The Research Of Extracts Of Bioactive Site Of Zhushima Sustained Release Pellets

Zushima is the stem cortex and root bark of Daphne giraldii Nitsche,a. folk herb used in west of China. It is efficacious in the treatment of rheumatoid arthritis, and which showed characteristic of good curative effects, wide uses, less side effects. Zhushima cumarins is the extracts of bioactive site of Zhushima. To meet clinical need for long time use of drugs for prevent and trearment of rheumatoid arthritis. to attain the aim of reducing times of administration and side effects. In addition. the ADME process of the main ingredient in Zushima - Daphnetin was also research Systematically by our laboratory the bioactive part of Zushima was also screened, and its physical and chemical properties were also researched in detail. On this basis, as a model drug, the bioactive part of Zushima is prepared and researched on its kinetic characteristics of intestinal absorption. In this paper, the centrifugal granulation method was employed to prepare Zushima pellets. Then the pellets were subjected to a coating process to produce sustained release characteristics.Determining on the Daphnetin content of extracts of Zushima through HPLC and the total coumarins content through ultraviolet spectrometry, the same time, carrying on methods investigation to found the standard quality control of Zushima. The accuracy, stability, repeatability and recovery of determining method all accord with the relevant regulations.Through literature review, combined with the physicochemical properties of coumarins, we choose Percolation extraction method that not only is simple, but also meet the requirements and organic solvent extraction (EtoAc).And the extraction and purification process is optimized by single-factor and orthogonal design. Ultimately Preparation of the total coumarin is determined, thus, it was beneficial to prepare sustained release pellets next step.The absorption of Daphnetin of extracts from small intestine was studied by utilizing in situ re- circulate perfusion, with different concentration of Daphnetin. The results indicated 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 concentrations, which showed that the absorption of Daphnetin complied with the passive trans- port mechanism and first order kinetics. We also studied the absorption of Daphnetin of TCZ, the permeability rate constant of which decreased, and half life prolonged, compared with pure Daphnetin. This change might be related to the other coumarins of TCZ. The results of the present experiment can be useful for improving the bioavailability of orally administrating TCZ and preparing sustained release dosage form.Effect of formulation and technology factors on drug release of centrifugal granulator and the film coating method of air floating fluid bed were investigated. The sustained release pellets were prepared by a centrifugal granulator and air floating fluid bed.Our study could enrich the research contents of the second development of Traditional Chinese Medicine (TCM) and biopharmaceutics. It also could provide some new thoughts and methods for developing effective, qualitative and standard TCM patent prescription.