Study On Structural Characterization, Quality Control And Pharmacokinetic Of DBZ

Cardiovascular and cerebrovascular diseases(CDV) is the "first killer which threat to human health",the research and development of highly effective new drugs is the main means to remedy the disease,and also the hot topic in the field of medicine research.Bomylβ-(3,4-dihydroxyphenyl)-α-hydroxypropionate(Abbreviation:DBZ) is a new compound which was advanced from in-depth study of Compound Danshen Dripping Pills,Decoction of Radix Salviae Miltiorrrhizae and Fufang Danshen Tablets,and was synthesized with technologies of organic synthesis and modern pharmacology by the research center where the auther works.The compound also presented a strong efficiency for againsting acute myocardial ischemia and lowering blood pressure in rats.In this thesis,DBZ was selected as a target for the investigation on its structrual identification,quality control and establishment of the analyzing method of pharmacokinetic study in vivo.The above investigation could play an important role in developing DBZ as one grade innovative medicine.The main contents of this thesis are showed as following:1.Mass spectroscopy,infrared spectroscopy and nuclear magnetic resonance spectroscopy method were used for the identification of DBZ.The results showed that the molecular weight of DBZ is 334.2,and its chemical name is 1,7,7-trimethylbicyclo[2.2.1]heptan-2- y1 3-(3,4-dihydroxyphenyl)-2-hydroxy-propanoate. With the proposed synthetic method,the reacting product has the properties of optical isomers and bimodal peak in reverse liquid chroamtogram.2.A new quality controling method was established for the research on characteristics, physico-chemical constants,identification,examination and determination of DBZ.The results of residual solvents showed that there are no ether,acetone,tetrahydrofuran,ethyl acetate and methanol by investigating three parallel DBZ samples.In addition,the residual quantity of alcohol is lower than 0.5%.Methodology of related substances and determination showed that the linear range of DBZ is 5～1000 mg·L^-1,and the detection limit is 10.0 ng, demonstrating that the method is specific,sensitive and could be used for quality control of DBZ.The results of stability experment indicated that DBZ is lack of stability under high temperature and strong light,demonstating that it should be stocked without high temperature and strong light. 3.A new high performance liquid chromatography(HPLC) method for analysis of the DBZ in plasma was established.Moreover,the pharmacokinetics of DBZ was studied by the method in healthy rabbit.The results showed that the linear range of DBZ is 0.08¹9.92 mg·L^-1,the detection limit is 14.4 ng.The recovery,relative standard deviations(RSD) of precision and stability were accorded in the requirements of biological sample analysis in Food and drug administration.The time - concentration curve of DBZ with the intravenous dosage of 30 mg·kg^-1 confirmed to the model of three compartment,indicating that the method could be used to pre-clinical pharmacokinetic and bioequivalence study.