A device containing immobilized chelator to remove aluminum from TPN solutions

描述(申请人提供)：在美国每年约47万名早产儿童中，有很高比例的人在出生后需要静脉喂养，因为他们不能容忍口服喂养。这是通过完全肠外营养(TPN)解决方案实现的，该解决方案由成分溶液：小容量和大容量肠外营养(SVP和LVP)配制而成。铝是一些SVP中的常见污染物，尤其是葡萄糖酸钙溶液。过量的铝会对骨骼系统和大脑产生毒性。铝中毒的可能性在人类中明显更大，例如早产儿，他们的肾功能下降，因为肾脏排泄铝。照顾新生儿的医务人员多年来一直建议，这些溶液中的铝需要大幅减少，以避免铝中毒。FDA对这些成分溶液实施了标签要求，设定了LVP中的最大铝浓度，并要求对SVP中的最大Al浓度进行说明。这只是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。基于之前开发结合铝(螯合剂)的新化学品的工作，长期目标是开发一种包含螯合剂的流过过滤装置，该装置固定在小的聚合物珠子上，以从溶液中去除铝。基于计算化学的结果，预测了新型固定化螯合剂与铝的结合强度，建议合成3个在这一应用中预测有效的新的螯合剂，并用3种不同的系链合成其中的1个，将其连接到树脂珠上(创建固定化的螯合剂)。然后对这些新型的螯合剂进行表征，以确定它们与铝的稳定常数，以及它们在葡萄糖酸钙溶液中对络合铝的速率和效率。建议将这种固定化的螯合剂装入滤芯中，当SVP溶液通过滤芯从SVP储存瓶分配到最终的TPN溶液中时，该滤芯可用于从SVP溶液中去除铝。 项目简介：这项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，从静脉溶液中去除有毒污染物铝(Al)。这将消除铝对早产儿和通过静脉输液暴露于铝的其他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。

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.