目的 制备蛇床子素纳米混悬温敏凝胶（osthole nanosuspension thermosensitive gel，Ost-NS-TG），进行质量评价，并对其治疗特应性皮炎（atopic dermatitis，AD）的药效作用进行研究。方法 以胶凝温度为评价指标，采用单因素实验结合正交设计优化温敏凝胶的处方；并对制备的Ost-NS-TG的性状、胶凝温度、胶凝时间、pH值、黏度、ζ电位、载药量、释放度以及皮肤刺激性进行质量评价，通过小鼠背部皮损评价、小鼠抓挠行为评价、组织病理学观察以及小鼠血清与皮损组织中的炎症因子检测评价Ost-NS-TG治疗AD的药效作用。结果 Ost-NS-TG的最佳制备工艺为泊洛沙姆407用量18%，泊洛沙姆188用量4%，Ost-NS冻干粉用量5%；Ost-NS-TG的胶凝温度为（32.67±0.06）℃；胶凝时间为（60.88±1.62）s；pH值为6.68±0.03；ζ电位为（-32.90±0.89）mV；Ost-NS-TG载药量为（6.96±0.01）mg/mL。Ost-TG和Ost-NS-TG在144 h时的累积释放率分别为60.67%和86.54%，表明Ost-NS-TG显示出更优的释放特性；质量评价结果显示，Ost-NS-TG具有良好的皮肤安全性。药效学实验结果表明，Ost-NS-TG能够改善小鼠皮损情况，并能降低小鼠血清与皮损组织中炎症因子免疫球蛋白E（immunoglobulin E，IgE）、白细胞介素-4（interleukin-4，IL-4）、γ干扰素（interferon-γ，IFN-γ）的表达水平。结论 Ost-NS-TG的处方工艺简单，具有良好的缓释与透皮性能，并对AD有一定的治疗作用。

Objective To prepare osthole nanosuspension thermosensitive gel (Ost-NS-TG), evaluate its quality, and study for its pharmacodynamics in the treatment of atopic dermatitis. Methods A single-factor experiment combined with orthogonal design was used to optimize the prescription of the temperature-sensitive gel using the gelling temperature as the evaluation index; and quality evaluation of the prepared Ost-NS-TG in terms of properties, gelling temperature, gelling time, pH value, viscosity, ζ potential, drug loading capacity, release and skin irritation was carried out. Finally, the pharmacodynamics of Ost-NS-TG for the treatment of atopic dermatitis was evaluated by dorsal skin lesion scoring, scratching behavior observation, histopathological examination, and detection of inflammatory factors in serum and skin lesion tissues of mice. Results The optimal preparation process of Ost-NS-TG was 18% of Poloxamer 407, 4% of Poloxamer 188, and 5% of Ost-NS lyophilized powder. The gelation temperature of Ost-NS-TG was (32.67 ± 0.06) ℃. The gelation time was (60.88 ± 1.62) s; pH value was 6.68 ± 0.03; the ζ potential was (-32.90 ± 0.89) mV. The drug loading of Ost-NS-TG was (6.96 ± 0.01) mg/mL. The cumulative release rates of Ost-TG and Ost-NS-TG at 144 h were 60.67% and 86.54%, respectively, indicating that Ost-NS-TG exhibits better release characteristics.. The results of the quality evaluation showed that Ost-NS-TG had good dermal safety. The results of pharmacodynamic experiments showed that Ost-NS-TG was able to improve the skin lesions in mice and reduce the expression levels of inflammatory factors immunoglobulin E (IgE), interleukin-4 (IL-4), and interferon-γ (IFN-γ) in serum and skin lesion tissues of mice. Conclusion Ost-NS-TG has a simple and stable prescription process, good slow release and transdermal properties, and has a certain therapeutic effect on atopic dermatitis.

R283.6

国家中医药管理局高水平建设学科（zyyzdxk-2023272）