MEMBRANE-MEDIATED SORPTIVE HEMOPERFUSION

血液灌流用于治疗一些血液中含有危及生命的药物或其他有毒化合物的患者。然而，由于相关的副作用，如血小板减少症和“全身炎症”，这些治疗方法并没有达到预期的效果，此外，传统的血液灌流方案有将微颗粒（栓子）释放到患者血流中的风险。本文提出的传统血液灌流装置的新方法采用了一种改进的体外透析样系统，有望克服传统血液灌流装置的许多缺点。二期研究将开发一种血液灌流系统，然后在动物身上进行测试，以确定其有效性和安全性。茶碱将作为试验药物，拟议的血液灌流系统将用于安全、快速地将这种药物的毒性血液水平降低到治疗浓度。此外，将确定该系统对血液成分的影响，如溶血、血小板损失、葡萄糖、电解质和酶水平的变化。渐进式系统设计和质量保证将按照FDA的指导方针进行。拟议的商业应用：这种新的和改进的体外清除毒素的方法将导致药物过量的更有效和更安全的治疗。如果成功，这项研究将产生一种比现在更有效、更安全的治疗方法，并将用于医院和急诊诊所。它也有望应用于侵袭性癌症化疗（即直接器官或肿瘤灌注后去除化疗药物）。建议的方法，应尽量减少吸附去除正常存在于血液中的有益物质，可能扩展到治疗某些形式的慢性肾功能和肝功能不全。

Hemoperfusion is used to treat some patients with life-threatening blood levels of drugs or other toxic compounds. These treatments, however, are not as effective as they could be because of associated side effects such as thrombocytopenia and "whole body inflammation," furthermore, conventional hemoperfusion protocol risks releasing micro particles (emboli) into the blood stream of patients. A new approach to conventional hemoperfusion devices proposed herein employs a modified extracorporeal dialysis-like system which is anticipated to overcome many of the disadvantages of conventional hemoperfusion devices. Phase II research will develop a hemoperfusion system that will then be tested with animals to determine efficacy and safety. Theophylline will be used as the test drug and the proposed hemoperfusion system will be employed to safely and rapidly reduce toxic blood levels of this drug to therapeutic concentrations. Furthermore, the effects of the proposed system on blood components as determined by hemolysis, platelet loss, and changes in glucose, electrolytes, and enzyme levels will be ascertained. Evolutionary system design and quality assurance will be practiced following FDA guidelines. PROPOSED COMMERCIAL APPLICATIONS: This new and improved method for extracorporeal clearance of toxins will lead to a more efficient and safer treatment of drug overdose. If successful, the research will result in a more efficacious and safer treatment than is now available, and will be used in hospitals and emergency medical clinics. Applications are also expected in aggressive cancer chemotherapies (i.e., removal of chemotherapeutic agents following direct organ or tumor perfusion). The proposed approach, which should minimize sorptive removal of desirable substances normally present in the blood, might be extended to treat some forms of chronic renal and hepatic insufficiencies.