探讨重组人干扰素(rhIFN)α2b与临床常用儿童雾化吸入药物配伍给药的可行性。

于2016年12月至2017年5月，选择临床常用的6种儿童雾化药物，即吸入用硫酸沙丁胺醇溶液、吸入用布地奈德混悬液、硫酸特布他林雾化液、吸入用异丙托溴铵溶液、注射用盐酸氨溴索和地塞米松磷酸钠注射液各1 mL，分别与1 mL rhIFNα2b注射液配伍后的混合溶液为研究对象，并将其分别纳入硫酸沙丁胺醇组、布地奈德组、硫酸特布他林组、异丙托溴铵组、盐酸氨溴索组和地塞米松磷酸钠组。同时，选择1 mL生理盐水与1 mL rhIFNα2b注射液配伍后的混合溶液作为对照组。观察7组混合溶液的外观，并进行pH值检测。采用人羊膜细胞Wish细胞株/水疱性口炎病毒(VSV)株微量病毒抑制法，对7组混合溶液雾化前及雾化后冷凝液的rhIFNα2b生物学活性进行检测，并进行统计学比较。通过比较rhIFNα2b、6种儿童雾化吸入药物及其混合溶液雾化后冷凝液的高效液相色谱法(HPLC)图谱，以分析rhIFNα2b与儿童雾化吸入药物配伍雾化后冷凝液中，是否存在新均质生成或原物质消失，同时采用HPLC检测7组混合溶液雾化后冷凝液中rhIFNα2b蛋白成分含量。

①7组混合溶液混合后0、30、60 min时，均未发现沉淀物、气泡和颜色改变，pH值基本保持恒定。②7组雾化前混合溶液、雾化后冷凝液中，rhIFNα2b生物学活性组内比较，差异均无统计学意义(P>0.05)；7组雾化前混合溶液、雾化后冷凝液中的rhIFNα2b生物活性，分别与对照组雾化前、后比较，差异亦均无统计学意义(P>0.05)。③HPLC检测结果显示，rhIFNα2b分别与吸入用硫酸沙丁胺醇溶液、吸入用布地奈德混悬液、硫酸特布他林雾化液、注射用盐酸氨溴索或地塞米松磷酸钠注射液配伍雾化后冷凝液中，均未发现新物质生成，并且rhIFNα2b和这5种儿童雾化吸入药物的分子结构，均未发生改变。rhIFNα2b与吸入用异丙托溴铵溶液配伍雾化后冷凝液的HPLC图谱中，rhIFNα2b和异丙托溴铵的HPLC图谱峰均消失，二者可能发生化学反应，生成新的物质。④与对照组混合溶液雾化后冷凝液的rhIFNα2b蛋白成分含量(90.1%)相比较，硫酸沙丁胺醇组和盐酸氨溴索组混合溶液雾化后冷凝液的rhIFNα2b蛋白成分含量增加(分别为94.5%、97.2%)，硫酸特布他林组与对照组基本一致(90.2%)，布地奈德组和地塞米松磷酸钠组降低(分别为72.9%、79.5%)。异丙托溴铵组混合溶液雾化后冷凝液中，rhIFNα2b及其异构体蛋白成分含量，均基本为0。

rhIFNα2b分别与吸入用硫酸沙丁胺醇溶液、吸入用布地奈德混悬液、硫酸特布他林雾化液、注射用盐酸氨溴索或地塞米松磷酸钠注射液配伍雾化后冷凝液中，药物结构均未发生改变，rhIFNα2b蛋白成分大部分保留；与吸入用异丙托溴铵溶液配伍雾化后冷凝液中，药物结构发生改变，rhIFNα2b蛋白成分基本消失。rhIFNα2b与上述药物配伍能否应用于临床，尚需相关药理和毒理动物试验和临床试验进一步研究、证实。

To explore whether human recombinant interferon (rhIFN) α2b can be compatible to common atomization inhalation drug for children in clinical practice.

From December 2016 to May 2017, six kinds of mixed solution of 1 mL six kinds of clinical atomization inhalation drugs for children, salbutamol sulfate solution for inhalation, budesonide suspension for inhalation, terbutaline sulphate solution for nebulization, ipratropium bromide solution for inhalation, ambroxol hydrochloride for injection, dexamethasone sodium phosphate injection, respectively and 1 mL rhIFNα2b injecta were chosen as the research subjects, and were included into salbutamol sulfate group, budesonide group, terbutaline sulfate group, ipratropium bromide group, ambroxol hydrochloride group and dexamethasone sodium phosphate group, respectively. At the same time, the mixed solution of 1 mL physiological saline solution and 1 mL rhIFNα2b injecta was chosen as control group. The appearance inspection and detection of the mixture pH value were carried out in 7 groups. The rhIFNα2b biological activities in the mixture before atomization and condensate after atomization of 7 group were detected by Wish/vesicular stomatitis virus (VSV) micro-virus inhibition method and were compared by statistical methods. By comparing the high performance liquid chromatography (HPLC) maps of rhIFNα2b, six kinds of atomization inhalation drugs for children and their condensate after atomization, to analyze whether new substance or loss of the original composition could be found or not after compatible atomization. At the same time, protein contents of rhIFNα2b in 7 groups were also determined after compatible atomization by HPLC.

①At 0, 30, 60 min after the mixture in 7 groups, color change, bubble and precipitation were not found in appearance inspection, and the pH value of mixture maintained nearly constant. ②Compared with the mixture before atomization, the biological activity of rhIFNα2b had no significant loss in the condensate after mixture atomization in every group (P>0.05). Compared with control group, the differences in the biological activity of rhIFNα2b in the mixture before atomization or in the condensate after atomization in 7 groups were not statistically significant (P>0.05). ③The results of HPLC showed that, none new substance were found in the condensate after the compatible atomization between rhIFNα2b and anyone of the five kinds of common atomization inhalation drugs, salbutamol sulfate solution for inhalation, budesonide suspension for inhalation, terbutaline sulphate solution for nebulization, ambroxol hydrochloride for injection and dexamethasone sodium phosphate injection. And it had no influence on the chemical structures of rhIFNα2b and those five kinds of common atomization inhalation drugs. But the rhIFNα2b and ipratropium bromide peaks all were disappeared in the HPLC map of collection solution after their compatible atomization. ④The protein contents of rhIFNα2b in the condensate after mixture atomization in salbutamol sulfate group and ambroxol hydrochloride group (94.5% and 97.2%, respectively) were more than that in control group (90.1%). The protein content of rhIFNα2b in the condensate after mixture atomization in terbutaline sulfate group (90.2%) was almost the same with that in control group. The protein contents of rhIFNα2b in the condensate after mixture atomization in the budesonide group and dexamethasone sodium phosphate group (72.9% and 79.5%, respectively) were less than that in control group. The protein contents of rhIFNα2b and its isomers were basically 0 in the condensate after mixture atomization in ipratropium bromide group.

After the atomization of rhIFNα2b with salbutamol sulfate solution for inhalation, budesonide suspension for inhalation, terbutaline sulphate solution for nebulization, ambroxol hydrochloride for injection and dexamethasone sodium phosphate injection, respectively, the molecular structure of rhIFNα2b and anyone of the aboved drugs are not changed, and the rhIFNα2b proteins are mostly retained in the condensate after atomization. But after the atomization of rhIFNα2b with ipratropium bromide solution for inhalation, their molecular structures are changed, and rhIFNα2b proteins almost disappear in the condensate after atomization. However, further studies on pharmacological and toxicological animal tests and clinical trials are required to confirm whether rhIFNα2b can be compatible to the aboved drugs and used in clinical practice.