Study On Preparation Technology Of Total Alkaloids In Lanzixin And Its Drop Pill As Well As In Vitro And In Vivo Evulation

The aim of this study was the preparation as well as in vitro and in vivo evaluation of total alkaloids (TAL) extracted from the seed embryo of Nelumbo nucifera Gaertn, based on dispersing formation-drop pill. According to the physico-chemical property and clinical requirement, the solid dispersion of TAL was wished to play immediate effect and enhanced the bioavailability. Firstly, the work extracted the four isoquinoline alkaloid: liensinine, isoliensinine, neferine and lotusine, from the seed embryo of Nelumbo nucifera Gaertn.and their structures were determined by spectroscopic methods, including UV, IR, EI-MS ¹H-NMR,¹³ C-NMR as well as determined the purity with TLC and HPLC-UV methods. Then the extract of Lianzixin was divided into lipid soluble and water-soluble alkaloids with macroporous adsorptive resins. Compared to the pharmacodynamic action of both, we had chosen the active site of treating the arrhythmia-lipid soluble total alkaloids (TAL). The study established the UV and HPLC determination methods, and determined the content of liensinine, isoliensinine, neferine in TAL. The study focused on the technology of TAL extact, purification by macroporous adsorptive resins and refinement. However, the study innovatively found the quality standard of TAL. At last we study the technology of preparation of drop pills and in vitro and in vivo evaluation. To utilize orthogonal experiments, we optimize the technology of preparation and condition of dropping condition.Moreover, drop pill was carried out on a differential scanning calorimeter (DSC) to evaluate the formation of solid dispersion. However, the study innovatively found the quality standard of TAL drop pill. The pharmacokinetic profiles of TAL following an oral administration of TAL or its solid dispersion were evaluated in rabbits. Diosmosis effect in sublingually mucous membrane was in vitro evaluated preliminary. Differential Scanning calorimetry scans were done for the PEG 6000/4000 solid dispersion prepared by fusion method. The endothermic peak of solid dispersion occurred at about around the melting point of the corresponding polymeric carriers, which indicates complete formation of solid solution system in both. Quality standard In vitro dissolution rate and the pharmacokinetic profiles of TAL following an oral administration of TAL solid dispersion could be used to evaluate the quality of drop pill. And the quality is control and stability. The in vivo bioavailability study showed that solid dispersion formation was found to be significantly different from TAL with regard to the extent of absorption as indicated by the area under plasma concentration-time curve. Moreover solid dispersion formation is significantly different from TAL with respect to time of peak plasma concentration (T_max) and maximum plasma concentration (C_max). It is concluded from this pilot study that the faster dissolution of solid dispersion formation appeared to be compared well with more enhancing absorption of TAL, and enhanced bioavailability in rabbits. Due to the time of the study, Diosmosis effect in sublingually mucous membrane in vivo evaluation need further study.In conclusion, TAL is active site of treating the arrhythmia. The study established extract technology and quality standard of TAL, the result indicated that the technology of the preparation of drop pill was controlled and stability as well as possessed immediate effect and high bioavailability.