CN1557297A - Gingko lactone powder injection and its preparation method - Google Patents
Gingko lactone powder injection and its preparation method Download PDFInfo
- Publication number
- CN1557297A CN1557297A CNA2004100139379A CN200410013937A CN1557297A CN 1557297 A CN1557297 A CN 1557297A CN A2004100139379 A CNA2004100139379 A CN A2004100139379A CN 200410013937 A CN200410013937 A CN 200410013937A CN 1557297 A CN1557297 A CN 1557297A
- Authority
- CN
- China
- Prior art keywords
- bilobalide
- injectable powder
- preparation
- meglumine
- injection
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000000843 powder Substances 0.000 title claims abstract description 38
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 238000002347 injection Methods 0.000 title claims abstract description 12
- 239000007924 injection Substances 0.000 title claims abstract description 12
- SQOJOAFXDQDRGF-UHFFFAOYSA-N ginkgolide b Chemical compound O=C1OC2CC(C(C)(C)C)C34C(O)C(=O)OC4OC41C32C(O)C1OC(=O)C(C)C41O SQOJOAFXDQDRGF-UHFFFAOYSA-N 0.000 title 1
- MOLPUWBMSBJXER-YDGSQGCISA-N bilobalide Chemical compound O([C@H]1OC2=O)C(=O)[C@H](O)[C@@]11[C@@](C(C)(C)C)(O)C[C@H]3[C@@]21CC(=O)O3 MOLPUWBMSBJXER-YDGSQGCISA-N 0.000 claims abstract description 98
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 16
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 claims abstract description 16
- 229960003194 meglumine Drugs 0.000 claims abstract description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000000243 solution Substances 0.000 claims description 11
- 238000012856 packing Methods 0.000 claims description 10
- 238000007710 freezing Methods 0.000 claims description 9
- 230000008014 freezing Effects 0.000 claims description 9
- 238000001914 filtration Methods 0.000 claims description 7
- 238000009413 insulation Methods 0.000 claims description 7
- 238000001035 drying Methods 0.000 claims description 5
- 239000012982 microporous membrane Substances 0.000 claims description 5
- 238000001816 cooling Methods 0.000 claims description 4
- 238000001291 vacuum drying Methods 0.000 claims description 4
- 238000009740 moulding (composite fabrication) Methods 0.000 claims description 3
- 230000000694 effects Effects 0.000 abstract description 6
- 239000000463 material Substances 0.000 abstract description 2
- 239000000203 mixture Substances 0.000 abstract description 2
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 abstract 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 8
- 238000000465 moulding Methods 0.000 description 8
- 239000007788 liquid Substances 0.000 description 7
- 239000002671 adjuvant Substances 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 238000000034 method Methods 0.000 description 4
- 229910052759 nickel Inorganic materials 0.000 description 4
- 230000036760 body temperature Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 230000007928 solubilization Effects 0.000 description 3
- 238000005063 solubilization Methods 0.000 description 3
- 239000008215 water for injection Substances 0.000 description 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 241000218628 Ginkgo Species 0.000 description 2
- 235000011201 Ginkgo Nutrition 0.000 description 2
- 235000008100 Ginkgo biloba Nutrition 0.000 description 2
- 208000026106 cerebrovascular disease Diseases 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 238000009777 vacuum freeze-drying Methods 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention discloses one kind of bilobalide powder for injection and features its composition including bilobalide, meglumine and hydroxypropyl-beta-cyclodextrin in the weight ratio of 1 to 0.2-0.5 to 6-9. The present invention also discloses the preparation process of the bilobalide powder for injection. The bilobalide powder for injection has supplementary material capable of dissolving bilobalide completely without destroying its structure, and bilobalide as the main material is slightly soluble in water and easily soluble in acetone. The key point of the present invention is to select hydroxypropyl-beta-cyclodextrin as the solubilkizing supplementary material to raise the solubility of bilobalide greatly, and this raises the bioavailability of bilobalide and the curative effect of the injection greatly.
Description
Technical field
The present invention relates to a kind of pharmaceutical preparation of Chinese herbal medicine extract bilobalide, particularly a kind of bilobalide injectable powder; The invention still further relates to the preparation method of this kind injectable powder.
Background technology
Bilobalide is the active substance that extract to obtain from Folium Ginkgo, for the extracting method of bilobalide detailed bibliographical information has been arranged.Bilobalide might be developed to the clinical treatment medicine that plays an important role as the higher platelet antagonism factor of a kind of activity in the pathological processes such as shock that thrombosis, organ-graft refection, senile dementia, acute inflammation, heart allergy, endotoxin cause.Because bilobalide is slightly soluble in water, be the key of moulding process so select the adjuvant of tool solubilization.And bilobalide preparation of the prior art mostly exists shortcoming such as bioavailability reduction, poor stability, curative effect of medication are slow, cost height.
Summary of the invention
Technical problem to be solved by this invention is at the deficiencies in the prior art, a kind of bilobalide injectable powder of preventing and treating cardiovascular and cerebrovascular disease that provide a kind of bioavailability height, act on rapidly, preparation stability is strong.The present invention also provides the preparation method of this kind bilobalide injectable powder.
Technical problem to be solved by this invention is to realize by following technical scheme.The present invention is a kind of bilobalide injectable powder, is characterized in, its main component and weight content ratio are bilobalide: meglumine: HP-=1: (0.2-0.5): (6-9).
Technical problem to be solved by this invention can also further realize by following technical scheme.Above-described a kind of bilobalide injectable powder is characterized in that its main component and weight content ratio are bilobalide: meglumine: HP-=1: 0.3: 7.This is an optimized technical scheme of the present invention.
Technical problem to be solved by this invention can also further realize by following technical scheme.The present invention is a kind of preparation method of bilobalide injectable powder, is characterized in, get HP-, meglumine and add the dissolving of injection water, solution I, 70-90 ℃ of insulation, standby; Other gets bilobalide and adds proper amount of acetone and make its dissolving, it is slowly added in the solution I dissolve again, is incubated 50-70 minute, puts then and is chilled to room temperature, filter, and filtering with microporous membrane again, packing, lyophilizing, promptly.
Technical problem to be solved by this invention can also further realize by following technical scheme.The preparation method of above-described a kind of bilobalide injectable powder is characterized in, its freeze-dry process is ,-15 ℃ of freeze formings earlier, and ℃ frozen cooling again-40, freezing vacuum drying down after 30 hours, slowly heats up, until 25 ℃ of cappings.
Compared with prior art, the present invention has following advantage: directly be instilled into blood by intravenous injection when one, injectable powder of the present invention uses, can reduce medicine in the loss that gastrointestinal destroys and absorption does not cause entirely, improve bioavailability of medicament; Two, injectable powder of the present invention is used for the control of cardiovascular and cerebrovascular disease, and effect is rapid, and the curative effect of medication height has increased stability of formulation; Three, the selected adjuvant of injectable powder of the present invention can dissolve (or promoting dissolving) bilobalide fully, and do not destroy its structure, the raw material bilobalide is slightly soluble in water, easily be dissolved in acetone, selecting the adjuvant of tool solubilization is the key of moulding process, the present invention is in preparation dosing process, by selecting for use powder pin supporter HP-as adjuvant with solubilization, can increase the dissolubility of raw material greatly, the availability of bilobalide is improved, the curative effect of medication of injectable powder is improved, save cost simultaneously.
The specific embodiment
Embodiment 1.A kind of bilobalide injectable powder, its main component and weight content be,
Bilobalide 50.0g
Meglumine 15.0g
HP-350.0g makes the 5000ml injection, 1000 of packing, and lyophilizing, promptly.
Embodiment 2.A kind of bilobalide injectable powder, its main component and weight content be,
Bilobalide 50.0g
Meglumine 10.0g
HP-300.0g makes the 5000ml injection, 1000 of packing, and lyophilizing, promptly.
Embodiment 3.A kind of bilobalide injectable powder, its main component and weight content be,
Bilobalide 50.0g
Meglumine 20.0g
HP-400.0g makes the 5000ml injection, 1000 of packing, and lyophilizing, promptly.
Embodiment 4.A kind of bilobalide injectable powder, its main component and weight content be,
Bilobalide 500.0
Meglumine 250.0g
HP-4500.0g
Make the 50000ml injection, 10000 of packing, lyophilizing, promptly.
Embodiment 5.A kind of preparation method of bilobalide injectable powder is got HP-350 gram, meglumine 15 grams add the dissolving of 5000ml water for injection, solution I, 80 ℃ of insulations, standby; Other gets bilobalide 50 gram and adds proper amount of acetone and make its dissolving, it is slowly added in the solution I dissolve again, be incubated 60 minutes, and put then and be chilled to room temperature, filtration, filtering with microporous membrane again, 1000 of packing, lyophilizing, promptly.
Embodiment 6.A kind of preparation method of bilobalide injectable powder is got HP-375 gram, meglumine 17.5 grams add the dissolving of 5000ml water for injection, solution I, 75 ℃ of insulations, standby; Other gets bilobalide 50 gram and adds proper amount of acetone and make its dissolving, it is slowly added in the solution I dissolve again, be incubated 55 minutes, and put then and be chilled to room temperature, filtration, filtering with microporous membrane again, 1000 of packing, lyophilizing, promptly.
Embodiment 7.A kind of preparation method of bilobalide injectable powder is got HP-325 gram, meglumine 12.5 grams add the dissolving of 5000ml water for injection, solution I, 85 ℃ of insulations, standby; Other gets bilobalide 50 gram and adds proper amount of acetone and make its dissolving, it is slowly added in the solution I dissolve again, is incubated 65 minutes, put then and be chilled to room temperature, filter, again filtering with microporous membrane, 1000 of packing, lyophilizing, its freeze-dry process is, first-15 ℃ of freeze formings, ℃ frozen cooling again-40, freezing vacuum drying down, after 36 hours, slowly heat up, until 25 ℃ of cappings, promptly.
Embodiment 8.Not commensurability adjuvant is to mouldability influence experiment.
Medicinal liquid preparation: get HP-, meglumine adds injection water 1000ml dissolving, 80 ℃ of insulations, standby; Other gets ginkgo lactone material 50g, add proper amount of acetone and make dissolving, slowly add in the solution of above-mentioned insulation and dissolve, be incubated 60 minutes, put cold, filter, filtrate packing (5ml/ bottle), (-15 ℃ of elder generations are freezing 2 hours in lyophilizing, ℃ pre-freeze 3 hours again-40 after waiting to freeze, put in the small frozen exsiccator lyophilizing 48 hours), observe mouldability, see the following form.
During the molding of powder pin, the atrophy shape is arranged, porous nickel.During the molding of powder pin, a small amount of caking is arranged, porous nickel.During the molding of powder pin, there is not obviously caking, loose, porous nickel.During the molding of powder pin, there is not obviously caking, loose, porous nickel.During the molding of powder pin, caking is arranged, protrusion of surface, hole is inhomogeneous.During the molding of powder pin, caking is arranged, protrusion of surface, hole is inhomogeneous.</entry></row></tbody></tgroup></table></tables>
As can be known from the above table, add not commensurability adjuvant, it is different that mouldability and medicinal liquid are separated out crystallization content influence, takes all factors into consideration and select experimental result, i.e. raw material for use No. 5: HP-: meglumine=1: 7: 0.3 is the best.
Embodiment 9.Freeze-dry process condition preferred.
Mainly contain two factors in the freezing conditions: to the influence of mouldability: the temperature of freezing body before freezing speed, the vacuum drying; Influence to freeze drying rate: the heating curve during vacuum freeze-drying.Following preferred on small-sized freeze dryer:
1, the medicinal liquid bottle is put cryogenic refrigerator-40 ℃ direct pre-freeze to freezing body temperature degree-40 ℃, puts small frozen exsiccator (40 ℃) lyophilizing 48 hours again.
2, medicinal liquid bottle elder generation is refrigerated to for-15 ℃ and freezes, and puts cryogenic refrigerator-40 a ℃ pre-freeze reduction again and freezes the body temperature degree to-40 ℃.Put small frozen exsiccator (40 ℃) lyophilizing 48 hours.
3, medicinal liquid bottle elder generation is refrigerated to for-15 ℃ and freezes, and puts cryogenic refrigerator-40 a ℃ pre-freeze reduction again and freezes the body temperature degree to-40 ℃.Put in the small frozen exsiccator-40 ℃ of lyophilizing 12 hours, ℃ lyophilizing is 12 hours again-25 ,-10 ℃ of lyophilizing 12 hours.
More than three kinds of result of the tests: 1) direct-40 ℃ of pre-freezes of medicinal liquid, powder body is inhomogeneous, and the crack is arranged.2) the powder pin uniformity is good.3) powder pin good evenness, drying time is short.Therefore, the cooling initial velocity can not be too fast when medicinal liquid was freezing, and to freeze temperature, the lyophilizing certain hour is gradient increased temperature slowly, can quicken lyophilizing.
Claims (4)
1, a kind of bilobalide injectable powder is characterized in that, its main component and weight content ratio are bilobalide: meglumine: HP-=1: (0.2-0.5): (6-9).
2, a kind of bilobalide injectable powder according to claim 1 is characterized in that its main component and weight content ratio are bilobalide: meglumine: HP-=1: 0.3: 7.
3, a kind of preparation method of bilobalide injectable powder is characterized in that, get HP-, meglumine and add the dissolving of injection water, solution I, 70-90 ℃ of insulation, standby; Other gets bilobalide and adds proper amount of acetone and make its dissolving, it is slowly added in the solution I dissolve again, is incubated 50-70 minute, puts then and is chilled to room temperature, filter, and filtering with microporous membrane again, packing, lyophilizing, promptly.
4, the preparation method of a kind of bilobalide injectable powder according to claim 2 is characterized in that, its freeze-dry process is ,-15 ℃ of freeze formings earlier, and ℃ frozen cooling again-40, freezing vacuum drying down after at least 30 hours, slowly heats up, until 25 ℃ of cappings.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410013937 CN1232251C (en) | 2004-01-14 | 2004-01-14 | Gingko lactone powder injection and its preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410013937 CN1232251C (en) | 2004-01-14 | 2004-01-14 | Gingko lactone powder injection and its preparation method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1557297A true CN1557297A (en) | 2004-12-29 |
| CN1232251C CN1232251C (en) | 2005-12-21 |
Family
ID=34351193
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410013937 Expired - Lifetime CN1232251C (en) | 2004-01-14 | 2004-01-14 | Gingko lactone powder injection and its preparation method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1232251C (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100341502C (en) * | 2006-04-18 | 2007-10-10 | 张国清 | Vein administration ginkgolactone B powder injection and its preparation method |
| WO2007124668A1 (en) * | 2006-04-28 | 2007-11-08 | Shenzhen Neptunus Pharmaceutical Co., Ltd. | Pharmaceutical composition comprising high concentrate of polydatin |
| CN100464747C (en) * | 2006-07-26 | 2009-03-04 | 孙毅 | Medicine composition containing bailobalide |
| CN101502539B (en) * | 2009-03-21 | 2011-05-11 | 山西振东泰盛制药有限公司 | Method for preparing ginkgo leaf extract cyclodextrin inclusion compound and preparation |
| CN105486792A (en) * | 2015-11-23 | 2016-04-13 | 江苏康缘药业股份有限公司 | Detection method for macromolecular compounds in diterpene ginkgolides meglumine injection and preparation raw materials thereof |
-
2004
- 2004-01-14 CN CN 200410013937 patent/CN1232251C/en not_active Expired - Lifetime
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100341502C (en) * | 2006-04-18 | 2007-10-10 | 张国清 | Vein administration ginkgolactone B powder injection and its preparation method |
| WO2007124668A1 (en) * | 2006-04-28 | 2007-11-08 | Shenzhen Neptunus Pharmaceutical Co., Ltd. | Pharmaceutical composition comprising high concentrate of polydatin |
| CN100464747C (en) * | 2006-07-26 | 2009-03-04 | 孙毅 | Medicine composition containing bailobalide |
| CN101502539B (en) * | 2009-03-21 | 2011-05-11 | 山西振东泰盛制药有限公司 | Method for preparing ginkgo leaf extract cyclodextrin inclusion compound and preparation |
| CN105486792A (en) * | 2015-11-23 | 2016-04-13 | 江苏康缘药业股份有限公司 | Detection method for macromolecular compounds in diterpene ginkgolides meglumine injection and preparation raw materials thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1232251C (en) | 2005-12-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Chi et al. | Chinese herb microneedle patch for wound healing | |
| CN1298386C (en) | Prepn process of slow release parathyroid hormone microballoon | |
| JP2007532173A5 (en) | ||
| CN101229138A (en) | Pantoprazole sodium freeze-dried powder injection and preparing method thereof | |
| CN105078905A (en) | Preparation method of doxycycline hyclate freeze-dried powder injection | |
| CN1232251C (en) | Gingko lactone powder injection and its preparation method | |
| WO2013044788A1 (en) | Low impurity content caspofungin preparation, method for preparing same, and use thereof | |
| CN101524345B (en) | Medicine composition without any excipients and preparation process thereof | |
| CN108079022A (en) | A kind of hirudo extract and preparation method and application | |
| CN1568929A (en) | Cosmetics containing humic acid and application of humic acid in cosmetics | |
| CN102058548A (en) | Ambroxol hydrochloride composition for injection and preparation method thereof | |
| CN101829065B (en) | Lansoprazole composition freeze-dried powder for injection | |
| JPH0374643B2 (en) | ||
| CN1526399A (en) | Diammonium glycyrrhizinate freeze drying powder for injection and its prepn | |
| CN103655490A (en) | Idarubicin hydrochloride pharmaceutical composition and preparation method thereof | |
| CN1176656C (en) | Freeze-drying composition for injection | |
| CN1795927A (en) | Composite of total flavone phospholipid of safflower, and preparation method | |
| CN104107172B (en) | The preparation method of sivelestat sodium injection freeze-dried powder | |
| CN1465339A (en) | Nano-grade medicine microball and preparation process thereof | |
| CN1269815C (en) | Novel process for preparation of silybum mariamum extractive methylglucamine | |
| CN101045038A (en) | Process for preparing gallo lactone freeze-dried powder injection with good solubility | |
| CN1524521A (en) | Troxerutin for injection and method for preparing the same | |
| CN101732496A (en) | Zhisuning granules and preparation method thereof | |
| IL309789A (en) | Semaglutide depot systems and use thereof | |
| CN1640390A (en) | Novel sodium houttuynin lyophilized powder for injection and its preparing method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CX01 | Expiry of patent term | ||
| CX01 | Expiry of patent term |
Granted publication date: 20051221 |