| Poly (N-acryloylmorpholine) (PAcM), a new type of amphiphilic polymer is of great interest for the potential value in biomedical application, especially in both preparing macromolecular prodrugs and modifying enzyme surfaces, due to its biocompatible, non-toxic and low immunogenic properties. Based on previous research work, the synthesis and characterization of PAcM oligomer were accomplished in this study. Meanwhile, its synthetic process, conjugation with drugs and hydrolysis kinetic behavior of PAcM prodrugs were also investigated.Firstly, the three-step synthetic reactions initiated from methacrylate were chosen as an appropriate pathway to prepare N-acryloylmorpholine monomer. The synthetic conditions including proportion of substrates, reaction temperature, catalysts and polymerization inhibitor were investigated as influence factors on the conversion rates, and then a process suitable for industrial production was finally determined.Secondly, using 2,2'-Azoisobutyronitritle (AIBN) as initiator, 2-mercaptoethanol as chain transfer agents, Poly (N-acryloylmorpholine) which has a terminated hydroxyl function had been prepared through free radical polymerization reaction. The raw product was finally fractionated by means of solvent-non-solvent precipitation techniques and the narrow distributed PAcM oligomer whose Mp ≈ 5 kD was isolated.Thirdly, We connected the oligomeric carriers of PAcM with naproxen, flurbiprofen, ketoprofen by means of ester bonding .Then prodrugs were purified and isolated.Lastly, we constructed an effective and accurate method to determine the concentration of naproxen by HPLC. We can concluded that the concentration of naproxen is higher in the stimulated gastric fluid than in the intestine liquid and the prodrugs may represent an effective way to prolong the pharmacological activity by a gradual release of free drugs from the macromolecular matrix.
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