Chelating polymeric particles intended for the therapy of Wilson¡¯s disease

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• 作者：Michaela ?kodov¨¢ ; Jan Ku?ka ; Miroslav Vetr¨ªk ; Jan Skopal ; Zuzana Walterov¨¢ ; Ond?ej Sedl¨¢?ek ; Petr ?t¨§p¨¢nek ; Jana Mattov¨¢ ; Pavla Pou?kov¨¢ ; Petr Urb¨¢nek ; Martin Hruby
• 关键词：Wilson&rsquo ; s disease ; Polymer beads ; Copper metabolism ; Selective sorbent ; Amines
• 刊名：Reactive and Functional Polymers
• 出版年：2013
• 出版时间：November, 2013
• 年：2013
• 卷：73
• 期：11
• 页码：1426-1431
• 全文大小：745 K

文摘

Wilson¡¯s disease is a genetic disorder that leads to a high accumulation of copper in multiple organs with subsequent toxic effects. In this paper, a gentle therapy to eliminate harmful copper concentrations in patients with Wilson¡¯s disease is proposed using an oral administration of insoluble polymeric sorbents containing selective chelating groups for copper(II). The sorbents contained triethylenetetramine, N,N-di(2-pyridylmethyl)amine, 8-hydroxyquinoline or 8-hydroxyquinoline-5-sulfonic acid chelating groups bound to a methacrylate-based macroporous support. Nearly quantitative copper(II) uptake within minutes was achieved in buffers modeling the pH range present in the gastric environment (pH 2.0 and 4.0). The sorbents demonstrated chelating selectivity for copper(II) against zinc(II) with ratios of up to 1321. The sorbents demonstrated sufficient stability of the copper complexes against rechelation using studies in a model environment for the small intestine (the presence of chelating amino acids, pH 6.8).