多指标正交试验优化辛香喷鼻纳米乳剂对小鼠变应性鼻炎模型药效学研究  

Optimization of extraction process of XinXiang Nanoemulsion Spray using multi-index orthogonal experiment and effect of XinXiang Nanoemulsion Spray on pharmacodynamics in allergic rhinitis mice

作　　者：路曼琪 付廷明 袁海霞[1] 宋宇尘 陈天翼 韩新民[1] LU Man-qi;FU Ting-ming;YUAN Hai-xia;SONG Yu-chen;CHEN Tian-yi;HAN Xin-min(Medicine First School of Clinical Medicine,Nanjing University of Chinese Medicine,Nanjing 210023,Jiangsu Province,China;Jiangsu Botanical Medicine Refinement Engineering Research Center,College of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210023,Jiangsu Province,China)

机构地区：[1]南京中医药大学第一临床医学院,南京210023 [2]南京中医药大学药学院江苏省植物药深加工工程技术研究中心,南京210023

出　　处：《中国临床药理学杂志》2020年第13期1807-1811,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金面上基金资助项目(81873013);江苏省研究生科研与实践创新计划基金资助项目(KYCX19-1209)。

摘　　要：目的多指标综合优化辛香喷鼻纳米乳剂制剂工艺,研究对变应性鼻炎(AR)小鼠的药效学作用及机制。方法用L9(34)正交试验对中药水提醇沉工艺优化,用多指标综合评分法确定最优提取工艺参数。按照优化工艺制备第1制剂至第3制剂。按照体重将BALB/c小鼠随机分为6组:正常组、模型组、阳性药组和第1实验组至第3实验组。基础致敏后,第1次卵清白蛋白(OVA)滴鼻激发当日开始给药。阳性药组鼻腔给药糠酸莫米松鼻喷雾剂54.54 mg·kg^-1·d^-1;第1实验组和第2实验组分别鼻腔给药第1制剂和第2制剂,剂量均为2.73 mg·kg^-1·d^-1;第3实验组鼻腔给药第1制剂2.73 mg·kg^-1·d^-1,同时灌胃给药第3制剂6.54 g·kg^-1·d^-1。各组均给药7 d。以酶联免疫吸附法检测免疫球蛋白E(IgE)、卵白蛋白特异性IgE抗体(OVA-sIgE)水平以及白细胞介素-33(IL-33)水平。结果辛香喷鼻纳米乳剂的水提醇沉工艺:加入10倍量水,煎煮3 h,煎煮2次,含醇量65%,静置过夜。正常组、模型组、阳性药组和第1实验组至第3实验组的OVA-sIgE水平分别为(1.79±0.04),(2.89±0.27),(1.81±0.31),(2.09±0.41),(1.43±0.20)和(1.90±0.74)μg·mL^-1;这6组的IgE水平分别为(76.88±17.91),(247.56±2.96),(172.50±6.36),(133.85±11.98),(166.46±2.49)和(208.66±3.89)ng·mL^-1;这6组的IL-33水平分别为(116.77±3.15),(211.57±8.41),(116.68±18.28),(90.40±7.89),(137.51±7.13)和(165.26±5.71)pg·mL^-1。上述指标:模型组与空白组比较,差异均有统计学意义(P<0.05或P<0.01);阳性药组和第1实验组至第3实验组与模型组比较,差异均有统计学意义(P<0.05或P<0.01)。结论辛香喷鼻纳米乳剂制剂工艺已达到标志性成分最高转移率和质量稳定的要求。辛香喷鼻纳米乳剂对AR小鼠有明显疗效,其可能通过抑制胸腺细胞因子水平发挥抗AR效应。Objective To study multi-index comprehensive optimization of the technology of XinXiang Nanoemulsion Spray preparation and effect of XinXiang Nanoemulsion Spray on pharmacodynamics in allergic rhinitis(AR)mice.Methods The L9(34)orthogonal test was used to optimize the traditional Chinese medicine water extraction process,and the multi-index comprehensive scoring method was used to determine the optimal extraction process parameters.According to the optimized process,the first preparation to the third preparation are prepared.BALB/c mice were randomly divided into 6 groups:blank group,model group,positive drug group(mometasone furonate nasal spray at a dose of 54.54 mg·kg^-1·d^-1)and experimental-1,-2,-3 groups.Administration began on the day of the first ovalbumin(OVA)titration after basal sensitization.Experimental-1,-2 groups:the first and second preparations were administered to the nasal cavity respectively,and the dose was 2.73 mg·kg^-1·d^-1;experimental-3 group:the nasal dose of the first preparation was 2.73 mg·kg^-1·d^-1,and the oral dose of the third preparation was 6.54 g·kg^-1·d^-1.Each group was given 7 d.The levels of ovalbumin-specific immunoglobulin E(IgE)、antibodies(OVA-sI gE)and interleukin-33(IL-33)were detected by enzyme-linked immunosorbent assay.Results The water extraction and alcohol precipitation process of Xin Xiang Nanoemulsion Spray:adding 10 times of water,boiling for 3 h,boiling for 2 times,alcohol content 65%,and letting it settle overnight.The OVA-sI gE levels in blank group,model group,positive drug group and experimental-1,-2,-3 groups were respectively(1.79±0.04),(2.89±0.27),(1.81±0.31),(2.09±0.41),(1.43±0.20)and(1.90±0.74)μg·mL^-1;the IgE content in the 6 groups were respectively(76.88±17.91),(247.56±2.96),(172.50±6.36),(133.85±11.98),(166.46±2.49)and(208.66±3.89)ng·mL^-1;the IL-33 content in the 6 groups were respectively(116.77±3.15),(211.57±8.41),(116.68±18.28),(90.40±7.89),(137.51±7.13)and(165.26±5.71)pg·mL^-1.Comparison between model group an

关 键 词：辛香喷鼻纳米乳剂 变应性鼻炎 提取工艺 胸腺 细胞因子 

分 类 号：R28[医药卫生—中药学]