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齿痛消炎灵颗粒中5种成分在大鼠体内的药动学研究
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          张子建 ,张婉婉 ,张洁茹 ,王伟然 ,张炜曼 ,王春英 (1.河北省中医院口腔科,石家庄 050011;2.河北医
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          科大学药学院药物分析教研室,石家庄 050017;3.新疆科技学院医学院,新疆 库尔勒 841000)
          中图分类号  R969.1      文献标志码  A      文章编号  1001-0408(2023)15-1815-06
          DOI  10.6039/j.issn.1001-0408.2023.15.05
          摘  要  目的  研究齿痛消炎灵颗粒中芍药苷、橙皮苷、柚皮素、芒柄花素和甘草次酸5种成分在大鼠体内的药动学。方法  取6只
          雄性SD大鼠,禁食不禁水12 h后一次性灌胃齿痛消炎灵颗粒(5.0 g/kg),分别于给药后的不同时间点经眼内眦取血。血浆样品经
          乙腈沉淀蛋白预处理后(磺胺甲噁唑为内标),采用液相色谱-串联质谱(LC-MS/MS)法检测血浆中5种成分的浓度;采用DAS 3.0
          软件,计算各成分的药动学参数。结果  大鼠灌胃齿痛消炎灵颗粒后,5种成分中芒柄花素的tmax、t1/2均最短(分别为0.25、0.39 h);柚
          皮素和甘草次酸的tmax较短,但t1/2较长,且柚皮素的药-时曲线出现了双峰现象;与其他3个成分相比,芍药苷和橙皮苷的cmax、AUC
          与体外成分含量高低不成正比。结论  齿痛消炎灵颗粒中芒柄花素、柚皮素、甘草次酸均在大鼠体内迅速吸收,芍药苷、橙皮苷均
          吸收较慢。
          关键词  齿痛消炎灵颗粒;大鼠;药动学;液相色谱-串联质谱

          Pharmacokinetic study of five ingredients from Chitong xiaoyanling granules in rats
          ZHANG Zijian ,ZHANG Wanwan ,ZHANG Jieru ,WANG Weiran ,ZHANG Weiman ,WANG Chunying                2, 3
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         (1.  Dept.  of  Stomatology,  Hebei  Provincial  TCM  Hospital,  Shijiazhuang  050011,  China;2.  Dept.  of
          Pharmaceutical  Analysis,  School  of  Pharmacy,  Hebei  Medical  University,  Shijiazhuang  050017,  China;
          3. Medical College, Xinjiang University of Science & Technology, Xinjiang Kuerle 841000, China)
          ABSTRACT   OBJECTIVE  To  study  the  pharmacokinetics  of  paeoniflorin,  hesperidin,  naringenin,  formononetin  and  enoxolone
          from  Chitong  xiaoyanling  granules  in  rats.  METHODS  Six  male  SD  rats  fasted  but  not  deprived  of  water  for  12  h  were  given
          Chitong xiaoyanling granules (5.0 g/kg) intragastrically at one time. Blood was collected from inner canthus of rats at different time
          points  after  administration.  Plasma  samples  were  pretreated  with  acetonitrile  precipitated  protein (sulfamethoxazole  as  internal
          standard), and the concentrations of 5 ingredients in plasma were determined by liquid chromatography-tandem mass spectrometry
         (LC-MS/MS).  The  pharmacokinetic  parameters  of  each  ingredient  were  calculated  using  DAS  3.0  software.  RESULTS  After
          intragastric administration of Chitong xiaoyanling granules, tmax and t1/2 of formononetin were the shortest among 5 ingredients (0.25
          h  and  0.39  h,  respectively).  For  naringenin  and  enoxolone,  the  tmax  was  shorter,  but  t1/2  was  longer,  and  there  was  an  obvious
          double-peak  phenomenon  in  the  drug-time  curve  of  naringenin.  Compared  with  the  other  three  components,  cmax  and  AUC  of
          paeoniflorin  and  hesperidin  were  not  directly  proportional  to  the  content  of  in  vitro  components.  CONCLUSIONS  Formononetin,
          naringin  and  enoxolone  in  Chitong  xiaoyanling  granules  were  absorbed  rapidly  in  rats,  while  paeoniflorin  and  hesperidin  were
          absorbed slowly.
          KEYWORDS    Chitong xiaoyanling granules; rat; pharmacokinetics; LC-MS/MS



              齿痛消炎灵颗粒是由 10 味中药(石膏、荆芥、防风、                     用,主要用于治疗风热上攻引起的牙龈肿痛、牙周炎、牙
          青皮、牡丹皮、地黄、青黛、细辛、白芷及甘草)组成的复                         髓炎、口干、口臭、便秘以及发热头痛等病症                   [1―3] 。目前
          方制剂,收载于《中国药典》,具有解热、镇痛、消炎的作                         对该制剂的研究多集中于其质量标准的完善和临床疗
                                                             效的观察上     [4―6] ,而缺少其药动学方面的相关研究。基
             Δ 基金项目 河北省自然科学基金资助项目(No.H2020206404);
          河北省中医药管理局科研计划项目(No.2020162)                        于此,本研究采用专属性好、灵敏度高的液相色谱-串联
             *第一作者 副主任医师。研究方向:口腔医学。电话:0311-                  质谱(liquid  chromatography-tandem  mass  spectrometry,
          69095238。E-mail:zjzh3@163.com
                                                             LC-MS/MS)法,同时测定大鼠给予齿痛消炎灵颗粒后血
             # 通信作者 教授,博士。研究方向:中药质量控制和体内过程。
          电话:0311-86266419。E-mail:wangcy730301@163.com       浆中具有明显抗炎活性的芍药苷、橙皮苷、柚皮素、芒柄


          中国药房  2023年第34卷第15期                                              China Pharmacy  2023 Vol. 34  No. 15    · 1815 ·
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