SBIR Phase II: Novel approach to the oral delivery of biologically active peptide analogs

SBIR II 期：生物活性肽类似物口服给药的新方法

• 批准号: 1456396
• 负责人: Scott Shandler
• 金额: $ 75万
• 依托单位: Longevity Biotech, Inc
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-15 至 2017-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1456396&HistoricalAwards=false
• 关键词: SBIR; Phase; II; Novel; approach

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project is very significant. Current peptide-based drugs constitute important tools in human healthcare, and development of new peptide-based drugs represents a growing proportion of the pharmaceutical research effort. Current peptide drugs addressing widespread diseases such as type 2 diabetes (T2DM) and osteoporosis have sales above $1 billion. These drugs must be delivered by injection. This SBIR aims for new drugs with comparable heath benefits that can be taken in pill form, because the convenience of oral delivery, relative to injection, would rapidly capture most of the market. The high stability engendered by our design strategy should enable drug development for diseases that currently cannot be treated. Thus, the commercial potential of this project is high. Orally delivered replacements for injectable drugs would have a substantial broader impact because they would enhance patient compliance. Inadequate treatment of T2DM for example, leads to adverse health consequences that degrade productivity and quality of life for patients. Increased compliance resulting from a general ability to deliver peptide drugs in pill form would vastly improve outcomes for patients, including the specific patients populations targeted by our current programs. The proposed project is motivated by fundamental questions about the way drug molecules are processed in the human body. Drug candidates cannot address a human disease unless they reach the appropriate sites within the body and then persist in those sites. The proposed research focuses on a particular class of bioactive compounds called "peptides." Peptides can act in powerful and favorable ways within the body, with high specificity of action (which minimizes "side effects"), but they are subject to very rapid destruction after administration. This weakness of peptides requires that they be injected regularly, but peptide drugs would be much more useful if they could be taken orally. This SBIR Phase I project examines unique peptide-like molecules that are designed to retain the favorable pharmaceutical action of peptides themselves but to resist degradation mechanisms within the body that rapidly destroy peptides. The stomach is the most destructive site for peptides, and this project aims to generate peptide-like molecules that are sufficiently robust to survive the stomach and reach the small intestine, where they can be absorbed. Achieving these molecular design goals would have high intellectual merit in addition to advancing drug design.

这个小企业创新研究（SBIR）第二阶段项目的更广泛的影响/商业潜力非常重要。 目前的肽类药物是人类医疗保健的重要工具，新的肽类药物的开发在药物研究工作中所占的比例越来越大。 目前，针对2型糖尿病（T2 DM）和骨质疏松症等广泛疾病的肽类药物的销售额超过10亿美元。 这些药物必须通过注射给药。 该SBIR的目标是可以以药丸形式服用的具有可比健康益处的新药，因为相对于注射，口服给药的便利性将迅速占领大部分市场。 我们的设计策略所产生的高稳定性应该使目前无法治疗的疾病的药物开发成为可能。 因此，该项目的商业潜力很大。 口服替代注射药物将产生更广泛的影响，因为它们将提高患者的依从性。 例如，T2 DM治疗不足会导致不良健康后果，降低患者的生产力和生活质量。 以药丸形式递送肽类药物的一般能力所导致的依从性增加将极大地改善患者的结局，包括我们当前计划所针对的特定患者人群。 该项目的动机是关于药物分子在人体内加工方式的基本问题。 候选药物不能解决人类疾病，除非它们到达体内的适当部位，然后在这些部位持续存在。 拟议的研究集中在一类特殊的生物活性化合物，称为“肽”。肽可以在体内以强大和有利的方式发挥作用，具有高度的作用特异性（最大限度地减少“副作用”），但它们在给药后会很快被破坏。 肽的这种弱点要求它们定期注射，但如果它们可以口服，肽药物将更加有用。 SBIR第一阶段项目研究了独特的肽样分子，这些分子旨在保留肽本身的有利药物作用，但抵抗体内快速破坏肽的降解机制。 胃是肽最具破坏性的部位，该项目旨在产生肽样分子，这些分子足够强大，能够在胃中存活并到达小肠，在那里它们可以被吸收。 实现这些分子设计目标除了推进药物设计外，还具有很高的智力价值。