Cremonesi P, Strada D, Galimberti G, Sportoletti G
Arzneimittelforschung. 1984;34(9):948-52.
A product containing a high amount of iron and maintaining all the necessary characteristics of stability and solubility for a drug can be prepared by succinylating the proteins, in the specific case the milk proteins, before the reaction with the iron salt. For these derivatives a particular advantage can be achieved, the iron succinyl protein precipitates at the pH of the stomach further keeping the iron bonded and it re-solubilizes at pH higher than 7, the intestine pH level. Electrophoresis indicates that the iron succinyl protein is homogeneous and gel filtration shows an apparent high molecular weight that contributes to the stability of the complexed iron. The preliminary structure determined by analytical and physical-chemical methods indicates that iron, in the form of oligomeric complexes, is tightly bonded to the protein not in chelated structures with basic residues but involving several sites of the protein chain. The solubility of the iron complex is assured by the increased availability of carboxyl groups that follows the succinylation reaction.
通过在与铁盐反应之前使蛋白质（在特定情况下为乳蛋白）琥珀酰化，可以制备出一种含有大量铁且保持药物所有必要稳定性和溶解性特征的产品。对于这些衍生物，可以实现一个特殊的优势，即琥珀酰铁蛋白在胃的pH值下沉淀，进一步保持铁的结合状态，并且在高于7（肠道pH值水平）的pH值下重新溶解。电泳表明琥珀酰铁蛋白是均一的，凝胶过滤显示出明显的高分子量，这有助于复合铁的稳定性。通过分析和物理化学方法确定的初步结构表明，以寡聚体复合物形式存在的铁紧密结合在蛋白质上，不是与碱性残基形成螯合结构，而是涉及蛋白质链的多个位点。琥珀酰化反应后羧基可用性的增加确保了铁复合物的溶解性。
