目的 制备黄芩素（BE）-槐定碱（SR）共无定形体系（BE-SR CM），系统评估该体系改善BE表观溶解度及物理稳定性的效能，并探究其体外抑菌活性。方法 采用旋转蒸发法制备物质的量比为1∶1、2∶1、3∶1的BE-SR CM；结合X射线粉末衍射（XRPD）、差示扫描量热（DSC）、偏光显微镜（POM）、傅里叶变换红外光谱（FT-IR）等固态表征技术验证体系制备效果；运用分子动力学模拟技术分析不同比例共无定形体系中分子间相互作用模式及关键作用位点；通过表观溶解度测定、物理稳定性考察及体外抑菌实验，明确最优物质的量比的BE-SR CM。结果 固态表征结果证实，旋转蒸发法可成功制备均一稳定的BE-SR CM，分子动力学模拟进一步揭示体系中BE与SR分子间存在显著氢键相互作用；表观溶解度测定表明，BE-SR CM在pH 6.8、7.4缓冲液中的溶解度显著优于BE及BE与SR的物理混合物，pH 6.8缓冲液BE-SR CM（1∶1）的溶解度较BE原料药提升8.9倍；所有BE-SR CM在25℃、60%相对湿度条件下储存9个月后均无结晶析出，表现出优异的物理稳定性；体外抑菌实验证实，BE-SR CM的抑菌活性显著优于BE与SR物理混合物及单一药物，其中BESR CM（1∶1、3∶1）抑菌效果尤为突出，对耐甲氧西林金黄色葡萄球菌（MRSA）的最小抑菌浓度（MIC）均为16μg·mL^-1，显著优于BE单独用药组(MIC=32μg·mL^-1)。结论 BE-SR CM（1∶1）可显著提升BE的表观溶解度，兼具优异的物理稳定性，且能有效增强其对MRSA的抑菌活性，是改善BE制剂学性能的理想载体形式。

Objective To prepare the co-amorphous system of baicalein（BE） and sophoridine（SR）（BE-SR CM）, systematically evaluate its efficacy in improving the apparent solubility and physical stability of BE, and explore its antibacterial activity in vitro. Methods BE-SR CM with molar ratios of 1∶1, 2∶1, and 3∶1 were prepared by rotary evaporation. The preparation effect was verified by solid-state characterization techniques such as X-ray powder diffraction（XRPD）, differential scanning calorimetry（DSC）, polarizing microscopy（POM）, and Fourier transform infrared spectroscopy（FT-IR）. Molecular dynamics simulation was used to analyze the intermolecular interaction patterns and key interaction sites in the co-amorphous systems with different molar ratios. The optimal molar ratio of BE-SR CM was determined through apparent solubility measurement, physical stability assessment, and in vitro antibacterial experiments. Results Solid-state characterization results confirmed that the rotary evaporation method could successfully prepare uniform and stable BE-SR CM. Molecular dynamics simulation further revealed significant hydrogen bond interactions between BE and SR molecules in the system. Apparent solubility measurement indicated that the solubility of BE-SR CM in pH 6.8 and 7.4 buffer solutions was significantly higher than that of BE and BE-SR physical mixtures. The solubility of BE-SR CM（1∶1） in pH 6.8 buffer solution was 8.9 times higher than that of BE. All BE-SR CM showed no crystallization after storage at 25 ℃and 60% relative humidity for nine months, demonstrating excellent physical stability. In vitro antibacterial experiments confirmed that the antibacterial activity of BE-SR CM is significantly superior to that of the physical mixture of BE and SR as well as the single drugs. Among them, BE-SR CM（1∶1 and 3∶1） had particularly outstanding antibacterial effects, with a minimum inhibitory concentration（MIC） of 16 μg·mL^-1 against methicillin-resistant Staphylococcus aureus（MRSA）, which was significantly better than the BE monotherapy group(MIC = 32 μg·mL^-1). Conclusion BE-SR CM（1∶1） can significantly improve the apparent solubility of BE, has excellent physical stability, and can effectively enhance its antibacterial activity against MRSA. It is an ideal carrier form for improving the formulation properties of BE.

R285.5

湖北省科技厅自然科学基金面上项目(2023AFB964); 湖北省自然科学基金中医药创新发展联合基金项目(2023AFD153); 湖北省技术创新计划重大项目(2024BCA002)