目的 制备盐酸小檗碱粉雾剂，肺部给药后考察其对于金黄色葡萄球菌肺炎的药效作用。方法 通过正交试验优化喷雾干燥条件，制备盐酸小檗碱粉雾剂；对其肺部沉积、流动性、外观形态进行研究；并评价该制剂对金黄色葡萄球菌肺炎大鼠的药效作用。结果 最终确定在130℃的进口温度、610 L/h的气体体积流量下，以3 mL/min的进料体积流量，通过喷雾干燥制备盐酸小檗碱粉雾剂。盐酸小檗碱粉雾剂肺部沉积率（FPF）76.4%，空气动力学直径为4.61 μm。稳定指数（SI）≈1，充气能比（AR）=1.76 > 1，充气能量（AE₁₀）=2.1 mJ<10 mJ。对金黄色葡萄球菌的药效学评价，表面盐酸小檗碱粉雾剂可以有效改善肺炎大鼠的病理状态，显著降低肺炎大鼠白细胞、中性粒细胞的数量（P<0.05），以及炎症因子（TNF-α、IL-1β及IL-6）的水平。结论 盐酸小檗碱粉雾剂通过肺部给药可以直达病变部位，对金黄色葡萄球菌肺炎具有显著的治疗作用。

Objective To prepare berberine hydrochloride dry powder inhalation, and investigate its pharmacological effect on Staphylococcus aureus pneumonia after pulmonary administration. Methods Berberine hydrochloride dry powder by spray drying and the experimental conditions was optimized by orthogonal experiment. The lung deposition, fluidity and appearance were characterized. The pharmacodynamic effects of the preparations on S. aureus pneumonia were performed with SD rats. Results A berberine hydrochloride dry powder was prepared at an inlet temperature of 130℃ with a gas volume flow of 610 L/h and a feed volume flow of 3 mL/min. The berberine hydrochloride dry powder had a lung deposition rate (FPF) of 76.4% and an aerodynamic diameter of 4.61 μm. The stability index (SI) ≈ 1, the aeration energy ratio (AR)=1.76 > 1, and the inflation energy (AE₁₀)=2.1 mJ < 10 mJ. Through the pharmacodynamic evaluation of S. aureus, we can know that the berberine hydrochloride dry powder inhalation effectively improved the pathological state of pneumonia rats, and significantly reduced (P < 0.05) the number of WBC, neutrophils, and the expression of inflammatory factors (TNF-α, IL-1β, and IL-6) in pneumonia rats. Conclusion Berberine hydrochloride dry powder inhalation can directly reach the lesion site through pulmonary administration, so it has significant therapeutic effect on S. aureus pneumonia.

R283.6

国家自然科学基金面上项目（81873013）