CN1883497A - Ginsenoside Rh2 hydroxypropyl-beta-cyclodextrin inclusion compound and preparation method thereof - Google Patents
Ginsenoside Rh2 hydroxypropyl-beta-cyclodextrin inclusion compound and preparation method thereof Download PDFInfo
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- CN1883497A CN1883497A CN 200510043936 CN200510043936A CN1883497A CN 1883497 A CN1883497 A CN 1883497A CN 200510043936 CN200510043936 CN 200510043936 CN 200510043936 A CN200510043936 A CN 200510043936A CN 1883497 A CN1883497 A CN 1883497A
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Abstract
The invention provides a hydroxypropyl-beta-cyclodextrin inclusion compound of ginsenoside Rh2, wherein the ratio of ginsenoside Rh2 and hydroxypropyl-beta-cyclodextrin is 1:1-300. The invention also provides the process for preparing the inclusion compound and the preparations prepared from the inclusion compound.
Description
Technical field
The present invention relates to ginsenoside Rh2's preparation and preparation method, be specifically related to ginsenoside Rh2's hydroxypropyl-beta-cyclodextrin inclusion and preparation and preparation method.
Background technology
The ginsenoside Rh
2For extracting the one pack system chemical compound that obtains in the Radix Ginseng, belong to glycol saponins, it can suppress the propagation and the growth of tumor cell by inducing differentiation or apoptosis, but very low to normal tissue toxicity, see [Xu Jingda, Changbai Mountain Chinese medicine research and development, 1996,5 (5): 48].Li Shi discovers the ginsenoside Rh
2Have tangible propagation to suppress and apoptosis-induced effect to the C6 glioma cell, this effect has period specific.He thinks Rh
2Be the active skull cap components of Radix Ginseng, toxicity is low, molecular weight is little, and is fat-soluble, by blood brain barrier, is a kind of potential chemotherapeutic easily, sees [Li Dianyou etc., Norman Bethune Medical University's journal, 2000,26 (4): 342].
Because ginsenoside Rh
2For fat-soluble, therefore prepare the especially solubilizing agents of a large amount of use of needs toxic side effect during injection of preparation, as use polyoxyethylene castor oil class surfactants such as (Cremophor-EL), such surfactant has sensitization, a large amount of anaphylactoid incidence rates in back of using are higher, see [Wei Xiaohui waits Chinese Journal ofPharmaceuticals 2001,32 (4): 188-192].Given this, the inventor provides a kind of ginsenoside Rh2's hydroxypropyl-beta-cyclodextrin inclusion and preparation and preparation method.
Summary of the invention
The invention provides a kind of ginsenoside Rh2's hydroxypropyl-beta-cyclodextrin inclusion.
The invention provides the preparation method of a kind of ginsenoside Rh2's hydroxypropyl-beta-cyclodextrin inclusion.
The present invention also provides a kind of ginsenoside Rh2's hydroxypropyl-beta-cyclodextrin inclusion preparation.
Clathrate provided by the invention is made of by weight following raw material: the ginsenoside Rh2: HP-=1: 1-300 is preferably 1: 60-200.
The preparation method of clathrate provided by the invention is:
The ginsenoside Rh2 is dissolved in the organic solvent by above-mentioned weight ratio, HP-is soluble in water by above-mentioned weight ratio, the aqueous solution strong agitation that will contain HP-, slowly drip ginsenoside Rh2's solution, all adding the back continues to stir 2-24 hour, use 0.45 μ m micropore chlorine membrane filtration, filtrate is concentrated, eliminate organic solvent, add an amount of water for injection, again dissolving, cross 0.22 μ m microporous filter membrane, the filtrate lyophilization, the white powder that must loosen is ginsenoside Rh2's clathrate.
Wherein, organic solvent is generally in the mixed solvent of chloroform, methanol, water or the mixed solvent of dichloromethane, methanol, water in or in the methanol, also can be dimethyl sulfoxide, tween and mix reagent.
Clathrate of the present invention can also adopt following method preparation: as polishing, be about to ginsenoside Rh2's adding and grind in the equal HP-, grind all, cold drying gets clathrate.Or employing spray drying method for preparation.The raw material that can be used for preparing oral formulations with the clathrate of this quadrat method preparation.
The preparation method of clathrate injection freeze-dried powder of the present invention is: after adding water for injection in the above-mentioned clathrate, add mannitol or lactose, regulate to wait and ooze, use the ultrafilter depyrogenation of molecular cut off 5000 then, filtrate is with 0.22 μ m filtering with microporous membrane degerming, packing, lyophilization gets the injection freeze-dried powder.
Clathrate among the present invention can directly use or use with pharmaceutical compositions, can exist with forms such as injectable powder, tablet, capsule, soft capsule, drop pill.Make capsule as clathrate is directly incapsulated, also can add certain adjuvant and make tablet, can also add and make freeze-dried powder after regulating osmotic pressure adjuvant such as lyophilizations such as mannitol, lactose.
HP-among the present invention is a cyclodextrin derivative, has the tubular molecular structure, and molecular weight is 1540, has water-solublely, and the enclose amount is big, the characteristics that toxicity is low, and can be used for injection; Characteristics such as the ginsenoside Rh2 is the natural component that extracts from Radix Ginseng, and molecular weight is 640, belongs to small-molecule substance and for fat-soluble, and toxicity is low.The present invention utilizes the cyclodextrin inclusion compound effect, with ginsenoside Rh2's enclose, makes it water-soluble, improves its stability and bioavailability simultaneously.
The present invention is further illustrated below by the specific embodiment, but and do not mean that the present invention only limits to this.
The specific embodiment:
The preparation of preparation example 1 ginsenoside Rh2's hydroxypropyl-beta-cyclodextrin inclusion
Getting HP-10000mg is dissolved in the 100ml water, strong agitation, get ginsenoside Rh2 100mg and be dissolved in chloroform: methanol: water is in 6: 4: 1 the solvent, in the aqueous solution that contains HP-, dropwise add, stirred then 4 hours, use 0.45 μ m filtering with microporous membrane, filtrate decompression is concentrated into original volume 1/3, to eliminate organic solvent, add water for injection to 1 times of commercial weight, with 0.22 μ m filtration sterilization, aseptic then lyophilization, get the white loose powder, be ginsenoside Rh2's hydroxypropyl-beta-cyclodextrin inclusion, detect through HPLC, contain ginsenoside Rh2 85mg in this clathrate, inclusion rate 85%.
The preparation of preparation example 2 ginsenoside Rh2s' hydroxypropyl-beta-cyclodextrin inclusion
Getting HP-800mg is dissolved in the 30ml water, strong agitation, get ginsenoside Rh2 200mg and be dissolved in chloroform: methanol: water is in 6: 4: 1 the solvent, in the aqueous solution that contains HP-, dropwise add, stirred then 4 hours, use 0.45 μ m filtering with microporous membrane, filtrate decompression is concentrated into original volume 1/3, to eliminate organic solvent, add water for injection to 1 times of commercial weight, with 0.22 μ m filtration sterilization, aseptic then lyophilization, get the white loose powder, be ginsenoside Rh2's hydroxypropyl-beta-cyclodextrin inclusion, detect through HPLC, contain ginsenoside Rh2 20mg in this clathrate, inclusion rate 10%.
The preparation of preparation example 3 ginsenoside Rh2s' hydroxypropyl-beta-cyclodextrin inclusion
Get ginsenoside Rh 2 150mg and join 1500mg and grind in the uniform HP-, ground 3 hours, drying under reduced pressure, clathrate.
The preparation of preparation example 4 ginsenoside Rh2s' hydroxypropyl-beta-cyclodextrin inclusion
Get ginsenoside Rh 2 200mg and join 2000mg and grind in the uniform HP-, ground 3 hours, spray drying, clathrate.
Preparation example 5 injection ginsenoside Rh2s' hydroxypropyl-beta-cyclodextrin inclusion freeze-dried powder
After getting clathrate that preparation example 1 makes and adding water for injection, add an amount of mannitol, regulate to wait and oozes, use the ultrafilter depyrogenation of molecular cut off 5000 then, filtrate is with 0.22 μ m filtering with microporous membrane degerming, packing, and lyophilization must the injection freeze-dried powder.
Preparation example 6 ginsenoside Rh2s' hydroxypropyl-beta-cyclodextrin inclusion tablet, capsule
Get the clathrate that preparation example 1 makes, add appropriate amount of auxiliary materials, as mannitol, lactose, starch etc., tabletting is made tablet or is made capsule.
Claims (8)
1. a ginsenoside Rh2 hydroxypropyl-beta-cyclodextrin inclusion is made of by weight following raw material: ginsenoside Rh2: HP-=1: 1-300.
2. the described clathrate of claim 1, preferred weight ratio is: the ginsenoside Rh2: HP-=1: 60-200.
3. the preparation method of a ginsenoside Rh2 hydroxypropyl-beta-cyclodextrin inclusion, the ginsenoside Rh2 that will be dissolved in organic solvent joins in the intensively stirred aqueous solution that contains HP-, the ginsenoside Rh2: HP-=1: 1-300, stir after be drying to obtain.
4. the described preparation method of claim 3, the ginsenoside Rh2 is dissolved in the organic solvent, HP-is soluble in water, ginsenoside Rh2: HP-=1: 1-300, the aqueous solution strong agitation that will contain HP-, slowly drip ginsenoside Rh2's solution, after all adding, continue to stir 2-24 hour, use 0.45 μ m filtering with microporous membrane, filtrate is concentrated, eliminate organic solvent, add water for injection and dissolve again, cross 0.22 μ m microporous filter membrane, the filtrate lyophilization promptly.
5. claim 3 or 4 described preparation methoies, organic solvent are selected from mixed solvent or dimethyl sulfoxide, tween and the mix reagent of the mixed solvent of chloroform, methanol, water or dichloromethane, methanol, water.
6. a ginsenoside Rh2 hydroxypropyl-beta-cyclodextrin inclusion injection freeze-dried powder, by following raw material by weight forming: the ginsenoside Rh2: HP-=1: 1-300 also comprises the injectable drug carrier; Join in the aqueous solution that contains HP-by the ginsenoside Rh2 that will be dissolved in organic solvent, after the stirring, drying forms clathrate soluble in water; Add pharmaceutical carrier, get clathrate preparation, i.e. injection freeze-dried powder.
7. the injection freeze-dried powder shown in the claim 6 after adding water for injection in the described clathrate, adds mannitol or lactose, regulate to wait and to ooze, use the ultrafilter depyrogenation of molecular cut off 5000 then, filtrate is with 0.22 μ m filtering with microporous membrane degerming, packing, lyophilization are promptly.
8. a ginsenoside Rh2 hydroxypropyl-beta-cyclodextrin inclusion oral formulations, by following raw material by weight forming: the ginsenoside Rh2: HP-=1: 1-300 also comprises excipient substance; Join in the aqueous solution that contains HP-by the ginsenoside Rh2 that will be dissolved in organic solvent, after the stirring, drying forms clathrate soluble in water; Add excipient substance, make oral formulations.
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| Application Number | Priority Date | Filing Date | Title |
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| CN 200510043936 CN1883497A (en) | 2005-06-24 | 2005-06-24 | Ginsenoside Rh2 hydroxypropyl-beta-cyclodextrin inclusion compound and preparation method thereof |
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| CN 200510043936 CN1883497A (en) | 2005-06-24 | 2005-06-24 | Ginsenoside Rh2 hydroxypropyl-beta-cyclodextrin inclusion compound and preparation method thereof |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103054892A (en) * | 2012-12-24 | 2013-04-24 | 云南省药物研究所 | Gracillin-hydroxypropyl-beta-cyclodextrin inclusion compound and preparation method thereof |
| CN102091114B (en) * | 2009-12-15 | 2014-11-26 | 河北以岭医药研究院有限公司 | Traditional Chinese medicament freeze-drying injection and preparation method thereof |
| CN105770908A (en) * | 2016-04-20 | 2016-07-20 | 昆明理工大学 | Ginsenoside cyclodextrin inclusion compound and preparation method thereof |
| CN110547465A (en) * | 2019-08-06 | 2019-12-10 | 上海麒稷健康科技有限公司 | Brain nerve nutrition composition and preparation method thereof |
| CN116251060A (en) * | 2023-04-24 | 2023-06-13 | 朗天药业(湖北)有限公司 | Digoxin injection and preparation method thereof |
-
2005
- 2005-06-24 CN CN 200510043936 patent/CN1883497A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102091114B (en) * | 2009-12-15 | 2014-11-26 | 河北以岭医药研究院有限公司 | Traditional Chinese medicament freeze-drying injection and preparation method thereof |
| CN103054892A (en) * | 2012-12-24 | 2013-04-24 | 云南省药物研究所 | Gracillin-hydroxypropyl-beta-cyclodextrin inclusion compound and preparation method thereof |
| CN105770908A (en) * | 2016-04-20 | 2016-07-20 | 昆明理工大学 | Ginsenoside cyclodextrin inclusion compound and preparation method thereof |
| CN110547465A (en) * | 2019-08-06 | 2019-12-10 | 上海麒稷健康科技有限公司 | Brain nerve nutrition composition and preparation method thereof |
| CN116251060A (en) * | 2023-04-24 | 2023-06-13 | 朗天药业(湖北)有限公司 | Digoxin injection and preparation method thereof |
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