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三色散凝胶贴膏原料药提取工艺的优化
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          冯明庆    1, 2* ,杨 楠 ,方 媛 ,廖太阳 ,王培民 ,刘子修 (1. 南京中医药大学附属医院骨伤科,南京
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          210029;2.江苏省中医院骨伤科,南京 210029)
          中图分类号  R965;R943      文献标志码  A      文章编号  1001-0408(2023)23-2841-07
          DOI  10.6039/j.issn.1001-0408.2023.23.05

          摘  要  目的  对三色散凝胶贴膏原料药的提取工艺进行优化。方法  将SD大鼠分为空白组、模型组、传统工艺组、水提组和醇提
          组,每组5只,采用前交叉韧带横断术建立膝骨关节炎模型,考察不同提取方式所得凝胶贴膏对膝骨关节炎大鼠的药效学影响。
          分别以冷、热痛阈值与疼痛介质降钙素基因相关肽(CGRP)、环氧合酶2(COX-2)、P物质(SP)、前列腺素E2(PGE2)含量为指标进
          行镇痛实验;对大鼠滑膜组织进行HE染色,观察大鼠滑膜细胞增殖、炎症细胞浸润、血管入侵程度,并以白细胞介素1β(IL-1β)、
          肿瘤坏死因子α(TNF-α)、IL-6蛋白与mRNA表达水平为指标进行抗炎实验,对比各组大鼠的抗炎镇痛效果差异。以加醇倍数、提
          取时间、提取次数作为正交试验考察因素,以蔓荆子黄素、士的宁和马钱子碱含量为评价指标并计算综合评分,优选出三色散凝胶
          贴膏原料药的提取工艺并进行验证实验。结果  与模型组比较,各给药组大鼠的冷痛阈值和热痛阈值(除传统工艺组外)均显著升
          高(P<0.05),疼痛介质CGRP、COX-2、SP、PGE2含量均显著下降(P<0.05);滑膜组织炎症细胞浸润减少、纤维化程度减轻,胶原
          沉积减少,可见少量毛细血管增生;滑膜组织中IL-1β、IL-6、TNF-α蛋白与mRNA表达水平均显著降低(P<0.05)。与传统工艺组
          比较,醇提组大鼠的大部分检测指标显著降低(P<0.05),而水提组大鼠仅热痛阈值和滑膜组织中IL-6 mRNA表达水平显著降低
         (P<0.05)。三色散凝胶贴膏原料药的最佳提取工艺为取适量三色散细粉,加8倍量55%乙醇,加热回流提取90 min,提取2次;3
          次验证实验结果显示,蔓荆子黄素、士的宁与马钱子碱含量平均值分别为0.007%、0.092%、0.214%,RSD均小于5%。结论  优化的
          三色散凝胶贴膏原料药提取工艺稳定、可行,有利于提高该制剂药效。
          关键词  三色散;凝胶贴膏;提取工艺;药效学;含量测定

          Optimization of the extraction technology for the raw drugs of Sanse powder gel paste
          FENG Mingqing ,YANG Nan ,FANG Yuan ,LIAO Taiyang ,WANG Peimin ,LIU Zixiu (1.  Dept.  of
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          Orthopedics  and  Traumatology,  the  Affiliated  Hospital  of  Nanjing  University  of  Chinese  Medicine,  Nanjing
          210029,  China;2.  Dept.  of  Orthopedics  and  Traumatology,  Jiangsu  Provincial  Hospital  of  Chinese  Medicine,
          Nanjing 210029, China)
          ABSTRACT   OBJECTIVE  To  optimize  the  extraction  technology  for  the  raw  drugs  of  Sanse  powder  gel  paste.  METHODS  SD
          rats  were  divided  into  blank  group,  model  group,  traditional  technology  group,  water  extraction  group  and  ethanol  extraction
          group,  with  5  rats  in  each  group. Anterior  cruciate  ligament  transection  was  used  to  construct  knee  osteoarthritis  model,  and  the
          pharmacodynamic  effects  of  different  extraction  methods  on  arthritic  rats  were  investigated. Analgesic  experiments  were  conducted
          using  cold  and  hot  pain  thresholds  and  pain  mediators  calcitonin  gene-related  peptide (CGRP),  cyclooxygenase-2 (COX-2),
          substance  P (SP),  and  prostaglandin  E2 (PGE2)  contents  as  indicators.  HE  staining  was  performed  on  the  synovial  membrane  of
          rats  to  observe  the  degree  of  synovial  cell  proliferation,  inflammatory  infiltration  and  vascular  invasion,  and  anti-inflammatory
          experiments were conducted using protein and mRNA expressions of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and
          IL-6 as indicators. The analgesic and anti-inflammatory effects were compared among those groups. In the orthogonal test, ethanol
          dosage, extraction time and extraction times were used as evaluation factors, and the contents of casticin, strychnine and toxiferine
          were  taken  as  evaluation  indicators;  comprehensive  score  was  calculated.  The  validation  experiments  were  carried  out  after
          optimizing the extraction technology of the raw drugs of Sanse powder gel paste. RESULTS Compared with the model group, the
                                                             cold  and  heat  pain  thresholds  of  drug  administration  groups
             Δ 基金项目 国家自然科学基金面上项目(No.82274545);江苏
                                                            (except  for  the  traditional  technology  group)  were  all
          省中医药科技发展专项项目(No.2020ZX12);江苏省医学重点学
          科/实验室建设项目(No.js2252);江苏省中医院高峰学术人才项目                increased  significantly (P<0.05),  while  the  contents  of  pain
         (No.Y2021rc02)                                      mediators  CGRP,  COX-2,  SP  and  PGE2  were  all  decreased
             *第一作者 硕士研究生。研究方向:中药防治膝骨关节炎。
                                                             significantly (P<0.05). HE staining showed that inflammatory
          E-mail:1184518489@qq.com
             # 通信作者 副主任药师,博士。研究方向:中医药防治膝骨关节                  cell  infiltration,  fibrosis  and  collagen  deposition  were
          炎。E-mail:liuzixiu3221@126.com                      decreased  in  the  administration  groups;  a  small  amount  of


          中国药房  2023年第34卷第23期                                              China Pharmacy  2023 Vol. 34  No. 23    · 2841 ·
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