Chi Yu-Ming, Nakamura Motoyuki, Zhao Xi-Ying, Yoshizawa Toyokichi, Yan Wen-Mei, Hashimoto Fumio, Kinjo Junei, Nohara Toshihiro, Sakurada Shinobu
Seiwa Pharmaceutical Ltd., Kitaibaraki, Ibaraki, Japan.
Biol Pharm Bull. 2006 Mar;29(3):489-93. doi: 10.1248/bpb.29.489.
The oral anti-inflammatory activity of 4,4'-dihydroxy-alpha-truxillic acid (1) was compared with that of two other nonsteroidal anti-inflammatory drugs, loxoprofen sodium (LOX) and diclofenac sodium (DIC). The activity of 1 against the inflammatory pain response induced by formalin was comparable to that of LOX, but weaker than that of DIC. In the monosodium urate (MSU)-induced acute inflammatory model, 1 showed stronger anti-inflammatory activity than both LOX and DIC. The ED50 value for 1 was 4.5 micromol/kg, while the values for LOX and DIC were 65 and 25 micromol/kg, respectively. Otherwise, the oral single-dose toxicity of 1 was investigated in both sexes of Sprague-Dawley rats administered once at a dose of 2000 mg/kg. 1 showed no death, clinical signs, changes in body weight or pathological findings related to the treatment. In addition, no mutagenicity was observed in the reverse mutation assay. Furthermore, 1 did not show any ulcerogenic activity at doses ranging from 30 to 300 mg/kg in rat. Thus, 1 might be considered to be an effective anti-inflammatory agent with no deleterious adverse effect.
将4,4'-二羟基-α-曲克芦丁酸（1）的口服抗炎活性与其他两种非甾体抗炎药洛索洛芬钠（LOX）和双氯芬酸钠（DIC）进行了比较。1对福尔马林诱导的炎性疼痛反应的活性与LOX相当，但弱于DIC。在尿酸钠（MSU）诱导的急性炎症模型中，1显示出比LOX和DIC更强的抗炎活性。1的半数有效剂量（ED50）值为4.5微摩尔/千克，而LOX和DIC的值分别为65和25微摩尔/千克。此外，在给予2000毫克/千克剂量的Sprague-Dawley大鼠两性中研究了1的口服单剂量毒性。1未显示出与治疗相关的死亡、临床体征、体重变化或病理结果。此外，在回复突变试验中未观察到致突变性。此外，1在大鼠中30至300毫克/千克的剂量范围内未显示出任何致溃疡活性。因此，1可能被认为是一种有效的抗炎剂，没有有害的不良反应。
