CN1251675C - Powder injection of ginko and dipyridamole and its preparing method - Google Patents
Powder injection of ginko and dipyridamole and its preparing method Download PDFInfo
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- CN1251675C CN1251675C CN 200410039123 CN200410039123A CN1251675C CN 1251675 C CN1251675 C CN 1251675C CN 200410039123 CN200410039123 CN 200410039123 CN 200410039123 A CN200410039123 A CN 200410039123A CN 1251675 C CN1251675 C CN 1251675C
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- ginkgo
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- 229960002768 dipyridamole Drugs 0.000 title claims abstract description 32
- 238000002347 injection Methods 0.000 title claims abstract description 31
- 239000007924 injection Substances 0.000 title claims abstract description 31
- IZEKFCXSFNUWAM-UHFFFAOYSA-N dipyridamole Chemical compound C=12N=C(N(CCO)CCO)N=C(N3CCCCC3)C2=NC(N(CCO)CCO)=NC=1N1CCCCC1 IZEKFCXSFNUWAM-UHFFFAOYSA-N 0.000 title claims abstract description 30
- 238000000034 method Methods 0.000 title claims abstract description 12
- 244000194101 Ginkgo biloba Species 0.000 title abstract description 10
- 235000008100 Ginkgo biloba Nutrition 0.000 claims abstract description 117
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- Medicines Containing Plant Substances (AREA)
Abstract
The present invention discloses a gingko-didyridamole powder injection for injection and a preparation method thereof, which is characterized in that the powder injection is prepared from the effective components of gingko total flavone, gingko total lactone and dipyridamole extracted and purified from traditional Chinese medicine ginkgo biloba by mix. The gingko total flavone is extracted by ethanol extraction and water precipitation and purified by a macropore adsorption resin method, and thus, the content of the gingko total flavone is increased; the gingko total lactone is extracted by the ethanol extraction and the water precipitation and is purified by a CO2 supercritical extraction method, and thus, the content of the gingko total lactone is increased and determined in the injection; simultaneously, the content of the ineffective toxic component ginkgolic acid is further reduced and limited in the injection. The powder injection is prepared from the extracted and purified effective components of the ginkgo biloba, and dipyridamole by mix in a certain proportion according to the requirements of powder injection forms. Compared with gingko-didyridamole injection sold on a market, the gingko-didyridamole powder injection prepared by the process of the present invention has stronger pharmacological action.
Description
Affiliated technical field
The invention belongs to medical pharmaceutical field, be specifically related to a kind of preparation method of ginkgo damo powder injection.
Background technology
Platelet activating factor PAF is produced and excretory a kind of interior originality phospholipid by platelet and multiple inflammatory cell, PAF finds that so far the most effective platelet gathers derivant, has wide biological activity, PAF not only can cause thrombosis and cardiovascular and cerebrovascular disease, can also cause other diseases such as asthma, shock, inflammation, gastric ulcer, nephropathy etc.Lot of documents and patent certificate Ginkgo total lactones are natural, single-minded, the efficient antagonisies of platelet activating factor PAF, and its pharmacological action has: to the rejection in central nervous system's protective effect, the protective effect, Antishock function, anti-allergic effects, antibacterial and anti-inflammation functions, anti-organ transplantation to ischemic injuries, reduce anal veins and press and improve whole body blood vessel toleration.Therefore, Ginkgo total lactones is to have the very effective site of high bioactivity in the Folium Ginkgo extract, is indispensable effective ingredient in the ginkgo agent.Ginkgo total flavones has numerous pharmacological actions such as the blood vessel of expansion, antiinflammatory, analgesia, free radical resisting, blood fat reducing, antitumor and leukemia, therefore, and the pharmacological action that the content of raising Folium Ginkgo total flavones can improve gingko leaf preparation.
Ginkgoic acid is a kind of organic acid that contains in the Folium Ginkgo, this organic acid is a kind of sensitizer, toxicity is bigger, pharmacological evaluation shows, ginkgoic acid can make the people malaise symptoms such as nausea,vomiting,diarrhea, loss of appetite occur, therefore, Folium Ginkgo extract is during as drug and food, content that should strict control ginkgoic acid.
The quality standard of " National Drug Administration's national drug standards " first 213 pages records Ginkgo Leaf Extract and Dipyridamole Injection is that every 1ml contains Semen Ginkgo total flavones 0.90-1.10mg, dipyridamole 0.36-0.44mg does not do requirement to the content and the limiting the quantity of of Folium Ginkgo toxic component ginkgoic acid of the effective site Ginkgo total lactones of Folium Ginkgo; The standard of consulting international Folium Ginkgo extract is: Ginkgo total flavones＞24%, and Ginkgo total lactones＞6%, its effective site content of ginkgoic acid＜5ppm is lower, and toxic component content is higher.
Summary of the invention
Based on above situation, the present invention has used modern crafts means macroporous adsorbent resin method that Ginkgo total flavones is carried out purification to Folium Ginkgo, makes its content greater than 40%, utilization CO
2The supercritical extraction Purification Technology of Ginkgolides makes its content greater than 10%, removes invalid toxic component ginkgoic acid, and its content is defined as less than 1ppm.
The present invention seeks to use macroporous adsorbent resin method and CO
2The organic combination of supercritical extraction, the content of raising Folium Ginkgo effective site Ginkgo total flavones, Ginkgo total lactones farthest improves the pharmacologically active of ginkgo bilobate extract injectable powder, and further improves its drug effect, utilization CO
2Supercritical extraction is removed the poisonous invalid components ginkgoic acid of Folium Ginkgo, reduces its content, reduces the side effect of ginkgo bilobate extract injectable powder.And be mixed in proportion with Folium Ginkgo extract and the dipyridamole that extracts behind the purification, make the ginkgo bilobate extract injectable powder according to the requirement of injectable powder.
The present invention is achieved by the following technical solutions.
One. process recipes
Get dry Folium Ginkgo, put into the Chinese medicine multi-function extractor, extract, extract altogether 24 times with the ethanol of 50%-70%, each 1-3 hour, extract the back merging filtrate, filtrate decompression is condensed into the 3-4 extractum doubly to crude drug, and extractum adds 3-6 times of distilled water, transferring pH value with acid is 2-6, sedimentation three times is filtered, and is divided into filtrate and residue.Getting filtrate and go up macroporous resin column, is the distilled water eluting of 2-6 with pH value earlier, and the eluting distilled water is 10-15 a times of column volume; The reuse pH value is the 10%-30% ethanol elution of 2-6, and eluting ethanol is 6-10 times of column volume; Be the 60%-80% ethanol elution of 5-6 at last with pH value, eluting ethanol is 6-10 times of column volume, and eluent reclaims ethanol, and it is standby that concentrate drying is pulverized the back.Get above-mentioned residue, put into CO after the drying and crushing
2In the extraction kettle of supercritical extraction equipment, extraction kettle pressure is 15-40Mpa, and extraction temperature is 50-70 ℃, flow is 5-10L/h, behind the extraction kettle conditional stability, starts and carries the agent pump, squeeze into a certain amount of agent of carrying, carry agent and be in ethanol, the acetone one or both and mix and form.The pressure of extraction-container 1,2 is 4-6Mpa, and resolution temperature is 30-50 ℃, behind extraction-container 1,2 conditional stabilitys, extracts time 1-3 hour, when the extraction-container no liquid flows out, takes out the material in the extraction kettle.Standby after the drying and crushing, material discards in the extraction-container.With the Folium Ginkgo extract behind the purification and dipyridamole in 1～3: 3～1 ratio is mixed, and makes the ginkgo bilobate extract injectable powder according to the requirement of injectable powder.
Two. check and analysis
1. the content of Folium Ginkgo extract of the present invention and commercially available Semen Ginkgo Folium Ginkgo extract relatively
Total flavones, Ginkgo total lactones are the important effective site of Folium Ginkgo extract, the height of its content is determining the pharmacologically active of ginkgo bilobate extract injectable powder, ginkgoic acid is a toxic component in the Folium Ginkgo, should limit its content, therefore, we illustrate practical significance of the present invention by the content of these three kinds of materials of check and analysis.
Raw material: Folium Ginkgo extract of the present invention (Qianluchun Science and Technology Co., Ltd., Beijing's laboratory provides)
Commercially available Folium Ginkgo extract (Beijing Luse Jinke Biotechnology Co., Ltd)
(1) Ginkgo total flavones check and analysis
The utilization high performance liquid chromatography detects.
High performance liquid chromatograph: day island proper Tianjin LC-10A of company chromatograph of liquid
Detector: day island proper Tianjin company UV-detector
Reagent: 0.4% phosphoric acid (analytical pure), methanol (analytical pure) Beijing Chemical Plant provide
Standard substance: the calibrating of Quercetin Chinese biological provides
Chromatographic condition: the octadecylsilane chemically bonded silica filler, 0.4% phosphoric acid solution: methanol (1: 1) is stream
Moving phase.
Assay method: precision is measured reference substance solution and need testing solution, injects high performance liquid chromatograph respectively, note
The record chromatogram, Zui Da three peaks wherein, by retention time be followed successively by Quercetin (Q),
Kaempferol (K), isorhamnetin (I) calculate Q, K, I with external standard method, calculate with following formula
Content of total flavone:
Q*2.50+K*2.59+I*2.44
Through detecting and calculating, Ginkgo total flavones content is as shown in table 1.
(2) check and analysis of Ginkgo total lactones
The utilization high performance liquid chromatography detects.
High performance liquid chromatograph: day island proper Tianjin LC-10A of company chromatograph of liquid
Detector: day island proper Tianjin RID-6A of company differential photodetector
Reagent: methanol (analytical pure), oxolane (analytical pure), ethyl acetate (analytical pure) are by the Beijing Chemical Plant
Provide
Standard substance: bilobalide, ginkalide A, B, C standard substance are carried by Shenyang Pharmaceutical University's crude drug laboratory
Supply.
Chromatograph and testing conditions: with the octane bonded silica gel is filler, water: methanol: oxolane (75: 20: 5) is stream
Moving phase, differential refractive index detector, 30 ℃ of column temperatures, flow velocity 1.0ml/min.
Algoscopy: get each 50 μ l of reference substance solution and need testing solution, inject chromatograph of liquid, survey
Fixed, calculate bilobalide and ginkalide A with external standard, B, the content of C, summation is promptly
Get the total amount of terpene lactone.
Through detecting and calculating, the Ginkgo total lactones amount is as shown in table 1.
(3) check and analysis of ginkgoic acid
Use anti-phase patina high performance liquid chromatography to carry out check and analysis.
High performance liquid chromatograph: day island proper Tianjin LC-10A of company chromatograph of liquid
Detector: day island proper Tianjin company UV-detector
Reagent: methanol (analytical pure), acetic acid (analytical pure) are provided by the Beijing Chemical Plant
Standard substance: ginkgoic acid reference substance Shenyang Pharmaceutical University crude drug laboratory provides.
Chromatograph and testing conditions: chromatographic column is Waters C18ODS (21mm * 150mm, 5 μ m), stream
Moving is methanol mutually: 5% acetic acid aqueous solution (90: 10), flow velocity 0.25mLmin
-1,
30 ℃ of column temperatures.
Algoscopy: get each 20 μ l of reference substance solution and need testing solution, inject chromatograph of liquid, measure, calculate with external standard
The content of ginkgoic acid.
Through detecting and calculating, ginkgoic acid is as shown in table 1.
The comparison of table 1 ginkgo leaf component
| Ginkgo total flavones g/g | Percentage composition | Ginkgo total lactones g/g | Percentage composition | Ginkgoic acid ug/g | ppm | |
| Folium Ginkgo extract of the present invention | 0.5089 | 50.1％ | 0.1134 | 11.3％ | 0.8 | 0.8 |
| Folium Ginkgo extract | 0.2765 | 27.7％ | 0.0753 | 7.5％ | 4.3 | 4.3 |
Have according to the method described above and carry out twice check and analysis, calculating data is shown in table 2 and table 3:
The comparison of table 2 ginkgo leaf component
| Ginkgo total flavones g/g | Percentage composition | Ginkgo total lactones g/g | Percentage composition | Ginkgoic acid ug/g | ppm | |
| Folium Ginkgo extract of the present invention | 0.4906 | 49.1％ | 0.1127 | 11.3％ | 0.7 | 0.7 |
| Folium Ginkgo extract | 0.2714 | 27.1％ | 0.0693 | 6.9％ | 4.1 | 4.1 |
The comparison of table 3 ginkgo leaf component
| Ginkgo total flavones g/g | Percentage composition | Ginkgo total lactones g/g | Percentage composition | Ginkgoic acid ug/g | ppm | |
| Folium Ginkgo extract of the present invention | 0.5121 | 51.2％ | 0.1095 | 11.0％ | 0.7 | 0.7 |
| Folium Ginkgo extract | 0.2693 | 26.9％ | 0.0723 | 7.2％ | 4.8 | 4.8 |
Conclusion: can obtain by above data, it is high many that the effective site content that the Ginkgo total flavones that technology of the present invention obtains, Ginkgo total lactones obtain than traditional handicraft is wanted, and the ginkgoic acid content of the Folium Ginkgo extract that technology of the present invention obtains is than low many of the content of the ginkgoic acid of traditional handicraft.Therefore, technology of the present invention has sizable practical significance.
2. Folium Ginkgo extract content relatively in ginkgo bilobate extract injectable powder of the present invention and the commercially available Ginkgo Leaf Extract and Dipyridamole Injection.
Raw material: ginkgo bilobate extract injectable powder of the present invention (Qianluchun Science and Technology Co., Ltd., Beijing's laboratory provides)
Commercially available Ginkgo Leaf Extract and Dipyridamole Injection (Nanjing, Nanjing Pharmacy stock Co., Ltd produces, available from the Temple of the White Dagoba, Beijing medicine wholesaling firm)
Method: check and analysis Ginkgo total flavones, Ginkgo total lactones, ginkgoic acid assay calculate through check and analysis with 1, obtain table 4:
The comparison of two kinds of ginkgo-dipyridamine injection Semen Ginkgoes of table 4 composition
| Ginkgo total flavones | Ginkgo total lactones | Ginkgoic acid | |
| Ginkgo bilobate extract injectable powder of the present invention | 125mg/g | 41mg/g | Do not detect |
| Commercially available Ginkgo Leaf Extract and Dipyridamole Injection | 0.92mg/ml | 0.17mg/ml | 3PPM |
Conclusion: we can obtain through calculating by experiment, ginkgo bilobate extract injectable powder of the present invention and commercially available Ginkgo Leaf Extract and Dipyridamole Injection are relatively, Ginkgo total flavones, Ginkgo total lactones content content in the bosom friend improve greatly, and limiting the quantity of of ginkgoic acid do not detect at ginkgo bilobate extract injectable powder of the present invention, proves absolutely that technology of the present invention has practical significance.
Two. pharmacological examples
Embodiment one
Utilize thrombosis method mensuration ginkgo bilobate extract injectable powder of the present invention and commercially available Ginkgo Leaf Extract and Dipyridamole Injection to the thrombotic influence of rat.
1. experiment medicine: normal saline (blank group) is provided by Qianluchun Science and Technology Co., Ltd., Beijing's laboratory.
Commercially available Ginkgo Leaf Extract and Dipyridamole Injection (Nanjing, Nanjing Pharmacy stock Co., Ltd produces, available from the Temple of the White Dagoba, Beijing medicine wholesaling firm)
Ginkgo bilobate extract injectable powder of the present invention (Qianluchun Science and Technology Co., Ltd., Beijing's laboratory provides)
2. the rat of laboratory animal: body weight 300-400 gram is 30, and male and female are regardless of.Be divided into three groups, 10 every group.
3. experimental technique: with rat anesthesia (pentobarbital sodium 30-40mg/kg, ip), dorsal position is fixed, separate trachea, insert a plastic bushing, and separation right common carotid artery and left external jugular vein, put into a long silk thread of 6 centimetres in the stage casing of polyethylene tube, with heparin-saline solution, be full of polyethylene tube, after an end of polyethylene tube inserts left external jugular vein, inject anticoagulant heparin accurately by polyethylene tube, and then the other end of polyethylene tube inserted right common carotid artery, and open bulldog clamp, blood flow to polyethylene tube from right common carotid artery, return left external jugular vein, open blood flow Herba Clinopodii after 15 minutes takes out silk thread rapidly and weighs, and gross weight deducts silk thread weight and promptly gets thrombus weight.The animal wet weight of thrombus of blank group and other two groups of administration groups is carried out record, calculate, as shown in table 5:
The thrombus weight of each administration group of table 5
| Blank group mg | Commercially available Ginkgo Leaf Extract and Dipyridamole Injection mg | Ginkgo bilobate extract injectable powder mg of the present invention | |
| Wet weight of thrombus | 1.89 | 1.01 | 0.65 |
Conclusion: from pharmacological evaluation, we can obtain, ginkgo bilobate extract injectable powder of the present invention, commercially available Ginkgo Leaf Extract and Dipyridamole Injection all have utmost point significant difference (P＜0.01) with blank group, there were significant differences for ginkgo bilobate extract injectable powder and commercially available Ginkgo Leaf Extract and Dipyridamole Injection (P＜0.05), therefore, ginkgo bilobate extract injectable powder of the present invention has stronger pharmacological action.
Embodiment two
Utilization is measured the influence to rat myocardial infarction situation of ginkgo bilobate extract injectable powder of the present invention and commercially available Ginkgo Leaf Extract and Dipyridamole Injection in body-centered flesh infarction method.
1. experiment medicine: commercially available Ginkgo Leaf Extract and Dipyridamole Injection (production of Nanjing, Nanjing Pharmacy stock Co., Ltd) is available from the Temple of the White Dagoba, Beijing medicine wholesaling firm.
Ginkgo bilobate extract injectable powder of the present invention is provided by Qianluchun Science and Technology Co., Ltd., Beijing's laboratory
2. laboratory animal: 20 of male rat 250-300 grams are divided into two groups.
3. experimental technique: get 20 of male rats, after the urethane 0.65g/kg abdominal cavity light anaesthesia, back of the body position is fixing, be connected to artificial respirator with more than half rubber bulb, practice artificial respiration, rat chest unhairing, sterilization, cut about 2 centimetres of skin along left mid-clavicular line, separate basic unit in the 4th or the 5th intercostal passivity, open the thoracic cavity, cut off pericardium, the light right side thorax of pressing, extrude heart, after Coronary vein place joint is pricked left coronary artery between arterial cone and the left auricle, heart is put back to the thoracic cavity, sew up the thoracic cavity rapidly, stop the artificial respiration, with two kinds of preparations 10 rats are experimentized respectively, it is as shown in table 6 to obtain data computation:
The pharmacology of table 6 ginkgo-dipyridamine injection relatively
| Obvious effective rate | Effective percentage | Inefficiency | Total effective rate | |
| Commercially available Ginkgo Leaf Extract and Dipyridamole Injection | 16.5％ | 54.2％ | 29.3％ | 70.7％ |
| Ginkgo bilobate extract injectable powder of the present invention | 34.7％ | 57.6％ | 7.7％ | 92.3％ |
Can learn ginkgo bilobate extract injectable powder of the present invention significantly (P＜0.01) difference of having compared with commercially available Ginkgo Leaf Extract and Dipyridamole Injection extremely from testing us.
Conclusion: can obtain the ginkgo bilobate extract injectable powder of the present invention stronger pharmacological action of comparing with commercially available Ginkgo Leaf Extract and Dipyridamole Injection by above pharmacological evaluation.
Four. preparation embodiment
Embodiment one
Get dry Folium Ginkgo 1000 grams, put into the Chinese medicine multi-function extractor, the ethanol with 50% extracts, and extracts altogether 2 times, each 1 hour, extract the back merging filtrate, filtrate decompression is condensed into the 3-4 extractum doubly to crude drug, and extractum adds 3 times of distilled water, transferring pH value with acid is 2, sedimentation three times is filtered, and is divided into filtrate and residue.Getting filtrate and go up macroporous adsorptive resins, is earlier 2 distilled water eluting with pH value, and the eluting distilled water is 10 times of column volume; The reuse pH value is 2 10% ethanol elution, and eluting ethanol is 6 times of column volume; Be 5 60% ethanol elution at last with pH value, eluting ethanol is 6 times of column volume, and eluent reclaims ethanol, and it is standby that concentrate drying is pulverized the back.Get above-mentioned residue, put into CO after the drying and crushing
2In the extraction kettle of supercritical extraction equipment, extraction kettle pressure is 15Mpa, and extraction temperature is 50 ℃, flow is 5L/h, behind the extraction kettle conditional stability, starts and carries the agent pump, squeeze into a certain amount of agent of carrying, carrying agent is dehydrated alcohol, and extraction-container 1,2 is respectively 4Mpa, and resolution temperature is 30 ℃, behind extraction-container 1,2 conditional stabilitys, 1 hour extraction time, when the extraction-container no liquid flows out, take out the material in the extraction kettle.Standby after the drying and crushing, material discards in the extraction-container.Folium Ginkgo extract behind the purification 156.3 grams are mixed with dipyridamole 312.6 grams, make the ginkgo bilobate extract injectable powder according to the requirement of injectable powder.
Embodiment two
Get dry Folium Ginkgo 2000 grams, put into the Chinese medicine multi-function extractor, the ethanol with 60% extracts, and extracts altogether 3 times, each 2 hours, extract the back merging filtrate, filtrate decompression is condensed into the 3-4 extractum doubly to crude drug, and extractum adds 4 times of distilled water, with acid table tone pitch is 4, sedimentation three times is filtered, and is divided into filtrate and residue.Getting filtrate and go up macroporous adsorptive resins, is earlier 5 distilled water eluting with pH value, and the eluting distilled water is 13 times of column volume; The reuse pH value is 5 20% ethanol elution, and eluting ethanol is 8 times of column volume; Be 5.5 70% ethanol elution at last with pH value, eluting ethanol is 8 times of column volume, and eluent reclaims ethanol, and it is standby that concentrate drying is pulverized the back.Get above-mentioned residue, put into CO after the drying and crushing
2In the extraction kettle of supercritical extraction equipment, extraction kettle pressure is 25Mpa, and extraction temperature is 55 ℃, flow is 7.5L/h, behind the extraction kettle conditional stability, starts and carries the agent pump, squeeze into a certain amount of agent of carrying, carrying agent is acetone, and extraction-container 1,2 is respectively 4.5Mpa, and resolution temperature is 35 ℃, behind extraction-container 1,2 conditional stabilitys, 2 hours extraction time, when the extraction-container no liquid flows out, take out the material in the extraction kettle.Standby after the drying and crushing, material discards in the extraction-container.Folium Ginkgo extract behind the purification 274.5 grams are mixed in proportion with dipyridamole 823.5 grams, make the ginkgo bilobate extract injectable powder according to the requirement of injectable powder.
Embodiment three
Get dry Folium Ginkgo 1500 grams, put into the Chinese medicine multi-function extractor, the ethanol with 70% extracts, and extracts altogether 4 times, each 3 hours, extract the back merging filtrate, filtrate decompression is condensed into the 3-4 extractum doubly to crude drug, and extractum adds 6 times of distilled water, transferring pH value with acid is 6, sedimentation three times is filtered, and is divided into filtrate and residue.Getting filtrate and go up macroporous adsorptive resins, is earlier 6 distilled water eluting with pH value, and the eluting distilled water is 15 times of column volume; The reuse pH value is 6 30% ethanol elution, and eluting ethanol is 10 times of column volume; Be 6 80% ethanol elution at last with pH value, eluting ethanol is 10 times of column volume, and eluent reclaims ethanol, and it is standby that concentrate drying is pulverized the back.Get above-mentioned residue, put into CO after the drying and crushing
2In the extraction kettle of supercritical extraction equipment, extraction kettle pressure is 40Mpa, and extraction temperature is 70 ℃, flow is 10L/h, behind the extraction kettle conditional stability, starts and carries the agent pump, squeeze into a certain amount of agent of carrying, carrying agent is dehydrated alcohol: acetone=1: 1, and extraction-container 1,2 is respectively 6Mpa, and resolution temperature is 50 ℃, behind extraction-container 1,2 conditional stabilitys, 3 hours extraction time, when the extraction-container no liquid flows out, take out the material in the extraction kettle.Standby after the drying and crushing, material discards in the extraction-container.Folium Ginkgo extract behind the purification 210.3 grams are mixed in proportion with dipyridamole 210.3 grams, make the ginkgo bilobate extract injectable powder according to the requirement of injectable powder.
Embodiment four
Get dry Folium Ginkgo 1000 grams, put into the Chinese medicine multi-function extractor, the ethanol with 65% extracts, and extracts altogether 3 times, each 3 hours, extract the back merging filtrate, filtrate decompression is condensed into the 3-4 extractum doubly to crude drug, and extractum adds 5 times of distilled water, transferring pH value with acid is 5, sedimentation three times is filtered, and is divided into filtrate and residue.Getting filtrate and go up macroporous adsorptive resins, is earlier 5 distilled water eluting with pH value, and the eluting distilled water is 14 times of column volume; The reuse pH value is 4 25% ethanol elution, and eluting ethanol is 8 times of column volume; Be 6 75% ethanol elution at last with pH value, eluting ethanol is 8 times of column volume, and eluent reclaims ethanol, and it is standby that concentrate drying is pulverized the back.Get above-mentioned residue, put into CO after the drying and crushing
2In the extraction kettle of supercritical extraction equipment, extraction kettle pressure is 30Mpa, and extraction temperature is 60 ℃, flow is 8L/h, behind the extraction kettle conditional stability, starts and carries the agent pump, squeeze into a certain amount of agent of carrying, carrying agent is dehydrated alcohol: acetone=1: 2, and extraction-container 1,2 is respectively 5Mpa, and resolution temperature is 35 ℃, behind extraction-container 1,2 conditional stabilitys, 3 hours extraction time, when the extraction-container no liquid flows out, take out the material in the extraction kettle.Standby after the drying and crushing, material discards in the extraction-container.Folium Ginkgo extract behind the purification 160.8 grams are mixed in proportion with dipyridamole 241.2 grams, make the ginkgo bilobate extract injectable powder according to the requirement of injectable powder.
Embodiment five
Get dry Folium Ginkgo 1000 grams, put into the Chinese medicine multi-function extractor, the ethanol with 60% extracts, and extracts altogether 3 times, each 3 hours, extract the back merging filtrate, filtrate decompression is condensed into the 3-4 extractum doubly to crude drug, and extractum adds 6 times of distilled water, transferring pH value with acid is 5, sedimentation three times is filtered, and is divided into filtrate and residue.Getting filtrate and go up macroporous resin column, is earlier 6 distilled water eluting with pH value, and the eluting distilled water is 15 times of column volume; The reuse pH value is 5 10%-30% ethanol elution, and eluting ethanol is 10 times of column volume; Be 6 75% ethanol elution at last with pH value, eluting ethanol is 10 times of column volume, and eluent reclaims ethanol, and it is standby that concentrate drying is pulverized the back.Get above-mentioned residue, put into CO after the drying and crushing
2In the extraction kettle of supercritical extraction equipment, extraction kettle pressure is 30Mpa, and extraction temperature is 70 ℃, and flow is 10L/h, behind the extraction kettle conditional stability, starts and carries the agent pump, squeezes into a certain amount of agent of carrying, and carrying agent is ethanol: acetone=1: 1.The pressure of extraction-container 1,2 is 6Mpa, and resolution temperature is 50 ℃, behind extraction-container 1,2 conditional stabilitys, 3 hours extraction time, when the extraction-container no liquid flows out, takes out the material in the extraction kettle.Standby after the drying and crushing, material discards in the extraction-container.Folium Ginkgo extract behind the purification 158.4 grams are mixed with dipyridamole 79.2 grams, make the ginkgo bilobate extract injectable powder according to the requirement of injectable powder.
Embodiment six
Get dry Folium Ginkgo 2000 grams, put into the Chinese medicine multi-function extractor, the ethanol with 70% extracts, and extracts altogether 4 times, each 3 hours, extract the back merging filtrate, filtrate decompression is condensed into the 3-4 extractum doubly to crude drug, and extractum adds 5 times of distilled water, transferring pH value with acid is 4, sedimentation three times is filtered, and is divided into filtrate and residue.Getting filtrate and go up macroporous resin column, is earlier 5 distilled water eluting with pH value, and the eluting distilled water is 12 times of column volume; The reuse pH value is 4 25% ethanol elution, and eluting ethanol is 7 times of column volume; Be 5 65% ethanol elution at last with pH value, eluting ethanol is 8 times of column volume, and eluent reclaims ethanol, and it is standby that concentrate drying is pulverized the back.Get above-mentioned residue, put into CO after the drying and crushing
2In the extraction kettle of supercritical extraction equipment, extraction kettle pressure is 200Mpa, and extraction temperature is 65 ℃, and flow is 8L/h, behind the extraction kettle conditional stability, starts and carries the agent pump, squeezes into a certain amount of agent of carrying, and carrying agent is acetone.The pressure of extraction-container 1,2 is 5Mpa, and resolution temperature is 35 ℃, behind extraction-container 1,2 conditional stabilitys, 2 hours extraction time, when the extraction-container no liquid flows out, takes out the material in the extraction kettle.Standby after the drying and crushing, material discards in the extraction-container.Folium Ginkgo extract behind the purification 276.2 grams are mixed with dipyridamole 92.1 grams, make the ginkgo bilobate extract injectable powder according to the requirement of injectable powder.
Embodiment seven
Get dry Folium Ginkgo 1500 grams, put into the Chinese medicine multi-function extractor, the ethanol with 60% extracts, and extracts altogether 4 times, each 3 hours, extract the back merging filtrate, filtrate decompression is condensed into the 3-4 extractum doubly to crude drug, and extractum adds 6 times of distilled water, transferring pH value with acid is 6, sedimentation three times is filtered, and is divided into filtrate and residue.Getting filtrate and go up macroporous resin column, is earlier 5 distilled water eluting with pH value, and the eluting distilled water is 13 times of column volume; The reuse pH value is 4 25% ethanol elution, and eluting ethanol is 10 times of column volume; Be 6 75% ethanol elution at last with pH value, eluting ethanol is 9 times of column volume, and eluent reclaims ethanol, and it is standby that concentrate drying is pulverized the back.Get above-mentioned residue, put into CO after the drying and crushing
2In the extraction kettle of supercritical extraction equipment, extraction kettle pressure is 25Mpa, and extraction temperature is 65 ℃, and flow is 8L/h, behind the extraction kettle conditional stability, starts and carries the agent pump, squeezes into a certain amount of agent of carrying, and carrying agent is dehydrated alcohol.The pressure of extraction-container 1,2 is 6Mpa, and resolution temperature is 50 ℃, behind extraction-container 1,2 conditional stabilitys, 3 hours extraction time, when the extraction-container no liquid flows out, takes out the material in the extraction kettle.Standby after the drying and crushing, material discards in the extraction-container.Folium Ginkgo extract behind the purification 210.5 grams are mixed with dipyridamole 140.1 grams, make the ginkgo bilobate extract injectable powder according to the requirement of injectable powder.
Claims (2)
1. ginkgo damo powder injection, it is characterized in that: this injectable powder is to be made by the effective site of 1-3 parts by weight of Chinese traditional medicine Folium Ginkgo extraction and the dipyridamole of 3-1 weight portion, the content of Folium Ginkgo effective site Ginkgo total flavones is 125mg/g in this injectable powder, the content of Ginkgo total lactones is 41mg/g, and ginkgoic acid should be less than 1PPM.
2. prepare the method for the described ginkgo damo powder injection of claim 1, it is characterized by:
(1) gets dry Folium Ginkgo, put into the Chinese medicine multi-function extractor, extract, extract 2-4 time altogether, each 1-3 hour, extract the back merging filtrate with the ethanol of 50%-70%;
(2) filtrate decompression is condensed into the 3-4 extractum doubly to crude drug, and extractum adds 3-6 times of distilled water, and transferring pH value with acid is 2-6, and sedimentation three times is filtered, and is divided into filtrate and residue;
(3) getting (2) middle filtrate and go up macroporous resin column, is the distilled water eluting of 2-6 with pH value earlier, and the eluting distilled water is 10-15 a times of column volume; The reuse pH value is the 10%-30% ethanol elution of 2-6, and eluting ethanol is 6-10 times of column volume; Be the 60%-80% ethanol elution of 5-6 at last with pH value, eluting ethanol is 6-10 times of column volume, and eluent reclaims ethanol, and it is standby that concentrate drying is pulverized the back;
(4) get residue in (2), put into CO after the drying and crushing
2In the extraction kettle of supercritical extraction equipment, extraction kettle pressure is 15-40Mpa, extraction temperature is 50-70 ℃, flow is 5-10L/h, behind the extraction kettle conditional stability, start and carry the agent pump, squeeze into a certain amount of agent of carrying, carry agent and be in ethanol, the acetone one or both and mix and form, when the pressure stability of extraction-container 1,2 at 4-6Mpa, resolution temperature extracts after being stabilized in 30-50 ℃, 1-3 hour extraction time, when the extraction-container no liquid flows out, take out the material in the extraction kettle, standby after the drying and crushing, material discards in the extraction-container;
(5) Folium Ginkgo extract behind two kinds of purification in (3), (4) is mixed, obtain the raw material of ginkgo bilobate extract injectable powder, mix, be prepared into the ginkgo bilobate extract injectable powder according to the requirement of injectable powder with dipyridamole.
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| CN101175506B (en) * | 2005-05-03 | 2012-06-06 | 威玛舒培博士两合公司 | Method for preparing a ginkgo extract having a reduced content of 4'-o-methyl pyridoxine and/or biflavones |
| DE102005061948A1 (en) * | 2005-05-03 | 2006-11-16 | Bioplanta Arzneimittel Gmbh | Improved process for the preparation of 4'-O-methylpyridoxine and / or biflavone-poor ginkgo extracts |
| CN1939357B (en) * | 2005-09-27 | 2010-12-15 | 博安兄弟制药（中国）有限公司 | A kind of preparation method of ginkgo damole injection |
| CN103739611A (en) * | 2013-12-26 | 2014-04-23 | 哈尔滨誉衡药业股份有限公司 | Preparation method and preparation of traditional Chinese medicine raw material |
| CN104800218A (en) * | 2014-01-27 | 2015-07-29 | 贵州益佰制药股份有限公司 | Ginkgo dipyridolum composition, preparation thereof, preparation method of composition, and preparation method of preparation |
| CN105770007B (en) * | 2016-03-03 | 2019-11-22 | 广西壮族自治区兽医研究所 | A method for extracting total flavonoids in myrtle leaves |
| CN107184616B (en) * | 2017-05-07 | 2018-04-27 | 珠海亿邦医药有限公司 | A kind of preparation method of Ginkgo Damo injection |
| CN107647407A (en) * | 2017-11-14 | 2018-02-02 | 宜昌东方昌绿茶业有限公司 | A kind of method that flavonol is extracted from ginkgo leave tea |
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