evaluation and invention of endotoxin detoxifying material for clinical application

1)评估PMX-F的能力和临床应用：在此之前，PMX-F在内毒素注入的狗和小鼠休克模型上的循环动力学和存活率方面已经被证明是有效的。然后这种治疗方法也在大肠杆菌注入的脓毒性休克模型上得到了验证。PMX-F能吸附水和含蛋白血清溶液中的内毒素。肿瘤坏死因子吸附良好。但是人们发现血液中内毒素的测量不可靠。所有商业化的测量工具都无法让人相信。为此，我们尝试和发明了新的样品处理方法和前处理方法。现在新方法差不多归档了。通过该方法，PMX-F可吸附患者血液中的内毒素。3)在确定了人用PMX-F柱的规模和灭菌方法后，得到福利部的许可，开始了临床试验。并对10例脓毒性休克患者进行了DHP治疗。这种治疗的有效性和安全性至少在人类病例中得到了证实协议;病例：脓毒症患者柱数：170ml/容积PMX-F用于DHP流速：60 - 200ml/min抗凝血剂：肝素或甲磺司他持续时间：2小时监测：血气、血液循环动力学因子（Swan-Gantz）、血液化学因子、代谢因子、4)PMX-F治疗脓毒症休克疗效的相关机制：血液中内毒素的减少难以证实，因为内毒素的测量方法不可信。新的概念强调，注入的内毒素在循环血液中停留的时间比它被认为立即消失的时间长。内毒素的毒性作用也依然存在。另一方面，血浆对内毒素的解毒能力得到了证实，但并不明显。从血液中去除内毒素是治疗内毒素休克的有效方法。

1) Evaluation of the capacities of PMX-F and clinical application: Until this Grant, PMX-F was already proofed efficient in circulatory dynamics and survival rate on the endotoxin infused shock models of the dogs and mice. And then this treatment was certified also on the E.coli infused septic shock model of dogs. PMX-F could adsorb endotoxin from water and serum (protein contained solution. Tumor necrosis factor was also adsorbed well.2) But measurement of endotoxin in the blood was found to be unreliable. All the commercialized measurement kits could not be believed. So we have tried and invent new method and pretreatment of the sample. Now new method is almost archived. By this new method, PMX-F adsorb endotoxin from the blood of patients.3) After establishments of size and the method of sterilization of PMX-F colomn for human, clinical trial was started under the permission by the Welfare Ministry. And 10 patients with septic shock were treated by this column with DHP. The efficacies and safety of this treatment were certified in the human cases at the least.1 Protocol; Case :septic patients Column:170ml/volume of PMX-F for DHP Flow rate:60 - 200ml/min Anticoagulant:Heparin or Nafamstat mesilate Duration: 2 hours Monitors: glood gases, circulatory dynamic factors(Swan-Gantz) chemical factors of blood, metabolic factors,4) Mechanism related to the efficacy on septic shock by PMX-F: The reduction of endotoxin in the blood was difficult to certify, because the measurement method of endotoxin could not be believed. New concepts was stressed that the infused endotoxin stayed in the circulating blood so long time than that it was thought to disappear from immediately. And toxic effects of endotoxin also remains. On the other hand the endotoxin detoxifying abilities by plasma was certified but not so much. Endotoxin removal from the blood had the right as an effective treatment for endotoxin shock.