filtration, washed, and vacuum dried for 4–6 h to obtain a water-insoluble zinc glycyrrhizate precursor. S2, Under conditions of 600–800 rpm, the water-insoluble zinc glycyrrhizate precursor obtained in step S1 is added to 50–60 mL of water. o In an aqueous solution of an organic ligand with a concentration of 10–20% (w / v), the solution is stirred at a constant temperature for 40–80 min, cooled to room temperature, allowed to stand for 5–10 h, and filtered to obtain a clear and transparent solution. S3: At 400–600 rpm, the clear and transparent solution obtained in step S2 is added to a low-carbon alcohol, a salting-out agent is added, the temperature is gradually decreased, crystals are precipitated, the crystals are separated by vacuum filtration, the crystals are washed, and vacuum dried for 6–8 h to obtain highly water-soluble zinc glycyrrhizate.

[0008] This invention sequentially transforms naturally insoluble zinc glycyrrhizate (see Figure 1) into highly water-soluble zinc glycyrrhizate with a specific crystalline structure (see Figure 2) through three steps: precursor synthesis, ligand exchange, and recrystallization purification, combined with optimization of organic ligands.

[0009] The purpose of step S1 is to generate a water-insoluble zinc glycyrrhizate initial complex (precursor). Step S2 utilizes an organic ligand to achieve a crucial transformation towards water solubility. The organic ligand, through stronger coordination with zinc ions, replaces part of the glycyrrhizate ion, forming a novel water-soluble glycyrrhizic acid-zinc-organic ligand ternary mixed ligand complex. This process transforms the solid precursor into a clear solution, achieving a change from insoluble to soluble. Step S3 induces crystallization through a dual-driven process of antisolvent precipitation and salting out, resulting in a fixed and excellent crystalline structure.

[0010] In some embodiments, in step S1, the glycyrrhizic acid in the glycyrrhizic acid / glycyrrhizate aqueous solution reacts with the Zn in the zinc salt aqueous solution. 2+ The molar ratio is (1.5~2.5):1.

[0011] In some embodiments, in step S1, the zinc salt comprises any one of zinc sulfate, zinc chloride, zinc acetate, and zinc citrate.

[0012] In some embodiments, the preparation steps of the organic ligand in step S2 are as follows: Under nitrogen protection, 2-aminophenol is dissolved in chlorosulfonic acid, stirred at 35-45°C for 2 hours, poured into ice water at -5-5°C and stirred for 30-50 minutes, filtered to obtain a white solid, washed, and vacuum dried for 3-5 hours to obtain a sulfonated precursor; Under nitrogen protection, the sulfonated precursor is dissolved in DMF, DIPEA is added, cooled to -5-5°C, EDC·HCl and HOBt are added sequentially, stirred for 5-15 minutes, and then DMF containing p-carboxybenzoic acid is added dropwise, and the reaction is carried out at room temperature for 10-15 hours; After the reaction is completed, the organic phase is extracted, washed, dried, and rotary evaporated to obtain a crude product; The crude product is recrystallized and vacuum dried for 5-8 hours to obtain the organic ligand.

[0013] The organic ligand is derived from 2-aminophenol, which introduces a sulfonic acid group onto the benzene ring via reaction with chlorosulfonic acid. The amino group of the sulfonated product is then amidated with p-carboxybenzoic acid to yield an aromatic amide compound containing both sulfonic acid and carboxyl groups. The sulfonic acid group is a highly water-soluble group, ensuring excellent water solubility of the final ligand and its metal complex; the carboxyl group can react with Zn²⁺. + Metal ions form stable coordination bonds.

[0014] Although traditional citric acid has multiple carboxyl groups, its molecules are small, and the spatial structure and hydrophilicity of the ternary complex formed with zinc and glycyrrhizic acid are limited. The organic ligand provided by this invention has both strong coordinating carboxyl groups and strong hydrophilic sulfonic acid groups. In step S2, this organic ligand can more effectively coordinate with zinc in the insoluble precursor to form a novel soluble complex with a looser structure and a surface rich in hydrophilic sulfonic acid groups, laying the foundation for subsequent crystallization.

[0015] In addition, compared to citric acid, which has a simple structure and flexible conformation, the organic ligand provided by this invention has a rigid aromatic ring skeleton. When it is integrated into the complex in step S2, its specific molecular shape, size, and spatial arrangement of functional groups act as a molecular template or structure directing agent during the crystallization process in S3. Furthermore, during the salting out and gradient cooling processes in S3, this complex molecule tends to pack into the crystal lattice in a manner with the lowest energy and the most ordered arrangement. This is because the rigid structure of the ligand restricts the randomness of molecular arrangement, thereby inducing and stabilizing a specific crystal structure. Simultaneously, a strict cooling procedure ensures that this thermodynamically favorable crystal form dominates the entire crystallization process, avoiding the formation of impurities or amorphous products.

[0016] In some embodiments, the ratio of 2-aminophenol to chlorosulfonic acid is 1 g: (0.8 to 1.5) mL.

[0017] Control the ratio of 2-aminophenol to chlorosulfonic acid to ensure complete reaction while avoiding excessive exothermic reaction and splashing.

[0018] In some embodiments, in step S2, the mass ratio of the water-insoluble zinc glycyrrhizate precursor to the organic ligand is 1:(1.0 to 1.4).

[0019] In some embodiments, in step S3, the lower alcohol comprises at least one of n-butanol, isobutanol, primary butanol, tert-butanol, n-propanol, or isopropanol.

[0020] In some embodiments, in step S3, the volume ratio of the clear, transparent solution to the lower alcohol is 1:(3-8).

[0021] In some embodiments, the specific operation of the gradient cooling in step S3 is as follows: in the first stage, the temperature is reduced to 5-15℃ at a rate of 0.1-0.5℃ / min, and in the second stage, the temperature is reduced to -5-5℃ at a rate of 0.1-0.5℃ / min and kept at this temperature for aging and crystal growth for 2-4 hours.

[0022] Another aspect of the present invention provides the application of the highly water-soluble zinc glycyrrhizate obtained by the above preparation method in daily chemical products.

[0023] The zinc glycyrrhizate with a fixed crystalline structure provided by this invention, due to its excellent water solubility and stability, can be conveniently applied to a variety of personal care products and exhibits excellent efficacy: In oral care products (such as mouthwash and toothpaste), it can exert antibacterial and anti-inflammatory effects, effectively preventing and improving oral inflammation problems such as gingivitis and periodontitis. In shampoos and scalp care products, it can inhibit pathogenic fungi such as Malassezia scalp, reduce dandruff production, relieve itching caused by scalp inflammation, and help improve hair loss problems caused by it. In skin care products (such as lotions, serums, and creams), it has soothing, anti-allergic, and anti-irritant properties, effectively inhibiting and improving acne and repairing damaged skin barriers.

[0024] Compared with the prior art, the present invention has the following beneficial effects: 1. The present invention transforms naturally insoluble zinc glycyrrhizate into highly water-soluble zinc glycyrrhizate with a specific crystal structure through three steps: precursor synthesis, ligand exchange, and recrystallization purification, combined with the optimization of organic ligands.

[0025] 2. This invention obtains an aromatic amide compound containing both sulfonic acid and carboxyl groups through sulfonation and amidation reactions, which can be used as an organic ligand to replace traditional citric acid, thus solving the problems of weak coordination ability, insufficient water solubility, or inability to induce specific crystal forms of traditional ligands. Attached Figure Description

[0026] Figure 1 shows the structural formula of naturally insoluble zinc glycyrrhizate.

[0027] Figure 2 shows the structural formula of highly water-soluble zinc glycyrrhizate. Detailed Implementation

[0028] The present invention will be described below with reference to specific embodiments. It should be noted that the following embodiments are examples of the present invention and are used only to illustrate the invention, not to limit it. Other combinations and various modifications within the scope of the present invention can be made without departing from its spirit or scope.

[0029] Preparation Example 1 The preparation steps of the organic ligand are as follows: Under nitrogen protection, 10 g of 2-aminophenol was dissolved in 10 mL of chlorosulfonic acid, stirred at 40 °C for 2 h, poured into ice water at 0 °C and stirred for 30 min, filtered to obtain a white solid, washed with ice water, and dried under vacuum at 60 °C and -0.09 MPa for 4 h to obtain the sulfonated precursor; Under nitrogen protection, 5 g of the sulfonated precursor was dissolved in 100 mL of DMF, 5 mL of DIPEA was added, cooled to 0 °C, and 5.0 g of EDC·HCl and 3.8 g of HOBt were added sequentially, stirred for 10 min, and then 10 mL of DMF containing 4.2 g of p-carboxybenzoic acid was added dropwise, and the reaction was carried out at room temperature for 12 h; After the reaction was completed, the organic phase was extracted with ethyl acetate, washed with saturated NaCl solution, dried with anhydrous sodium sulfate, and rotary evaporated to obtain the crude product; The crude product was recrystallized twice with a 1:1 volume ratio ethanol aqueous solution (lowering to 5 °C at 1 °C / min and holding for 2 h), and dried under vacuum at 45 °C and -0.09 MPa for 6 h to obtain the organic ligand.

[0030] Example 1 A method for preparing highly water-soluble zinc glycyrrhizinate includes the following steps: S1, preparing a 17% (w / v) aqueous solution of glycyrrhizic acid (adjusting the pH to 6.0 ± 0.1 with 1 M NaOH solution) and a 10% (w / v) aqueous solution of zinc acetate using 10 g of glycyrrhizic acid and 3.4 g of zinc acetate hexahydrate; and then preparing the aqueous solution at 400 rpm and 55 rpm. o Under C conditions, zinc acetate aqueous solution was added to glycyrrhizic acid aqueous solution over 45 min, and the mixture was kept at this temperature and stirred for 45 min. The temperature was then lowered to 25°C, allowed to stand for 12 h, and the filter cake was separated by vacuum filtration. The filter cake was then processed using 40... o C. Wash the filter cake with deionized water until the conductivity of the washing liquid is <50 μS / cm, and dry it at 65℃ and -0.09 MPa for 5 h to obtain a water-insoluble zinc glycyrrhizate precursor; S2. Add 10 g of the water-insoluble zinc glycyrrhizate precursor obtained in step S1 to 80 g of 55 g solution at 700 rpm. oIn an aqueous solution of organic ligand with a C concentration of 15% (w / v) (pH adjusted to 6.0 with 0.5 M NaOH solution), the solution was kept at a constant temperature and stirred for 60 min, then cooled to 25°C. o C. Let stand for 6 hours, filter, and obtain a clear and transparent solution; S3. At 400-600 rpm, add the clear and transparent solution obtained in step S2 to 5 times the volume of n-butanol, add 0.3 wt% sodium sulfate as a salting-out agent, and gradually lower the temperature (in the first stage, lower to 10℃ at a rate of 0.3℃ / min, and in the second stage, lower to 0℃ at a rate of 0.2℃ / min and maintain the temperature for aging and crystal growth for 3 hours) to precipitate crystals. Separate the crystals by vacuum filtration and use -5 o The crystals were washed with n-butanol and dried at 50°C and -0.09 MPa for 7 hours to obtain highly water-soluble zinc glycyrrhizate.

[0031] Example 2 A method for preparing highly water-soluble zinc glycyrrhizate includes the following steps: S1, preparing a 15% (w / v) aqueous solution of glycyrrhizic acid (adjusting the pH to 6.0 ± 0.1 with 1M NaOH solution) and a 5% (w / v) aqueous solution of zinc citrate using 10g glycyrrhizic acid and 1.8g zinc citrate respectively; [The following steps are described:] [The solution is prepared at 300 rpm and 50 rpm...] o Under C conditions, zinc citrate aqueous solution was added to glycyrrhizic acid aqueous solution over 30 minutes, and the mixture was kept at this temperature and stirred for 30 minutes. The temperature was then lowered to 25°C, allowed to stand for 12 hours, and the filter cake was separated by vacuum filtration. The solution was then used to separate the filter cake. o C. Wash the filter cake with deionized water until the conductivity of the washing liquid is <50 μS / cm, and dry it at 60℃ and -0.09 MPa for 6 h to obtain a water-insoluble zinc glycyrrhizate precursor; S2. Add 10 g of the water-insoluble zinc glycyrrhizate precursor obtained in step S1 to 70 g of 50 g water at 600 rpm. o In an aqueous solution of organic ligand with a concentration of 20% (w / v) (pH adjusted to 6.0 with 0.5 M NaOH solution), the solution was kept at a constant temperature and stirred for 60 min, then cooled to 25°C. o C. Let stand for 6 hours, filter, and obtain a clear and transparent solution; S3. At 400 rpm, add the clear and transparent solution obtained in step S2 to 3 times the volume of n-propanol, add 0.3 wt% sodium sulfate as a salting-out agent, and perform gradient cooling (the first stage decreases to 5℃ at a rate of 0.5℃ / min, and the second stage decreases to -5℃ at a rate of 0.5℃ / min and maintains the temperature for aging and crystal growth for 2 hours), precipitate crystals, separate the crystals by vacuum filtration, and use -10 o The crystals were washed with n-propanol of C and dried at 45°C and -0.09 MPa for 8 hours to obtain highly water-soluble zinc glycyrrhizate.

[0032] Example 3A method for preparing highly water-soluble zinc glycyrrhizate includes the following steps: S1, preparing a 20% (w / v) aqueous solution of glycyrrhizic acid (adjusted to pH 6.0±0.1 with 1 M NaOH solution) and a 15% (w / v) aqueous solution of zinc chloride (maintained at pH 6.0±0.2 with 0.5 M NaAc-HAc buffer) using 10 g of glycyrrhizic acid and 1.3 g of zinc chloride respectively; and then preparing the solution at 500 rpm and 60 rpm. o Under C conditions, zinc chloride aqueous solution was added to glycyrrhizic acid / glycyrrhizate aqueous solution over 60 min, and the mixture was kept at this temperature and stirred for 60 min. The temperature was then lowered to 25°C, allowed to stand for 12 h, and the filter cake was separated by filtration. The solution was then used to separate the filter cake. o C. Wash the filter cake with deionized water until the conductivity of the washing liquid is <50 μS / cm, and dry it at 70℃ and -0.09 MPa for 4 h to obtain a water-insoluble zinc glycyrrhizate precursor; S2. Add 10 g of the water-insoluble zinc glycyrrhizate precursor obtained in step S1 to 100 g of 60 at 800 rpm. o In a 10% (w / v) aqueous solution of organic ligand (pH adjusted to 6.0 with 0.5 M NaOH solution), the solution was kept at a constant temperature and stirred for 60 min, then cooled to 25°C. o C. Let stand for 6 hours, filter, and obtain a clear and transparent solution; S3. At 400 rpm, add the clear and transparent solution obtained in step S2 to 8 times the volume of isobutanol, add 0.3 wt% sodium sulfate as a salting-out agent, and perform gradient cooling (the first stage decreases to 15℃ at a rate of 0.1℃ / min, and the second stage decreases to 0℃ at a rate of 0.1℃ / min and maintains the temperature for aging and crystal growth for 4 hours), precipitate crystals, separate the crystals by vacuum filtration, and use 0 o The crystals were washed with isobutanol of C and dried at 55°C and -0.09 MPa for 8 hours to obtain highly water-soluble zinc glycyrrhizate.

[0033] Example 4 This embodiment provides a method for preparing highly water-soluble zinc glycyrrhizate. The specific implementation method is the same as that in Embodiment 1, except that the organic ligand used in step S2 is replaced by an equal amount of citric acid.

[0034] Example 5 This embodiment provides a method for preparing highly water-soluble zinc glycyrrhizate. The specific implementation method is the same as that in Embodiment 1, except that the organic ligand used in step S2 is replaced by an equal amount of malic acid.

[0035] Comparative Example 1This comparative example provides a method for preparing highly water-soluble zinc glycyrrhizate. The specific implementation method is the same as in Example 1, except that step S3 is adjusted as follows: S3, at 400-600 rpm, the clear and transparent solution obtained in step S2 is added to 5 times the volume of n-butanol, and 0.3 wt% sodium sulfate is added as a salting-out agent. The temperature is lowered to 0°C at a rate of 0.5°C / min and maintained at this temperature for 3 hours to allow crystal formation. Crystals are precipitated, and the crystals are separated by filtration. o The crystals were washed with n-butanol and dried at 50°C and -0.09 MPa for 7 hours to obtain highly water-soluble zinc glycyrrhizate.

[0036] Comparative Example 2 A method for preparing zinc glycyrrhizate includes the following steps: preparing a 17% (w / v) aqueous solution of glycyrrhizic acid (adjusting the pH to 6.0 ± 0.1 with 1 M NaOH solution) and a 10% (w / v) aqueous solution of zinc acetate using 10 g of glycyrrhizic acid and 3.4 g of zinc acetate hexahydrate; and operating the equipment at 400 rpm and 55 rpm respectively. o Under C conditions, zinc acetate aqueous solution was added to glycyrrhizic acid aqueous solution over 45 min, and the mixture was kept at this temperature and stirred for 45 min. The temperature was then lowered to 25°C, allowed to stand for 12 h, and the filter cake was separated by vacuum filtration. The filter cake was then processed using 40... o The filter cake was washed with deionized water until the conductivity of the washing liquid was <50 μS / cm, and then dried at 65℃ and -0.09 MPa for 5 h to obtain zinc glycyrrhizate.

[0037] The performance tests of zinc glycyrrhizinate provided in Examples 1-5 and Comparative Example 1 were conducted as follows, and the results are shown in Table 1: 1. Appearance: Visual observation.

[0038] 2. Water solubility: Tested in deionized water at 25℃.

[0039] Table 1 Performance Test Results

[0040] In Table 1, the zinc glycyrrhizate provided in Examples 1-5 and Comparative Examples 1-2 are all white or off-white crystalline powders. The water solubility of the zinc glycyrrhizate in Examples 1-3 is greater than 50 mg / ml, classifying it as highly soluble. Compared to Comparative Example 2, which did not use organic ligands, and Examples 4 and 5, which used citric acid and malic acid, the organic ligands used in Examples 1-3 are more conducive to inducing the formation of highly water-soluble zinc glycyrrhizate with a specific crystalline structure. Combining Comparative Example 1 and Example 1, it can be seen that gradient cooling helps stabilize the crystal form during crystallization, allowing highly water-soluble zinc glycyrrhizate to dominate.

[0041] The embodiments and comparative examples described above do not limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the above-disclosed technical content to create equivalent embodiments without departing from the scope of the present invention. Any simple modifications, equivalent changes and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. A method for preparing highly water-soluble zinc glycyrrhizate, characterized in that, The process includes the following steps: S1, preparing an aqueous solution of glycyrrhizic acid / glycyrrhizate with a concentration of 15–20% (w / v) and an aqueous solution of zinc salt with a concentration of 5–15% (w / v); and operating the equipment at 300–500 rpm and 50–60 rpm respectively. o Under conditions C, the zinc salt aqueous solution is added to the glycyrrhizic acid / glycyrrhizate aqueous solution over 30–60 min, and stirred at this temperature for 30–60 min. The mixture is then cooled to room temperature and allowed to stand for 10–15 h. The filter cake is separated by suction filtration, washed, and vacuum dried for 4–6 h to obtain a water-insoluble zinc glycyrrhizate precursor. S2, Under conditions of 600–800 rpm, the water-insoluble zinc glycyrrhizate precursor obtained in step S1 is added to 50–60 mL of water. o In an aqueous solution of an organic ligand with a concentration of 10–20% (w / v), the solution is stirred at a constant temperature for 40–80 min, cooled to room temperature, allowed to stand for 5–10 h, and filtered to obtain a clear and transparent solution. S3: At 400–600 rpm, the clear and transparent solution obtained in step S2 is added to a low-carbon alcohol, a salting-out agent is added, the temperature is gradually decreased, crystals are precipitated, the crystals are separated by vacuum filtration, the crystals are washed, and vacuum dried for 6–8 h to obtain highly water-soluble zinc glycyrrhizate.

2. The method for preparing highly water-soluble zinc glycyrrhizate according to claim 1, characterized in that, In step S1, the glycyrrhizic acid in the glycyrrhizic acid / glycyrrhizate aqueous solution reacts with the Zn in the zinc salt aqueous solution. 2+ The molar ratio is (1.5~2.5):

1.

3. The method for preparing highly water-soluble zinc glycyrrhizate according to claim 2, characterized in that, In step S1, the zinc salt comprises any one of zinc sulfate, zinc chloride, zinc acetate, and zinc citrate.

4. The method for preparing highly water-soluble zinc glycyrrhizate according to claim 1, characterized in that, In step S2, the preparation steps of the organic ligand are as follows: Under nitrogen protection, 2-aminophenol is dissolved in chlorosulfonic acid, stirred at 35-45°C for 2 hours, poured into ice water at -5-5°C and stirred for 30-50 minutes, filtered to obtain a white solid, washed, and vacuum dried for 3-5 hours to obtain a sulfonated precursor; Under nitrogen protection, the sulfonated precursor is dissolved in DMF, DIPEA is added, cooled to -5-5°C, EDC·HCl and HOBt are added sequentially, stirred for 5-15 minutes, and then DMF containing p-carboxybenzoic acid is added dropwise, and the reaction is carried out at room temperature for 10-15 hours; After the reaction is completed, the organic phase is extracted, washed, dried, and rotary evaporated to obtain a crude product; The crude product is recrystallized and vacuum dried for 5-8 hours to obtain the organic ligand.

5. The method for preparing highly water-soluble zinc glycyrrhizate according to claim 4, characterized in that, The ratio of 2-aminophenol to chlorosulfonic acid is 1 g: (0.8-1.5) mL.

6. The method for preparing highly water-soluble zinc glycyrrhizate according to claim 1, characterized in that, In step S2, the mass ratio of the water-insoluble zinc glycyrrhizate precursor to the organic ligand is 1:(1.0 to 1.4).

7. The method for preparing highly water-soluble zinc glycyrrhizate according to claim 1, characterized in that, In step S3, the lower alcohol comprises at least one of n-butanol, isobutanol, primary butanol, tert-butanol, n-propanol, or isopropanol.

8. The method for preparing highly water-soluble zinc glycyrrhizate according to claim 1, characterized in that, In step S3, the volume ratio of the clear, transparent solution to the low-carbon alcohol is 1:(3-8).

9. The method for preparing highly water-soluble zinc glycyrrhizate according to claim 1, characterized in that, In step S3, the specific operation of the gradient cooling is as follows: in the first stage, the temperature is reduced to 5-15℃ at a rate of 0.1-0.5℃ / min, and in the second stage, the temperature is reduced to -5-5℃ at a rate of 0.1-0.5℃ / min and kept at this temperature for aging and crystal growth for 2-4 hours.

10. The application of highly water-soluble zinc glycyrrhizate obtained by the preparation method according to any one of claims 1 to 9 in daily chemical products.

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