| Harmine(HM), an effective alkaloid ingredient in natural product, was extracted from Preganum harmala seeds which was used by Uygur and Mongolian as a traditional medicine from very early time. It has been reported in China recently that harmine and related compounds had significant cytostatic and cytocidial effects on cancer cells. So harmine hydrochloride gelatin microspheres(HM-GMS) for hepatic arterial embolization was prepared in this paper, and a series of experiments of HM-GMS has been done in the preparation, properties, drug release character in vitro, stabilities, characteristics of pharmacokinetics and embolization effects as well as antineoplasm effect mechanism of HM.In order to prepare HM-GMS successfully, interaction between drug and carriers was studied at first. Gelatin was chosen as carrier of microspheres because of its characters of biodegradationable, low toxicity and no interaction between drugs. In preparation technology for HM-GMS, the pharmaceutical investigation was performed using odd factor design, including the effect of different gelatin, different kinds of phase of oil, different emulsifiers and different conditions of emulsification, different dehydration agent and the sequence of dehydration, etc. Finally, the optimum formulation of HM-GMS was achieved by employing orthogonal design. HM-GMS showed light yellow color, spherical with a rough surface. The mean percent of yield of three batches HM-GMS was 86.63%, the drug loading was 34.45%, and the embedding ratio was 63.00%.In the studies on the interrelated properties of HM-GMS, optical and electron microscope were used to observe the morphogenesis, size and size distributions ofmicrospheres, the average count diameter was 63.0 u m, the volume diameter was 69.6 um, the span was 0.769, particle size and size distribution was nearly normality. Other parameters such as bulk density, angle of repose, swelling ratio, sediment volume ratio, the surface electric charge, the organic volatile impurities, and the biocompatibility were also studied. The experiment results suggested that the HM-GMS had fine fluidity, and low amount of organic volatile impurities, the zeta electric potential of HM-GMS was -16.614mv, in meglumine and 0.5% tragacanth, microspheres had certain settling stabilization, they did not cause hemolytic of red blood cells and the cell poisonous was lower than hydroxycamptothecine. All above pharmaceutical features supported that HM-GMS may be suitable for hepatic arterial embolization.In the investigation of stabilities of HM-GMS, accelerated test, room temperature test were studied. The results showed that the HM-GMS exhibited good stability under these conditions. On the other hand, the DTA method was used to study pyrolyzation. The pyrolyzative and active energy was 93.37KJ/mol, frequency factor was 2.304 X 1013/min, which showed the heat stabilization of HM-GMS was available. 10Kgy 60Co method was to used to sterilize HM-GMS, and no different substances was found.In the studies on the properties of the HM-GMS in vitro release we compared there methods and chose the continuous flowing methods to study the characteristics of drugs release, which can stimulate the actual state in vivo. The influence of the release mediums, their pH and flow rate were investigate respectively. The results showed that drug release speed was much faster in water than in other release mediums. The release rate showed no distinctive difference when the pH of phosphate buffer increased. Flow rate had the effect on the drug release, and the release profile in vitro could be described by the two-phase dynamic model.Hepatic arterial embolization was carried out on rabbits and dogs for studying the behavior in vivo. Statistic treatment of pharmacokinetic meters showed great difference in MRT between microsphere group and solution group in dogs as well as in rabbits. These results demonstrated that HM-GMS had the property of sustained release.The study of embolization effect of HM-GMS was employed angiograms method,and ALT, AS...
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