CN1768753A - Medicinal composition containing bilobalide B and its preparation process and usage - Google Patents
Medicinal composition containing bilobalide B and its preparation process and usage Download PDFInfo
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- CN1768753A CN1768753A CN 200510109596 CN200510109596A CN1768753A CN 1768753 A CN1768753 A CN 1768753A CN 200510109596 CN200510109596 CN 200510109596 CN 200510109596 A CN200510109596 A CN 200510109596A CN 1768753 A CN1768753 A CN 1768753A
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- ginkalide
- ethyl acetate
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Abstract
The invention discloses a medicinal composition containing bilobalide B, which comprises Ligustrazine phosphate and bilobalide B by the weight ratio of 10-500 : 1. the invention also discloses the process for preparing the pharmaceutical composition.
Description
Technical field
The invention belongs to field of medicaments, be specifically related to a kind of medicinal composition containing bilobalide B and preparation method thereof and purposes, more particularly, relate to a kind of pharmaceutical composition that combines by ligustrazine phosphate and ginkalide B, its preparation method and the application aspect preparation treatment ischemic cardio cerebrovascular diseases medicine thereof.
Background technology
Bilobalide is the main active in the Semen Ginkgo, can eliminate platelet aggregation, suppress thrombosis, can prevent atherosclerosis, and cardiac muscle, cerebral ischemia are had good protective effect etc.; Mainly contain ginkalide A, B, C etc., wherein ginkalide B is the strongest component of its pharmacologically active.
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.Wherein said Semen Ginkgo extrac is the mixture of plurality of active ingredients, and the active component ginkalide B only accounts for a few part wherein.Curative effect is not an ideal very in zoopery afterwards and the clinical practice.
At present, after back of no-trump ginkalide B purification still and ligustrazine phosphate carry out assembly with certain proportion, make the report that medicine carries out clinical use.
Summary of the invention
At above the deficiencies in the prior art, research worker of the present invention is through a large amount of tests, and preparing with ginkalide B and ligustrazine phosphate is main active, according to a certain weight ratio, and the pharmaceutical composition of better efficacy.
An object of the present invention is to disclose a kind of medicinal composition containing bilobalide B.
Another object of the present invention is the preparation method that discloses above-mentioned medicinal composition containing bilobalide B.
Another purpose of the present invention is the purposes that discloses above-mentioned medicinal composition containing bilobalide B.
Medicinal composition containing bilobalide B of the present invention can be prepared into the available dosage form on the various pharmaceuticss, therefore can make 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.
Ginkalide B of the present invention, its purity is more than 90%.The ginkalide B that meets above-mentioned purity regulation of any method preparation can be used for preparing medicinal composition containing bilobalide B of the present invention.
In the medicinal composition containing bilobalide B of the present invention, ligustrazine phosphate content is 10-500 times of ginkalide B; The 50-200 that is preferably ligustrazine phosphate content and is ginkalide B doubly; More preferably ligustrazine phosphate content is 100 times of ginkalide B.
Ginkalide B extract of the present invention also can adopt following method preparation:
Be the Semen Ginkgo extrac among the CN200410083882.9 with application number or meet that " Folium Ginkgo extract of Chinese pharmacopoeia standard is as initiation material, with the raw material water dissolution, defat with petroleum ether, ethyl acetate extraction, sodium bicarbonate solution washing, ethyl acetate liquid concentrates, dilution, ultrafiltration, filtrate concentrates, drying, the method for preparative hplc column purification obtains.
More specifically, ginkalide B of the present invention is prepared from through following step:
With the water dissolution of raw material with 5 times of amounts, behind defat with petroleum ether, aqueous solution merges ethyl acetate extraction liquid with isopyknic ethyl acetate extraction 5 times, and with the sodium bicarbonate solution washing of 0.1mol/L 4 times, the ethyl acetate liquid after the washing is washed with water to neutrality; Ethyl acetate liquid is concentrated, and concentrated solution thin up to relative density is 1.05, is 200 and 600 ultrafiltration membrance filter with molecular cut off, collects and is rich in the solution that molecular weight is 200-600, and is concentrated, drying, last C
18The reversed-phase preparative chromatography post, with 70%-90% alcoholic solution eluting, equal-volume is collected eluent, and the eluent that is rich in ginkalide B is mixed, and concentrates, and drying promptly gets ginkalide B.
Medicinal composition containing bilobalide B of the present invention 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.The various dosage forms of medicinal composition containing bilobalide B of the present invention can be according to the conventional production method preparation of pharmaceutical field.Such as using ligustrazine phosphate, ginkalide B to mix, be made into required dosage form then with one or more carriers.
Medicinal composition containing bilobalide B 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 100 times of proportionings of ginkalide B weight, curative effect is best.Experimental result sees Table 1.
The experiment of table 1 active component proportion optimization
| Ligustrazine phosphate: ginkalide B (g/g) | Pharmacological action |
| 800∶1 600∶1 500∶1 400∶1 300∶1 200∶1 | ± ± + + + ++ |
| 100∶1 50∶1 10∶1 5∶1 1∶1 | +++ ++ + ± ± |
Annotate: ± expression pharmacological action is poor; + expression pharmacological action is general; ++ the expression pharmacological action is better; +++expression pharmacological action 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, ginkalide B 1mg.
Usage is as follows: intravenous drip, one time one bottle, 10～15 days is a course of treatment.
Medicinal composition containing bilobalide B of the present invention replenishes synergism mutually by ginkalide B and ligustrazine phosphate, can play beyond thought effect.Ginkalide B can be eliminated platelet aggregation, suppress thrombosis, can prevent atherosclerosis, and cardiac muscle, cerebral ischemia are had good protective effect; Ligustrazine phosphate absorbs and drains rapidly, can play a role by blood-CSF barrier.
Medicinal composition containing bilobalide B of the present invention is the compound preparation that ginkalide B 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.
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 ginkalide B 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 5 times of amounts, behind defat with petroleum ether, aqueous solution merges ethyl acetate extraction liquid with isopyknic ethyl acetate extraction 5 times, and with the sodium bicarbonate solution washing of 0.1mol/L 4 times, the ethyl acetate liquid after the washing is washed with water to neutrality; Ethyl acetate liquid is concentrated, and concentrated solution thin up to relative density is 1.05, is 200 and 600 ultrafiltration membrance filter with molecular cut off, collects and is rich in the solution that molecular weight is 200-600, and is concentrated, drying, last C
18The reversed-phase preparative chromatography post, with 70% alcoholic solution eluting, equal-volume is collected eluent, and the eluent that is rich in ginkalide B is mixed, and concentrates, and drying promptly gets ginkalide B.
Embodiment 2
With the water dissolution of raw material with 5 times of amounts, behind defat with petroleum ether, aqueous solution merges ethyl acetate extraction liquid with isopyknic ethyl acetate extraction 5 times, and with the sodium bicarbonate solution washing of 0.1mol/L 4 times, the ethyl acetate liquid after the washing is washed with water to neutrality; Ethyl acetate liquid is concentrated, and concentrated solution thin up to relative density is 1.05, is 200 and 600 ultrafiltration membrance filter with molecular cut off, collects and is rich in the solution that molecular weight is 200-600, and is concentrated, drying, last C
18The reversed-phase preparative chromatography post, with 90% alcoholic solution eluting, equal-volume is collected eluent, and the eluent that is rich in ginkalide B is mixed, and concentrates, and drying promptly gets ginkalide B.
Embodiment 3
With the water dissolution of raw material with 5 times of amounts, behind defat with petroleum ether, aqueous solution merges ethyl acetate extraction liquid with isopyknic ethyl acetate extraction 5 times, and with the sodium bicarbonate solution washing of 0.1mol/L 4 times, the ethyl acetate liquid after the washing is washed with water to neutrality; Ethyl acetate liquid is concentrated, and concentrated solution thin up to relative density is 1.05, is 200 and 600 ultrafiltration membrance filter with molecular cut off, collects and is rich in the solution that molecular weight is 200-600, and is concentrated, drying, last C
18The reversed-phase preparative chromatography post, with 80% alcoholic solution eluting, equal-volume is collected eluent, and the eluent that is rich in ginkalide B is mixed, and concentrates, and drying promptly gets ginkalide B.
Embodiment 4
Take by weighing above-mentioned ginkalide B 0.4g, 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 ginkalide B 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 ginkalide B 5g, 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 ginkalide B 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 6
Take by weighing above-mentioned ginkalide B 1g, ligustrazine phosphate 50g, 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 ginkalide B 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 7
Take by weighing above-mentioned ginkalide B 0.5g, ligustrazine phosphate 100g, can finally make 1000 in tablet.Will the ginkalide B 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 the medicinal composition containing bilobalide B tablet.
Embodiment 8
Take by weighing above-mentioned ginkalide B 0.032g, ligustrazine phosphate 16g, can finally make capsule.Behind ginkalide B extract, ligustrazine phosphate and 80 gram starch, 80 gram Pulvis Talci mixings, cross 100 mesh sieves, encapsulated, get the medicinal composition containing bilobalide B capsule.
Experimental example 1
This experimental example is that (every bottle contains ligustrazine phosphate (C for the medicinal composition containing bilobalide B bulk capacity injection of the embodiment of the invention 4
8H
12N
2H
3PO
4H
2O) 100mg, ginkalide B 1.0mg, 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 medicinal composition containing bilobalide B bulk capacity injection of the embodiment of the invention 4
8H
12N
2H
3PO
4H
2O) 100mg, ginkalide B 1.0mg, 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 ginkalide B and ligustrazine phosphate assay item, the retention time at test sample peak should be consistent with the corresponding peak of reference substance retention time.
This product shows sodium salt and muriatic identification (two appendix III of Chinese Pharmacopoeia version in 2000).
More than 3 kinds of experiments be the qualitative reactions of the contained component of medicinal composition containing bilobalide B of the present invention, illustrate and contain definite component in the medicinal composition containing bilobalide B of the present invention.
Experimental example 3
This experimental example is that (every bottle contains ligustrazine phosphate (C for the medicinal composition containing bilobalide B bulk capacity injection of the embodiment of the invention 4
8H
12N
2H
3PO
4H
2O) 100mg, ginkalide B 1.0mg, 2.25g sodium chloride) in the detection by quantitative of component.Every ml bilobalide-containing B should be 3.60-4.40 μ g, ligustrazine phosphate (C
8H
12N
2H
3PO
4H
2O) should be 0.36-0.44mg.
The ginkalide B assay according to " under Semen Ginkgo extrac item of Chinese pharmacopoeia version in 2000 in the assay high performance liquid chromatography under the terpene lactone measure.
The ligustrazine phosphate assay is measured according to the content assaying method among the application number CN200410083882.9.
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 2.
Table 2 assay result
| Lot number | Ginkalide B (μ g) | Ligustrazine phosphate (mg) |
| 20031001 20031002 20031003 | 3.84 4.08 4.12 | 0.42 0.37 0.41 |
Positive control drug is the method preparation in the patent documentation of CN200410083882.9 according to application number; Medicine of the present invention is bulk capacity injection according to the preparation of embodiment 4 methods.
Pharmacology embodiment 1: to the influence experiment of anoxia in mice endurance
Get 30 of healthy Kunming mouses, body weight 20～24g.Be divided into the normal control group at random, positive controls, medicine group of the present invention.Every group 10, male and female half and half, sub-cage rearing.Each organizes respectively that intravenous injection gives relative medicine, and matched group is given the normal saline of respective volume, and 1 time/d, 7d continuously.After the last administration 1 hour, it was the 150ml port grinding bottle that mice is placed volume respectively, in put 1 5g sodica calx, its time-to-live of airtight observation.The results are shown in Table 3.
The influence of table 3 pair mice normobaric hypoxia (X ± S)
| Group | Mus number (only) | Mean survival time (min) |
| Normal control group positive controls medicine group of the present invention | 10 10 10 | 16.56±3.24 25.08±3.20 ** 28.74±3.10 **# |
Annotate: compare with the normal control group:
*P＜0.01; Compare with positive controls: #P＜0.05.
Pharmacology embodiment 2: to the anoxybiotic protective effect experiment of mouse cardiac muscle
Get 30 of healthy Kunming mouses, body weight 18～22 g are divided into 3 groups at random, are divided into the normal control group at random, positive drug group, medicine group of the present invention.Every group of male and female half and half, sub-cage rearing.Each organizes respectively that intravenous injection gives relative medicine, and matched group is given the normal saline of respective volume.Medication: 1 time/day, continuous 7 days.Back fixation was separated trachea with urethane 1.2g/kg intraperitoneal injection of anesthesia in 1 hour after the last administration, with the bulldog clamp folder pipe of holding one's breath, observed electrocardio with electrocardiogram equipment, and write down the little mousetrap with stopwatch and hold one's breath time of Guan Houzhi electrocardio disappearance.The results are shown in Table 4.
The anoxybiotic influence of table 4 pair mouse cardiac muscle (X ± S)
| Group | Mus number (only) | Mean survival time (min) |
| Normal control group positive controls medicine group of the present invention | 10 10 10 | 6.64±0.78 10.37±0.72 ** 12.26±0.64 **# |
Annotate: compare with the normal control group:
*P＜0.01; Compare with positive controls: #P＜0.05.
Pharmacology embodiment 3: to the influence of rat thrombus in vivo formation
Rat is divided into 3 groups at random, 10 every group, is respectively the normal control group, positive drug group, medicine group of the present invention.Each organizes respectively that vein gives relative medicine, and matched group is given the normal saline of respective volume, control group administered physiological saline.Every day 1 time, successive administration 7 days, after the last administration 1 hour, rat is used 10% chloral hydrate, it is fixing to press 0.3g/kg body weight anesthesia back, separates left common carotid artery, on the thrombosis instrument with 2mA galvanism blood vessel 7min after, the record thrombus formation time.The results are shown in Table 5.
The influence that table 5 pair rat thrombus in vivo forms (X ± S)
| Group | Mus number (only) | Thrombus formation time (min) |
| Normal control group positive controls medicine group of the present invention | 10 10 10 | 625.3±72.5 734.7±87.6 **786.4±92.4 **# |
Annotate: compare with the normal control group:
*P＜0.01; Compare with positive controls: #P＜0.05.
By above-mentioned pharmacological evaluation as can be seen, medicinal composition containing bilobalide B of the present invention has raising than the curative effect of existing preparation.
Claims (9)
1. a medicinal composition containing bilobalide B is characterized in that, described pharmaceutical composition contains ligustrazine phosphate and ginkalide B, and wherein contained ligustrazine phosphate weight is 10～500 times of ginkalide B weight.
2. pharmaceutical composition according to claim 1 is characterized in that, wherein ligustrazine phosphate weight is 50～200 times of ginkalide B weight.
3. pharmaceutical composition according to claim 2 is characterized in that, wherein ligustrazine phosphate weight is 100 times of ginkalide B weight.
4. the described preparation of drug combination method of one of claim 1～3, it is characterized in that described ginkalide B is by with raw material water dissolution, defat with petroleum ether, ethyl acetate extraction, the sodium bicarbonate solution washing, ethyl acetate liquid concentrates, dilution, ultrafiltration, filtrate concentrates, drying, and the method for preparative hplc column purification obtains.
5, preparation of drug combination method according to claim 4 is characterized in that, the preparation method of described ginkalide B is:
With the water dissolution of raw material with 5 times of amounts, behind defat with petroleum ether, aqueous solution merges ethyl acetate extraction liquid with isopyknic ethyl acetate extraction 5 times, and with the sodium bicarbonate solution washing of 0.1mol/L 4 times, the ethyl acetate liquid after the washing is washed with water to neutrality; Ethyl acetate liquid is concentrated, and concentrated solution thin up to relative density is 1.05, is 200 and 600 ultrafiltration membrance filter with molecular cut off, collects and is rich in the solution that molecular weight is 200-600, and is concentrated, drying, last C
18The reversed-phase preparative chromatography post, with 70%-90% alcoholic solution eluting, equal-volume is collected eluent, and the eluent that is rich in ginkalide B is mixed, concentrate, drying, promptly.
6. according to the described pharmaceutical composition of one of claim 1～3, it is characterized in that, described compositions 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. pharmaceutical composition according to claim 6 is characterized in that described preparation is a bulk capacity injection, contains 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 |
|---|---|---|---|
| CNB200510109596XA CN100367963C (en) | 2005-10-28 | 2005-10-28 | Medicinal composition containing bilobalide B and its preparation process and usage |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB200510109596XA CN100367963C (en) | 2005-10-28 | 2005-10-28 | Medicinal composition containing bilobalide B and its preparation process and usage |
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|---|---|
| CN1768753A true CN1768753A (en) | 2006-05-10 |
| CN100367963C CN100367963C (en) | 2008-02-13 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105412367A (en) * | 2015-12-22 | 2016-03-23 | 桂林双象生物科技有限公司 | Making method of compound raw tea of gingko and Adinandra nitida Merr.ex H.L.Li |
| WO2016066100A1 (en) * | 2014-10-30 | 2016-05-06 | 成都百裕科技制药有限公司 | Pharmaceutical composition containing ginkgolide b and adp receptor antagonist, preparation method thereof and use thereof |
| CN105561309A (en) * | 2014-10-30 | 2016-05-11 | 成都百裕科技制药有限公司 | Pharmaceutical composition containing ginkgolide B and thrombin inhibitor and preparation method and application of pharmaceutical composition |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1124275C (en) * | 2000-06-02 | 2003-10-15 | 天津大学 | Method of preparing ginkalide A and B as medicine from ginkgo leaf or its extract |
| CN1320890C (en) * | 2003-10-28 | 2007-06-13 | 阿尔贝拉医药(中国)有限公司 | Ginkgo medicine composition, its preparing method and its use |
-
2005
- 2005-10-28 CN CNB200510109596XA patent/CN100367963C/en active Active
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016066100A1 (en) * | 2014-10-30 | 2016-05-06 | 成都百裕科技制药有限公司 | Pharmaceutical composition containing ginkgolide b and adp receptor antagonist, preparation method thereof and use thereof |
| CN105561309A (en) * | 2014-10-30 | 2016-05-11 | 成都百裕科技制药有限公司 | Pharmaceutical composition containing ginkgolide B and thrombin inhibitor and preparation method and application of pharmaceutical composition |
| CN105561308A (en) * | 2014-10-30 | 2016-05-11 | 成都百裕科技制药有限公司 | Pharmaceutical composition containing ginkgolide B and adenosine diphosphate receptor antagonist and preparation method and application of pharmaceutical composition |
| CN105561309B (en) * | 2014-10-30 | 2019-03-19 | 成都百裕制药股份有限公司 | A kind of pharmaceutical composition and its preparation method and application containing ginkolide B and thrombin inhibitor |
| CN105561308B (en) * | 2014-10-30 | 2019-03-19 | 成都百裕制药股份有限公司 | A kind of pharmaceutical composition and its preparation method and application containing ginkolide B and ADP receptor resistant |
| US10322105B2 (en) | 2014-10-30 | 2019-06-18 | Chengdu Baiyu Pharmaceutical Co., Ltd | Pharmaceutical composition containing Ginkgolide B and ADP receptor antagonist, preparation method thereof and use thereof |
| US10751321B2 (en) | 2014-10-30 | 2020-08-25 | Chengdu Baiyu Pharmaceutical Co., Ltd | Pharmaceutical composition containing Ginkgolide B and ADP receptor antagonist, preparation method thereof and use thereof |
| CN105412367A (en) * | 2015-12-22 | 2016-03-23 | 桂林双象生物科技有限公司 | Making method of compound raw tea of gingko and Adinandra nitida Merr.ex H.L.Li |
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| Publication number | Publication date |
|---|---|
| CN100367963C (en) | 2008-02-13 |
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