A preparation method of glycyrrhizin di-potassium salt based on deep removal of heavy metals by chelating resin

Abstract

The present application relates to the field of chemistry, and provide a kind of preparation method of glycyrrhizin dipotassium salt based on chelating resin deep removal heavy metal, comprising the following steps: glycyrrhizin monoammonium salt is added to alkaline pure water solution, stirring, adjust pH to 7.5~8.5, obtain solution;The obtained solution is passed through mixed resin column, flush mixed resin column, combine effluent, concentrate and dry, obtain glycyrrhizin dipotassium salt;Wherein, the mixed resin in the mixed resin is the composition of cation exchange resin and new chelating resin.The preparation method of the present application is simple and reasonable, green and environmental protection, in the preparation process, using cation exchange resin and new chelating resin promote glycyrrhizin dipotassium salt purification, so that the residual alcohol content in the obtained glycyrrhizin dipotassium salt is ≤500mg / kg, residual ammonia content is ≤40mg / kg, and lead, cadmium, arsenic, mercury content is all ≤0.2mg / kg.

Description

Technical Field

[0001] This invention belongs to the field of chemistry, specifically relating to a method for preparing dipotassium glycyrrhizate salt for deep removal of heavy metals based on chelating resin. Background Technology

[0002] Dipotassium glycyrrhizate, as an important natural product, possesses significant biological and pharmacological activities and is widely used in pharmaceuticals, food, and cosmetics. However, during the preparation of dipotassium glycyrrhizate, the raw material, monoammonium glycyrrhizate, contains alcohols, ammonia, and heavy metal ions (such as lead, cadmium, and mercury), which seriously affects the quality and safety of the product.

[0003] Chinese patent CN 107722102 B discloses a method for preparing dipotassium glycyrrhizate with low residual alcohol and ammonia. The method uses monoammonium glycyrrhizate as raw material and uses pure water as solvent in the preparation process. A certain amount of potassium hydroxide (or potassium carbonate) is added to dissolve the monoammonium glycyrrhizate in alkaline pure water. Then, it is converted by hydrogen-form strong acid cation exchange resin to obtain dipotassium glycyrrhizate. The preparation method is simple, reasonable and environmentally friendly, and reduces the residual alcohol and ammonia in the dipotassium glycyrrhizate prepared by the original production process. However, its ability to remove heavy metal ions is very limited.

[0004] Therefore, there is an urgent need to develop a method for preparing dipotassium glycyrrhizate based on chelating resin for deep removal of heavy metals, which can effectively remove heavy metal ions while ensuring low residual alcohol and low residual ammonia in dipotassium glycyrrhizate, thereby further improving the purity and safety of dipotassium glycyrrhizate. Summary of the Invention

[0005] To address the existing technical problems, the present invention aims to provide a method for preparing dipotassium glycyrrhizate salt with deep heavy metal removal based on chelating resin. The preparation method of the present invention is simple, reasonable, and environmentally friendly. During the preparation process, cation exchange resin and novel chelating resin are used together to promote the purification of dipotassium glycyrrhizate salt, resulting in a residual alcohol content ≤500 mg / kg, a residual ammonia content ≤40 mg / kg, and lead, cadmium, arsenic, and mercury contents all ≤0.2 mg / kg.

[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0007] This invention provides a method for preparing dipotassium glycyrrhizate for deep removal of heavy metals based on chelating resin, comprising the following steps:

[0008] S1. Add glycyrrhizic acid monoammonium salt to an alkaline pure aqueous solution, stir, and adjust the pH to 7.5-8.5 to obtain a solution;

[0009] S2. Pass the solution obtained in step S1 through a mixed resin column, rinse the mixed resin column, combine the effluents, concentrate and dry to obtain dipotassium glycyrrhizate; wherein, the mixed resin in the mixed resin column is a combination of cation exchange resin and novel chelating resin.

[0010] The reaction mechanism and function of this invention are as follows:

[0011] 1. In this invention, monoammonium glycyrrhizate is added to an alkaline aqueous solution to fully dissolve it. During this process, the monoammonium glycyrrhizate is converted to tripotassium glycyrrhizate, and the potassium ions displace the ammonium ions in the product, causing most of the ammonium ions to escape from the solution as ammonia gas. Next, the tripotassium glycyrrhizate solution is slowly passed through a mixed resin column, converting it to dipotassium glycyrrhizate. Simultaneously, any remaining trace amounts of ammonium ions and heavy metal ions in the solution are further removed by the mixed resin column through ion exchange and coordination. Therefore, the preparation method of this invention is simple and reasonable. The preparation process uses pure water as a solvent, eliminating the use of organic solvents, making it not only environmentally friendly and safe, but also resulting in extremely low residual alcohol and ammonia levels in the dipotassium glycyrrhizate, further improving its quality.

[0012] 2. This invention first increases the porosity and specific surface area of ​​aminomethyl polystyrene resin by swelling it in N,N-dimethylformamide, thereby improving the efficiency of subsequent reactions and the resin's adsorption capacity. Next, a methoxycarbonyl group is introduced through reaction with methyl acrylate, allowing N-aminoethylpiperazine to be successfully grafted onto resin 1, enhancing the resin's chelating ability for heavy metal ions. Finally, the applicant grafts 5-chloro-1,3,4-thiadiazole-2-amine onto resin 2, forming a group with strong chelating ability. The thiazole and amino groups work synergistically, enhancing the resin's chelating ability for heavy metal ions, thus efficiently removing heavy metals, ensuring that the content of lead, cadmium, arsenic, and mercury in dipotassium glycyrrhizate is ≤0.2 mg / kg.

[0013] In some embodiments, the alkaline substance in the alkaline pure aqueous solution in step S1 is potassium hydroxide or potassium carbonate.

[0014] In some embodiments, the stirring temperature in step S1 is 40–60°C.

[0015] In some embodiments, the flow rate of the solution through the mixed resin column in step S2 is 0.5–1.5 BV / h, and the temperature is 25–40°C.

[0016] In some embodiments, the ratio of the glycyrrhizic acid monoammonium salt to the mixed resin is 1 g: (1.5-3.5) mL.

[0017] In some embodiments, the cation exchange resin is a hydrogen-form strong acid cation exchange resin.

[0018] Preferably, the hydrogen-form strong acid cation exchange resin is any one of macroporous resin D001, Purolite C100E resin, and Lanxess SP112 resin.

[0019] In some embodiments, the volume ratio of the cation exchange resin to the novel chelating resin is (2-4):1.

[0020] In some embodiments, the method for preparing the novel chelating resin includes the following steps:

[0021] Q1. Wash the aminomethyl polystyrene resin with an ethanol aqueous solution 3-4 times, filter, take it out and place it in N,N-dimethylformamide, seal it, stir and swell for 10-15 hours, filter it to obtain the pretreated resin.

[0022] Q2. Mix the pretreated resin obtained in step Q1, methanol and methyl acrylate, react at room temperature for 18-30 h, filter under reduced pressure, extract with anhydrous ethanol for 7-10 h, wash with ethanol aqueous solution, and dry to obtain resin 1.

[0023] Q3. Mix the resin 1 obtained in step Q2, methanol, and N-aminoethylpiperazine, react at room temperature for 18-30 h, filter under reduced pressure, wash with ethanol aqueous solution, and dry to obtain resin 2.

[0024] Q4. Mix the resin 2 obtained in step Q3, toluene, and 5-chloro-1,3,4-thiadiazole-2-amine, introduce an inert gas, add a catalyst, heat to 65-100℃ and react for 5-8 hours, wash and dry to obtain a novel chelating resin.

[0025] In some embodiments, the mass ratio of the pretreated resin to methyl acrylate in step Q2 is 1:(3.5-4.5).

[0026] In some embodiments, the mass ratio of resin 1 and N-aminoethylpiperazine in step Q3 is 1:(1.6-2.2).

[0027] In some embodiments, the mass ratio of resin 2 and 5-chloro-1,3,4-thiadiazole-2-amine in step Q4 is 1:(2.2-2.8).

[0028] In some embodiments, the residual alcohol content of the dipotassium glycyrrhizate obtained by any of the above preparation methods is ≤500mg / kg, the residual ammonia content is ≤40mg / kg, and the content of lead, cadmium, arsenic, and mercury is ≤0.2mg / kg.

[0029] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0030] 1. The preparation method of the present invention is simple, reasonable, green and environmentally friendly. In the preparation process, cation exchange resin and novel chelating resin are used to promote the purification of dipotassium glycyrrhizate, so that the residual alcohol content in the obtained dipotassium glycyrrhizate is ≤500mg / kg, the residual ammonia content is ≤40mg / kg, and the contents of lead, cadmium, arsenic and mercury are all ≤0.2mg / kg.

[0031] 2. This invention synthesizes a novel chelating resin, forming groups with strong chelating ability. The thiazole and amino groups work together to produce a synergistic effect, thereby enhancing the resin's chelating ability for heavy metal ions, thus efficiently removing heavy metals in the preparation process of dipotassium glycyrrhizate. Detailed Implementation

[0032] 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.

[0033] Dipotassium glycyrrhizate was prepared according to the proportions and methods of each raw material specified in the following examples and comparative examples.

[0034] To facilitate implementation of this invention by those skilled in the art, the manufacturers of some raw materials for the embodiments and comparative examples are described below:

[0035] Hydrogen-form strong acid cation exchange resin: Purolite C100E resin, purchased from Bengbu Sanyi Technology Co., Ltd.;

[0036] Aminomethyl polystyrene resin: purchased from TCI (Shanghai) Chemical Industry Development Co., Ltd.;

[0037] Chelating resin: Purolite S930 resin, purchased from Shanghai Kaiping Resin Co., Ltd.;

[0038] Unless otherwise specified, all other raw materials can be purchased from the market.

[0039] Preparation Example 1

[0040] The preparation method of the novel chelating resin column A includes the following steps:

[0041] Q1. Wash the aminomethyl polystyrene resin four times with a 50% ethanol aqueous solution, filter for 3 min, take out 40 g of the filtered aminomethyl polystyrene resin and place it in 200 mL of N,N-dimethylformamide, seal with plastic wrap, stir and swell for 12 h, filter, and obtain the pretreated resin.

[0042] Q2. Mix 20g of pretreated resin obtained in step Q1, 200mL of methanol and 80g of methyl acrylate, react at room temperature for 24h, filter under reduced pressure, extract with anhydrous ethanol by Soxhlet extraction for 8h, wash with 50% ethanol aqueous solution until the resin is neutral, and dry under vacuum at 70℃ for 12h to obtain resin 1.

[0043] Q3. Mix 15g of resin 1 obtained in step Q2, 150mL of methanol, and 28.5g of N-aminoethylpiperazine, react at room temperature for 24h, filter under reduced pressure, wash with 20% ethanol aqueous solution until the resin is neutral, and dry under vacuum at 70℃ for 12h to obtain resin 2.

[0044] Q4. Mix 12g of resin 2 obtained in step Q3, 120mL of toluene, and 30g of 5-chloro-1,3,4-thiadiazole-2-amine, purge with nitrogen gas, add 0.6g of sodium hydroxide, heat to 80℃ and react for 6.5h. Wash once with toluene and once with deionized water, then wash once with a mixture of acetone and diethyl ether (volume ratio of acetone and diethyl ether is 1:1). Dry under vacuum at 70℃ for 12h to obtain a novel chelating resin A.

[0045] Preparation Example 2

[0046] The preparation method of the novel chelating resin B is the same as that of Preparation Example 1, except that the amount of N-aminoethylpiperazine added in step Q3 is 22.5g.

[0047] Preparation Example 3

[0048] The preparation method of the novel chelating resin C is the same as that of Preparation Example 1, except that the amount of 5-chloro-1,3,4-thiadiazole-2-amine added in step Q4 is 25.2g.

[0049] Example 1

[0050] A method for preparing dipotassium glycyrrhizate for deep removal of heavy metals based on chelating resin includes the following steps:

[0051] S1. Dissolve 480g of potassium hydroxide in 2000mL of purified water to obtain an alkaline purified aqueous solution. Add 400g of glycyrrhizic acid monoammonium salt to the alkaline purified aqueous solution, heat to 50℃ and stir for 45min. Adjust the pH to 8.0 to obtain the solution.

[0052] S2. The solution obtained in step S1 is passed through a mixed resin column (mixed resin volume 1000 mL) at a flow rate of 1 BV / h and a temperature of 35℃. The mixed resin column is then rinsed with 2000 mL of purified water at 35℃. The effluents are combined, and the pH is adjusted to 6.5 with a 20 wt% potassium hydroxide aqueous solution. The solution is concentrated under reduced pressure to 800 mL and spray-dried at an inlet air temperature of 125℃ to obtain dipotassium glycyrrhizate.

[0053] The mixed resin in the mixed resin column is a composition of hydrogen-form strong acid cation exchange resin and novel chelating resin A, and the volume ratio of hydrogen-form strong acid cation exchange resin to novel chelating resin A is 3:1.

[0054] Example 2

[0055] A method for preparing dipotassium glycyrrhizate for deep removal of heavy metals based on chelating resin includes the following steps:

[0056] S1. Dissolve 480g of potassium hydroxide in 2000mL of purified water to obtain an alkaline purified aqueous solution. Add 400g of glycyrrhizic acid monoammonium salt to the alkaline purified aqueous solution, heat to 40℃ and stir for 60min. Adjust the pH to 7.5 to obtain the solution.

[0057] S2. The solution obtained in step S1 is passed through a mixed resin column (mixed resin volume 1000 mL) at a flow rate of 0.5 BV / h and a temperature of 25°C. The mixed resin column is then rinsed with 2000 mL of purified water at 25°C. The effluents are combined, and the pH is adjusted to 6.5 with a 20 wt% potassium hydroxide aqueous solution. The solution is concentrated under reduced pressure to 800 mL and spray-dried at an inlet air temperature of 125°C to obtain dipotassium glycyrrhizate.

[0058] The mixed resin in the mixed resin column is a composition of hydrogen-form strong acid cation exchange resin and novel chelating resin A, and the volume ratio of hydrogen-form strong acid cation exchange resin to novel chelating resin A is 2:1.

[0059] Example 3

[0060] A method for preparing dipotassium glycyrrhizate for deep removal of heavy metals based on chelating resin includes the following steps:

[0061] S1. Dissolve 480g of potassium hydroxide in 2000mL of purified water to obtain an alkaline purified aqueous solution. Add 400g of glycyrrhizic acid monoammonium salt to the alkaline purified aqueous solution, heat to 60℃ and stir for 30min, and adjust the pH to 8.5 to obtain a solution.

[0062] S2. The solution obtained in step S1 is passed through a mixed resin column (mixed resin volume 1000 mL) at a flow rate of 1.5 BV / h and a temperature of 40℃. The mixed resin column is then rinsed with 2000 mL of purified water at 40℃. The effluents are combined, and the pH is adjusted to 6.5 with a 20 wt% potassium hydroxide aqueous solution. The solution is concentrated under reduced pressure to 800 mL and spray-dried to obtain dipotassium glycyrrhizate.

[0063] The mixed resin in the mixed resin column is a composition of hydrogen-form strong acid cation exchange resin and novel chelating resin A, and the volume ratio of hydrogen-form strong acid cation exchange resin to novel chelating resin A is 4:1.

[0064] Example 4

[0065] A method for preparing dipotassium glycyrrhizate based on chelating resin for deep removal of heavy metals is the same as in Example 1, except that in step S2, an equal amount of novel chelating resin B is used instead of novel chelating resin A.

[0066] Example 5

[0067] A method for preparing dipotassium glycyrrhizate based on chelating resin for deep removal of heavy metals is the same as in Example 1, except that in step S2, an equal amount of novel chelating resin C is used instead of novel chelating resin A.

[0068] Example 6

[0069] A method for preparing dipotassium glycyrrhizate for deep removal of heavy metals based on chelating resin is the same as in Example 1, except that the volume ratio of hydrogen-type strong acidic cation exchange resin and novel chelating resin A in step S2 is 1.5:1.

[0070] Comparative Example 1

[0071] A method for preparing dipotassium glycyrrhizate based on chelating resin for deep removal of heavy metals is the same as in Example 1, except that in step S2, an equal amount of commercially available chelating resin is used instead of the novel chelating resin A.

[0072] Effect evaluation:

[0073] The dipotassium glycyrrhizate prepared in Examples 1-6 and Comparative Example 1 were tested and analyzed. The specific results are shown in Table 1.

[0074] Performance testing:

[0075] (1) The residual ethanol content, i.e., the residual alcohol content, was determined by gas chromatography.

[0076] (2) The ammonia ions in the sample were separated and quantitatively analyzed by ion chromatography, and the residual ammonia content was determined.

[0077] (3) The total content of heavy metals (lead, cadmium, arsenic and mercury) was determined according to the General Chapter 2321 of Part IV of the Chinese Pharmacopoeia 2020.

[0078] Table 1

[0079] Serial Number residual alcohol mg / kg residual ammonia mg / kg heavy metals mg / kg Example 1 432 32 0.71 Example 2 484 36 0.70 Example 3 426 30 0.78 Example 4 434 32 0.84 Example 5 432 32 0.98 Example 6 438 42 0.69 Comparative Example 1 434 32 1.24

[0080] As shown in Table 1, the residual alcohol content of dipotassium glycyrrhizate obtained in Examples 1-3 is ≤500mg / kg, the residual ammonia content is ≤40mg / kg, the total content of heavy metals (lead, cadmium, arsenic, mercury) is ≤0.8mg / kg, and the contents of lead, cadmium, arsenic, and mercury are all ≤0.2mg / kg.

[0081] Compared to Example 1, in the preparation of the novel chelating resin, Example 4 changed the mass ratio of resin 1 and N-aminoethylpiperazine, reducing the amino group; Example 5 changed the mass ratio of resin 2 and 5-chloro-1,3,4-thiadiazole-2-amine, reducing the thiazole group and weakening the synergistic effect, thus decreasing the resin's chelating ability for heavy metal ions; and Comparative Example 1 replaced the novel chelating resin A with an equal amount of commercially available chelating resin, reducing the chelating groups and decreasing the chelating ability for heavy metal ions. All of the above will increase the heavy metal content in the product.

[0082] Compared to Example 1, Example 6 changed the volume ratio of cation exchange resin and novel chelating resin. Although it did not affect the efficient removal of heavy metals, it caused the ammonia content to exceed the standard.

[0083] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present application in any way. Although the present application discloses the preferred embodiment as described above, it is not intended to limit the present application. Any changes or modifications made by those skilled in the art without departing from the scope of the technical solution of the present application using the disclosed technical content are equivalent to equivalent implementation cases. Any simple modifications, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention without departing from the scope of the technical solution of the present invention are still within the scope of the technical solution.

Claims

1. A method for preparing dipotassium glycyrrhizate based on chelating resin for deep removal of heavy metals, characterized in that, It includes the following steps: S1. Add glycyrrhizic acid monoammonium salt to an alkaline pure aqueous solution, stir, and adjust the pH to 7.5-8.5 to obtain a solution; S2. Pass the solution obtained in step S1 through a mixed resin column, rinse the mixed resin column, combine the effluents, concentrate and dry to obtain dipotassium glycyrrhizate; wherein, the mixed resin in the mixed resin column is a combination of cation exchange resin and novel chelating resin; The volume ratio of the cation exchange resin to the novel chelating resin is (2) 4): 1; The preparation method of the novel chelating resin includes the following steps: Q1. Wash the aminomethyl polystyrene resin with an aqueous ethanol solution for 3 minutes. Four times, filter by suction, and then place in N, N In dimethylformamide, seal and stir to allow swelling for 10 minutes. After 15 hours, the mixture was filtered to obtain pretreated resin. Q2. Mix the pretreated resin obtained in step Q1, methanol, and methyl acrylate, and react at room temperature for 18 minutes. After 30 hours, the mixture was filtered under reduced pressure and extracted with anhydrous ethanol. After 10 hours, wash with an ethanol-water solution and dry to obtain resin 1; Q3. Combine the resin 1, methanol, and N obtained in step Q2. A mixture of aminoethylpiperazine was reacted at room temperature for 18 days. After 30 hours, the mixture was filtered under reduced pressure, washed with an ethanol-water solution, and dried to obtain resin 2. Q4. The resin 2, toluene, and 5 obtained in step Q3 chlorine 1,3,4 Thiadiazole 2 Amine mixtures are introduced, an inert gas is passed through, a catalyst is added, and the mixture is heated to 65°C. 100℃ reaction 5 After 8 hours, the resin was washed and dried to obtain a novel chelating resin.

2. The method for preparing dipotassium glycyrrhizate based on chelating resin for deep removal of heavy metals according to claim 1, characterized in that, The alkaline substance in the alkaline pure aqueous solution mentioned in step S1 is potassium hydroxide or potassium carbonate.

3. The method for preparing dipotassium glycyrrhizate based on chelating resin for deep removal of heavy metals according to claim 1, characterized in that, The stirring temperature in step S1 is 40–60°C.

4. The method for preparing dipotassium glycyrrhizate based on chelating resin for deep removal of heavy metals according to claim 1, characterized in that, In step S2, the solution is passed through the mixed resin column at a flow rate of 0.5–1.5 BV / h and a temperature of 25–40 °C.

5. The method for preparing dipotassium glycyrrhizate based on chelating resin for deep removal of heavy metals according to claim 1, characterized in that, The cation exchange resin is a hydrogen-form strong acid cation exchange resin.

6. The method for preparing dipotassium glycyrrhizate based on chelating resin for deep removal of heavy metals according to claim 1, characterized in that, Resin 1 and N mentioned in step Q3 The mass ratio of aminoethylpiperazine is 1:(1.6). 2.2).

7. The method for preparing dipotassium glycyrrhizate based on chelating resin for deep removal of heavy metals according to claim 1, characterized in that, Resins 2 and 5 mentioned in step Q4 chlorine 1,3,4 Thiadiazole 2 The mass ratio of amines is 1:(2.2). 2.8).

8. According to claim 1 The method for preparing dipotassium glycyrrhizate based on chelating resin for deep removal of heavy metals as described in any one of the seven claims is characterized in that, The dipotassium glycyrrhizate obtained by the preparation method has a residual alcohol content of ≤500mg / kg, a residual ammonia content of ≤40mg / kg, and a lead, cadmium, arsenic, and mercury content of ≤0.2mg / kg.