CN101597296B - Novel method for efficiently extracting and producing artemisinin by ionic liquid - Google Patents
Novel method for efficiently extracting and producing artemisinin by ionic liquid Download PDFInfo
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- CN101597296B CN101597296B CN2008101144160A CN200810114416A CN101597296B CN 101597296 B CN101597296 B CN 101597296B CN 2008101144160 A CN2008101144160 A CN 2008101144160A CN 200810114416 A CN200810114416 A CN 200810114416A CN 101597296 B CN101597296 B CN 101597296B
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Abstract
The invention relates to a novel method for efficiently extracting and producing artemisinin by ionic liquid. The raw material of artemisia apiacea is ground; the artemisia apiacea is ultrasonically and intensively extracted by the mixture of imidazole ionic liquid halide salt and water; the artemisinin extract solution is obtained after the process of liquid and solid separation; the artemisinin extract solution is extracted by organic extracting agent to obtain extract liquor rich in artemisinin; the organic extracting agent is steamed and recycled to obtain crude artemisinin; and the crude artemisinin is redissolved and is processed by the column chromatography, the recrystallization and the like to obtain high-purity artemisinin. The ionic liquid extracting liquid can be reused and then regenerated by macroporous resin. The non-volatile, nonexplosive and environmental-friendly solvent which is the ionic liquid is used for extracting the artemisinin and the organic solvent is used for extracting the enriched artemisinin, thereby the ionic liquid can be reused, the artemisinin can be extracted and produced easily and conveniently by large scale, and the difficult problem of using explosive and flammable solvent with strong volatility in the process of extracting and separating the artemisinin is effectively solved.
Description
Technical field
The present invention relates to a kind of green solvent-ionic liquid that utilizes, the method for extraction from sweet wormwood, enrichment, artemisinin purifying belongs to the biochemical engineering technical field.
Background technology
Sweet wormwood (Artemisia annua L.) claims again for composite family annual herb plant, to be distributed widely in China various places by Herba Artemisiae annuae.Sweet wormwood is used as medicine and sees the book copied on silk " 52 Bingfang " of No. three tomb of Han dynasty in Mawangdui unearthed (B.C. about 168 years) the earliest, and the back is all on the books in books such as Shennong's Herbal, Compendium of Material Medica, and it is the antimalarial herbal medicine that China's traditional Chinese medical science tradition is used.Sweet wormwood contains multiple volatility and non-volatile medicinal ingredients, and wherein volatile component is mainly volatile oil, and involatile constituent mainly contains Artemisinin, Qinghaosu I, second element, third element and arteannuinic acid, tonka bean camphor, flavones, beans Zi alcohol etc.Artemislnin content is subjected to geographical environment, collection period in the wild sweet wormwood, (Xu advances, pharmacy progress, 2002,26 (5): 274-278) to gather all multifactor influences such as position, temperature.
The seventies in 20th century, China's researcher on the basis of arrangement folk remedy, extraction separation the Artemisinin monomer, and identify that by methods such as chemical reaction, spectroscopic data and X ray single crystal diffractions it is a kind of sesquiterpene lactone that contains peroxy-radical.Artemisinin (artemisinin) is a kind of colourless acicular crystal, because it has special peroxy-radical, it is to thermally labile, is subject to wet, the influence of heat and reducing substance and decompose (Li.Y.Med.Abro., 1999,14 (3): 102-107).Artemisinin is the unique medicine of enjoying independent intellectual property rights and obtaining international endorsement of China.Since two thousand one, the artemisinin-based antimalarial drug thing is regarded as the current malaria medicine for the treatment of the most safely and effectively by the World Health Organization, existing 51 countries and regions, the whole world are specified medicine with it as antimalarial, be used to replace quinine and chloroquine etc. to cause drug-fast medicine (Wang Qunhong, foreign medical science Chinese medicine fascicle, 2005,27 (4): 203-206).
The method of extracting Artemisinin at present from sweet wormwood is divided into volatile organic solvent and super subcritical CO from extracting solvent
2Extract; Be divided into ultrasound-enhanced and microwave reinforced from enhancement method." the industrial naptha method " of institute of materia medica, Yunnan (CN1092073), " acetone-silica gel column chromatography " of institute of Chinese materia medica, Shandong (CN87101346A), " methylbenzene extraction method " (Enzyme Microbial Technol. of Paniego, 1996,18 (7): 526-530) and " methyl alcohol-alcohol-ether " extraction method (Planta Med. of people such as Vonwiller, 1993,59:563) be organic solvent extraction.Though organic solvent extraction is easy and simple to handle, be easy to industrialization, solvent is inflammable, explosive, high volatility, has potential safety hazard, simultaneously serious environment pollution.Super subcritical CO
2Extract (CN1095381A, though CN1869037A) solvent green, safety are high pressure resistant to requiring equipment, disposable input height.Ultrasound-enhanced (Zhao Bing, chemical industry metallurgical, 2000,21 (3): 310-313) extract Artemisinin with microwave reinforced (CN00120351.7), all adopt volatile organic solvent, though extraction time shortens, solvent consumption reduces, yield improves, but still has general safety of organic solvent extraction and pollution problem.
At present, the research of ionic liquid extract organism and natural product aspect report is also less.Lee's spare time etc. shows the solubility study of hydrophobicity imidazole ion liquid to aldehydes matter: ion liquid dissolving aldehydes matter performance and conventional organic solvents quite (process engineering journal, 2005,5 (2): 148-15 ".Rogers etc. studied aromatics the solvability of several imidazole ion liquids (Chem.Commun., 1998,16:1765-1766).Gu etc. studied wetting ability chloridization 1-methyl-3-butyl imidazole extraction separation taurine (Sepn.Pur.Tech., 2004,35:153-159).Phillips etc. utilize hydrophilic imidazoles villaumite to extract silk fiber and obtain better effects (Am.Chem.Soc., 2004,126 (44): 14350-14351).
The present invention is raw material with the sweet wormwood, is extraction agent with the glyoxaline ion liquid halide salts, and water is for reducing the thinner of system viscosity, at the ultrasound-enhanced Artemisinin that extracts down.Utilize organic extractant extracting and enriching Artemisinin from the Artemisinin extracting solution, realize ion liquid regeneration simultaneously and recycle.Organic extraction obtains the Artemisinin crude product after evaporating mutually and reclaiming organic extractant, and the Artemisinin crude product dissolves again after chromatography, the further refining high purity Artemisinin that obtains of recrystallization.The ionic liquid extracting phase can be recycled, and can utilize macroporous resin to regenerate after repeatedly recycling.The present invention have extraction agent do not fire, non-volatile, loss is little, power consumption is low, no potential safety hazard, easy and simple to handle, be easy to characteristics such as industrialization, can be used for the large-scale production of Artemisinin efficient green and realize the sweet wormwood comprehensive utilization of resources.
Goal of the invention and content
The object of the invention provide a kind of from sweet wormwood rapid scale extract the method for Artemisinin.Adopt the present invention to extract Artemisinin and can effectively solve the problem that existing Artemisinin extractive technique uses inflammable, explosive organic solvent to exist.The present invention relates to a kind of novel method of ionic liquid high efficiency extraction Artemisinin, mainly may further comprise the steps:
1) with the sweet wormwood raw material pulverizing, cross the 10-80 mesh sieve, press solid-liquid than 1: 5-1: 70 (W/V) add the mixed solution of glyoxaline ion liquid halide salts and water, at ultrasonic power 1-100W/cm
2, ultrasonic frequency 20-80kHz under the temperature 20-60 ℃ of condition, extracted 5-60 minute, adopted centrifugal or filtered and carry out liquid-solid separation, obtained containing the extracting solution of Artemisinin;
2) extracting solution that step 1) is obtained is by the Artemisinin extracting solution: organic solvent is 1: 1-20: 1 (V/V) extraction 1-5 time, and the separation organic phase gets the Artemisinin extraction liquid, and extracting phase-ionic liquid recycles;
3) with step 2) the organic extract liquid evaporation concentration that obtains reclaim behind the organic solvent the Artemisinin crude product;
4) the Artemisinin crude product that step 3) is obtained dissolves again, with column chromatography and recrystallization further refining the high purity Artemisinin;
5) with step 2) after the ionic liquid raffinate that obtains recycles 2-8 time, add macroporous adsorbent resin regeneration, whip attachment 0.5-10 hour, filter or the centrifugation resin, obtain regenerated ionic liquid extract liquid.
Embodiment 1
1) dry artemisia leaf is pulverized, and crosses 10 mesh sieves, gets 10 gram Sweet Wormwood Herbs and adds 25 milliliters of chlorination 1-ethyl-3-Methylimidazoles and 25 ml waters, 20 ℃ of supersound extraction 5 minutes, power 100W/cm
2, frequency 20kHz, extracting solution 4000rpm centrifugation gets the Artemisinin extracting solution after 5 minutes;
2) extracting solution that step 1) is obtained separates the organic extraction phase with equal volume benzene extraction 1 time, gets the Artemisinin pregnant solution;
3) with step 2) pregnant solution after solvent is reclaimed in evaporation the Artemisinin crude product, purity 〉=40%, extraction rate reached to 80%;
4) after the ionic liquid extracting phase recycles 2 times, add macroporous resin AB-8, behind the stirring 30min, the filtering separation macroporous resin obtains ionic liquid regeneration extracting solution.
Embodiment 2
1) gets Sweet Wormwood Herb 10 grams of pulverizing and cross 20 mesh sieves, add 50 milliliters of bromination 1-ethyl-3-Methylimidazoles and 500 ml waters, 60 ℃ of supersound extraction 60 minutes, power 10W/cm
2, frequency 20kHz, extracting solution 4000rpm centrifugation gets the Artemisinin extracting solution after 5 minutes;
2) extracting solution that step 1) is obtained separates the organic extraction phase with the chloroform extraction of its 50% volume 2 times, the Artemisinin pregnant solution;
3) with step 2) pregnant solution after solvent is reclaimed in evaporation the Artemisinin crude product, purity 〉=42%, extraction rate reached to 88%;
4) after the ionic liquid extracting phase recycles 6 times, add macroporous resin X-5, stir after 1 hour, the filtering separation macroporous resin obtains ionic liquid regeneration extracting solution.
Embodiment 3
1) gets Sweet Wormwood Herb 10 grams of pulverizing and cross 80 mesh sieves, add 100 milliliters bromination 1-ethyl-3-Methylimidazole and 400 ml waters, 50 ℃ of supersound extraction 60 minutes, power 1W/cm
2, frequency 80kHz, extracting solution 4000rpm centrifugation gets the Artemisinin extracting solution after 5 minutes;
2) extracting solution that step 1) is obtained is with the ethyl acetate extraction of its 5% volume 3 times, separate the organic extraction phase, the Artemisinin pregnant solution;
3) step 2) pregnant solution gets Artemisinin crude product, purity 〉=51%, extraction rate reached to 92% after solvent is reclaimed in evaporation;
4) after the ionic liquid extracting phase recycles 3 times, add macroporous resin ADS-17, stir after 5 hours, the filtering separation macroporous resin obtains ionic liquid regeneration extracting solution.
Embodiment 4
1) gets Sweet Wormwood Herb 10 grams of pulverizing and cross 60 mesh sieves, add 200 milliliters iodate 1-ethyl-3-Methylimidazole and 500 ml waters, 40 ℃ of supersound extraction 40 minutes, power 50W/cm
2, frequency 30kHz, extracting solution 4000rpm centrifugation gets the Artemisinin extracting solution after 5 minutes;
2) extracting solution that step 1) is obtained separates the organic extraction phase with its 5% volumes of acetic acid ethyl ester extraction 4 times, gets the Artemisinin pregnant solution;
3) step 2) pregnant solution gets Artemisinin crude product, purity 〉=60%, extraction rate reached to 95% after solvent is reclaimed in evaporation;
4) the Artemisinin crude product that step 3) is obtained can get the pure product of purity 〉=98% with ethyl alcohol recrystallization;
5) after the ionic liquid extracting phase recycles 8 times, add macroporous resin ADS-7, stir after 10 hours, the filtering separation macroporous resin obtains ionic liquid regeneration extracting solution.
Embodiment 5
1) gets Sweet Wormwood Herb 10 grams of pulverizing and cross 60 mesh sieves, add 100 milliliters bromination 1-ethyl-3-Methylimidazole and 400 ml waters, 50 ℃ of supersound extraction 40 minutes, power 50W/cm
2, frequency 20kHz, extracting solution 4000rpm centrifugation gets the Artemisinin extracting solution after 10 minutes;
2) extracting solution that step 1) is obtained gets toluene extraction 5 times with its 10% volume, separates the organic extraction phase, gets the Artemisinin pregnant solution;
3) step 2) pregnant solution gets Artemisinin crude product, purity 〉=45%, extraction rate reached to 98% after solvent is reclaimed in evaporation;
4) the Artemisinin crude product that step 3) is obtained dissolves again with ethanol, and silica gel column chromatography, recrystallization can get the pure product of purity 〉=99% excessively;
5) after the ionic liquid extracting phase recycles 4 times, add macroporous resin AB-8, stir after 8 hours, the filtering separation macroporous resin obtains ionic liquid regeneration extracting solution.
The above; only for part embodiment of the present invention, but protection scope of the present invention is not limited thereto, and any those skilled in the art that are in the technical scope that the present invention discloses; the variation that can expect easily or replacement all should be encompassed within protection scope of the present invention.
Claims (3)
1. the novel method of an efficiently extracting and producing artemisinin by ionic liquid, it may further comprise the steps:
1) with the sweet wormwood raw material pulverizing, cross the 10-80 mesh sieve, press solid-liquid than 1: 5-1: 70W/V adds the mixed solution of glyoxaline ion liquid halide salts and water, at ultrasonic power 1-100W/cm
2, ultrasonic frequency 20-80kHz under the temperature 20-60 ℃ of condition, extracted 5-60 minute, obtained containing the extracting solution of Artemisinin through liquid-solid separation;
2) extracting solution that step 1) is obtained is in the Artemisinin extracting solution: the organic extractant ratio is 1: 1-20: 1V/V extraction 1-5 time, and the separation organic phase gets the Artemisinin extraction phase, and extracting phase-ionic liquid recycles;
3) with step 2) organic extraction that obtains evaporate mutually reclaim behind the organic extractant the Artemisinin crude product;
4) the Artemisinin crude product that step 3) is obtained dissolves again, with column chromatography, recrystallization further refining the high purity Artemisinin;
5) with step 2) after the ionic liquid raffinate that obtains recycles 2-8 time, added the macroporous adsorbent resin whip attachment 0.5-10 hour, filter or the centrifugation resin, obtain regenerated ionic liquid extract liquid;
Abovementioned steps 1) the glyoxaline ion liquid halide salts is one or more in chlorination 1-ethyl-3-Methylimidazole, bromination 1-ethyl-3-Methylimidazole and the iodate 1-ethyl-3-Methylimidazole in; Step 2) organic extractant that uses is in benzene, toluene, ethyl acetate, the trichloromethane one or more.
2. Artemisinin extracting method according to claim 1 is characterized in that: the ratio of glyoxaline ion liquid halide salts and water is 1 in the described mixed solution of step 1): 1-1: 10V/V.
3. Artemisinin extracting method according to claim 1 is characterized in that, the macroporous resin that described step 4) is used is among ADS-7, ADS-17, X-5, AB-7, the AB-8 one or more.
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Cited By (1)
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| CN104788527B (en) * | 2015-03-24 | 2017-05-03 | 浙江工商大学 | Method for extracting tripterine efficiently with ionic liquid |
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| CN103059038B (en) * | 2012-12-13 | 2016-02-24 | 大兴安岭林格贝寒带生物科技股份有限公司 | The production technique of enriching and purifying Artemisinin in a kind of Herba Artemisiae annuae |
| CN103483350A (en) * | 2013-06-25 | 2014-01-01 | 重庆华方武陵山制药有限公司 | Ultrasonic reflux extraction method of artemisinin |
| CN104277084B (en) * | 2013-07-07 | 2018-01-16 | 云南健牛生物科技有限公司 | Polarity or the extracting method of low pole active constituent content in a kind of raising Chinese medicine |
| CN103408566B (en) * | 2013-07-17 | 2016-04-20 | 张家港威胜生物医药有限公司 | A kind of extraction technology for artemisia annua element |
| CN104327091A (en) * | 2013-11-30 | 2015-02-04 | 钟延华 | Extraction method for artemisinin |
| CN104497002A (en) * | 2013-12-05 | 2015-04-08 | 广西仙草堂制药有限责任公司 | Extraction method of artemisinin |
| CN105646519B (en) * | 2014-11-28 | 2018-09-25 | 北京罗瑞生物科技有限公司 | A kind of method of ultrasound extraction with aqueous solution qinghaosu |
| CN104987341A (en) * | 2015-06-29 | 2015-10-21 | 兰捷 | Method for extracting artemisinin from sweet wormwood |
| CN106632389B (en) * | 2016-11-15 | 2019-01-08 | 浙江工业大学 | The method of qinghaosu is extracted in a kind of artemisia annua |
| CN107312015A (en) * | 2017-06-21 | 2017-11-03 | 禹州市天源生物科技有限公司 | A kind of technique of efficiently extracting and producing artemisinin by ionic liquid |
| CN111592612B (en) * | 2020-05-20 | 2021-07-20 | 中国科学院过程工程研究所 | Polyion liquid inhibitor and preparation method and application thereof |
| CN113528488B (en) * | 2021-08-17 | 2022-09-27 | 南昌大学 | Method for preparing high-quality crude hyaluronidase product by stirring and adsorbing resin |
| CN113583017B (en) * | 2021-08-27 | 2023-02-10 | 中国科学院过程工程研究所 | Method for selectively extracting and separating artemisinin/arteannuin by using hydrophilic ionic liquid |
| CN113735874B (en) * | 2021-09-01 | 2023-02-21 | 中国科学院过程工程研究所 | Method for selectively extracting and separating artemisinin/arteannuin by using hydrophobic ionic liquid |
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Cited By (1)
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| CN104788527B (en) * | 2015-03-24 | 2017-05-03 | 浙江工商大学 | Method for extracting tripterine efficiently with ionic liquid |
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