Multifunctional injectable agent for endoscopic mucosal resection

内镜下粘膜切除多功能注射剂

• 批准号: 10481496
• 负责人: Chao Liu
• 金额: $ 24.98万
• 依托单位: ALEO BME, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-15 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10481496
• 关键词: Address; Adopted; Alginates; Behavior; Boston; Calcium; Calcium Binding; Calcium ion; Cell Survival; Cicatrix; Clinical; Coagulation Process; Competitive Binding; Complex; Crosslinker; Data; Development; Devices; Diagnosis; Disease; Dissection; Evaluation; Excision; FDA approved; Failure; Family suidae; Food Industry; Gastrointestinal Diseases; Gastrointestinal Neoplasms; Gastrointestinal tract structure; Gel; Goals; Height; Hemorrhage; Hemostatic Agents; Hemostatic function; Hydrogels; In Vitro; Incidence; Inflammation; Injectable; Injections; Lesion; Life; Lifting; Liquid substance; Lower Gastrointestinal Tract; Medical; Methods; Mucous Membrane; Operative Surgical Procedures; Outcome; Perforation; Performance; Pharmacologic Substance; Phase; Preparation; Prevalence; Procedures; Property; Research Proposals; Residual state; Risk; Safety; Saline; Severities; Small Business Innovation Research Grant; Sodium; Sterile coverings; Superficial Lesion; Suspensions; System; Thinness; Time; Tissues; Ulcer; United States; Viscosity; biomaterial compatibility; cost; crosslink; design; gastrointestinal; healing; improved; minimally invasive; operation; particle; pre-clinical; pressure; prevent; sealant; wound; wound healing

Project Summary The global submucosal injection solution market is estimated to be around $3 billion according to the incidence and prevalence rates of medical diagnoses known to be associated with endoscopic mucosal resection/endoscopic submucosal dissection (EMR/ESD), and the market is driven by the need to improve injectability and prolonged submucosal elevation. To date, only three submucosal lift solutions, EleviewTM (Aries Pharmaceuticals, Inc), OriseTM Gel (Boston Scientific), and EverliftTM (GI supply) are approved by FDA in the United States. These products are limited either by the inconsistent submucosal lift duration in preclinical and clinical settings or by their unsatisfactory injectability. Also, none of the products are able to address the bleeding problem, one of the most common complications for EMR/ESD. The primary goal of the Phase I proposal is to develop Aleo BME’s proprietary multifunctional submucosal injection agent (Aleo BMESolution) that can facilitate the safe surgical removal of gastrointestinal neoplasms via EMR/ESD, and enable post-surgical bleeding management. Aleo BMESolution is a mixed fluid gel composition mainly composed of sodium alginate (SA) as the gelling component, calcium-binding oligomer as the key modifier, and calcium ions as the crosslinker. The novelty lies in its design strategy in which a unique combination of a fluid gel concept borrowed from the food industry and a competitive binding mechanism via the introduction of a calcium-binding modifier was adopted to simultaneously achieve low injection pressure for relatively high viscosity solutions and much-improved hemostatic property. The Rigor of The Prior Research of the proposal is strongly supported by our preliminary data, including: 1) Aleo BMESolution is a shear-thinning alginate fluid gel that is a suspension of calcium- crosslinked gelled particles weakly held together via inter-particle interactions; 2) The tactic addition of oligomeric modifiers into alginate fluid gels significantly reduces the injection pressure of the system even at elevated calcium concentrations; 3) After injection into the confined submucosal space, a thickened hydrogel cushion is formed; 4) After resection, the residual of thickened fluid gels form a stable protective sealant (dressing) on the wound. 5) The addition of calcium-binding oligomeric modifiers makes it possible to make the shear-thinning mucoadhesive/mucoprotective fluid gels with elevated concentrations of alginate and calcium which synergistically contribute to the much-needed hemostaic properties of Aleo BMESolution. The expected outcome of this proposal is that we will develop an all-in-one multifunctional submucosal injection agent with superior performance over the existing products, such as desirable injection pressure, prolonged submucosal life, preferred rheological properties and shelf life, excellent biocompatibility, and unparalleled hemostatic function, to address ever-increasing needs in the underserved EMR/ESD injection solution market.

项目摘要 根据发病率，全球粘膜下注射溶液市场估计约为30亿美元。 和已知与内镜粘膜相关的医学诊断的患病率 切除术/内镜粘膜下剥离术（EMR/ESD），市场是由需要改善 可注射性和延长的粘膜下升高。迄今为止，只有三种粘膜下提升解决方案，EleviewTM（Aries FDA批准了OriseTM凝胶（Boston Scientific）和EverliftTM（GI供应）， 美国的这些产品受到临床前和临床试验中不一致的粘膜下提升持续时间的限制， 临床环境或其不令人满意的可注射性。此外，没有一种产品能够解决出血问题 问题，EMR/ESD最常见的并发症之一。第一阶段提案的主要目标是 开发Aleo BME专有的多功能粘膜下注射剂（Aleo BMESolution）， 通过EMR/ESD安全手术切除胃肠道肿瘤，并使术后出血 管理Aleo BME溶液是一种混合流体凝胶组合物，主要由海藻酸钠（SA）作为 胶凝组分、作为关键改性剂的钙结合低聚物和作为交联剂的钙离子。的 新奇之处在于它的设计策略，其中一个独特的组合，流体凝胶的概念借鉴了食品 通过引入钙结合改性剂， 同时对于相对高粘度溶液实现低注射压力 止血性能。我们的初步研究结果有力地支持了该提案的先前研究的严谨性。 数据，包括：1）Aleo BME溶液是一种剪切稀化藻酸盐流体凝胶，是钙的悬浮液， 交联的胶凝颗粒通过颗粒间相互作用弱地保持在一起; 2）低聚物的有规加成 将改性剂引入藻酸盐流体凝胶中显著降低了系统的注射压力， 钙浓度; 3）在注射到受限的粘膜下空间后， 4）切除后，增稠的流体凝胶的残留物在组织上形成稳定的保护性密封剂（敷料）。 伤口5)钙结合低聚物改性剂的加入使得剪切稀化成为可能。 具有高浓度藻酸盐和钙的粘膜粘附/粘膜保护流体凝胶， 协同有助于Aleo BME溶液急需的止血特性。预期 该建议的结果是，我们将开发一种多功能粘膜下注射剂， 与现有产品相比具有上级性能，例如理想的注射压力、延长的粘膜下 使用寿命、优选的流变性能和保质期、优异的生物相容性和无与伦比的止血效果 功能，以满足服务不足的EMR/ESD注入解决方案市场日益增长的需求。