新型pH敏感性壳聚糖-酮洛芬药物的制备表征及控释性能研究

Synthesis and Characterization New pH-Sensitive Chitosan-Ketoprofen Drug and Exploration Its Drug Release Properties

目的设计智能控释药物合成路线,制备新型药物壳聚糖-酮洛芬(CTS-KPF),并对其进行结构表征和体外释药性能考察。方法利用液相均相法将酮洛芬(ketoprofen,KPF)接枝至线性聚合物壳聚糖(chitosan,CTS)的分子链上,得到壳聚糖-酮洛芬。傅里叶变换红外光谱(FT-IR)、核磁共振波谱(CP/MAS13C-NMR、1H-NMR)表征壳聚糖-酮洛芬的结构,扫描电镜(SEM)观察壳聚糖-酮洛芬的表观形貌,X-射线衍射(XRD)法考察壳聚糖-酮洛芬的结晶性能变化;紫外-可见分光光度法(UV-Vis)分析壳聚糖-酮洛芬在不同pH条件下的释放性能,建立壳聚糖-酮洛芬体外释药模型。结果设计的合成路线合理,成功合成了壳聚糖-酮洛芬;傅里叶变换红外光谱、核磁共振波谱13C-NMR、1H-NMR和扫描电镜以及X-射线衍射验证了壳聚糖-酮洛芬的合成反应机制及其分子结构;壳聚糖-酮洛芬在模拟体液中的释药具有预期的pH敏感性,倾向于较低pH的模拟胃液中释放。结论壳聚糖-酮洛芬是一种pH-敏感性高分子药物,相关结果可为壳聚糖基pH-敏感性高分子智能药物的研究提供参考。

OBJECTIVE To prepare the new drug chitosan-ketoprofen（ CTS-KPF）,and evaluate its characteristies in vitro release. METHODS The drug ketoprofen（ KPF） molecules was grafted to the molecular chain the linear polymer chitosan（ CTS） by homogeneous liquid phase method,preparing the new drug CTS-KPF. The fourier transform infrared spectrum（ FT-IR） and the nuclear magnetic resonance spectroscopy（ CP / MAS13C-NMR,1H-NMR） was used to characterize the structure CTS-KPF; the scanning electron microscopy（ SEM） was used to observe the CTS-KPF apparent morphology; the X-ray diffraction（ XRD） was used to study the change crystallinity CTS-KPF and the ultraviolet-visible spectrophotometry（ UV-Vis） was used to analyze the drug release performance under different pH conditions and establish the model CTS-KPF releasing drug in vitro. RESULTS The synthetic route is reasonable and the CTS-KPF new pH-sensitive drug was synthezed successfully. The FT-IR,CP / MAS ^13C-NMR,^1H-NMR,SEM and XRD verified the chemical reaction mechanism and the molecular structure CTS-KPF. The CTS-KPF drug release performance in simulated body fluid indicates that the CTS-KPF has desired pH-sensitive and it tend to release in low pH simulated gastric fluid. CONCLUSION CTS-KPF is a pH-sensitive polymer drug,the results can provide a reference for the research pH-sensitive polymer smart drugs based on CTS.