Studies On The Quality Control Of Ophiopogon Japonicus As An Ingredient Of Shenmai Injection Formula

The quality control level of traditional Chinese medicine (TCM) industry is low and restricts its development. In order to improve the quality control level of TCM, the research on three critical units—hemical material basis, analytical methods and production processes in TCM quality control should be strengthed via modern science and technology.Shenmai Injection is one of the major TCM composed of Panax ginseng (Hongshen) and Ophiopogon japonicus (Maidong). However, the quality control of Shenmai Injection is still inadequacies because the research on O. japonicus is less. In this thesis, chemical material basis, analytical methods and production processes for O. japonicus were studied. This study will raise the quality control level of O. japonicus and provide a good example for TCM quality control.The main innovation and academic contributions of this dissertation are summarized as follows:1. Column chromatography techniques were used to isolate the chemical constituents of O. japonicus grown in Zhejiang province.12compounds were obtained and11of them were identified via MS and NMR spectral analysis. Compounds8-10were new homoisoflavanones, compound1was a new steroidal saponins and compound5was isolated from Ophiopogon genus for the first time.2. A qualitative method was established by HPLC-MS" according to the MS" fragmentation patterns of6steroidal saponins. Steroidal saponins in O. japonicus and other formulas including O. japonicus could be identified rapidly without reference substance according to this method. It preliminary conquered that steroidal saponins were difficult to isolate and identify. Developed the fingerprint of O. japonicus by HPLC-MS and identified the peaks in fingerprint based on the HPLC-MS" method and literatures.3. A quantitative method for simultaneous determination of three steroidal saponins was developed via HPLC-MS. It preliminary overcome the disadvantages that steroidal saponins were difficult to determine because of their low content and non chromophores in O. japonicus.The sample pretreatment of this method was simple compared with previous analytical methods. It could be used to distinguish different origin of O. japonicus and evaluated the samples from production process. It provided a fast and feabile way to improve the quality control level of O. japonicus.4.4operating units of Shenmai Injection production process including12batches under normal operation condition (BNOC) and some batches under abnormal operation condition (BAOC) were prepared in lab scale. The HPLC-MS fingerprint combined with multivariate data analysis techniques were used to distinguish the abnormal compounds in fingerprint caused by the changes of operating parameters in BAOC. It could find the operating parameters affecting the quality of0. japonicus intermediates in the unit operation. This approach supplied a new strategy to evaluate the manufacture process of O. japonicus.5. The performance of ceremic membranes and ultrafiltration membranes in the pass rate of three steroidal saponins and the clearance of total solid were investigated respectively and observed the best pore size of ceremic membrane and MWCO of ultrafiltration membrane. The suitable operating parameters were obtained by the research on the process of micro filtration and ultrafiltration. Preliminary studied the fouling problem of membrane material. This work not only provided the strategy for the ultrafiltration process of Shenmai Injection but also gave a new production process for O. japonicus. Researched on the loss of steroidal saponins in the activated carbon adsorption process and discussed its adsorption mechanism.