A device containing immobilized chelator to remove aluminum from TPN solutions

描述（由申请人提供）：美国每年约470,000名早产儿童中有很大一部分在出生后需要静脉喂养，因为他们不能耐受口服喂养。这是通过总肠外营养（TPN）溶液完成的，该溶液由成分溶液制备：小体积和大体积肠外营养（svp和LVPs）。铝（Al）是一些svp中常见的污染物，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。人类，如肾功能下降的早产儿，由于肾脏排泄Al，因此Al毒性的可能性要大得多。照顾新生儿的医务人员多年来一直建议，这些溶液中的Al需要大大降低，以避免Al引起的毒性。FDA对这些成分溶液实施了标签要求，设定了LVPs中的最大Al浓度，并要求声明SVPs中的最大Al浓度。这仅仅记录了估计的最大铝浓度。它不是实际的Al浓度，也不会减少svp中的Al。基于先前开发结合Al（螯合剂）的新化学物质的工作，长期目标是开发一种包含螯合剂的流动过滤装置，该装置固定在小聚合物珠上，以去除溶液中的Al。基于计算化学预测新型固定化螯合剂与Al结合强度的结果，提出了3种预测在该应用中有效的新型螯合剂，并将其中1种新型螯合剂与3种不同的系链结合，将其连接到树脂珠上（形成固定化螯合剂）。这些新型螯合剂将被表征，以确定它们与Al的稳定常数，以及它们在葡萄糖酸钙溶液中引入时对络合Al的速率和效率。建议将这种固定化螯合剂装入一个滤筒，当SVP溶液通过滤筒从SVP储存瓶分配到最终的TPN溶液时，该滤筒可用于从SVP溶液中去除Al。

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.