Ricci Francesca, Murgia Xabier, Razzetti Roberta, Pelizzi Nicola, Salomone Fabrizio
R&D Department, Chiesi Farmaceutici, Parma, Italy.
Department of Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland, Saarbrücken, Germany.
Pediatr Res. 2017 Feb;81(2):369-375. doi: 10.1038/pr.2016.231. Epub 2016 Nov 3.
CHF5633 is a new generation synthetic surfactant containing both SP-B and SP-C analogues developed for the treatment of respiratory distress syndrome. Here, the optimal dose and its performance in comparison to the animal-derived surfactant poractant alfa were investigated.
In vitro surfactant activity was determined by means of the Wilhelmy balance and the capillary surfactometer. The dose-finding study was performed in preterm rabbits with severe surfactant deficiency. CHF5633 doses ranging from 50 to 300 mg/kg were used. Untreated animals and animals treated with 200 mg/kg of poractant alfa were included for comparison.
In vitro, minimum surface tension (γ) was decreased from values above 70 to 0 mN/m by both surfactants, and they formed rapidly a film at the air-liquid interface. In vivo studies showed a clear dose-dependent improvement of lung function for CHF5633. The pulmonary effect of CHF5633 200 mg/kg dose was comparable to the pulmonary response elicited by 200 mg/kg of poractant alfa in preterm rabbits.
CHF5633 is as efficient as poractant alfa in our in vitro and in vivo settings. A clear dose-dependent improvement of lung function could be observed for CHF5633, with the dose of 200 mg/kg being the most efficient one.
CHF5633是一种新一代合成表面活性剂，含有SP - B和SP - C类似物，用于治疗呼吸窘迫综合征。在此，研究了其最佳剂量及其与动物源性表面活性剂猪肺磷脂相比的性能。
通过Wilhelmy天平法和毛细管表面张力仪测定体外表面活性剂活性。在严重表面活性剂缺乏的早产兔中进行剂量探索研究。使用的CHF5633剂量范围为50至300mg/kg。纳入未治疗的动物以及用200mg/kg猪肺磷脂治疗的动物作为对照。
在体外，两种表面活性剂均将最小表面张力（γ）从70mN/m以上的值降低至0mN/m，并且它们在气液界面迅速形成一层膜。体内研究表明CHF5633对肺功能有明显的剂量依赖性改善。在早产兔中，200mg/kg剂量的CHF5633的肺部效应与200mg/kg猪肺磷脂引起的肺部反应相当。
在我们的体外和体内实验中，CHF5633与猪肺磷脂一样有效。CHF5633可观察到明显的剂量依赖性肺功能改善，200mg/kg剂量最为有效。
