Improvemrnt of Drug Absorption in Gastro intestinal Tract

消化道结构改变与吸收能力的关系及Peyer's贴片对吸收的促进作用。吸收增强剂C10和PC均能提高细胞内钙水平。升高后，C10通过激活肌动球蛋白环级联打开紧密连接，而PC通过不同的机制打开连接。葡萄糖没有表现出增强作用。白蛋白和豆蛋白A在兔Peyer's补丁中的吸收率高于空肠。显示了使用Peyer贴片增强大分子的可能性。在肽酶中，外显肽酶表现出增强吸收的作用，显示出可能的新型增强剂。维生素A对抗癌药物引起的膜损伤的抑制作用。虽然没有成功地利用IEC-6来研究维生素A的机制，但它清楚地表明维生素A可以抑制甲氨蝶呤引起的肠道吸收能力下降和结构改变。葡萄糖转运体吸收的改善。用联线法测定脑啡碱的一部分三肽t1 - gly - gly （TGG）与葡萄糖和半乳糖的关系。每一次糖偶联均抑制TGG的降解，提高其可吸收性。依赖Na^+的输运至少对吸收起了部分作用。糖偶联对氨基肽酶有抑制作用，对脑啡肽酶无抑制作用。脑啡肽酶抑制剂增加了糖偶联脑啡肽的稳定性和可吸收性。这些发现表明糖偶联可以改善多肽的吸收。合成了对乙酰氨基酚的糖偶联物，其部分吸收是通过葡萄糖转运体进行的。其吸光度大小为α -葡萄糖苷> -葡萄糖苷> -半乳糖糖苷。这一命令与先前报告的命令一致。

Relation between the Modified Structure of Digestive Tract and Absorption Ability, and the Absorption Improvement by Peyer's Patch. Absorption enhancers, both of C10 and PC increased the intracellular Ca level. Following the increase, C10 opened the tight junction by the activation of actomyosin ring cascade, but it was shown clearly that PC opened the junction b the different mechanism. Glucose did not show the enhancing effect. The absorbability of BSA and concanavalin A was larger in the rabbit Peyer's patch than in jejunum. The possibility to use Peyer's patch to enhance the macromolecules was shown. Among peptidases, the exo peptidases exhibited the absorption enhancing effect, showing the possible new type enhancer. Inhibition Effect of Vitamin A on Membrane Damage induced by Anticancer Drug. IEC-6 was not used successfully to investigate the vitamin A mechanism, but it was shown clearly that vitamin A inhibits the decrease of absorbability of intestins as well as structural change induced by methotrexate.Improvement of Absorption by Glucose Transporter.Tripeptide Tyr-Gly-Gly (TGG) which is a part of enkephaline was with glucose and galactose by coupline method. Every sugar-coupling inhibited the degradation of TGG and increased the absorbability. Na^+-dependent transport worked partly at least for the absorption. Aminopeptidase was inhibited by the sugar-coupling, but enkephalinase was not. The enkephalinase inhibitor increased the stability and absorbability of the sugar-coupled enkephalin. These findings suggests the absorption improvement peptides by sugar coupling. Sugar conjugates with acetaminophen were synthesized, and their absorptions proceeded partly by glucose transporter. The order of absorbability was alpha-glucoside > beta-glucode > beta-galactoside. This order coincided with the former reported one.