Prolonged release amino cpds. prodn. - by reacting (meth)acrylic acid ester or amide reaction products with amino acids and copolymerizing

摘要

New process converts active substance with an NH2 group into polymeric form, intended for prolonged release of the active substance by enzymatic cleavage. A substd. amide or ester of acrylic or methacrylic acid having a chain of is not 3 atoms in the side-chain terminating in the C-atom of the carboxyl group is condensed with the alpha-amino group of an L-amino acid. The active cpd. is then bound via its NH2 group to the carboxyl group of the amino acid. The resulting monomer is copolymerized with a hydrophilic monomer based on N-alkyl-(meth)acrylamide, or N, N-dialkylacrylamide ('alkyl' being 1-6C). The hydrophilic monomer may contain 1-3 OH groups or glycol (meth)acrylate ('glycol' being ethylene, propylene, butylene, diethylene or triethylene glycol, or homologous 2-6C polyglycols). The copolymerization can be carried out in the presence of smaller amts. of further monomers, which can act as crosslinking agents. The polymers permit regulation of the physical and biological behaviour of the active substance by variation of the character and molecular weight of the polymeric carrier. Rate of enzymatic cleavage can also be regulated by the length of the side-chain. The active substance is protected against premature excretion and against inactivation (e.g. histamine can be protected against the action of histaminase). Examples of L amino acids which can be used are phenylalanine, tyrosine, alanine, citrulline and ornithine. In an example, a copolymer contg. 97.6 mol. % N-(2-hydroxypropyl)-methacrylamide and 2.4 mol. % N-methacryloylglycylphenylalanyl nitroanilide is produced by direct copolymerization. The copolymer is used as a substrate for enzymatic cleavage by chymotrypsin.