Study on atomization compatibility between recombinant human interferon alpha 2b and atomization inhalation drugs for children

Abstract

Objective To explore whether human recombinant interferon (rhIFN) α2b can be compatible to common atomization inhalation drug for children in clinical practice. Methods 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. Results 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. Conclusions 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. Key words: Recombinant human interferon alpha 2b; Atomization inhalation drugs for children; Compatibility of drugs; Atomization; Child