A method for extracting liquiritin from crude glycyrrhizin

Abstract

The present application relates to the technical field of traditional Chinese medicine extraction and separation, and particularly relates to a method for extracting glycyrrhizin from glycyrrhizin crude product and an extract containing glycyrrhizin prepared by the method. The method comprises the following steps: mixing solvents, adjusting pH value, controlling difference in solvent polarity of an extraction system, controlling extraction temperature, layering, vacuum concentration and spray drying to obtain glycyrrhizin finished product. The present application realizes efficient extraction and enrichment of glycyrrhizin by using purified water, ethyl acetate and n-heptane to form a composite extraction system based on the difference in solvent polarity.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine extraction and separation technology, specifically to a method for extracting glycyrrhizin from crude glycyrrhizin, and an extract containing glycyrrhizin prepared by the method. Background Technology

[0002] Liquiritin (systematic name 4',7-dihydroxydihydroflavonoid-4'-O-β-D-glucopyranoside) is the main flavonoid active ingredient in licorice. It belongs to the dihydroflavonoid class of compounds and has a variety of pharmacological activities, including antioxidant, antiarrhythmic, antiulcer, antiviral, neuroprotective, and myocardial cell membrane protection. It has important application value in the pharmaceutical field.

[0003] Currently, most existing glycyrrhizin extraction processes use licorice as a raw material. For example, Chinese patent document CN101073595A discloses a method for extracting total flavonoids and total saponins from licorice, and patent CN109549966A reports an ultrasound-assisted method for preparing licorice extract. However, extraction methods using licorice as a raw material make it difficult to achieve targeted separation of the effective components in glycyrrhizin, and the bitter components contained in glycyrrhizin limit its application range. Summary of the Invention

[0004] The purpose of this invention is to provide a method for extracting glycyrrhizin from crude glycyrrhizin. Using crude glycyrrhizin as a raw material for extracting glycyrrhizin not only enriches the glycyrrhizic acid in glycyrrhizin but also effectively reduces bitter components, achieving comprehensive and efficient utilization of glycyrrhizin and overcoming the application limitations of related materials.

[0005] To achieve the above objectives, the technical solution adopted by the present invention is as follows: A method for extracting glycyrrhizin from crude glycyrrhizin, comprising the following steps:

[0006] 1) Solvent mixing: Crude glycyrrhizin is mixed with purified water and mechanically stirred to obtain a raw material mixture;

[0007] 2) Adjust pH value: Control the pH value of the raw material mixture within the neutral to slightly alkaline range; stir;

[0008] 3) Controlling the difference in solvent polarity in the extraction system: Ethyl acetate and n-heptane are added sequentially to form a composite extraction system by utilizing the difference in solvent polarity;

[0009] 4) Control the extraction temperature;

[0010] 5) Layering: After extraction, allow the mixture to stand at room temperature to separate and collect the organic phase.

[0011] 6) Concentrate under reduced pressure to obtain a concentrate;

[0012] 7) Spray drying: Add hot water to the concentrate, stir and mix, then spray dry to obtain the glycyrrhizin product.

[0013] In a preferred embodiment, the glycyrrhizin content in the finished product is >5%.

[0014] Furthermore, in step 1), the weight ratio of crude glycyrrhizin to purified water is 1:8 to 1:10.

[0015] In a preferred embodiment, in step 2), the mixture is stirred at a speed of 40-80 r / min for 15-30 min. In step 2), the pH value of the raw material mixture is controlled within the neutral-to-slightly alkaline range of 6.5-7.5. In step 2), the pH value is adjusted by adding alkaline solution.

[0016] In the preferred embodiment, in step 4), the temperature of the composite extraction system is controlled at 50~60℃, and the constant temperature pulping extraction time is 0.5~1.5h.

[0017] Furthermore, in step 5), after extraction, allow the mixture to stand at room temperature for 30 min to 1 h to separate into layers.

[0018] In a preferred embodiment, the mixing time in step 7) is 2-10 minutes.

[0019] More specifically, the method utilizes the polarity difference of different solvents for pulping and extraction: First, add water at a volume 10 times the weight of the feed material, adjust the pH of the system to 6.5-7.5 using a 1% sodium hydroxide solution, and stir at 60 rpm for 15-30 min. Then, add ethyl acetate and n-heptane sequentially, and continue pulping at 50-60℃ for 1 hour. After completion, allow the system to stand for 30 min to 1 hour to separate the layers until a clear interface is formed, and then collect the organic phase. Concentrate the organic phase under reduced pressure at 60℃ to maintain good flowability of the material. Before discharging, add hot water and mix for 5 min. Finally, spray dry to obtain the glycyrrhizin product.

[0020] The present invention also discloses the glycyrrhizin extract obtained by the aforementioned method for extracting glycyrrhizin from crude glycyrrhizin.

[0021] This invention uses glycyrrhizin as a raw material and employs a process that utilizes purified water, ethyl acetate, and n-heptane to form a composite extraction system based on the difference in solvent polarity. This process achieves highly efficient extraction and enrichment of glycyrrhizin, with the following specific beneficial effects:

[0022] 1. High extraction efficiency: The glycyrrhizin content in the obtained glycyrrhizin extract is consistently above 5%, which is a significant improvement compared to the 1.70% content in the raw material;

[0023] 2. Excellent impurity removal effect: It effectively reduces the bitter components in glycyrrhizin, thus broadening the application scenarios of glycyrrhizin;

[0024] 3. Simple and controllable process: The operation steps are simple, the conditions are mild, and it is suitable for industrial production, realizing the high-value comprehensive utilization of glycyrrhizin. Detailed Implementation

[0025] The present invention will be described in detail below with reference to specific embodiments.

[0026] Example 1

[0027] 1) Solvent Mixing: Weigh 100g of crude glycyrrhizin (glycyrrhizin content 1.70%, glycyrrhizic acid content 10.9%, % is mass content; glycyrrhizin is a by-product extracted from the mother liquor obtained during the production of glycyrrhizic acid monoammonium salt; the preparation process is as follows: after crushing licorice, extract the extract by hot reflux of ethanol, stir in a reaction vessel, heat the hot water to 65℃, slowly add ammonia water dropwise into the vessel, monitor the pH of the reaction solution, and stop adding when the pH of the reaction solution reaches 5.0; after keeping the reaction at this temperature for 2 hours, transfer to an ammoniation crystallization vessel, stir and crystallize for more than 4 hours with chilled water, the final temperature must be below 20℃, release the liquid and filter it through a filter press to obtain crude glycyrrhizic acid monoammonium salt; after filtration... The mother liquor was collected; the mother liquor obtained by pressure filtration according to the above steps was concentrated under single-effect vacuum at a concentration temperature of 65℃ and a vacuum degree of ≤-0.06MPa; after concentration until alcohol-free, the concentrate obtained from single-effect concentration was transferred to an alkalization kettle, and the concentrate was adjusted to an alkalization solution with a pH of 7.5 using sodium hydroxide solution; the screw pump power was turned on, the water inlet valve was opened, and the screw pump frequency controller was turned on to adjust the frequency. When the air inlet temperature reached 130℃, water was flowed for 30 minutes, and feeding was started. The air inlet temperature was maintained at 175℃, the feeding frequency was controlled between 11-15, and the atomization frequency was between 38-40; spray drying was performed to obtain crude glycyrrhizin, and purified water (weight ratio 1:10) was added and mechanically stirred until uniform;

[0028] 2) Adjust the pH value using a 1% sodium hydroxide solution: control the pH value of the mixed solution system at 6.5; stir at 60 r / min for 15 min;

[0029] 3) Controlling the difference in solvent polarity in the extraction system: Ethyl acetate and n-heptane are added sequentially to form a composite extraction system by taking advantage of the difference in solvent polarity; wherein the ratio of the mixture obtained in step 2) to ethyl acetate is 100g:1000mL, and the ratio of the mixture obtained in step 2) to n-heptane is 100g:1000mL.

[0030] 4) Control the extraction temperature: The temperature of the composite extraction system is controlled at 50℃, and the constant temperature pulping and extraction time is 1 hour;

[0031] 5) Layer separation: After extraction, allow to stand at room temperature for 30 minutes to separate the layers;

[0032] 6) Vacuum concentration: The vacuum concentration temperature is set at 60℃, and the concentration is carried out until the solid content is 45wt%.

[0033] 7) Spray drying: Add 60℃ hot water and stir for 5 minutes. Spray dry (inlet air temperature 165℃, screw pump frequency: 35.3Hz; nozzle frequency 32.10Hz) to obtain glycyrrhizin extract. Analysis showed that the glycyrrhizin content in the glycyrrhizin extract obtained in this example was 5.66%, and the glycyrrhizic acid content was increased to 13.91%, with a yield of 17.0%.

[0034] Example 2

[0035] 1) Solvent mixing: Weigh 100g of crude glycyrrhizin (glycyrrhizin content 1.70%, glycyrrhizic acid content 10.9%, preparation as in Example 1), add purified water (weight ratio 1:9), and mechanically stir until uniform;

[0036] 2) Adjust the pH value using a 1% sodium hydroxide solution: control the pH value of the mixed solution system at 7.0; stir at 60 r / min for 20 min;

[0037] 3) Controlling the difference in solvent polarity in the extraction system: Ethyl acetate and n-heptane are added sequentially to form a composite extraction system by taking advantage of the difference in solvent polarity; wherein the ratio of the mixture obtained in step 2) to ethyl acetate is 100g:1000mL, and the ratio of the mixture obtained in step 2) to n-heptane is 100g:1000mL.

[0038] 4) Control the extraction temperature: The temperature of the composite extraction system is controlled at 55℃, and the constant temperature pulping and extraction time is 1 hour;

[0039] 5) Layer separation: After extraction, allow to stand at room temperature for 45 minutes to separate the layers;

[0040] 6) Vacuum concentration: The vacuum concentration temperature is set at 60℃, and the concentration is carried out until the solid content is 50wt%;

[0041] 7) Spray drying: Add 70℃ hot water and stir for 5 minutes. Spray dry (inlet air temperature 175℃, screw pump frequency: 35.3Hz; nozzle frequency 32.10Hz) to obtain glycyrrhizin extract. Analysis showed that the glycyrrhizin content in the glycyrrhizin extract obtained in this example was 5.63%, the glycyrrhizic acid content increased by 14.08%, and the yield was 16.5%.

[0042] Example 3

[0043] 1) Solvent mixing: Weigh 100g of crude glycyrrhizin (glycyrrhizin content 1.70%, glycyrrhizic acid content 10.9%, preparation as in Example 1), add purified water (weight ratio 1:8), and mechanically stir until uniform;

[0044] 2) Adjust the pH value using a 1% sodium hydroxide solution: control the pH value of the mixed solution system at 7.5; stir at 60 r / min for 30 min; wherein the ratio of the mixed solution obtained in step 2) to ethyl acetate is 100 g: 900 mL, and the ratio of the mixed solution obtained in step 2) to n-heptane is 100 g: 900 mL;

[0045] 3) Controlling the difference in solvent polarity in the extraction system: Ethyl acetate and n-heptane are added sequentially to form a composite extraction system by utilizing the difference in solvent polarity;

[0046] 4) Control the extraction temperature: The temperature of the composite extraction system is controlled at 60℃, and the constant temperature pulping and extraction time is 1 hour;

[0047] 5) Layer separation: After extraction, allow to stand at room temperature for 1 hour to separate the layers;

[0048] 6) Vacuum concentration: The vacuum concentration temperature is set at 60℃, and the concentration is carried out until the solid content is 45wt%.

[0049] 7) Spray drying: Add 65℃ hot water and stir for 5 minutes. Spray dry (inlet air temperature 155℃, screw pump frequency: 35.3Hz; nozzle frequency 32.10Hz) to obtain glycyrrhizin extract. Analysis showed that the glycyrrhizin extract obtained in this example contained 5.60% glycyrrhizin and 13.62% glycyrrhizic acid, with a yield of 15.9%.

[0050] Comparative Example 1

[0051] Compared to Example 1, glycyrrhizin was replaced with licorice. Everything else was the same as in Example 1. Testing showed that the glycyrrhizin extract obtained in this comparative example contained 1.25% glycyrrhizin and 3.08% glycyrrhizic acid, with a yield of 3.8%. It is evident that when the process of this example is used to extract licorice, the extracted glycyrrhizin and glycyrrhizic acid contents are both low, and the yield is significantly lower than that of the example.

[0052] Comparative Example 2

[0053] Compared with Example 1, the ratio of the mixture obtained in step 2) to ethyl acetate was modified to 100g:1500mL, and the ratio of the mixture obtained in step 2) to n-heptane was modified to 100g:1500mL. All other steps remained the same as in Example 1. The glycyrrhizin extract prepared in this comparative example contained 4.02% glycyrrhizin and 12.30% glycyrrhizic acid, with a yield of 9.9%. This shows that the mass-volume ratio of the mixture to ethyl acetate and n-heptane has a significant impact on the glycyrrhizin content, glycyrrhizic acid content, and yield of the glycyrrhizin extract.

[0054] Comparative Example 3

[0055] Compared to Example 1, in step 3), n-heptane was replaced with n-hexane or diethyl ether, while the rest remained the same as in Example 1. When n-heptane in step 3) was replaced with n-hexane, the glycyrrhizin extract obtained contained 4.82% glycyrrhizin and 12.40% glycyrrhizic acid, with a yield of 10.5%. When n-heptane in step 3) was replaced with diethyl ether, the glycyrrhizin extract obtained contained 4.31% glycyrrhizin and 10.62% glycyrrhizic acid, with a yield of 10.4%. This comparative example shows that n-heptane in step 3) is relatively important for the glycyrrhizin content, glycyrrhizic acid content, and yield of the glycyrrhizin extract.

[0056] The above embodiments are only used to illustrate the technical solutions of the present invention. Those skilled in the art should understand that the above embodiments do not limit the present invention in any way. All technical solutions obtained by equivalent substitution or equivalent transformation fall within the protection scope of the present invention.

Claims

1. A method for extracting glycyrrhizin from crude glycyrrhizin, characterized in that, Includes the following steps: 1) Solvent mixing: Crude glycyrrhizin is mixed with purified water and mechanically stirred to obtain a raw material mixture; 2) Adjust pH value: Control the pH value of the raw material mixture within the neutral to slightly alkaline range; stir; 3) Controlling the difference in solvent polarity in the extraction system: Ethyl acetate and n-heptane are added sequentially to form a composite extraction system by utilizing the difference in solvent polarity; 4) Control the extraction temperature; 5) Layering: After extraction, allow the mixture to stand at room temperature to separate and collect the organic phase. 6) Concentrate under reduced pressure to obtain a concentrate; 7) Spray drying: Add hot water to the concentrate, stir and mix, then spray dry to obtain the glycyrrhizin product.

2. The method for extracting glycyrrhizin from crude glycyrrhizin according to claim 1, characterized in that, The glycyrrhizin product contains >5% glycyrrhizin.

3. The method for extracting glycyrrhizin from crude glycyrrhizin according to claim 1, characterized in that, In step 1), the weight ratio of crude glycyrrhizin to purified water is 1:8 to 1:

10.

4. The method for extracting glycyrrhizin from crude glycyrrhizin according to claim 1, characterized in that, In step 2), stir at a speed of 40~80 r / min for 15~30 min.

5. The method for extracting glycyrrhizin from crude glycyrrhizin according to claim 1, characterized in that, In step 2), the pH value of the raw material mixture is controlled within the neutral to slightly alkaline range of 6.5 to 7.

5.

6. The method for extracting glycyrrhizin from crude glycyrrhizin according to claim 1, characterized in that, In step 2), the pH value is adjusted by adding an alkaline solution.

7. The method for extracting glycyrrhizin from crude glycyrrhizin according to claim 1, characterized in that, In step 4), the temperature of the composite extraction system is controlled at 50~60℃, and the constant temperature pulping and extraction time is 0.5~1.5h.

8. The method for extracting glycyrrhizin from crude glycyrrhizin according to claim 1, characterized in that, In step 5), after extraction, allow the mixture to stand at room temperature for 30 min to 1 h to separate into layers.

9. The method for extracting glycyrrhizin from crude glycyrrhizin according to claim 1, characterized in that, The mixing time in step 7) is 2-10 minutes.

10. Glycyrrhizin obtained by the method for extracting glycyrrhizin from crude glycyrrhizin according to any one of claims 1-9.