CN101491519B - Bilobalide injector and preparation method thereof - Google Patents
Bilobalide injector and preparation method thereof Download PDFInfo
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- CN101491519B CN101491519B CN2008100187154A CN200810018715A CN101491519B CN 101491519 B CN101491519 B CN 101491519B CN 2008100187154 A CN2008100187154 A CN 2008100187154A CN 200810018715 A CN200810018715 A CN 200810018715A CN 101491519 B CN101491519 B CN 101491519B
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- injection
- ginkalide
- bilobalide
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- cosolvent
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Abstract
The invention relates to the field of pharmaceutical preparations, in particular to a ginkgolides B injection and a preparation method thereof. The preparation method is characterized in that a mixed solvent of polyethylene glycol 600 and alcohol is added as a latent solvent. The ginkgolides B injection has steady quality, and cannot precipitate crystals after the long-term storage.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to a kind of bilobalide injector and preparation method thereof.
Background technology
Along with the development to Folium Ginkgo research, now prove: the active component of Folium Ginkgo mainly is flavone and lactone compound.Bilobalide is that a class of only finding in Folium Ginkgo has the important component of special construction and remarkable pharmacologically active, does not find as yet so far to be present in other any plants.The more important thing is that they have unique pharmacological action and therapeutic value.Ginkgolide compound has: ginkalide A (BN52020), ginkalide B (BN52021), ginkalide C (BN52022), bilobalide M (BN52023), bilobalide J (BN52024) and bilobalide, proved that bilobalide is strong platelet activating factor (plateletacllvatfactor, PAF) receptor antagonist.Clear and definite along with to effective ingredient in the Folium Ginkgo, the single active ingredient new drug becomes the target that countries such as France, Britain, Germany and the U.S. competitively develop over past ten years.To the further investigation of effective ingredient in the Folium Ginkgo find its terpene lactone especially ginkalide B have stronger medical value, its content in Folium Ginkgo is about 0.2%, his activity is the strongest, research also many more.
It is clinical that the ginkalide B preparation has been applied to II, III phase at present abroad.Be used for tests such as shock, burn, apoplexy, transplant rejection and hemodialysis clinically, also have the report of clinical research at home, this will point out the ginkalide B preparation and to treat cardiovascular and cerebrovascular disease for prevention provide a kind new medicine.The injection bioavailability is much higher than oral formulations, so injection is the preferred dosage form of ginkalide B.Because ginkalide B is insoluble in water, ginkalide B is made comparatively difficulty of injection.CN1517088A discloses a kind of method for preparing Folium Ginkgo extract, and it is by adding poloxamer 188 with hydrotropy; CN1827099A discloses with ethanol, surfactant and has prepared injection of ginkgolide B with hydrotropy; CN1843351A discloses a kind of method for preparing injection of ginkgolide B with sodium carbonate and propylene glycol as cosolvent; CN101053554A discloses the method for preparing injection of ginkgolide B with the meglumine hydrotropy; CN1513449A discloses a kind of by adding polyglycols 300 or the PEG400 method with hydrotropy.
If it is improper that cosolvent is selected, can cause in storage that so medicine separates out, this can influence medicine effect, brings hidden danger for simultaneously the safety of treatment.
Summary of the invention
The invention discloses a kind of ginkalide B injection of (being called for short GB), its steady quality, Long-term Storage can not separated out.
Bilobalide B injection of the present invention contains ginkalide B, cosolvent and water for injection, and cosolvent is selected Macrogol 600 and ethanol mixed solvent for use, and by volume, Macrogol 600: ethanol is 1: 30-30: 1.Preferred Macrogol 600: the ethanol volume ratio is 1: 3-3: 1.
The weight ratio of ginkalide B and above-mentioned cosolvent preferred 1: 0.1-100.
Above-mentioned injection also can add propylene glycol and/or surfactant.
The w/v of ginkalide B and propylene glycol is preferably 1: 0.004-0.4.Further preferred 1: 0.01-1: 0.1.
The w/v of ginkalide B and surfactant is 1: 0.001-0.02.Further preferred 1: 0.005-1: 0.01.
The preferred tween of above-mentioned surfactant.
Bilobalide B injection of the present invention can be prepared by following method: with cosolvent ginkalide B is dissolved substantially, fully stir or supersound process dissolving extremely fully, adding water for injection to ginkalide B concentration again is 0.01mg/ml～10mg/ml, with sodium citrate solution or sodium acetate solution, behind the regulator solution PH3-9, filtration, embedding, sterilization are promptly.
The present invention has greatly improved the dissolubility of ginkalide B with Macrogol 600 (be called for short PEG600) and ethanol mixed solvent as cosolvent, and accelerated test and long term test show that bilobalide B injection quality stability of the present invention all is better than the injection that other cosolvents prepare.The bilobalide B injection test and the result that are several different cosolvent preparations below compare:
The bilobalide B injection test and the result of several different cosolvent preparations
Annotate: poloxamer 188 aqueous solutions are according to 1: 1 ratio wiring solution-forming with poloxamer 188 (mg) and water (ml)
As seen from the above table, when adopting Macrogol 600 and ethanol as cosolvent, the GB dissolubility, product stability under the refrigerated condition, and compatibility liquid dissolubility all has significantly raising.
The specific embodiment
Embodiment 1
Prescription: 10mg/5ml
Raw material 1000mg
PEG-600200ml
EtOH 200ml
Add the injection water to 500ml
Embodiment 2
Prescription: 10mg/5ml
Raw material 1000mg
PEG-600100ml
EtOH 300ml
Add the injection water to 500ml
Embodiment 3
Prescription: 10mg/5ml
Raw material 1000mg
PEG-600300ml
EtOH 100ml
Add the injection water to 500ml
Embodiment 4
Prescription: 10mg/5ml
Raw material 1000mg
PEG-600200ml
EtOH 100ml
Propylene glycol 100ml
Add the injection water to 500ml
Embodiment 5
Prescription: 10mg/5ml
Raw material 1000mg
PEG-600100ml
EtOH 200ml
Propylene glycol 100ml
Add the injection water to 500ml
Embodiment 6
Prescription: 10mg/5ml
Raw material 1000mg
PEG-600300ml
EtOH 100ml
Propylene glycol 50ml
Tween 80 10ml
Add the injection water to 500ml
Claims (6)
1. bilobalide B injection, wherein contain ginkalide B, cosolvent and water for injection, it is characterized in that: the weight ratio 1 of ginkalide B and cosolvent: 0.1-100, cosolvent are Macrogol 600 and ethanol mixed solvent, by volume, Macrogol 600: ethanol is 1: 3-3: 1.
2. injection according to claim 1 wherein also contains propylene glycol and/or tween.
3. injection according to claim 2, wherein the w/v of ginkalide B and propylene glycol is 1: 0.004-0.4.
4. injection according to claim 3, wherein the w/v of ginkalide B and propylene glycol is 1: 0.01-1: 0.1.
5. injection according to claim 2, wherein the w/v of ginkalide B and tween is 1: 0.001-0.02.
6. injection according to claim 5, wherein the w/v of ginkalide B and tween is 1: 0.005-1: 0.01.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008100187154A CN101491519B (en) | 2008-01-22 | 2008-01-22 | Bilobalide injector and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008100187154A CN101491519B (en) | 2008-01-22 | 2008-01-22 | Bilobalide injector and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101491519A CN101491519A (en) | 2009-07-29 |
| CN101491519B true CN101491519B (en) | 2011-09-28 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2008100187154A Expired - Fee Related CN101491519B (en) | 2008-01-22 | 2008-01-22 | Bilobalide injector and preparation method thereof |
Country Status (1)
| Country | Link |
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| CN (1) | CN101491519B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102058578A (en) * | 2011-01-07 | 2011-05-18 | 中国药科大学 | Preparation method of ginkgolide preparation |
| CN113730347A (en) * | 2021-09-30 | 2021-12-03 | 山东仁和制药有限公司 | Ginkgo diterpene lactone injection and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1513449A (en) * | 2003-06-20 | 2004-07-21 | 梅世昌 | Prepn. method for injection of ginkgolide |
| CN1827099A (en) * | 2006-04-18 | 2006-09-06 | 张国清 | Intravenous administered injection of ginkgolide B, its preparation method and application |
-
2008
- 2008-01-22 CN CN2008100187154A patent/CN101491519B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1513449A (en) * | 2003-06-20 | 2004-07-21 | 梅世昌 | Prepn. method for injection of ginkgolide |
| CN1827099A (en) * | 2006-04-18 | 2006-09-06 | 张国清 | Intravenous administered injection of ginkgolide B, its preparation method and application |
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| Publication number | Publication date |
|---|---|
| CN101491519A (en) | 2009-07-29 |
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