高载药量萘普生微乳的制备及其抗炎镇痛作用实验研究

目的:制备载药量高的萘普生微乳,并对其进行抗炎、镇痛作用的初步药效学研究。方法:以聚山梨酯-80为表面活性剂、十四酸异丙酯为油相、乙醇为助表面活性剂,用相转变温度法制备萘普生微乳。以1%的双氯芬酸钠凝胶剂作为阳性对照药,低、中、高剂量的萘普生微乳分组局部涂抹给药后分别用二甲苯诱导小鼠耳廓肿胀、卡拉胶诱发大鼠足跖肿胀以研究萘普生微乳的抗炎作用;用热板法和扭体法观察萘普生微乳对小鼠的镇痛作用。结果:所制微乳载药量达4.2%。中、高剂量的萘普生微乳给药后能显著抑制二甲苯所致小鼠耳廓肿胀及卡拉胶所致大鼠足跖肿胀,并能明显提高小鼠的痛阈,减少小鼠醋酸刺激的扭体次数(P<0.01或P<0.05)。与阳性对照药比较,中、高剂量的萘普生微乳均显示相近或更强的抗炎镇痛作用。结论:采用相转变温度法制备的萘普生微乳对大鼠及小鼠的炎症及痛反应模型均有抑制作用,有望成为萘普生的新型给药制剂。

Study on Preparation of Naproxen Microemulsion with High Drug-loading Rate and Its Anti-inflammatory and Analgesic Effect

OBJECTIVE： To prepare Naproxen microemulsion with high drug-loading rate and study its anti-inflammatory and analgesic effect. METHODS： Naproxen microemulsion was prepared by phase transfer temperature （PIT） method with polysorbate-80 as surfactants, alcohol as cosurfactant and isopropyl myristate as oil phase. 1% dichlofenac sodium gel was used as positive control. High-dose group, medium-dose group and low-dose group were treated with Naproxen microemulsion. Then xylene and carrageenan were used to induce ear edema in mice and pedal swelling in rats respectively in order to study anti-inflammatory effect of Naproxen microemulsion. The hot-plate test and writhing test were adopted to study the analgesic effect. RESULTS： Drug-loading rate of preparation reached 4.2 %. Xylene-inducing ear edema in mice and carrageen-inducing pedal swelling in rats were relieved significantly by treating with middle dose and high dose Naproxen microemulsion. The threshold of pain in mice was also increased and writhing times caused by acetic acid decreased （P〈0.01 or P〈0.05）. Medium dose and high dose Naproxen microemulsion was equal or superior to positive control in anti-inflammatory and analgesic effect. CONCLUSION： Naproxen microemulsion prepared by PIT method shows obvious anti-inflammatory and analgesic effect in mice and rats, which may be a new type of naproxen preparation.