CN1785216A - Medicinal composition contg. total ginkgo flavone, its prepn. method and use - Google Patents
Medicinal composition contg. total ginkgo flavone, its prepn. method and use Download PDFInfo
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- CN1785216A CN1785216A CN 200510109594 CN200510109594A CN1785216A CN 1785216 A CN1785216 A CN 1785216A CN 200510109594 CN200510109594 CN 200510109594 CN 200510109594 A CN200510109594 A CN 200510109594A CN 1785216 A CN1785216 A CN 1785216A
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- ginkgo total
- pharmaceutical composition
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- ligustrazine phosphate
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Abstract
A medicinal composition used for preparing the medicines to treat the ischemic cardiovascular and cerebrovascular diseases is proportionally prepared from ligustrazine phosphate and gingko flavone. Its preparing process is also disclosed.
Description
Technical field
The invention belongs to medical technical field, be specifically related to a kind of Semen Ginkgo total flavones pharmaceutical composition and preparation method thereof and purposes of containing, more particularly, relate to a kind of pharmaceutical composition that combines by ligustrazine phosphate and Ginkgo total flavones, its preparation method and the application aspect preparation treatment ischemic cardio cerebrovascular diseases medicine thereof.
Background technology
Ginkgo total flavones is the main active in the Semen Ginkgo, has dilating coronary blood vessel, cerebrovascular, blood circulation promoting and blood stasis dispelling, improves symptom and memory function that cerebral ischemia produces.The content of total flavones in Folium Ginkgo is 0.5%～1% (W/W), mainly exists with the glycosides form, and main aglycon is Quercetin, kaempferol and isorhamnetin.
Ligustrazine phosphate is 2 phosphate monohydrate (C
8H
12N
2H
3PO
4H
2O),, have antiplatelet aggregative activity, and accumulative platelet is had depolymerisation, expansion small artery, microcirculation improvement, cerebral blood flow increasing and function of promoting blood circulation to disperse blood clots for white or off-white color crystalline powder.Ligustrazine phosphate absorbs and drains rapidly, can pass through blood-CSF barrier.The clinical ischemic cerebrovascular (as cerebral blood supply insufficiency, cerebral thrombosis, cerebral embolism) that is used for.
Application number is that the patent documentation of CN200410083882.9 discloses a kind of ginkgo medicine composition, its preparation method and purposes, and the crude drug of usefulness is Folium Ginkgo extract and ligustrazine phosphate.Folium Ginkgo extract wherein adopts the method for alcohol extraction, purification with macroreticular resin to obtain.Prepared Semen Ginkgo extrac is the mixture of plurality of active ingredients, except containing Ginkgo total flavones (content is about 25%), secondly also contains a large amount of bilobalides and other compositions.
But in pharmacological evaluation and clinical practice thereafter, above-mentioned ginkgo medicine composition has demonstrated the unstability of therapeutical effect.
Summary of the invention
At the deficiency of above technology, research worker of the present invention has been carried out a large amount of follow-up studies to it.Research worker of the present invention finds in follow-up pharmacological evaluation and clinical practice, and different Folium Ginkgo extract (in Ginkgo total flavones) and ligustrazine phosphate are with identical ratio compatibility, and its pharmacological action all has different with therapeutic effect.In view of this, the Ginkgo total flavones in the above-mentioned preparation in the Semen Ginkgo extrac can only be the index components of content, and the height of Ginkgo total flavones content is not represented the quality of curative effect.To this, further research has been carried out in a large amount of zoopery of research worker utilization of the present invention.Research worker of the present invention is found, when the content of Ginkgo total flavones in the Semen Ginkgo extrac reaches 50% when above, the pharmacological action of pharmaceutical composition of the present invention and the good stability of therapeutic effect, the content's index and the curative effect index of Ginkgo total flavones have reached unification, and quality controllable and curative effect is controlled to have reached unification.
An object of the present invention is to disclose a kind of Semen Ginkgo total flavones pharmaceutical composition that contains.
Another purpose of the present invention is to disclose the above-mentioned Semen Ginkgo total flavones preparation of drug combination method that contains.
Another object of the present invention is to disclose the above-mentioned purposes that contains Semen Ginkgo total flavones pharmaceutical composition.
The Semen Ginkgo total flavones pharmaceutical composition that contains of the present invention can be prepared into available dosage form on the various pharmaceuticss, therefore can use said composition also can contain one or more adjuvant; Such as sodium chloride, starch, Pulvis Talci and magnesium stearate etc., the acceptable adjuvant of pharmaceutical field.
Ligustrazine phosphate of the present invention can adopt the raw material that meets medicinal standard.
The present invention contains in the Semen Ginkgo total flavones pharmaceutical composition, and ligustrazine phosphate content is 2-10 times of Ginkgo total flavones; The 4-6 that is preferably ligustrazine phosphate content and is Ginkgo total flavones doubly; More preferably ligustrazine phosphate content is 5 times of Ginkgo total flavones.
Ginkgo total flavones extract of the present invention, the purity of wherein contained Ginkgo total flavones must reach more than 50%.
Ginkgo total flavones extract of the present invention can be any method preparation, as long as the purity of wherein contained Ginkgo total flavones reaches more than 50%.
Ginkgo total flavones extract of the present invention also can adopt following method preparation:
With in please or meet that " Folium Ginkgo extract of Chinese pharmacopoeia standard is as initiation material number for the Semen Ginkgo extrac among the CN200410083882.9.With the raw material water dissolution, cold preservation is filtered, high speed centrifugation, and the polyamide column purification, the eluent ultrafiltration concentrates, and exsiccant method promptly gets Ginkgo total flavones extract of the present invention.
Specifically, Ginkgo total flavones extract of the present invention prepares by the following method:
The water dissolution that raw material is doubly measured with 10-15,4 ℃ of-10 ℃ of cold preservations 24 hours, filter, filtrate centrifugal 20 minutes with 10000 rev/mins speed, supernatant is crossed the polyamide column of having handled well, washes to colourless the alcoholic solution eluting of the 10%-20% of 4 times of column volumes of reuse earlier with water, the alcoholic solution eluting of the 60%-70% of reuse 5-6 times column volume, collect the ethanol elution of high concentration, behind the decompression recycling ethanol, thin up to relative density is 1.05, it with molecular cut off 200 and 600 ultrafiltration membrance filter, the solution that molecular weight is 200-600 is rich in collection, concentrates drying, pulverize, promptly get Ginkgo total flavones extract of the present invention.
The Semen Ginkgo total flavones pharmaceutical composition that contains of the present invention can be prepared into available dosage form on the various pharmaceuticss, as injectable powder, lyophilized injectable powder, tablet, capsule, small-volume injection, bulk capacity injection, preferred dosage form is small-volume injection, bulk capacity injection.
The various dosage forms that contain Semen Ginkgo total flavones pharmaceutical composition of the present invention can be according to the conventional production method preparation of pharmaceutical field.Such as using ligustrazine phosphate, Ginkgo total flavones to mix, be made into required dosage form then with one or more carriers.
The Semen Ginkgo total flavones pharmaceutical composition that contains of the present invention needs to add an amount of sodium chloride as isoosmotic adjusting agent when being prepared into bulk capacity injection.
Research worker of the present invention is tested discovery in a large number, and synergism is best when ligustrazine phosphate weight in the ginkgo medicine composition is 5 times of proportionings of Ginkgo total flavones weight, curative effect is best.
The present invention most preferably specification of ginkgo medicine composition bulk capacity injection is the 250ml/ bottle, and every bottle contains ligustrazine phosphate 100mg, Ginkgo total flavones 20mg.
Usage is as follows: intravenous drip, one time one bottle, 10～15 days is a course of treatment.
The Semen Ginkgo total flavones pharmaceutical composition that contains of the present invention replenishes synergism mutually by Ginkgo total flavones and ligustrazine phosphate, can play beyond thought effect.Ginkgo total flavones has dilating coronary blood vessel, cerebrovascular, blood circulation promoting and blood stasis dispelling, improves symptom and memory function that cerebral ischemia produces.Ligustrazine phosphate absorbs and drains rapidly, can play a role by blood-CSF barrier.
The Semen Ginkgo total flavones pharmaceutical composition that contains of the present invention is the compound preparation that Ginkgo total flavones and ligustrazine phosphate form by the special ratios assembly, and its absorption and drainage can be passed through blood-cerebrospinal fluid barrier rapidly.By the two additional mutually body that acts synergistically on, give full play to blood circulation promoting and blood stasis dispelling, anti-platelet aggregation is arranged, blood vessel dilating, the microcirculation improvement effect, the smelting that is applicable to ischemic cardio cerebrovascular diseases is treated, as cerebral blood supply insufficiency, cerebral thrombosis, cerebral embolism, cerebral vasospasm, brain insufficiency, alzheimer disease, parkinson, apoplexy, hypertension, hyperlipidemia, arteriosclerosis, coronary heart disease, angina pectoris, myocardial infarction.Also can be used for the microcirculation pathological changes that hepatic fibrosis, diabetes cause, vasculitis etc.
Method in the patent documentation of commercially available Folium Ginkgo employing application number CN200410083882.9 is prepared into Semen Ginkgo extrac or directly uses commercially available Folium Ginkgo extract.Above-mentioned Folium Ginkgo extract and ligustrazine phosphate are prepared into the ejection preparation of same concentrations (in Ginkgo total flavones); carry out to anoxia in mice endurance influence, to the anoxybiotic protection of mouse cardiac muscle, to zooperies such as rat thrombus in vivo formation, the stability of observe the curative effect.Experimental result sees Table 1.
For the ease of comparing, determine experimental index with following method: every group experimental result is the ratio of organizing the experimental result meansigma methods.
Table 1 experimental result
| Group | Experimental result (ratio) |
| 1 2 3 4 5 6 7 8 | 0.92 1.04 1.00 0.88 0.97 1.12 1.05 1.07 |
By above-mentioned experimental result as can be seen, under the identical prerequisite of Folium Ginkgo extract (in Ginkgo total flavones content) content, each pharmacological action of organizing medicine still has difference, demonstrates the unstability of therapeutic effect.
Method in the patent documentation of application number CN200410083882.9 is prepared into Semen Ginkgo extrac or directly uses commercially available Folium Ginkgo extract and further extract with preparation method of the present invention and obtain Ginkgo total flavones extract of the present invention, be prepared into the ejection preparation of same concentrations (in Ginkgo total flavones) again with ligustrazine phosphate, carry out zoopery, the stability of observe the curative effect.Experimental result sees Table 2.
Table 2 experimental result
| Group | Experimental result (ratio) |
| 1 2 3 4 5 6 7 8 | 1.02 0.98 0.96 1.01 1.00 1.04 0.96 1.03 |
By above-mentioned experimental result as can be seen, the present invention contains Semen Ginkgo total flavones pharmaceutical composition under the identical prerequisite of Folium Ginkgo total flavones extract (in Ginkgo total flavones content) content, it is little that each organizes the pharmacological action difference of medicine, demonstrates the stability of therapeutic effect.
Can infer further that thus the present invention contains Semen Ginkgo total flavones pharmaceutical composition and demonstrates outside the stability of good therapeutic effect, and the easier control of carrying out clinical consumption in clinical practice, thereby can reduce the generation of untoward reaction greatly.
The specific embodiment
Further describe the present invention with embodiment below, help understanding, but described embodiment only is used to illustrate the present invention rather than restriction the present invention the present invention and advantage thereof, better effects if.
The following crude drug that is used for preparing Ginkgo total flavones extract of the present invention is that commercially available Folium Ginkgo is adopted the Semen Ginkgo extrac that the method for application number CN200410083882.9 patent documentation is prepared into or directly is commercially available Folium Ginkgo extract.
Embodiment 1
With the water dissolution of raw material with 10 times of amounts, 4 ℃ of cold preservations 24 hours, filter, filtrate centrifugal 20 minutes with 10000 rev/mins speed, supernatant is crossed the polyamide column of having handled well, washes to colourless 10% alcoholic solution eluting of 4 times of column volumes of reuse earlier with water, 60% alcoholic solution eluting of 5 times of column volumes of reuse, collect the ethanol elution of high concentration, behind the decompression recycling ethanol, thin up to relative density is 1.05, it with molecular cut off 200 and 600 ultrafiltration membrance filter, the solution that molecular weight is 200-600 is rich in collection, concentrates drying, pulverize, promptly get Ginkgo total flavones extract of the present invention.Assay Ginkgo total flavones content is 55%.
Embodiment 2
With the water dissolution of raw material with 15 times of amounts, 10 ℃ of cold preservations 24 hours, filter, filtrate centrifugal 20 minutes with 10000 rev/mins speed, supernatant is crossed the polyamide column of having handled well, washes to colourless 20% alcoholic solution eluting of 4 times of column volumes of reuse earlier with water, 70% alcoholic solution eluting of 6 times of column volumes of reuse, collect the ethanol elution of high concentration, behind the decompression recycling ethanol, thin up to relative density is 1.05, it with molecular cut off 200 and 600 ultrafiltration membrance filter, the solution that molecular weight is 200-600 is rich in collection, concentrates drying, pulverize, promptly get Ginkgo total flavones extract of the present invention.Assay Ginkgo total flavones content is 60%.
Embodiment 3
With the water dissolution of raw material with 12 times of amounts, 6 ℃ of cold preservations 24 hours, filter, filtrate centrifugal 20 minutes with 10000 rev/mins speed, supernatant is crossed the polyamide column of having handled well, washes to colourless 15% alcoholic solution eluting of 4 times of column volumes of reuse earlier with water, 65% alcoholic solution eluting of 5 times of column volumes of reuse, collect the ethanol elution of high concentration, behind the decompression recycling ethanol, thin up to relative density is 1.05, it with molecular cut off 200 and 600 ultrafiltration membrance filter, the solution that molecular weight is 200-600 is rich in collection, concentrates drying, pulverize, promptly get Ginkgo total flavones extract of the present invention.Assay Ginkgo total flavones content is 53%.
Embodiment 4
Take by weighing above-mentioned (containing Semen Ginkgo total flavones 20g) Ginkgo total flavones extract, ligustrazine phosphate 100g, can be made into the 100000ml medicinal liquid, finally make 400 bottles of bulk capacity injections (specification is the 250ml/ bottle).In dense preparing tank, add an amount of 85 ℃ of waters for injection, in dense preparing tank, drop into 900g sodium chloride, fully stir and make dissolving fully, add active carbon by 0.04% of preparation cumulative volume, heat 90 ℃, be incubated 20 minutes, be cooled to 50 ℃, the medicinal liquid decarbonization filtering to dilute preparing tank, is added ligustrazine phosphate and Ginkgo total flavones extract in dilute preparing tank, fully stir and make dissolving fully, add active carbon by 0.02% of preparation cumulative volume, left standstill 20 minutes, and added water for injection to the dosing amount, transferring PH is 4.8 ± 0.2, with the medicinal liquid decarbonization filtering, medicinal liquid is again through end-filtration, and embedding is filled nitrogen by bottle during embedding in infusion bottle, sterilization promptly gets infusion products.
Embodiment 5
Take by weighing above-mentioned (containing Semen Ginkgo total flavones 20g) Ginkgo total flavones extract, ligustrazine phosphate 40g, can be made into the 100000ml medicinal liquid, finally make 400 bottles of bulk capacity injections (specification is the 250ml/ bottle).In dense preparing tank, add an amount of 85 ℃ of waters for injection, in dense preparing tank, drop into 900g sodium chloride, fully stir and make dissolving fully, add active carbon by 0.04% of preparation cumulative volume, heat 90 ℃, be incubated 20 minutes, be cooled to 50 ℃, the medicinal liquid decarbonization filtering to dilute preparing tank, is added ligustrazine phosphate and Ginkgo total flavones extract in dilute preparing tank, fully stir and make dissolving fully, add active carbon by 0.02% of preparation cumulative volume, left standstill 20 minutes, and added water for injection to the dosing amount, transferring PH is 4.8 ± 0.2, with the medicinal liquid decarbonization filtering, medicinal liquid is again through end-filtration, and embedding is filled nitrogen by bottle during embedding in infusion bottle, sterilization promptly gets infusion products.
Embodiment 6
Take by weighing above-mentioned (containing Semen Ginkgo total flavones 5g) Ginkgo total flavones extract, ligustrazine phosphate 50g, can be made into the 2000ml medicinal liquid, finally make 1000 of small-volume injections.In preparing tank, add an amount of 48 ℃ of waters for injection, add ligustrazine phosphate and Ginkgo total flavones extract again, fully stir and make dissolving fully, add active carbon by 0.02% of preparation cumulative volume, left standstill 20 minutes, and added water for injection to the dosing amount, transferring PH is 4.5, with the medicinal liquid decarbonization filtering, medicinal liquid is again through end-filtration, and embedding is in ampoule, and ampoule fills nitrogen by propping up during embedding, sterilization promptly gets small-volume injection.
Embodiment 7
Take by weighing above-mentioned (containing Semen Ginkgo total flavones 50g) Ginkgo total flavones extract, ligustrazine phosphate 200g, can be made into the 1000ml medicinal liquid, finally make 1000 of small-volume injections.Add an amount of 48 ± 2 ℃ of waters for injection in preparing tank, add ligustrazine phosphate and Ginkgo total flavones extract again, fully stirring is dissolved it fully, add the Dextran 40 excipient, add active carbon by 0.02% of preparation cumulative volume, left standstill 20 minutes, add water for injection to the dosing amount, transferring PH is 4.8, with the medicinal liquid decarbonization filtering, medicinal liquid is again through end-filtration, medicinal liquid fill behind end-filtration (loading amount 1.0ml/ props up), the freeze-dried powder product is made in lyophilizing behind the false add plug.
Embodiment 8
Take by weighing above-mentioned (containing Semen Ginkgo total flavones 20g) Ginkgo total flavones extract, ligustrazine phosphate 100g, can finally make 1000 in tablet.Will the Ginkgo total flavones extract, ligustrazine phosphate mixes with 80 gram starch mixings after granulate with starch slurry, cross 20 mesh sieve granulate, drying adds 1 gram magnesium stearate compacting in flakes, promptly gets to contain Semen Ginkgo total flavones pharmaceutical composition tablet.
Embodiment 9
Take by weighing above-mentioned (containing Semen Ginkgo total flavones 2g) Ginkgo total flavones extract, ligustrazine phosphate 16g, can finally make capsule.Behind Ginkgo total flavones extract, ligustrazine phosphate and 80 gram starch, 80 gram Pulvis Talci mixings, cross 100 mesh sieves, encapsulated, must contain the agent of Semen Ginkgo total flavones medicament composition capsule.
Experimental example 1
This experimental example is that (every bottle contains ligustrazine phosphate (C for the Semen Ginkgo total flavones pharmaceutical composition bulk capacity injection that contains of the embodiment of the invention 4
8H
12N
2H
3PO
4H
2O) 100mg, Ginkgo total flavones 20mg, 2.25g sodium chloride) detection of injection inspection item of appearance character, pH value, heavy metal and other regulation.
√ character this product is that little yellow is to lurid clear liquid.
√ pH value pH value should be 3.5-5.5 (two appendix VI of Chinese Pharmacopoeia version in 2000).
√ heavy metal precision is measured this product 25ml, puts in the crucible, and water bath method is checked (two appendix VIII of Chinese Pharmacopoeia version in 2000 H, second method) in accordance with the law, contains heavy metal and must not cross 5/1000000ths.
The √ pyrogen: get this product, check (two appendix XI of Chinese Pharmacopoeia version in 2000 D) in accordance with the law, dosage is slowly injected 10ml by the every 1kg of rabbit body weight, should be up to specification.
√ other: should meet under the injection item relevant every regulation (2000 editions two appendix I B of Chinese Pharmacopoeia).
Experimental example 2
This experimental example is that (every bottle contains ligustrazine phosphate (C for the Semen Ginkgo total flavones pharmaceutical composition bulk capacity injection that contains of the embodiment of the invention 4
8H
12N
2H
3PO
4H
2O) 100mg, Ginkgo total flavones 20mg, 2.25g sodium chloride) in the qualitative determination of key component.
Get this product 2ml, add 2 of bismuth potassium iodides, promptly generate salmon precipitation.
In the chromatogram that writes down under Ginkgo total flavones and ligustrazine phosphate assay item, the retention time at test sample peak should be consistent with the corresponding peak of reference substance retention time.
More than 2 kinds of experiments for the present invention contains the qualitative reaction of the contained component of Semen Ginkgo total flavones pharmaceutical composition, illustrating that the present invention contains in the Semen Ginkgo total flavones pharmaceutical composition contains definite component.
Experimental example 3
This experimental example is that (every bottle contains ligustrazine phosphate (C for the Semen Ginkgo total flavones pharmaceutical composition bulk capacity injection that contains of the embodiment of the invention 4
8H
12N
2H
3PO
4H
2O) 100mg, Ginkgo total flavones 20mg, 2.25g sodium chloride) in the detection by quantitative of component.Every ml contains the Semen Ginkgo total flavones and should be 72-88 μ g, ligustrazine phosphate (C
8H
12N
2H
3PO
4H
2O) should be 0.36-0.44mg.
The Ginkgo total flavones assay is measured according to high performance liquid chromatography (two appendix VD of Chinese Pharmacopoeia version in 2000).
Chromatographic condition and system suitability experiment are filler with octadecylsilane chemically bonded silica; With methanol-0.4% phosphoric acid (55: 45) is mobile phase; The detection wavelength is 368nm.Number of theoretical plate calculates by the Quercetin peak should be not less than 2500, and separating degree presses Quercetin and the isorhamnetin peak calculates, should be greater than 1.5.
The preparation precision of reference substance solution takes by weighing through the exsiccant Quercetin of phosphorus pentoxide, kaempferol and isorhamnetin reference substance, adds methanol and makes the mixed solution that every 1ml contains 0.03mg, 0.03mg, 0.02mg, in contrast product solution.
The preparation precision of need testing solution is measured this product 100ml, 50 ℃ are evaporated to about 5ml, add methanol 8ml, 18% hydrochloric acid 3ml, put in the water-bath reflux 1.5 hours, and be cooled to room temperature rapidly, move in the 25ml measuring bottle, add methanol and be diluted to scale, shake up, filter through filter membrane (aperture must not greater than 0.45 μ m), as need testing solution.
Accurate respectively reference substance solution and each the 20 μ l of need testing solution of drawing of algoscopy inject high performance liquid chromatograph, measure, and calculate the content of three kinds of flavone aglycone respectively, are converted into the content of total flavonoids with following formula.
Total flavonoids content=(quercetin content+kaempferol content+isorhamnetin content) * 2.51
The ligustrazine phosphate assay is measured according to high performance liquid chromatography (two appendix V of Chinese Pharmacopoeia version in 2000 D).
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica; With methanol-water (50: 50) is mobile phase; The detection wavelength is 295nm.Number of theoretical plate calculates by the ligustrazine phosphate peak should be not less than 2000.
Algoscopy is got this product, adds the mobile phase dissolving and is diluted to the solution that contains 20 μ g among every 1ml, gets 20 μ l and injects chromatograph of liquid, the record chromatogram; It is an amount of that other gets the ligustrazine phosphate reference substance, measures with method, presses external standard method with calculated by peak area.
According to the embodiment of the invention 4 by three batches of lab scale preparations, 200 bottles every batch, measure as followsly, every ml content results sees Table 3.
Table 3 assay result
| Lot number | Ginkgo total flavones (μ g) | Ligustrazine phosphate (mg) |
| 1 2 3 | 78.5 76.4 83.6 | 0.41 0.38 0.39 |
Claims (9)
1. one kind contains Semen Ginkgo total flavones pharmaceutical composition, it is characterized in that, described pharmaceutical composition contains ligustrazine phosphate and Ginkgo total flavones extract, and the purity of Ginkgo total flavones is greater than 50% in the Ginkgo total flavones extract, and ligustrazine phosphate content is 2-10 times of Ginkgo total flavones.
2. pharmaceutical composition according to claim 1 is characterized in that, wherein ligustrazine phosphate content be Ginkgo total flavones 4-6 doubly.
3. pharmaceutical composition according to claim 1 is characterized in that, wherein ligustrazine phosphate content is 5 times of Ginkgo total flavones.
4. the described preparation of drug combination method of one of claim 1～3 is characterized in that, wherein the Ginkgo total flavones extract is with the raw material water dissolution, and cold preservation is filtered, high speed centrifugation, and the polyamide column purification, the eluent ultrafiltration concentrates, and exsiccant method obtains.
5, preparation of drug combination method according to claim 4, it is characterized in that, wherein the Ginkgo total flavones extract is the water dissolution that raw material is doubly measured with 10-15,4 ℃ of-10 ℃ of cold preservations 24 hours, filter, filtrate centrifugal 20 minutes with 10000 rev/mins speed, supernatant is crossed the polyamide column of having handled well, washes to colourless the alcoholic solution eluting of the 10%-20% of 4 times of column volumes of reuse earlier with water, the alcoholic solution eluting of the 60%-70% of reuse 5-6 times column volume, collect the ethanol elution of high concentration, behind the decompression recycling ethanol, thin up to relative density is 1.05, it with molecular cut off 200 and 600 ultrafiltration membrance filter, the solution that molecular weight is 200-600 is rich in collection, concentrates drying, pulverize, promptly.
6. according to the described pharmaceutical composition of one of claim 1～3, it is characterized in that, described pharmaceutical composition can be prepared into the available dosage form on the various pharmaceuticss, as injectable powder, lyophilized injectable powder, tablet, capsule, small-volume injection, bulk capacity injection, preferred dosage form is small-volume injection, bulk capacity injection.
7. according to the described pharmaceutical composition of one of claim 1～3, it is characterized in that described preparation is a bulk capacity injection, contain an amount of sodium chloride in the bulk capacity injection as isoosmotic adjusting agent.
8. treat ischemic cardio cerebrovascular diseases according to the described pharmaceutical composition of one of claim 1～3 as preparation, as the application of cerebral blood supply insufficiency, cerebral thrombosis, cerebral embolism, cerebral vasospasm, brain insufficiency, alzheimer disease, parkinson, apoplexy, hypertension, hyperlipidemia, arteriosclerosis, coronary heart disease, angina pectoris, each disease medicament aspect of myocardial infarction.
9. the microcirculation pathological changes that causes as preparation treatment hepatic fibrosis, diabetes according to the described pharmaceutical composition of one of claim 1～3, the application of each disease medicament aspect of vasculitis.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510109594 CN1785216A (en) | 2005-10-28 | 2005-10-28 | Medicinal composition contg. total ginkgo flavone, its prepn. method and use |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510109594 CN1785216A (en) | 2005-10-28 | 2005-10-28 | Medicinal composition contg. total ginkgo flavone, its prepn. method and use |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103833650A (en) * | 2013-12-12 | 2014-06-04 | 吉林长舜制药有限公司 | Ligustrazine phosphate compound and medicine composition containing the ligustrazine compound and gingko leaf effective ingredient |
| CN105535925A (en) * | 2016-01-13 | 2016-05-04 | 安徽生物肽产业研究院有限公司 | Components and preparation method of leech biological activity small peptide medicine composition |
| CN106491665A (en) * | 2016-09-26 | 2017-03-15 | 合肥信达膜科技有限公司 | A kind of GINKGO BILOBA EXTRACT film separation system and method |
-
2005
- 2005-10-28 CN CN 200510109594 patent/CN1785216A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103833650A (en) * | 2013-12-12 | 2014-06-04 | 吉林长舜制药有限公司 | Ligustrazine phosphate compound and medicine composition containing the ligustrazine compound and gingko leaf effective ingredient |
| CN103833650B (en) * | 2013-12-12 | 2015-02-25 | 吉林长舜制药有限公司 | Ligustrazine phosphate compound and medicine composition containing the ligustrazine compound and gingko leaf effective ingredient |
| CN105535925A (en) * | 2016-01-13 | 2016-05-04 | 安徽生物肽产业研究院有限公司 | Components and preparation method of leech biological activity small peptide medicine composition |
| CN106491665A (en) * | 2016-09-26 | 2017-03-15 | 合肥信达膜科技有限公司 | A kind of GINKGO BILOBA EXTRACT film separation system and method |
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