Method for extracting and purifying artemisinin

Abstract

The invention provides an extraction and purification method of artemisinin, and belongs to the technical field of artemisinin. The method comprises the following steps: adding artemisia apiacea powder into an ionic liquid solution, introducing carbon dioxide, extracting and filtering under an ultrasonic treatment condition, adding a magnetic extractant and an imprinting extractant into filtrate, heating, stirring, extracting and filtering, separating the adsorbed magnetic extractant and imprinting extractant from solids through an external magnetic field, respectively adding the magnetic extractant and imprinting extractant into an elution solvent, and eluting to obtain an eluent; the method comprises the following steps of: respectively obtaining an artemisinin eluent and an artemisinin eluent, removing a solvent under reduced pressure to obtain artemisinin, adding an artemisinin product into a methanol aqueous solution, washing, and crystallizing at low temperature to obtain the high-purity artemisinin. The extraction and purification method of artemisinin is simple, conditions are mild, high-efficiency and high-purity separation and purification of artemisinin can be achieved, and the purity gt of artemisinin is obtained; therefore, the application value of the method is greatly improved.

Description

Technical Field

[0001] The present invention relates to the technical field of artemisinin, and specifically relates to a method for extracting and purifying artemisinin. Background Art

[0002] Artemisinin is a colorless needle-shaped crystal and a sesquiterpene lactone containing a peroxide group. Chinese scientist Tu Youyou first discovered and successfully extracted artemisinin from Artemisia annua. The combination therapy mainly based on artemisinin drugs is the most effective means for treating malaria at present, with advantages such as rapid effect, low toxicity, and safety. With the continuous in-depth research, researchers have found that artemisinin drugs also have various pharmacological effects such as anti-tumor, treatment of polycystic ovary syndrome, anti-diabetes, immune regulation, anti-virus, and prevention of cardiovascular diseases.

[0003] There are two production methods of artemisinin: artificial synthesis or extraction from the natural plant Artemisia annua. At present, there have been many reports on the methods for extracting, separating, and purifying artemisinin.

[0004] For example, Chinese Patent Application CN107827904A discloses a method for purifying artemisinin, which includes the following steps: S1. After the artemisinin extraction solution is separated and purified by column chromatography, a column eluate is obtained; S2. Take the column eluate and concentrate it at 40 - 85°C. The volume after concentration is 1 / 10 - 1 / 20 of that before concentration. After standing for crystallization, the crude product is taken out and dried for standby; S3. Add alcohol to the crude product, dissolve it, stand for crystallization, filter, and take the crystal to obtain artemisinin. The artemisinin purification method provided by this patent can effectively reduce the content of impurity B and control the content of impurity B below 0.2%. However, since this purification method uses column separation for purification, it is not conducive to large-scale industrial production, and the recovery rate of artemisinin is relatively low.

[0005] Another example is Chinese Invention Patent CN102219790B, which discloses a green extraction process for artemisinin, including (1) drying treatment of raw materials; (2) primary preparation of artemisinin: after the treated raw materials are extracted with petroleum ether and separated, the supernatant is eluted through a silica gel column. When crystals start to precipitate after concentrating the obtained eluate, crystallization is carried out in a crystallization tank for 15 - 20 hours. After crystallization is completed, filtration is carried out to obtain crude artemisinin crystals; (3) refining of artemisinin: dissolve the crude artemisinin crystals obtained in step (2) in a precipitation tank and let it stand. Take the supernatant and filter it precisely. Concentrate the filtrate, crystallize for 15 - 20 hours, and then remove the mother liquor to obtain fine artemisinin. This method saves energy and reduces consumption, and solves the problem that artemisinin is decomposed by heat during the extraction process, which affects the yield. However, the process flow takes a long time, such as each crystallization is more than 15 hours, seriously affecting the experimental efficiency; and the use of a silica gel column for purification results in a relatively low recovery rate of artemisinin. Summary of the Invention

[0006] The object of the present invention is to provide a method for extracting and purifying artemisinin, which is simple in method and mild in conditions, and can achieve the efficient and high-purity separation and purification of artemisinin. The obtained artemisinin has a purity > 99.99%, greatly improving its application value.

[0007] The technical solution of the present invention is realized as follows:

[0008] The present invention provides a method for extracting and purifying artemisinin. Artemisia annua powder is added to an ionic liquid solution, carbon dioxide is introduced, and extraction is carried out under ultrasonic treatment conditions. After filtration, a magnetic extractant and an imprinted extractant are added to the filtrate, and extraction is carried out by heating and stirring. After filtration, the solid is separated by an external magnetic field to obtain the adsorbed magnetic extractant and imprinted extractant, which are respectively added to an elution solvent for elution to obtain an artemene eluate and an artemisinin eluate. The solvent is removed under reduced pressure to obtain artemene. The artemisinin product is washed with an aqueous methanol solution and crystallized at low temperature to obtain high-purity artemisinin.

[0009] As a further improvement of the present invention, the ionic liquid is selected from at least one of 1-butyl-3-methylimidazolium hexafluorophosphate, 1-ethyl-3-methylimidazolium tetrafluoroborate, 1-butylpyridinium hexafluorophosphate, tetrabutylammonium hexafluorophosphate, tetraethylphosphonium triphenylphosphate, 1-butylpyrrole hexafluorophosphate, and 1-vinyl-3-butylimidazolium hexafluorophosphate. The elution solvent is a mixed solution of n-hexane and diethyl ether with a volume ratio of 75-85:15-25.

[0010] As a further improvement of the present invention, the ventilation rate of carbon dioxide is 5-10 mL / min, the power of the ultrasonic treatment conditions is 1500-2500 W, and the extraction time is 2-4 h; the mass ratio of the artemisia annua powder, the magnetic extractant, and the imprinted extractant is 15-20:1-3:2-5; the temperature of the heating and stirring extraction is 45-55 °C, and the time is 1-2 h. The temperature of the low-temperature crystallization is 1-2 °C, and the concentration of the aqueous methanol solution is 60-80 wt%.

[0011] As a further improvement of the present invention, the preparation method of the magnetic extractant is as follows:

[0012] S1. Magnetic iron oxide particles are added to ethanol, and a silane coupling agent with a double bond is added. The reaction is carried out by heating and stirring, separated by a magnet, washed, and dried to obtain modified magnetic iron oxide particles;

[0013] S2. The modified magnetic iron oxide particles and the ionic liquid are added to water, an initiator is added, and the reaction is carried out by heating. After separation by a magnet, washing, and drying, ionic liquid-modified magnetic iron oxide particles are obtained;

[0014] S3. Add the ionic liquid-modified magnetic Fe₃O₄ particles to the graphene oxide aqueous dispersion, stir to disperse evenly, spray dry, and reduce with hydrazine hydrate vapor to obtain the magnetic extractant.

[0015] As a further improvement of the present invention, in step S1, the mass ratio of the magnetic Fe₃O₄ particles to the silane coupling agent with a double bond is 10:3 - 4, the temperature of the heating and stirring reaction is 45 - 55 °C, and the time is 2 - 4 h; in step S2, the mass ratio of the modified magnetic Fe₃O₄ particles, the ionic liquid and the initiator is 7 - 10:3 - 4:0.1 - 0.12, the temperature of the heating reaction is 60 - 70 °C, and the time is 3 - 5 h; in step S3, the solid-liquid ratio of the ionic liquid-modified magnetic Fe₃O₄ particles to the graphene oxide aqueous dispersion is 1:3 - 5 g / mL, the concentration of the graphene oxide aqueous dispersion is 0.5 - 1 mg / mL, and the time of the reduction with hydrazine hydrate vapor is 10 - 12 h.

[0016] As a further improvement of the present invention, the silane coupling agent with a double bond is selected from at least one of KH570, A151, and A171, the ionic liquid is selected from at least one of 1-vinyl-3-butylimidazolium tetrafluoroborate, 1-vinyl-3-ethylimidazolium tetrafluoroborate, 1-vinyl-3-methylimidazolium tetrafluoroborate, and 1-vinyl-3-hexylimidazolium tetrafluoroborate, and the initiator is selected from at least one of sodium persulfate, potassium persulfate, and ammonium persulfate.

[0017] As a further improvement of the present invention, the preparation method of the imprinted extractant is as follows:

[0018] T1. Add the silica nanospheres to the graphene oxide aqueous dispersion, spray dry to obtain graphene oxide@silica nanospheres, add the graphene oxide@silica nanospheres to ethanol, add the silane coupling agent with a double bond, heat and stir to react, centrifuge, wash, and dry to obtain the modified silica nanospheres;

[0019] T2. Add the ionic liquid, acrylamide, artemisinin, methyl methacrylate, crosslinking agent, and modified silica nanospheres to water, add the initiator, heat to react, centrifuge, wash, and dry to obtain the copolymer;

[0020] T3. Add the copolymer to the elution solvent for heating and reflux elution, centrifuge, wash, and dry to obtain the imprinted extractant.

[0021] As a further improvement of the present invention, in step T1, the solid-liquid ratio of the silica nanospheres and the graphene oxide aqueous dispersion is 1:3 - 5 g / mL, the concentration of the graphene oxide aqueous dispersion is 0.5 - 1 mg / mL, the mass ratio of the graphene oxide@silica nanospheres to the silane coupling agent with a double bond is 10:2 - 3, the temperature of the heating and stirring reaction is 40 - 50 °C, and the time is 2 - 4 h; in step T2, the mass ratio of the ionic liquid, acrylamide, artemisinin, methyl methacrylate, crosslinking agent, modified silica nanospheres and initiator is 1 - 3:6 - 8:2 - 4:1 - 3:0.05 - 0.1:5 - 7:0.01 - 0.012; in step T3, the elution solvent is a mixed solution of n-hexane and ether, and the volume ratio is 75 - 85:15 - 25.

[0022] As a further improvement of the present invention, the silane coupling agent with a double bond is selected from at least one of KH570, A151, and A171, the ionic liquid is selected from at least one of 1-vinyl-3-butylimidazolium tetrafluoroborate, 1-vinyl-3-ethylimidazolium tetrafluoroborate, 1-vinyl-3-methylimidazolium tetrafluoroborate, and 1-vinyl-3-hexylimidazolium tetrafluoroborate, the initiator is selected from at least one of sodium persulfate, potassium persulfate, and ammonium persulfate, and the crosslinking agent is ethylene glycol dimethacrylate.

[0023] As a further improvement of the present invention, the purity of the high-purity artemisinin > 99.99%.

[0024] The present invention has the following beneficial effects:

[0025] The present invention prepares a magnetic extractant, which uses magnetic iron tetroxide particles as a carrier, is modified on the surface with a silane coupling agent with a double bond, and copolymerizes with an ionic liquid with a double bond after having a double bond, thereby obtaining a composite in which the ionic liquid is copolymerized on the surface of the magnetic iron tetroxide particles. The C=C in the ionic liquid can form a π-π interaction with the artemene unsaturated bond, enabling the ionic liquid to recognize artemene at the molecular level, and thus achieving a highly selective separation of the two. At the same time, the problem of difficult recycling of ionic liquids in an aqueous solution system is also overcome. In addition, the surface is spray-dried and coated with wrinkled graphene oxide and reduced to graphene. The large π bond of the benzene ring of graphene can also efficiently adsorb artemene by forming a π-π interaction. At the same time, the prepared magnetic extractant can be magnetically separated, thereby efficiently separating artemene and solving the technical problem of difficult separation between artemene and artemisinin.

[0026] The present invention prepares an imprinted extractant. Using silica nanospheres as the carrier, the surface is coated with wrinkled graphene oxide by spray drying, greatly increasing the specific surface area of the carrier. Further modified with a silane coupling agent with double bonds, the double bonds of the carrier are copolymerized with ionic liquid, acrylamide, and methyl methacrylate, and crosslinked with ethylene glycol dimethacrylate. Artemisinin is used as the porogen, thus obtaining the imprinted extractant, which has a rigid structure and greatly improves the mechanical properties of the polymer-coated spheres. At the same time, the ionic liquid polymer has both the characteristics of ionic liquid and polymer, overcomes the fluidity of ionic liquid, has lower loss during the treatment process, and can also solve the problem of easy residue of ionic liquid in the liquid-liquid extraction system. At the same time, it has good compatibility in the ionic liquid dispersion system and is not easy to flocculate and affect the extraction and separation effect. After eluting to remove the porogen artemisinin, the pore size formed in the prepared imprinted extract is highly similar to that of artemisinin, and it can efficiently selectively adsorb artemisinin in the extract to achieve the efficient separation of artemisinin. Artemisinene is often easily confused due to its similar structure, but artemisinene is more likely to nucleophilize with the magnetic extractant due to its C=C double bond, thus realizing the efficient separation of artemisinin and artemisinene.

[0027] In the extraction process of the present invention, an ionic liquid is used as the extractant, and the physical and chemical effects of ultrasonic waves are utilized to enhance the heat and mass transfer efficiency of the extraction process, thereby realizing a method for efficient extraction of natural products. At the same time, carbon dioxide is introduced to increase the polarity of the ionic liquid, thereby increasing the extraction rate of artemisinin by the ionic liquid. During the heating process, carbon dioxide escapes from the ionic liquid, accelerating the interaction between artemisinin and the extractant, thereby promoting its adsorption by the extractant. At the same time, the introduction of a magnetic extractant and an imprinted extractant overcomes the problem of easy residue of ionic liquid in the drug. Instead of separating artemisinin from the ionic liquid, it only needs to separate the extractant, and the magnetic extractant can be separated by magnetic separation to obtain the imprinted extractant adsorbed with a large amount of artemisinin. The purified artemisinin can be obtained by elution, and the purity of the product is further improved by low-temperature crystallization.

[0028] The method for extraction and purification of artemisinin of the present invention is simple and the conditions are mild, which can realize the efficient and high-purity separation and purification of artemisinin. The purity of the obtained artemisinin is >99.99%, greatly improving its application value. Detailed implementation manners

[0029] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0030] Graphene oxide, sheet diameter: 0.5 - 5 μm; thickness: 0.8 - 1.2 nm.

[0031] Preparation Example 1 Preparation of Magnetic Extractor

[0032] The method is as follows:

[0033] S1. Add 10 g of magnetic iron oxide particles to 150 mL of ethanol, add 3 g of silane coupling agent A151 with double bonds, heat to 45 °C, stir and react for 2 h, separate by magnet, wash, and dry to obtain modified magnetic iron oxide particles;

[0034] S2. Add 7 g of modified magnetic iron oxide particles and 3 g of 1 - vinyl - 3 - butylimidazolium tetrafluoroborate to 200 mL of water, add 0.1 g of sodium persulfate, heat to 60 °C, stir and react for 3 h, separate by magnet, wash, and dry to obtain ionic liquid - modified magnetic iron oxide particles;

[0035] S3. Add 10 g of ionic liquid - modified magnetic iron oxide particles to 30 mL of 0.5 mg / mL graphene oxide aqueous dispersion, stir and mix for 10 min, spray - dry, and reduce with hydrazine hydrate vapor for 10 h to obtain the magnetic extractor.

[0036] Preparation Example 2 Preparation of Magnetic Extractor

[0037] The method is as follows:

[0038] S1. Add 10 g of magnetic iron oxide particles to 150 mL of ethanol, add 4 g of silane coupling agent A171 with double bonds, heat to 55 °C, stir and react for 4 h, separate by magnet, wash, and dry to obtain modified magnetic iron oxide particles;

[0039] S2. Add 10 g of modified magnetic iron oxide particles and 4 g of 1 - vinyl - 3 - methylimidazolium tetrafluoroborate to 200 mL of water, add 0.12 g of potassium persulfate, heat to 70 °C, stir and react for 5 h, separate by magnet, wash, and dry to obtain ionic liquid - modified magnetic iron oxide particles;

[0040] S3. Add 10 g of ionic liquid - modified magnetic iron oxide particles to 50 mL of 1 mg / mL graphene oxide aqueous dispersion, stir and mix for 10 min, spray - dry, and reduce with hydrazine hydrate vapor for 12 h to obtain the magnetic extractor.

[0041] Preparation Example 3 Preparation of Magnetic Extractor

[0042] The method is as follows:

[0043] S1. Add 10 g of magnetic iron oxide particles to 150 mL of ethanol, add 3.5 g of silane coupling agent KH570 with double bonds, heat to 50 °C, stir and react for 3 h, separate by magnet, wash, and dry to obtain modified magnetic iron oxide particles;

[0044] S2. Add 8.5 g of modified magnetic iron oxide particles and 3.5 g of 1-vinyl-3-ethylimidazolium tetrafluoroborate to 200 mL of water, add 0.11 g of ammonium persulfate, heat to 65 °C, stir and react for 4 h, separate by magnet, wash, and dry to obtain ionic liquid-modified magnetic iron oxide particles;

[0045] S3. Add 10 g of ionic liquid-modified magnetic iron oxide particles to 40 mL of 0.7 mg / mL graphene oxide aqueous dispersion, stir and mix for 10 min, spray dry, and reduce with hydrazine hydrate vapor for 11 h to obtain a magnetic extractant.

[0046] Comparative Preparation Example 1

[0047] Compared with Preparation Example 3, the difference is that step S2 is not carried out.

[0048] Specifically as follows:

[0049] S1. Add 10 g of magnetic iron oxide particles to 150 mL of ethanol, add 3.5 g of silane coupling agent KH570 with double bonds, heat to 50 °C, stir and react for 3 h, separate by magnet, wash, and dry to obtain modified magnetic iron oxide particles;

[0050] S2. Add 10 g of modified magnetic iron oxide particles to 40 mL of 0.7 mg / mL graphene oxide aqueous dispersion, stir and mix for 10 min, spray dry, and reduce with hydrazine hydrate vapor for 11 h to obtain a magnetic extractant.

[0051] Comparative Preparation Example 2

[0052] Compared with Preparation Example 3, the difference is that step S3 is not carried out.

[0053] Specifically as follows:

[0054] S1. Add 10 g of magnetic iron oxide particles to 150 mL of ethanol, add 3.5 g of silane coupling agent KH570 with double bonds, heat to 50 °C, stir and react for 3 h, separate by magnet, wash, and dry to obtain modified magnetic iron oxide particles;

[0055] S2. Add 8.5 g of modified magnetic iron oxide particles and 3.5 g of 1-vinyl-3-ethylimidazolium tetrafluoroborate to 200 mL of water, add 0.11 g of ammonium persulfate, heat to 65 °C, stir and react for 4 h, separate with a magnet, wash, and dry to obtain ionic liquid-modified magnetic iron oxide particles, which are magnetic extractants.

[0056] Preparation of the imprinted extractant in Preparation Example 4

[0057] The method is as follows:

[0058] T1. Add 10 g of silica nanospheres to 30 mL of 0.5 mg / mL graphene oxide aqueous dispersion, spray dry to obtain graphene oxide@silica nanospheres. Add 10 g of graphene oxide@silica nanospheres to 200 mL of ethanol, add 2 g of silane coupling agent A171 with double bonds, heat to 40 °C, stir and react for 2 h, centrifuge, wash, and dry to obtain modified silica nanospheres;

[0059] T2. Add 1 g of 1-vinyl-3-methylimidazolium tetrafluoroborate, 6 g of acrylamide, 2 g of artemisinin, 1 g of methyl methacrylate, 0.05 g of ethylene glycol dimethacrylate, and 5 g of modified silica nanospheres to 150 mL of water, add 0.01 g of ammonium persulfate, heat to 70 °C, stir and react for 5 h, centrifuge, wash, and dry to obtain a copolymer;

[0060] T3. Add 10 g of the copolymer to 100 mL of an elution solvent, heat under reflux for 10 h, centrifuge, wash, and dry to obtain the imprinted extractant;

[0061] The elution solvent is a mixed solution of n-hexane and diethyl ether with a volume ratio of 75:15.

[0062] Preparation of the imprinted extractant in Preparation Example 5

[0063] The method is as follows:

[0064] T1. Add 10 g of silica nanospheres to 50 mL of 1 mg / mL graphene oxide aqueous dispersion, spray dry to obtain graphene oxide@silica nanospheres. Add 10 g of graphene oxide@silica nanospheres to 200 mL of ethanol, add 3 g of silane coupling agent A151 with double bonds, heat to 50 °C, stir and react for 4 h, centrifuge, wash, and dry to obtain modified silica nanospheres;

[0065] T2. Add 3 g of 1-vinyl-3-hexylimidazolium tetrafluoroborate, 8 g of acrylamide, 4 g of artemisinin, 3 g of methyl methacrylate, 0.1 g of ethylene glycol dimethacrylate, and 7 g of modified silica nanospheres to 150 mL of water. Add 0.012 g of potassium persulfate, heat to 70 °C, stir and react for 5 h, centrifuge, wash, and dry to obtain a copolymer;

[0066] T3. Add 10 g of the copolymer to 100 mL of an elution solvent, heat under reflux for elution for 10 h, centrifuge, wash, and dry to obtain an imprinted extractant;

[0067] The elution solvent is a mixed solution of n-hexane and ether with a volume ratio of 85:25.

[0068] Preparation of the imprinted extractant in Preparation Example 6

[0069] The method is as follows:

[0070] T1. Add 10 g of silica nanospheres to 40 mL of a 0.7 mg / mL graphene oxide aqueous dispersion, spray dry to obtain graphene oxide@silica nanospheres. Add 10 g of graphene oxide@silica nanospheres to 200 mL of ethanol, add 2.5 g of a silane coupling agent KH570 with double bonds, heat to 45 °C, stir and react for 3 h, centrifuge, wash, and dry to obtain modified silica nanospheres;

[0071] T2. Add 2 g of 1-vinyl-3-butylimidazolium tetrafluoroborate, 7 g of acrylamide, 3 g of artemisinin, 2 g of methyl methacrylate, 0.07 g of ethylene glycol dimethacrylate, and 6 g of modified silica nanospheres to 150 mL of water. Add 0.011 g of sodium persulfate, heat to 70 °C, stir and react for 5 h, centrifuge, wash, and dry to obtain a copolymer;

[0072] T3. Add 10 g of the copolymer to 100 mL of an elution solvent, heat under reflux for elution for 10 h, centrifuge, wash, and dry to obtain an imprinted extractant;

[0073] The elution solvent is a mixed solution of n-hexane and ether with a volume ratio of 80:20.

[0074] Comparative Preparation Example 3

[0075] Compared with Preparation Example 6, the difference is that graphene oxide is not added in step T1.

[0076] Specifically as follows:

[0077] T1. Add 10 g of silica nanospheres to 200 mL of ethanol, add 2.5 g of the silane coupling agent KH570 with double bonds, heat to 45 °C, stir and react for 3 h, centrifuge, wash, and dry to obtain modified silica nanospheres;

[0078] T2. Add 2 g of 1-vinyl-3-butylimidazolium tetrafluoroborate, 7 g of acrylamide, 3 g of artemisinin, 2 g of methyl methacrylate, 0.07 g of ethylene glycol dimethacrylate, and 6 g of modified silica nanospheres to 150 mL of water, add 0.011 g of sodium persulfate, heat to 70 °C, stir and react for 5 h, centrifuge, wash, and dry to obtain a copolymer;

[0079] T3. Add 10 g of the copolymer to 100 mL of an elution solvent, heat under reflux for 10 h, centrifuge, wash, and dry to obtain an imprinted extractant;

[0080] The elution solvent is a mixed solution of n-hexane and ether with a volume ratio of 80:20.

[0081] Comparative Preparation Example 4

[0082] Compared with Preparation Example 6, the difference is that 1-vinyl-3-butylimidazolium tetrafluoroborate is not added in step T2.

[0083] Specifically as follows:

[0084] T1. Add 10 g of silica nanospheres to 40 mL of a 0.7 mg / mL graphene oxide aqueous dispersion, spray dry to obtain graphene oxide@silica nanospheres, add 10 g of graphene oxide@silica nanospheres to 200 mL of ethanol, add 2.5 g of the silane coupling agent KH570 with double bonds, heat to 45 °C, stir and react for 3 h, centrifuge, wash, and dry to obtain modified silica nanospheres;

[0085] T2. Add 7 g of acrylamide, 3 g of artemisinin, 2 g of methyl methacrylate, 0.07 g of ethylene glycol dimethacrylate, and 6 g of modified silica nanospheres to 150 mL of water, add 0.011 g of sodium persulfate, heat to 70 °C, stir and react for 5 h, centrifuge, wash, and dry to obtain a copolymer;

[0086] T3. Add 10 g of the copolymer to 100 mL of an elution solvent, heat under reflux for 10 h, centrifuge, wash, and dry to obtain an imprinted extractant;

[0087] The elution solvent is a mixed solution of n-hexane and ether with a volume ratio of 80:20.

[0088] Comparative Preparation Example 5

[0089] Compared with Preparation Example 6, the difference lies in that modified silica nanospheres were not added in Step T2.

[0090] Specifically as follows:

[0091] T1. Add 2 g of 1-vinyl-3-butylimidazolium tetrafluoroborate, 7 g of acrylamide, 3 g of artemisinin, 2 g of methyl methacrylate, and 0.07 g of ethylene glycol dimethacrylate to 150 mL of water. Add 0.011 g of sodium persulfate, heat to 70 °C, stir and react for 5 h, centrifuge, wash, and dry to obtain a copolymer.

[0092] T2. Add 10 g of the copolymer to 100 mL of an elution solvent, heat under reflux for 10 h, centrifuge, wash, and dry to obtain an imprinted extractant.

[0093] The elution solvent is a mixed solution of n-hexane and ether with a volume ratio of 80:20.

[0094] Example 1

[0095] This example provides a method for extracting and purifying artemisinin, including the following steps:

[0096] Add 15 g of artemisinin powder (the artemisinin is from Bozhou Traditional Chinese Medicine Base in Anhui, and the artemisinin powder is prepared by powdering and drying) to 200 mL of 1-butyl-3-methylimidazolium hexafluorophosphate solution, introduce carbon dioxide with a ventilation rate of 5 mL / min, extract under ultrasonic treatment at 1500 W for 2 h, filter, add 1 g of the magnetic extractant prepared in Preparation Example 1 and 2 g of the imprinted extractant prepared in Preparation Example 4 to the filtrate, heat to 45 °C, stir and extract for 1 h, filter, and the solid is separated by an external magnetic field to obtain the adsorbed magnetic extractant and imprinted extractant, which are respectively added to the elution solvent for elution to obtain an artemene eluate and an artemisinin eluate, and the solvent is removed under reduced pressure to obtain artemene. The artemisinin product is washed with a 60 wt% methanol aqueous solution and crystallized at 1 °C to obtain high-purity artemisinin; the elution solvent is a mixed solution of n-hexane and ether with a volume ratio of 75:15.

[0097] Example 2

[0098] This example provides a method for extracting and purifying artemisinin, including the following steps:

[0099] Add 20 g of Artemisia annua powder (the Artemisia annua is from the traditional Chinese medicine base in Bozhou, Anhui, and the powder is obtained by powdering and drying) to 200 mL of 1-ethyl-3-methylimidazolium tetrafluoroborate solution, introduce carbon dioxide with a ventilation rate of 10 mL / min, extract under ultrasonic treatment at 2500 W for 4 h, filter, add 3 g of the magnetic extractant prepared in Preparation Example 2 and 5 g of the imprinted extractant prepared in Preparation Example 5 to the filtrate, heat to 55 °C, stir and extract for 2 h, filter, and separate the adsorbed magnetic extractant and imprinted extractant through an external magnetic field. Add them to the elution solvent for elution respectively to obtain the artemisinene eluate and artemisinin eluate, remove the solvent under reduced pressure to obtain artemisinene, wash the artemisinin product with an aqueous methanol solution of 80 wt%, and crystallize at 2 °C to obtain high-purity artemisinin; the elution solvent is a mixed solution of n-hexane and diethyl ether with a volume ratio of 85:25.

[0100] Example 3

[0101] This example provides a method for extracting and purifying artemisinin, including the following steps:

[0102] Add 17 g of Artemisia annua powder (the Artemisia annua is from the traditional Chinese medicine base in Bozhou, Anhui, and the powder is obtained by powdering and drying) to 200 mL of 1-butyl-3-methylimidazolium hexafluorophosphate solution, introduce carbon dioxide with a ventilation rate of 7 mL / min, extract under ultrasonic treatment at 2000 W for 3 h, filter, add 2 g of the magnetic extractant prepared in Preparation Example 3 and 3 g of the imprinted extractant prepared in Preparation Example 6 to the filtrate, heat to 50 °C, stir and extract for 1.5 h, filter, and separate the adsorbed magnetic extractant and imprinted extractant through an external magnetic field. Add them to the elution solvent for elution respectively to obtain the artemisinene eluate and artemisinin eluate, remove the solvent under reduced pressure to obtain artemisinene, wash the artemisinin product with an aqueous methanol solution of 70 wt%, and crystallize at 2 °C to obtain high-purity artemisinin; the elution solvent is a mixed solution of n-hexane and diethyl ether with a volume ratio of 80:20.

[0103] Comparative Example 1

[0104] Compared with Example 3, the difference is that the magnetic extractant is prepared from Comparative Preparation Example 1.

[0105] Comparative Example 2

[0106] Compared with Example 3, the difference is that the magnetic extractant is prepared from Comparative Preparation Example 2.

[0107] Comparative Example 3

[0108] Compared with Example 3, the difference is that the imprinted extractant is prepared from Comparative Preparation Example 3.

[0109] Comparative Example 4

[0110] Compared with Example 3, the difference lies in that the imprint extractant is prepared from Comparative Preparation Example 4.

[0111] Comparative Example 5

[0112] Compared with Example 3, the difference lies in that the imprint extractant is prepared from Comparative Preparation Example 5.

[0113] Comparative Example 6

[0114] Compared with Example 3, the difference lies in that the magnetic extractant is replaced by an equal amount of the imprint extractant.

[0115] Comparative Example 7

[0116] Compared with Example 3, the difference lies in that no carbon dioxide is introduced.

[0117] 17 g of Artemisia annua powder (Artemisia annua is from Bozhou Traditional Chinese Medicine Base in Anhui Province, and the powder is prepared by pulverizing and drying to obtain Artemisia annua powder) is added to 200 mL of 1-butyl-3-methylimidazolium hexafluorophosphate solution, and extracted under ultrasonic treatment at 2000 W for 3 h. After filtration, 2 g of the magnetic extractant prepared in Preparation Example 3 and 3 g of the imprint extractant prepared in Preparation Example 6 are added to the filtrate, heated to 50 °C, and stirred for extraction for 1.5 h. After filtration, the solid is separated by an external magnetic field to obtain the adsorbed magnetic extractant and imprint extractant, which are respectively added to the elution solvent for elution to obtain the artemene eluate and artemisinin eluate. The solvent is removed under reduced pressure to obtain artemene. The artemisinin product is added and washed with an aqueous methanol solution of 70 wt%, and crystallized at 2 °C to obtain high-purity artemisinin; the elution solvent is a mixed solution of n-hexane and diethyl ether with a volume ratio of 80:20.

[0118] Test Example 1

[0119] The purity and yield of the high-purity artemisinin prepared in Examples 1-3 and Comparative Examples 1-7 were tested, and the results are shown in Table 1.

[0120] Table 1

[0121]

[0122]

[0123] As can be seen from the above table, the extraction and purification methods in Examples 1-3 of the present invention have a higher yield, and the high-purity artemisinin prepared has a higher purity.

[0124] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. A method for extracting and purifying artemisinin, characterized in that, Add artemisia powder to an ionic liquid solution, introduce carbon dioxide, extract under ultrasonic treatment conditions, filter, add a magnetic extractant and an imprinted extractant to the filtrate, extract by heating and stirring, filter, and use an external magnetic field to separate the adsorbed magnetic extractant and imprinted extractant from the solid. Then add them to an elution solvent for elution respectively to obtain an artemisene eluate and an artemisinin eluate. Remove the solvent under reduced pressure to obtain artemisene. The artemisinin product is washed with an aqueous methanol solution and crystallized at low temperature to obtain high-purity artemisinin.

2. The method for extracting and purifying artemisinin according to claim 1, wherein The ionic liquid is selected from at least one of 1-butyl-3-methylimidazolium hexafluorophosphate, 1-ethyl-3-methylimidazolium tetrafluoroborate, 1-butylpyridinium hexafluorophosphate, tetrabutylammonium hexafluorophosphate, tetraethylphosphonium triphenylphosphate, 1-butylpyrrolidinium hexafluorophosphate, and 1-vinyl-3-butylimidazolium hexafluorophosphate. The elution solvent is a mixed solution of n-hexane and diethyl ether with a volume ratio of 75-85:15-25.

3. The method for extracting and purifying artemisinin according to claim 1, wherein The ventilation volume of the carbon dioxide is 5-10 mL / min, the power of the ultrasonic treatment conditions is 1500-2500 W, and the extraction time is 2-4 h; the mass ratio of the artemisia powder, magnetic extractant, and imprinted extractant is 15-20:1-3:2-5; the temperature of the heating and stirring extraction is 45-55 °C, and the time is 1-2 h. The temperature of the low-temperature crystallization is 1-2 °C, and the concentration of the aqueous methanol solution is 60-80 wt%.

4. The method for extracting and purifying artemisinin according to claim 1, characterized in that, The preparation method of the magnetic extractant is as follows: S1. Add magnetic iron oxide particles to ethanol, add a silane coupling agent with a double bond, react by heating and stirring, separate with a magnet, wash, and dry to obtain modified magnetic iron oxide particles. S2. Add the modified magnetic iron oxide particles and the ionic liquid to water, add an initiator, react by heating, separate with a magnet, wash, and dry to obtain ionic liquid-modified magnetic iron oxide particles. S3. Add the ionic liquid-modified magnetic iron oxide particles to a graphene oxide aqueous dispersion, stir to disperse evenly, spray dry, and reduce with hydrazine hydrate vapor to obtain a magnetic extractant.

5. The method for extracting and purifying artemisinin according to claim 4, characterized in that, In step S1, the mass ratio of the magnetic iron oxide particles to the silane coupling agent with a double bond is 10:3-4, the temperature of the heating and stirring reaction is 45-55 °C, and the time is 2-4 h; in step S2, the mass ratio of the modified magnetic iron oxide particles, ionic liquid, and initiator is 7-10:3-4:0.1-0.12, the temperature of the heating reaction is 60-70 °C, and the time is 3-5 h; in step S3, the solid-liquid ratio of the ionic liquid-modified magnetic iron oxide particles to the graphene oxide aqueous dispersion is 1:3-5 g / mL, the concentration of the graphene oxide aqueous dispersion is 0.5-1 mg / mL, and the time of the hydrazine hydrate vapor reduction is 10-12 h.

6. The method for extracting and purifying artemisinin according to claim 4, wherein The silane coupling agent with double bonds is selected from at least one of KH570, A151, and A171. The ionic liquid is selected from at least one of 1-vinyl-3-butylimidazolium tetrafluoroborate, 1-vinyl-3-ethylimidazolium tetrafluoroborate, 1-vinyl-3-methylimidazolium tetrafluoroborate, and 1-vinyl-3-hexylimidazolium tetrafluoroborate. The initiator is selected from at least one of sodium persulfate, potassium persulfate, and ammonium persulfate.

7. The method for extracting and purifying artemisinin according to claim 1, characterized in that, The preparation method of the imprinted extractant is as follows: T1. Add silica nanospheres to the graphene oxide aqueous dispersion, spray dry to obtain graphene oxide@silica nanospheres. Add the graphene oxide@silica nanospheres to ethanol, add the silane coupling agent with double bonds, heat and stir for reaction, centrifuge, wash, and dry to obtain modified silica nanospheres; T2. Add the ionic liquid, acrylamide, artemisinin, methyl methacrylate, crosslinking agent, and modified silica nanospheres to water, add the initiator, heat for reaction, centrifuge, wash, and dry to obtain a copolymer; T3. Add the copolymer to the elution solvent for heating and reflux elution, centrifuge, wash, and dry to obtain the imprinted extractant.

8. The method for extracting and purifying artemisinin according to claim 7, wherein In step T1, the solid-liquid ratio of the silica nanospheres to the graphene oxide aqueous dispersion is 1:3 - 5 g / mL, the concentration of the graphene oxide aqueous dispersion is 0.5 - 1 mg / mL, the mass ratio of the graphene oxide@silica nanospheres to the silane coupling agent with double bonds is 10:2 - 3, the temperature of the heating and stirring reaction is 40 - 50 °C, and the time is 2 - 4 h; in step T2, the mass ratio of the ionic liquid, acrylamide, artemisinin, methyl methacrylate, crosslinking agent, modified silica nanospheres, and initiator is 1 - 3:6 - 8:2 - 4:1 - 3:0.05 - 0.1:5 - 7:0.01 - 0.012; in step T3, the elution solvent is a mixed solution of n-hexane and diethyl ether, and the volume ratio is 75 - 85:15 - 25.

9. The method for extracting and purifying artemisinin according to claim 7, characterized in that, The silane coupling agent with double bonds is selected from at least one of KH570, A151, and A171. The ionic liquid is selected from at least one of 1-vinyl-3-butylimidazolium tetrafluoroborate, 1-vinyl-3-ethylimidazolium tetrafluoroborate, 1-vinyl-3-methylimidazolium tetrafluoroborate, and 1-vinyl-3-hexylimidazolium tetrafluoroborate. The initiator is selected from at least one of sodium persulfate, potassium persulfate, and ammonium persulfate. The crosslinking agent is ethylene glycol dimethacrylate.

10. The method for extracting and purifying artemisinin according to claim 1, wherein The purity of the high-purity artemisinin > 99.99%.

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