[关键词]
[摘要]
目的 制备橙皮素与盐酸巴马汀共无定形（hesperetin and palmatine hydrochloride co-amorphous system，Hes-PH CAS），旨在开发橙皮素新固体形态、提高橙皮素溶解度和溶出度。方法 采用旋转蒸发法获得Hes-PH CAS，通过粉末X射线衍射仪、差示扫描量热仪、动态水蒸气吸附仪、固体核磁共振波谱仪等仪器分析技术对Hes-PH CAS的固态特性进行表征，并利用高效液相色谱仪考察其溶解度及溶出行为，并进一步通过自由基清除率、细胞增殖抑制率评估其抗氧化活性和抗肿瘤活性。结果 Hes-PH CAS具有单一玻璃化转变温度（glass transition temperature，Tg，104.5 ℃）及分子间氢键作用。该共无定形同时改变了橙皮素和盐酸巴马汀2种药物的溶解度和溶出行为，提高橙皮素的溶解度而降低盐酸巴马汀的溶解度，促进橙皮素的释放而延缓盐酸巴马汀的释放。抗氧化及抗肿瘤实验结果表明，Hes-PH CAS的自由基清除率和HT-29/HCT 116细胞增殖抑制率均高于原料药，而且共无定形中2种药物对自由基清除率、细胞增殖抑制率具有一定的增效作用。结论 所制备的Hes-PH CAS提高了橙皮素溶解度和溶出度，2种药物组分展现出更好的抗氧化和抗肿瘤作用。
[Key word]
[Abstract]
Objective Hesperetin and palmatine hydrochloride co-amorphous system (Hes-PH CAS) was prepared to develop new solid forms and improve the solubility and dissolution of hesperetin. Methods Hes-PH CAS was obtained via the rotary evaporation method. The solid-state characteristics were characterized by powder X-ray diffraction, differential scanning calorimetry, dynamic vapor sorption and solid-state nuclear magnetic resonance, respectively. The solubility and dissolution behavior were investigated by high-performance liquid chromatography. Furthermore, the antioxidant and antitumor activities were analyzed through radical scavenging assay and cell proliferation studies. Results Hes-PH CAS possessed a single glass transition temperature (Tg = 104.5 ℃) and exhibited intermolecular interactions. The co-amorphous simultaneously influenced the solubility and dissolution of both drugs, increasing hesperetin solubility while decreasing palmatine hydrochloride solubility, and promoting hesperetin release while delaying palmatine hydrochloride release. The antioxidant and anti-tumor results demonstrated that the free radical scavenging rate and HT-29/HCT 116 cell inhibition rate of Hes-PH CAS were higher than those of the individual raw materials, indicating a synergistic effect between the two drugs in terms of both free radical scavenging and cell inhibition. Conclusion The prepared Hes-PH CAS improved the solubility and dissolution of hesperetin, with two pharmaceutical components exhibiting good antioxidant and antitumor effects.
[中图分类号]
R283.6
[基金项目]
福州市科技计划项目(2024-SG-009); 闽江学院引进人才预研项目(MJY23007); 大学生创新训练项目(202410395034)
