Labrasol® is a self-emulsifying excipient that contains saturated polyglycolysed C6-C14 glycerides and this additive is known to improve the intestinal absorption of poorly absorbed drugs after oral administration. However, the effects of formulations similar to Labrasol® on the intestinal absorption of poorly absorbed drugs have not been characterized. In this study, we used insulin as a model peptide drug and examined the absorption-enhancing effects of Labrasol® and its related formulations for insulin absorption in rats. The co-administration of Labrasol-related formulations with insulin reduced the blood glucose levels. Among these formulations, Capryol 90 was the most effective additive. Notably, the effect of Capryol 90 was greater at pH 3.0 than at pH 7.0. Additionally, almost no mucosal damage was observed in the presence of these formulations, as these formulations did not affect the activity of lactate dehydrogenase (LDH) and the amount of protein released from the small intestine. In mechanistic studies, Capryol 90 improved the stability of insulin and suppressed the association with insulin under acidic conditions. The loosening of the tight junctions (TJs) could be the underlying mechanism by which Capryol 90 improved intestinal insulin absorption via a paracellular route. These findings suggest that Capryol 90 is an effective absorption enhancer for improving the intestinal absorption of insulin, without inducing serious damage to the intestinal epithelium.

中文翻译：

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Capryol 90，一种新型的大鼠吸收增强剂，增强了肠道对胰岛素的吸收：对口服胰岛素递送的影响。

Labrasol®是一种自乳化赋形剂，包含饱和的聚乙二醇水解的C6-C14甘油酯，并且已知该添加剂可改善口服后吸收不良的药物在肠道的吸收。但是，尚未鉴定类似于Labrasol®的制剂对吸收不良的药物的肠道吸收的影响。在这项研究中，我们将胰岛素用作模型肽药物，并研究了Labrasol®及其相关制剂对大鼠胰岛素吸收的吸收增强作用。拉布拉索尔相关制剂与胰岛素的共同给药降低了血糖水平。在这些配方中，Capryol 90是最有效的添加剂。值得注意的是，在pH 3.0下，Capryol 90的作用大于在pH 7.0下。另外，在这些制剂的存在下几乎没有观察到粘膜损伤，因为这些制剂不影响乳酸脱氢酶（LDH）的活性和从小肠释放的蛋白质的量。在机理研究中，Capryol 90在酸性条件下改善了胰岛素的稳定性并抑制了与胰岛素的缔合。紧密连接（TJ）的松动可能是Capryol 90通过细胞旁途径改善肠道胰岛素吸收的潜在机制。这些发现表明，Capryol 90是一种有效的吸收促进剂，可改善胰岛素的肠道吸收，而不会引起对肠道上皮的严重损害。在机理研究中，Capryol 90在酸性条件下改善了胰岛素的稳定性并抑制了与胰岛素的缔合。紧密连接（TJ）的松动可能是Capryol 90通过细胞旁途径改善肠道胰岛素吸收的潜在机制。这些发现表明，Capryol 90是一种有效的吸收促进剂，可改善胰岛素的肠道吸收，而不会引起对肠道上皮的严重损害。在机理研究中，Capryol 90在酸性条件下改善了胰岛素的稳定性并抑制了与胰岛素的缔合。紧密连接（TJ）的松动可能是Capryol 90通过细胞旁途径改善肠道胰岛素吸收的潜在机制。这些发现表明，Capryol 90是一种有效的吸收促进剂，可改善胰岛素的肠吸收，而不会引起对肠上皮的严重损害。