Zhu Bingqing, Ding Zhenfeng, Rong Xiaoyi, Li Shengqiang, Mei Xuefeng
Pharmaceutical Analytical & Solid-State Chemistry Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
Pharmaceuticals (Basel). 2025 Jan 13;18(1):90. doi: 10.3390/ph18010090.
Silymarin, an extract from milk thistle, is widely recognized for its therapeutic potential in treating liver disorders. However, its clinical utility is limited by the poor solubility and low bioavailability of its key active ingredient, Silybin. In this study, we sought to address this issue through the development of a novel cocrystal of Silyin. Silybin-L-proline cocrystal was synthesized and the physicochemical properties of the cocrystal were characterized by PXRD, TGA, DSC, and FTIR. Dissolution tests were conducted in various pH solutions, and the impact of precipitation inhibitors was evaluated. Furthermore, pharmacokinetic study in rats were performed to assess the bioavailability. The dissolution studies demonstrated that the cocrystal has a significant improvement in dissolution performance, particularly in acidic environments. Furthermore, the use of precipitation inhibitors, such as PVP, prolonged the supersaturation period for adequate absorption. Pharmacokinetic studies in rats revealed that the cocrystal exhibited a 16-fold increase in bioavailability compared to the raw Silybin extract, outperforming the commercial Silybin-phosphatidylcholine complex. The Silybin-L-proline cocrystal significantly enhances dissolution and bioavailability, indicating its potential to improve the therapeutic efficacy of Silybin in clinical applications.
水飞蓟素是从水飞蓟中提取的一种物质，因其在治疗肝脏疾病方面的治疗潜力而被广泛认可。然而，其关键活性成分水飞蓟宾的溶解度差和生物利用度低限制了它的临床应用。在本研究中，我们试图通过开发一种新型的水飞蓟宾共晶体来解决这个问题。合成了水飞蓟宾-L-脯氨酸共晶体，并通过粉末X射线衍射（PXRD）、热重分析（TGA）、差示扫描量热法（DSC）和傅里叶变换红外光谱（FTIR）对共晶体的物理化学性质进行了表征。在不同pH值的溶液中进行了溶出试验，并评估了沉淀抑制剂的影响。此外，还对大鼠进行了药代动力学研究以评估生物利用度。溶出研究表明，该共晶体的溶出性能有显著改善，尤其是在酸性环境中。此外，使用沉淀抑制剂（如聚乙烯吡咯烷酮（PVP））可延长过饱和期以实现充分吸收。大鼠药代动力学研究表明，与水飞蓟宾粗提取物相比，该共晶体的生物利用度提高了16倍，优于市售的水飞蓟宾-磷脂酰胆碱复合物。水飞蓟宾-L-脯氨酸共晶体显著提高了溶出度和生物利用度，表明其在临床应用中具有提高水飞蓟宾治疗效果的潜力。
