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）：美国每年过早出生的约470,000名儿童中有很高的比例需要出生后静脉注射，因为他们不容忍口服喂养。这是通过总肠胃外营养（TPN）溶液来完成的，该溶液是根据组件解决方案制备的：小和大容量寄宿生物（SVPS和LVP）。铝（AL）是某些SVP的常见污染物，尤其是葡萄糖酸钙溶液。过多的Al会对骨骼系统和大脑产生毒性。由于肾脏排泄AL，肾功能降低的人类（例如早产儿）的毒性潜力明显更大。照顾新生儿的医务人员已经建议多年来，这些解决方案中的AL需要大大降低，以避免AL诱导的毒性。 FDA针对这些组件解决方案实现了标记要求，该解决方案设置了LVP中最大浓度的浓度，并且需要对SVP中的最大AL浓度表示。这仅记录了估计的最大浓度。它不是实际的浓度，也不是SVP中的AL。基于先前的工作来开发结合Al（螯合剂）的新化学物质，长期目标是开发一个含有螯合剂的流通滤器装置，该机构固定在小聚合物珠上，以从溶液中去除Al。基于使用计算化学获得的结果，该结果预测了与Al的新型固定螯合剂结合的强度，因此提议合成3个新的螯合剂，这些新螯合剂预计在此应用中有效，并将其中1个与3个不同的tethers合成，将其与3个不同的tethers合成，这些螯合剂将其与Inmbead（形成Immobiliend chelators）联系起来。然后，这些新型螯合剂将被表征，以确定其Al的稳定性常数以及在Ca葡萄糖酸盐溶液中引入时对复杂Al的速率和效率。提议将此固定的螯合剂加载到过滤器墨盒中，该墨盒可用于从SVP解决方案中取出Al，因为它们通过墨盒从SVP存储瓶中分配到最终的TPN溶液中。 项目叙述：拟议的工作将开发新的化学物质（螯合剂），可以将其放入医疗装置中，以从静脉注射溶液中去除有毒污染物的铝（AL）。这将消除AL对过早婴儿和其他通过静脉内液体暴露于AL的患者产生毒性的潜力，从而解决了迄今已逃脱的数十年问题。