摘要
该文设计了利用纳滤传质模型定量计算迷迭香酸分子状态的教学实验.实验以丹参中代表性的酚酸为研究对象,计算了迷迭香酸的纳滤膜通量、传质系数和截留率,构建了迷迭香酸分子态比例定量计算数学模型,对制药过程中的醇沉、树脂吸附、澄清过滤、浓缩、干燥等工艺的转移率和成分存在状态进行了相关性分析,研究了制药工艺成分量值传递的内在机制.实验结果表明,迷迭香酸存在状态对制药工艺中的成分转移率有重要影响.这一结论对提升生产过程的规范化和标准化很有意义.本实验与制药生产热点问题相结合,通过科研反哺教学,有助于增强学生的科研素养和实践能力,并实现科研应用与教学拓展的协同提升.
Abstract
[Objective]The pharmaceutical process's component transmission behavior is determined by its molecular state.Currently,infrared spectroscopy,nuclear magnetic resonance,differential thermal analysis,high-resolution scanning electron microscopy,and other techniques are used to analyze the molecular state of pharmacological components.Nevertheless,to apply the aforementioned technologies,the components must be isolated from the original solution.Using the detection principle,a qualitative analysis of the component status can be produced,but the precise ratio of ionic,molecular,and other states cannot be determined.In this work,a teaching experiment was designed for the quantitative calculation of the molecular state of rosmarinic acid using a nanofiltration mass transfer model.[Methods]Using the theory that"nanofiltration mass transfer coefficient can represent the difficulty of components passing through nanofiltration membrane pores,and is a manifestation of comprehensive separation of multiple states of existence,"this study developed an experimental teaching program based on the nanofiltration mass transfer model for the quantitative analysis of drug ingredient molecular states.Given that rosmarinic acid has a pKa of 4.01,a 5％hydrochloric acid solution was used,and the mass concentration was adjusted to 0.210 mg/mL.The pH of the rosmarinic acid monomer component solution was 2.01,implying that 99％of the molecular state of rosmarinic acid was present.The rosmarinic acid solution was put in the liquid storage tank,and the system pressures of the nanofiltration apparatus were changed to 0.6,0.8,1.0,1.2,and 1.4 MPa,respectively.The nanofiltration liquid and membrane flux(Jv)were then collected at an appropriate pressure.Using high-performance liquid chromatography,the rosmarinic acid solution and filtrate were identified,and the retention rate(R)was computed.The linear equation of ln[(l-R)Jv/R]and the nanofiltration mass transfer coefficient of rosmarinic acid(k)were fitted using the correlation among k and R and Jv.Subsequently,the power function equations for k and rosmarinic acid concentration(C)were fitted,and the extracted liquid of Salvia miltiorrhiza was separated using nanofiltration,with the proportion of rosmarinic acid molecular states determined using the power function equations of the concentration and mass transfer coefficient of this monomeric component.Furthermore,the relationship between the transfer rate and the component molecular states during the alcohol precipitation,resin adsorption,clarity filtration,concentration,and drying processes was investigated.[Results]Rosmarinic acid had a molecular proportion of 33.62％in Salvia miltiorrhiza extract.Rosmarinic acid's solubility in ethanol solution fell as its molecular proportion dropped,and it was easily adsorbed by polysaccharide,protein,and colloid components during alcohol precipitation,resulting in a decrease in alcohol precipitation transfer rate.Rosmarinic acid was difficult to adsorb on the surface of the macroporous resin,and the transfer rate increased as the aqueous solution flowed out.Rosmarinic acid had a substantial interfacial adsorption impact on the surface of the microfiltration membrane,leading to component loss.The results showed that the existence of rosmarinic acid had a significant effect on the component transfer rate in the pharmaceutical process,which aided in the standardization of the manufacturing process.[Conclusions]This experiment combined important pharmaceutical issues with scientific research to feed teaching,develop students'scientific research literacy and practical ability,and realize the collaborative improvement of scientific research application and teaching expansion.
基金项目
全国中医药高等教育规划教育科研课题(十四五)(2023)(YB-23-36)
江苏省高等教育质量保障与评价研究课题(2021-Y19)
江苏省教育科学规划课题青年专项(十四五)(C/2023/01/91)
全国中医药研究生教育研究课题(YJS-YB-2023-06)
维普
万方数据