STUDIES ON BENEXATE.CD - EFFECT OF INCLUSION COMPOUND FORMATION ON THE ANTIULCER ACTIVITY OF BENEXATE, THE EFFECTIVE INGREDIENT OF BENEXATE.CD
STUDIES ON BENEXATE.CD - EFFECT OF INCLUSION COMPOUND FORMATION ON THE ANTIULCER ACTIVITY OF BENEXATE, THE EFFECTIVE INGREDIENT OF BENEXATE.CD
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DOI：
10.1254/fpj.91.377
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发表时间：
1988-06-01
影响因子：
--
通讯作者：
YAMADA, H
中科院分区：
文献类型：
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作者：
MURANUSHI, N;YOSHIDA, M;YAMADA, H
贝奈克酯 - CD是一种新型口服抗溃疡药，是贝奈克酯与β - 环糊精（β - CD）的包合物。本报告研究了包合物形成对贝奈克酯 - CD的有效成分贝奈克酯抗溃疡活性的意义。为评估溶解性的改善情况，比较了贝奈克酯从各种药物剂型溶入日本药典第一液（一种胃液模型）的溶出特性。贝奈克酯本身几乎不溶，但贝奈克酯与β - CD的物理混合物显示贝奈克酯的溶解度有所增加。另一方面，贝奈克酯 - CD呈现出过饱和溶出曲线，其峰值浓度比物理混合物的溶解度高8倍。当以粉末剂型给幽门结扎大鼠口服贝奈克酯 - CD时，在胃中观察到类似的过饱和溶出行为，且胃组织中的贝奈克酯水平高于给予贝奈克酯或物理混合物时的水平。贝奈克酯 - CD极大地抑制了由盐酸 - 乙醇摄入引起的溃疡形成，但给予贝奈克酯或物理混合物治疗后无明显抑制作用。这些结果表明，贝奈克酯必须形成包合物才能发挥强大的抗溃疡活性。
Benexate.cntdot.CD, a new orally active antiulcer agent, is an inclusion compound of benexate and .beta.-cyclodextrin (.beta.-CD). The present report investigated the significance of complex formation on the antiulcer activity of benexate, the effective ingredient of benexate .cntdot. CD. To evaluate the improvement of solubility, the dissolution properties of benexate from various pharmaceutical forms into the 1st fluid of the Pharmacopoeia of Japan, a model of gastric juice, were compared. Benexate itself was hardly soluble, but the physical mixture of benexate and .beta.-CD showed a solubility increase of benexate. On the other hand, benexate.cntdot.CD showed a supersaturated dissolution curve and its peak concentration was 8 times higher than the solubility of the physical mixture. When benexate.cntdot.CD was administered orally to pylorus ligated rats in the powder formulation, the similar supersaturated dissolution behavior was observed in the stomach, and the benexate level in gastric tissue was higher than that in benexate or the physical mixture administration. Benexate.cntdot.CD extremely inhibited the ulcer formation caused by HCl-ethanol ingestion, but there was no significant inhibition after treatment with benexate or the physical mixture. These results indicated that it is necessary for benexate to form an inclusion compound in order to exert a strong antiulcer activity.