Zoppetti G, Caramazza I, Murakami Y, Ohno T
Italfarmaco Research Center, Milan, Italy.
Biochim Biophys Acta. 1992 Dec 8;1156(1):92-8. doi: 10.1016/0304-4165(92)90101-y.
We have compared the physico-chemical behaviors alone and in the presence of a synthetic bilayer membrane, in aqueous solution and the bioavailability after intraduodenal administration to rabbits, of the two heparin diamine salts ITF-300 and ITF-331 with those of the heparin-amine salt ITF-1175. The three salts have similar structures but different characteristics of compounds tend to form aggregates in solution, but at different critical concentrations. The compounds induce fusion of single-walled vesicles of a synthetic peptide lipid into multi-walled lamellae. The minimal concentrations of the compounds required for the formation of such lamellae differ. This behavior in solution explains the differences in absorption in the animal model. This makes it possible to correlate enhanced heparin bioavailability with the structural nature of the diamine counter-ions used to prepare heparin salts.
我们比较了两种肝素二胺盐ITF - 300和ITF - 331与肝素胺盐ITF - 1175在水溶液中单独存在以及在合成双层膜存在下的物理化学行为，以及十二指肠内给药给兔子后的生物利用度。这三种盐具有相似的结构，但化合物的不同特性倾向于在溶液中形成聚集体，但临界浓度不同。这些化合物会诱导合成肽脂质的单壁囊泡融合成多壁薄片。形成这种薄片所需的化合物最低浓度不同。溶液中的这种行为解释了动物模型中吸收的差异。这使得将增强的肝素生物利用度与用于制备肝素盐的二胺抗衡离子的结构性质相关联成为可能。
