CN101891740A - Method for extracting laburnine from upper part of thermopsis lanceolate - Google Patents
Method for extracting laburnine from upper part of thermopsis lanceolate Download PDFInfo
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- CN101891740A CN101891740A CN 201010240158 CN201010240158A CN101891740A CN 101891740 A CN101891740 A CN 101891740A CN 201010240158 CN201010240158 CN 201010240158 CN 201010240158 A CN201010240158 A CN 201010240158A CN 101891740 A CN101891740 A CN 101891740A
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Abstract
The invention discloses a method for extracting laburnine from the upper part of thermopsis lanceolate. The method comprises the following steps of: (A1) pulverizing the upper part of thermopsis lanceolate which is collected in a full bloom stage, extracting and concentrating to obtain an extract; (A2) acidizing the extract by using acid water, separating to remove impurities which are insoluble in acid to obtain an acid water liquor containing the laburnine; (A3) alkalizing the acid water liquor and extracting by using an organic solvent to obtain total alkaloids mainly containing the laburnine; (A4) dissolving the total alkaloids in water, extracting by using an organic solvent, recovering the organic solvent and crystallizing to obtain the laburnine with higher purity; and (A5) dissolving the higher-purity laburnine obtained in the step (A4) in an organic solvent and carrying out column chromatography to obtain a laburnine product of which the purity is more than 99 percent.
Description
Technical field
The invention belongs to the pharmaceutical technology field, be specifically related to from top, lanceolata Huang Hua meadow, extract the method for Tocosamine.
Background technology
The yellow China of lanceolata (T. lanceolata R.Br.) has another name called Herba Thermopsis Lanceolatae, Thermopsis lupinoides (L.) Link., is that pulse family (leguminoseae) Thermopsis lupinoides (L.) Link. belongs to (Thermopsis) per nnial herb.The main substep of this platymiscium in Qinghai of China, provinces and regions such as the Inner Mongol, Ningxia, Sichuan, Gansu, also there are distribution in Russia, Mongolia, are born in meadow, desert, high mountain steppe meadow, sand dune, underbrush and limit, field, roadside, idol enters the farmland.
According to the literature, seed, flower, cauline leaf, the root of the yellow China of lanceolata are all poisonous, are because it contains a large amount of Tocosamines.The Flower of Chinese Peashrub bases is meant that intramolecularly has three ring or the quinolizidine kind alkaloid compounds of Fourth Ring structure of a-pyridone ring, mainly comprises the rhombinin (anagyrine), thermopsine (thermopsine) of Tocosamine (cytisine), N-Methylcytisine (N-methylcytisine) and the Fourth Ring structure of tricyclic structure etc.The Tocosamine in the yellow Central China of lanceolata has extremely strong physiologically active, the aqueous solution with Tocosamine 0.15% supplies muscle or intravenous injection clinically, rescue is because of reflectivity breathlessness, shock and the asphyxia neonatorum etc. of performing the operation and wound causes, recent research shows, this Alkaloid also has many-sided pharmacological actions such as anti-arrhythmia, anti-microbial infection, antiulcer agent, leukocyte increasing, and particularly this compounds has stronger antitumour activity.In addition, there is research to claim phosphorated Tocosamine derivative also to have hepatoprotective effect; Tocosamine is the main raw material of a kind of novel smoking deterent " Varenicline " of Pfizer Inc.'s production; The pesticide composition that contains Tocosamine is a kind of agricultural chemicals of high-efficiency broad spectrum.
The Tocosamine in the yellow Central China of lanceolata extracts, and mainly is being extracted as the master from seed at present, and the Tocosamine purity of extracting from seed is lower, the production cost height.
Therefore, there is defective in prior art, needs to improve perfect.
Summary of the invention
Technical problem to be solved by this invention is at the deficiencies in the prior art, and a kind of method of extracting Tocosamine from top, lanceolata Huang Hua meadow is provided.
For achieving the above object, the invention provides a kind of method of from top, lanceolata Huang Hua meadow, extracting Tocosamine, wherein, may further comprise the steps: A1, pulverize the top, lanceolata Huang Hua meadow that full-bloom stage is gathered, through extracting, concentrate medicinal extract, A2 with the sour water acidifying of described medicinal extract, separates and removes the disacidify insoluble impurities, obtain containing the acid liquid of Tocosamine, A3 with described acid liquid alkalization, extracts with organic solvent again, the total alkaloids that is mainly contained Tocosamine, A4 is dissolved in water with described total alkaloids, extracts with organic solvent again, reclaim organic solvent and crystallization, obtain the higher Tocosamine of purity; A5, the higher Tocosamine of described purity that steps A 4 is obtained is dissolved in organic solvent, and carries out column chromatography, obtains the Tocosamine product of purity more than 99%.
Described method, wherein, operation below described steps A 1 concrete execution the: top, described lanceolata Huang Hua meadow is crushed to the 10-20 order, pack in the stainless steel multi-function extractor, the 12 times of amounts of methyl alcohol that add 75%-85% altogether, divide 3 thermal backflows to extract, united extraction liquid is evaporated to relative density 1.15-1.20.
Described method, wherein, among described steps A 3 and the A4, the regulator solution pH value is to 10-13, with the organic solvent extraction, do not have tangible alkaloid reaction to thin-layer chromatography till.
Described method, wherein, described step with the organic solvent extraction repeats more than twice.
Described method, wherein, described column chromatography uses alumina column to carry out.
Described method, wherein, described aluminum oxide order number is the 60-300 order.
Described method, wherein, described organic solvent is one or more mixtures in toluene, dimethylbenzene, methylene dichloride, trichloromethane, ether, the ethyl acetate.
Described method, wherein, described acidification step adopts one of hydrochloric acid, sulfuric acid, phosphoric acid to carry out.
Described method, wherein, described alkalinization step adopts one of sodium hydroxide, yellow soda ash, sodium bicarbonate, strong aqua to carry out.
Described method, wherein, in the described crystallisation step, recrystallisation solvent adopts one or more mixing in acetone, ethanol, the ethyl acetate.
Operational path of the present invention is simple, and the product cost that makes is low, purity can reach more than 99%.
Description of drawings
Fig. 1 is a process flow sheet of the present invention;
Fig. 2 is a Tocosamine reference substance high-efficient liquid phase chromatogram, peak 1 retention time 5.047 wherein, peak height 148150 peak areas, 1151629 areas (%) 100.0000;
Fig. 3 is the high-efficient liquid phase chromatogram of embodiment 1 sample, wherein peak 1 retention time 5.034 peak height 145466 peak areas, 1135225 areas (%) 100.0000;
Fig. 4 is the high-efficient liquid phase chromatogram of embodiment 2 samples, wherein peak 1 retention time 5.026 peak height 145687 peak areas, 1142127 areas (%) 100.0000;
Fig. 5 is the high-efficient liquid phase chromatogram of embodiment 3 samples, wherein peak 1 retention time 5.030 peak height 148150 peak areas, 1151629 areas (%) 100.0000.
Embodiment
Below by specific embodiment, the present invention is described in detail.
Condition and result that thin-layer chromatography of the present invention detects:
1, thin layer plate:
(1), commercially available silica gel G plate (Haiyang Chemical Plant, Qingdao)
(2), self-control silica gel G plate: get the silica gel G that thin-layer chromatography is used, the sodium carboxymethyl cellulose solution furnishing pasty state with 0.5% is stirred to no bubble, makes thin layer plate, faces with preceding to activate 30min under 105 ℃ condition.
2, reference substance: Tocosamine (content is more than 99.5%)
3, developping agent:
Ethyl acetate: methyl alcohol volume ratio 3: 2
4, developer: the Dragendorff's reagent of improvement
5, thin-layer chromatography result: Rf value 0.23
Exsiccant lanceolata Huang Hua meadow top 500kg with the full-bloom stage collection, be crushed to the 10-20 order, in the 4.5 tons of stainless steel multi-function extractors of packing into, divide the methyl alcohol that adds 2500kg, 2000kg, 1500kg 75% for three times, heating and refluxing extraction, Heating temperature 62-65 ℃, 2 hours for the first time extraction time, 2 hours for the second time, 1 hour for the third time, merge No. three times extracting solution, be evaporated to relative density 1.15 (heat is surveyed), get medicinal extract 162kg.
In medicinal extract, add dilute hydrochloric acid solution, regulate pH value 2-3 alkaloid is dissolved in the sour water, separate and remove the disacidify insoluble impurities.The sour water layer adds strong aqua alkalization, regulates pH value 10-11, with xylene extraction for several times, do not have tangible alkaloid reaction to thin-layer chromatography till, reclaim dimethylbenzene, total alkaloids medicinal extract is 15.1kg.This total alkaloids is dissolved in the water, regulates pH value 10-11, with xylene extraction for several times, do not have tangible alkaloid reaction to thin-layer chromatography till, reclaim dimethylbenzene and get Tocosamine yellow crystal 1.70kg.With Tocosamine yellow crystal acetic acid ethyl dissolution, cross 60-100 order alumina column, reclaim ethyl acetate, there is a large amount of little yellow needle crystal to separate out fractional crystallization, drying in the solution, obtain Tocosamine 1.25kg, yield is 2.5 ‰, and detecting purity with high performance liquid chromatography is 98.7%, as shown in Figure 3.
Embodiment 2:
Exsiccant lanceolata Huang Hua meadow top 500kg with the full-bloom stage collection, be crushed to the 10-20 order, in the 4.5 tons of stainless steel multi-function extractors of packing into, divide the methyl alcohol that adds 2500kg, 2000kg, 1500kg 85% for three times, heating and refluxing extraction, Heating temperature 62-65 ℃, 2 hours for the first time extraction time, 2 hours for the second time, 1 hour for the third time, merge No. three times extracting solution, be evaporated to relative density 1.20 (heat is surveyed), get medicinal extract 149kg.
In medicinal extract, add dilute hydrochloric acid solution, regulate pH value 3-4 alkaloid is dissolved in the sour water, separate and remove the disacidify insoluble impurities.The sour water layer adds 20% sodium hydroxide solution alkalization, regulates pH value 12-13, with dichloromethane extraction for several times, do not have tangible alkaloid reaction to thin-layer chromatography till, reclaim methylene dichloride, total alkaloids medicinal extract is 13.7kg.This total alkaloids is dissolved in the water, regulates pH value 12-13, with dichloromethane extraction for several times, do not have tangible alkaloid reaction to thin-layer chromatography till, reclaim methylene dichloride and get Tocosamine yellow crystal 1.66kg.With Tocosamine yellow crystal acetone solution, cross 100-200 order alumina column, reclaim acetone, there is a large amount of little yellow needle crystal to separate out in the solution, fractional crystallization, drying obtains Tocosamine 1.38kg, yield is 2.76 ‰, and detecting purity with high performance liquid chromatography was 99.0% (as shown in Figure 4).
Embodiment 3:
Exsiccant lanceolata Huang Hua meadow top 500kg with the full-bloom stage collection, be crushed to the 10-20 order, in the 4.5 tons of stainless steel multi-function extractors of packing into, divide the methyl alcohol that adds 2500kg, 2000kg, 1500kg80% for three times, heating and refluxing extraction, Heating temperature 62-65 ℃, 2 hours for the first time extraction time, 2 hours for the second time, 1 hour for the third time, merge No. three times extracting solution, be evaporated to relative density 1.19 (heat is surveyed), get medicinal extract 156kg.
In medicinal extract, add dilute hydrochloric acid solution, regulate pH value 2-3 alkaloid is dissolved in the sour water, separate and remove the disacidify insoluble impurities.The sour water layer adds 10% sodium hydroxide solution alkalization, regulates pH value 12-13, with chloroform extraction for several times, do not have tangible alkaloid reaction to thin-layer chromatography till, reclaim trichloromethane, total alkaloids medicinal extract is 14.5kg.This total alkaloids is dissolved in the water, regulates pH value 12-13, with chloroform extraction for several times, do not have tangible alkaloid reaction to thin-layer chromatography till, reclaim trichloromethane and get Tocosamine yellow crystal 1.88kg.With Tocosamine yellow crystal acetone solution, cross 200-300 order alumina column, reclaim acetone, there is a large amount of little yellow needle crystal to separate out in the solution, fractional crystallization, drying obtains Tocosamine 1.47kg, yield is 2.94 ‰, and detecting purity with high performance liquid chromatography was 99.2% (as shown in Figure 5).
The high performance liquid chromatography testing conditions that adopts in the foregoing description 1 to 3 is:
Chromatographic column: C18 post (4.6mm * 250mm, 5um) moving phase: 0.05mol/L sodium dihydrogen phosphate (phosphoric acid 2ml): methyl alcohol: sodium perchlorate (85ml: 15ml: 1.0g);
Detect wavelength: 306nm
Flow velocity: 1ml/min
Column temperature: 25 ℃
Sample introduction concentration: 0.1mg/Ml
Sample size: 10uL; Theoretical plate number is calculated by the Tocosamine peak should be not less than 5000.
Should be understood that, for those of ordinary skills, can be improved according to the above description or conversion, and all these improvement and conversion all should belong to the protection domain of claims of the present invention.
Claims (10)
1. a method of extracting Tocosamine from top, lanceolata Huang Hua meadow is characterized in that, may further comprise the steps: A1, the top, lanceolata Huang Hua meadow that full-bloom stage is gathered is pulverized, and obtain medicinal extract through extracting, concentrating; A2 with the sour water acidifying of described medicinal extract, separates and removes the impurity that is insoluble to acid, obtains containing the acid liquid of Tocosamine; A3 with described acid liquid alkalization, again with the organic solvent extraction, is mainly contained the total alkaloids of Tocosamine; A4 is dissolved in water with described total alkaloids, with the organic solvent extraction, reclaims organic solvent and crystallization again, obtains the higher Tocosamine of purity; A5, the higher Tocosamine of described purity that steps A 4 is obtained is dissolved in organic solvent, and carries out column chromatography, obtains the Tocosamine product of purity more than 99%.
2. method according to claim 1, it is characterized in that, operation below described steps A 1 concrete execution the: top, described lanceolata Huang Hua meadow is crushed to the 10-20 order, pack in the stainless steel multi-function extractor, divide and add the methyl alcohol thermal backflow extraction that concentration is 75%-85% for 3 times, the weight that adds methyl alcohol for 3 times altogether is 12 times of top, described lanceolata Huang Hua meadow, merges described thermal backflow and extracts the extracting solution that obtains, and is evaporated to relative density 1.15-1.20.
3. method according to claim 2 is characterized in that, among described steps A 3 and the A4, the regulator solution pH value is to 10-13, with the organic solvent extraction, do not have tangible alkaloid reaction to thin-layer chromatography till.
4. method according to claim 3 is characterized in that, described step with the organic solvent extraction repeats more than twice.
5. method according to claim 1 is characterized in that, described column chromatography uses alumina column to carry out.
6. method according to claim 1 is characterized in that, described aluminum oxide order number is the 60-300 order.
7. according to the arbitrary described method of claim 1 to 6, it is characterized in that described organic solvent is one or more mixtures in toluene, dimethylbenzene, methylene dichloride, trichloromethane, ether, the ethyl acetate.
8. according to the arbitrary described method of claim 1 to 6, it is characterized in that described acidification step adopts one of hydrochloric acid, sulfuric acid, phosphoric acid to carry out.
9. according to the arbitrary described method of claim 1 to 6, it is characterized in that described alkalinization step adopts one of sodium hydroxide, yellow soda ash, sodium bicarbonate, strong aqua to carry out.
10. according to the arbitrary described method of claim 1 to 6, it is characterized in that in the described crystallisation step, recrystallisation solvent adopts one or more mixing in acetone, ethanol, the ethyl acetate.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103588773A (en) * | 2013-11-07 | 2014-02-19 | 东南大学 | Method for extracting and separating cytisine |
| CN104961739A (en) * | 2015-07-22 | 2015-10-07 | 陕西省西安植物园 | Method for extracting eulexine from aboveground parts of thermopsis lanceolate |
| CN106188057A (en) * | 2016-07-21 | 2016-12-07 | 西安岳达生物科技股份有限公司 | A kind of separating and extracting process of eulexine |
| CN107266448A (en) * | 2017-07-25 | 2017-10-20 | 王答祺 | Prepare the new technology of sparteine |
| WO2019144204A1 (en) * | 2018-01-29 | 2019-08-01 | Sopharma Ad | Method for isolation of cytisine |
| CN111374997A (en) * | 2020-03-25 | 2020-07-07 | 青海民族大学 | Method for preparing PD-1/PD-L1 inhibitor from wakame |
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| CN101624393A (en) * | 2009-08-04 | 2010-01-13 | 王答祺 | Method for extracting cytosine and thermopsine from thermopsis lanceolata seeds |
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Cited By (13)
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|---|---|---|---|---|
| CN103588773A (en) * | 2013-11-07 | 2014-02-19 | 东南大学 | Method for extracting and separating cytisine |
| CN103588773B (en) * | 2013-11-07 | 2016-01-06 | 东南大学 | A kind of extraction and separation method of Tocosamine |
| CN104961739A (en) * | 2015-07-22 | 2015-10-07 | 陕西省西安植物园 | Method for extracting eulexine from aboveground parts of thermopsis lanceolate |
| CN106188057A (en) * | 2016-07-21 | 2016-12-07 | 西安岳达生物科技股份有限公司 | A kind of separating and extracting process of eulexine |
| CN107266448A (en) * | 2017-07-25 | 2017-10-20 | 王答祺 | Prepare the new technology of sparteine |
| JP7083920B2 (en) | 2018-01-29 | 2022-06-13 | ソファーマ アクツィオネルノ ドロジェストヴォ | Cytisinicline isolation method |
| CN111698997A (en) * | 2018-01-29 | 2020-09-22 | 索非药剂有限公司 | Method for separating cytisine |
| JP2021512169A (en) * | 2018-01-29 | 2021-05-13 | ソファーマ アクツィオネルノ ドロジェストヴォ | Cytisine Isolation Method |
| WO2019144204A1 (en) * | 2018-01-29 | 2019-08-01 | Sopharma Ad | Method for isolation of cytisine |
| US11384080B2 (en) | 2018-01-29 | 2022-07-12 | Sopharma Ad | Method for isolation of cytisine |
| US11505552B2 (en) | 2018-01-29 | 2022-11-22 | Sopharma Ad. | Method for isolation of cytisine |
| AU2018403991B2 (en) * | 2018-01-29 | 2022-12-01 | Sopharma Ad | Method for isolation of cytisine |
| CN111374997A (en) * | 2020-03-25 | 2020-07-07 | 青海民族大学 | Method for preparing PD-1/PD-L1 inhibitor from wakame |
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Application publication date: 20101124 |