CN103800294B - A kind of broom shape carries hydroxycamptothecin sustained-release particle and preparation method thereof - Google Patents
A kind of broom shape carries hydroxycamptothecin sustained-release particle and preparation method thereof Download PDFInfo
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- CN103800294B CN103800294B CN201310731877.3A CN201310731877A CN103800294B CN 103800294 B CN103800294 B CN 103800294B CN 201310731877 A CN201310731877 A CN 201310731877A CN 103800294 B CN103800294 B CN 103800294B
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Abstract
The invention discloses one " broom shape " and carry sustained-release particle of hydroxy camptothecin and preparation method thereof, that the polyethylene glycol-polylactic acid polyglycolic acid (MePEG-PLGA) of hydroxy camptothecin (10-HCPT) and methoxy group is dissolved in organic solvent altogether, inject the decentralized photo of membrane emulsifier, aqueous solution containing a small amount of polyvinyl alcohol (PVA) is injected the continuous phase of membrane emulsifier, employing SPG membrane is template, under the pressure of nitrogen, make decentralized photo solution enter continuous phase rapidly, obtain the suspension of the sustained-release particle (MePEG-PLGA-HCPT) carrying hydroxy camptothecin, above-mentioned suspension vacuum is revolved steaming, after removing organic solvent, with microporous filter membrane ultrafiltration to remove not wrapped side's shape drug crystallization, again gained suspension is placed in freezer dryer vacuum freeze-drying 24h, namely " broom shape " MePEG-PLGA-HCPT sustained-release particle is obtained.Method of the present invention is reliable, easy and simple to handle, obtained irregular particle drug loading and envelop rate high, slow release effect is good, is specially adapted to tumor by local medication or 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 (i.e. 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 comparatively wide, has obvious inhibitory action, with conventional antitumor drug without cross resistance to the synthesis of nucleic acid particularly DNA.At present, clinically ascitic type liver cancer, colorectal cancer, gastric cancer, nonsmall-cell lung cancer and leukemic treatment is mainly used in.
The toxic and side effects of 10-hydroxycamptothecine is comparatively large, and main manifestations is: bone marrow depression, causes leukopenia, gastrointestinal reaction, urinary tract stimulation etc., and along with dosage increasing, incidence rate and the intensity of untoward reaction also linearly increase.These toxicities limit the clinical practice of hydroxy camptothecin.HCPT belongs to time-dependent medicine, therefore in the concentration affecting HCPT curative effect and time factor, 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, sees 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 preparing a kind of " broom shape ", increase the stability of HCPT, realize high medicine carrying, sustained release, reduce dosage, reduce 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 prepares elementary nanoparticle
After 10-HCPT and MePEG-PLGA is dissolved in organic solvent altogether, inject the decentralized photo of membrane emulsifier, aqueous solution containing a small amount of PVA is injected the continuous phase of membrane emulsifier, employing SPG membrane is template, under the pressure of certain pure nitrogen gas, make decentralized photo solution enter continuous phase rapidly, obtain MePEG-PLGA-HCPT suspension.
2. the separation of nanoparticle, purification
Above-mentioned suspension vacuum being revolved boils off except organic solvent, with 1 μm of filtering with microporous membrane to remove not wrapped side's shape drug crystallization, again gained suspension is placed in freezer dryer vacuum freeze-drying 24h, namely obtains " broom shape " MePEG-PLGA-HCPT sustained-release particle.
Accompanying drawing explanation
Fig. 1 is the scanning electron microscopic 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 ratio and the tablets in vitro curve of pure drug hydroxy camptothecine.
Detailed description of the invention
Embodiment 1
After 20mg10-HCPT and 20mgMePEG-PLGA is dissolved in 80mL acetone altogether, inject the decentralized photo charging aperture of membrane emulsifier, aqueous solution containing 0.25%PVA is injected the continuous phase of membrane emulsifier, 1.1 μm of SPG films are adopted to be template, under the pressure of 100KPa pure nitrogen gas, make decentralized photo solution enter continuous phase rapidly, obtain MePEG-PLGA-HCPT suspension, above-mentioned suspension vacuum being revolved boils off except after acetone, with 1 μm of filtering with microporous membrane, again gained suspension is placed in freezer dryer vacuum freeze-drying 24h, namely MePEG-PLGA-HCPT powder is obtained, its drug loading is 38.3%, Fig. 1 provides the scanning electron microscope (SEM) photograph of nanoparticle prepared by embodiment 1.
Embodiment 2
After 20mg10-HCPT and 20mgMePEG-PLGA is dissolved in 80mL acetone altogether, inject the decentralized photo charging aperture of membrane emulsifier, aqueous solution containing 0.25%PVA is injected the continuous phase of membrane emulsifier, 0.6 μm of SPG film is adopted to be template, under the pressure of 100KPa pure nitrogen gas, make decentralized photo solution enter continuous phase rapidly, obtain MePEG-PLGA-HCPT suspension, above-mentioned suspension vacuum being revolved boils off except after acetone, with 1 μm of filtering with microporous membrane, again gained suspension is placed in freezer dryer vacuum freeze-drying 24h, namely MePEG-PLGA-HCPT powder is obtained, its drug loading is 32.7%.
Embodiment 3
After 20mg10-HCPT and 40mgMePEG-PLGA is dissolved in 80mL acetone altogether, inject the decentralized photo charging aperture of membrane emulsifier, ultra-pure water containing 0.25%PVA is injected the continuous phase of membrane emulsifier, 0.4 μm of SPG film is adopted to be template, under the pressure of 50KPa pure nitrogen gas, make decentralized photo solution enter continuous phase rapidly, obtain MePEG-PLGA-HCPT suspension, above-mentioned suspension vacuum being revolved boils off except acetone, with 1 μm of filtering with microporous membrane, again gained suspension is placed in freezer dryer vacuum freeze-drying 24h, namely MePEG-PLGA-HCPT powder is obtained, its drug loading is 21.4%.
Embodiment 3
After 20mg10-HCPT and 40mgMePEG-PLGA is dissolved in 80mL acetone altogether, inject the decentralized photo charging aperture of membrane emulsifier, aqueous solution containing 0.25%PVA is injected the continuous phase of membrane emulsifier, 0.3 μm of SPG film is adopted to be template, under the pressure of 100KPa pure nitrogen gas, make decentralized photo solution enter continuous phase rapidly, obtain MePEG-PLGA-HCPT suspension, above-mentioned suspension vacuum being revolved boils off except acetone, with 1 μm of filtering with microporous membrane, again gained suspension is placed in freezer dryer vacuum freeze-drying 24h, namely MePEG-PLGA-HCPT powder is obtained, its drug loading is 23.4%, envelop rate can be 39.3%.Fig. 2 gives the MePEG-PLGA-HCPT particle of the different carrying drug ratios prepared by embodiment 1-3 respectively and the tablets in vitro curve of pure drug hydroxy camptothecine.
Problem:
Embodiment 1: with containing the aqueous solution of 0.25%PVA, but the embodiment is below by the aqueous solution containing 0.25%PVA, how the water containing PVA is ultra-pure water, is the aqueous solution of embodiment 1 more accurate?
Aqueous solution is just passable.
Claims (4)
1. one kind " broom shape " carries the preparation method of the sustained-release particle of hydroxy camptothecin, after the polyethylene glycol-polylactic acid polyglycolic acid (MePEG-PLGA) of hydroxy camptothecin (10-HCPT) and oxygen base end-blocking is dissolved in organic solvent altogether, inject the decentralized photo of membrane emulsifier, aqueous solution containing 0.25% polyvinyl alcohol (PVA) is injected the continuous phase of membrane emulsifier, employing aperture is the SPG membrane of 0.3 ~ 2 μm is template, under the pressure of nitrogen, make decentralized photo solution enter continuous phase rapidly, obtain sustained-release particle (MePEG-PLGA-HCPT) suspension carrying hydroxy camptothecin, above-mentioned suspension vacuum is revolved steaming, to remove after organic solvent with filtering with microporous membrane to remove not wrapped side's shape drug crystallization, again gained suspension is placed in freezer dryer vacuum freeze-drying, namely " broom shape " MePEG-PLGA-HCPT sustained-release particle is obtained, the consumption of above-mentioned hydroxy camptothecin is 20mg, the consumption of the polyethylene glycol-polylactic acid polyglycolic acid of above-mentioned oxygen base end-blocking is 20mg or 40mg.
2. one according to claim 1 " broom shape " carries the preparation method of the sustained-release particle of hydroxy camptothecin, and it is characterized in that, its decentralized photo is dissolved the organic solution of 10-HCPT and MePEG-PLGA.
3. one according to claim 1 " broom shape " carries the preparation method of the sustained-release particle of hydroxy camptothecin, it is characterized in that the organic solvent of decentralized photo is: dimethyl sulfoxide, acetone, dimethyl formamide, acetonitrile.
4. one according to claim 1 " broom shape " carries the preparation method of the slow release nanometer particle of hydroxy camptothecin, it is characterized in that with 1 μm of 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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| CN103800294B true CN103800294B (en) | 2015-12-30 |
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