目的 制備乳香沒藥精油（FMO）自微乳化給藥系統(tǒng)（FMO-SMEDDSs），并評價(jià)其抗炎鎮(zhèn)痛效果。方法 水蒸氣蒸餾法提取FMO，考察FMO與不同種類油相、乳化劑和助乳化劑的配伍相容性并確定了FMO-SMEDDSs的處方組成，最終根據(jù)偽三元相圖法得到其處方配比；以熱力學(xué)穩(wěn)定性、動(dòng)態(tài)光散射、透射電鏡等實(shí)驗(yàn)手段評價(jià)FMO-SMEDDSs的理化性質(zhì)。將 SD 大鼠隨機(jī)分為 5 組 ：對照組、模型組、布洛芬（陽性藥 ，20 mg·kg^-1）組、FMO（生藥劑量 90 mg·kg^-1）組、FMOSMEDDSs （90 mg·kg^-1）組，每天ig給藥2次，連續(xù)給藥7 d，對照組與模型組ig生理鹽水；除對照組外，其余4組大鼠均在右后足跖sc 40.0%甲醛溶液0.1 mL，6 h后用千分尺測量大鼠右后足厚度，并計(jì)算腫脹度和腫脹抑制率；ELISA試劑盒法分別檢測致炎足足底組織中前列腺素E₂（PGE₂）水平，血清白細(xì)胞介素-6（IL-6）、腫瘤壞死因子-α（TNF-α）水平。通過小鼠扭體法評價(jià)布洛芬（40 mg·kg^-1）組、FMO（180 mg·kg^-1）組、FMO-SMEDDSs（180 mg·kg^-1）的鎮(zhèn)痛效果。結(jié)果 根據(jù)配伍相容性及偽三元相圖結(jié)果，分別選擇肉豆蔻酸異丙酯（IPM）、聚山梨酯 80 和異丙醇作為 FMO-SMEDDSs 的油相、乳化劑和助乳化劑，配比為 4∶4∶2；FMO-SMEDDSs形成的微乳平均粒徑為（57.8±1.1）nm，PDI為（0.216±0.014），Zeta電位為（-11.5±0.05）mV，在透射電鏡下可觀察到微乳呈球狀，F(xiàn)MO-SMEDDSs熱力學(xué)穩(wěn)定性良好。與模型組比較，布洛芬、FMO、FMOSMEDDSs組大鼠的致炎足腫脹度及腫脹率均顯著降低（P＜0.05），PGE₂、TNF-α和IL-6水平顯著降低（P＜0.05）；與FMO組比較，F(xiàn)MO-SMEDDSs組大鼠致炎足腫脹度及腫脹率進(jìn)一步顯著降低（P＜0.05），PGE₂、TNF-α和IL-6水平進(jìn)一步顯著降低（P＜0.05）。與模型組比較，ig布洛芬、FMO以及FMO-SMEDDSs后均能顯著延長小鼠扭體反應(yīng)潛伏期，顯著減少15 min內(nèi)的扭體次數(shù)（P＜0.05）；相對于FMO組，F(xiàn)MO-SMEDDSs抑制小鼠扭體反應(yīng)作用更明顯。結(jié)論 成功制備FMO-SMEDDSs，其具有良好的抗炎鎮(zhèn)痛的作用。

Objective To prepare frankincense and myrrh essential oils (FMO) self microemulsifying drug delivery systems (FMOSMEDDSs) and evaluate their anti-inflammatory and analgesic effects. Methods The FMO was extracted by steam distillation method. The formulation composition of FMO-SMEDDSs was determined by investigating its compatibility with different oil phases, emulsifiers and co-emulsifiers. Finally, the formulation proportion of FMO-SMEDDSs was obtained according to the pseudo ternary phase diagram method. The physical and chemical properties of FMO-SMEDDSs were evaluated by thermodynamic stability, dynamic light scattering and transmission electron microscopy. SD rats were randomly divided into five groups: control group, model group, ibuprofen (positive drug, 20 mg·kg^-1) group, FMO (crude drug dose, 90 mg·kg^-1) group, and FMO-SMEDDSs (90 mg·kg^-1) group. Rats were ig administered twice daily for seven consecutive days. Rats in control group and model group were ig administered with saline. Except for the control group, 0.1 mL of 40.0% formaldehyde solution was injected into the right hind foot of rats in the other four groups. After six hours, the thickness of the right hind foot of the rats was measured with a micrometer, and the swelling degree and swelling inhibition rate were calculated. The levels of prostaglandin E₂(PGE₂), serum interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the inflammatory plantar tissue of the foot were detected by ELISA kit method. Meanwhile, the analgesic effect of ibuprofen (positive drug, 20 mg·kg^-1), FMO (crude drug dose, 90 mg·kg^-1), and FMO-SMEDDSs (crude drug dose, 90 mg·kg^-1) was evaluated by mouse twisting metho. Results According to the compatibility and pseudo ternary phase diagram, isopropyl myristate (IPM), Tween 80 and isopropanol were selected as the oil phase, emulsifier and co emulsifier of FMOSMEDDSs, with the ratio of 4∶4∶2. The average particle size of microemulsion formed by FMO-SMEDDSs was (57.8±1.1) nm, PDI was (0.216±0.014), and Zeta potential was (-11.5 ± 0.05) mV. Under the transmission electron microscope, it could be observed that the microemulsion was spherical. Compared with the model group, the inflammatory foot swelling degree and swelling rate of rats in the ibuprofen, FMO, and FMO-SMEDDSs groups were significantly reduced (P＜0.05), PGE₂, IL-6, and TNF- α levels significantly decreased (P＜0.05). Compared with the FMO group, the degree and rate of swelling of the inflamed feet in the FMOSMEDDSs group were further significantly reduced (P＜0.05), PGE₂, IL-6, and TNF- α levels significantly decreased (P＜0.05). Compared with the model group, ig ibuprofen, FMO, and FMO-SMEDDSs significantly prolonged the latency of writhing reaction in mice and significantly reduced the number of writhing times within 15 min (P＜0.05). Compared with FMO group, FMOSMEDDSs had a more significant inhibitory effect on mouse torsion response. Conclusion FMO-SMEDDSs have been successfully prepared and have good anti-inflammatory and analgesic effects.

河北省中醫(yī)藥管理局科研計(jì)劃項(xiàng)目（2019181）