目的 对不同煎煮时间的百合地黄汤（Baihe Dihuang Decoction，BDD）的汤液进行相态拆分和表征，探究煎煮过程中的相态变化及成分分布规律，为阐明中药复方成分协同起效的物质基础提供参考。方法 分别煎煮BDD 20、40、60、80、100、120 min制得汤液，采用“高速离心-透析”法分离得到沉淀相态和纳米相态溶液；通过扫描电子显微镜、激光粒径仪、紫外-可见分光光谱及傅里叶变换红外光谱表征2种相态；采用HPLC法构建BDD及其不同相态的指纹图谱，并结合化学计量学方法筛选不同相态的关键差异成分，并对主要关键差异成分进行含量测定。结果 BDD纳米相态粒径最小，原药液粒径最大；纳米相态的粒径随着煎煮时间的延长先增加后减少并趋于稳定，且纳米相态稳定性逐渐增强。随着煎煮时间的延长，多糖、蛋白质含量逐渐增加，且纳米相态及沉淀相态中均含有大量多糖。光谱分析结果显示，不同煎煮时间的BDD原药液和各相态的化学成分结构大致相似，但官能团的含量存在差异；指纹图谱结合层次聚类分析（hierarchical cluster analysis，HCA）及偏最小二乘-判别分析（partial least squares-discriminant analysis，PLS-DA）结果显示，BDD及其不同相态化学成分种类相似，但含量存在显著区别，煎煮时间对成分的影响较相态更小，并筛选出12种不同相态的关键差异成分。5种指标成分梓醇、王百合苷C、王百合苷A、王百合苷B、异毛蕊花糖苷在纳米相态中的平均含量高于沉淀相态及原药液。结论 BDD在煎煮过程相互作用，使药效成分在各相态间的含量呈现较大差异，其中纳米相态实现了有效成分的富集，推测其可能为BDD的主要有效相态。

Objective To investigate the phase changes and component distribution patterns during the decoction process by performing phase separation and characterization of Baihe Dihuang Decoction (BDD, 百合地黄汤) at different decoction times, and provide a reference for elucidating the material basis of synergistic effects of components in traditional Chinese medicine formulas. Methods BDD was decocted for 20, 40, 60, 80, 100, and 120 min to obtain the decoctions. The sediment phase and nanophase solutions were separated using the “high-speed centrifugation-dialysis” method. The two phases were characterized by scanning electron microscope, laser particle size analyzer, ultraviolet-visible spectroscopy and Fourier transform infrared spectroscopy. The fingerprint spectra of BDD and its different phases were constructed using HPLC method, and chemometric methods were applied to screen key differential components among different phases, followed by content determination of the main differential components. Results The nanophase of BDD exhibited the smallest particle size, while the original decoction showed the largest particle size. The particle size of the nanophase initially increased and then decreased with prolonged decoction time, eventually stabilizing, and the stability of nanophase gradually enhanced. The contents of polysaccharides and proteins increased progressively with prolonged decoction time, and both the nano-sized fraction and the precipitated fraction were found to be rich in polysaccharides. Spectral analysis revealed that the chemical structures of components in the original decoction and each phase at different decoction times were generally similar, but differences in functional group contents were observed. Fingerprint analysis combined with hierarchical cluster analysis (HCA) and partial least squares-discriminant analysis (PLS-DA) showed that the types of chemical components in different phases of BDD were similar, but their contents differed significantly. The effect of decoction time on components was smaller than that of phase state. A total of 12 key differential components among different phases were screened. The average contents of five indicator components catalpol, regaloside C, regaloside A, regaloside B, isoverbascoside in the nanophase were higher than those in the sediment phase and the original decoction. Conclusion During the decoction process, BDD interacts with each other, resulting in significant differences in the content of active ingredients among various phases. The nanophase achieves enrichment of active components, suggesting that it may be the main effective phase of BDD.

R283.6

国家自然科学基金资助项目（82505002）；湖南省自然科学基金资助项目（2024JJ8151）；湖南省自然科学基金资助项目（2025JJ60642）；湖南省卫生健康高层次人才项目（湘卫函［2024］182号）