心血管疾病严重影响老年犬的健康和生活质量，川芎嗪为治疗心血管疾病的有效中药活性成分，共晶可增加其溶解度并提高生物利用度。但共晶药物的吸收途径及机制尚不明确，是该领域亟需解决的科学问题。本课题组前期工作表明，川芎嗪共晶因结构不同在溶解后会形成不同的分子聚集体和分子间作用力，从而影响药物吸收。基于此，本项目以四种川芎嗪共晶(共晶形成物结构类似，单晶结构截然不同)为模型药物，结合细胞生物学、分子生物学和微观形态学等知识，利用Caco-2细胞考察共晶药物的细胞摄取和跨细胞转运行为，利用Caco-2/HT29-MTX细胞共培养体系、大鼠肠黏液以及在体肠管分别在细胞、组织和动物水平考察其在黏膜的扩散行为，结合激光共聚焦显微镜和透射电子显微镜观察共晶药物通过细胞和黏液层的完整过程。本项目为明确共晶药物体内吸收途径及机制提供科学依据，为中药共晶的深入研究奠定基础，为难溶性中药活性成分的研发提供新思路。

Cardiovascular diseases seriously affect the health and life quality of elderly dogs. ligustrazine is an effective traditional Chinese medicine active ingredient for treating cardiovascular diseases. Co-crystals can increase ligustrazine solubility and increase its bioavailability. However, the absorption pathway and mechanism of co-crystal are still not clear, and this is a scientific problem urgently to be solved in this field. The previous work showed that due to the different structures of ligustrazine co-crystals, different molecular aggregates and intermolecular forces will be formed after dissolution, which will affect the drug absorption. Based on this, this project uses four ligustrazine co-crystals (the structures of co-crystal coformers are similar but the single crystal structures are completely different) as model drugs, combining with cytobiology, molecular biology and micromorphology, using Caco-2 cells to investigate the cell uptake and transcellular transport behavior of those co-crystal, using the Caco-2 / HT29-MTX cell co-culture system, rat intestinal mucus, and intestinal mucosa in vivo to investigate the diffusion behavior in mucus. Laser scanning confocal microscope and transmission electron microscopy were used to observe the complete process of co-crystal through cells and mucus layers. This project will clarify the in vivo absorption pathway and mechanism of co-crystal, promote the deep study of co-crystal of Chinese medicine, and provide new ideas for the research of insoluble active ingredients of Chinese medicine.