• Clinical and Experimental Pediatrics
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• 제62권5호
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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.

• 한국자기공명학회논문지
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• 제5권1호
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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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• 제33권1호
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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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• 제36권5호
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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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• 제61권10호
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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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• 제18권2호
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• pp.189-196
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• 2011

목적: 최근 폐표면활성제는 태변흡인증후군 환자에서 호흡곤란을 호전시키기 위한 치료 중 하나로 사용되고 있다. 본 연구에서는 태변흡인증후군에서 폐표면활성제가 치료결과로서 호흡기지표에 미치는 영향을 살펴보았다. 방법: MEDLINE, EMBASE, CENTRAL 등의 주요 데이터베이스 및 초록 등을 검색하여 2011년 6월까지 보고된 관련 무작위 배정연구를 선별하였다. OI 또는 a/A $PO_2$와 같은 호흡기 지표를 포함한 자료를 추출하여 폐표면활성제 보충요법과 폐표면활성제 세정요법 각각에 대해 메타분석을 수행하였다. 비뚤림 위험 및 임상적, 통계적 이질성을 평가하였다. 결과: 두 건의 폐표면활성제 보충요법 연구와 두 건의 폐표면 활성제 세정요법 연구가 분석에 포함되었다. 폐표면활성제 보충요법의 경우 OI에서는 두 연구 결과 사이의 이질성이 큰 반면, a/A $PO_2$에서는 보충요법 후 시간이 경과할 수록 군 간의 차이가 유의하게 나타났다(12시간째 WMD 0.08, 95% CI 0.04, 0.12; 24시간째 WMD 0.17, 95% CI 0.06, 0.28). 폐표면활성제 세정요법의 경우 통합하여 분석하였을 때 치료군이 대조군에 비해 임상 경과가 좋은 경향을 보였으나 통계적인 유의성은 확보하지는 못하였다. 결론: 태변흡인증후군에서 폐표면활성제 사용은 임상경과를 호전시키는 것으로 보인다. 기존의 연구수가 제한되어 있고 대상환자의 중증도 및 폐표면활성제 투여방법 또한 서로 다르므로 추가적인 연구를 통한 보충적인 근거가 도움이 될 것이다.

• Neonatal Medicine
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• 제15권2호
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• pp.142-151
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• 2008

목 적 : 신생아 호흡 곤란 증후군의 치료에 우리나라에서 널리 사용되고 있는 국내 제제인 Newfactan$^{(R)}$은 Surfacten$^{(R)}$과의 비교연구는 있었지만 다른 제제와의 비교연구는 그 동안 이루어지지 않았다. 이에 본 연구는 유럽에서 널리 사용되고 있는 돼지 폐에서 추출된 modified natural surfactants인 Curosurf$^{(R)}$와 Newfactan$^{(R)}$과의 치료효과를 비교하고자 본 연구를 실시 하게 되었다. 방 법 : 2004년 4월부터 2006년 12월까지 신생아 중환자실에 신생아 호흡 곤란 증후군으로 진단되어 폐 표면 활성제를 투여받았고 출생체중이 2,500 g 이하이면서 재태연령이 35주 이하인 신생아 중 주요 선천성 기형과 태변흡입 증후군이 있었던 경우를 제외한 65명을 대상으로 하였고 이들을 Curosurf$^{(R)}$를 투여 받은 군 31명과 Newfactan $^{(R)}$을 투여 받은 군 34명으로 나누어 두 제제를 사용한 환아들의 임상적 특성과 초기 투여 반응, 합병증을 의무기록을 토대로 분석하여 비교하였다. 결 과 : Curosurf$^{(R)}$ 투여군과 Newfactan$^{(R)}$ 투여군 사이에 출생체중, 재태 기간, 산모의 병력상 특징에서 두 군간에 차이는 없었고, 폐 표면활성제 투여 후의 호흡지표의 변화에서 두 군 모두 투여 2시간 후부터 의미 있는 호흡지표의 개선을 보였으나 두 군간에는 차이가 없었고, 폐 표면활성제를 재투여한 빈도와 입원기간 중에 사망률도 두 군 사이에 차이가 없었다. 장기 치료효과인 인공호흡기 사용기간, 산소 투여기간, 퇴원당시의 나이를 비교해 봤을 때 산소 투여기간이 Newfactan$^{(R)}$ 투여군에서 31.3${\pm}$21.2일, Curosurf$^{(R)}$ 투여군에서 24.6${\pm}$26.2일로 Newfactan$^{(R)}$ 투여군에서 산소 투여기간이 더 길었지만 통계적으로 유의하지는 않았다. 기흉, 폐출혈, 동맥관 개존, 뇌실내 출혈 등의 급성기 합병증은 두 군간에 차이가 없었으며, 기관지 폐 형성이상의 빈도는 Newfactan$^{(R)}$ 투여군이 35.5%, Curosurf$^{(R)}$ 투여군이 26.9%로 Newfactan $^{(R)}$ 투여군에서 약간 더 높은 경향을 나타내었지만 통계적으로 의미있는 차이는 아니었다. 미숙아 망막증, 뇌실주위 연화증, 괴사성 장염등의 장기 합병증의 발생에서도 두 군 사이에 의미있는 차이는 없었다. 결 론 : Newfactan$^{(R)}$ 과 Curosurf$^{(R)}$ 두 제제의 투여 후의 초기 치료반응 및 장기 투여효과, 급만성 합병증의 발생빈도에 있어서 유의한 차이를 보이지 않았다.