The Research Of Delayed-Release Drug Delivery Systems On Hirudo Extract

Objective:Taking the Whitmania pigra as the research object.The active component which was extracted from the Whitmania pigra, was regarded as the target for us to study its Pharmacological mechanism. And the active component was also used as the model d rug for us to prepare the colon delayed-release pellets and to make up the OCCDS.Method:The optimum extraction process of Whitmania pigra was selected by means of c omparing the effect with different extraction method by the indicator of pharmacodyn amic. And the Structure characteristics of the active component could be judged while the extract was hydrolyzed by the Gastrointestinal protease. Then the effect of the ext ract on APTT, PT, TT and the and the platelet aggregation was used to study the mech anism of its anticoagulation and anti-thrombotic. In this paper, Extrusion-spheronizati on technique was introduced to prepare colon sustained-release pellets by using MCC, PVPP and Eudragit as coating materials. BCA method was adopted to determine its c ontent as to explore the released behavior.Results:An extract method was established which used cold-maceration first and then hot dipping with normal saline as solvent. The extract can extend the CT and BT of rats r emarkably, restrain the formation of thrombus of tail vein and reduce the mortality of cerebral thrombosis. It can also extend the APTT and PT and restrain the platelet aggr egation which the revellent generates. The activity was lost after the extract was hydro lyzed by proteases. The researchers prepared the pH rely on-delay type of the colon la te release preparation with the extract as model medicine and determined the technolo gical parameters and formulation. Three groups of preparation were investigated by si milar factor method, both f2>50. It demonstrated the release was consistent. The expe riences which the preparation was released in vitro and transported in vivo demonstrat ed the preparation was begun to release at caecum. According to the micrographs, the coating of delayed release pellet was begun to fracture at caecum and the release was started here. The results of examination of preparations pharmacodynamics demonstra ted the efficacy strength of late release preparations were higher than the isodose ordi nary preparations. And the drug released performance could be evaluated by studying the in vitro released degrees and its transport release behavior and efficacy in mice.Conclusions:The main active constituents from the extract of Whitmania pigra are proteins. Its anticoagulation and antithrombosis were related to the extended APTT and TT and th e restrained platelet aggregation. The mechanism may be the restraint which the proth rombin transforms into thrombin. It interdicts the process of fibrinogen transforms into fibrin. The Endogenous way and Exogenous way are to block the occurrence of blood coagulation. On the other hand, it could also block the activation of the platelet driven by ADP and inhibit the platelet metabolism. And the preparation could be released steady in the end of small intestinal and colon parts which could successfully avoid being destroyed by the Stomach acid and gastrointestinal protease was reliable and easy to operate. The research constructs the OCCDS of protein and peptide which contributed to improve the bioavailability of drugs.