摘要
目的 研究淫羊藿治疗化疗致周围神经病变(chemotherapy-induced peripheral neuropathy,CIPN)的有效部位,并制备磷脂复合物以提高其渗透性,为制剂设计提供实验依据。方法 以复合率为评价指标,采用单因素试验结合Box-Behnken试验设计考察有效部位磷脂复合物的制备工艺,对磷脂复合物的形成进行表征,以朝藿定A、B、C及淫羊藿苷为评价指标测定其平衡溶解度与油水分配系数(lg P),并考察其体外释放行为。结果 确定磷脂复合物的最佳工艺条件为无水乙醇为反应溶剂,有效部位与大豆卵磷脂投料比为1∶2.7,药物质量浓度为13.5 mg/mL,反应温度为37℃,反应时间为2 h,复合率达到(96.21±0.22)%。紫外光谱、红外光谱、差示扫描量热分析表征验证了淫羊藿有效部位磷脂复合物的形成。有效部位通过磷脂复合物改性后,4种成分的溶解度提高2~3倍,lg P>1,药物的溶解性和渗透性得到显著提高。体外释放结果显示,4种成分的24 h体外累积释放率处于48%~74%,释放过程以一级动力学为主,释放机制为溶蚀和扩散的共同作用。结论 采用磷脂复合物技术对有效部位进行了改性,为淫羊藿治疗CIPN的进一步开发与利用奠定了基础。
Objective To study the effective parts of Epimedii Folium in the treatment of chemotherapy-induced peripheral neuropathy(CIPN), and prepare phospholipid complex to improve its permeability, so as to provide experimental basis for preparation design.Methods Taking the compound rate as evaluation index, the preparation process of phospholipid complex of effective parts was investigated by single factor test combined with box Behnken test design, and the formation of phospholipid complex was characterized. Taking epimedin A, B, C and icariin as evaluation indexes, its solubility and oil-water partition coefficient were measured, and its release behavior in vitro was investigated. Results The optimum conditions for the preparation of phospholipid complex were as follows: anhydrous ethanol was used as the reaction solvent, ratio of drug to soybean lecithin was 1:2.7, the drug concentration was 13.5 mg/mL, the reaction temperature was 37 ℃, the reaction time was 2 h, and the compound rate reached(96.21 ± 0.22)%. The formation of phospholipid complex in the effective parts of Epimedii Folium was verified by UV, IR and differential scanning calorimetry. After the effective parts were modified by phospholipid complex, the solubility of the four components was increased by about 2—3 times, lg P > 1, and the solubility and permeability of the drug were significantly improved.The results of in vitro release showed that the 24 h cumulative release rate of the four components was between 48% and 74%. The release process was dominated by first-order kinetics, and the release mechanism was the joint action of dissolution and diffusion.Conclusion The effective parts were modified by phospholipid complex technology, which laid a foundation for the further development and utilization of Epimedii Folium in the treatment of CIPN.
作者
梅凯
兰海
李鑫
李婷婷
郝逗逗
王灵敏
王昕怡
陈佳佳
刘葭
吴清
MEI Kai;LAN Hai;LI Xin;LI Ting-ting;HAO Dou-dou;WANG Ling-min;WANG Xin-yi;CHEN Jia-jia;LIUJia;WU Qing(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China)
出处
《中草药》
CAS
CSCD
北大核心
2022年第12期3662-3669,共8页
Chinese Traditional and Herbal Drugs
基金
北京市自然科学基金面上项目(7192109)。