权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

evaluation and invention of endotoxin detoxifying material for clinical application

内毒素解毒材料的临床应用评价及发明

基本信息

批准号：
62870051
负责人：
KODAMA Masashi
金额：
$ 13.82万
依托单位：
Shiga University of Medical Science School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1989
项目状态：
已结题

项目摘要

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.

1)PMX-F的性能评价及临床应用：在此之前，PMX-F在犬和小鼠内毒素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，这种治疗方法也在注入大肠杆菌的败血症休克狗模型上得到了验证。PMX-F能吸附水和血清(含蛋白质溶液)中的内毒素。肿瘤坏死因子也被很好地吸附了2)，但血液中的内毒素测定被发现是不可靠的。所有商业化的测量试剂盒都不能相信。因此，我们尝试和发明了新的方法和样品的前处理方法。现在，新的方法几乎被存档了。通过这种新的方法，PMX-F吸附了患者血液中的内毒素。3)在建立了PMX-F柱的大小和灭菌方法后，经福利部批准，开始了临床试验。并对10例感染性休克患者进行了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验证1协议；病例：败血症患者柱：170ml/体积PMX-F DHP流速：60-200ml/min抗凝剂：肝素或甲磺酸那非他汀持续时间：2小时监测仪：血液中的气体、循环动力因子(Swan-Gantz)血液的化学因素、代谢因素，4)PMX-F治疗感染性休克的相关机制：由于不能相信内毒素的测定方法，因此很难证明血液中内毒素的减少。新的概念强调，注入的内毒素在循环血液中停留的时间比人们认为的立即消失的时间要长。而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认证，但还不是很多。清除血液中的内毒素有权作为治疗内毒素休克的有效方法。