Treatment of GERD Using Biodegradable Materials to Enhance Gastric Yield Pressure and GEJ Compliance Dynamics

使用生物可降解材料治疗胃食管反流病以增强胃屈服压和胃食管结合部顺应性动态

• 批准号: 10256155
• 负责人: Ryan Balko
• 金额: $ 39.96万
• 依托单位: ESCHARA MEDICAL, LLC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2022-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10256155
• 关键词: Achievement; Address; Adverse effects; Adverse event; Affect; Anatomy; Animals; Barrett Esophagus; Caring; Characteristics; Chronic; Clinical; Clinical Trials; Collagen; Communities; Deglutition; Deglutition Disorders; Deposition; Development; Device Designs; Device Removal; Devices; Engineering; Ensure; Eructation; Esophageal Adenocarcinoma; Esophagitis; Esophagogastric Junction; Esophagus; FDA approved; Failure; Family suidae; Feasibility Studies; Fibrosis; Flatulence; Food; Foreign Bodies; Foreign-Body Reaction; Freezing; Functional disorder; Fundoplication; Gases; Gastroenterology; Gastroesophageal reflux disease; Goals; Gold; Grant; Health; Hernia; Hiatal Hernia; Histologic; Image; Implant; Inferior esophageal sphincter structure; Lead; Length; Life Style Modification; Location; Magnetic Resonance Imaging; Magnetism; Measures; Medical; Modeling; Nature; Operative Surgical Procedures; Outcome; Pathologic; Patient Care; Patients; Performance; Pharmaceutical Preparations; Phase; Physiological; Population; Positioning Attribute; Postoperative Complications; Postoperative Period; Preparation; Procedures; Proton Pump Inhibitors; Recrudescences; Reflux; Relaxation; Repeat Surgery; Risk; Scanning; Small Business Innovation Research Grant; Sphincter; Stomach; Surgical sutures; Symptoms; Techniques; Technology; Tensile Strength; Testing; Time; Tissues; Tubular formation; Ulcer; Vagus nerve structure; Validation; Vomiting; base; commercialization; community intervention; design; experience; experimental study; falls; improved; in vivo; in vivo evaluation; innovation; migration; minimal risk; minimally invasive; nerve injury; novel; porcine model; premature; preservation; pressure; prevent; programs; prototype; reduce symptoms; repaired; response; side effect; standard care; success; tool

PROJECT SUMMARY Gastroesophageal reflux disease (GERD) affects 8-33% of the global population. GERD can lead to esophagitis, strictures, ulcerations and Barrett's esophagus (BE). Patients with BE have up to an 125-fold increased risk of developing esophageal adenocarcinoma—a devastating outcome which is fatal in roughly 80-90% of cases. Currently, the gold standard treatment for GERD remains long-term proton pump inhibitors, i.e. PPI therapy, or laparoscopic Nissen fundoplication (LNF). However, PPI therapy fails to control GERD symptoms in 25%-42% of patients, and the chronic use of PPIs is associated with serious adverse effects. Moreover, LNF is technically exacting, and currently fewer than 1% of the eligible GERD population pursue surgery due to concerns of postoperative complications and surgical failure. Thus, an alternative surgical treatment is needed to close the “therapy gap”. Re cently, LINX magnetic sphincter augmentation surgery (MSA) has become an alternative surgical option to address the therapy gap (FDA-approved, January, 2012; Torax Medical, MN), The LINX device is a ring of magnets permanently placed laparoscopically around the gastroesophageal junction (GEJ). Although the side-effect profile of MSA is somewhat superior to LNF, unfortunately, high rates of postoperative dysphagia are routinely seen after LINX placement along with low rates of device erosion. To address these issues and improve GERD therapy, we have developed an entirely new class of GERD treatment: a novel biodegradable device. Our device is called the Eschara suture collar and consists of a dense, tubular matrix of bioabsorbable suture material that will create a ring of collagen around the lower esophageal sphincter, in the region of the GEJ. As the material biodegrades within a matter of days, it loses tensile strength, thus avoiding any dysphagia. Within a matter of weeks, the suture collar material totally absorbs and, via a foreign body reaction, leaves behind a collar of collagen that supplies the appropriate amount of LES augmentation to demonstrably improve LES effacement characteristics, increase yield pressure, decrease compliance at the GEJ, and increase functional LES length, thereby preventing pathologic acid reflux. We developed the Eschara device in order to provide an ideal GERD solution with the following advantages over LNF and LINX: 1) Correct GERD pathophysiology, 2) preserve natural physiological swallowing, belching, and vomiting, minimize dysphagia, 3) cause minimal risk to the vagus nerve, 4) no risk of erosion, 5) MRI, and all imaging, compatible, 6) simple manufacturing, 7) Enable simplified Hiatal Hernia repair, and 8) eliminate the need for continued PPI use. To ensure adequate performance of the Eschara suture collar prototype, we will 1) fabricate and develop the design; then 2) test and validate it in an in vivo swine model. Based on the results of initial experiments, we will: 3) Fabricate and develop the second round of design iteration; 4) perform second swine experiment. This Phase 1 SBIR proposal prepares us for an SBIR Phase II grant aimed at achieving design freeze, regulatory preparation, and commercialization. Also, we will critically evaluate our suture model to determine whether the Eschara technology could efficiently meet the needs of the GERD market and be a successful alternative to current surgical techniques, leading to improved care for GERD patients.

项目总结 胃食道反流病(GERD)影响全球人口的8%-33%。GERD可导致食管炎、狭窄、 溃疡和巴雷特食道(BE)。BE患者发生食道疾病的风险增加125倍 腺癌--这是一种毁灭性的结果，在大约80%-90%的病例中是致命的。目前，黄金标准治疗 对于GERD，仍需长期使用质子泵抑制剂，即PPI疗法或腹腔镜Nissen胃底折叠术(LNF)。 然而，在25%-42%的患者中，PPI治疗未能控制GERD症状，长期使用PPI与 有严重的不良反应。此外， LNF在技术上是严格的，目前不到符合条件的GERD的1% 由于担心术后并发症和手术失败，人们寻求手术。因此，另一种手术方式 需要治疗来弥合“治疗差距”。回复 最近，LINX磁性括约肌扩大术(MSA)已经成为 解决治疗缺口的替代手术选择(FDA批准，2012年1月；Torax Medical，MN)，LINX 该装置是在腹腔镜下永久放置在胃食道交界处(GEJ)周围的一圈磁铁。尽管 不幸的是，MSA的副作用在一定程度上优于LNF， 术后吞咽困难发生率高 都是例行的 在LINX放置后可见，同时器件腐蚀率较低。 为了解决这些问题并改进GERD治疗，我们开发了一种全新的GERD治疗方法：一种新的治疗方法 可生物降解装置。我们的装置被称为Eschara缝合环，由致密的可生物吸收的管状基质组成 缝合材料将在GEJ区域的下食道括约肌周围形成胶原环。作为 材料在几天内生物降解，失去抗拉强度，从而避免任何吞咽困难。在一件事上 几周后，缝合衣领材料完全吸收，并通过异物反应留下一层胶原蛋白衣领， 提供适量的LES增强，以明显改善LES消除特性，增加 屈服压力，降低GEJ的顺应性，增加功能性LES长度，从而防止病理性酸 回流。我们开发Eschara设备是为了提供理想的GERD解决方案，该解决方案具有以下优势 LNF和LINX：1)正确的GERD病理生理学，2)保留自然的生理性吞咽、打嗝和呕吐， 最大限度地减少吞咽困难，3)对迷走神经造成最小的风险，4)没有侵蚀的风险，5)MRI，和所有的成像，兼容， 6)制造简单，7)能够简化裂孔疝修补术，8)不再需要继续使用PPI。 为了确保Eschara缝合领原型的足够性能，我们将1)制造和开发设计；然后2) 在活体猪模型中进行测试和验证。在初步实验结果的基础上，我们将：3)制作和开发 第二轮设计迭代；4)进行第二次猪实验。此第1阶段SBIR计划使我们为 SBIR第二阶段赠款旨在实现设计冻结、监管准备和商业化。此外，我们还将严格执行 评估我们的缝合模型以确定Eschara技术是否可以有效地满足GERD的需求 并成为当前外科技术的成功替代品，从而改善对GERD患者的护理。