论文部分内容阅读
目的:用环糊精改善鼻腔吸收促进剂去氧胆酸钠(SDC)的鼻纤毛毒性。方法:分别用红细胞溶血实验、蟾蜍上腭模型和扫描电镜观察环糊精对SDC细胞膜破坏作用和鼻纤毛毒性的影响。SDC和β-环糊精(β-CD)之间的包合作用采用差示热分析法和X-衍射法进行验证。结果:当SDC与β-CD或二甲基-β-环糊精(DM-β-CD)的摩尔比为1:1和1:2时能完全掩盖SDC的溶血作用。用蟾蜍上腭模型评价时,加入摩尔比1:2或1:3的SDC与β-CD或DM-β-CD的混合液使SDC的相对纤毛持续运动时间由原来的0％提高至50％以上。大鼠鼻腔连续给予1:2摩尔比的SDC-β-CD溶液一周后,扫描电镜显示粘膜纤毛无明显改变。差示热分析法和X-衍射结果显示SDC能与β-CD形成包合物。结论:加入β-CD或DM-β-CD能显著降低SDC的溶血作用和鼻纤毛毒性,两者的最佳比例是SDC与环糊精摩尔比1:2。环糊精的这种保护作用与形成包合物有关。
OBJECTIVE: To improve nasal cilia toxicity of sodium deoxycholate (SDC), a nasal absorption enhancer, with cyclodextrin. Methods: The erythrocyte hemolysis test, toad palate model and scanning electron microscopy were used to observe the effect of cyclodextrin on SDC cell membrane disruption and nasal cilia toxicity. Inclusion between SDC and β-cyclodextrin (β-CD) was verified by differential thermal analysis and X-ray diffraction. RESULTS: The hemolysis of SDC was completely masked when the molar ratio of SDC to β-CD or DM-β-CD was 1: 1 and 1: 2. Toad palate model evaluation, adding a mixture of SDC and β-CD or DM-β-CD with a molar ratio of 1: 2 or 1: 3 increased the relative ciliary sustained movement time of SDC from 0% to 50% the above. One week after the administration of 1: 2 molar ratio of SDC-β-CD solution to the nasal cavity of rat, scanning electron microscopy showed no significant change in mucociliary cilia. Differential thermal analysis and X-ray diffraction results show that SDC can form inclusion complex with β-CD. CONCLUSION: The addition of β-CD or DM-β-CD can significantly reduce the hemolysis and nasal cilia toxicity of SDC. The optimal ratio of SDC to cyclodextrin is 1: 2. This protective effect of cyclodextrins is related to the formation of inclusion complexes.