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Abstract：
BACKGROUND: To ensure pharmaceutical quality, chemistry, manufacturing and control (CMC) research is essential. However, due to the inherent complexity of Chinese medicine (CM), CMC study of CM remains a great challenge for academia, industry, and regulatory agencies. Recently, quality-marker (Q-marker) was proposed to establish quality standards or quality analysis approaches of Chinese medicine, which sheds a light on Chinese medicine\'s CMC study.
OBJECTIVE: Here manufacture processes of Panax Notoginseng Saponins (PNS) is taken as a case study and the present work is to establish a Q-marker based research strategy for CMC of Chinese medicine.
METHODS: The Q-markers of Panax Notoginseng Saponins (PNS) is selected and established by integrating chemical profile with pharmacological activities. Then, the key processes of PNS manufacturing are identified by material flow analysis. Furthermore, modeling algorithms are employed to explore the relationship between Q-markers and critical process parameters (CPPs) of the key processes. At last, CPPs of the key processes are optimized in order to improving the process efficiency.
RESULTS: Among the 97 identified compounds, Notoginsenoside R1, ginsenoside Rg1, Re, Rb1 and Rd are selected as the Q-markers of PNS. Our analysis on PNS manufacturing show the extraction process and column chromatography process are the key processes. With the CPPs of each process as the inputs and Q-markers\' contents as the outputs, two process prediction models are built separately for the extraction process and column chromatography process of Panax notoginseng, which both possess good prediction ability. Based on the efficiency models of extraction process and column chromatography process we constructed, the optimal CPPs of both processes are calculated.
CONCLUSIONS: Our results show that the Q-markers derived from CMC research strategy can be applied to analyze the manufacturing processes of Chinese medicine to assure product\'s quality and promote key processes\' efficiency simultaneously.
OBJECTIVE: Here manufacture processes of Panax Notoginseng Saponins (PNS) is taken as a case study and the present work is to establish a Q-marker based research strategy for CMC of Chinese medicine.
METHODS: The Q-markers of Panax Notoginseng Saponins (PNS) is selected and established by integrating chemical profile with pharmacological activities. Then, the key processes of PNS manufacturing are identified by material flow analysis. Furthermore, modeling algorithms are employed to explore the relationship between Q-markers and critical process parameters (CPPs) of the key processes. At last, CPPs of the key processes are optimized in order to improving the process efficiency.
RESULTS: Among the 97 identified compounds, Notoginsenoside R1, ginsenoside Rg1, Re, Rb1 and Rd are selected as the Q-markers of PNS. Our analysis on PNS manufacturing show the extraction process and column chromatography process are the key processes. With the CPPs of each process as the inputs and Q-markers\' contents as the outputs, two process prediction models are built separately for the extraction process and column chromatography process of Panax notoginseng, which both possess good prediction ability. Based on the efficiency models of extraction process and column chromatography process we constructed, the optimal CPPs of both processes are calculated.
CONCLUSIONS: Our results show that the Q-markers derived from CMC research strategy can be applied to analyze the manufacturing processes of Chinese medicine to assure product\'s quality and promote key processes\' efficiency simultaneously.
摘要：
背景：为了确保药品质量，化学,制造和控制(CMC)研究至关重要。然而,由于中医(CM)固有的复杂性，CMC对CM的研究仍然是学术界面临的巨大挑战，工业,和监管机构。最近,质量标记(Q-marker)是为建立中药质量标准或质量分析方法而提出的,这为中药的CMC研究提供了启示。
目的：以三七总皂苷（PNS）的生产工艺为例，建立基于Q标记的中药CMC研究策略。
方法：三七总皂苷（PNS）的Q标记是通过整合化学谱和药理活性来选择和建立的。然后，通过物料流分析确定了PNS制造的关键过程。此外，采用建模算法来探索Q标记与关键过程参数（CPPs）之间的关系。最后,优化关键过程的CPP以提高过程效率。
结果：在97个鉴定的化合物中，三七皂苷R1,人参皂苷Rg1,Re,选择Rb1和Rd作为PNS的Q-标记。我们对PNS制造的分析表明，提取工艺和柱层析工艺是关键工艺。以每个进程的CPP为输入，以Q标记内容为输出，分别建立了三七提取过程和柱层析过程的两个过程预测模型,两者都具有良好的预测能力。基于提取过程和柱层析过程的效率模型，我们构建了,计算两个过程的最优CPPs。
结论：我们的结果表明，CMC研究策略得出的Q标记可用于分析中药的生产过程，以确保产品质量并提高关键过程的效率。同时。
目的：以三七总皂苷（PNS）的生产工艺为例，建立基于Q标记的中药CMC研究策略。
方法：三七总皂苷（PNS）的Q标记是通过整合化学谱和药理活性来选择和建立的。然后，通过物料流分析确定了PNS制造的关键过程。此外，采用建模算法来探索Q标记与关键过程参数（CPPs）之间的关系。最后,优化关键过程的CPP以提高过程效率。
结果：在97个鉴定的化合物中，三七皂苷R1,人参皂苷Rg1,Re,选择Rb1和Rd作为PNS的Q-标记。我们对PNS制造的分析表明，提取工艺和柱层析工艺是关键工艺。以每个进程的CPP为输入，以Q标记内容为输出，分别建立了三七提取过程和柱层析过程的两个过程预测模型,两者都具有良好的预测能力。基于提取过程和柱层析过程的效率模型，我们构建了,计算两个过程的最优CPPs。
结论：我们的结果表明，CMC研究策略得出的Q标记可用于分析中药的生产过程，以确保产品质量并提高关键过程的效率。同时。
