目的 考察富馬酸比索洛爾鼻噴劑及其附加劑對(duì)蟾蜍上顎纖毛運(yùn)動(dòng)的影響。方法 以生理鹽水作為對(duì)照,10 mg/mL去氧膽酸鈉溶液作為陽(yáng)性對(duì)照,比較100 μL富馬酸比索洛爾鼻噴劑、25 mg/mL富馬酸比索洛爾溶液、5 mg/mL三氯叔丁醇溶液以及30 mg/mL 2,6-二甲基-β-環(huán)糊精(2,6-DM-β-CD)溶液對(duì)離體、在體蟾蜍上顎黏膜纖毛持續(xù)運(yùn)動(dòng)時(shí)間(LTCM),并觀察組織形態(tài)的變化。結(jié)果 離體實(shí)驗(yàn)中對(duì)照組測(cè)得的LTCM為最大值,黏膜表面和纖毛清晰完整,纖毛運(yùn)動(dòng)活躍。25 mg/mL富馬酸比索洛爾溶液、5 mg/mL三氯叔丁醇溶液和30 mg/mL 2,6-DM-β-CD溶液組黏膜纖毛持續(xù)擺動(dòng)30～50 min后,以生理鹽水沖洗后,則又很快恢復(fù)擺動(dòng),而且持續(xù)時(shí)間很長(zhǎng),且黏膜表面完整,未見(jiàn)纖毛脫落現(xiàn)象。在體實(shí)驗(yàn)中對(duì)照組黏膜表面完整,纖毛運(yùn)動(dòng)非常活躍,測(cè)得其LTCM為300 min,富馬酸比索洛爾鼻噴劑組與對(duì)照組比較,差異無(wú)顯著性。結(jié)論 富馬酸比索洛爾鼻噴劑及其附加劑經(jīng)鼻腔給藥后對(duì)鼻黏膜纖毛的毒性較小且為短暫和可逆的,為今后研究該藥物的鼻腔給藥新制劑提供了重要參考。

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.

內(nèi)蒙古醫(yī)科大學(xué)附屬醫(yī)院科研基金項(xiàng)目(NYFYYB2010009)