两种中药特色大品种生产过程快速质控体系构建的关键技术研究及应用

发布时间：2018-04-24 14:07

本文选题：疏血通注射液 + 芪胶升白胶囊　；参考：《浙江大学》2017年博士论文

【摘要】：在2015年屠呦呦荣获诺贝尔奖和国家提出"一带一路"战略布局的背景下,中药国际化时代已经到来。虽然中药行业发展迅速并已经形成了一定规模的产业体系,但是由于中药的复杂性和生产过程的不稳定,我国中药的质量检测方法及控制手段相对落后,导致我国中药制剂质量难以保证,从一定程度上制约了中药国际化的进程。中药国际化要求应用现代科学理论和高新技术手段对中药进行现代化研究,建立中药及其生产过程的质量控制体系尤为重要。中药制剂质量的影响因素除了药材本身,还有其各个生产加工环节。因此,中药材的基础研究和质量控制手段仍需加强,同时还要重视建立中药生产过程的质量控制体系。近年来,得益于化学计量学的快速发展,光谱分析技术作为快速分析技术在中药领域的应用越加成熟,特别是近红外光谱(Near-infrared Spectroscopy,NIRS)分析技术用于中药及生产过程中的快速质量控制研究。本研究以中药特色大品种疏血通注射液和芪胶升白胶囊为对象,开展了基于光谱分析技术构建原药材和关键生产工艺环节的快速质量控制体系研究,具体包含以下两个方面:(1)以中药特色大品种疏血通注射液为研究对象,将NIRS分析技术结合化学计量学用于其生产过程的快速质控体系构建。首先开展动物药水蛭和地龙的质量控制体系,与植物药相比其研究相对落后。本文运用NIRS结合化学计量学,建立水分、可溶性固形物、次黄嘌呤、多糖和多肽的定量分析模型,同时考察了异常点诊断方法对模型的影响程度。结果表明,马氏距离(MD)、学生化残差-杠杆值(LD)和主成分得分诊断(PCSD)三者联合更能全面诊断异常点,所建立的方法能够对质控指标进行快速准确的定量分析,所建模型稳定可靠。同理,采用PLS法分别建立可溶性固形物、次黄嘌呤、多糖和多肽为的定量校正模型,从而构建浸渍过程、冻融过程和膜过滤过程的快速质控体系。(2)以中药特色大品种苗药芪胶升白胶囊为研究对象,构建其生产过程的快速质控体系。以淫羊藿苷、黄芪甲苷、总黄酮和总皂苷等为质量控制指标,分别建立了原药材、提取过程和浓缩过程的快速质量控制方法。原药材以淫羊藿和黄芪为研究对象,基于NIRS和中红外光谱(MIRS)分析技术,建立了淫羊藿苷、总黄酮、黄芪甲苷和总皂苷的快速定量分析模型,结果表明,近红外和中红外(NIR+MIR)光谱数据整合后所建立的模型性能更优,相关系数都达到0.99以上。提取液以水为溶剂不适合采用MIRS分析技术,所以提取过程的快速质控体系构建采用NIRS快速检测淫羊藿苷、总黄酮和总皂苷的含量变化。浓缩过程的快速质控体系构建采用NIRS和MIRS快速检测密度值、淫羊藿苷、总黄酮和总皂苷的含量变化,结果表明,NIR+MIR光谱数据整合后所建立的模型性能均比基于单一的NIRS和MIRS要好,相关系数都在0.99以上。
[Abstract]:In 2015, Tu Youyou won the Nobel Prize and proposed Belt and Road's strategic layout. Although the traditional Chinese medicine industry has developed rapidly and has formed a certain scale industrial system, due to the complexity of traditional Chinese medicine and the instability of the production process, the quality detection methods and control means of Chinese traditional medicine are relatively backward. The quality of Chinese traditional medicine preparations is difficult to guarantee, which restricts the internationalization of traditional Chinese medicine to some extent. The internationalization of traditional Chinese medicine requires the application of modern scientific theory and high-tech means to study the modernization of traditional Chinese medicine. It is particularly important to establish the quality control system of Chinese medicine and its production process. In addition to the quality of traditional Chinese medicine preparation itself, there are various production and processing links. Therefore, the basic research and quality control methods of traditional Chinese medicine should be strengthened, and the quality control system of traditional Chinese medicine should be established. In recent years, thanks to the rapid development of chemometrics, spectral analysis technology as a rapid analysis technology in the field of traditional Chinese medicine has become more and more mature. In particular, Near-infrared Spectroscopy (NIR) analysis technology is used to study the rapid quality control of traditional Chinese medicine and its production. Taking Shuxuetong injection and Qijiaoshengbai capsule as the objects, the rapid quality control system of the original medicinal materials and the key production process was studied based on the spectral analysis technology. Taking Shuxuetong injection as the research object, the NIRS analysis technology combined with chemometrics was used to construct the rapid quality control system in the production process of Shuxuetong injection. First, the quality control system of the animal medicine leech and Geosaurus was developed, and the research was relatively backward compared with the plant medicine. In this paper, a quantitative analysis model of water, soluble solids, Hypoxanthine, polysaccharides and polypeptides was established by means of NIRS combined with chemometrics. The results show that the combination of Markov distance (MD), student-based residual-lever value (LDV) and principal component score (PCSD) can diagnose outliers more comprehensively. The established method can be used for rapid and accurate quantitative analysis of quality control indexes, and the established model is stable and reliable. Similarly, the PLS method was used to establish the quantitative calibration models of soluble solids, Hypoxanthine, polysaccharides and polypeptides respectively, so as to construct the impregnation process. The rapid quality control system of freeze-thaw process and membrane filtration process. Taking icariin, astragaloside A, total flavonoids and total saponins as quality control indexes, a rapid quality control method for raw medicinal materials, extraction process and concentration process was established. A rapid quantitative analysis model of icariin, total flavone, astragaloside A and total saponins was established based on NIRS and mid-infrared spectroscopy (Mir) analysis of Herba Epimedii and Astragalus membranaceus. The results showed that the quantitative analysis of Icariin, total flavone, astragaloside A and total saponins was rapid. The performance of NIR and Mir NIR MIR-based models is better than that of NIR data, and the correlation coefficient is above 0.99. Water as solvent was not suitable for MIRS analysis, so the rapid quality control system of extraction process was constructed to detect the changes of Icariin, flavonoids and saponins by NIRS. The rapid quality control system of concentration process was constructed by using NIRS and MIRS to detect the density of icariin, total flavonoids and total saponins, and the changes of Icariin, total flavonoids and total saponins were analyzed. The results show that the performance of the model is better than that based on single NIRS and MIRS, and the correlation coefficient is above 0.99.
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R286.0

【参考文献】