CN101768160A - Preparation method of sipeimine - Google Patents
Preparation method of sipeimine Download PDFInfo
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- CN101768160A CN101768160A CN201010103115A CN201010103115A CN101768160A CN 101768160 A CN101768160 A CN 101768160A CN 201010103115 A CN201010103115 A CN 201010103115A CN 201010103115 A CN201010103115 A CN 201010103115A CN 101768160 A CN101768160 A CN 101768160A
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- ethanol
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- ethyl acetate
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- imperialine
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/54—Improvements relating to the production of bulk chemicals using solvents, e.g. supercritical solvents or ionic liquids
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Abstract
The invention relates to a preparation method of sipeimine. The process steps comprise: crushing fritillaria raw materials, adopting supercritical CO2 as solvent, using ethyl acetate as entrainer, extraction pressure of 25-40MPa, extraction temperature of 40-60 degrees C., static immersion for 1-3 hours, analysis pressure of 6-15MPa, analysis temperature 50-60 degrees C., dynamic extraction time of 150-250min; the extract is absorbed through macroporous resin, the gradientelution of ethyl acetate- ethanol-petroleum ether is conducted, and then petroleum ether impurity-removing, ethanol recrystallization are conducted for the eluent. The process has high extraction efficiency, ideal purity, and short production circle.
Description
Technical field:
The present invention relates to a kind of preparation method of sipeimine, especially a kind of employing supercritical CO
2Extract, the column chromatography absorption and purification prepares the method for Imperialine.
Background technology:
Imperialine is Sipeimine again, is a kind of alkaloid.
Molecular formula: C
27H
43NO
3Molecular weight: 429.64;
Molecular structural formula:
Character: Imperialine is a kind of colourless prism-shaped crystallization, and 269 ℃ of fusing points are soluble in chloroform, ethyl acetate, are dissolved in methyl alcohol, ethanol, acetone, ether, water insoluble and sherwood oil.
Pharmacological research shows, Imperialine has tangible relexation to isolated guinea pig ileum, rabbit duodenum and rat uterus and whole dog small intestine, the guinea-pig isolated trachea contraction that carbachol is caused has stronger restraining effect, the similar Papaverine of its spasmolysis can resist the caused spasm of Ovisot, histamine diphosphate and bariumchloride; Simultaneously also can expand peripheral blood vessel, but electrocardiogram(ECG is not had influence.
Lilium Liliaceae (Liliaceae) herbaceous plant, its underground bulb is subsphaeroidal or conical, surperficial off-white color.As herbal medicine commonly used, the preventing phlegm from forming and stopping coughing moistening lung, Unibract Fritillary Bulb is used for chronic cough of deficiency lung, cough due to consumptive disease, cough caused by dryness-heat, lung carbuncle, scrofula, carbuncle is swollen, acute mastitis; Sinkiang Fritillary Bulb is used for the cough due to lung-heat, the few phlegm of dry cough, and deficiency of Yin labor is coughed, and coughs sputum streaked with blood.Main component is an alkaloid, and contains saponin(e and micro-metals.
The domestic Imperialine that extracts from plant, raw material mainly is Sinkiang Fritillary Bulb and Unibract Fritillary Bulb.Imperialine content in Sinkiang Fritillary Bulb and Unibract Fritillary Bulb is lower, and mostly existing extraction process is ethanol percolate extraction, ammoniacal liquor and mixing solutions lixiviate.As " orthogonal experiment is preferably coughed peace lozenge extraction process " that Song Weizhong delivers, the document adopts 70% ethanol percolate extraction, and extraction time is long." assay of the total saponins of 4 kinds of Unibract Fritillary Bulbs, total alkaloids and Sipeimine " that Zhao De delivers forever, the document adopts moistening, the E-C-ethanol lixiviate of ammoniacal liquor, chloroform extraction, solvent-oil ratio is big, and separation obtains the Sipeimine monomer.Zhu Ziqing [natural medicinal ingredients extraction separation and preparation, Chinese Medicine science and technology press, 1994:346.] proposes to mix and stir with sodium carbonate solution, benzene, acid are extracted successively, alkalization, ether extracts repeatedly, the Anhydrous potassium carbonate drying, peroxidation aluminium post, through ethyl acetate-methyl alcohol-ammoniacal liquor (20: 1: 1) wash-out, get the Imperialine crystallization, this method complex operation, the solvent complexity, organic solvent residual is many.Therefore provide a kind of simple to operate, quick, carry the rate height, Imperialine preparation technology that purity is high has realistic meaning.
Summary of the invention:
The objective of the invention is for a kind of method for preparing Imperialine from Sinkiang Fritillary Bulb or Unibract Fritillary Bulb is provided.This technology extraction yield height, the purity ideal easily enlarges industrial production.
The present invention realizes by the following technical solutions:
A kind of preparation method of sipeimine is characterized in that comprising following steps:
1) supercritical CO
2Extraction:, add alkaline ethanol solution and soak with raw material pulverizing 60-100 order; Logical CO
2Ethyl acetate is made entrainment agent, collects extract;
2) resin absorption: above-mentioned extract is added macroporous resin, and earlier with sherwood oil wash-out impurity, again through ethyl acetate-ethanol-sherwood oil mixing solutions gradient elution, tlc detects, and collects elutriant;
3) recrystallization: above-mentioned elutriant reclaims reagent to small volume, places crystallization, and leach crystallisate and add petroleum ether, the saturated dissolving of 95% alcohol reflux, crystallization 1-3 time leaches cryodrying and promptly gets product.
Described raw material is the bulb of liliaceous plant Fritillaria walujewii Regel, Fritillaria pallidiflora Schrenk, the leaf roll bulb of fritillary, the Gansu bulb of fritillary or the dark violet bulb of fritillary.
Described static immersing solvent: alkaline ethanol is the ethanol of pH10, and alcohol concn is 70-90%, and the optional sodium hydroxide of alkali, potassium hydroxide, yellow soda ash or ammoniacal liquor soaked 1-3 hour.
Described supercritical extraction condition: the entrainment agent add-on is the 10-20% of material quantity, and extracting pressure 25-40MPa extracts 40-60 ℃ of temperature, CO
2Flow 1-5ml/g crude drug/min, dynamic extraction 150min-250min; Resolve pressure 6-15MPa, resolution temperature 50-60 ℃.
Described macroporous resin adsorption condition: macroporous resin can be selected D101, D180, HPD100 or AB-8 macroporous adsorbent resin for use.
Described condition of gradient elution: 4-5 times of column volume wash-out of first ethyl acetate-ethanol-sherwood oil (2: 1: 2), TLC detects, and has Imperialine to flow out, and uses ethyl acetate-ethanol-sherwood oil (8: 1: 1) wash-out again instead, to there not being the Imperialine flow point.
Described crystallization condition: the Imperialine flow point is concentrated into the 1/4-1/5 of its volume, recrystallization 2-3 time, rearing crystal time at least 8 hours.
In sum, there is following advantage in the present invention: supercritical CO
2Extraction extraction yield height, solvent load is little, stable in properties, production safety, product purity height.
Further specify the present invention below in conjunction with embodiment, but the scope of protection of present invention is not limited to following embodiment.
Embodiment:
Tlc (differentiating that with reference to version Chinese Pharmacopoeia Sinkiang Fritillary Bulb in 2005 item is down) is adopted in the detection of Imperialine among the following embodiment,
Concrete grammar is as follows:
The thin-layer chromatography condition:
Thin layer plate: the thin layer plate of 2% sodium hydroxide preparation;
Developping agent: chloroform-ethyl acetate-methanol-water (8: 8: 3: 2) lower floor's solution of placing below 10 ℃;
Launch, dry, spray shows identical brown spot with rare bismuth potassium iodide test solution and 3% Sodium Nitrite alcohol test solution on the position identical with the reference substance chromatogram.
Embodiment 1:
Get bulb of fritillary pulverizing medicinal materials 60 orders, get 5kg and drop into extraction column, added 100mlpH earlier and be 10 75% alcohol immersion 2 hours, sealing will be extracted temperature and be brought up to 50 ℃, and the knockout tower temperature transfers to 60 ℃, extracts pressure 38MPa, parsing pressure 10MPa, CO
2Gas is emitted from steel cylinder, is chilled to 0-5 ℃ through behind the gas purifier in liquefied pot, liquefaction.Enter storage tank with high-pressure metering pump with CO
2Send into preheater with the 500ml ethyl acetate, arrive assigned temperature and pressure by preheater, carrying ethyl acetate secretly by the extraction column bottom enters together with material and contacts, flow velocity 1.0L/min regulates the tower internal pressure, when extracting pressure to 40MPa, resolve pressure to 10MPa, open relief valve, by relief valve control above-mentioned parameter, dynamic extraction 3 hours.Emit extract after the shutdown; collect extract; cross the D101 macroporous resin adsorption, measure 4BV sherwood oil wash-out impurity after, earlier with ethyl acetate-ethanol-sherwood oil (2: 1: 2) wash-out; thin layer detects; use ethyl acetate-ethanol-sherwood oil (8: 1: 1) wash-out when the Imperialine flow point is arranged again instead, do not finish wash-out, collect this section flow point to there being the Imperialine flow point; reclaim reagent to 1/4 of its volume, place crystallization 8 hours.Leach coarse-grain thing 3.6g, the coarse crystallization thing is placed crystallization 12 hours with the saturated dissolving of 95% alcohol reflux, leach, and recrystallization 3 times, cryodrying gets product 1.86g, content 98.8%.
Embodiment 2:
Get bulb of fritillary pulverizing medicinal materials 80 orders, get 8kg and drop into extraction column, added 160mlpH earlier and be 10 80% alcohol immersion 1 hour, sealing will be extracted temperature and be brought up to 40 ℃, and the knockout tower temperature transfers to 50 ℃, extracts pressure 35MPa, parsing pressure 8MPa, CO
2Gas is emitted from steel cylinder, is chilled to 0-5 ℃ through behind the gas purifier in liquefied pot, liquefaction.Enter storage tank with high-pressure metering pump with CO
2Send into preheater with the 1200ml ethyl acetate, arrive assigned temperature and pressure by preheater, carrying ethyl acetate secretly by the extraction column bottom enters together with material and contacts, flow velocity 1.0L/min regulates the tower internal pressure, when extracting pressure to 35MPa, resolve pressure to 8MPa, open relief valve, by relief valve control above-mentioned parameter, dynamic extraction 200 minutes.Emit extract after the shutdown; collect extract; cross the HPD100 macroporous resin adsorption, measure 5BV sherwood oil wash-out impurity after, earlier with ethyl acetate-ethanol-sherwood oil (2: 1: 2) wash-out; thin layer detects; use ethyl acetate-ethanol-sherwood oil (8: 1: 1) wash-out when the Imperialine flow point is arranged again instead, do not finish wash-out, collect this section flow point to there being the Imperialine flow point; reclaim reagent to 1/5 of its volume, place crystallization.Leach coarse-grain thing 5.7g, the coarse crystallization thing is placed crystallization 10 hours with the saturated dissolving of 95% alcohol reflux, leach, and recrystallization 2 times, cryodrying gets product 2.6g, content 99%.
Embodiment 3:
Get bulb of fritillary pulverizing medicinal materials 100 orders, get 6kg and drop into extraction column, added 120mlpH earlier and be 10 90% alcohol immersion 1 hour, sealing will be extracted temperature and be brought up to 45 ℃, and the knockout tower temperature transfers to 55 ℃, extracts pressure 25.5MPa, parsing pressure 6MPa, CO
2Gas is emitted from steel cylinder, is chilled to 0-5 ℃ through behind the gas purifier in liquefied pot, liquefaction.Enter storage tank with high-pressure metering pump with CO
2Send into preheater with the 600ml ethyl acetate, arrive assigned temperature and pressure by preheater, carrying ethyl acetate secretly by the extraction column bottom enters together with material and contacts, flow velocity 1.0L/min regulates the tower internal pressure, when extracting pressure to 35MPa, resolve pressure to 8MPa, open relief valve, by relief valve control above-mentioned parameter, dynamic extraction 200 minutes.Emit extract after the shutdown; collect extract; cross the D180 macroporous resin adsorption, measure 4BV sherwood oil wash-out impurity after, earlier with ethyl acetate-ethanol-sherwood oil (2: 1: 2) wash-out; thin layer detects; use ethyl acetate-ethanol-sherwood oil (8: 1: 1) wash-out when the Imperialine flow point is arranged again instead, do not finish wash-out, collect this section flow point to there being the Imperialine flow point; reclaim reagent to 1/5 of its volume, place crystallization.Leach coarse-grain thing 4.2g, the coarse crystallization thing is placed crystallization 13 hours with the saturated dissolving of 95% alcohol reflux, leach, and recrystallization 3 times, cryodrying gets product 2.2g, content 98.7%.
Embodiment 4:
Get bulb of fritillary pulverizing medicinal materials 80 orders, get 2kg and drop into extraction column, added 40mlpH earlier and be 10 85% alcohol immersion 1.5 hours, sealing will be extracted temperature and be brought up to 40 ℃, and the knockout tower temperature transfers to 60 ℃, extracts pressure 28MPa, parsing pressure 8MPa, CO
2Gas is emitted from steel cylinder, is chilled to 0-5 ℃ through behind the gas purifier in liquefied pot, liquefaction.Enter storage tank with high-pressure metering pump with CO
2Send into preheater with the 400ml ethyl acetate, arrive assigned temperature and pressure by preheater, carrying ethyl acetate secretly by the extraction column bottom enters together with material and contacts, flow velocity 1.0L/min regulates the tower internal pressure, when extracting pressure to 25MPa, resolve pressure to 6MPa, open relief valve, by relief valve control above-mentioned parameter, dynamic extraction 2 hours.Emit extract after the shutdown; collect extract; cross the AB-8 macroporous resin adsorption, measure 4BV sherwood oil wash-out impurity after, earlier with ethyl acetate-ethanol-sherwood oil (2: 1: 2) wash-out; thin layer detects; use ethyl acetate-ethanol-sherwood oil (8: 1: 1) wash-out when the Imperialine flow point is arranged again instead, do not finish wash-out, collect this section flow point to there being the Imperialine flow point; reclaim reagent to 1/4 of its volume, place crystallization.Leach coarse-grain thing 1.45g, the coarse crystallization thing is placed crystallization 15 hours with the saturated dissolving of 95% alcohol reflux, leach, and recrystallization 3 times, cryodrying gets product 0.75g, content 98%.
Claims (7)
1. preparation method of sipeimine is characterized in that comprising following steps:
1) supercritical CO
2Extraction:, add alkaline ethanol solution and soak with raw material pulverizing 60-100 order; Logical CO
2Ethyl acetate is made entrainment agent, collects extract;
2) resin absorption: above-mentioned extract is added macroporous resin, and earlier with sherwood oil wash-out impurity, again through ethyl acetate-ethanol-sherwood oil mixing solutions gradient elution, tlc detects, and collects elutriant;
3) recrystallization: above-mentioned elutriant reclaims reagent to small volume, places crystallization, and leach crystallisate and add petroleum ether, the saturated dissolving of 95% alcohol reflux, crystallization 1-3 time leaches cryodrying and promptly gets product.
2. preparation method as claimed in claim 1 is characterized in that described raw material is the dry bulb of liliaceous plant Fritillaria walujewii Regel, Fritillaria pallidiflora Schrenk, the leaf roll bulb of fritillary, the Gansu bulb of fritillary or the dark violet bulb of fritillary.
3. preparation method as claimed in claim 1 is characterized in that described static immersing solvent: alkaline ethanol is the ethanol of pH10, and alcohol concn is 70-90%, the optional sodium hydroxide of alkali, potassium hydroxide, yellow soda ash or ammoniacal liquor, static immersing 1-3 hour.
4. preparation method as claimed in claim 1 is characterized in that described supercritical extraction condition: the entrainment agent add-on is the 10-20% of material quantity, and extracting pressure 25-40MPa extracts 40-60 ℃ of temperature, CO
2Flow 1-5ml/g crude drug/min, dynamic extraction 150min-250min; Resolve pressure 6-15MPa, resolution temperature 50-60 ℃.
5. preparation method as claimed in claim 1 is characterized in that described macroporous resin adsorption condition: macroporous resin can be selected D101, D180, HPD100 or AB-8 macroporous adsorbent resin for use.
6. preparation method as claimed in claim 1, it is characterized in that described condition of gradient elution: 4-5 times of column volume wash-out of first ethyl acetate-ethanol-sherwood oil (2: 1: 2), TLC detects, there is Imperialine to flow out, use ethyl acetate-ethanol-sherwood oil (8: 1: 1) wash-out again instead, to there not being the Imperialine flow point.
7. preparation method as claimed in claim 1 is characterized in that described crystallization condition: the Imperialine flow point is concentrated into the 1/4-1/5 of its volume, recrystallization 2-3 time, rearing crystal time at least 8 hours.
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| CN201010103115A CN101768160A (en) | 2010-02-01 | 2010-02-01 | Preparation method of sipeimine |
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| CN201010103115A CN101768160A (en) | 2010-02-01 | 2010-02-01 | Preparation method of sipeimine |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102210803A (en) * | 2011-05-18 | 2011-10-12 | 北京中医药大学 | Extraction and enrichment method of fritillaria total alkaloids |
| CN102477062A (en) * | 2010-11-25 | 2012-05-30 | 苏州宝泽堂医药科技有限公司 | Method for extracting liquidambaric acid from supercritical fluid |
| CN103251790A (en) * | 2013-05-06 | 2013-08-21 | 乌鲁木齐欧易生物医学科技有限公司 | Method for extracting total alkaloids from fritillaria pallidiflora |
| CN103721025A (en) * | 2013-12-17 | 2014-04-16 | 新疆伊禧堂生物科技有限公司 | Process for preparing fritillaria pallidiflora total alkaloids |
| CN104984035A (en) * | 2015-07-24 | 2015-10-21 | 浙江万里学院 | Preparation method of fritillary flower extract |
| CN105693814A (en) * | 2016-04-15 | 2016-06-22 | 中国科学院新疆理化技术研究所 | Isosteroidal alkaloid compounds in Siberian fritillary bulb and preparation method and application thereof |
| CN110283227A (en) * | 2019-06-10 | 2019-09-27 | 上海诗丹德标准技术服务有限公司 | A kind of preparation method of imperialine |
-
2010
- 2010-02-01 CN CN201010103115A patent/CN101768160A/en active Pending
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102477062A (en) * | 2010-11-25 | 2012-05-30 | 苏州宝泽堂医药科技有限公司 | Method for extracting liquidambaric acid from supercritical fluid |
| CN102210803A (en) * | 2011-05-18 | 2011-10-12 | 北京中医药大学 | Extraction and enrichment method of fritillaria total alkaloids |
| CN102210803B (en) * | 2011-05-18 | 2012-09-19 | 北京中医药大学 | Extraction and enrichment method of fritillaria total alkaloids |
| CN103251790A (en) * | 2013-05-06 | 2013-08-21 | 乌鲁木齐欧易生物医学科技有限公司 | Method for extracting total alkaloids from fritillaria pallidiflora |
| CN103721025A (en) * | 2013-12-17 | 2014-04-16 | 新疆伊禧堂生物科技有限公司 | Process for preparing fritillaria pallidiflora total alkaloids |
| CN104984035A (en) * | 2015-07-24 | 2015-10-21 | 浙江万里学院 | Preparation method of fritillary flower extract |
| CN104984035B (en) * | 2015-07-24 | 2019-01-01 | 浙江万里学院 | A kind of preparation method of fritillaria flower extract |
| CN105693814A (en) * | 2016-04-15 | 2016-06-22 | 中国科学院新疆理化技术研究所 | Isosteroidal alkaloid compounds in Siberian fritillary bulb and preparation method and application thereof |
| CN110283227A (en) * | 2019-06-10 | 2019-09-27 | 上海诗丹德标准技术服务有限公司 | A kind of preparation method of imperialine |
| CN110283227B (en) * | 2019-06-10 | 2021-10-08 | 上海诗丹德标准技术服务有限公司 | Preparation method of sipeimine |
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Application publication date: 20100707 |