CN103800294A - Broom-shaped hydroxycamptotecin-loaded sustained-release particle and preparation method thereof - Google Patents
Broom-shaped hydroxycamptotecin-loaded sustained-release particle and preparation method thereof Download PDFInfo
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- CN103800294A CN103800294A CN201310731877.3A CN201310731877A CN103800294A CN 103800294 A CN103800294 A CN 103800294A CN 201310731877 A CN201310731877 A CN 201310731877A CN 103800294 A CN103800294 A CN 103800294A
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Abstract
The invention discloses a broom-shaped hydroxycamptotecin-loaded sustained-release particle and a preparation method thereof. The preparation method comprises the following steps: dissolving hydroxycamptothecine (10-HCPT) and methoxyl-terminated polyethylene glycol- poly(dl-lactide-co-glycolide) (MePEG-PLGA) in an organic solvent, injecting into a disperse phase of a membrane emulsifier, and injecting an aqueous solution containing little polyvinyl acetate (PVA) into a continuous phase of the membrane emulsifier; leading the solution of the disperse phase to quickly enter the continuous phase at nitrogen pressure by adopting a porous glass membrane as a template to obtain suspension of the hydroxycamptotecin-loaded sustained release particle (MePEG-PLGA-HCPT); distilling the suspension in vacuum, removing the organic solvent, removing uncoated square medicinal crystal by ultrafiltration of a microporous filter membrane, and lyophilizing the suspension in vacuum in a lyophilizer for 24 hours to obtain the broom-shaped MePEG-PLGA-HCPT sustained-release particle. The method is reliable, and convenient to operate; the prepared irregular particle is high in drug-loading amount and encapsulation rate, is excellent in sustained release effect, and is particularly suitable for tumor local medication and tumor post-operation medication.
Description
Technical field
The invention belongs to pharmaceutical field, specifically hydroxy camptothecin is prepared into nanoparticle of " broom " shape and preparation method thereof.
Background technology
Hydroxy camptothecin (HCPT, another name hydroxycamptothecin, 10-hydroxycamptothecine) is the derivant of isolated a kind of indoles alkaloid (being camptothecine) from China distinctive Nyssaceae Fructus seu radix camptothecae acuminatae (Fructus Camptothecae Acuminatae) platymiscium Fructus seu radix camptothecae acuminatae (Fructus Camptothecae Acuminatae), belongs to natural anticarcinogen.Its anticancer spectrum is wider, to nucleic acid particularly DNA synthetic have obvious inhibitory action, with conventional antitumor drug without cross resistance.At present, be clinically mainly used in ascitic type liver cancer, colorectal cancer, gastric cancer, nonsmall-cell lung cancer and leukemic treatment.
The toxic and side effects of 10-hydroxycamptothecine is larger, and main manifestations is: bone marrow depression, cause leukopenia, gastrointestinal reaction, urinary tract stimulation etc., and along with dosage strengthens, the incidence rate of untoward reaction and intensity are also linear to be increased.These toxicities have limited the clinical practice of hydroxy camptothecin.HCPT belongs to time-dependent medicine, therefore in the concentration and time factor that affect HCPT curative effect, the time is principal element.HCPT in vivo metabolism is very fast, and the half-life is only 5min.In addition, because HCPT sodium-salt parenteral solution is unstable, see that light easily decomposes, can lessen the curative effect, increase untoward reaction.
Summary of the invention
The object of the invention is sustained-release particle and the method thereof of the hydroxy camptothecin of preparation a kind of " broom shape ", increase the stability of HCPT, realize high medicine carrying, sustained release, reduces dosage, reduces the object of toxic and side effects.Mainly be used as local injection and the rear medication of tumor post-operation excision of tumor.
The object of the invention is to be achieved through the following technical solutions:
1. film emulsion process is prepared elementary nanoparticle
10-HCPT and MePEG-PLGA are dissolved in after organic solvent altogether, inject the decentralized photo of membrane emulsifier, the aqueous solution that contains a small amount of PVA is injected to the continuous phase of membrane emulsifier, adopting cellular glass film is template, under the pressure of certain pure nitrogen gas, make decentralized photo solution enter rapidly continuous phase, obtain MePEG-PLGA-HCPT suspension.
2. the separation of nanoparticle, purification
Above-mentioned suspension vacuum is revolved and boiled off except organic solvent, with 1 μ m filtering with microporous membrane to remove not wrapped side's shape drug crystallization, again gained suspension is placed in to freezer dryer vacuum freeze-drying 24h, obtains " broom shape " MePEG-PLGA-HCPT sustained-release particle.
Accompanying drawing explanation
Fig. 1 is the scanning electron microscope picture of " broom shape " hydroxycamptothecin sustained-release particle of preparation, and wherein (b, c) is the partial enlarged drawing of (a).
Fig. 2 is the MePEG-PLGA-HCPT particle of different carrying drug ratios and the tablets in vitro curve of pure medicine hydroxy camptothecin.
The specific embodiment
Embodiment 1
20mg10-HCPT and 20mg MePEG-PLGA are dissolved in after 80mL acetone altogether, inject the decentralized photo charging aperture of membrane emulsifier, the aqueous solution that contains 0.25%PVA is injected to the continuous phase of membrane emulsifier, adopting 1.1 μ mSPG films is template, under the pressure of 100KPa pure nitrogen gas, make decentralized photo solution enter rapidly continuous phase, obtain MePEG-PLGA-HCPT suspension, above-mentioned suspension vacuum is revolved and boiled off except after acetone, with 1 μ m filtering with microporous membrane, again gained suspension is placed in to freezer dryer vacuum freeze-drying 24h, obtain MePEG-PLGA-HCPT powder, its drug loading is 38.3%, Fig. 1 provides the scanning electron microscope (SEM) photograph of nanoparticle prepared by embodiment 1.
Embodiment 2
20mg10-HCPT and 20mg MePEG-PLGA are dissolved in after 80mL acetone altogether, inject the decentralized photo charging aperture of membrane emulsifier, the aqueous solution that contains 0.25%PVA is injected to the continuous phase of membrane emulsifier, adopting 0.6 μ mSPG film is template, under the pressure of 100KPa pure nitrogen gas, make decentralized photo solution enter rapidly continuous phase, obtain MePEG-PLGA-HCPT suspension, above-mentioned suspension vacuum is revolved and boiled off except after acetone, with 1 μ m filtering with microporous membrane, again gained suspension is placed in to freezer dryer vacuum freeze-drying 24h, obtain MePEG-PLGA-HCPT powder, its drug loading is 32.7%.
Embodiment 3
20mg10-HCPT and 40mg MePEG-PLGA are dissolved in after 80mL acetone altogether, inject the decentralized photo charging aperture of membrane emulsifier, the ultra-pure water that contains 0.25%PVA is injected to the continuous phase of membrane emulsifier, adopting 0.4 μ mSPG film is template, under the pressure of 50KPa pure nitrogen gas, make decentralized photo solution enter rapidly continuous phase, obtain MePEG-PLGA-HCPT suspension, above-mentioned suspension vacuum is revolved and boiled off except acetone, with 1 μ m filtering with microporous membrane, again gained suspension is placed in to freezer dryer vacuum freeze-drying 24h, obtain MePEG-PLGA-HCPT powder, its drug loading is 21.4%.
Embodiment 3
20mg10-HCPT and 40mg MePEG-PLGA are dissolved in after 80mL acetone altogether, inject the decentralized photo charging aperture of membrane emulsifier, the aqueous solution that contains 0.25%PVA is injected to the continuous phase of membrane emulsifier, adopting 0.3 μ mSPG film is template, under the pressure of 100KPa pure nitrogen gas, make decentralized photo solution enter rapidly continuous phase, obtain MePEG-PLGA-HCPT suspension, above-mentioned suspension vacuum is revolved and boiled off except acetone, with 1 μ m filtering with microporous membrane, again gained suspension is placed in to freezer dryer vacuum freeze-drying 24h, obtain MePEG-PLGA-HCPT powder, its drug loading is 23.4%, envelop rate can be 39.3%.Fig. 2 has provided the MePEG-PLGA-HCPT particle of the different carrying drug ratios of being prepared by embodiment 1-3 respectively and the tablets in vitro curve of pure medicine hydroxy camptothecin.
Problem:
Embodiment 1: with the aqueous solution that contains 0.25%PVA, but embodiment below will contain the aqueous solution of 0.25%PVA, how to be ultra-pure water containing the water of PVA, is the aqueous solution of embodiment 1 more accurate?
Aqueous solution just can.
Claims (5)
1. one kind " broom shape " carries the preparation method of the sustained-release particle of hydroxy camptothecin, that the polyethylene glycol-polylactic acid polyglycolic acid (MePEG-PLGA) of hydroxy camptothecin (10-HCPT) and oxygen base end-blocking is dissolved in after organic solvent altogether, inject the decentralized photo of membrane emulsifier, the aqueous solution that will contain a small amount of polyvinyl alcohol (PVA) injects the continuous phase of membrane emulsifier, adopting cellular glass film is template, under the pressure of nitrogen, make decentralized photo solution enter rapidly continuous phase, obtain carrying sustained-release particle (MePEG-PLGA-HCPT) suspension of hydroxy camptothecin, above-mentioned suspension vacuum is revolved to steaming, remove after organic solvent with filtering with microporous membrane to remove not wrapped side's shape drug crystallization, again gained suspension is placed in to freezer dryer vacuum freeze-drying, obtain " broom shape " MePEG-PLGA-HCPT sustained-release particle.
2. one according to claim 1 " broom shape " is carried the preparation method of the sustained-release particle of hydroxy camptothecin, it is characterized in that using membrane emulsifier, and film is cellular glass film, and its aperture is 0.3～2 μ m.
3. one according to claim 1 and 2 " broom shape " is carried the preparation method of the sustained-release particle of hydroxy camptothecin, it is characterized in that, its decentralized photo is the organic solution of having dissolved 10-HCPT and MePEG-PLGA, and continuous phase is the aqueous solution that has dissolved a small amount of PVA.
4. one according to claim 1 and 2 " broom shape " is carried sustained-release particle of hydroxy camptothecin and preparation method thereof, it is characterized in that the organic solvent that decentralized photo is used is: dimethyl sulfoxide, acetone, dimethyl formamide, acetonitrile.
5. one according to claim 1 and 2 " broom shape " is carried slow release nanometer particle of hydroxy camptothecin and preparation method thereof, it is characterized in that with 1 μ m filtering with microporous membrane to remove not wrapped side's shape drug crystallization.
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| CN201310731877.3A CN103800294B (en) | 2013-12-26 | 2013-12-26 | A kind of broom shape carries hydroxycamptothecin sustained-release particle and preparation method thereof |
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| CN201310731877.3A CN103800294B (en) | 2013-12-26 | 2013-12-26 | A kind of broom shape carries hydroxycamptothecin sustained-release particle and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107837204A (en) * | 2017-11-09 | 2018-03-27 | 苏州纳康生物科技有限公司 | A kind of narrow ditribution particle diameter emulsion with skin anti-aging effect and preparation method thereof |
| CN108990991A (en) * | 2018-07-19 | 2018-12-14 | 北京工业大学 | A kind of preparation method for the nanoparticle containing fluazinam based on poly lactide-glycolide acid |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101352420A (en) * | 2008-09-08 | 2009-01-28 | 厦门大学 | Hydroxycamptothecin sustained-release microsphere and preparation method thereof |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101352420A (en) * | 2008-09-08 | 2009-01-28 | 厦门大学 | Hydroxycamptothecin sustained-release microsphere and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 谢黎崖等: "载羟基喜树碱聚乳酸微球的制备与体外释药研究", 《中国新药杂志》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107837204A (en) * | 2017-11-09 | 2018-03-27 | 苏州纳康生物科技有限公司 | A kind of narrow ditribution particle diameter emulsion with skin anti-aging effect and preparation method thereof |
| CN108990991A (en) * | 2018-07-19 | 2018-12-14 | 北京工业大学 | A kind of preparation method for the nanoparticle containing fluazinam based on poly lactide-glycolide acid |
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