Study On Preparation Of PLLA Copolymer And Performance Of Microspheres

Polylactic acid (PLA) is a high performance biomedical polymer material, but there are also some limitations in use. For example, intermediate product of PLA degradation is lactic acid, which will cause aseptic inflammation in the body, resulting in adverse reactions; chemical structure of PLA is lack of reactive functional groups; its hydrophilic is poor, and its degradation cycle is uncertain.In order to improve performance of poly(L-lactic acid) (PLLA), we taken L-lactic acid and chitosan (CS) as raw materials in this dissertation. CS, a kind of alkaline polyelectrolyte containing hydrophilic group, and PLLA were copolymerized through the role of efficient catalysts. Grafting copolymers of PLLA and CS (PLCS) were prepared to microspheres by the solvent evaporation method, and PLCS microspheres were compared with PLLA microspheres. The results of the research were expanded at the following points:First, the influence factors in the progress of preparing PLCS were studied according to monofactor method and multifactor orthogonalizing design method.The ratio of raw materials (-NH2: LA), the amount of catalyst (DCC:DMAP:LA), the reaction concentration of lactic acid and reaction time could affect PLCS characterize in evidence. The optimum preparation condition was: the ratio of raw materials was 1:15, the amount of catalyst was 1:0.053:1, the reaction concentration of lactic acid was 1.88mol/L, the reaction time was 24h. The copolymer prepared by the optimun preparation method was high yield and its contact angle was small.Second, we prepared Urapidil Hydrochloride-PLLA microspheres and Urapidil Hydrochloride-PLCS microspheres, and researched the characteristics of them. The result showed that, under the condition of the same dosing ratio, the drag loading efficiency of PLCS microspheres was always more than it of PLLA microspheres whether ethanol was added to organic phase or not. Urapidil Hydrochloride-PLLA microspheres and Urapidil Hydrochloride-PLCS microspheres were smooth, regular in morphology, good decentralization, and both of their average particle sizes were narrow size distribution.Third, in vitro release of Urapidil Hydrochloride from microspheres was performed by oscillating in constant temperature. The release study indicated that the Urapidil Hydrochloride-PLLA microspheres, Urapidil Hydrochloride-PLCS microspheres and coating CS on Urapidil Hydrochloride-PLLA microspheres exhibited sustained-release capacity, and the kinetics of all these microspheres in vitro release could be described by Higuchi equation. PLCS microspheres released the drug faster than PLLA microspheres and coating CS on PLLA microspheres. The time of maximum cumulative drug release rate of PLCS microspheres was shorter than that of another two kinds of microspheres.