Development of a novel SP-B peptide lung surfactant

新型SP-B肽肺表面活性剂的研制

• 批准号: 8532016
• 负责人: Gary Fujii
• 金额: $ 95.75万
• 依托单位: MOLECULAR EXPRESS, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8532016
• 关键词: Acute; Acute Lung Injury; Acute respiratory failure; Adsorption; Adult Respiratory Distress Syndrome; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Antibiotics; Apoproteins; Biological; Biological Assay; Cell Line; Chemical Surfactants; Chemistry; Clinical; Clinical Research; Consultations; Contractor; Contracts; Cyclic GMP; Development; Documentation; Drug Formulations; Ensure; Equilibrium; Erythrocytes; FDA approved; Future; Genetic Materials; Grant; Human; Infasurf; International; Kilogram; Laboratories; Laboratory Research; Lead; Lipids; Lung; Manufactured Materials; Measures; Methods; Modeling; Molecular Conformation; Monitor; Newborn Respiratory Distress Syndrome; Patients; Peptide Synthesis; Peptides; Pharmaceutical Preparations; Pharmacology and Toxicology; Phase; Preparation; Process; Production; Protocols documentation; Pulmonary Surfactant-Associated Protein B; Pulmonary Surfactants; Qualifying; Rattus; Relative (related person); Research; Resistance; Retinal Cone; Sampling; Small Business Innovation Research Grant; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis; Surface; Survanta; Synthesis Chemistry; System; Techniques; Testing; Therapeutic Agents; Toxic effect; Translational Research; Viscosity; analytical method; base; cytotoxicity; gene therapy; innovation; lung injury; manufacturing process; manufacturing process development; meetings; novel; oxidation; peptide B; scale up; solid state; surfactant

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.

描述（由申请人提供）：这项竞争性更新 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 Super Mini-B (S-MB) 肽，并结合了生物表面活性剂中最活跃的脱辅基蛋白人类表面活性剂蛋白 (SP)-B 的关键功能区域。我们最初的第二阶段资助重点关注通过固态化学合成的 S-MB，并记录了含有固态 S-MB 和脂质的合成 Minisurf” 表面活性剂的高活性。这一更新申请继续了 Minisurf” 表面活性剂的商业开发。该提案将扩大 S-MB 肽和 Minisurf" 表面活性剂产品的生产，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。将生产和测试 Minisurf" 表面活性剂产品的中试批次，以确保该工艺符合要求。 稳健，分析控制适当并且保持功效。选定的 Minisurf” 表面活性剂试点批次的样品将进行稳定性测试，并发送给承包商进行符合 GLP 的药理学和毒理学研究。该提案还规定在拨款期间与 FDA 积极协商，以促进 IND 准备的成功。这些活动的成功执行将导致开发出一种新颖的、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、 以及对现有动物和合成表面活性剂药物的抑制性。