In Situ Gelable Filler for Obliteration of Cerebral Aneurysm

原位凝胶填充剂用于闭塞脑动脉瘤

• 批准号: 7273992
• 负责人: Weiliam Chen
• 金额: $ 17.77万
• 依托单位: ENDOMEDIX, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7273992
• 关键词: Aneurysm; Autopsy; Biocompatible; Biological; Canis familiaris; Carbohydrates; Caring; Catheters; Cerebral Aneurysm; Characteristics; Chitosan; Clinical; Clinical Research; Coagulation Process; Cross-Linking Reagents; Dextrans; Fibrosis; Filler; Future; General Population; Goals; Hydrogels; In Situ; In Vitro; Intracranial Aneurysm; Invasive; Liquid substance; Modeling; Modification; Numbers; Outcome; Performance; Phase; Platinum; Prevalence; Property; Rate; Recurrence; Reporting; Risk; Rupture; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Staging; Therapeutic; Therapeutic Embolization; Therapeutic Uses; Time; Toxic effect; Translating; Validation; base; biomaterial compatibility; cytotoxicity; dextran; efficacy evaluation; improved; in vivo; response; scale up; size; success

DESCRIPTION (provided by applicant): The prevalence of intracranial aneurysms is about 1.6% in the general population; with a rupture rate of approximately 1% per year. This translates into approximately 30,000 cases per year in the U.S. It is estimated that an equal number of unruptured aneurysms, usually discovered incidentally, are also treated. Endovascular therapy has recently evolved as a minimally invasive treatment for cerebral aneurysms and is slowly becoming almost the mainstay of care; it generally involves the deployment of metallic microcoils into the aneurysm dome through a catheter. Theoretically, aneurysm embolization is achieved via coils that induce arterial stasis within the dome leading to clotting and later fibrosis with ultimately obliteration. The major limitation of microcoils was underscored by autopsy reports compiled indicating incomplete obliteration of most aneurysms. Attempts to enhance the performance of metallic coils have hitherto shown limited success. Liquid embolic agents have been developed but their performance characteristics have to be greatly improved before they can be acceptable universally by clinicians. The goal of this project is to develop a biocompatible and biodegradable in situ gelable carbohydrate hydrogel without the limitations of the liquid embolic agents currently available for aneurysm filling. The hydrogel properties and composition will be further optimized and the non-cytotoxicity will be validated. Sufficient clinical grade materials will be produced for future in vivo and clinical studies. The project will be concluded after performing in vivo efficacy evaluations in canine aneurysm models. This Phase I SBIR project will set the stage for developing a liquid embolic agent which is easier to use and the therapeutic outcome of treating an aneurysm can be improved by shortening the time to complete occlusion.

描述（由申请人提供）：普通人群中颅内动脉瘤的患病率约为 1.6%；每年破裂率约为1%。这意味着美国每年约有 30,000 例病例。据估计，通常偶然发现的同等数量的未破裂动脉瘤也得到了治疗。血管内治疗最近已发展成为脑动脉瘤的微创治疗方法，并逐渐成为几乎主要的治疗方法；它通常涉及通过导管将金属微线圈部署到动脉瘤圆顶中。理论上，动脉瘤栓塞是通过线圈实现的，线圈诱导动脉穹窿内的动脉停滞，导致凝血，随后纤维化，最终闭塞。尸检报告强调了微线圈的主要局限性，表明大多数动脉瘤未完全消除。迄今为止，提高金属卷材性能的尝试所取得的成功有限。液体栓塞剂已经被开发出来，但其性能特征必须大大改善才能被临床医生普遍接受。该项目的目标是开发一种生物相容性和可生物降解的原位凝胶碳水化合物水凝胶，不受目前可用于动脉瘤填充的液体栓塞剂的限制。水凝胶的性质和组成将进一步优化，并验证非细胞毒性。将生产足够的临床级材料用于未来的体内和临床研究。该项目将在犬动脉瘤模型中进行体内疗效评估后结束。该第一期 SBIR 项目将为开发一种更易于使用的液体栓塞剂奠定基础，并且可以通过缩短完全闭塞的时间来改善动脉瘤的治疗效果。