阿司匹林-烟酰胺-锌络合物的合成及镇痛作用和不良反应

Aspirin-niacinamide-zinc complex:synthesis, analgesia and safety

目的:合成阿司匹林-烟酰胺-锌络合物(商品名:佛立沙,WUY),并进行镇痛作用和不良反应的初步研究。方法:阿司匹林与硫酸锌制备成阿司匹林锌,再与烟酰胺合成WUY。化学结构经元素分析及IR,1HNMR, 13CNMR和MS确定。采用小鼠醋酸扭体法和热板法研究镇痛作用。大鼠口服后测定对胃的刺激性。结果:WUY的熔点为141～143℃,酸碱中和法和EDTA法分别测含量均大于99．0％,收率61．0％。WUY 100和200 mg·kg-1可明显延长小鼠热痛反应潜伏期(均为P<0．01),提高小鼠的痛阈值。WUY 100和200 mg·kg-1对小鼠扭体反应次数有明显抑制作用(均为P<0．01),且比阿司匹林(200 mg·kg-1)强。WUY 2 000 mg·kg-1引起大鼠胃黏膜损伤与阿司匹林500 mg·kg-1起的损伤相当,小鼠灌胃的LD50为2456 mg·kg-1。结论:WUY合成简单,收率稳定,具有比阿司匹林更强的镇痛作用和更低的不良反应。

Objective：To synthesize aspirin-niacinamide-zinc complex （Wuyisa, WUY） and assess the analgesic effects and safety of WUY. Methods： Following after the preparation of zinc aspirinate via a reaction of aspirin with zinc, WUY was synthesized via the combination of zinc aspirinate to niacinamide. The chemical structure of WUY was elucidated by element analysis, IR, ^1HNMR, ^13 CNMR and MS. The analgesic effect of WUY was evaluated using the methods of Hest-induced pain response and acetic acid-induced writhing in mice. The safety of the GI system was evaluated based on the ulcerogenic effects of the complex in rats. Results： The total yield of the complex was 61.0% and the purity was measured to be 〉 99.0% by both neutralization and EDTA chelomery. WUY （100 and 200mg·kg^-1） significantly increased the incubation period of hot-plate reaction and showed significantly suppressive effects on writhing induced by acetic acid （P 〈0.01 ）. A high dose of WUY （2 000 mg·kg^-1 ） that was equivalent to aspirin （500 mg·kg^-1 ） caused gastric mucosal damage. The LDso of the complex was 2 456 mg·kg^-1. Conclusion ： The analgesic effect of WUY was more potent than aspirin.