Biodegradable polymers derived from amino acids

This report describes general methods for the synthesis of biodegradable poly(amide anhydrides) and poly(amide esters) based on naturally occurring amino acids. The polymers were synthesized from dicarboxylic acids prepared by amidation of the amino group of an amino acid with a cyclic anhydride, or by amide coupling of two amino acids with a diacid chloride. This approach was demonstrated by the synthesis of polymers based on alanine and proline. Homo- and copolyanhydrides with sebacic acid of β-alanyl succinamide, and N,N'-bis(β-alanine)-1,3-benzene dicarboxamide, were synthesized by melt or solution polymerization. The copolymers prepared in solution had molecular weights up to 4500, while the copolymers prepared by melt condensation had higher molecular weights of about 30 000. Polymers were also prepared directly from the reaction of an amino acid and a diacid chloride. These polymers were soluble in dichloromethane and had molecular weights in the range 800-4800. A polyester of l-prolyl succinamide was prepared by melt condensation of the methyl ester derivative of the diacid and propylene glycol with acid catalysis. The polymer was transparent and pliable, and had a weight average molecular weight of 33 000. The poly(amide anhydrides) based on alanine and sebacic acid display a nearly linear degradation pattern with complete degradation in vitro after 5-10 d (phosphate buffer, pH 7.4 at 37°C).