Uchiyama T, Yamamoto A, Hatano H, Fujita T, Muranishi S
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Japan.
Biol Pharm Bull. 1996 Dec;19(12):1618-21. doi: 10.1248/bpb.19.1618.
The effectiveness and local toxicity of absorption enhancers on the absorption of phenol red (PR) from the large intestine of rats were examined using an in situ loop method. The absorption enhancers used in this study were sodium glycocholate (GC-Na), sodium taurocholate (TC-Na), sodium deoxycholate (DC-Na), EDTA, sodium salicylate (Sal-Na), sodium caprate (Cap-Na), diethyl maleate (DM), N-lauryl-beta-D-maltopyranoside (LM) and mixed micelles (MM), all used at a concentration of 20 mM. Local toxicity was also investigated by assessing protein and phospholipid release as biological markers. DC-Na and MM were the most effective absorption enhancers, but they caused considerable release of proteins and phospholipids. GC-Na, TC-Na and LM, which caused little or only slight membrane damage, promoted PR absorption. Sal-Na, DM and EDTA did not enhance PR absorption. Overall, a correlation exists between the area under the curve of PR and protein and phospholipid release in the presence of absorption enhancers. However, GC-Na, TC-Na and LM promoted the absorption of PR with low toxicity. From these results, we concluded that GC-Na, TC-Na and LM are effective absorption enhancers which have low levels of toxicity at a concentration of 20 mM.
采用原位肠袢法，研究了吸收促进剂对大鼠大肠中酚红（PR）吸收的有效性及局部毒性。本研究中使用的吸收促进剂为甘氨胆酸钠（GC-Na）、牛磺胆酸钠（TC-Na）、脱氧胆酸钠（DC-Na）、乙二胺四乙酸（EDTA）、水杨酸钠（Sal-Na）、癸酸钠（Cap-Na）、马来酸二乙酯（DM）、N-月桂酰-β-D-麦芽糖苷（LM）和混合胶束（MM），所有促进剂的使用浓度均为20 mM。还通过评估蛋白质和磷脂的释放作为生物学标志物来研究局部毒性。DC-Na和MM是最有效的吸收促进剂，但它们会导致蛋白质和磷脂大量释放。GC-Na、TC-Na和LM对膜造成的损伤很小或仅有轻微损伤，可促进PR的吸收。Sal-Na、DM和EDTA不能增强PR的吸收。总体而言，在存在吸收促进剂的情况下，PR曲线下面积与蛋白质及磷脂释放之间存在相关性。然而，GC-Na、TC-Na和LM在低毒性的情况下促进了PR的吸收。根据这些结果，我们得出结论，GC-Na、TC-Na和LM是有效的吸收促进剂，在浓度为20 mM时毒性较低。
