(S)-萘普生反酯衍生物在不同pH条件下脂水分配系数的测定  

Determination of lipo-hydro partition coefficients of(S)-naproxen reverse esters at different pH values

作　　者：唐静怡[1,2] 石磊[3] 向阳芳[1,2] 徐智[1] 罗健[1] 

机构地区：[1]中南大学湘雅医院药剂科,长沙410008 [2]中南大学药学院,长沙410013 [3]湖南大学化学化工学院,长沙410082

出　　处：《中国新药杂志》2013年第10期1210-1213,共4页Chinese Journal of New Drugs

基　　金：湖南省自然科学基金(07JJ3022)

摘　　要：目的:萘普生属芳基丙酸类非甾体抗炎药,为降低其胃肠道不良反应,提高其生物利用度,将其改造为(S)-萘普生反酯前药。方法:因药物的吸收与药物本身的脂水分配系数等理化性质紧密相关,为预测(S)-萘普生反酯衍生物的吸收状况,本实验采用摇瓶法使其在不同pH缓冲体系中达到平衡,紫外分光光度法测定并计算(S)-萘普生反酯衍生物在不同pH环境下的表观脂水分配系数,探讨药物分子结构与介质pH值对其表观脂水分配系数的影响。结果:引入基团不同,(S)-萘普生反酯衍生物的吸光度(A)与lgP大小均不同;同一衍生物于不同pH环境中,lgP大小也有差异,且各(S)-萘普生反酯衍生物均在pH弱酸性条件下达到lgP最大值。结论:(S)-萘普生反酯衍生物的脂水分配系数与其自身分子结构紧密相关,与介质的pH环境等影响因素有关。Objective ：To determine the lipo-hydro partition coefficients of a series of （S）-naproxen reverse esters which are transformed from （S）-naproxen,an aryl propionic nonsteroidal anti-inflammatory drug, in order to decrease the gastrointestinal tract side effect and increase the stability in vivo. Methods： Partition balance of （S）- naproxen reverse esters between n-oetanol and different pH buffer solutions were reached by flask shaking method, and the absorbances of （S）-naproxen reverse esters at different pH values were determined by ultraviolet spectro- photometer,then the lipo-hydro partition coefficients were computed. Results：The absorbances and lgP values of （S）-naproxen reverse esters with different introduced groups were different from each other;the lgP of each deriva- tive varied at different pH values at room temperature, and the maximum lgP values of all of the derivatives ap- peared in weak acidic buffer solution. Conclusion： The lipo-hydro coefficients of （S）-naproxen reverse esters closely correlate to the molecular structures,and are affected by the pH value of the medium.

关 键 词：(S)-萘普生反酯衍生物 脂水分配系数 酸碱度 分子结构 

分 类 号：R94[医药卫生—药剂学] R971.1[医药卫生—药学]