CN1317283C - Bilobalide extraction and purification process - Google Patents
Bilobalide extraction and purification process Download PDFInfo
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- CN1317283C CN1317283C CNB2005100412661A CN200510041266A CN1317283C CN 1317283 C CN1317283 C CN 1317283C CN B2005100412661 A CNB2005100412661 A CN B2005100412661A CN 200510041266 A CN200510041266 A CN 200510041266A CN 1317283 C CN1317283 C CN 1317283C
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Abstract
The present invention discloses a technology for extracting and purifying ginkgolide, which comprises the following steps: dried gingko leaves are weighed and pulverized, and then are extracted by using ethanol or methanol of which the weight is increased by several times of that of medicinal materials; after the ethanol or methanol is recovered by extraction liquid, impurities are removed by defatting solvent; after extraction and secondary impurity removal, a crude product is obtained; the crude product is recrystallized by using ethanol; after the crude product is filtered and dried, a purified ginkalide product is obtained. The technology has the advantages of low cost, little pollution, high safety and high purity of the obtained ginkalide.
Description
Technical field
The invention belongs to field of traditional Chinese medicine pharmacy, what relate to is the technology of extracting purifying Ginkgo Leaf main active ingredient bilobalide from Ginkgo Leaf.
Background technology
Ginkgolide compound is the active platelet-activating factor antagonist of the consistent Strong that generally acknowledges of domestic and foreign literature.Platelet activation factor is the important medium of multiple disease incidences such as cardiovascular and cerebrovascular.Shenyang Pharmaceutical University opened pre-sun etc. and studies have shown that Ginkgolide B is the platelet activation factor potent inhibitor calendar year 2001, and Ginkgolide A, C etc. have synergy.Can reduce the death time of mouse with bilobalide 32mg/kg; 4,8,16mg/kg can reduce MCAO rat cerebral infarction scope, improves behavior disorder and cerebral tissue pathomorphism.The beautiful grade of the Wang Qiu of China Medicine University in the same year studies have shown that bilobalide 10,20,40mg/kg obviously improve the rats with cerebral ischemia neurobehavioral, and cerebral infarct size and brain water content significantly reduce; Studies show that bilobalide has reduces MDA, the LD content in the brain tissue homogenate behind the ischemic, improves SOD and GSH activity.The cerebral tissue pathological section confirms that bilobalide has provide protection to neurocyte.Conclusion is that bilobalide has provide protection to focal cerebral ischemia in rats.It is all in ischemic tissue that literature research is thought, because platelet aggregation reduces tissue blood flow's amount, influences this histocyte functional recovery.If the volume of blood flow deficiency of cerebral tissue then can cause multiple cerebral ischemia or apoplexy.Ginkgolide compound has obtained the support approval of document and lot of experiments in the clinical treatment that can be used for ishemic stroke and cerebral infarction.Based on this, to the research of ginkgolide compound in the Ginkgo Leaf, development and application has become the focus of current new drug development.But bilobalide content is low in the Ginkgo Leaf, is used to extract the technology cost height of bilobalide at present, and yield is low, can't satisfy scientific research, production and demands of applications.Seek the bilobalide extraction process of optimizing, also be one of problem of everybody research in recent years for this reason.
Summary of the invention
The purpose of this invention is to provide the bilobalide that a kind of cost is low, yield is high, security is good extracts and purifying process.
The objective of the invention is to realize by following measures:
A kind of extraction of bilobalide and purifying process comprise the following step:
Take by weighing the ginkgo cured leaf, pulverize, add the ethanol or the methanol extraction of several times amount by medicinal material weight, extracting solution reclaims the degreasing solvent removal of impurities of alcohol back, extraction, removal of impurities again, raw product, use ethyl alcohol recrystallization, filtration, the dry bilobalide highly finished product that get.
Described extraction and purifying process, wherein the used ethanol of ginkgo cured leaf extraction is that concentration is 5% ethanol～95% ethanol, and methyl alcohol is that concentration is 5% methyl alcohol～anhydrous methanol, and the consumption of ethanol or methyl alcohol is 2～10 times of medicinal material weight.
Described extraction and purifying process, wherein degreasing solvent is tetracol phenixin, kerosene or gasoline.
Described extraction and purifying process, wherein extraction solvent is butanone, propyl carbinol, ether, chloroform or ethyl acetate.
Described extraction and purifying process, wherein the removal of impurities solvent is saturated limewater, 0.4-5% borax solution, 0.5-5% potassium bicarbonate solution or 5-15% sodium acetate soln again.
Described extraction and purifying process, wherein the bilobalide recrystallization solution is that concentration is 40～95% ethanolic solns, the bilobalide drying temperature is 80～90 ℃.
Advantage of the present invention:
1, this law adopts solvent method to extract the purifying bilobalide, cuts off domestic resin column commonly used at present and other sorbent materials and produces bilobalide.This law is simple to operate, and the workshop appliance less investment need not be set up special workshops such as resin column.
2, this law removal of impurities solvent is a gasoline, liming, borax solution, and more cheap than prices such as sherwood oil commonly used at present, chloroforms, cost is low, and is safe.
3, this law extraction commonly used solvent is a dilute alcohol solution, and is littler, cheap than acetone soln toxicity commonly used at present.
4, this law extraction bilobalide rate of transform reaches more than 60% and (the results are shown in Table 1).
Three batches of bilobalide sample detection of table 1 the present invention result
| Batch | 031016 | 031028 | 031110 |
| Charging capacity (kg) bilobalide must be measured (g) rate of transform (%) | 60 53.1 88.5 | 60 53.6 89.3 | 60 54.5 90.8 |
5, this law is extracted Ginkgolide A, B, C and bilobalide total content up to more than 92%, and wherein Ginkgolide B content reaches more than 40% and (the results are shown in Table 2).
Table 2 extracts a plurality of lot number measurement results of bilobalide by the present invention
| Lot number | Total bilobalide (%) | Ginkgolide B (%) |
| 040105 040107 040109 | 104.1 103.8 104.0 | 49.8 49.9 49.9 |
6, major impurity ginkgolic acid content can be less than 2/1000000ths (the results are shown in Table 3) in this law extraction bilobalide.
Table 3 the present invention extracts major impurity ginkgolic acid assay result in the bilobalide
| Lot number | 031016 | 031028 | 031110 |
| Total ginkgolic acids (PPM) | 0.13 | 0.15 | 0.13 |
Above-mentioned table 1,2,3 measurement results are all measured according to high performance liquid chromatography (appendix VID of Chinese Pharmacopoeia version in 2005).(lot number the 031016,031028, the 040109th, by the bilobalide that embodiment prepares for 2 minutes 3 times, lot number the 031110,040105, the 040107th, the bilobalide for preparing for 4 minutes 3 times by embodiment)
Embodiment
The invention will be further elaborated by the following examples, but do not limit the present invention.
Embodiment 1
Take by weighing Ginkgo Leaf 200 grams and pulverize, add 80% alcohol reflux 3 times, the each consumption of ethanol is 8 times of medicinal material weight, and each return time is 2 hours.Merge No. 3 times extracting solution, reclaim ethanol to there not being the alcohol flavor, with gasoline degreasing 5 times, water merges butanone liquid with butanone extraction 5 times, wash removal of impurities again with saturated limewater, reclaim butanone liquid, get the bilobalide crude product, with 40% ethanol liquid recrystallization, place, filter, 90 ℃ of dryings get the bilobalide highly finished product.
The bilobalide rate of transform reaches more than 60% after measured, and Ginkgolide A, B, C and bilobalide total content are up to more than 92%, and wherein Ginkgolide B content reaches more than 40%, and major impurity ginkgolic acid content is less than 2/1000000ths.
Embodiment 2
Take by weighing Ginkgo Leaf 200 grams and pulverize, add 70% alcohol reflux 3 times, the each consumption of ethanol is 7 times of medicinal material weight, and return time was respectively 2.5,2.5,2 hours.Merge No. 3 times extracting solution, reclaim ethanol to there not being the alcohol flavor, with tetrachloro charcoal degreasing 5 times, water extracted with diethyl ether 6 times, merge ether solution, 0.4% borax solution washs removal of impurities again, reclaims ether, get the bilobalide crude product, with 50% ethanol liquid recrystallization, place, filter, 90 ℃ of dryings get the bilobalide highly finished product.
The bilobalide rate of transform reaches more than 60% after measured, and Ginkgolide A, B, C and bilobalide total content are up to more than 92%, and wherein Ginkgolide B content reaches more than 40%, and major impurity ginkgolic acid content is less than 2/1000000ths.
Embodiment 3
Take by weighing Ginkgo Leaf 200 grams and pulverize, add 10% methyl alcohol temperature lixiviate and get 3 times, the each consumption of methyl alcohol is 10 times of medicinal material weight, and temperature is soaked each 5 hours of time.Merge No. 3 times extracting solution, reclaim methyl alcohol, with tetrachloro charcoal degreasing 5 times, water extracted with diethyl ether 6 times, merge ether solution, wash removal of impurities again, reclaim ether with 0.5% potassium bicarbonate solution, get the bilobalide crude product, with 70% ethanol liquid recrystallization, place, filter, 80 ℃ of dryings get the bilobalide highly finished product.
The bilobalide rate of transform reaches more than 60% after measured, and Ginkgolide A, B, C and bilobalide total content are up to more than 92%, and wherein Ginkgolide B content reaches more than 40%, and major impurity ginkgolic acid content is less than 2/1000000ths.
Embodiment 4
Take by weighing Ginkgo Leaf 200 grams and pulverize, add 70% alcohol reflux 3 times, the ethanol consumption is respectively 8,6,5 times of medicinal material weight, and return time was respectively 3.0,2.5,2.0 hours.Merge No. 3 times extracting solution, with gasoline degreasing 6 times, water ethyl acetate extraction 6 times, combined ethyl acetate liquid, wash removal of impurities again with 5% sodium-acetate, reclaim ethyl acetate, get the bilobalide crude product, with 80% ethanol liquid recrystallization, place, filter, 80 ℃ of dryings get the bilobalide highly finished product.
The bilobalide rate of transform reaches more than 60% after measured, and Ginkgolide A, B, C and bilobalide total content are up to more than 92%, and wherein Ginkgolide B content reaches more than 40%, and major impurity ginkgolic acid content is less than 2/1000000ths.
Embodiment 5
Take by weighing Ginkgo Leaf 200 grams and pulverize, add 70% methyl alcohol temperature lixiviate and get 3 times, the each consumption of methyl alcohol is 4 times of medicinal material weight, and temperature is soaked each 2 hours of time.Merge No. 3 times extracting solution, reclaim methyl alcohol, with tetrachloro charcoal degreasing 5 times, water chloroform extraction 6 times, combined chloroform liquid washs removal of impurities again with 0.5% potassium bicarbonate solution, reclaims chloroform, get the bilobalide crude product, with 90% ethanol liquid recrystallization, place, filter, 80 ℃ of dryings get the bilobalide highly finished product.
The bilobalide rate of transform reaches more than 60% after measured, and Ginkgolide A, B, C and bilobalide total content are up to more than 92%, and wherein Ginkgolide B content reaches more than 40%, and major impurity ginkgolic acid content is less than 2/1000000ths.
Embodiment 6
Take by weighing Ginkgo Leaf 200 grams and pulverize, add 60% alcohol reflux 3 times, the each consumption of ethanol is 8 times of medicinal material weight, and return time was respectively 3,3,2.5 hours.Merge No. 3 times extracting solution, reclaim ethanol to there not being the alcohol flavor, with tetrachloro charcoal degreasing 5 times, water n-butanol extraction 6 times, merge propyl carbinol liquid, 0.4% borax solution washs removal of impurities again, reclaims propyl carbinol, get the bilobalide crude product, with 95% ethanol liquid recrystallization, place, filter, 90 ℃ of dryings get the bilobalide highly finished product.
The bilobalide rate of transform reaches more than 60% after measured, and Ginkgolide A, B, C and bilobalide total content are up to more than 92%, and wherein Ginkgolide B content reaches more than 40%, and major impurity ginkgolic acid content is less than 2/1000000ths.
Claims (5)
1, a kind of extraction of bilobalide and purifying process is characterized in that comprising the following step:
Take by weighing the ginkgo cured leaf, pulverize, the ethanol or the methanol extraction that add the several times amount by medicinal material weight, extracting solution reclaims the degreasing solvent removal of impurities of alcohol back, and saturated limewater, 0.4-5% borax solution, 0.5-5% potassium bicarbonate solution or the removal of impurities of 5-15% sodium acetate soln are adopted in extraction again, get raw product, use ethyl alcohol recrystallization, filter, the dry bilobalide highly finished product that get.
2, extraction according to claim 1 and purifying process, it is characterized in that it is that concentration is 5% ethanol～95% ethanol that the ginkgo cured leaf extracts used ethanol, methyl alcohol is that concentration is 5% methyl alcohol～anhydrous methanol, and the consumption of ethanol or methyl alcohol is 2～10 times of medicinal material weight.
3, extraction according to claim 1 and purifying process is characterized in that degreasing solvent is tetracol phenixin, kerosene or gasoline.
4, extraction according to claim 1 and purifying process is characterized in that extraction solvent is butanone, propyl carbinol, ether, chloroform or ethyl acetate.
5, extraction according to claim 1 and purifying process is characterized in that the bilobalide recrystallization solution is that concentration is 40～95% ethanolic solns, and the bilobalide drying temperature is 80～90 ℃.
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| CNB2005100412661A CN1317283C (en) | 2005-07-29 | 2005-07-29 | Bilobalide extraction and purification process |
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| CNB2005100412661A CN1317283C (en) | 2005-07-29 | 2005-07-29 | Bilobalide extraction and purification process |
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Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1830981B (en) * | 2006-04-17 | 2010-05-12 | 四川科伦药业股份有限公司 | Emulsum injection for treating cerebrovascular diseases, and its preparation art |
| CN103159779A (en) * | 2011-12-15 | 2013-06-19 | 张加明 | Industrialization production technology for extracting bilobalide from Ginkgo testa |
| CN102491983A (en) * | 2011-12-20 | 2012-06-13 | 徐州康泰生物制品有限公司 | Method for preparing high-purity ginkgolides |
| CN102659808B (en) | 2012-04-23 | 2014-10-29 | 成都百裕科技制药有限公司 | Extraction separation method of ginkgolides |
| CN107915742B (en) * | 2017-12-29 | 2019-02-22 | 江苏康缘药业股份有限公司 | A kind of extraction separation method of ginkgo diterpenoid-lactone |
| CN108329328B (en) * | 2018-05-09 | 2020-09-11 | 桂林医学院 | Method for extracting bilobalide |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1594319A (en) * | 2004-06-30 | 2005-03-16 | 江苏吴中苏药医药开发有限责任公司 | Process for extracting ginkgolide, ginkgolide injection and process for preparing same |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1594319A (en) * | 2004-06-30 | 2005-03-16 | 江苏吴中苏药医药开发有限责任公司 | Process for extracting ginkgolide, ginkgolide injection and process for preparing same |
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Effective date of registration: 20090116 Address after: No. 28, Pioneer Road, hi tech Zone, Sichuan, Chengdu: 610041 Co-patentee after: Xue Yonghong Patentee after: Sichuan nwei traditional Chinese medicine research and Development Co., Ltd. Address before: No. 28, Pioneer Road, hi tech Zone, Sichuan, Chengdu: 610041 Patentee before: Sichuan Enwei TCM Research & Development Co., Ltd. |
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Effective date of registration: 20200909 Address after: 610041, No. 28, pioneering Road, hi tech Zone, Sichuan, Chengdu Patentee after: SICHUAN ENWEI TCM RES & DEV Co. Address before: 610041, No. 28, pioneering Road, hi tech Zone, Sichuan, Chengdu Co-patentee before: Xue Yonghong Patentee before: SICHUAN ENWEI TCM RES & DEV Co. |