In vitro and in vivo comparison between poractant alfa and the new generation synthetic surfactant CHF5633
In vitro and in vivo comparison between poractant alfa and the new generation synthetic surfactant CHF5633
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DOI：
10.1038/pr.2016.231
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发表时间：
2017-02-01
影响因子：
3.6
通讯作者：
Salomone, Fabrizio
中科院分区：
文献类型：
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作者：
Ricci, Francesca;Murgia, Xabier;Salomone, Fabrizio
背景：CHF5633是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，研究了最佳剂量及其与动物源性表面活性剂α的性能比较。方法：采用威廉衡法和毛细管表面仪测定其体外表面活性剂活性。对表面活性剂严重缺乏的早产家兔进行了剂量测定研究。所使用的CHF5633剂量为50至300 mg/kg。将未处理的动物和饲喂200 mg/kg α α饲料的动物进行比较。结果：两种表面活性剂均使体外最小表面张力（γ (min)）从70以上降低到0 mN/m，并在气液界面迅速形成膜。体内研究显示，CHF5633对肺功能有明显的剂量依赖性改善。200 mg/kg剂量的CHF5633对早产家兔的肺效应与200 mg/kg的猪α α引起的肺反应相当。结论：CHF5633在体外和体内均具有与重要α - α相同的作用。CHF5633对肺功能的改善具有明显的剂量依赖性，其中200 mg/kg的剂量最有效。
BACKGROUND: 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.METHODS: 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.RESULTS: In vitro, minimum surface tension (gamma(min)) 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.CONCLUSION: 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.