Researh On Preparation Technology And Structural Confirmation Of Bulk Pharmaceutical Chemicals Of Tetrandrine

Objective: To research the extraction and separation & purification techniques of Bulk Pharmaceutical Chemicals(BPC)of Tetrandrine and confirm the structure of pilot products;to establish the stable and feasible preparation technology for the BPC of Tetrandrine;to provide the evidence for the pilot-scale,quality and stability researches.Methods: 1.The research on extraction technique for the BPC of Tetrandrine:(1)Establish the measurement method for the Tetrandrine content in the Tetrandrine Alkaloid extract and verify the methodology.(2)Select the extraction solvent and extraction method by the signal factor experiment and based on it,optimize the extraction process parameters by the homogeneous design of experimentation.2.The research on separation & purification technique for the BPC of Tetrandrine:(1)Select the adsorbent and eluent and based on it,design three schemes to optimize the separation & purification process parameters by the comparative research method.(2)Research the purification and drying techniques for the BPC of Tetrandrine and determine the optimal process parameters.3.The research on structural confirmation for the BPC of Tetrandrine:Confirm the structure of prepared Tetrandrine by means of elemental in analysis,ultraviolet,infrared,mass spectrum,high resolution mass spectrum,nuclear magnetism,nuclear magnetism two-dimensional spectrum,optical rotation,X diffraction and thermal analysis.4.The existing preparation technology of Tetrandrine API was compared with the preparation technology developed by our research institute in production cost,efficiency,final yield,product quality,automation degree,safety and environmental protection.Results: 1.In the research of extraction technique,the HPLC content measurement method established for the Tetrandrine in Tetrandrine Alkaloid by the laboratory is stable and reliable with high accuracy degree,and all the indicators verified for the methodology accord with the regulations;the optimal extraction technique is the Alkaline Ethanol Reflux Extraction Method: the dosage of quick lime is 6% of raw material quantity;the ethanol concentration is85%;the liquid-to-solid ratio is 5:1;the extraction frequency is three times;the extraction time is three hours each time;and the powder size is 100 meshes.2.In the research of separation & purification technique,the optimal separation process is the Reversed-phase Preparative High-performance Liquid Chromatography: the fixed phase is flash AQ C18 100 (?)(120g,20～45μm);the mobile phase is 3:1,the ratio of 0.06% Diethylamine Methanol and water;the sample solution concentration is 35 mg Tetrandrine Alkaloid extract/m L;the sample volume is 20 m L;the flow velocity is 35 m L/min;the measurement wavelength is 282nm;and the monitoring wavelength is 254 nm.The optimal purification & drying process is to be decompressed and concentrated with recrystallization and vacuum drying.3.In the research of structural confirmation,by all the analytical methods,the results of tested samples are in accordance with those of reference products and those in literature reports.4.In general,the preparation technology of Tetrandrine API developed by our research institute is better than the existing preparation technology.Conclusion: The research determines the preparation technique for the BPC of Tetrandrine and confirms the sample prepared by the technique is the Tetrandrine,which provides the evidence for the pilot-scale,quality and stability researches.