目的 考察富马酸比索洛尔鼻喷剂及其附加剂对蟾蜍上颚纤毛运动的影响。方法 以生理盐水作为对照,10 mg/mL去氧胆酸钠溶液作为阳性对照,比较100 μL富马酸比索洛尔鼻喷剂、25 mg/mL富马酸比索洛尔溶液、5 mg/mL三氯叔丁醇溶液以及30 mg/mL 2,6-二甲基-β-环糊精(2,6-DM-β-CD)溶液对离体、在体蟾蜍上颚黏膜纤毛持续运动时间(LTCM),并观察组织形态的变化。结果 离体实验中对照组测得的LTCM为最大值,黏膜表面和纤毛清晰完整,纤毛运动活跃。25 mg/mL富马酸比索洛尔溶液、5 mg/mL三氯叔丁醇溶液和30 mg/mL 2,6-DM-β-CD溶液组黏膜纤毛持续摆动30～50 min后,以生理盐水冲洗后,则又很快恢复摆动,而且持续时间很长,且黏膜表面完整,未见纤毛脱落现象。在体实验中对照组黏膜表面完整,纤毛运动非常活跃,测得其LTCM为300 min,富马酸比索洛尔鼻喷剂组与对照组比较,差异无显著性。结论 富马酸比索洛尔鼻喷剂及其附加剂经鼻腔给药后对鼻黏膜纤毛的毒性较小且为短暂和可逆的,为今后研究该药物的鼻腔给药新制剂提供了重要参考。

Objective To investigate the effect of Bisoprolol Fumarate Nasal Spray and its formulation additives on the ciliary movement of toad palate. Methods Normal saline (0.9%) and 10 mg/mL sodium deoxyycholate solution were used as control and positive control, respectively. The lasting time of ciliary movement (LTCM) of 100 μL Bisoprolol Fumarate Nasal Spray, 25 mg/mL bisoprolol fumarate, 5 mg/mL chlorobutanol, and 30 mg/mL 2,6-DM-β-CD was compared in vitro and in vivo. Also the changes of toad palate models were observed. Results In vitro experiment results indicated that the LTCM of control group was the maximum, and the mucosal surface and the cilia were clear and complete, and the ciliary movement was active. LTCMs of 25 mg/mL bisoprolol fumarate, 5 mg/mL chlorobutanol, and 30 mg/mL 2,6-DM-β-CD group were 30-50 min, and had a longer swing time after washed with normal saline. The mucosal surface was complete with no cilia off phenomenon. In vivo experiment results indicated that the LTCM of control group was 300 min, and mucosal surface was complete, and cilia movement was very active. There were no significant differences between control group and Bisoprolol Fumarate Nasal Spray group. Conclusion Nasal cilitoxicity of Bisoprolol Fumarate Nasal Spray and its formulation additives after nasal administration is mild, transient, and reversible which can provide reference for studying a new nasal preparation of Bisoprolol Fumarate in future.

内蒙古医科大学附属医院科研基金项目(NYFYYB2010009)