Development of a human lung surfactant, derived from extracted amniotic fluid.
Using a surfactant preparation of human origin for the treatment of the respiratory distress syndrome (RDS) instead of an animal-derived surfactant will minimize immunological problems. Therefore we isolated surfactant material from human amniotic fluid. Protein and phospholipid fractions of extracted human amniotic fluid (HAFS) were separated by Lipidex 5000 or acidulated LH20 liquid chromatography systems. Fractions of HAFS, the phospholipid or the recombined phospholipid-protein fractions, were tested in the 27-day fetal rabbit model. The results were compared with the results of the corresponding fractions of extracted ovine lung lavage (EOS) and of the already clinically tested surfactant Curosurf. The in situ surface activity of HAFS, EOS, and of their combined phospholipid + protein fractions (200 mg/kg body wt.) resulted in a lung compliance which was significantly higher than the control (saline) values. The compliances of HAFS, EOS, their combined fractions, and Curosurf were similar, but the lung stability values (V5) differed significantly among these surfactant extracts. The best V5 values (greater than or equal to 0.020 ml/g body wt.) were found after installing EOS or its LH20 phospholipid + protein fractions. HAFS had a poor stabilizing capacity which increased significantly after Lipidex chromatography and even more after enrichment of the Lipidex material with 10% palmitic acid. The Lipidex HAFS + 10% palmitic acid surfactant is at present the best obtainable human surfactant extract. Further development is in progress for the clinical application of this surfactant in preterm neonates.
Department of Obstetrics and Gynaecology, Leiden University Medical Centre, The Netherlands.
G C
GC
Gorree
J
J
Egberts
G C
GC
Bakker
A
A
Beintema
M A
MA
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D000653:Amniotic Fluid / Q000737:chemistry*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002853:Chromatography, Liquid; D005865:Gestational Age; D006801:Humans; D008168:Lung / Q000254:growth & development / Q000502:physiology; D008170:Lung Compliance; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000494:pharmacology; D011663:Pulmonary Surfactants / Q000302:isolation & purification / Q000494:pharmacology*; D011817:Rabbits; D012756:Sheep
D010169:Palmitic Acids; D011663:Pulmonary Surfactants; D019308:Palmitic Acid