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）：美国每年约有 470,000 名早产儿，其中很大一部分在出生后需要静脉喂养，因为他们不耐受口服喂养。这是通过全肠外营养 (TPN) 溶液来实现的，该溶液由以下组分溶液制备：小容量和大容量肠外营养剂（SVP 和 LVP）。铝 (Al) 是一些 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。对于肾功能下降的早产儿等人类来说，铝中毒的可能性要大得多，因为肾脏会排泄铝。照顾新生儿的医务人员多年来一直建议，需要大幅降低这些溶液中的铝含量，以避免铝引起的毒性。 FDA 对这些成分解决方案实施了标签要求，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铝浓度。它不是实际的铝浓度，也不会减少 SVP 中的铝含量。基于先前开发结合铝（螯合剂）的新化学品的工作，长期目标是开发一种包含固定在小聚合物珠上的螯合剂的流通过滤装置，以去除溶液中的铝。基于使用计算化学获得的结果，预测了新型固定化螯合剂与 Al 的结合强度，建议合成 3 种预计在该应用中有效的新型螯合剂，并合成其中 1 种具有 3 种不同螯合剂的新型螯合剂。系绳，将其连接到树脂珠（产生固定的螯合剂）。然后对这些新型螯合剂进行表征，以确定它们与 Al 的稳定性常数以及引入葡萄糖酸钙溶液时络合 Al 的速率和效率。建议将这种固定螯合剂装入滤筒中，当 SVP 溶液通过滤筒从 SVP 存储瓶分配到最终的 TPN 溶液中时，该滤筒可用于去除 SVP 溶液中的 Al。 项目叙述：拟议的工作将开发新的化学品（螯合剂），可将其放入医疗设备中，以去除静脉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输液接触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得到解决的问题。