A device containing immobilized chelator to remove aluminum from TPN solutions

一种含有固定化螯合剂的装置，用于从 TPN 溶液中去除铝

• 批准号: 7393043
• 负责人: Robert Allen Yokel
• 金额: $ 9.96万
• 依托单位: ALKYMOS, INC
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7393043
• 关键词: AA Spectrophotometry; Admixture; Adult; Affinity; Aluminum; Award; Binding; Birth; Brain; Calcium; Calcium Gluconate; Caring; Chelating Agents; Chemicals; Child; Cholestasis; Class; Clinical Research; Complex; Daily; Devices; Economic Development; Egtazic Acid; Encephalopathies; Felis catus; Funding; Goals; Guidelines; Health Personnel; Human; IV Fluid; Intravenous; Intravenous Feeding; Kentucky; Kidney; Knowledge; Label; Legal patent; Length; Ligands; Link; Liver; Marketing; Measures; Medical Device; Metabolic Bone Diseases; Modification; Needles; Neonatal Intensive Care Units; Oral; Parenteral Nutrition; Patients; Phase; Plant Resins; Polymers; Polystyrenes; Premature Infant; Production; Rate; Renal function; Reporting; Research; Research Ethics Committees; Residual state; Resolution; Skeletal system; Small Business Technology Transfer Research; Solutions; Testing; Total Parenteral Nutrition; Toxic effect; United States Food and Drug Administration; Universities; Visit; Work; base; chemical binding; computational chemistry; computer studies; feeding; functional group; gluconate; hydroxamate; mental development; neonate; novel; potentiometric titration; programs

DESCRIPTION (provided by applicant): A high percentage of the ~ 470,000 children born prematurely each year in the US require intravenous feeding after birth because they do not tolerate oral feeding. This is accomplished with a total parenteral nutrition (TPN) solution, which is prepared from component solutions: small and large volume parenterals (SVPs and LVPs). Aluminum (Al) is a common contaminant in some SVPs, particularly calcium gluconate solution. Excessive Al can produce toxicity to the skeletal system and brain. The potential for Al toxicity is significantly greater in humans, such as premature infants, who have reduced renal function, because the kidneys excrete Al. Medical personnel who care for neonates have suggested for years that the Al in these solutions needs to be greatly decreased to avoid Al-induced toxicity. The FDA implemented a labeling requirement for these component solutions that sets a maximum Al concentration in LVPs and requires a statement of the maximum Al concentration in SVPs. This merely documents estimated maximum Al concentration. It is not the actual Al concentration nor does this reduce the Al in SVPs. Based on prior work to develop new chemicals that bind Al (chelators), the long-term objective is to develop a flow-through filter device containing a chelator that is immobilized on small polymer beads to remove Al from solutions. Based on results obtained using computational chemistry, which predicted the strength of binding of novel immobilized chelators with Al, it is proposed to synthesize 3 new chelators which are predicted to be effective in this application, and to synthesize 1 of these new chelators with 3 different tethers, that link it to a resin bead (creating immobilized chelators). These novel chelators will then be characterized to determine their stability constants with Al and their rate and efficiency to complex Al when introduced in Ca gluconate solution. It is proposed to load this immobilized chelator into a filter cartridge that can be used to remove Al from the SVP solutions as they are dispensed through the cartridge from the SVP storage bottles into the final TPN solution. Project Narrative: The proposed work will develop new chemicals (chelators) that can be put into a medical device to remove a toxic contaminant, aluminum (Al), from intravenous solutions. This will remove the potential for Al to produce toxicity to premature infants and other patients who are exposed to Al through intravenous fluids, solving a decades-old problem that has escaped resolution to date.

描述（由申请人提供）：在美国每年约470，000名早产儿中，有很高比例的儿童在出生后需要静脉喂养，因为他们不耐受口服喂养。这是通过全胃肠外营养（TPN）溶液来实现的，TPN溶液由以下组分溶液制备：小体积和大体积胃肠外（SVP和LVP）。铝（Al）是某些SVP中的常见污染物，特别是葡萄糖酸钙溶液。过量的铝会对骨骼系统和大脑产生毒性。铝毒性的潜力是显着更大的人，如早产儿，谁有肾功能下降，因为肾脏排泄铝。医疗人员谁照顾新生儿多年来建议，这些解决方案中的铝需要大大减少，以避免铝诱导的毒性。FDA对这些组分溶液实施了标签要求，规定了LVP中的最大铝浓度，并要求声明SVP中的最大铝浓度。这仅记录了估计的最大Al浓度。这不是实际的铝浓度，也不会减少SVP中的铝。基于先前开发结合Al的新化学品（螯合剂）的工作，长期目标是开发一种含有螯合剂的流通式过滤器装置，该螯合剂固定在小聚合物珠上以从溶液中去除Al。基于使用预测新型固定化螯合剂与Al的结合强度的计算化学获得的结果，提出合成3种预测在该应用中有效的新型螯合剂，并合成这些新型螯合剂中的1种，其具有3种不同的系链，将其连接到树脂珠（产生固定化螯合剂）。这些新的螯合剂，然后将其特征在于，以确定其与铝的稳定常数和它们的速度和效率，以配合铝时，引入葡萄糖酸钙溶液。建议将该固定化螯合剂加载到滤芯中，当SVP溶液通过滤芯从SVP储存瓶分配到最终TPN溶液中时，滤芯可用于从SVP溶液中去除Al。 项目叙述：拟议的工作将开发新的化学品（螯合剂），可以放入医疗设备中，以去除静脉注射溶液中的有毒污染物铝（Al）。这将消除铝对早产儿和其他通过静脉注射暴露于铝的患者产生毒性的可能性，解决了一个数十年来一直未能解决的问题。