Continuous gradient forward and reverse flow forward and reverse rotation extraction method for artemisinin

Abstract

An artemisinin continuous gradient forward and reverse flow forward and reverse rotation extraction method belongs to the technical field of artemisinin extraction, and comprises the following steps: enabling an artemisia apiacea material to sequentially pass through a plurality of extraction sections connected in series along a first direction; injecting the extraction solvent along the direction opposite to the overall direction of the material, and controlling by a solvent bridge pipe, so that the solvent sequentially and reversely fills the subsequent sections to form a continuous gradient forward and reverse flow extraction environment in which the solvent flow direction is the same as the material flow direction in part of the sections and opposite to the material flow direction in part of the sections; in the extraction process, materials are stirred in a periodic positive and negative rotation mode, and an ultrasonic field is applied to a specific section for assistance; the device is a special system for implementing the method. According to the method disclosed by the invention, the extraction yield of the artemisinin is remarkably improved through the cooperation of'gradient forward and reverse flow design ', 'dynamic forward and reverse rotation stirring' and'ultrasonic assistance ', the extraction time is shortened to about 2 hours, and the production efficiency is greatly improved.

Description

Technical Field

[0001] This invention belongs to the field of artemisinin extraction technology, specifically relating to a continuous gradient forward and countercurrent extraction method for artemisinin. Background Technology

[0002] Artemisinin is a crucial raw material for first-line antimalarial drugs. It is a sesquiterpene lactone compound with antimalarial activity extracted from the plant Artemisia annua, belonging to the Asteraceae family. Its application value in the pharmaceutical field is widely recognized, and it is an effective antimalarial drug. Currently, the main extraction methods for artemisinin include solvent extraction, ethanol reflux extraction, supercritical fluid extraction, and microwave-assisted extraction. Solvent extraction suffers from low extraction efficiency, high solvent consumption, and long extraction time. While supercritical fluid extraction offers advantages such as high extraction efficiency and good product purity, it requires significant equipment investment and stringent operating conditions, limiting the large-scale industrial production of artemisinin. Therefore, the applicant's research team developed a highly efficient, energy-saving, and environmentally friendly artemisinin extraction method, namely the "Dynamic Co-current and Countercurrent Extraction Method for Artemisinin." By setting up three extraction tanks—co-current, transition, and countercurrent—dynamic stirring under co-current and countercurrent conditions is achieved, resulting in significant improvements in yield and energy consumption compared to static extraction methods. A national invention patent application (application number 2025103134453) was filed in early 2025.

[0003] However, after nearly a year of continued practice, it was found that the rotating shaft stabilizer installed inside the tank severely hindered the advancement of artemisinin material. The method still has the drawback of a long extraction time, and the yield can be further improved. Summary of the Invention

[0004] The technical problem to be solved by the present invention is to provide a continuous gradient countercurrent extraction method for artemisinin, which achieves efficient extraction through an integrated design of "continuous gradient flow + ultrasonic assistance + composite solvent synergy".

[0005] To solve the above-mentioned technical problems, the technical solution adopted in this invention is a continuous gradient co-current and counter-current extraction method for artemisinin, comprising the following steps: S1: Material conveying steps: Artemisia annua material is conveyed sequentially in the first direction through the downstream feeding section, the first transition section, the countercurrent extraction section, the second transition section, the downstream extraction section, the third transition section, and the countercurrent slag discharge section.

[0006] S2: Solvent gradient countercurrent step: The extraction solvent is injected into the countercurrent slag discharge section in a direction generally opposite to the first direction, and the solvent is controlled to fill the co-current extraction section through the third transition section, the countercurrent extraction section through the second transition section, and the co-current feed section through the first transition section in sequence, so that the flow path of the solvent and the flow path of the material form a continuous gradient co-current and countercurrent contact.

[0007] S3: Dynamic stirring step: During the extraction process, the material located in the co-current feeding section, counter-current extraction section, co-current extraction section and counter-current slag discharge section is periodically stirred in both forward and reverse directions.

[0008] S4: Extraction step: Collect artemisinin-rich extract from the downstream feed section.

[0009] The preferred equipment is as follows: The equipment used in the continuous gradient forward and reverse flow extraction method includes a forward flow feed tank, a first countercurrent transition extraction tank, a countercurrent extraction tank, a second countercurrent transition extraction tank, a forward flow extraction tank, a third countercurrent transition extraction tank, and a countercurrent slag discharge tank. These tanks are connected by 45° bevel welding. Each of the forward flow feed tank, countercurrent extraction tank, forward flow extraction tank, and countercurrent slag discharge tank is equipped with a stirring shaft. The stirring shaft is rotatably and sealed to the tank walls at both ends of its respective tank. No stabilizing frame is installed inside the tank. The stirring shaft is equipped with spiral stirring and propulsion blades. Each of the forward flow feed tank, countercurrent extraction tank, forward flow extraction tank, and countercurrent slag discharge tank has a forward flow connection to the stirring shaft at its left outer end. A reverse-flow stepper motor is used. The feed inlet is located above the left side wall of the co-current feed tank, and the slag outlet and solvent injection pipe are located below the left side wall of the counter-current slag outlet tank. A first solvent bridge pipe connects the left side of the third counter-current transition extraction tank to the co-current extraction tank. A second solvent bridge pipe connects the right side of the co-current extraction tank to the left side of the counter-current extraction tank. A third solvent bridge pipe connects the right side of the first counter-current transition extraction tank to the co-current feed tank. An extract collection pipe is located above the right side wall of the co-current feed tank. A delivery pump is installed on the extract collection pipe, the solvent injection pipe, and the three solvent bridge pipes. A solvent heater is installed on the solvent injection pipe.

[0010] The drive motor of the stirring shaft is a forward and reverse stepper motor. When it is necessary to push the material forward, the forward and reverse stepper motor is adjusted to always rotate in the forward direction. When it is necessary to stir the material, the forward and reverse stepper motor is adjusted to rotate in the forward and reverse directions intermittently.

[0011] The first, second, and third countercurrent transition extraction tanks are each equipped with an ultrasonic transducer on their outer walls. When in use, an ultrasonic field of 280-350W and 20-40kHz is applied to destroy the cell walls of Artemisia annua leaves through ultrasonic cavitation effect, while enhancing the solubility of artemisinin by the composite solvent and shortening the extraction time.

[0012] The selection process is carried out according to the following steps: S1: After drying and pulverizing the Artemisia annua leaves, pass them through a 40-60 mesh sieve and feed them into the feed tank through the inlet. Start the forward and reverse stepper motor (speed 8-16 r / min). The spiral stirring and propulsion blades in the feed tank gradually fill the Artemisia annua leaves and push them to the right (first overall direction). Then, it is pushed into the countercurrent extraction tank through the first countercurrent transition extraction tank. Then, the spiral stirring and propulsion blades in the countercurrent extraction tank gradually fill the Artemisia annua leaves and push them to the left (still in the first overall direction). Then, it is pushed into the cocurrent extraction tank through the second countercurrent transition extraction tank. Then, the spiral stirring and propulsion blades in the cocurrent extraction tank gradually fill the Artemisia annua leaves and push them to the right (still in the first overall direction). Then, it is pushed into the countercurrent slag discharge tank through the third countercurrent transition extraction tank. Then, the spiral stirring and propulsion blades in the countercurrent slag discharge tank gradually fill the Artemisia annua leaves and push them to the left (still in the first overall direction) and gradually fill them.

[0013] S2: Input the solvent into the solvent heater and heat it. Then turn on the infusion pump on the solvent injection pipe to inject the solvent from the solvent injection pipe into the countercurrent slag tank and gradually fill the countercurrent slag tank and the third countercurrent transition extraction tank (opposite to the first overall direction); this section is the first gradient countercurrent extraction.

[0014] S3: Turn on the infusion pump on the first solvent bridge pipe to input the solvent in the third countercurrent transition extraction tank into the cocurrent extraction tank through the first solvent bridge pipe, and gradually fill the cocurrent extraction tank and the second countercurrent transition extraction tank with the solvent starting from the left end of the cocurrent extraction tank (in the same direction as the first overall direction); this section is the second gradient cocurrent extraction.

[0015] S4: Turn on the infusion pump on the second solvent bridge tube to input the solvent at the right end of the co-current extraction tank into the counter-current extraction tank through the second solvent bridge tube, and gradually fill the counter-current extraction tank and the first counter-current transition extraction tank with the solvent starting from the left end of the counter-current extraction tank (opposite to the first overall direction); this section is the third gradient counter-current extraction.

[0016] S5: Turn on the infusion pump on the third solvent bridge pipe to input the solvent in the first countercurrent transition extraction tank into the co-current feed tank through the third solvent bridge pipe, and gradually fill the co-current feed tank with solvent starting from the left end (in the same direction as the first overall direction); this section is the fourth gradient co-current extraction.

[0017] S6: After the Artemisia annua leaves have filled the feed tank, the first countercurrent transition extraction tank, the countercurrent extraction tank, the second countercurrent transition extraction tank, the co-current extraction tank, the third countercurrent transition extraction tank, and the countercurrent slag discharge tank, simultaneously fill the feed tank, the first countercurrent transition extraction tank, the countercurrent extraction tank, the second countercurrent transition extraction tank, the co-current extraction tank, the third countercurrent transition extraction tank, and the countercurrent slag discharge tank with solvent. Then, continue to turn on the forward and reverse stepper motor for slow dynamic stirring and extraction. Use intermittent forward and reverse stirring with 7-10 minutes forward rotation + 1 minute pause + 2-3 minutes reverse rotation + 1 minute pause to ensure that the artemisinin material passes through the tank throughout the entire process. The total processing time is 120-135 minutes, and finally it is discharged from the slag outlet of the countercurrent slag discharge tank.

[0018] S7: Simultaneously activate the ultrasonic transducer, adopting an intermittent ultrasonic mode of "30-60s operation + 10s pause" to enhance artemisinin dissolution.

[0019] S8: Turn on the infusion pump on the extract collection tube to output and collect the solvent flowing into the feed tank, thus obtaining artemisinin extract.

[0020] S9: Input the artemisinin extract into the chromatography column for separation, obtain artemisinin and recover the solvent.

[0021] S10: Artemisia annua leaf residue is discharged from the slag outlet and fed into a desqueezer for drying, and the solvent is recovered.

[0022] Furthermore, the solvent is a composite solvent, wherein the main solvent and the green synergist are injected and mixed in a ratio of 100:4-6, and after being mixed evenly, the mixture is sent to a solvent heater and heated to 35-50°C; the main solvent is petroleum ether or ethyl acetate, and the green synergist is ethanol or lactate.

[0023] According to practical statistics, the extraction time of artemisinin using this method is reduced to about 2 hours, and the yield of artemisinin is over 99.8%, which is 0.8 percentage points higher than the original yield of 99.0%.

[0024] Compared with the prior art, the beneficial effects of the present invention are as follows: 1. Significantly improved extraction efficiency and yield: The designed four-stage continuous gradient co-current and counter-current process creates a continuous high concentration difference driving force, making extraction more complete; combined with forward and reverse stirring, it prevents material caking and channeling, and the ultrasonic cavitation effect enhances mass transfer. The synergy of multiple technologies enables the artemisinin yield to be stable at over 99.8%.

[0025] 2. The extraction cycle is significantly shortened: continuous countercurrent contact between materials and solvent, dynamic stirring and the enhanced effect of ultrasound together shorten the total extraction time from more than 3 hours to about 2 hours, and the production efficiency is increased by about 30%.

[0026] 3. Reduced solvent loss: The closed and continuous system and efficient extraction process reduce solvent evaporation and retention, resulting in high solvent recovery and a loss rate of approximately 1%.

[0027] 4. Good compatibility between the device and the process: The dedicated device eliminates the internal support that obstructs the flow of materials and adopts end bearing support. The smooth propulsion and unique solvent bridge design perfectly realize the process requirements of the method of this invention, and the operation is stable and reliable. Attached Figure Description

[0028] Figure 1 This is a schematic diagram of the continuous gradient forward and countercurrent extraction device and the path of materials and solvents in this invention.

[0029] 1. Co-current feed tank; 2. First countercurrent transition extraction tank; 3. Countercurrent extraction tank; 4. Second countercurrent transition extraction tank; 5. Co-current extraction tank; 6. Third countercurrent transition extraction tank; 7. Countercurrent slag discharge tank; 8. Stirring shaft; 9. Spiral stirring propulsion blades; 10. Feed inlet; 11. Slag outlet; 12. Solvent injection pipe; 13. First solvent bridge pipe; 14. Second solvent bridge pipe; 15. Third solvent bridge pipe; 16. Extract collection pipe; 17. Infusion pump; 18. Solvent heater; 19. Ultrasonic transducer; 20. Forward and reverse stepper motor. Detailed Implementation

[0030] The present invention will be further described below with reference to the embodiments. The following embodiments are intended to illustrate the present invention and not to further limit the present invention, and should not be used to limit the scope of protection of the present invention.

[0031] As shown in the figure, this scheme requires a continuous gradient forward and reverse flow extraction device, which includes a forward flow feed tank 1, a first counter-current transition extraction tank 2, a counter-current extraction tank 3, a second counter-current transition extraction tank 4, a forward flow extraction tank 5, a third counter-current transition extraction tank 6, and a counter-current slag discharge tank 7. The tanks are connected by 45° bevel welding. Each of the forward flow feed tank 1, counter-current extraction tank 2, forward flow extraction tank 3, and counter-current slag discharge tank 4 is equipped with a stirring shaft 8. The stirring shaft 8 is rotatably and sealed on the tank walls at both ends of its respective tank and suspended along the axis within the tank. The stirring shaft 8 is equipped with spiral stirring and propulsion blades 9. Each of the forward flow feed tank 1, counter-current extraction tank 3, forward flow extraction tank 5, and counter-current slag discharge tank 7 has a forward and reverse flow stepper motor 20 connected to the stirring shaft 8 at its left outer end. The left end of the forward flow feed tank 1 has an inlet / outlet... The feed inlet 10, the countercurrent slag discharge tank 7 has a slag outlet 11 and a solvent injection pipe 12 below the left end tank wall; the third countercurrent transition extraction tank 6 is connected to the left end of the cocurrent extraction tank 5 by a first solvent bridge pipe 13, the right end of the cocurrent extraction tank 5 is connected to the left end of the countercurrent extraction tank 3 by a second solvent bridge pipe 14, the first countercurrent transition extraction tank 2 is connected to the right end of the cocurrent feed tank 1 by a third solvent bridge pipe 15, the right end of the cocurrent feed tank 1 has an extract collection pipe 16 above the right end tank wall; the extract collection pipe 16, the solvent injection pipe 12 and the three solvent bridge pipes are all equipped with a delivery pump 17; the solvent injection pipe is equipped with a solvent heater 18; the right side wall of the first countercurrent transition extraction tank 2, the second countercurrent transition extraction tank 4 and the third countercurrent transition extraction tank 6 are each equipped with an ultrasonic transducer 19.

[0032] Based on the above-mentioned apparatus, artemisinin was dynamically extracted using continuous gradient countercurrent and forward / countercurrent methods, following these steps: Example

[0033] S1: 220 kg of dried and pulverized Artemisia annua leaf powder (artemisinin content 18‰) is fed into the feed tank 1 through the inlet 10. The forward and reverse stepper motor 20 is started to rotate forward at 12 r / min. The Artemisia annua leaves are gradually pushed to the right and filled by the spiral stirring and propulsion blades 9 in the feed tank 1. Then, it is pushed to the countercurrent extraction tank 3 through the first countercurrent transition extraction tank 2. Then, the Artemisia annua leaves are gradually filled and pushed to the left by the spiral stirring and propulsion blades 9 in the countercurrent extraction tank 3. Then, it is pushed to the cocurrent extraction tank 5 through the second countercurrent transition extraction tank 4. Then, the Artemisia annua leaves are gradually pushed to the right and filled by the spiral stirring and propulsion blades 9 in the cocurrent extraction tank 5. Then, it is pushed to the countercurrent slag discharge tank 7 through the third countercurrent transition extraction tank 6. Then, the Artemisia annua leaves are pushed to the left and gradually filled by the spiral stirring and propulsion blades 9 in the countercurrent slag discharge tank 7.

[0034] S2: Simultaneously, 735L of solvent is fed into the solvent heater 18 and heated to 43°C. Then, the infusion pump 17 on the solvent injection pipe 12 is turned on to inject the solvent from the solvent injection pipe 12 into the countercurrent slag tank 7, and the countercurrent slag tank 7 and the third countercurrent transition extraction tank 6 are gradually filled. This section is the first gradient countercurrent extraction. The solvent used here is a composite solvent, which is obtained by injecting and mixing petroleum ether and ethanol at a volume ratio of 100:5.

[0035] S3: Turn on the infusion pump 17 on the first solvent bridge pipe 13 to input the solvent in the third countercurrent transition extraction tank 6 into the cocurrent extraction tank 5 through the first solvent bridge pipe 13, and gradually fill the cocurrent extraction tank 5 and the second countercurrent transition extraction tank 4 with the solvent starting from the left end of the cocurrent extraction tank 5; this section is the second gradient cocurrent extraction.

[0036] S4: Turn on the infusion pump 17 on the second solvent bridge pipe 14 to input the solvent at the right end of the co-current extraction tank 5 into the countercurrent extraction tank 3 through the second solvent bridge pipe 14, and gradually fill the countercurrent extraction tank 3 and the first countercurrent transition extraction tank 2 with the solvent starting from the left end of the countercurrent extraction tank 3; this section is the third gradient countercurrent extraction.

[0037] S5: Turn on the infusion pump 17 on the third solvent bridge pipe 15 to input the solvent in the first countercurrent transition extraction tank 2 into the co-current feed tank 1 through the third solvent bridge pipe 15, and gradually fill the co-current feed tank 1 with solvent starting from the left end; this section is the fourth gradient co-current extraction.

[0038] S6: After the Artemisia annua leaves have filled the feed tank 1, the first countercurrent transition extraction tank 2, the countercurrent extraction tank 3, the second countercurrent transition extraction tank 4, the co-current extraction tank 5, the third countercurrent transition extraction tank 6, and the countercurrent slag discharge tank 7, simultaneously fill these tanks with solvent. Then, continue to turn on the forward and reverse stepper motor 20 for slow dynamic stirring and extraction. Use a speed of 12 r / min and an intermittent forward and reverse stirring mode of 10 minutes forward rotation + 1 minute pause + 3 minutes reverse rotation + 1 minute pause to make the artemisinin material move slowly in the tank. The total time is 128 minutes, and finally it is discharged from the slag outlet of the countercurrent slag discharge tank.

[0039] S7: Simultaneously turn on the ultrasonic transducer 19, adjust and apply a 315W, 30kHz ultrasonic field, and use intermittent ultrasonic action of "30s working + 10s pause" to enhance the dissolution of artemisinin.

[0040] S8: Turn on the infusion pump 17 on the extract collection tube 16 to output and collect the solvent flowing into the feed tank 1, thus obtaining artemisinin extract.

[0041] S9: The artemisinin extract was fed into a chromatography column for separation, yielding 3.9553 kg of artemisinin, and the solvent was recovered.

[0042] S10: Artemisia annua leaf residue is discharged from the residue outlet 11 and fed into a desqueezer for drying, and the solvent is recovered.

[0043] Measurements showed that the total recovery of the compound solvent was 727.58L, the solvent consumption was 7.42L, and the solvent consumption rate was 1.01%; the artemisinin yield was 3.9553kg, and the yield was approximately 99.88% (3.9553 ÷ (220kg × 18‰)); the extraction time was only 128 minutes, which was reduced to nearly 2 hours. Example

[0044] S1: 220 kg of dried and pulverized Artemisia annua leaf powder (artemisinin content 18‰) that has passed through a 50-mesh sieve is fed into the feed inlet 10 of the feed tank 1. The forward and reverse stepper motor 20 is started to rotate forward at a speed of 8 r / min. The Artemisia annua leaves are gradually pushed to the right and filled by the spiral stirring and propulsion blades 9 in the feed tank 1. Then, it is pushed to the countercurrent extraction tank 3 through the first countercurrent transition extraction tank 2. Then, the Artemisia annua leaves are gradually filled and pushed to the left by the spiral stirring and propulsion blades 9 in the countercurrent extraction tank 3. Then, it is pushed to the cocurrent extraction tank 5 through the second countercurrent transition extraction tank 4. Then, the Artemisia annua leaves are gradually pushed to the right and filled by the spiral stirring and propulsion blades 9 in the cocurrent extraction tank 5. Then, it is pushed to the countercurrent slag discharge tank 7 through the third countercurrent transition extraction tank 6. Then, the Artemisia annua leaves are gradually pushed to the left and filled by the spiral stirring and propulsion blades 9 in the countercurrent slag discharge tank 7.

[0045] S2: Simultaneously, 728L of solvent is fed into the solvent heater 18 and heated to 35°C. Then, the infusion pump 17 on the solvent injection pipe 12 is turned on to inject the solvent from the solvent injection pipe 12 into the countercurrent slag discharge tank 7, and the countercurrent slag discharge tank 7 and the third countercurrent transition extraction tank 6 are gradually filled. This section is the first gradient countercurrent extraction. The solvent used here is a composite solvent, which is obtained by injecting and mixing petroleum ether and ethanol in a volume ratio of 100:4 and mixing them evenly.

[0046] S3: Turn on the infusion pump 17 on the first solvent bridge pipe 13 to input the solvent in the third countercurrent transition extraction tank 6 into the cocurrent extraction tank 5 through the first solvent bridge pipe 13, and gradually fill the cocurrent extraction tank 5 and the second countercurrent transition extraction tank 4 with the solvent starting from the left end of the cocurrent extraction tank 5; this section is the second gradient cocurrent extraction.

[0047] S4: Turn on the infusion pump 17 on the second solvent bridge pipe 14 to input the solvent at the right end of the co-current extraction tank 5 into the countercurrent extraction tank 3 through the second solvent bridge pipe 14, and gradually fill the countercurrent extraction tank 3 and the first countercurrent transition extraction tank 2 with the solvent starting from the left end of the countercurrent extraction tank 3; this section is the third gradient countercurrent extraction.

[0048] S5: Turn on the infusion pump 17 on the third solvent bridge pipe 15 to input the solvent in the first countercurrent transition extraction tank 2 into the co-current feed tank 1 through the third solvent bridge pipe 15, and gradually fill the co-current feed tank 1 with solvent starting from the left end; this section is the fourth gradient co-current extraction.

[0049] S6: After the Artemisia annua leaves have filled the feed tank 1, the first countercurrent transition extraction tank 2, the countercurrent extraction tank 3, the second countercurrent transition extraction tank 4, the co-current extraction tank 5, the third countercurrent transition extraction tank 6, and the countercurrent slag discharge tank 7, simultaneously fill these tanks with solvent. Then, continue to turn on the forward and reverse stepper motor 20 for slow dynamic stirring and extraction. Use an intermittent forward and reverse stirring mode with a speed of 8 r / min, rotating forward for 10 minutes + pausing for 1 minute + reversing for 3 minutes + pausing for 1 minute, so that the artemisinin material moves slowly in the tank. The total time is 133 minutes, and finally it is discharged from the slag outlet of the countercurrent slag discharge tank.

[0050] S7: Simultaneously turn on the ultrasonic transducer 19, adjust and apply an ultrasonic field of 280W and 20kHz, and use intermittent ultrasonic action of "30s working + 10s pause" to enhance the dissolution of artemisinin.

[0051] S8: Turn on the infusion pump 17 on the extract collection tube 16 to output and collect the solvent flowing into the feed tank 1, thus obtaining artemisinin extract.

[0052] S9: The artemisinin extract was fed into a chromatography column for separation, yielding 3.9533 kg of artemisinin, and the solvent was recovered.

[0053] S10: Artemisia annua leaf residue is discharged from the residue outlet 11 and fed into a desqueezer for drying, and the solvent is recovered.

[0054] Measurements showed that the total recovery of the compound solvent was 720.14L, the solvent consumption was 7.86L, and the solvent consumption rate was 1.08%; the artemisinin yield was 3.9533kg, and the yield was 3.9533÷(220kg×18‰)≈99.83%; the extraction time was only 133 minutes, which was reduced to nearly 2 hours. Example

[0055] S1: 220 kg of dried and pulverized Artemisia annua leaf powder (artemisinin content 18‰) that has passed through a 40-mesh sieve is fed into the feed inlet 10 of the feed tank 1. The forward and reverse stepper motor 20 is started to rotate forward at a speed of 16 r / min. The Artemisia annua leaves are gradually pushed to the right and filled by the spiral stirring and propulsion blades 9 in the feed tank 1. Then, it is pushed to the countercurrent extraction tank 3 through the first countercurrent transition extraction tank 2. Then, the Artemisia annua leaves are gradually filled and pushed to the left by the spiral stirring and propulsion blades 9 in the countercurrent extraction tank 3. Then, it is pushed to the cocurrent extraction tank 5 through the second countercurrent transition extraction tank 4. Then, the Artemisia annua leaves are gradually pushed to the right and filled by the spiral stirring and propulsion blades 9 in the cocurrent extraction tank 5. Then, it is pushed to the countercurrent slag discharge tank 7 through the third countercurrent transition extraction tank 6. Then, the Artemisia annua leaves are pushed to the left and gradually filled by the spiral stirring and propulsion blades 9 in the countercurrent slag discharge tank 7.

[0056] S2: Simultaneously, 742L of solvent is fed into the solvent heater 18 and heated to 50°C. Then, the infusion pump 17 on the solvent injection pipe 12 is turned on to inject the solvent from the solvent injection pipe 12 into the countercurrent slag discharge tank 7, and the countercurrent slag discharge tank 7 and the third countercurrent transition extraction tank 6 are gradually filled. This section is the first gradient countercurrent extraction. The solvent used here is a composite solvent, which is obtained by injecting and mixing petroleum ether and ethanol in a volume ratio of 100:6 and mixing them evenly.

[0057] S3: Turn on the infusion pump 17 on the first solvent bridge pipe 13 to input the solvent in the third countercurrent transition extraction tank 6 into the cocurrent extraction tank 5 through the first solvent bridge pipe 13, and gradually fill the cocurrent extraction tank 5 and the second countercurrent transition extraction tank 4 with the solvent starting from the left end of the cocurrent extraction tank 5; this section is the second gradient cocurrent extraction.

[0058] S4: Turn on the infusion pump 17 on the second solvent bridge pipe 14 to input the solvent at the right end of the co-current extraction tank 5 into the countercurrent extraction tank 3 through the second solvent bridge pipe 14, and gradually fill the countercurrent extraction tank 3 and the first countercurrent transition extraction tank 2 with the solvent starting from the left end of the countercurrent extraction tank 3; this section is the third gradient countercurrent extraction.

[0059] S5: Turn on the infusion pump 17 on the third solvent bridge pipe 15 to input the solvent in the first countercurrent transition extraction tank 2 into the co-current feed tank 1 through the third solvent bridge pipe 15, and gradually fill the co-current feed tank 1 with solvent starting from the left end; this section is the fourth gradient co-current extraction.

[0060] S6: After the Artemisia annua leaves have filled the feed tank 1, the first countercurrent transition extraction tank 2, the countercurrent extraction tank 3, the second countercurrent transition extraction tank 4, the co-current extraction tank 5, the third countercurrent transition extraction tank 6, and the countercurrent slag discharge tank 7, simultaneously fill these tanks with solvent. Then, continue to turn on the forward and reverse stepper motor 20 for slow dynamic stirring and extraction. Use a speed of 16 r / min and an intermittent forward and reverse stirring mode of 10 minutes forward rotation + 1 minute pause + 3 minutes reverse rotation + 1 minute pause to make the artemisinin material move slowly in the tank. The total time is 123 minutes, and finally it is discharged from the slag outlet of the countercurrent slag discharge tank.

[0061] S7: Simultaneously turn on the ultrasonic transducer 19, adjust and apply an ultrasonic field of 350W and 40kHz, and use intermittent ultrasonic action of "30s working + 10s pause" to enhance the dissolution of artemisinin.

[0062] S8: Turn on the infusion pump 17 on the extract collection tube 16 to output and collect the solvent flowing into the feed tank 1, thus obtaining artemisinin extract.

[0063] S9: The artemisinin extract was fed into a chromatography column for separation, yielding 3.9521 kg of artemisinin, and the solvent was recovered.

[0064] S10: Artemisia annua leaf residue is discharged from the residue outlet 11 and fed into a desqueezer for drying, and the solvent is recovered.

[0065] Measurements showed that the total recovery of the compound solvent was 733.69L, the solvent consumption was 8.31L, and the solvent consumption rate was 1.12%; the artemisinin yield was 3.9521kg, and the yield was 3.9553 ÷ (220kg × 18‰) ≈ 99.80%; the extraction time was only 123 minutes, which was reduced to nearly 2 hours.

[0066] This method employs intermittent countercurrent and cocurrent flow of solvent and material, along with continuous gradient cocurrent and countercurrent dynamic stirring, combined with ultrasonic extraction. This effectively improves the extraction efficiency of artemisinin, reduces solvent consumption, and significantly shortens the extraction time. The continuous extraction time is now just over 2 hours, a substantial reduction from the previous 3 hours.

Claims

1. A method for extracting artemisinin using a continuous gradient countercurrent extraction process, characterized in that... Includes the following steps: S1: Material conveying steps: Artemisia annua material is conveyed sequentially in the first direction through the downstream feeding section, the first transition section, the countercurrent extraction section, the second transition section, the downstream extraction section, the third transition section, and the countercurrent slag discharge section; S2: Solvent gradient countercurrent step: The extraction solvent is injected into the countercurrent slag discharge section in a direction generally opposite to the first direction, and the solvent is controlled to fill the co-current extraction section through the third transition section, the countercurrent extraction section through the second transition section, and the co-current feed section through the first transition section in sequence, so that the flow path of the solvent and the flow path of the material form a continuous gradient co-current and countercurrent contact. S3: Dynamic stirring step: During the extraction process, the material located in the co-current feeding section, counter-current extraction section, co-current extraction section and counter-current slag discharge section is periodically stirred in both forward and reverse directions; S4: Extraction step: Collect artemisinin-rich extract from the downstream feed section.

2. The extraction method according to claim 1, characterized in that... In step S2, the transfer of the solvent is achieved through a solvent bridge pipe and a delivery pump connected between the corresponding sections.

3. The extraction method according to claim 1, characterized in that... An ultrasonic field is applied to the first transition section, the second transition section, and / or the third transition section to assist in extraction.

4. The extraction method according to claim 3, characterized in that... The ultrasonic field is applied in an intermittent pulse mode.

5. The extraction method according to claim 1, characterized in that... The extraction solvent is a composite solvent containing a main solvent and a green synergist. The main solvent is selected from petroleum ether or ethyl acetate, and the green synergist is selected from ethanol or lactate.

6. The extraction method according to claim 1 or 5, characterized in that... In step S2, the extraction solvent is heated to 35-50°C and then injected.

7. The extraction method according to claim 1, characterized in that... The periodic forward and reverse stirring pattern described in step S3 is as follows: rotate forward for a period of time, then pause, then rotate in reverse for a period of time, then pause, and repeat this process.

8. An artemisinin continuous gradient countercurrent extraction apparatus for implementing the extraction method according to any one of claims 1-7, characterized in that, include: The following tanks are connected in series to form a material channel: a feed tank (1), a first countercurrent transition extraction tank (2), a countercurrent extraction tank (3), a second countercurrent transition extraction tank (4), a cocurrent extraction tank (5), a third countercurrent transition extraction tank (6), and a countercurrent slag discharge tank (7). The co-current feed tank (1), counter-current extraction tank (3), co-current extraction tank (5) and counter-current slag discharge tank (7) are all equipped with stirring shafts (8), and the stirring shafts (8) are equipped with spiral stirring and propulsion blades (9). Each stirring shaft (8) is connected to a stepper motor (20) that can drive it to rotate forward and backward. The forward flow feed tank (1) is provided with a feed inlet (10) and an extract collection pipe (16), and the countercurrent slag discharge tank (7) is provided with a slag discharge outlet (11) and a solvent injection pipe (12). The first solvent bridge pipe (13) connects the input end of the third countercurrent transition extraction tank (6) and the cocurrent extraction tank (5); The second solvent bridge pipe (14) connects the output end of the co-current extraction tank (5) with the input end of the counter-current extraction tank (3); The third solvent bridge pipe (15) connects the input end of the first countercurrent transition extraction tank (2) and the forward flow feed tank (1); Each of the extract collection tube (16), solvent injection tube (12) and solvent bridge tube is equipped with an infusion pump (17).

9. The extraction apparatus according to claim 8, characterized in that, An ultrasonic transducer (19) is provided on at least one of the first countercurrent transition extraction tank (2), the second countercurrent transition extraction tank (4), and the third countercurrent transition extraction tank (6).

10. The extraction apparatus according to claim 8, characterized in that, A solvent heater (18) is provided on the solvent injection pipe (12).

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