Development of a novel SP-B peptide lung surfactant

描述（由申请人提供）：该竞争性更新SBIR提案扩展了我们目前对新型合成脂质/肽肺表面活性剂的II期转化研究，该新型合成脂质/肽肺表面活性剂含有高度活性的Super Mini-B（S-MB）肽，该肽结合了人表面活性蛋白（SP）-B（生物表面活性剂中最具活性的载脂蛋白）的关键功能区域。我们最初的第二阶段资助主要集中在通过固态化学合成的S-MB上，并记录了含有固态S-MB与脂质结合的合成Minisurf表面活性剂的高活性。此次更新申请延续了Minisurf表面活性剂的商业开发。本提案将扩大S-MB肽和Minisurf”表面活性剂产品的生产规模，开发用于分析S-MB肽和Minisurf”表面活性剂产品的有效QA/QC方法，并证明与实验室研究规模批次的Minisurf”表面活性剂的生物等效性。将生产和检测Minisurf表面活性剂产品的中试批次，以确保工艺耐用、分析控制适当并保持有效性。选定的Minisurf表面活性剂中试批次的样品将进行稳定性研究，并发送给承包商进行符合GLP的药理学和毒理学研究。该提案还规定在授予期间与FDA进行积极磋商，以促进IND的成功准备。这些活动的成功执行将导致开发一种新型的、具有商业吸引力的Minisurf合成表面活性剂产品，该产品在制造经济性、活性和抗抑制性方面优于目前的动物和合成表面活性剂药物。 公共卫生相关性：该SBIR竞争性更新补助金将继续开发一种合成外源性肺表面活性物质产品，与现有药物相比，该产品在生产，活性和抑制抗性方面具有显着优势。这种创新的表面活性剂产品有望在治疗新生儿呼吸窘迫综合征（NRDS）、临床急性肺损伤（ALI）和急性呼吸窘迫综合征（ARDS）引起的严重急性呼吸衰竭患者方面具有巨大的未来效用。本授权中的合成表面活性剂也可潜在地用于其他肺部治疗剂的新型递送系统，如抗生素、抗炎药或遗传物质（基因治疗）。

DESCRIPTION (provided by applicant): This competitive renewal SBIR proposal extends our current Phase II translational research on novel synthetic lipid/peptide lung surfactants containing the highly active Super Mini-B (S-MB) peptide incorporating crucial functional regions of human surfactant protein (SP)-B, the most active apoprotein in biologic surfactant. Our initial Phase II grant focused on S-MB synthesized by solid-state chemistry, and documented the high activity of synthetic Minisurf" surfactant containing solid-state S-MB combined with lipids. This renewal application continues the commercial development of Minisurf" surfactant. This proposal will scale-up the production of the S-MB peptide and the Minisurf" surfactant product, develop effective QA/QC methods for analyzing the S-MB peptide and Minisurf" surfactant product, and demonstrate biological equivalency to laboratory research scale batches of Minisurf" surfactant. Pilot lots of the Minisurf" surfactant product will be manufactured and teste to ensure that the process is robust, the analytical controls are appropriate and the efficacy is maintained. Samples from selected pilot lots of Minisurf" surfactant will be placed on stability and sent to a contractor to conduct GLP-compliant pharmacology and toxicology studies. The proposal also provides for active consultation with the FDA during the grant to facilitate successful IND preparation. Successful execution of these activities will lead to the development of a novel, commercially-attractive Minisurf" synthetic surfactant product having significant advantages in manufacturing economy, activity, and inhibition resistance over current animal and synthetic surfactant drugs. PUBLIC HEALTH RELEVANCE: This SBIR competitive renewal grant will continue the development of a synthetic exogenous lung surfactant product having significant advantages in manufacture, activity and inhibition resistance compared to current drugs. This innovative surfactant product is expected to have great future utility in treating patients with severe acute respiratory failure from the neonatal respiratory distress syndrome (NRDS), clinical acute lung injury (ALI), and the acute respiratory distress syndrome (ARDS). The synthetic surfactant in this grant can also potentially be used in novel delivery systems for other pulmonary therapeutic agents such as antibiotics, anti-inflammatory drugs, or genetic materials (gene therapy).