应用中药物质组释放动力学理论研究银翘解毒丸的缓释动力学及其同步性

Application of the theories of materiomic release kinetics to the evaluation of the sustained release kinetics and synchronicity of Yinqiaojiedu honeyed pills

将银翘解毒丸切割成1/4、1/8、1/12和1/16的等分块状颗粒,采用桨法装置,在100 r.min-1下测定其释放度,以紫外吸收光谱法结合Kalman滤波法对银翘解毒丸物质组进行定量,分别测定整丸及其等剂量按不同切割方式获得的等分块状颗粒的释放度,获得银翘解毒丸的物质组释放动力学特征。实验结果显示银翘解毒丸具有明显的缓释特征,在充分切割时也维持释放达2～4 h;银翘解毒丸的释放速率与切割方式呈现明显的相关性,物质组释放度曲线的Weibull分布参数Td和T50随着丸剂切割程度的增加而减小,提示大蜜丸的服用方式可能影响其体内药代动力学特征;整丸和等分切割块状颗粒的物质组释放同步性有明显差异,整丸的释放同步性特征明显高于切割后颗粒的释放同步性。本文以物质组释放动力学定量地刻画了传统剂型大蜜丸剂的缓释特征,从释放动力学角度阐释了＂丸者缓也＂的科学内涵;以取样间隔释放的物质组特征增量等参数为指标,可视化地评价了中药物质组释放同步性特征。中药物质组释放/溶出动力学理论为传统剂型的评价和给药系统设计提供了释放动力学的方法学基础。

Yinqiaojiedu honeyed pills were equally divided into 1/4, 1.8, 1/12, and 1/16 parts. The materiomics release rates within 12 h of the intact Yinqiaojiedu honeyed pills and the divided granules were determined by the paddle method with a rotate speed at 100 r · min^-1 and the materiome was quantified by UV-scan and Kalman filter methods. The intact Yinqiaojiedu honeyed pills behaved typical sustained release profiles, while the well-divided portions also maintained a sustained release profile over 2 -4 h. The release rates were well correlated with the extents for the divisions of the pills. The Weibull distribution parameters, Td and T50, were reduced in line with the particle size, indicating that the ways of administration of the pills may play a role in the in vivo pharmacokinetics of the pills. The visualization results showed obvious difference of materiomic release synchronicities between the intact pills and the equally divided particles, and the divisions enhanced the asynchronization. Therefore the novel theory of materiomic release/dissolution kinetics of traditional Chinese medicines （TCMs） quantitatively proved the traditional dosage form, namely, honeyed pills, as a prototype of the sustained-release dosage form with a visualization of the scientific connotation to the old saying in the classics of TCM, Pills, the moderate ones in action （丸者缓也）. In terms of materiome increase for each period of the release profiles, the materiomic release synchronicity was visually demonstrated. The novel theories provided methodological basis for the evaluation of traditional dosage forms and the design of the modern drug delivery systems for TCMs.