目的 制备野黄芩素纳米晶体（scutellarein nanocrystals，Scu-NCs），进行药剂学性质研究，并考察其对小鼠皮肤干燥瘙痒模型的治疗效果。方法 采用反溶剂沉淀技术制备Scu-NCs，并通过冷冻干燥技术将其固化成固体粉末；测定Scu-NCs的平均粒径、分散系数、ζ电位并观察其微观结构；差示扫描量热法（differential scanning calorimetry，DSC）及傅里叶变换红外光谱法（Fourier transform infrared spectroscopy，FTIR）分析其晶型及化学结构的变化；测试其体外药物溶出速率和其凝胶剂的体外释放度；评价野黄芩素及Scu-NCs凝胶剂经皮给药对丙酮/乙醚和水（acetone-ether-water，AEW）诱导的小鼠干皮瘙痒模型的止痒作用。结果 制备得到的Scu-NCs平均粒径为（379.1±1.7）nm，多分散系数（polydispersity index，PDI）值为0.238±0.081，ζ电位为（25.50±0.25）mV；野黄芩素纳米化后野黄芩素的晶型和化学结构未发生明显变化；Scu-NCs冷冻干燥后粒径无明显变化；野黄芩素纳米化后提高了药物2 h内的溶出速率、溶出度及Scu-NCs凝胶剂6 h内的体外释放度；与AEW模型组相比，野黄芩素、Scu-NCs凝胶剂给药组可明显降低小鼠1 h内抓挠次数，抑制颈背部表皮增厚及皮肤中白细胞介素-6（interleukin-6，IL-6）、白细胞介素-1β（interleukin-1β，IL-1β）、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）的表达，且Scu-NCs对AEW模型抑制效果更明显。结论 Scu-NCs粒径较小且均匀，其纳米化后晶型和化学结构没有发生明显改变；将野黄芩素制备成纳米晶体后，可明显改善药物的溶出度与体外释放度，对皮肤局部慢性瘙痒具有更好的治疗效果。

Objective To prepare scutellarein nanocrystals (Scu-NCs), investigate their pharmaceutical characteristics and their therapeutic effects on a mouse model of dry and itchy skin. Methods The Scu-NCs were prepared by anti-solvent precipitation technique and solidified into solid powder by freeze-drying technique; The average particle size, dispersion coefficient, ζ potential, and microstructure of Scu-NCs were determined; Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) were used to analyze the changes in crystalline shape and chemical structure of Scu-NCs; The dissolution rate of the drug and the release degree of the gel in vitro were tested; and the itch-relieving effects of the transdermal administration of scutellarein and Scu-NCs gel on the mouse model of dry and itchy skin induced by acetone/ethyl ether and water (AEW) were evaluated. Results The average particle size of the prepared Scu-NCs was (379.1 ± 1.7) nm, the polydispersity index (PDI) value was 0.238 ± 0.081, and the ζ potential was (25.50 ± 0.25) mV; The crystalline shape and chemical structure of scutellarein after nano conversion did not change significantly; There was no significant change in the particle size of Scu-NCs after freeze-drying; The nano conversion of scutellarein improved the drug dissolution rate within 2 h, dissolution degree and the release degree of the Scu-NCs gel in vitro within 6 h; Compared with the AEW model group, the scutellarein and Scu-NCs gel administration group could significantly reduce the number of scratching within 1 h, inhibit epidermal thickening of the nape of the neck and expression of interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the skin, and the inhibitory effect of Scu-NCs was more obvious on the AEW model. Conclusion The particle size of Scu-NCs was small and uniform, and there was no significant change in the crystal shape and chemical structure after its nano conversion; The preparation of scutellarein into nanocrystals significantly improved the dissolution and in vitro release degree of the drug, and provided a better therapeutic effect on local chronic itching of the skin.

R283.6

泰州市“凤城英才计划”青年科技人才托举工程；南京中医药大学自然科学基金项目（XZR2020099）