Koli: A non-surgical solution for gallstone disease

症状性胆石症影响美国近500万人，消耗超过 每年63亿美元。当胆结石从宽阔的胆囊体移出并进入胆囊壁时，就会发生并发症 连接胆囊和小肠的狭窄的导管系统。胆结石的发病率增加 随着年龄的增长，在女性和肥胖者中更高。其他危险因素包括怀孕、激素替代 治疗、快速减肥、糖尿病、克罗恩病、家族病史、高龄和长时间禁食。AS 西式饮食在全球范围内获得吸引力，全球胆结石发病率在#年迅速上升。 手术治疗并不总是可用的地区。 当今治疗胆石症最常见和最有效的治疗方法是手术切除胆石症 胆囊癌，或称胆囊癌切除术。不幸的是，手术并不总是一种选择。患者可能无法 因心脏或肺部疾病无法控制而导致全身麻醉等合并症而耐受手术 不可能的，或者他们有暂时性的疾病延误手术，例如最近的心脏病发作，中风，或 败血症。随着等待时间的延长和有胆结石相关并发症的患者，复发胆结石相关并发症的风险增加 手术禁忌症或时间安排延迟会增加发生胆结石相关疾病的风险 并发症。急性胆囊炎可能迫使这些非常严重的患者决定进行紧急手术。 高死亡率和高发病率风险。 KōLi开发了一种非手术替代疗法来治疗胆石症。一种小型植入式过滤器是 应用于胆囊腔内，以预防胆结石阻塞胆总管出口的并发症。 管风琴。Kōli用一种旨在高风险下安全的微创门诊手术取代了手术。 患者，包括老年人、孕妇和最近有心肌梗死、中风或手术的患者。KōLi适合 现有的转诊和报销模式将利用传统的超声波和透视技术， 并将通过介入放射学、胃肠病学或普通外科手术进行。 该公司的技术是在美国国家科学基金会SBIR奖(#1248295)和私人支持下开发的 投资。在过去的5年里，KōLi从概念验证的角度提出了他们的新型胆结石过滤系统 试验台测试，类似GLP的大型动物研究，最近成功地完成了人类第一个临床试验 在菲律宾的可行性研究。 目前迭代的Kōli系统依赖于锋利的带刺锚来穿透 并将自我膨胀的过滤器固定在适当的位置。穿透性锚定会带来以下风险 穿孔、结疤和机械故障。一旦部署，锚定设备将无法移除，除非 做手术。为了应对这些风险，Kōli与Hoowaki，LLC合作，集成了一种新型的反迁移微处理器 浮到我们的过滤系统中，而不是带刺的锚。此方法将消除与以下各项相关的风险 目前的锚和过滤系统将更容易制造，更容易部署，并完全 放置后最长可拆卸数月。该项目代表了第一次将微型表面植入物 在胆道系统中使用，也是胃肠病学中许多创新应用的起点。 这项直接到第二阶段的奖励将资助过滤系统的高级开发，包括 采用创新的微表面纹理涂层来取代目前的带刺金属锚， 不透射线的钽标记物的集成，以及在长凳和大型动物中对更新系统的验证 这些活动的研究完成将使公司能够开始与FDA进行提交前的讨论 将作为第二阶段申请的基础的早期可行性研究。

Symptomatic gallstone disease affects nearly 5 million people in the United States and consumes over $6.3B annually. Complications occur when gallstones move from the wide body of the gallbladder and enter the narrow system of ducts connecting the gallbladder to the small intestine. The incidence of gallstones increases with age and is higher in women and obese people. Other risk factors include pregnancy, hormone replacement therapy, rapid weight loss, diabetes, Crohn's disease, family history, older age, and prolonged fasting. As Western-style diets gain traction across the globe, the worldwide rate of gallstone disease is rising quickly in areas where surgical treatment is not always available. The most common and effective treatment for gallstone disease today is surgical removal of the gallbladder, or cholecystectomy. Unfortunately, surgery is not always an option. Patients may be unable to tolerate surgery due to comorbidities such as uncontrolled heart or lung diseases which make general anesthesia impossible or they have temporary conditions which delay surgery, for example a recent heart attack, stroke, or sepsis. The risk of a recurrent gallstone-related complication increases with waiting time and patients with a surgical contraindication or scheduling delays are subject to increasing risk of developing gallstone-related complications. Acute cholecystitis can force a decision to perform emergency surgery in these patients with very high mortality and morbidity risks. Kōli has developed a non-surgical alternative to treat gallstone disease. A small implantable filter is deployed in the gallbladder to prevent complications associated with gallstones obstructing the outlet of the organ. Kōli replaces surgery with a minimally invasive outpatient procedure designed to be safe in high risk patients, including the elderly, pregnant women, and patients with recent MI, stroke, or surgery. Kōli fits into existing referral and reimbursement patterns, would utilize conventional ultrasound and fluoroscopic techniques, and will be performed by interventional radiology, gastroenterology, or general surgery. The company’s technology was developed with support from an NSF SBIR award (#1248295) and private investment. Over the past 5 years, Kōli has advanced their novel gallstone filtering system from proof-of-concept bench testing, GLP-like large animal studies, and recently completed a successful first-in-human clinical feasibility study in the Philippines. The current iteration of the Kōli system relies on sharp barbed anchors to penetrate the luminal wall of the gallbladder and hold the self-expanding filter in place. Penetrating anchors carry risks associated with perforation, scarring, and mechanical failure. Once deployed, the anchored device cannot be removed without surgery. To address these risks, Kōli has partnered with Hoowaki, LLC to integrate a novel anti-migration micro surface into our filtering system in place of barbed anchors. This approach will eliminate risks associated with the current anchors and the filtering system will be easier to manufacture, easier to deploy, and completely removable up to months after placement. This project represents the first time a micro surfaced implant will be used in the biliary system and a starting point for a number of innovative applications in gastroenterology. This Direct to Phase II award will fund advanced development of the filtering system, including incorporation of an innovative micro surface textured coating to replace the current barbed metal anchors, integration of radiopaque tantalum markers, and validation of the updated system in bench and large animal studies Completion of these activities will allow the company to begin pre-submission discussions with FDA for an early feasibility study that will form the basis of a Phase IIB application.