Synthesis Of N-isopropyl Acrylamide Graft Polymerization And Its Products In Pharmaceutical Applications

In this thesis,the important monomer N-isopropylacrylamide(NIPA)was synthesized, which is a representative monomer for synthesis of environmental sensitive materials.The target production was prepared by using Ritter reaction and acryloyl chloride methods respectively.Reaction conditions such as solvent,proportion of reactants,reaction time,reaction temperature and dosage of acids were investigated systemic.The optimum technical conditions were gotten based on analyzing the influence factors of yield ratio.Moreover, thermosensitive copolymers were prepared by graft copolymerization of NIPA onto chitosan (CS)under chemical andγ-ray irradiation initiators respectively.By the research of CS-g-NIPA copolymerization,we investigated regularity of the different copolymers' graft ratio(G%),graft efficiency(GE%)and lower critical solution temperature(LCST).The produced copolymers'LCST in 35℃and 38℃were picked out being used to drug delivery system.The drug delivery behavior of CS-g-NIPA copolymer was studied by using berberine as the drug model.The detailed experiments are as follows:1.We prepared NIPA in Ritter Reaction.The results indicate that using petroleum ether as solvent,the proportion of isopropanol and acrylonitrile is 2:1,isopropanol and acid 1:1.25,temperature is 60℃,3.5h,we can get the best results,and the yield ratio is upon 67%.2.We prepared NIPA by acryloyl chloride and isopropylammonium.Using petroleum ether as solvent,we got acryloyl chloride by acryloyl acid and sulfuryl dichloride in room temperature.Afterward we prepared the target production NIPA in the best experimental condition,whichi was as follows:acryloyl chloride,isopropylammonium, triethylamine in terms of 1:1:1,in ice-salt bath 1.5h.The yield ratio is 76%.3.The recrystal productions of two methods are white pin shape crystals which are characterized by spectra methods.Melting point is 65-66℃,and all of the spectra such as IR,~1H NMR,and GC-MS indicate that the object is the target production NIPA.4.We prepared CS-g-NIPA copolymers with ammonium persulfate as initiator,and got LCST by spectrophotometer which can measure changes of copolymers' transmittance with temperature.The regularity of the different copolymers'GE%,G%and LCST were investigated.The results indicate that there is a change point of LCST when G% is upon 60%.5.We prepared CS-g-NIPA copolymers byγ-ray irradiation initiators.The influences of GE%and G%with irradiation dose between 250 and 4000Gy,and with differences of ratio between CS and NIPA were investigated.Moreover,copolymers' LCST on different conditions was gotten by spectrophotometer.The results indicate that the copolymers are temperature sensitive when G%is upon 70%,and LCST rise with G% increasing.6.Using CS-g-NIPA copolymers as pharmaceutical excipients,we investigated dissolution of berberine in simulate gastric juice.The results indicate that CS-g-NIPA copolymer pharmaceutical excipients are great effect on sustained release.The effection is greater when copolymer's LCST is below the body temperature.