In Situ Gelable Filler for Obliteration of Cerebral Aneurysm

描述（由申请人提供）：一般人群中颅内动脉瘤的患病率约为1.6%;破裂率约为每年1%。这意味着美国每年约有30，000例病例。据估计，通常偶然发现的未破裂动脉瘤也会得到治疗。血管内治疗最近已发展为脑动脉瘤的微创治疗，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弹簧圈部署到动脉瘤圆顶中。理论上，动脉瘤栓塞是通过弹簧圈实现的，弹簧圈诱导圆顶内的动脉停滞，导致凝血和随后的纤维化，最终闭塞。汇编的尸检报告强调了微弹簧圈的主要局限性，表明大多数动脉瘤不完全闭塞。迄今为止，增强金属线圈性能的尝试显示出有限的成功。液体栓塞剂已经被开发出来，但是在它们能够被临床医生普遍接受之前，它们的性能特征必须得到极大的改善。本项目的目标是开发一种生物相容性和可生物降解的原位可胶凝碳水化合物水凝胶，而不受目前可用于动脉瘤填充的液体栓塞剂的限制。将进一步优化水凝胶的性质和组成，并验证其无细胞毒性。将生产足够的临床级材料用于未来的体内和临床研究。在犬动脉瘤模型中进行体内有效性评价后，将结束该项目。该I期SBIR项目将为开发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时间来改善动脉瘤治疗的治疗结果。

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.