目的 基于成分存在状态定量计算模型，分析丹参注射液（Danshen Injection，DI）的醇沉工艺中酚酸类成分的传递规律。方法 以DI中水溶性酚酸类成分丹参素钠、原儿茶醛、迷迭香酸、丹酚酸B为检测指标，基于纳滤传质数学模型，收集膜通量、截留率数据，拟合溶质传质系数，以分子态单体成分为参照，构建成分存在状态定量计算模型，进而分析中间体密度1.05、1.15、1.25 g/mL时，指标性成分醇沉至75%、85%的转移率与成分存在状态及相对分子质量的相关性，以期解明醇沉精制机制。结果 存在状态定量计算幂函数方程的相关性系数均大于0.99，DI中间体的密度为1.05～1.25 g/mL时，丹参素钠、原儿茶醛、迷迭香酸、丹酚酸B分子态比例分别为1.14%～5.25%、66.70%～80.25%、10.51%～19.11%、1.13%～11.44%，对密度-分子态比例-醇沉转移率进行相关性分析，醇沉体积分数由75%增加至85%，转移率下降比例排序为丹参素钠＞丹酚酸B＞迷迭香酸＞原儿茶醛，成分存在状态为影响醇沉转移率的主导因素，且与成分相对分子质量存在一定相关性。结论 构建了DI中间体中酚酸类成分分子状态定量计算方法，初步阐明醇沉精制机制，有助于制剂醇沉工艺的标准化控制。

Objective To explore the transfer rules of phenolic acids in the alcohol precipitation process of Danshen Injection (DI) based on molecular state quantitative calculation model. Methods In the experiment, sodium danshensu, protocatechuic aldehyde, rosmarinic acid and salvianolic acid B were selected as indexes for exploring the alcohol-precipitation mechanism. Based on the mathematical model of nanofiltration mass transfer, membrane flux and rejection were collected to calculate the solute mass transfer coefficients, and the quantitative calculation model of molecular state was established with molecular monomer components as reference of DI. Furthermore, the correlation among the transfer rate, molecular state and molecular weight was analyzed with the densities of 1.05, 1.15, 1.25 g/mL of concentrated solution under the alcohol precipitation of 75% and 85%. Results The power function equation of molecular state quantitative calculation was set up successfully with the regression coefficients (R² > 0.99), as the density of intermediate in DI was 1.05—1.25 g/mL, the molecular proportions of sodium danshensu, protocatechuic aldehyde, rosmarinic acid and salvianolic acid B were 1.14%—5.25%, 66.70%—80.25%, 10.51%—19.11% and 1.13%—11.44%, respectively. The correlation analysis of “density- molecular state ratio- alcohol precipitation transfer rate” showed that alcohol precipitation concentration increased from 75% to 85%, and the decreasing rate of transfer rate was in the order of sodium danshensu > salvianolic acid B > rosmarinic acid > protocatechualdehyde. Therefore, the molecular state of phenolic acids was the main factor which affected the transfer rate of alcohol precipitation, and the relative molecular weight was correlated with the transfer rate. Conclusion The quantitative calculation method of molecular state was established for phenolic acids in the intermediate of DI, and the refining mechanism of alcohol precipitation was preliminarily expounded which was helpful for standardized control of preparation alcohol precipitation process.

国家自然科学基金资助项目(82274106);江苏省自然科学基金面上项目(BK20211303);江苏省333高层次人才培养工程;2021年度康缘中药学院创新创业项目(kyxysc06);2022年国家级大学生创新创业训练计划项目(103152022105)