目的 基于传质数学模型，研究热毒宁注射液（Reduning Injection，RI）生产过程中绿原酸存在状态与传递规律。方法 以绿原酸为检测指标，构建纳滤传质模型。选择单体分子态为参照，计算RI中间体溶液中绿原酸的存在状态；分析RI生产工艺过程绿原酸转移率变化与存在状态之间的相关性，探索RI浓缩过程中引起酚酸类物质传递差异的内在原因。结果 绿原酸在提取物溶液和RI中间体溶液中传质系数与溶质浓度幂值的回归系数均大于0.90，纳滤传质模型成立。绿原酸在RI中间体水溶液与乙醇溶液环境中，呈现分子态比例与浓缩转移率正相关性；其在金银花、青蒿中间体溶液中亦呈现相同趋势，表明成分存在状态为RI浓缩过程中引起酚酸类物质传递差异的内在原因。此外，绿原酸在相同溶液体系中，分子态稳定性高于离子态；在不同溶剂体系中，在乙醇溶液稳定性高于水溶液。结论 构建了RI中间体中绿原酸的分子状态定量计算方法，初步阐明其存在状态与物质传递呈正相关性，为制剂生产过程标准化控制提供支持。

Objective Based on the mathematical model of mass transfer, this study aimed to investigate the existence state and transfer principle of chlorogenic acid in the production process of Reduning Injection (RI, 热毒宁注射液) were investigated. Methods Using chlorogenic acid as the detection index, a nanofiltration mass transfer model was established., and choosing the monomer molecular state as the reference, calculated the existence state of chlorogenic acid in the intermediate solution of RI, analyzed the correlation between the change of chlorogenic acid transfer rate and the existence state of chlorogenic acid in the process of production of RI, and explored the intrinsic causes of the difference in the transfer of phenolic acids during the RI concentration process. Results The regression coefficients between the mass transfer coefficients of chlorogenic acid and the power value of solute concentration in the extract solution and the RI intermediate solution were all greater than 0.90, and the nanofiltration mass transfer model was established. chlorogenic acid showed a positive correlation between the ratio of molecular states and the concentration transfer rate in aqueous and ethanol solutions of RI intermediates, and the same trend was observed in solutions of Jinyinhua (Lonicerae Japonicae Flos) and Qinghao (Artemisiae Annuae Herba) intermediates, suggesting that the state of existence of the constituents is the intrinsic cause of the differences in phenolic acid transfer during RI concentration process. In addition, chlorogenic acid was more stable in the molecular state than in the ionic state in the same solution system, and more stable in the ethanol solution than in the aqueous solution in different solvent systems. Conclusion A quantitative calculation method for the molecular state of chlorogenic acid in the intermediate of RI has been constructed, and the positive correlation between its existence state and mass transfer has been initially elucidated, which can provide support for the standardized control of the production process of the preparation.

R283.6

国家自然科学基金项目(82274106);中药制药过程控制与智能制造技术全国重点实验室创新项目(NZYSKL240207);南京中医药大学中药学一流学科科学研究培育项目(ZYXPY2024-006)