The invention concerns the method of production of a polyanionic macromolecule which is a protein built, among others, from polar amino acids such as lysine, arginine, aspartic acid, glutamic acid), characteristic in that, as a result of the reaction between amine groups and the cyclic anhydride of dicarboxylic acid, the charge changes towards more negatively charged carrier. This reaction gives rise to better therapeutic properties of macromolecules modified in this way.