Higaki K, Yata T, Sone M, Ogawara K, Kimura T
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Res Commun Mol Pathol Pharmacol. 2001 Mar-Apr;109(3-4):231-40.
The absorption enhancement by the sodium salts of several fatty acids was investigated in rat large intestine for model compounds having a wide range of molecular weight. Sodium caprylate (C8), sodium caprate (C10), sodium laurate (C12), which are categorized in medium-chain fatty acid, and sodium oleate (C18:1), long-chain unsaturated fatty acid, were employed as lipoidal adjuvants. Phenol red (MW=354.4), glycyrrhizin (822.9), fluorescein isothiocyanate-dextran-4 (FD-4, 4400), FD-10 (9400) and FD-40 (38900) were selected as model compounds for the assessment of the enhancing effect of the lipoidal adjuvants. The absorption of phenol red was promoted at the highest level, about 20 times higher by C12 and C18:1 than the control. The absorption rate - time profiles calculated by deconvolution method showed that C12 takes effect most rapidly and efficiently. In the case of glycyrrhizin, four adjuvants including C12 showed almost the same improvement of the absorption, about 30-40 times larger than the control. C8 and sodium citrate did not significantly enhance the absorption of those model compounds. For FD-4, FD-10 and FD-40, C10, C12 and C18:1 revealed almost the same enhancing effect and the absorption of FD-4, FD-10 and FD-40 was enhanced about 80 times, 1000-1800 times and about 200 times, respectively, larger than the control. The enhancement ratio, the ratio of AUC with adjuvant to AUC of control, suggests that these lipoidal adjuvants would improve most efficiently the absorption of the compound having the molecular weight of around 10000. Furthermore, C12 was suggested to be an effective adjuvant for the compounds with the wide range of molecular weight.
在大鼠大肠中，针对一系列分子量范围的模型化合物，研究了几种脂肪酸钠盐对吸收的增强作用。辛酸（C8）钠、癸酸（C10）钠、月桂酸（C12）钠（均属于中链脂肪酸）以及油酸（C18:1）钠（长链不饱和脂肪酸）被用作脂质佐剂。选择酚红（分子量 = 354.4）、甘草酸（822.9）、异硫氰酸荧光素 - 葡聚糖 - 4（FD - 4，4400）、FD - 10（9400）和FD - 40（38900）作为模型化合物，以评估脂质佐剂的增强效果。酚红的吸收促进作用最为显著，C12和C18:1使其吸收比对照高约20倍。通过去卷积方法计算的吸收速率 - 时间曲线表明，C12起效最快且效率最高。对于甘草酸，包括C12在内的四种佐剂对吸收的改善几乎相同，比对照大30 - 40倍。C8和柠檬酸钠未显著增强这些模型化合物的吸收。对于FD - 4、FD - 10和FD - 40，C10、C12和C18:1显示出几乎相同的增强效果，FD - 4、FD - 10和FD - 40的吸收分别比对照增强约80倍、1000 - 1800倍和约200倍。增强率（即佐剂存在时的AUC与对照的AUC之比）表明，这些脂质佐剂能最有效地改善分子量约为10000的化合物的吸收。此外，C12被认为是对广泛分子量范围的化合物有效的佐剂。
