Protocatechuic The Bornyl Design, Synthesis And Metabolism Studies

Traditional Chinese medicine, a Chinese clinical treatment of disease mainly means, through the thousands of years of practice has accumulated rich experience of Chinese crude drug compatibility on application and theory. Chinese medicines as a source of innovative drug development, must be under the guidance of the theory of Chinese medicine, it would have the broader space for development. Therefore, based on the jun-shi compatible herbs theory, the author synthesized a new compounds, bornyl protocatechuate, and used metabolism and other means depth to investigative its pharmacokinetics, in vivo tissue distribution and metabolite changes. The author found bornyl protocatechuate could against the origin of blood stasis, consequently enhance the ability of the body to controlling blood circulation, resulting in promoting blood circulation and eliminating stasis. This paper proposed the new drug development idea can be developed a new drug clinical significance, and can in traditional Chinese medicine and natural products for the innovation of the foundation offer beneficial reference for the drug development and mode. This dissertation consist of five chapters, the main contents are as follows:1. The author design and synthesized bornyl protocatechuate, protocatechuic acid and borneol as raw materials.2. The author use the balanced dialysis combined with HPLC method for the determination of bornyl protocatechuate with rats plasma protein binding rate. Found in the experimental concentration range, the bornyl protocatechuater and rats plasma protein binding rate is higher.3. A novel high performance liquid chromatography/time-of-flight mass spectrometry method to determinate the bornyl protocatechuate in rat (or stasis rat) plasma and tissue was established, and applied it in its pharmacokinetic study and tissue distribution after intravenous injection bornyl protocatechuate. The statistical results indicated that the plasma concentration-time course of bornyl protocatechuate in rat (or stasis rat) confirmed to a3-compartment open model, and lasting effect, and the its tissue distribution was of c spleen>c heart＞c lung＞c brain＞c kidney>c liver (or c spleen＞c heart＞c liver＞c lung＞c brain＞c kidney), demonstrating that the method can be applied in studying the clinical and non-clinical pharmacokinetic of bornyl protocatechuate. The author found a methylated product of bornyl protocatechuate in vivo metabolic process, and identified the structure is bornyl vanillate.4. The author synthesized bornyl vanillate by direct esterification, vanillic acid and borneol as raw materials. 5. A novel high performance liquid chromatography/time-of-flight mass spectrometry method to determinate the bornyl vanillate in rat (or stasis rat) plasma and tissue was established, and applied it in its pharmacokinetic study and tissue distribution after intravenous injection bomyl protocatechuate. The statistical results indicated that the plasma concentration-time course of bornyl vanillate in rat (or stasis rat) confirmed to a1-compartment open model with long half-life and the its tissue distribution was of c lung>c heart＞c kidney＞c spleen＞c liver＞c brain(or c heart＞c kidney＞c spleen＞c lung＞c liver＞c brain), demonstrating that the method can be applied in studying the clinical and non-clinical pharmacokinetic of bornyl vanillate.