• Clinical and Experimental Pediatrics
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• v.62 no.5
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• pp.155-161
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• 2019

Following the first successful trial of surfactant replacement therapy for preterm infants with respiratory distress syndrome (RDS) by Fujiwara in 1980, several animal-derived natural surfactants and synthetic surfactants have been developed. Synthetic surfactants were designed to overcome limitations of natural surfactants such as cost, immune reactions, and infections elicited by animal proteins contained in natural surfactants. However, first-generation synthetic surfactants that are protein-free have failed to prove their superiority over natural surfactants because they lack surfactant protein (SP). Lucinactant, a second-generation synthetic surfactant containing the SP-B analog, was better or at least as effective as the natural surfactant, suggesting that lucinactant could act an alternative to natural surfactants. Lucinactant was approved by the U. S. Food and Drug Administration in March 2012 as the fifth surfactant to treat neonatal RDS. CHF5633, a second-generation synthetic surfactant containing SP-B and SP-C analogs, was effective and safe in a human multicenter cohort study for preterm infants. Many comparative studies of natural surfactants used worldwide have reported different efficacies for different preparations. However, these differences are believed to due to site variations, not actual differences. The more important thing than the composition of the surfactant in improving outcome is the timing and mode of administration of the surfactant. Novel synthetic surfactants containing synthetic phospholipid incorporated with SP-B and SP-C analogs will potentially represent alternatives to natural surfactants in the future, while improvement of treatment modalities with less-invasive or noninvasive methods of surfactant administration will be the most important task to be resolved.

• Journal of the Korean Magnetic Resonance Society
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• v.5 no.1
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• pp.37-45
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• 2001

Synthetic pulmonary surfactants consisting of a mixture of phospholipids with synthetic peptides based on human surfactant-associated protein SP-B were prepared. These surfactants were analyzed f3r their secondary structures by circular dichroism (CD) spectroscopy and NMR spectroscopy. Two synthetic peptides (SP-B(3), SP-B(4)) combined with the phospholipid mixture displayed significant surfactant properties. The CD spectra showed that the u-helical propensities of the peptides in DPC micelles. In the NMR spectroscopy, the tertiary structures of SP-B(3) show that it has $\alpha$-helical structure from Gln5 to Arg13 in DPC micelle and SP-B(4) show that they have $\alpha$-helical structure from Gln5 to Leu12 in DPC micelle. Based on these structures, truncated peptides originated from SP-B protein, can be designed as effective synthetic surfactants for clinical use.

• Journal of Pharmaceutical Investigation
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• v.33 no.1
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• pp.29-36
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• 2003

Clenbuterol, a selective ${\beta}_2-adrenergic$ receptor stimulant, has been introduced as a potent bronchodilator for patients with bronchial asthma, chronic obstructive bronchial disease, chronic bronchitis and pulmonary emphysema. The percutaneous permeation of clenbuterol was investigated in hairless mouse skin after application of 50/50 buffer(pH 10)/propylene glycol solvent mixture. The enhancing effects of various penetration enhancers such as terpenes, non-ionic surfactants, pyrrolidones, fatty acids and some other enhancers on the permeation of clenbuterol were evaluated using Franz diffusion cell. Among terpenes studied, 1,8-cineole was the most effective enhancer, which increased the permeability of clenbuterol approximately 39.33-fold compared with the control without penetration enhancer, followed by menthone with enhancement ratio of 23.57. Nonionic surfactants did not have significant enhancing effects. N-Lauryl-2-pyrrolidone increased the permeability of clenbuterol approximately 4.51-fold compared with the control. Lauric acid increased the permeability of clenbuterol approximately 35.57-fold with decreasing the lag time from 2.64 to 0.52 hr. Oleic acid, linoleic acid, linolenic acid and capric acid showed enhancement ratio of 22.62, 19.60, 17.45 and 16.51, respectively. $Labrafil^{\circledR}$ enhanced the permeability of clenbuterol 9.24-fold compared with that without enhancer.

• Journal of Pharmaceutical Investigation
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• v.36 no.5
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• pp.321-329
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• 2006

Albuterol, a selective ${\beta}_2$-adrenergic receptor stimulant, has been introduced as a potent bronchodilator for patients with bronchial asthma, chronic obstructive bronchial disease, chronic bronchitis and pulmonary emphysema. The percutaneous permeation of albuterol sulfate was investigated in hairless mouse skin in vitro with and without pretreatment with enhancers. The enhancing effects of ethanol and various penetration enhancers such as terpenes, non-ionic surfactants, pyrrolidones, and fatty acids on the permeation of albuterol sulfate were evaluated using Franz diffusion cells. Among terpenes studied, 1,8-cineole was the most effective enhancer, which increased the permeability of albuterol sulfate approximately 33-fold compared with the control without enhancer pretrement, followed by d-limonene with enhancement ratio of 21.79. 2-Pyrrolidone-5-carboxylic acid increased the permeability of albuterol sulfate approximately 5.5-fold compared with the control. Other pyrrolidones tested showed only slight permeability enhancing effect with enhancement ratio less than 2.8. Nonionic surfactants showed moderate enhancing effects. Lauric acid increased the permeability of albuterol sulfate approximately 30-fold with decreasing the lag time from 2.85 to 0.64 hr. Oleic acid and linoleic acid showed enhancement ratio of 24.55 and 22.91, respectively. These findings would allow a more rational approach for designing formulations for the transdermal delivery of albuterol sulfate and similar drugs.

• Clinical and Experimental Pediatrics
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• v.61 no.10
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• pp.315-321
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• 2018

Purpose: To investigate the effectiveness of transient intubation for surfactant administration and extubated to nasal continuous positive pressure (INSURE) for treatment of respiratory distress syndrome (RDS) and to identify the factors associated with INSURE failure in extremely premature infants. Methods: Eighty-four infants with gestational age less than 28 weeks treated with surfactant administration for RDS for 8 years were included. Perinatal and neonatal characteristics were retrospectively reviewed, and major pulmonary outcomes such as duration of mechanical ventilation (MV) and bronchopulmonary dysplasia (BPD) plus death at 36-week postmenstrual age (PMA) were compared between INSURE (n=48) and prolonged MV groups (n=36). The factors associated with INSURE failure were determined. Results: Duration of MV and the occurrence of BPD at 36-week PMA were significantly lower in INSURE group than in prolonged MV group (P<0.05), but BPD plus death at 36-week PMA was not significantly different between the 2 groups. In a multivariate analysis, a reduced duration of MV was only significantly associated with INSURE (P=0.001). During the study period, duration of MV significantly decreased over time with an increasing rate of INSURE application (P<0.05), and BPD plus death at 36-week PMA also tended to decrease over time. A low arterial-alveolar oxygen tension ratio (a/APO2 ratio) was a significant predictor for INSURE failure (P=0.001). Conclusion: INSURE was the noninvasive ventilation strategy in the treatment of RDS to reduce MV duration in extremely premature infants with gestational age less than 28 weeks.

• Neonatal Medicine
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• v.18 no.2
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• pp.189-196
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• 2011

Purpose: Surfactants have been used to improve oxygenation for infants with meconium aspiration syndrome (MAS). We evaluated the change of pulmonary indices after surfactant therapy for MAS through a systematic meta-analysis. Methods: Relevant randomized controlled studies (RCTs) were identified by database searches in MEDLINE, EMBASE, and CENTRAL, up to June 2011, and by additional hand searches. Data were extracted regarding pulmonary indices, such as the oxygen index and arterial alveolar oxygen gradient. Meta-analyses were separately conducted for the studies of surfactant lavage therapy and surfactant bolus therapy. The risk of bias was assessed, and clinical as well as statistical heterogeneities were also investigated. Results: Two RCTs for bolus surfactant therapy and two RCTs for surfactant lavage therapy were identified. The oxygenation index results were heterogeneous between the two studies in which bolus surfactant therapy was given, while a/A $PO_2$ showed significantly better results in the treatment group over time after use of surfactant (12 hours: WMD 0.08, 95% CI 0.04-0.12; 24 hours: WMD 0.17, 95% CI 0.06-0.28). For surfactant lavage therapy, both studies consistently suggested an interventional benefit in terms of the pulmonary indices although it did not reach statistical significance. Conclusion: Surfactant therapy appeared to improve oxygenation of infants with MAS. Since a limited number of RCTs are available in the current literature and those studies were also clinically heterogeneous in terms of illness severity and the method of surfactant use, further research is needed to gather evidence to support surfactant therapy in MAS.

• Neonatal Medicine
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• v.15 no.2
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• pp.142-151
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• 2008

Purpose : The aim of this study was to compare the clinical effects of modified porcine (Curosurf$^{(R)}$) and bovine (Newfactan$^{(R)}$) surfactants in the treatment of neonatal respiratory distress syndrome. Methods : Between April 2004 and December 2006, 65 neonates (birth weight ${\leq}$2,500 g and gestational age ${\leq}$35 weeks) with neonatal respiratory distress syndrome were treated in our neonatal intensive care unit with surfactant. Thirty-one neonates received Curosurf$^{(R)}$ and 34 neonates received Newfactan$^{(R)}$. The neonates were not enrolled if they had major congenital anomalies or meconium aspiration syndrome. We compared the changes in respiratory parameters after surfactant instillation, the incidences of acute and chronic complications, and the mortality between the two treatment groups. Results : Neonatal and maternal demographic characteristics were not different between the groups. The patterns of change in the respiratory parameters after surfactant instillation were not statistically different between the groups. The incidences of surfactant reinstillation and acute complications, such as pneumothorax, patent ductus arteriosus, pulmonary hemorrhage, and grade 3-4 intraventricular hemorrhage, were not different between the neonates who received Curosurf$^{(R)}$ and the neonates who received Newfactan$^{(R)}$. There were no statistically significant differences in the duration of mechanical ventilation, oxygen therapy, hospitalization, prevalence of bronchopulmonary dysplasia, periventricular leukomalacia, retinopathy of prematurity, necrotizing enterocolitis, and mortality between the groups. Conclusion : In the present comparative study, no significant differences in the clinical effects of Curosurf$^{(R)}$ and Newfactan$^{(R)}$ were observed.