Hydralazine / Music Neanderthal - Synthesis And Controlled Release Studies Polyacrylamide Macromolecular Prodrug

Two kinds macromolecular prodrugs were designed and synthesized with PHPMA as the carrier,then the products were characterized through IR、DSC、UV and Element analysis.The controlled release studies in vitro were performed by UV absorption in different buffer solutions simulating body environment.The first kind prodrug was PHPMA-HYD. The HPMA was synthesized by acylation reaction. With AIBN as radical initiator,PHPMA was synthesized by polymerization reaction.Different molecular-weight PHPMA were synthesized by changing the dosages of AIBN. Then the PHPMA-HYD were prepared by the reation of PHPMA and HYD with succinic anhydride as the linker. The product was characterized by DSC、UV and IR.The controlled release of prodrug studies were performed in different buffer solutions (pH=1.1、 pH=7.4、pH=10.0), the results showed that three prodrugs all can release the active compound of HYD slowly. At the same buffer solutions, the release rate of HYD for the different PHPMA-HYD were that:PHPMA11000-HYD> PHPMA17000-HYD> PHPMA24000-HYD.At the different buffer solutions,the release rate for the same prodrugs were that:pH=10.0>pH=7.4>pH=1.1.The second kind prodrug was PHPMA-LND. The PHPMA-LND were prepared by the reation of PHPMA and LND with DCC as the dehydrator. Three prodrugs were synthesized by changing the molecular-weight of PHPMA:PHPMA11000-LND、PHPMA17000-LND、 PHPMA24000-LND. Then the controlled release of prodrug studies were performed in different buffer solutions(pH=1.1、pH=7.4、pH=10.0),the results showed that three prodrugs all can release the active compound of LND slowly. At the same buffer solutions, the release rate of LND for the different PHPMA-LND were that:PHPMA11000-LND> PHPMA17000-LND>PHPMA24000-LND. At the different buffer solutions,the release rate for the same prodrugs were that:pH=10.0>pH=7.4>pH=1.1.The two kinds prodrugs were both performed in the pH=8.0buffer solution in the present of α-chymotrypsin,at the same time,with the no α-chymotrypsin one as a contrast experiment.The results showed that the present of α-chymotrypsin can quicken the rate of the prodrug to some degrees,but not obvious.