目的 制备延胡索乙素纳米混悬温敏凝胶（tetrahydropalmatine nanosuspension thermosensitive gel，THP-NS-TG），进行质量评价，并对其镇痛药效学进行研究。方法 单因素实验考察温敏基质泊洛沙姆407、胶凝温度调节剂泊洛沙姆188、生物黏附剂透明质酸钠、延胡索乙素纳米混悬冻干粉以及促透剂对胶凝温度的影响，并以延胡索乙素24 h累积透过量（Q₂₄）为指标考察THP-NS-TG的载药量、促透剂种类及用量，采用正交设计优化温敏凝胶的处方；并对制备的THP-NS-TG的性状、胶凝温度、pH值、黏度、含药量、释放度以及皮肤安全性进行质量评价，最后通过小鼠热板法镇痛实验、醋酸扭体实验评价THP-NS-TG的镇痛药效学。结果 THP-NS-TG的最佳制备工艺为泊洛沙姆407用量17%、THP-NS冻干粉用量5%（以延胡索乙素计）、水溶性氮酮用量7%、透明质酸钠用量0.4%。质量评价结果显示，THP-NS-TG的质量稳定、可控且皮肤用药安全。药效学实验结果表明，THP-NS-TG具有中枢、外周双重的镇痛作用，镇痛效果随着给药剂量的增加而增加。结论 THP-NS-TG的处方工艺简单、稳定，具有良好的缓释与透皮性能，对中枢和外周性疼痛均有一定的镇痛作用，并且镇痛效果与给药剂量存在正相关关系。

Objective To prepare tetrahydropalmatine nanosuspension thermosensitive gel (THP-NS-TG), evaluate its quality, and study its analgesic pharmacodynamics. Methods The effects of temperature-sensitive matrix poloxamer 407, gel temperature regulator poloxamer 188, bioadhesive sodium hyaluronate, tetrahydropalmatine nanosuspension lyophilized powder and penetration enhancer on gel temperature were investigated by single factor experiment. The drug loading and penetration enhancer types and dosage of temperature-sensitive gel were investigated by taking 24 h cumulative permeation (Q₂₄) tetrahydropalmatine as the indicator. The formulation of temperature-sensitive gel was optimized by orthogonal design. The properties, gel temperature, pH value, viscosity, drug content, release rate and skin safety of the prepared THP-NS-TG were evaluated. Finally, the analgesic pharmacodynamics of THP-NS-TG was evaluated by hot plate analgesia test and acetic acid-induced writhing test in mice. Results The optimal preparation process of THP-NS-TG was as follows : the amount of poloxamer 407 was 17%, THP-NS lyophilized powder was 5% (calculated based on tetrahydropalmatine), the amount of water-soluble azone was 7%, and the amount of sodium hyaluronate was 0.4%. The quality evaluation results showed that the quality of THP-NS-TG was stable, controllable and safe for skin medication. The results of pharmacodynamics experiments showed that THP-NS-TG had both central and peripheral analgesic effects. The analgesic effect increased with the increase of dosage. Conclusion The prescription process of THP-NS-TG is simple and stable. It has good sustained release and transdermal properties. It has certain analgesic effects on central and peripheral pain, and there is a positive correlation between the analgesic effect and the dosage.

R283.6

国家中医药管理局高水平建设学科（zyyzdxk-2023272）