[关键词]
[摘要]
目的 优化热毒宁注射液金银花和青蒿(金青)的醇沉工艺,并获得关键工艺参数与质量属性的关系方程,为醇沉过程自动化控制提供理论依据。方法 以新绿原酸、绿原酸、隐绿原酸、咖啡酸、断氧化马钱子苷转移率及醇沉液中固含量为指标,通过单因素试验设计,考察醇沉前液相对密度、醇沉前液温度、醇沉终点乙醇体积分数、醇沉搅拌速度、加醇速度、静置温度、静置时间7个因素对醇沉工艺的影响趋势,同时通过方差分析确定影响醇沉工艺的关键因素。再采用Box-Behnken响应面法对关键因素的参数范围进行进一步的研究与探讨。结果 单因素试验结合Box-Behnken响应面法研究得到金青醇沉的最佳工艺参数:搅拌速度为550 r/min、加醇体积流量为4.0 mL/s、醇沉终点乙醇体积分数75%、静置温度30 ℃、静置时间24 h、醇沉前液相对密度1.10 g/mL(25 ℃)、醇沉前液温度25 ℃,在此条件下新绿原酸、绿原酸、隐绿原酸、咖啡酸、断氧化马钱子苷转移率分别为94.8%、97.6%、97.4%、97.2%、96.1%,醇沉液中固含量为4.2%。结论 采用响应面法优化了热毒宁注射液金青的醇沉工艺,有助于进一步提升金青醇沉工艺的稳定性。
[Key word]
[Abstract]
Objective To optimize the alcohol precipitation process for Lonicerae Flos and Artemisiae Annuae Herba (LA) in Reduning Injection and obtain the relationship equation of the key process parameters and quality attributes, which could provided a theoretical basis of the control automization in the alcohol precipitation process. Methods With the transfer rates of neochlorogenic acid, chlorogenic acid, cryptochlorogenin acid, caffeic acid, secoxyloganin and solid content in precipitation liquid as evaluation indexes, the effect of the seven factors, such as relative density and the temperature of LA in liquid phase before alcohol precipitation, alcohol concentration in the end of alcohol precipitation, stirring speed in alcohol precipitation, adding alcohol speed, standing temperature, and standing time, on the alcohol precipitation process was investigated by the single factor experiment. By analysis of variance, the key factors that could influence the alcohol precipitation process were determined. Then the range of parameters of key factors was further studied and explored by Box-Behnken response surface methodology. Results The optimum preparation conditions of the alcohol precipitation process of LA were as follows: stirring speed was 550 r/min, adding alcohol speed was 4.0 mL/s, standing temperature was 30 ℃, standing time was 24 h, alcohol concentration was 75%, the relative density of LA was 1.10, and the temperature of LA was 25 ℃. Under these conditions, the transfer rates of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, caffeic acid, and secoxyloganin were 94.8%, 97.6%, 97.4%, 97.2%, and 96.1%, and the solid content was 4.2%. Conclusion The alcohol precipitation process of LA have been optimized by the response surface method, which could help to enhance the stability of the process.
[中图分类号]
[基金项目]
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)