DEVELOPMENT OF CALSURF: FIRST APPROVAL CHINESE
SURFACTAT FOR TREATMENT OF RDS
Dong SH1, Sun MY2, Yu HM2
1 Capital Institute of Pediatrics,
Beijing, China
2 Affiliated Children’s Hospital*
of Zhejiang University, Hangzhou, China
Preclinical Study: Calsurf was prepared from lung
lavage fluid of calf after high speed centrifugation and organic solvent
extraction by Beijing Double Crane Pharma. Calsurf contained 84.5%of total
phospholipid , phophatidylcholine accounted 75.6% of it, protein was 1.3%. The
minimum surface tension was 0.83 mN/M. In premature rabbits, after Calsurf
instillation, P-V curve and histological lung expansion improved
significantly. In lung lavaged rabbits during 3 hours period blood gases
and lung compliance were significantly better than controls. Safety tests
showed Calsurf was free from microorganisms and pyrogen. Toxicology study
showed it is acceptable for clinical use, but phargocyte granuloma can be
caused in lung with more dosis. Multicenter trial: 105 severe RDS infants
were randomly assigned to surfactant therapy (57 cases, mean B.W. 1850 g)
or control group (48 cases, mean B.W. 1900 g). 70mg/Kg Calsurf was
instilled into trachea at 14 hr of mean age in surfactant group. 4 cases
got second dose. At 0,8, 24 ,48, and 72 hr after treatment, the mean value
of a/A, MAP and FiO2 were all lower in
surfactant group. More infants in surfactant group required shorter time
for ventilator treatment, oxygen therapy and hospitalization. The incidence
(%) of complication in surfactant/control group were: IVH 17.5/19.1,
PDA7.9/27.1, barotrauma10.7/14.9, sepsis3.6/6.3, pulmonary haemorrhage
5.2/10.6 and mortality 5.4/8.5 respectively.
Head of
Collaborative Multicenter Study Group. Participants: Li KH3, Guo
J4, Xu YM5, Zhang YM6, Liu CQ7
and Chen KZ8 from Children’s Hospital of Beijing3,
Tianjin4, Nanjing5, Shanghai6, Hebei
Province7 Guangzhou8