CN1534038A - High effect production method of catharanthine - Google Patents
High effect production method of catharanthine Download PDFInfo
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- CN1534038A CN1534038A CNA200410013558XA CN200410013558A CN1534038A CN 1534038 A CN1534038 A CN 1534038A CN A200410013558X A CNA200410013558X A CN A200410013558XA CN 200410013558 A CN200410013558 A CN 200410013558A CN 1534038 A CN1534038 A CN 1534038A
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- vinealeucoblastine
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Abstract
A process for effectively preparing velban from vinca flower includes removing impurities, mixing with solvent, homogenizing, solid-liquid extracting, cavitation-suspension-extracting, filtering, concentrating liquid extract, regulating pH value, filtering, liquid-liquid extracting, concentrating and purifying. Its advantages are short period, high output rate (0.07-0.12%) and purity (98% or more), and no pollution.
Description
Affiliated technical field:
The present invention relates to a kind of vinealeucoblastine(VLB) high-efficiency method for producing, particularly a kind of vinealeucoblastine(VLB) high-efficiency method for producing that adopts homogenate abstraction technique and cavitation suspension extraction technology.
Background technology:
At present, vinealeucoblastine(VLB) and derivative thereof generally extract from Apocynaceae (Apocynaceae) plant Vinca (Catharanthus roseus) and obtain.
Current vinealeucoblastine(VLB) extracting method has:
1, from Vinca, extracts the novel process of anticancer active constituent, Patent Office of the People's Republic of China's publication number: CN1365978a; Open day: 2002.08.28; Application number: 011319879.9, this invention relates to the processing method of extracting vinealeucoblastine(VLB), vincristine(VCR) and ursolic acid in a kind of Vinca herb dry powder, adopt the winestone acid solution counter-current extraction → acid-soluble material of Vinca siccative abrasive dust → benzene diacolation → 3～10% from acid non-soluble substance, to obtain ursolic acid through column chromatography for separation → vinealeucoblastine(VLB) and vincristine(VCR).
2, the Process for the isolation of alkaloid components from the plant VincaRosea L. technology of separating bio alkali composition (a kind of from Vinca) United States Patent Office (USPO) publication number: 4172077; Open day: 1979.10.23; Application number: [HU] RI 638, it is raw material after pulverizing with Vinca that this invention relates to a kind of, the processing method of producing various vinca alkaloidses by different acidulated conditions.Behind raw material pulverizing → methyl alcohol, 2% aqueous sulfuric acid and toluene diacolation → concentrated percolate → different condition acidifying → purifying, obtain the operational path of product.
The production method ubiquity of above-mentioned vinealeucoblastine(VLB) that extraction time is longer, and extraction yield and yield are all lower, and production cost height, complex procedures are not easy to shortcomings such as popularization.
Summary of the invention:
The object of the invention be to provide a kind of with short production cycle, extraction yield is high, product purity and the high vinealeucoblastine(VLB) high-efficiency method for producing of yield.
In order to achieve the above object, the technical solution used in the present invention is: extract solvent with alcohol or acid alcohol after the Vinca removal of impurity and concentrate, concentrated solution adjust pH, filtration, the liquid-liquid extraction of cavitation suspendible, concentrate, obtain the vinealeucoblastine(VLB) finished product behind the purifying through homogenate liquid-solid extraction, cavitation suspendible liquid-solid extraction, filtration, extracting solution.
Advantage of the present invention is:
1. the present invention is with short production cycle, power consumption is few, environmentally safe.
2. advantages such as the present invention has replaced traditional material dry ground, heating is extracted or working methods such as mechanical stirring extraction and counter-current extraction, and it is simple to have a method flow, and solvent load is few.
3. the vinealeucoblastine(VLB) yield is 0.07～0.12 ‰, and purity is more than 98%.
Embodiment:
Be to further describe below to of the present invention:
The method flow that the present invention adopts is: extract solvent with alcohol or acid alcohol after the Vinca removal of impurity, and------------extracting solution concentrates, and---------liquid-liquid extraction of cavitation suspendible---concentrates---purifying---finished product to the concentrated solution adjust pH to cavitation suspendible liquid-solid extraction to the homogenate liquid-solid extraction in filtration in filtration.
(1) used Vinca is meant water ratio 20～85% Vinca, and it comprises following three kinds of situations:
The young stem and leaf of the new Vinca of gathering of a, its water ratio is 50～85%.
B is through artificial airing 1～3 day or 1～5 day Vinca of natural air drying, and its water ratio is 20～60%.
C is through extracting the dried Vinca of solvent soaking after 12～48 hours, and its water ratio is 30～70%.Used extraction solvent be 50～70%7 alcohol or 50～70% ethanol respectively with 1～10% tartrate or 1～10% vitriolic mixed extraction solvent.
(2) the homogenate liquid-solid extraction is to adopt the raw material after the removal of impurity to place refiner to carry out the homogenate liquid-solid extraction simultaneously with extracting solvent, and the homogenate time is 10～30 minutes, and raw meal particle size is 150～200 orders after the homogenate.
(3) cavitation suspendible liquid-solid extraction is to place extractor to adopt negative pressure 0.06～0.1MPa method air-breathing or malleation 0.1～0.6MPa air inlet to carry out vinealeucoblastine(VLB) respectively the material after the homogenate to extract, change extraction liquid extraction 2～4 times, each extraction 20～50min after-filtration, united extraction liquid.
(4) filtration can be adopted respectively and hold back component 0.02～10 μ m particle, the multi-hole micro leaching film of negative pressure 0.06～0.1MPa carries out suction filtration, holds back component 0.02～10 μ m particle, the multi-hole micro leaching film of malleation 0.2～1MPa carries out press filtration or rotating speed 1800～2400r/min, the whizzer of holding back component 0.02～10 μ m particle porous membrane carries out methods such as centrifuging, and the extracting solution after filtering is collected.
(5) to concentrate be to be 80～110 ℃ in temperature to extracting solution, and negative pressure is to extract solvent recuperation under 0.06～0.1MPa or the condition of normal pressure.
(6) the concentrated solution adjust pH is with 0.5～10% sulfuric acid or 0.5～10% tartrate the pH value of concentrated solution to be transferred to 1～3, leaving standstill 5～10min behind the mixing under negative pressure 0.06～0.1Mpa, with the pH value tone pitch 8～12 of strong aqua, leave standstill the 5min after-filtration again with concentrated solution.
(7) filter the method identical that adopt with (4), can adopt respectively and hold back component 0.02～10 μ m particle, the multi-hole micro leaching film of negative pressure 0.06～0.1MPa carries out suction filtration, holds back component 0.02～10 μ m particle, the multi-hole micro leaching film of malleation 0.2～1MPa carries out press filtration or rotating speed 1800～2400r/min, the whizzer of holding back component 0.02～10 μ m particle porous membrane carries out method, separating filtrate and filter cakes such as centrifuging.
(8) liquid-liquid extraction of cavitation suspendible is that (7) resulting filtrate is mixed with the extraction agent equal-volume, air-breathing or malleation is that cavitation suspendible liquid-liquid extraction 5～30min is carried out in 0.1～0.6MPa air inlet under negative pressure 0.06～0.1MPa condition, extraction agent adopts methylene dichloride, trichloromethane or sherwood oil, extraction times is 1～3 time, obtains the extraction liquid of methylene dichloride, trichloromethane or sherwood oil.
(9) concentrating is to be 30～60 ℃ in temperature, and negative pressure is to extract solvent recuperation under 0.06～0.1MPa or the condition of normal pressure, extraction liquid is concentrated into does the resulting solids in back and merge with the filter cake that (7) obtain, and is further purified.
(10) purifying can adopt recrystallization or silica gel partition chromatography to carry out, and used recrystallization solvent is that concentration is 75～95% ethanol, methyl alcohol or acetonitrile solution, and the silica gel column chromatography elutriant is to contain the methylene dichloride of 1～5% methyl alcohol or the solution of trichloromethane.
(11), be to reclaim solvent under 35～55 ℃ of conditions can obtain the vinealeucoblastine(VLB) product in negative pressure 0.06～0.1MPa, temperature with after the relevant composition merging of resulting elutriant.
Below embodiments of the invention are described in further detail:
Embodiment 1:
Getting new Vinca 50kg (water ratio 70%) and 70% extraction using alcohol agent 150kg drops into refiner and carries out the homogenate extraction while mixing, homogenate is squeezed into through underflow pump and is had that to hold back component be 0.02～10 μ m filter membrane, negative pressure is in the extractor of 0.1MPa, negative pressure-cavitation homogenous solid-liquid phase extraction 20～50min, suction filtration, material is again through 70% ethanol 250kg cavitation suspension extraction, repeat this operation 2～3 times, merging filtrate, the vinealeucoblastine(VLB) extraction yield is 0.09～0.14 ‰, filtrate is 80～110 ℃ through temperature, negative pressure is that 0.06～0.1MPa solvent recovery tower concentrates recovery ethanol, after sulfuric acid is regulated concentrated solution pH=2, negative pressure-cavitation homogenous solid-liquid phase 5～10min, leave standstill 5min, suction filtration, the aqueous solution of continuation usefulness pH=2 and the filter residue negative pressure-cavitation homogenous solid-liquid phase after the filtration 2～3 times, merge acid solution behind the suction filtration, regulate acid solution to pH=8～12 with strong aqua, suction filtration, filter cake keeps, filtrate and equal-volume sherwood oil place extractor to carry out the negative pressure-cavitation homogenous solid-liquid phase liquid-liquid extraction 2～3 times, time is 5～10min/ time, the petroleum ether extraction liquid that leaves standstill behind the separatory is 30～50 ℃ through temperature again, negative pressure is that 0.06～0.1MPa or non-pressurized solvent recuperation jar concentrate the recovery sherwood oil, extraction liquid is concentrated into dried, merge with the filter cake that obtains above again, after crystallization and column chromatography for separation, obtain vinealeucoblastine(VLB) 1.46g, purity 95.4%, obtain the vinealeucoblastine(VLB) 1.27g of purity more than 98.3%, yield 0.085 ‰ through recrystallization again.
Embodiment 2:
Getting 60% extraction using alcohol agent 150kg that Vinca 50kg (water ratio 40%) and sulfuric acid is modulated to pH=2 drops into refiner and carries out the homogenate extraction while mixing, homogenate is squeezed into through underflow pump and is had that to hold back component be 0.02～10 μ m filter membrane, negative pressure is in the extractor of 0.1MPa, negative pressure-cavitation homogenous solid-liquid phase extraction 20～50min, suction filtration, material is again through the 60% ethanol 250kg cavitation suspension extraction of pH=2, repeat this operation 2～4 times after, merging filtrate, this moment, the vinealeucoblastine(VLB) extraction yield was 0.08～0.12 ‰, filtrate is 80～110 ℃ through temperature, negative pressure be 0.06～0.1MPa solvent recovery tower concentrate reclaim concentrated solution, after concentrated solution is regulated pH value to 8～12 with strong aqua, leave standstill 5min, suction filtration, separating filtrate and filter cake, filtrate places extractor to carry out the negative pressure-cavitation homogenous solid-liquid phase liquid-liquid extraction 2～3 times with equal-volume methylene dichloride or trichloromethane again, time is 5～10min/ time, the methylene dichloride or the chloroform extraction liquid that leave standstill behind the separatory are 45～50 ℃ through temperature again, negative pressure is that 0.06～0.1Mpa or non-pressurized solvent recuperation jar concentrate recovery methylene dichloride or trichloromethane, obtain methylene dichloride or trichloromethane concentrated solution, it is concentrated into the filter cake of doing the back and obtaining above merges, carrying out wash-out through the partition column chromatography of silica gel again separates, eluent adopts methylene dichloride or the trichloromethane that contains 1～3% methyl alcohol, eluent reclaims and concentrates, and gets the vinealeucoblastine(VLB) finished product.Acidifying is after recrystallization obtains finished product purity is 99.1%, and weight is 2.49g, and yield is 0.083 ‰.
Embodiment 3:
Getting dried Vinca 15kg soaks behind the 24h with 50% extraction using alcohol agent 30kg and drops into refiner while mixing with 50% extraction using alcohol agent 50kg and carry out homogenate and extract, homogenate is squeezed into through underflow pump and is had that to hold back component be 0.02～10 μ m filter membrane, negative pressure is in the extractor of 0.1MPa, negative pressure-cavitation homogenous solid-liquid phase extraction 20-50min, suction filtration, material is again through 50% ethanol 150kg cavitation suspension extraction, repeat this operation 3～4 times, merging filtrate, the vinealeucoblastine(VLB) extraction yield is 0.08～0.12 ‰, filtrate is 80～110 ℃ through temperature, negative pressure is that 0.06～0.1MPa solvent recovery tower concentrates recovery ethanol, after sulfuric acid is regulated concentrated solution pH=2, negative pressure-cavitation homogenous solid-liquid phase 5～10min, leave standstill 5min, suction filtration, the aqueous solution of continuation usefulness pH=2 and the filter residue negative pressure-cavitation homogenous solid-liquid phase after the filtration 2～3 times, merge acid solution behind the suction filtration, regulate acid solution to pH 〉=10 with strong aqua, suction filtration, filter cake keeps, filtrate and equal-volume sherwood oil place extractor to carry out the negative pressure-cavitation homogenous solid-liquid phase liquid-liquid extraction 2～3 times, time is 5～10min/ time, the petroleum ether extraction liquid that leaves standstill behind the separatory is 30～40 ℃ through temperature again, negative pressure is that 0.06～0.1Mpa or non-pressurized solvent recuperation jar concentrate the recovery sherwood oil, extraction liquid is concentrated into dried, merge with the filter cake that obtains above again, after crystallization and column chromatography for separation, obtain vinealeucoblastine(VLB) 1.37g, purity 95.3%, obtain the vinealeucoblastine(VLB) 1.17g of purity more than 98.2%, yield 0.078 ‰ through recrystallization again.
Claims (9)
1, a kind of vinealeucoblastine(VLB) high-efficiency method for producing is characterized in that: extract solvent with alcohol or acid alcohol after the Vinca removal of impurity and concentrate, concentrated solution adjust pH, filtration, the liquid-liquid extraction of cavitation suspendible, concentrate, obtain the vinealeucoblastine(VLB) finished product behind the purifying through homogenate liquid-solid extraction, cavitation suspendible liquid-solid extraction, filtration, extracting solution.
2, according to the described vinealeucoblastine(VLB) high-efficiency method for producing of claim 1, it is characterized in that: described Vinca is meant water ratio 20～85% Vinca, and it comprises following three kinds of situations:
(1) young stem and leaf of new Vinca of gathering, its water ratio is 50～85%.
(2) through artificial airing 1～3 day or 1～5 day Vinca of natural air drying, its water ratio is 20～60%.
(3) through extracting the dried Vinca of solvent soaking after 12～48 hours, its water ratio is 30～70%.
3, according to the described vinealeucoblastine(VLB) high-efficiency method for producing of claim 1, it is characterized in that: described extraction solvent is 50～70%7 alcohol and 1～10% tartrate or 1～10% vitriolic mixed extraction solvent.
4, according to the described vinealeucoblastine(VLB) high-efficiency method for producing of claim 1, it is characterized in that: described homogenate liquid-solid extraction is to adopt Vinca to place refiner to carry out homogenate and extraction simultaneously with extracting solvent, and the homogenate extraction time is 10～30 minutes.
5, according to the described vinealeucoblastine(VLB) high-efficiency method for producing of claim 1, it is characterized in that: described cavitation suspendible liquid-solid extraction is to place extractor to adopt the air-breathing or malleation 0.1～0.6MPa air inlet of negative pressure 0.06～0.1MPa the material after the homogenate, and the extraction time is 20～50 minutes.
6, according to the described vinealeucoblastine(VLB) high-efficiency method for producing of claim 1, it is characterized in that: filter to adopt and hold back component 0.02～10 μ m particle, the multi-hole micro leaching film of negative pressure 0.06～0.1MPa carries out suction filtration, holds back component 0.02～10 μ m particle, the multi-hole micro leaching film of malleation 0.2～1MPa carries out press filtration or rotating speed 1800～2400r/min, and the whizzer of holding back component 0.02～10 μ m particle porous membrane carries out methods such as centrifuging.
7, according to the described vinealeucoblastine(VLB) high-efficiency method for producing of claim 1, it is characterized in that: it is to be 80～110 ℃ in temperature that described extracting solution concentrates, and negative pressure is to carry out under 0.06～0.1MPa condition.
8, according to the described vinealeucoblastine(VLB) high-efficiency method for producing of claim 1, it is characterized in that: described concentrated solution adjust pH is meant with 0.5～10% sulfuric acid or 0.5～10% tartrate the pH value of concentrated solution is transferred to 1～3, behind mixing under negative pressure 0.06～0.1MPa condition, left standstill 5～10 minutes, with ammoniacal liquor the pH value of concentrated solution is transferred to 8～12 again.
9, according to the described vinealeucoblastine(VLB) high-efficiency method for producing of claim 1, it is characterized in that: the liquid-liquid extraction of described cavitation suspendible is meant that the filtrate that the concentrated solution adjust pH is obtained after filtering mixes with the extraction agent equal-volume, air-breathing or malleation is 0.1～0.6MPa air inlet under negative pressure 0.06～0.1MPa condition, the extraction time is 5～30 minutes, and extraction agent adopts methylene dichloride, trichloromethane or sherwood oil.
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100336817C (en) * | 2005-07-12 | 2007-09-12 | 东北林业大学 | Method of chromatography preparing high purity catharanthine sulphate by continuous medium pressure column |
| CN100364996C (en) * | 2005-07-13 | 2008-01-30 | 东北林业大学 | Purification method of catharanthine and vincristine |
| CN101337972B (en) * | 2008-08-12 | 2010-09-15 | 中国热带农业科学院热带作物品种资源研究所 | Process for extracting vincaleuucoblastine from vinca |
| CN101638413B (en) * | 2009-08-28 | 2011-12-14 | 广州汉方现代中药研究开发有限公司 | Separation and purification method for vinca alkaloids |
| CN101522679B (en) * | 2006-09-20 | 2013-12-18 | 皮埃尔法布雷医药公司 | Fluorinated catharanthine derivatives, their preparation and their utilisation as vinca dimeric alkaloid precursors |
| CN104262362A (en) * | 2014-09-01 | 2015-01-07 | 海南希源化工科技有限公司 | Vinblastine extraction and purification method |
| CN104370911A (en) * | 2014-12-13 | 2015-02-25 | 海南希源化工科技有限公司 | Catharanthine tartrate preparation method |
-
2004
- 2004-02-18 CN CN 200410013558 patent/CN1218950C/en not_active Expired - Fee Related
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100336817C (en) * | 2005-07-12 | 2007-09-12 | 东北林业大学 | Method of chromatography preparing high purity catharanthine sulphate by continuous medium pressure column |
| CN100364996C (en) * | 2005-07-13 | 2008-01-30 | 东北林业大学 | Purification method of catharanthine and vincristine |
| CN101522679B (en) * | 2006-09-20 | 2013-12-18 | 皮埃尔法布雷医药公司 | Fluorinated catharanthine derivatives, their preparation and their utilisation as vinca dimeric alkaloid precursors |
| CN101337972B (en) * | 2008-08-12 | 2010-09-15 | 中国热带农业科学院热带作物品种资源研究所 | Process for extracting vincaleuucoblastine from vinca |
| CN101638413B (en) * | 2009-08-28 | 2011-12-14 | 广州汉方现代中药研究开发有限公司 | Separation and purification method for vinca alkaloids |
| CN104262362A (en) * | 2014-09-01 | 2015-01-07 | 海南希源化工科技有限公司 | Vinblastine extraction and purification method |
| CN104370911A (en) * | 2014-12-13 | 2015-02-25 | 海南希源化工科技有限公司 | Catharanthine tartrate preparation method |
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| CN1218950C (en) | 2005-09-14 |
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