新型苯并噁唑酮衍生物W3D的含量测定及体内抗炎活性研究  

Determination of a novel benzoxazolone derivative W3D and evaluation its antiinflammatory activity in vivo

作　　者：杨红 史新阳 张玥 罗捷然 唐莉[2] 李青山 YANG Hong;SHI Xinyang;ZHANG Yue;LUO Jieran;TANG Li;LI Qingshan(Shanxi University of Chinese medicine,Shanxi Key Laboratory of Innovative Drug for the Treatment of Serious Diseases Basing on the Chronic Inflammation,Jinzhong 030619,China;School of Pharmaceutical Science,Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西中医药大学基于炎性反应的重大疾病创新药物山西省重点实验室,山西晋中030619 [2]山西医科大学药学院,山西太原030001

出　　处：《药物评价研究》2023年第6期1249-1253,共5页Drug Evaluation Research

基　　金：国家自然科学基金资助项目(81602976);山西省应用基础研究项目(201901D211350)。

摘　　要：目的建立全新结构化合物4-(5'-二甲氨基)-萘磺酰氧基苯并噁唑酮(W3D)的含量测定方法,并对其进行体内抗炎活性评价。方法采用Diamonsil C_(18)(250 mm×4.6 mm,5μm)色谱柱,以甲醇-水(75∶25)为流动相,体积流量1.0 mL·min^(-1),检测波长257 nm,柱温28℃,测定W3D的峰面积,建立其含量测定方法;采用二甲苯致小鼠耳肿胀模型评价化合物W3D(25.000、12.500、6.250、3.125 mg·kg^(-1))体内抗炎活性。结果供试品主峰专属性良好,在1~100μg·mL^(-1)线性关系良好(R2=0.9999),精密度、重复性、稳定性的RSD分别为0.61%、0.19%、0.84%,回收率为99.55%(RSD=0.81%);与对照组比较,W3D各剂量组耳肿胀率均显著下降(P<0.05、0.01),12.5 mg·kg^(-1)组抑制率可达53.88%,优于阳性药塞来昔布。结论建立的HPLC法简便、准确,且专属性好,可用于W3D的含量检测;W3D具有较好的体内抗炎活性,作为新结构抗炎小分子化合物具有深入研究的价值。Objective To establish a method for determining the content of the novel compound 4-(5'-dimethylamino)-naphthalenesulfonyl-2(3H)-benzoxazolone(W3D),and to evaluate the anti-inflammatory activity in vivo.Methods HPLC method was performed on the Diamonsil C18 column(250 mm×4.6 mm,5μm)with the mobile phase consisted of methanol-water(75∶25)at a flow rate of 1.0 mL·min^(-1).The detection wavelength was set at 257 nm and the column temperature was 28℃.Xylene-induced mouse ear swelling model was used to evaluate the anti-inflammatory activity of W3D(25.000,12.500,6.250,and 3.125 mg·kg^(-1))in vivo.Results Under the above chromatographic conditions,the compound W3D could be completely separated.The linear range was 1—100μg·mL^(-1)(R^(2)=0.9999).RSD of precision,repeatability and stability were 0.61%,0.19%and 0.84%respectively,and the average recovery was 99.55%(RSD=0.81%).Compared with control group,the ear swelling rate of each dose group of W3D significantly decreased(P<0.05,0.01),and the inhibition rate of the 12.5 mg·kg^(-1) group reached 53.88%,which was better than the positive drug celecoxib.Conclusion The analytical method was simple,accurate and specific which could be used on the determination of the content of compound W3D.As a new compound with determinate anti-inflammatory activity in vivo,it was worth to carry out further research.

关 键 词：4-(5'-二甲氨基)-萘磺酰氧基苯并噁唑酮(W3D) 高效液相色谱(HPLC) 含量测定 抗炎 耳肿胀 

分 类 号：R917[医药卫生—药物分析学]