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[经皮非甾体抗炎药依托芬那酯凝胶对大鼠的抗水肿活性]

[Anti-edema activity of a trans-cutaneous non-steroidal anti-inflammatory agent, etofenamate gel, in rats].

作者信息

Nakamura H, Motoyoshi S, Yokoyama Y, Kadokawa T, Shimizu M

出版信息

Nihon Yakurigaku Zasshi. 1982 Aug;80(2):169-82.

PMID:7173740
Abstract

Local anti-inflammatory activity of etofenamate gel (5% etofenamate) was investigated in rats. Etofenamate gel (5--50 mg/paw) produced a dose related inhibition in the hind paw edema caused by carrageenin with a topical application to the inflamed paw, and its ED50-value was 33.0 mg/paw. A weak but significant inhibiton was seen with an application of 50 mg/paw to the non-inflamed paw, but not with 10 mg/paw. Anti-edema activity of oral etofenamate (ED50 = 8.49 mg/kg) was comparable to flufenamic acid. Against the hind paw edema caused by a mixture of kaolin and carrageenin, etofenamate gel showed a significant therapeutic activity with repeated application of 10--50 mg/paw to the inflamed paw, but not with 10 mg/paw to the non-inflamed paw. Etofenamate gel (50 mg/paw/day), applied topically to the inflamed hind paw of adjuvant rats, showed a significant therapeutic activity. The potency of oral etofenamate (4--8 mg/kg/day) in adjuvant rats was comparable to flufenamic acid. No gastrointestinal ulcer was produced by a topical application of etofenamate gel (up to 1,000 mg/rat) to the clipped skin, though oral etofenamate (40 mg/kg) produced the ulcer. From these results, it was suggested that etofenamate gel, applied to the skin of rats, showed local anti-edema activity approximately comparable to oral etofenamate, and the ratio of ulcerogenic effective to anti-edema dose of etofenamate gel was larger than that of oral etofenamate.

摘要

在大鼠中研究了依托芬那酯凝胶(5%依托芬那酯)的局部抗炎活性。依托芬那酯凝胶(5-50毫克/爪)局部应用于发炎的爪子时,对角叉菜胶引起的后爪水肿产生剂量相关的抑制作用,其半数有效剂量(ED50)值为33.0毫克/爪。将50毫克/爪应用于未发炎的爪子时可观察到微弱但显著的抑制作用,但10毫克/爪时则无此作用。口服依托芬那酯(ED50 = 8.49毫克/千克)的抗水肿活性与氟芬那酸相当。对于高岭土和角叉菜胶混合物引起的后爪水肿,依托芬那酯凝胶对发炎的爪子重复应用10-50毫克/爪时显示出显著的治疗活性,但对未发炎的爪子应用10毫克/爪时则无此作用。将依托芬那酯凝胶(50毫克/爪/天)局部应用于佐剂大鼠发炎的后爪时,显示出显著的治疗活性。口服依托芬那酯(4-8毫克/千克/天)对佐剂大鼠的效力与氟芬那酸相当。对剪毛后的皮肤局部应用依托芬那酯凝胶(高达1000毫克/大鼠)未产生胃肠道溃疡,而口服依托芬那酯(40毫克/千克)则会产生溃疡。从这些结果表明,应用于大鼠皮肤的依托芬那酯凝胶显示出与口服依托芬那酯大致相当的局部抗水肿活性,且依托芬那酯凝胶致溃疡有效剂量与抗水肿剂量的比值大于口服依托芬那酯。

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