高载药量萘普生凝胶的制备及抗炎镇痛作用研究

Preparation of Naproxen Gel with High Drug Content and Investigation of Its Anti-inflammatory and Analgesic Effect

目的:制备载药量高、渗透效果好的萘普生凝胶并考查其抗炎、镇痛作用。方法:以卡波姆980为凝胶基质、丙二醇为保湿剂、卡必醇为促渗剂和增溶剂制备不同载药量的萘普生凝胶。用二甲苯诱导小鼠耳廓肿胀,卡拉胶诱发大鼠足跖肿胀,考查萘普生凝胶的抗炎作用;用热板法和扭体法观察萘普生凝胶对小鼠的镇痛作用。以1%的双氯芬酸钠凝胶剂作为阳性对照药,1%、2%和4%的萘普生凝胶分组给药。结果:加入25%的卡必醇后,所制凝胶的载药量可达4%,其稳态渗透速率可达324.1μg.cm-2.h-1。2%和4%萘普生凝胶对二甲苯引起的小鼠耳肿胀、卡拉胶所致大鼠足跖肿胀和醋酸引起的小鼠疼痛扭体反应均有较好的抑制作用,并能明显提高热板法小鼠的痛阈,改善痛阈提高百分率。与阳性药物组相比,2%、4%的萘普生凝胶剂组均显示相近或更好的抗炎镇痛作用。结论:以卡必醇为促渗剂和增溶剂所制的萘普生凝胶经皮给药制剂,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。

Objective： To prepare naproxen gel with high drug content and permeation ability, and study its effect of anti-inflammatory and analgesic. METHOD： Usingcarbopol 980 as gel matrix, propylene glycol as humectant, transcutol as enhancer and solubilizing agent, naproxen gels with different drug content were prepared. Ear swell in mice were induced by xylene and paw edema in rats were induced by carrageenin to observe the anti-inflammation effect of naproxen gel, while hot-plate test and writhing test were adopted to study its analgesic effect. Animals were grouped according to the administration of 1%, 2% and 4% naproxen gel, with 1% diclofenac sodium gel taken as positive control. Results： Adding 25% transcutol in gel formulation, drug incorporated in gel can attain 4%, the obtained Js was 324. 19g·cm^-2·h^-1. 2% and 4% naproxen gel could reduce ear edema in mice, paw edema in rats and alleviate the pain caused by glacial acetic acid in rats. After 2% and 4% naproxen gel administrated in mice, percentages of pain threshold for hot-plate test were elevated remarkably. Compared with positive control, 2% and 4% naproxen gels exhibited similar or more effective anti-inflammatory and analgesic activity. Conclusion： naproxen gel used transcutol as enhancer and solubilizing agent possesses obvious anti-inflammatory and analgesic effects, which may be a promising new dosage form for transdermal delivery of naproxen.