Vatier J, Malikova-Sekera E, Vitre M T, Mignon M
l'INSERM U 10, CHU X. Bichat, Paris.
Therapie. 1992 Mar-Apr;47(2):99-104.
A valid in vitro evaluation of antacid capacity should consider: 1) the intragastric pH-range; 2) the antacid mechanism; 3) the dependence of antacid activity from intraluminal flux variations; 4) the interaction between proteins and antacids. Pharmacologically, a static method allows 1) to quantify H+ binding sites at different pH-end points of the titration: pH 3.0, 2.0 and 1.0 and 2) to characterize the antacid mechanism, neutralizing activity and/or buffering capacity. In dynamic conditions, using the "artificial stomach-duodenum" model the antacid-induced resistance to acidification was measured, the antacid mechanisms were characterized in regard to intraluminal gastroduodenal flux variations and the incidence of antacid activity on duodenal pH was evaluated. These procedures were applied to antacid evaluation of proteins, as natural antacids, and of drugs containing aluminium salts alone or combined with magnesium salts. Pharmacologically, antacid drugs exhibited a greater amount of H+ binding sites when titration end-point was pH 1.0 than pH 3.0 corresponding to the development of neutralizing activity and/or buffering capacity. In dynamic conditions, the drugs, like proteins, induced a potent resistance to acidification related to gastric emptying fluxes. Antacid effect was supported by neutralizing activity and/or by buffering capacity. It was prolonged by removal of H+ ions since lagtimes for recovering initial pH were longer than antacid total emptying, the dilution of intragastric content by H+ impoverished secretory flux contributing thus to prevent gastric acidification. At duodenal site, proteins and aluminium-containing antacids induced the same duodenal pH as controls, without antacids, while magnesium-containing antacids increased it.
1）胃内pH范围；2）抗酸机制；3）抗酸活性对管腔内通量变化的依赖性；4）蛋白质与抗酸剂之间的相互作用。从药理学角度来看，静态方法能够：1）在滴定的不同pH终点（pH 3.0、2.0和1.0）定量H⁺结合位点；2）表征抗酸机制、中和活性和/或缓冲能力。在动态条件下，使用“人工胃-十二指肠”模型测量抗酸剂诱导的抗酸化能力，根据管腔内胃十二指肠通量变化表征抗酸机制，并评估抗酸活性对十二指肠pH的影响。这些程序应用于作为天然抗酸剂的蛋白质以及单独含铝盐或与镁盐组合的药物的抗酸评估。从药理学角度来看，当滴定终点为pH 1.0时，抗酸药物比pH 3.0时表现出更多的H⁺结合位点，这与中和活性和/或缓冲能力的发展相对应。在动态条件下，这些药物与蛋白质一样，诱导出与胃排空通量相关的强大抗酸化能力。抗酸作用由中和活性和/或缓冲能力支持。由于恢复初始pH的滞后时间长于抗酸剂完全排空时间，H⁺离子的去除延长了抗酸作用，H⁺匮乏的分泌通量对胃内容物的稀释有助于防止胃酸化。在十二指肠部位，蛋白质和含铝抗酸剂诱导的十二指肠pH与无抗酸剂的对照组相同，而含镁抗酸剂则使其升高。
