IMMOBILIZED CHELATOR FOR EXTRACORPOREAL LEAD REMOVAL

用于体外除铅的固定化螯合剂

• 批准号: 3502129
• 负责人: CLARA M AMBRUS
• 金额: $ 4.45万
• 依托单位: HEMEX, INC.
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-01 至 1992-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3502129
• 关键词: atomic absorption spectrometry; blood disorder chemotherapy; blood proteins; calcium; chelating agents; chemical binding; chemical reaction; chemical synthesis; drug adverse effect; drug design /synthesis /production; extracorporeal circulation; gel filtration chromatography; heavy metals; human tissue; iminoacid; lead; lead poisoning; lyophilization; metal complex; molecular site; molecular weight; plasma; polysaccharides; polystyrenes; silicates; thiocarbamate

Recent reports estimate the number of children with lead intoxication at 230,000, the number of industrial workers with lead poisoning at 530,000. These number create a medical problem of alarming magnitude, because treatment with available chelators has serious side-effects. Even the chelator-lead complexes that for in the blood during treatment are damaging the kidneys during elimination. We have developed a polysulfone hollow-fiber device with immobilized chelators, for the extracorporeal removal of lead from blood and subsequently from storage sites. Since the chelator is immobilized the chelation process occurs outside of the circulation, and toxicity of lead and lead-chelator complex is eliminated. The goal in the Phase I studies is to explore the feasibility of developing a lead-chelator device of clinical significance. The following studies will be conducted: Chelator functions will be synthesized on various supports and lead binding capacity tested Colloidal suspensions will be prepared from these chelators and tested for capacity and lead specificity. By step- wise selection, the most promising agents will be loaded into hollow fiber cartridges and evaluated for capacity, specificity, and kinetics of lead removal. Results will help select the optimal chelator to develop for a prototype for clinical use with Phase II support.

最近的报告估计，铅中毒儿童的数量 23万产业工人铅中毒人数 530,000。 这些数字造成了令人震惊的医疗问题， 因为使用现有的螯合剂治疗具有严重的副作用。 甚至治疗期间血液中的螯合剂-铅复合物 在消除过程中会损害肾脏。 我们开发了一种聚砜中空纤维固定装置 螯合剂，用于体外去除血液中的铅 随后从存储地点。 由于螯合剂是固定的 螯合过程发生在循环之外，并且毒性 铅和铅螯合剂复合物被消除。 第一阶段研究的目标是探索可行性 开发具有临床意义的铅螯合剂装置。 这 将进行以下研究： 螯合剂功能将在各种支持物和先导物上合成 结合能力测试 胶体悬浮液将由以下物质制备 对这些螯合剂进行了容量和先导特异性测试。 按步骤- 明智的选择，最有前途的代理将被装入空心 纤维盒并评估容量、特异性和动力学 去除铅。 结果将有助于选择最佳螯合剂 在 II 期支持下开发临床使用的原型。

项目成果

Treatment of lead poisoning with an immobilized chelator comparison with conventional therapy.

使用固定螯合剂治疗铅中毒与常规疗法的比较。

• 发表时间: 2001
• 期刊: Research communications in molecular pathology and pharmacology.
• 作者: Ambrus,CM;Anthone,S;Stadler,A;Cameron,MS;Wells,K;Stadler,I;AmbrusJr,JL
• 通讯作者: AmbrusJr,JL