摘要
目的:研究酮洛芬-丹皮酚偶合物(Ket-Pae)的稳定性及其降解动力学。方法:RP-HPLC测定Ket-Pae的溶解度和油水分配系数,通过初步稳定性试验考察Ket-Pae稳定性,并进行不同pH条件和血浆中的降解动力学研究。结果:在高温条件下Ket-Pae有明显降解的现象;与酮洛芬和丹皮酚相比,Ket-Pae的水溶性降低200～300倍,lnP上升4倍左右;Ket-Pae的降解曲线呈V-型分布,pH=5时最稳定(t1/2=14.4d)。在血浆中的Ket-Pae降解半衰期很短(t1/2=1.3min),可迅速降解为酮洛芬和丹皮酚。结论:Ket-Pae的脂溶性增强,其稳定性受高温和pH的影响。
Objective：To study the stability and degradation kinetics of Ketoprofen-Paeonol conjugate（Ket-Pae）.Method：RP-HPLC method was used to determine the solubility and partition coefficient of Ket-Pae.Stability test was carried out to investigate the factors affecting Ket-Pae.The kinetic studies of Ket-Pae degradation were conducted in different pH buffer solutions and 80% rat plasma at 37 ℃.Result：Ket-Pae showed significant degradation phenomenon at high temperature.The solubility of Ket-Pae was decreased about 200 to 300 times compared with parent drugs in water while the lnP increased about 4 times.The degradation curve displayed a V-shape,and kept maximum stability at week acidic（pH 5.0,t1/2=11.4 d）.Ket-Pae degraded quickly with very short half life of 1.3 min in plasma,therefore easily released ketoprofen and paeonol.Conclusion：The lipophilicity of Ket-Pae is increased,its stability is affected by temperature and pH value.
出处
《中国中药杂志》
CAS
CSCD
北大核心
2010年第15期1943-1946,共4页
China Journal of Chinese Materia Medica
基金
国家"重大新药创制"科技重大专项(2009ZX09502-009)
江苏省高校自然科学研究计划(SZ132826)
科技部国际科技合作项目(2009DFA31330)
关键词
酮洛芬
丹皮酚
偶合物
稳定性
降解动力学
ketoprofen
paeonol
conjugate
stability
degradation kinetics
