【作者】 李文龙；

【导师】 瞿海斌；

【作者基本信息】 浙江大学 ， 药物分析学， 2011， 博士

【摘要】 当前中药工业面临的严峻挑战是：中药质量评价方法落后,生产过程缺乏先进的质量监控手段,药品质量难以提高。为此,本文围绕中药生产过程质控这一重要科技难题,以痰热清注射液为具体研究对象,综合运用现代仪器分析、药物分析信息学等技术,着重开展中药材及中药提取物质量近红外光谱快速分析方法、中药注射剂配液过程质量监控方法研究,建立了中药生产过程质控方法,并将研究成果与工业生产实践结合。主要研究内容及成果如下1.建立了基于NIR光谱技术的原料药材质量控制方法。对熊胆粉的真伪进行了判别分析；对黄芩药材生长方式和产地进行了鉴别,并对其中的4种黄酮类化合物的含量进行了快速测定；对金银花药材的产地进行了鉴别,并对其中的6种有机酸类化合物进行了快速测定；对连翘药材采收时期和产地进行了判别分析,并对原料药材中的青翘与黄翘的比例进行了快速分析。以上研究有助于工厂的原料采购和投料前检验,确保原料的质量稳定。2.利用NIR光谱技术对中药提取物进行了快速分析。建立了5种中药提取物中水分含量的测定模型；建立了熊胆粉提取物中2种胆酸、金银花提取物中6种有机酸、以及山羊角提取物中12种氨基酸的快速测定方法。3.研究了痰热清注射液成品中多项内控指标的快速测定方法。利用自制的配件实现了痰热清注射液的不开瓶检验；由于建模样品中待测指标波动较小,不利于建立稳健模型,为此配制了不同浓度的样品以扩大建模样品的代表性；进行了模型转移研究,扩大了所建模型的适用性。本部分研究可减轻成品检验的工作量,并可适当提高成品的抽检比例,以提高分析结果的可靠性。4.对痰热清注射液的配液过程进行了研究。建立了判别分析模型,用于识别不同浓度和pH值的总混液；建立了配液过程中4种中间体的快速定量分析方法,并对所建模型进行了更新。更多还原

【Abstract】 Currently, the big challenges in the traditional Chinese Medicine (TCM) industry are lacking of advanced manufacturing process supervisory techniques to renew the backward quality evaluation methods, so that the quality of TCMs is hard to be improved. For this reason, taking a TCM preparation, Tanreqing injection as the research carrier, this paper accordingly focused on the investigation of rapid analysis method for the quality assessment of TCM raw materials and extracts with near infrared spectroscopy (NIRS), and also the Process quality control methods for the liquid preparation process, by combination of the modern instrument analytical techniques and pharmaceutical analysis information technologies. Ultimately, the process quality control method of TCM was established, and the research findings were used in industrial practice. The main innovation and academic contributions of this dissertation are presented as follows:1. The rapid quality control methods for the TCM materials were established. Firstly, an NIRS method was developed for the authentication of bear bile powder; Secondly, an NIRS method was developed for the growth pattern and geographical origin discrimination and content determination of 4 flavonoids in Radix Scutellariae; Thirdly, an NIRS method was developed for the geographical origin discrimination and content determination of 6 organic acids in Lonicera japonica; Finally, the discrimination method of Fructus Forsythiae from different geographical origin and different harvesting stages was developed, and the proportion of Green forsythia in the raw materials was determined. This research is helpful to the raw material purchase and the quality testing before the raw materials put into production.2. The quality control method based on the NIRS technology for the TCM extracts is researched. An NIRS method was established for the measurement of moisture contents in 5 kinds of TCM extracts, and rapid analysis methods for the determination of UDCA and CDCA in the bear gall powder extracts,6 organic acids in Lonicera japonica extracts, and 12 amino acids in the Cornus Caprae Hircus extracts were also developed.3. The rapid NIRS determination method of the final product was established. A homemade accessory was used for the non-invasive analysis. And with the accessory, several internal control indexes were determined without opening the vials. Generally speaking, the quality of Tanreqing injection is stable, which will make the robust calibration models not easily to be developed. To resolve this issue, more representative samples were prepared, which can increase the representativeness of the calibration set effectively. The calibration transfer method was also researched for the more widely use of the models. This research can reduce the workload of product inspection to a large extent, and the sampling proportion can be increased properly, which will contribute to improve the reliability of determination results.4. Focus studies on the liquid preparation process were done to enhance the process understanding. Firstly, the method of discriminant analysis was established for the total mixing liquid samples with different concentration and pH values. Secondly, A method for rapid quantitative analysis of 4 kinds of Tanreqing injection intermediates was developed.更多还原