METHOD OF PREPARATION OF DTPA CROSSLINKED HYALURONIC ACID DERIVATIVES AND MODIFICATION OF SAID DERIVATIVES

摘要

The invention relates to the modification of hyaluronic acid by means of a protonized DTPA bis anhydride in a non-basic polar aprotic solvent in absence of any external base to form crosslinked products. The reaction runs via the formation of a complex and the acylating agent is the hyaluronan co-cation itself, i.e. protonized DTPA bis anhydride. The final crosslinked derivative (linker) comprises three carboxylic groups and three tertiary amines which are capable of complexing various metals effectively. The final DTPA crosslinked hyaluronic acid may also be hydrophobized by means of mono, bis or tris functional alkylating agents.