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，这些治疗并不像它们所能达到的那样有效，因为相关的副作用，如血小板减少和“全身炎症”，此外，传统的血液灌流方案有可能将微小颗粒(栓子)释放到患者的血流中。本文提出的一种传统血液灌流装置的新方法采用了一种改进的体外透析式系统，该系统有望克服传统血液灌流装置的许多缺点。第二阶段的研究将开发一种血液灌流系统，然后将在动物身上进行测试，以确定有效性和安全性。茶碱将被用作试验药物，拟议的血液灌流系统将被用于安全和快速地将该药物的毒性血液水平降低到治疗浓度。此外，还将确定建议的系统对血液成分的影响，如溶血、血小板丢失以及葡萄糖、电解质和酶水平的变化。循序渐进的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更有效和更安全的药物过量治疗。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，并将用于医院和紧急医疗诊所。还有望在侵袭性癌症化疗中得到应用(即，在器官或肿瘤直接灌注后去除化疗药物)。建议的方法应该最大限度地减少对血液中通常存在的理想物质的吸收清除，可以扩展到治疗某些形式的慢性肾和肝功能不全。

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.