中药挥发油对水蛭素经鼻给药的影响研究

Effects of Chinese Herbs′ Aetherolea on the Absorption of Hirudin Through Nasal Mucosa

目的以水蛭素为模型药物,探讨中药挥发油对蛋白/多肽类药经鼻黏膜吸收的影响,并考察中药挥发油的鼻纤毛毒性。方法用离体蟾蜍上颚黏膜模型,评价水蛭素及中药挥发油的鼻纤毛毒性;以同位素示踪法测定水蛭素,以离体猪鼻黏膜Valia-Chien水平扩散池法与在体大鼠鼻腔灌流实验,考察部分中药挥发油对水蛭素透鼻黏膜吸收的影响。结果离体实验结果表明,3%冰片和3%薄荷油对水蛭素鼻黏膜吸收促进作用较显著;在体实验结果表明,3%冰片和3%薄荷油组水蛭素的血药浓度显著高于阴性对照组,3%冰片和3%薄荷油组水蛭素的肾脏分布显著高于阴性对照组及其他实验组。纤毛毒性实验结果显示,中药挥发油对离体蟾蜍上颚黏膜纤毛影响由小到大的顺序为:1%冰片<1%薄荷油<3%冰片<1%石菖蒲油<1%细辛油<5%冰片<3%石菖蒲油<5%细辛油<5%薄荷油<5%石菖蒲油<3%细辛油<3%薄荷油。结论3%薄荷油和3%冰片对水蛭素透鼻黏膜吸收有较显著促进作用;中药挥发油对离体蟾蜍上颚黏膜纤毛均有不同程度的影响,但纤毛运动相对百分率大于60%,毒性较小。

OBJECTIVE To study the effects of Chinese herbs＇ aetheroleas on the absorption of protein/peptide drug through nasal mueosa and the nasal cilia toxicity of them taking natural hirudin as a model of protein/peptide drug. METHODS The nasal cilia toxicity of Chinese herbs＇ aetheroleas were evaluated by the Bufo palate ex vivo experiment, hirudin was marked and detected by isotope tracer method. The effects of Chinese herbs＇ aetheroleas on the absorption of protein/peptide drug through nasal mucosa were tested in the nasal mucosa of pig based on Valia-Chien infiltration pool in vitro and the perfusion experiments in rats in vivo. RESULTS 3% Borneo Camphor and 3% Peppermint had a significant enhancement on absorption of hirudin through nasal mucosa in vitro. 3% Borneo Camphor and 3% Peppermint had a significant enhancement on the plasma drug level and kidney drug level of hirudin in vito. Chinese herbs＇ aetheroleas showed somewhat effects on the continual moving time of cilia, and the effection array was sequenced as below： 1% Borneo Camphor 〈 1% Peppermint oil 〈 3 % Borneo Camphor 〈 1% Acori-Graminei oil 〈 1% Asarum oil 〈 5 % Borneo Camphor 〈 3 % Acori-Graminei oil 〈 5% Acori-Graminei oil 〈 5% Peppermint oil 〈 5% Acori-Graminei oil 〈 3% Asarum oil 〈 3% Peppermint oil. CONCLUSION 3% Borneo Camphor and 3% Peppermint oil has a significant enhancement on absorption of hirudin through nasal mucosa,and Chinese herbs＇ aetheroleas have different degrees effect on cilia of Bufo palate,relatively continual moving time of cilia are no less then 60%, indicate that the toxicity of them are at a low level.