目的 通過(guò)體外經(jīng)皮滲透試驗(yàn)和藥效學(xué)評(píng)價(jià)研究，篩選鹽酸丁卡因凝膠的最佳處方。方法 采用Valin-Chien雙室滲透擴(kuò)散池，以大鼠離體皮膚為透過(guò)介質(zhì)，以8 h的累積滲透量為指標(biāo)，考察促滲劑氮酮、丙二醇及中和劑三乙醇胺用量對(duì)體外透皮性能的影響，篩選出最優(yōu)處方。并采用小鼠熱板法對(duì)最佳處方制備的凝膠與市售制劑進(jìn)行對(duì)比，進(jìn)行藥效學(xué)評(píng)價(jià)。結(jié)果 最優(yōu)處方的組成為：鹽酸丁卡因5 g，卡波姆1 g，乙醇20 g，聚山梨酯-80 6 g，氮酮1 g，丙二醇10 g，三乙醇胺6 g，純化水補(bǔ)足至100 g。以最優(yōu)處方制得的凝膠8 h的累積滲透量和滲透速率分別為（416.9±9.95）μg/cm，（69.18±1.27）μg/（cm· h）。與市售制劑相比較，小鼠痛閾值在給藥后2 h內(nèi)顯著提高。結(jié)論 制得的鹽酸丁卡因凝膠基本性質(zhì)良好，具有較佳的體外經(jīng)皮滲透性，可進(jìn)一步開(kāi)發(fā)利用。

Objective To optimize the formulation of tetracaine hydrochloride gel and evaluate its characters both in vitro and in vivo. Methods The effects of azone amount, propylene glycol amount, and triethanolamine amount on the permeation ability, cumulative permeation rate and steady-state permeation rate at 8 h of tetracaine hydrochloride gel were evaluated using the Valin-Chien permeation cell with isolated skin. The pharmacodynamics of the optimized tetracaine hydrochloride gel was also evaluated in mice compared with the commercial preparation.Results The optimal formulation was composed with 5 g tetracaine hydrochloride, 20 g ethanol, 6 g Tween 80, 1 g azone, 10 g propylene glycol, 6 g triethanolamine, and purified water to 100 g. The accumulative permeation amount and penetration rate of the optimal tetracaine hydrochloride gel were (416.9±9.95) μg/cm and (69.18±1.27) μg/(cm·h) at 8 h. The pain threshold of mice was significantly improved within 2h after administration of the optimal tetracaine hydrochloride gel compared with that of the commercial preparation.Conclusion The ideal properties, better transdermal permeation in vitro and increased pharmacodynamics in mice were observed for the optimal tetracaine hydrochloride gel, which indicated that the tetracaine hydrochloride gel in this paper could be further developed and utilized.

國(guó)家"重大新藥創(chuàng)制"科技重大專項(xiàng)資助項(xiàng)目（2012ZX09301003-001-009）