Improved Removal of Protein-Bound Toxins in Dialysis

改善透析过程中蛋白质结合毒素的去除

• 批准号: 6584554
• 负责人: GREGORY R. COLLINS
• 金额: $ 9.98万
• 依托单位: NEPHROS, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6584554
• 关键词: acidity /alkalinity; albumins; biotechnology; biotherapeutic agent; blood filtration; chemical association; chemical conjugate; chronic renal failure; dialysis; dogs; erythrocytes; experimental designs; hemodialysis; high performance liquid chromatography; ionic strengths; ligands; method development; phenols; protein binding; renal toxin

DESCRIPTION (provided by applicant): End Stage Renal Disease (ESRD) is associated with an accumulation of "uremic" toxins in essentially three categories: small water-soluble compounds, larger middle molecules, and small protein bound molecules. Current treatment modalities do not address the removal of small protein-bound substances. This research targets an ionic-hemodiafiltration-based product that removes small protein-bound solutes from blood; this function is not addressed by existing technology. This can be an extension of our unique multistage diafiltration process, with two diafiltration steps in series and substitution fluid added in a middilution mode (US Patent #6303036); or can be integrated with standard dialysis technology. An agent is added to dialysate fluid entering a first stage, causing an ionic (pH) shift of the blood, thereby dissociating a significant portion of protein-bound toxins from their conjugated protein counterparts. Once unbound, the small toxins are transported across a semi-permeable membrane by diffusive/convective mechanisms. A second stage acts to return the ionic-altered blood to a normal condition before reinfusion. This Phase I research will qualify agents to be added to the dialysate fluid entering the first stage, so as to ensure safety and efficacy. PROPOSED COMMERCIAL APPLICATION: As of 2001, there were over 300,000 ESRD patients in the US, served by over 60,000 dialysis machines; this market is expected to exceed $500 million annually by 2008. Incorporating ionic technology will provide the unique benefit of removing protein-bound toxins, thereby reducing various comorbid conditions associated with toxic accumulation, improving overall patient health, and reducing associated hospitalizations, currently representing a $600 million+ annual expenditure. Additional applications include treatment of patients intoxicated with poisons or drugs with known protein binding characteristics.

描述（由申请人提供）：末期肾病（ESRD）与本质上三类的“尿毒症”毒素的积累有关：小水溶性化合物，较大的中间分子和小蛋白质结合的分子。当前的治疗方式不能解决切除小蛋白质结合物质的方法。 这项研究针对的是基于离子 - 稀释的产物，可去除血液中蛋白质结合的小溶质。现有技术无法解决此功能。这可以是我们独特的多阶段透明过程的扩展，并在串联的串联和替代流体中添加了两个渗透步骤（美国专利＃6303036）；也可以与标准透析技术集成。添加了一种药物进入第一阶段的透析液，从而导致血液的离子（pH）转移，从而从其共轭蛋白质对应物中解离了一大批蛋白质结合的毒素。一旦未结束，小毒素就会通过扩散/对流机制在半渗透膜上运输。第二阶段的作用是在再灌注之前将离子变化的血液恢复到正常状态。这一I阶段的研究将使代理将其添加到进入第一阶段的透析液中，以确保安全性和有效性。 拟议的商业应用程序：截至2001年，美国有30万名ESRD患者，由60,000多个透析机服务；预计到2008年，该市场预计每年将超过5亿美元。纳入离子技术将为消除蛋白质结合的毒素的独特好处，从而减少与有毒积累相关的各种合并症，改善了整体患者健康，并降低了相关的住院治疗，目前代表了6亿美元的年度支出。 其他应用包括治疗毒药或具有已知蛋白质结合特征的药物的患者。