The Synthesis Of Evodiamine Derivative And Preliminary Evaluation Of EVB Loaded With Nanoparticles

Evodiamine（EVO）was traditional Chinese medicinal herb, had thepharmacological effects of angiectasis, anti-inflammatory, increasedtemperature and antineoplastic. However,the oral absorption ofevodiamine was not completed and low bioavailability, those habits limitedtheir clinical application. In the present study, by modifying the structure ofevodiamine, synthesized the evodiamine butyryl derivatives (EVB) forimproving the bioavailability. EVB-NP prepared by thin film dispersionultrasound method, the prescription was optimized by Box-Behnkendesignis optimization method.The study includes following sections：The EVB was synthesized by one step synthesis method. Thereaction temperature was80℃, the molar ratio of the EVO to butyrylchloride was1:5, the molar ratio of the EVO to NaH was1:10, and reactiontime was24h.The solubility of EVB was3.09μg/mL, oil/water partitioncoefficient was1.06, compared with EVO, EVB solubility improved about17times and oil/water partition coefficient improved about2times. The pharmacokinetic study indicated that CL of EVB was lower,AUC0-tand absorption increased significantly.EVB-NP was prepared by thin film dispersion-ultrasonic method,encapsulation efficiency and drug loadings as examining index to optimizepreparation.The average encapsulation efficiency of EVB-NP was(86.25±0.54)%, average drug loadings was (3.40±0.15)%. The modelfitting results indicated that the drug release equation was Ritger-Peppasmodel. EVB-NP compared with EVB by the pharmacokinetic study, theAUC0-tof EVB-NP increased4times, CL was decreased30%. The resultindicated that the bioavailability of EVB increased obviously.