Development of a novel SP-B peptide lung surfactant

描述(由申请人提供)：这项竞争性续签SBIR建议扩展了我们目前对新型合成脂质/肽肺表面活性物质(S-MB)的第二阶段翻译研究，该合成脂质/肽肺表面活性物质含有高活性的超迷你-B多肽，其中含有生物表面活性物质中最活跃的载脂蛋白-B的关键功能区。我们最初的第二期拨款集中在用固态化学方法合成的S-MB，并证明了合成的含有固态S-MB与脂质结合的“微型硫磺”表面活性剂的高活性。这一续期申请延续了微型硫磺“表面活性剂”的商业开发。这项建议将扩大S-MB多肽和迷你表面活性剂产品的生产，为S-MB多肽和迷你表面活性物质产品的分析开发有效的QA/QC方法，并证明与实验室研究规模的迷你表面活性物质批次的生物等效性。将中试批量生产和试验，以确保过程稳健，分析控制适当，并保持有效性。选定的“迷你硫磺”表面活性剂样品将被置于稳定性状态，并被送往承包商进行符合GLP的药理学和毒理学研究。该提案还规定在拨款期间与FDA积极协商，以促进IND的成功制备。这些活动的成功实施将导致开发一种新型的、具有商业吸引力的“迷你硫磺”合成表面活性剂产品，与目前的动物和合成表面活性药物相比，该产品在制造经济性、活性和抗抑制性方面具有显著优势。

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.