目的 开发新的共晶以提高白藜芦醇的溶解度，进而为改善白藜芦醇生物利用度提供参考。方法 采用溶剂悬浮法制备了一种新的白藜芦醇-盐酸巴马汀共晶水合物（resveratrol-palmatine chloride cocrystal hydrate，RES-2PCl·H₂O），利用单晶X射线衍射、粉末X射线衍射和傅里叶变换红外光谱对其结构进行表征，并利用差示扫描量热、动态水蒸汽吸附、高效液相色谱分析等对共晶水合物的稳定性、溶解度及溶出速率等进行考察。结果 所制备的RES-2PCl·H₂O具有较高的纯度和均匀性，分子间存在较强的氢键作用，白藜芦醇、盐酸巴马汀及水分子通过O-H···O与O-H···Cl-的氢键作用形成一维链状结构，链与链间又通过C-H···O作用形成二维层状结构，层与层之间通过分子间弱作用力进而形成堆积结构。药物稳定性测试证实共晶水合物在高温、高湿或强光照射等长期储存条件下是物理稳定的。溶解性研究表明不溶性白藜芦醇与可溶性盐酸巴马汀共结晶影响了2种药物的溶解性能，且促进了白藜芦醇的释放同时延缓了盐酸巴马汀的释放。结论 制备并系统表征了一种新的RES-PCl共晶水合物，为利用共结晶技术开发白藜芦醇药物-药物共晶提供借鉴。

Objective To develop novel cocrystal to improve the solubility of resveratrol, and then provide reference for improving the bioavailability of resveratrol. Methods Resveratrol-palmatine chloride cocrystal hydrate (RES-2PCl·H₂O) was prepared by solvent suspension method. The structure was characterized by single crystal X-ray diffraction, powder X-ray diffraction and Fourier transform infrared spectroscopy. The stability, solubility and dissolution rate of cocrystal hydrate were investigated systematically by differential scanning calorimetry, dynamic water vapor adsorption and high performance liquid chromatography. Results The prepared RES-2PCl·H₂O has high purity and uniformity. In crystal structure of the cocrystal hydrate, there is strong hydrogen bonding between molecules. Resveratrol, palmatine hydrochloride and water molecules form one-dimensional chain structure through O-H···O and O-H···Cl^- hydrogen bonding, and two-dimensional layer structure is formed between chains through C-H·· O interaction, and stacking structure is formed between layers through intermolecular weak force. Pharmaceutical stability testing confirms the cocrystal hydrate is physically stable under long-term storage conditions such as high temperature, high humidity or strong light irradiation. Solubility studies show that cocrystallization between soluble palmatine hydrochloride and insoluble resveratrol compromises the dissolution properties of the two drugs. The release of resveratrol was improved while the release of palmatine hydrochloride was delayed. Conclusion A new kind of RES-PCl cocrystal hydrate is prepared and systematically characterized, which provides reference for the development of resveratrol drug-drug cocrystal by co-crystallization technology.

R283.6

福建省自然科学基金项目（2023J05245）；福建省中青年教师教育科研项目（JAT220328）