目的 应用统计过程控制技术研究建立青蒿金银花醇沉过程中实时放行标准。方法 收集29个批次共145个青蒿金银花醇沉样本作为训练集样本,测定样本中新绿原酸、绿原酸、隐绿原酸及固含物的量,应用统计过程控制技术建立4个指标的定量放行标准;并采用中心组合设计制备13个批次不同工艺条件下的青蒿金银花醇沉样本作为验证集,验证定量实时放行标准的准确性。结果 建立的定量放行标准范围分别为新绿原酸0.279~0.541mg/g,绿原酸1.941~2.610 mg/g,隐绿原酸0.453~0.570 mg/g,固含物3.565%~4.925%;验证集中与大生产实际工艺参数一致的1、4、8、9、10号样本的4个指标成分在定量放行标准之内。结论 建立的单变量过程统计方法能更好地监控生产过程,对终点样本进行判断,达到实时放行的目的。

Objective To study the application of statistical process control technology to establish the real-time release criteria of alcohol precipitation process of Artemisiae Annuae Herba and Lonicerae Flos.Methods Twenty-ninebatches of samples came from alcohol precipitation process of Artemisiae Annuae Herba and Lonicerae Flos were collected as the calibration set. The contents of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, and solid content were determined to establish the quantitative real-time release criteria based on statistical process control technology. Thirteen batches of alcohol precipitation process of Artemisiae Annuae Herba and Lonicerae Flos were prepared under the different process conditions by the central composite design. They were regarded as the validation set to test the dependability of the real-time release criteria. Results The established quantitative release ranges were neochlorogenic acid 0.279-0.541 mg/g, chlorogenic acid 1.941-2.610 mg/g, cryptochlorogenic acid 0.453-0.570 mg/g, and solid content3.565%-4.925%. The four index component contents of the samples 1, 4, 8, 9, and 10 from the validation set were within the range of the real-time release criteria. Conclusion Univariate statistical process control could be well monitored and understood of production process for Chinses materia medica.They are used to achieve the purpose of real-time release.

国家科技部"国家重大新药创制"项目:现代中药创新集群与数字制药技术平台(2013ZX09402203)