Hemorrhage Control During Brain Surgery

描述（由申请人提供）：脑外科手术期间的出血控制至关重要，因为颅内狭窄空间内不受控制的出血可迅速恶化为使人衰弱的并发症和死亡。大脑中通常不可能有结扎 由于血管的小尺寸和组织的脆弱性，在神经外科手术期间大部分眼睑出血是局部扩散/渗出型出血。脑外科手术期间的出血控制方法实际上几十年来没有改变;在脑外科手术期间部署通过压力、吸收和/或化学介导机制起作用的手术辅助装置用于止血。这些产品的缺点包括：（i）需要准备，（ii）与手术部位不共形/不粘附，（iii）需要手动加压，（iv）缺乏透明度-可视化止血状态的能力有限，（v）血液和/或哺乳动物来源的材料-疾病传播的风险，以及（v）肿胀。重要的是，这些产品的主要不足之处是作用缓慢，导致手术时间延长（风险和发病率），并经常产生不一致的结果。用凝血酶溶液饱和的明胶泡沫结合施加压力仍然是目前阻止弥漫性出血的金标准;该过程需要协调部署至少四种产品，包括明胶泡沫、凝血酶、棉塞和抽吸。我们正在开发一种非哺乳动物/非血液来源的生物相容性和生物可降解的、原位可胶凝的粘合剂/可成形/适形和非溶胀的透明水凝胶，其不需要制备，用于颅骨止血，其是非化学介导的，并且可以在接触时快速止血而无需任何止血剂。【透明的药剂，能够快速止血，让外科医生能够判断止血状态，加快下一步手术的决策。】使用价格极具竞争力的止血剂加速手术，最终将通过缩短手术和全身麻醉时间，节省手术室时间并降低发病率。我们的产品符合新的医疗保健经济学，保险公司越来越需要以更低的成本提供上级产品。在本项目的第一阶段开发了一个原型代理，并通过实验确定了其功效和性能标准。在第二阶段，我们将继续开发止血产品。主要目标是：（i）减少产品内毒素负荷以符合FDA的要求，（ii）最大化产品的一致性，（iii）简化当前的方法以降低未来的生产成本，（iv）为产品开发非动力辅助分配器以促进临床使用，（v）生产GLP级材料，（vi）ISO 10993生物相容性和毒理学验证，和（vii）在大型动物颅骨模型中对止血剂进行体内初步试验。

DESCRIPTION (provided by applicant): Bleeding control during brain surgery is of utmost importance, as uncontrolled bleeding inside the confined intracranial space can quickly degenerate into debilitating complications and death. Ligature is usually not possible in the brain due both to the small size of the vessels and the delicacy of the tissue as the majority of bleedings during neurosurgery is the topical diffuse/oozing type bleeding. The methods for bleeding control during brain surgery has practically not changed for decades; surgical aids that work by pressure, absorption, and/or chemical mediated mechanisms are deployed for hemostasis during brain surgery. The shortcomings of these products include: (i) require preparation, (ii) non-conformal/non-adhesive to the surgical site, (iii) require manual pressure, (iv) lack transparency - limited capacity to visualize the hemostasis status, (v) materials of bloo and/or mammalian origin - risk of disease transmission, and (v) swelling. Importantly, the major inadequacies of these products are slow acting leading to prolonging surgery (risk and morbidity) and often produce inconsistent results. Gelatin foam saturated with thrombin solution in conjunction with applying pressure is still the current gold-standard to stop diffuse bleeding; the process requires a coordinated deployment of at least four products including gelatin foam, thrombin, cottonoids, and suction. We are developing a non-mammalian/non-blood derived biocompatible and biodegradable, in situ gelable adhesive/formable/conformable and non-swelling transparent hydrogel that requires no preparation, for cranial hemostasis, it is non-chemically mediated and can quickly stop bleeding on contact without any adjuncts. [A transparent agent, capable of achieving hemostasis rapidly, enables the surgeons to determine the status of hemostasis and speed up the decision of moving onto the next step of the surgery.] Accelerating surgery with a highly competitively priced hemostatic agent will eventually result in considerable cost saving on operating room time and reduction of morbidity through shortening of surgery and general anesthesia. Our product conforms to the new healthcare economics where insurers are increasingly demanding superior products at lower costs. A prototype agent was developed in the Phase I of this project and its efficacy and performance criteria have been experimentally defined. In Phase II, we will continue to develop the hemostat product. The major goals are: (i) reduce the product endotoxin burden to comply with FDA's requirement, (ii) maximize the product's consistency, (iii) streamline the current methodologies to reduce the future production costs, (iv) develop a non-power assisted dispenser for the product to facilitate clinical use, (v) production of GLP grade materials, (vi) ISO10993 biocompatibility and toxicology validation, and (vii) in vivo pilot testing of the hemostat in a large animal cranial model.