Hydroxycamptothecin nanocrystal-loaded microspheres and preparation method thereof

Abstract

The invention discloses a hydroxycamptothecin nano-crystal loaded micro-sphere and a method for preparing the same.The method includes continuously leading liquefied carbon dioxide into a precipitation kettle by a high-pressure pump, filling the precipitation kettle with dimethyl sulfoxide and / or ethyl alcohol solvents via a nozzle, stopping filling the precipitation kettle with the solvents after the liquefied carbon dioxide is stabilized, and filling the precipitation kettle with hydroxycamptothecin and Zein solution via the nozzle; quickly and sufficiently mixing the solvents and the supercritical carbon dioxide with one another to obtain mixtures, allowing the mixtures to flow out of the precipitation kettle from a kettle bottom, recycling the mixtures and precipitating solute particles at the bottom of the precipitation kettle; acquiring hydroxycamptothecin nano-crystal and Zein co-precipitation mixtures; ultrasonically dispersing the co-precipitation mixtures in ethyl alcohol-water solution; preparing hydroxycamptothecin nano-crystal loaded Zein micro-sphere emulsion by the aid of an ultrasonic built-in dialysis device; freezing and drying the hydroxycamptothecin nano-crystal loaded micro-sphere emulsion.The hydroxycamptothecin nano-crystal loaded micro-sphere and the method have the advantages that the micro-sphere has smooth surfaces and is high in medicine loading capacity and medicine loading efficiency, narrow in particle size distribution and good in dispersibility; shortcomings in the aspect of stability, nano-toxicity, controlled sustained release behavior, targeting and the like of nano-crystals of medicines can be overcome by the aid of the hydroxycamptothecin nano-crystal loaded micro-sphere and the method.

Description

technical field [0001] The invention relates to the field of preparation and loading of drug nanocrystals, in particular to a hydroxycamptothecin nanocrystal-loaded microsphere and a preparation method thereof. Background technique [0002] Hydroxycamptothecin is a trace alkaloid isolated from the unique plant camptotheca in our country. It is an alkaloid with the strongest anti-tumor activity among more than 20 monomers isolated from camptotheca. Hydroxycamptothecin is insoluble in water, and the currently clinically used preparation of hydroxycamptothecin is its sodium salt injection. The structure of the lactone ring is destroyed, and the anticancer activity is only 10% of that of hydroxycamptothecin. [0003] The preparation of drug nanocrystals is an effective strategy to improve the efficacy of poorly water-soluble drugs, and has been applied in many drug dosage forms. The reduction of particle size can increase the specific surface area of ​​the drug, and enhance the...

AI Technical Summary

Problems solved by technology

[0005] The purpose of the present invention is to solve the deficiencies in technology, effectively avoid the problems of easy aggregation during the dispersion process of hydroxycamptothecin, and the uneven size distribution of the microspheres obtained by directly loading drug nanocrystals, and provide a drug-loading efficiency, good dispersibility, size and other problems. Uniform, controllable particle size, high yield and less residual solvent, releasing 70% of the mass drug-loaded hydroxycamptothecin nanocrystals for more than 72 hours, hydroxycamptothecin nanocrystal-loaded microspheres and a preparation method thereof

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