Otagiri M, Imai T, Koinuma H, Matsumoto U
Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
J Pharm Biomed Anal. 1989;7(8):929-35. doi: 10.1016/0731-7085(89)80017-2.
The interaction of coumarin anticoagulants with polyvinylpyrrolidone (PVP) was investigated using a fluorescence technique. The fluorescence intensities of warfarin and phenprocoumon were greatly enhanced following binding to PVP, while the fluorescence of 4-hydroxycoumarin was little enhanced in the presence of PVP. The enhanced fluorescence of warfarin and phenprocoumon bound to PVP can be explained by their incorporation into the hydrophobic environment in the PVP and by a decrease in the internal rotation of the alpha-substituted benzyl group in the drugs. The binding parameters of warfarin and phenprocoumon were estimated by the Klotz method; the binding constants for phenprocoumon and warfarin were found to be 2.6 X 10(4) and 2.2 X 10(4) M-1, respectively. The 13C-NMR measurements suggest the lactone moiety in the 4-hydroxycoumarin and the substituted benzene ring play an important role in the binding to PVP.
采用荧光技术研究了香豆素类抗凝剂与聚乙烯吡咯烷酮（PVP）的相互作用。华法林和苯丙香豆素与PVP结合后，其荧光强度显著增强，而在PVP存在的情况下，4-羟基香豆素的荧光增强很少。华法林和苯丙香豆素与PVP结合后荧光增强，这可以通过它们融入PVP的疏水环境以及药物中α-取代苄基内旋转的减少来解释。采用Klotz法估算了华法林和苯丙香豆素的结合参数；发现苯丙香豆素和华法林的结合常数分别为2.6×10⁴和2.2×10⁴ M⁻¹。¹³C-NMR测量表明，4-羟基香豆素中的内酯部分和取代苯环在与PVP的结合中起重要作用。
