The Research Of Extracts Of Bioactive Site Of Zhushima Pellets

Zushima is the stem cortex and root bark of Daphne giraldii Nitsche,a folk herb usedin west of China.It is efficacious in the treatment of rheumatoid arthritis,and which showedcharacteristic of good curative effects,wide uses,less side effects. Zhushima cumarins is theextracts of bioactive site of Zhushima.To meet clinical need for long time use of drugs forprevent and trearment of rheumatoid arthritis,to attain the aim of reducing times ofadministration and side effects,the thesis was aiming at the research of the extracts ofZhushima,consisting of preparation of solid dispersion,and then,preparing pellets.Thepellets were prepared by a centrifugal granulator.Determining on the Daphnetin content of extracts of Zushima through HPLC and thetotal coumarins content through ultraviolet spectrometry, the same time, carrying onmethods investigation to found the standard quality control of Zushima. The accuracy,stability, repeatability and recovery of determining method all accord with the relevantregulations.The physicochemical properties of coumarins were investigated,which were contentclosely with pharmaceutic form design.The studies on solubility showed that theequilibrium solubility of cumarins and daphnetin were 339.77 and 393.82μg/mLrespectively;Apparent oil-water partition coefficient of cumarins and daphnetin were 0.674å'Œ1.053 respectively.In additional,the result of sphericity showed the extracts has poorlyfluidity.The critical comparatively humidity is 40% and 20～35%,the balance time is 3days.The solubility results showed the extracts were poorly soluble.So the thesis preparedsolid dispersion which increased markedly the solubility and dissolution rate of theextracts.It was beneficial to prepare the pellets next step.The absorption of Daphnetin of extracts from small intestine was studied by utilizingin situ re- circulate perfusion,with different concentration of Daphnetin.The resultsindicated that the permeability rate constant of Daphnetin increased according to duodenum,jejunum, ileum. The pH of intestine regions had some effect on the absorption kinetics. The permeability coefficient value of drug was kept unchanged at different concentra-tions,which showed that the absorption of Daphnetin complied with the passive trans- portmechanism and first order kinetics.The parameters of absorption in situ.intestine of soliddispersion,such as Ka and PA,are increased markedly than extracts.The results of thepresent experiment can be useful for improving the bioavailability of orally administratingextracts and preparing sustained-release dosage form.Effect of formulation and technology factors on drug release of centrifugal granulatorand extrusion-spheronization were investigated. The pellets were prepared by a centrifugalgranulator.Our Study could enrich the research contents of the second development of TraditionalChinese Medicine (TCM) and biopharmaceutics.It also could provide some new thoughtsand methods for developing effective,qualitative and standard TCM patent prescription.