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，该表面活性剂含有高活性的Super Mini-B （S-MB）肽，该肽含有人表面活性剂蛋白(SP)-B的关键功能区域，SP -B是生物表面活性剂中最活性的载脂蛋白。我们最初的II期研究重点是固态化学合成S-MB，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。这一更新应用延续了Minisurf表面活性剂的商业化开发。本提案将扩大S-MB肽和Minisurf表面活性剂产品的生产规模，开发有效的QA/QC方法来分析S-MB肽和Minisurf表面活性剂产品，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。生产和测试miniurf”表面活性剂产品的中试批次，以确保工艺稳健，分析控制适当，并保持功效。从选定的“Minisurf”表面活性剂试验批次中提取的样品将被放置在稳定状态下，并发送给承包商进行符合glp的药理学和毒理学研究。该提案还规定在批准期间与FDA积极协商，以促进IND准备的成功。这些活动的成功实施将导致一种新型的、具有商业吸引力的“迷你”合成表面活性剂产品的开发，与目前的动物和合成表面活性剂药物相比，它在制造经济性、活性和抗抑制性方面具有显着优势。

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.