Preparation method of glycyrrhizin extract

Abstract

The preparation method of the glycyrrhizin extract comprises the following steps: S1, cleaning liquorice stems to remove impurities; s2, performing centrifugal drying on the cleaned liquorice stems; s3, putting the cleaned and dried liquorice stems into an extraction tank, and extracting a liquorice stem stock solution in an ethanol soaking extraction manner; s4, filtering the licorice stem stock solution, pouring the filtered licorice stem stock solution into a precipitation tank, and carrying out standing precipitation; s5, precipitating and layering the licorice stem stock solution in a precipitation tank, pumping the supernatant into a first concentration tank, and obtaining a licorice stem concentrated solution by adopting a reduced pressure distillation mode; s6, pumping the liquorice stem concentrated solution into an extraction tank, adding ethyl acetate, stirring, and standing for layering; and S7, pumping the supernatant in the extraction tank into a second concentration tank, and heating to recover ethyl acetate, thereby obtaining the glycyrrhizin extract. The solvent is recovered in a reduced pressure distillation mode, the production cost is reduced, environmental pollution is avoided, and the product quality is improved.

Description

Technical Field

[0001] The invention belongs to the field of pharmaceuticals, and in particular relates to a method for preparing glycyrrhizin extract. Background Art

[0002] In the hepatitis drug field, silibinin and glycyrrhizin are both important adjunctive therapies for liver disease, but they target different types of hepatitis. Ammonium glycyrrhizinate is primarily used for the treatment and detoxification of acute and chronic viral hepatitis with elevated alanine aminotransferase, while silibinin is used as an adjunctive treatment for acute and chronic hepatitis and early-stage liver cirrhosis.

[0003] The silybin and glycyrrhizin complex reagent combines silymarin and glycyrrhizin extract, which not only exerts the detoxification and transaminase-lowering effects of glycyrrhizin, but also makes up for the defect that silybin cannot treat acute poisoning.

[0004] The current preparation process of glycyrrhizin extract uses a water reflux extraction process, which has a long production cycle and requires a large amount of solvent, resulting in a low glycyrrhizin yield. Furthermore, the large amount of solvent used results in a low extraction rate of glycyrrhizin, which cannot fully utilize the active ingredients in the raw materials. During the concentration stage, direct heating and evaporation are not only energy-intensive but also prone to decomposition or denaturation of active ingredients such as glycyrrhizin due to high temperatures, affecting product quality. During the extraction of glycyrrhizin, a large amount of impurities are easily introduced, requiring subsequent tedious impurity removal operations, increasing production costs and process complexity.

[0005] Furthermore, traditional methods such as atmospheric distillation require high temperatures, which not only consumes significant energy but can also cause solvent decomposition and the generation of impurities, affecting the quality of the recovered solvent. This wastes resources and can also affect product safety due to residual solvent. Furthermore, if the large amounts of solvent used in the concentration and extraction processes cannot be effectively recovered, production costs will increase, and indiscriminate discharge can cause serious environmental pollution. Summary of the Invention

[0006] The present invention aims to provide a method for preparing a glycyrrhizin extract, so as to solve the technical problem of improving the extraction efficiency of glycyrrhizin when preparing the glycyrrhizin extract and efficiently recovering the concentration and extraction solvent.

[0007] To achieve the above-mentioned purpose, the specific technical scheme of the preparation method of a glycyrrhizin extract of the present invention is as follows:

[0008] A method for preparing glycyrrhizin extract comprises the following steps:

[0009] S1. Cleaning the licorice stems to remove impurities;

[0010] S2, centrifugally drying the cleaned licorice stems;

[0011] S3, placing the cleaned and dried licorice stems into an extraction tank, and extracting the licorice stem stock solution by ethanol immersion extraction;

[0012] S4, filtering the liquorice stem stock solution and pouring it into a sedimentation tank for static precipitation;

[0013] S5, the licorice stem stock solution is precipitated and layered in a precipitation tank, the supernatant is pumped into a first concentration tank, and a licorice stem concentrate is obtained by vacuum distillation;

[0014] S6. Pumping the concentrated liquorice stem solution into an extraction tank, adding ethyl acetate, stirring, and allowing to stand for stratification;

[0015] S7. The supernatant in the extraction tank is pumped into a second concentration tank, and ethyl acetate is recovered by vacuum distillation to obtain glycyrrhizin extract.

[0016] As a further improvement of the present invention, S1 comprises the following steps:

[0017] S1.1, use high-pressure water washing equipment to wash the surface of the licorice stem to remove surface impurities;

[0018] S1.2. Place the washed licorice stems in an ultrasonic cleaning tank filled with drinking water at a temperature of 30-40°C. The ultrasonic frequency is 40-60 kHz and the ultrasonic time is 15-20 minutes.

[0019] S1.3. Use a rolling cleaning device with a brush to scrub the licorice stems at a speed of 30 to 50 r / min while continuously spraying clean water.

[0020] As a further improvement of the present invention, in S2, the cleaned licorice stems are centrifuged in a centrifuge at a speed of 1500-2500 rpm for 10-20 minutes to preliminarily remove surface moisture; then the licorice stems are spread flat in a hot air drying oven and dried at a temperature of 40-50°C for 2-3 hours to reduce the moisture content of the licorice stems to below 10%.

[0021] As a further improvement of the present invention, S3 includes the following steps:

[0022] S3.1. Add licorice stems and 60% ethanol in a mass ratio of 1:8 to 1:10 to an extraction tank equipped with a stirring device. Ensure that the ethanol completely submerges the licorice stems. Stir at a speed of 60 to 80 r / min and soak for 2 hours.

[0023] S3.2. Heat the extraction tank until the liquid in the tank slowly reaches boiling state, and keep boiling and stirring for 60 minutes;

[0024] S3.3. Filter the liquorice stem stock solution in the extraction tank through a filter into a sedimentation tank to remove solid residue;

[0025] S3.4. Add water to the remaining licorice stems in the extraction tank, with a mass ratio of water to licorice stems of 1:6 to 1:8, stir at a speed of 60 to 80 r / min, and soak for 2 hours; after soaking, heat to boiling and keep boiling and stirring for 60 minutes.

[0026] As a further improvement of the present invention, in S4, the liquorice stem stock solution in the extraction tank is passed through a 100-120 mesh filter into a sedimentation tank, and is allowed to stand in the sedimentation tank for 6 hours to separate layers.

[0027] As a further improvement of the present invention, in S5, the supernatant in the sedimentation tank is extracted by a vacuum filtration device with a vacuum degree of -0.06 to -0.07 MPa, and then enters the first concentration tank after passing through a filter screen with a pore size of 0.2 to 0.5 μm. The vacuum degree in the first concentration tank is maintained at -0.08 to -0.09 MPa, and the first concentration tank is heated until the stock solution boils, while stirring the stock solution at a stirring speed of 30 to 50 r / min. When the density of the stock solution reaches 1.05 to 1.1 g / cm 3 The concentration was stopped when the temperature was 400 °C to obtain the liquorice stem concentrate.

[0028] As a further improvement of the present invention, in S6, the licorice stem concentrate is transferred to an extraction tank, ethyl acetate is added as an extraction solvent in a volume ratio of 1:1 to the concentrate, and the mixture is mixed evenly at a stirring speed of 150 to 200 r / min. After continuous stirring for 30 minutes, the mixed liquid in the extraction tank is allowed to stand for 12 hours.

[0029] As a further improvement of the present invention, the mixed liquid in the extraction tank in S7 is allowed to stand and separate, and the ethyl acetate in the upper layer is transferred to a second concentration tank. The ethyl acetate is recovered by vacuum distillation. The distillation temperature is controlled at 40 to 50°C and the vacuum degree is -0.08 to -0.09 MPa. As the ethyl acetate continues to evaporate, glycyrrhizin extract is obtained.

[0030] Beneficial effects:

[0031] S1 cleans the licorice stems, effectively removing impurities and preventing them from entering the subsequent extraction process, thereby reducing product quality issues and subsequent impurity removal costs caused by impurities. S2's centrifugal drying process initially removes a large amount of surface moisture through centrifugation, and then combines it with hot air drying. Compared to traditional drying methods such as simple air drying, this significantly shortens drying time. Precisely controlling the drying temperature prevents degradation of the active ingredients in licorice due to high temperatures, ensuring raw material quality, providing a high-quality raw material foundation for subsequent extraction processes, and improving overall production efficiency.

[0032] S3 uses ethanol to extract the original liquor of licorice stems. As a good organic solvent, ethanol can fully dissolve active ingredients such as glycyrrhizic acid. Compared with traditional methods such as water extraction, it has higher extraction efficiency and more concentrated extracted ingredients. S4-S5 remove insoluble matter and most of the solvent in the extract through filtration, precipitation, and vacuum distillation. Vacuum distillation uses negative pressure to lower the boiling point of the solvent and achieve concentration at a lower temperature. It not only avoids the destruction of the active ingredient of glycyrrhizic acid by high temperature, but also speeds up the concentration and reduces energy consumption. At the same time, it accurately controls the density of the concentrate to provide a solution of appropriate concentration for subsequent extraction.

[0033] S6 adds ethyl acetate for extraction, leveraging its good solubility in glycyrrhizin and low solubility in impurities to achieve efficient enrichment of glycyrrhizin and significantly improve the purity of the extract. S7 recovers ethyl acetate through vacuum distillation. At low temperatures of 40-50°C and a specific vacuum level, ethyl acetate can be efficiently recovered, and the recovered solvent can be reused, reducing production costs. Low-temperature vacuum distillation avoids impurities generated by high-temperature decomposition of the solvent, ensuring the quality of the recovered solvent while reducing environmental pollution caused by solvent emissions, meeting green and environmentally friendly production requirements. DETAILED DESCRIPTION

[0034] In order to better understand the purpose, structure and function of the present invention, the preparation method of the glycyrrhizin extract of the present invention is further described in detail.

[0035] Implementation example:

[0036] A method for preparing a glycyrrhizic acid glycoside extract comprises washing and drying the licorice stems, extracting the stock solution by ethanol immersion extraction, concentrating the stock solution by vacuum distillation, and then extracting the glycyrrhizic acid glycoside extract. The specific method is as follows:

[0037] Fresh licorice stems that meet medicinal standards are hand-picked to remove any visible signs of decay or discoloration. Weeds, gravel, and other foreign matter are also removed. The cleaned stems are then repeatedly rinsed with clean water to remove most dirt and impurities. The cleaned stems are then centrifuged at 2000 rpm for 15 minutes to initially remove a significant amount of surface moisture. The stems are then spread flat in a hot air drying oven set at 40°C for 3 hours, reducing their moisture content to below 10%.

[0038] The dried licorice stems were weighed and placed in an extraction tank equipped with a stirring device. Ethanol was added at a ratio of 1:8 (mass ratio) of licorice stems to 60% ethanol, ensuring that the stems were completely submerged. The stirring device was turned on and stirred at 60 rpm for 2 hours to promote the dissolution of the active ingredients. The extraction tank was then heated, slowly bringing the liquid inside to a slight boil. This was maintained at a slight boil for 60 minutes, with continuous stirring. The extract was then filtered through a 100-mesh filter into a sedimentation tank to initially remove solid residue. Drinking water was then added to the remaining licorice stems in the extraction tank at a ratio of 1:6 (mass ratio) and the mixture was soaked for another 2 hours. After soaking, the mixture was heated to a slight boil and maintained at a slight boil for 60 minutes, again with stirring. After the extraction, the extract was filtered through a 200-mesh filter and the filtrate was added to the sedimentation tank.

[0039] After the licorice stem extraction is complete, the resulting stock solution contains not only the desired active ingredients, such as glycyrrhizic acid, but also a significant amount of solvent and impurities. To ensure more efficient extraction and separation of the active ingredients, the stock solution must be concentrated. The licorice stem stock solution is first allowed to naturally settle in a sedimentation tank for six hours. During this process, insoluble impurities in the stock solution, such as fine particles that were not completely filtered out and macromolecular polymers formed during the extraction process, settle to the bottom under gravity. The sedimentation tank typically features a conical bottom design, facilitating the collection and discharge of impurities and significantly reducing the solid impurity content in the supernatant. After precipitation, the supernatant is pumped into the first concentration tank using a vacuum filtration device. This vacuum filtration device uses a vacuum pump to generate negative pressure, which forces the supernatant to pass rapidly through a filter cloth or screen under the pressure differential, further removing any possible fine particles. The filter cloth or screen typically has a pore size of 0.2 to 0.5 μm to effectively retain solid impurities and ensure relatively clear liquid entering the first concentration tank. During the filtration process, the vacuum level is maintained at -0.06 to -0.07 MPa to ensure a stable filtration rate and prevent equipment damage or filtrate quality degradation due to excessive pressure. The raw liquid is concentrated in the first concentration tank using vacuum distillation. The principle is that in an environment below normal pressure, the boiling point of the solution is lowered. This allows for evaporation and concentration at a relatively low temperature, preventing high temperatures from damaging the heat-sensitive active ingredients in licorice. The vacuum level is maintained at -0.08 to -0.09 MPa, at which the boiling point of the solution can be reduced to 60-70°C. The heating system generally uses steam or electric heating, transferring heat to the liquid in the first concentration tank via a jacket or coil. During the concentration process, the liquid must be continuously stirred to ensure uniform heating and avoid local overheating. The stirring speed is controlled at 30 rpm, and the condensation reflux device is simultaneously activated to recover evaporated solvent, achieving resource recycling. As concentration proceeds, the solvent in the solution continues to evaporate, and the concentration gradually increases. When the density of the concentrated solution reaches 1.05 g / cm 3Stop concentrating.

[0040] In the concentrated licorice stem extract, active ingredients such as glycyrrhizin are still mixed with other impurities. The purpose of extraction is to utilize the differences in solubility of different substances in immiscible solvents to transfer glycyrrhizin from the concentrate to another more suitable solvent, thereby achieving separation from impurities and further purification. Ethyl acetate is selected as the extraction solvent. Glycyrrhizin has good solubility in ethyl acetate, while most impurities have low solubility in it. Ethyl acetate is also immiscible with the aqueous phase in the concentrate, facilitating subsequent layer separation. The concentrate is transferred to an extraction tank, and ethyl acetate is slowly added in a 1:1 volume ratio of concentrate to ethyl acetate. The stirring device is turned on to allow the two liquids to mix quickly and evenly, promoting the transfer of active ingredients. The stirring device generally uses a paddle or turbine agitator, and the stirring speed is set to 150 r / min. This stirring speed ensures that the two liquids are fully mixed without causing excessive emulsification, which affects the subsequent layering effect. After adding ethyl acetate, stirring is continued for 30 minutes to allow the glycyrrhizin molecules in the concentrate to fully contact the ethyl acetate molecules. Since glycyrrhizin's solubility in ethyl acetate is greater than its solubility in the original concentrate, according to the distribution law, glycyrrhizin will gradually transfer from the concentrate to the ethyl acetate phase. Furthermore, stirring breaks down the interfacial resistance between the liquids, accelerating the diffusion process of the molecules and improving extraction efficiency. After stirring, the mixed solution in the extraction tank is allowed to stand for 12 hours to separate. Because the density of ethyl acetate is lower than that of the aqueous phase (the main component of the concentrate), the two immiscible liquids gradually separate under the action of gravity. The upper layer is the ethyl acetate phase, which is enriched with a large amount of active ingredients such as glycyrrhizin; the lower layer is the aqueous phase, which mainly contains unextracted impurities and a small amount of residual glycyrrhizin. After separation, the upper ethyl acetate phase is carefully transferred to a second concentration tank using a separatory funnel. The piston of the separatory funnel is slowly opened to control the flow rate to prevent the lower aqueous phase from mixing with the ethyl acetate phase. The ethyl acetate phase transferred to the second concentration tank is subjected to vacuum distillation to recover the ethyl acetate. The principle of vacuum distillation is similar to the previous concentration process. By reducing pressure, the boiling point of ethyl acetate is lowered, allowing evaporation and recovery at a lower temperature. The heating temperature is controlled at 40°C and the vacuum is -0.08 MPa. During the heating process, the ethyl acetate gradually evaporates, cools through a condenser, and is recovered in a collection container. As the ethyl acetate continues to evaporate, the remaining material in the second concentration tank gradually concentrates, ultimately yielding a thick glycyrrhizin extract.

[0041] The quality of the extract can be assessed through indicators such as appearance, odor, and active ingredient content. Glycyrrhizin extract should be a thick, brown to dark brown liquid with a characteristic licorice odor. Analytical methods such as high-performance liquid chromatography (HPLC) should ensure that the glycyrrhizin content meets certain standards, such as a purity of no less than 80% (the specific content can be adjusted based on product quality requirements).

[0042] In the raw material pretreatment stage, the preparation method of the present invention adopts a multi-step cleaning method S1 that combines high-pressure water washing, ultrasonic cleaning and brush rolling cleaning, which can thoroughly remove impurities, microorganisms and some harmful components attached to the surface of licorice stems. Among them, ultrasonic cleaning uses high-frequency vibration to enhance the cleaning effect, and combined with drinking water at an appropriate temperature, it can make the cleaning more comprehensive; brush rolling cleaning further physically removes stubborn impurities on the surface. In S2, the centrifugal speed and hot air drying temperature and time are precisely controlled to not only efficiently remove moisture but also avoid the loss or denaturation of licorice's active ingredients due to excessive temperature, laying a good foundation for subsequent extraction and ensuring the purity and active ingredient content of the raw materials. In S3, ethanol immersion is combined with heated micro-boiling extraction, and a secondary extraction operation is performed. The licorice stems are mixed with 60% ethanol in a specific ratio, combined with an appropriate stirring speed and soaking time, to fully soak the licorice stems, allowing the ethanol to effectively penetrate and dissolve components such as glycyrrhizic acid glycoside; heating to a micro-boiling state and maintaining stirring can accelerate the dissolution of the components and improve the extraction efficiency. The secondary extraction utilizes water soaking and heating to fully utilize the effective ingredients remaining in the licorice stems and maximize the extraction rate of glycyrrhizic acid glycoside. Compared with traditional extraction methods, the raw material utilization rate is significantly improved and resource waste is reduced. In S5, the licorice stem stock solution is treated by reduced pressure distillation. Under a vacuum degree of -0.08 to -0.09 MPa, the boiling point of the solution is reduced, allowing the concentration process to be carried out at a lower temperature. This not only avoids the damage of heat-sensitive components such as glycyrrhizic acid glycoside by high temperature, ensuring the activity and quality stability of the product, but also effectively shortens the concentration time and improves production efficiency. At the same time, by precisely controlling the density of the stock solution at the concentration endpoint, the concentration of the concentrate is ensured to meet the requirements of subsequent processes. In S6, ethyl acetate is used as the extraction solvent, and the stirring speed and extraction time are strictly controlled. The good solubility and selectivity of ethyl acetate for glycyrrhizic acid glycoside can be used to effectively separate and enrich glycyrrhizic acid glycoside, further remove impurities, and improve the purity of the extract. S7 uses vacuum distillation to recover ethyl acetate and the solvent from the concentration process. At relatively low distillation temperatures (40-50°C) and a specific vacuum level (-0.08 to -0.09 MPa), this allows for efficient solvent recovery and reduces production costs. Furthermore, compared to traditional atmospheric distillation, vacuum distillation requires lower temperatures, reducing energy consumption and effectively preventing impurities from decomposing the solvent at high temperatures. This ensures the quality of the recovered solvent, making it reusable and reducing solvent waste and environmental pollution, in line with green production principles.

[0043] It will be understood that the present invention is described by way of some embodiments, and it will be appreciated by those skilled in the art that various changes or equivalent substitutions may be made to these features and embodiments without departing from the spirit and scope of the present invention. In addition, under the teachings of the present invention, these features and embodiments may be modified to adapt to specific circumstances and materials without departing from the spirit and scope of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed herein, and all embodiments falling within the scope of the claims of this application are intended to be protected by the present invention.

Claims

1. A method for preparing glycyrrhizin extract, characterized in that: The following steps are involved: S1. Cleaning the licorice stems to remove impurities; S2, centrifugally drying the cleaned licorice stems; S3, placing the cleaned and dried licorice stems into an extraction tank, and extracting the licorice stem stock solution by ethanol immersion extraction; S4, filtering the liquorice stem stock solution and pouring it into a sedimentation tank for static precipitation; S5, the licorice stem stock solution is precipitated and layered in a precipitation tank, the supernatant is pumped into a first concentration tank, and a licorice stem concentrate is obtained by vacuum distillation; S6. Pumping the concentrated liquorice stem solution into an extraction tank, adding ethyl acetate, stirring, and allowing to stand for stratification; S7. The supernatant in the extraction tank is pumped into a second concentration tank, and ethyl acetate is recovered by vacuum distillation to obtain glycyrrhizin extract.

2. The method for preparing the glycyrrhizin extract according to claim 1, wherein S1 includes the following steps: S1.1, use high-pressure water washing equipment to wash the surface of the licorice stem to remove surface impurities; S1.

2. Place the washed licorice stems in an ultrasonic cleaning tank filled with drinking water at a temperature of 30-40°C. The ultrasonic frequency is 40-60 kHz and the ultrasonic time is 15-20 minutes. S1.

3. Use a rolling cleaning device with a brush to scrub the licorice stems at a speed of 30 to 50 r / min while continuously spraying clean water.

3. The method for preparing the glycyrrhizin extract according to claim 1, wherein In S2, the cleaned licorice stems are centrifuged in a centrifuge at a speed of 1500-2500 rpm for 10-20 minutes to preliminarily remove surface moisture; the licorice stems are then spread flat in a hot air drying oven and dried at a temperature of 40-50° C. for 2-3 hours to reduce the moisture content of the licorice stems to below 10%.

4. The method for preparing the glycyrrhizin extract according to claim 1, wherein S3 includes the following steps: S3.

1. Add licorice stems and 60% ethanol in a mass ratio of 1:8 to 1:10 to an extraction tank equipped with a stirring device. Ensure that the ethanol completely submerges the licorice stems. Stir at a speed of 60 to 80 r / min and soak for 2 hours. S3.

2. Heat the extraction tank until the liquid in the tank slowly reaches boiling state, and keep boiling and stirring for 60 minutes; S3.

3. Filter the liquorice stem stock solution in the extraction tank through a filter into a sedimentation tank to remove solid residue; S3.

4. Add water to the remaining licorice stems in the extraction tank, with a mass ratio of water to licorice stems of 1:6 to 1:8, stir at a speed of 60 to 80 r / min, and soak for 2 hours; after soaking, heat to boiling and keep boiling and stirring for 60 minutes.

5. The method for preparing the glycyrrhizin extract according to claim 1, wherein In S4, the liquorice stem stock solution in the extraction tank is passed through a 100-120 mesh filter into a sedimentation tank, and is allowed to settle in the sedimentation tank for 6 hours to separate layers.

6. The method for preparing the glycyrrhizin extract according to claim 1, wherein In S5, the supernatant in the sedimentation tank is extracted by a vacuum filtration device with a vacuum degree of -0.06 to -0.07 MPa, and then enters the first concentration tank after passing through a filter with a pore size of 0.2 to 0.5 μm. The vacuum degree in the first concentration tank is maintained at -0.08 to -0.09 MPa. The first concentration tank is heated until the stock solution boils, and the stock solution is stirred at a stirring speed of 30 to 50 r / min. When the density of the stock solution reaches 1.05 to 1.1 g / cm 3 The concentration was stopped when the temperature was 400 °C to obtain the liquorice stem concentrate.

7. The method for preparing the glycyrrhizin extract according to claim 1, wherein In S6, the licorice stem concentrate is transferred to an extraction tank, ethyl acetate is added as an extraction solvent in a volume ratio of 1:1 to the concentrate, and the mixture is mixed evenly at a stirring speed of 150 to 200 r / min. After continuous stirring for 30 minutes, the mixed solution in the extraction tank is allowed to stand for 12 hours.

8. The method for preparing the glycyrrhizin extract according to claim 1, wherein The mixed liquid in the extraction tank in S7 is allowed to stand and separate into layers, and the upper layer of ethyl acetate is transferred to a second concentration tank, and the ethyl acetate is recovered by vacuum distillation. The distillation temperature is controlled at 40 to 50° C. and the vacuum degree is -0.08 to -0.09 MPa. As the ethyl acetate continues to evaporate, glycyrrhizin extract is obtained.