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: 8314386
• 负责人: Gary Fujii
• 金额: $ 95.36万
• 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/8314386
• 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. 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).

描述（由申请人提供）：这一竞争性SBIR提案扩展了我们当前关于新型合成脂质/肽肺表面活性剂的转化研究，其中含有高活性的超级Mini-B（S-MB）肽，这些肽结合了人类表面活性剂蛋白（SP）的至关重要的功能区域（SP）-B，最活跃的Apoprote Aperototion curfactant。我们的初始II阶段赠款重点是由固态化学合成的S-MB，并记录了合成微型外的高活性“含有固态S-MB结合脂质的表面活性剂。这种更新施加了Minisurf的商业开发。该提案将扩大S-MB肽和Minisurf“表面活性剂产品，开发有效的质量质量药/QC方法来分析S-MB肽和Minisurf“表面活性剂产品”，并证明了生物学在实验室研究量表的生物学等效性，以确保“表面效果”。强大的分析控制是适当的，并且保持疗效。来自选定飞行员的样本许多微型外表面活性剂将保持稳定性，并发送给承包商进行符合GLP兼容的药理学和毒理学研究。该提案还规定，在授予期间，该提案还提供了与FDA的积极咨询，以促进成功的索引。以及对当前动物和合成表面活性剂药物的抑制性。 公共卫生相关性：与当前药物相比，该SBIR竞争性更新赠款将继续开发合成的外源肺表面活性剂产品在制造，活动和抑制耐药性方面具有显着优势。预计这种创新的表面活性剂产品将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）的严重急性呼吸衰竭患者方面具有巨大的未来效用。该赠款中的合成表面活性剂也可以用于其他肺部治疗剂的新型递送系统中，例如抗生素，抗炎药或遗传材料（基因治疗）。