乳香没药精油自微乳的制备与抗炎镇痛作用评价  

Preparation of frankincense and myrrh essential oils self microemulsifying drug delivery systems and evaluation of its anti-inflammatory and analgesic effects

作　　者：黎鹏 程永婷[2] 马峰[1] 任成波 孙建伟 张敬[1] LI Peng;CHENG Yongting;MA Feng;REN Chengbo;SUN Jianwei;ZHANG Jing(The First Affiliated Hospital of Hebei North University,Zhangjiakou 075000,China;Hebei North University,Zhangjiakou 075000,China;The 81st Army Group Hospital of the PLA,Zhangjiakou 075000,China)

机构地区：[1]河北北方学院附属第一医院,河北张家口075000 [2]河北北方学院,河北张家口075000 [3]中国人民解放军陆军解放军第81集团军医院,河北张家口075000

出　　处：《药物评价研究》2023年第4期795-802,共8页Drug Evaluation Research

基　　金：河北省中医药管理局科研计划项目(2019181)。

摘　　要：目的制备乳香没药精油(FMO)自微乳化给药系统(FMO-SMEDDSs),并评价其抗炎镇痛效果。方法水蒸气蒸馏法提取FMO,考察FMO与不同种类油相、乳化剂和助乳化剂的配伍相容性并确定了FMO-SMEDDSs的处方组成,最终根据伪三元相图法得到其处方配比;以热力学稳定性、动态光散射、透射电镜等实验手段评价FMO-SMEDDSs的理化性质。将SD大鼠随机分为5组:对照组、模型组、布洛芬(阳性药,20 mg·kg^(−1))组、FMO(生药剂量90 mg·kg^(−1))组、FMOSMEDDSs(90 mg·kg^(−1))组,每天ig给药2次,连续给药7 d,对照组与模型组ig生理盐水;除对照组外,其余4组大鼠均在右后足跖sc 40.0%甲醛溶液0.1 mL,6 h后用千分尺测量大鼠右后足厚度,并计算肿胀度和肿胀抑制率;ELISA试剂盒法分别检测致炎足足底组织中前列腺素E_(2)(PGE_(2))水平,血清白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平。通过小鼠扭体法评价布洛芬(40 mg·kg^(−1))组、FMO(180 mg·kg^(−1))组、FMO-SMEDDSs(180 mg·kg^(−1))的镇痛效果。结果根据配伍相容性及伪三元相图结果,分别选择肉豆蔻酸异丙酯(IPM)、聚山梨酯80和异丙醇作为FMO-SMEDDSs的油相、乳化剂和助乳化剂,配比为4∶4∶2;FMO-SMEDDSs形成的微乳平均粒径为(57.8±1.1)nm,PDI为(0.216±0.014),Zeta电位为(−11.5±0.05)mV,在透射电镜下可观察到微乳呈球状,FMO-SMEDDSs热力学稳定性良好。与模型组比较,布洛芬、FMO、FMOSMEDDSs组大鼠的致炎足肿胀度及肿胀率均显著降低(P<0.05),PGE2、TNF-α和IL-6水平显著降低(P<0.05);与FMO组比较,FMO-SMEDDSs组大鼠致炎足肿胀度及肿胀率进一步显著降低(P<0.05),PGE_(2)、TNF-α和IL-6水平进一步显著降低(P<0.05)。与模型组比较,ig布洛芬、FMO以及FMO-SMEDDSs后均能显著延长小鼠扭体反应潜伏期,显著减少15 min内的扭体次数(P<0.05);相对于FMO组,FMO-SMEDDSs抑制小鼠扭体反应作用更明显。结论成功制备FMO-SMEDDSs,其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 E_(2)(PGE_(2)),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±0.0

关 键 词：乳香没药精油 自微乳化给药系统 伪三元相图法 抗炎镇痛 前列腺素E2 白细胞介素-6 肿瘤坏死因子-α 

分 类 号：R943[医药卫生—药剂学]