CN107308221B - 飞扬肠胃炎胶囊在治疗盆腔炎性后遗症中的新用途 - Google Patents
飞扬肠胃炎胶囊在治疗盆腔炎性后遗症中的新用途 Download PDFInfo
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Abstract
本发明属于医药领域，具体涉及飞扬肠胃炎胶囊在治疗盆腔炎性后遗症中的新用途。本发明发现飞扬肠胃炎胶囊能有效降低盆腔炎性后遗症患者血清中的IL‑1β和TNF‑α含量；同时还能有效抑制盆腔炎性后遗症患者子宫组织中NF‑KB的表达，并促进Caspase‑3的表达。飞扬肠胃炎胶囊有望被开发作为预防和/或治疗盆腔炎性后遗症的药物。
Description
技术领域
本发明属于医药领域，具体涉及飞扬肠胃炎胶囊在治疗盆腔炎性后遗症中的新用途。
背景技术
盆腔炎(pelvic inflammatory disease，PID)是女性的一种常见病和多发病，西医将其定义为宫颈内口以上的女性内生殖器及其周围结缔组织、盆腔腹膜所发生的感染性疾病，主要包括子宫内膜炎、输卵管卵巢炎、盆腔腹膜炎、盆腔结缔组织炎等。根据病原体来源分为以链球菌、葡萄球菌等需氧菌为主的内源性致病菌和以支原体、衣原体、淋球菌为主的外源性致病菌；根据发病周期长短和缓急程度又可分为急性盆腔炎(acute pelvicinflammatory disease，APID)和慢性盆腔炎(chronic pelvic inflammatory disease，CPID)。女性生殖道是一个对外开放的器官，其中阴道口连接外部环境和生殖道，当阴道受到外界因素影响或机体免疫力下降时，外籍菌或过路菌成为致病菌，随阴道上行感染至盆腔从而引发炎症。
飞扬肠胃炎胶囊由飞扬草、火炭母、救必应三味中药组方而成，主要功效泻火解毒、除湿止痢，临床常用于治疗细菌性痢疾，急慢性肠胃炎。临床研究表明，飞扬肠胃炎片联合左氧氟沙星治疗急慢性肠胃炎有助于提高治疗效果，改善患者临床症状。
发明内容
本发明提供一种飞扬肠胃炎胶囊在制备预防和/或治疗盆腔炎性后遗症药物中的应用。
本发明提供一种飞扬肠胃炎胶囊在制备预防和/或治疗盆腔炎性后遗症药物中的应用，其剂量为1.2-2.4g/kg(对大鼠而言)。
上述应用，其特征在于所述飞扬肠胃炎胶囊能有效降低盆腔炎性后遗症患者血清中的IL-1β和TNF-α含量；此外，所述飞扬肠胃炎胶囊还能有效抑制盆腔炎性后遗症患者子宫组织中NF-KB的表达，同时促进Caspase-3的表达。
上述飞扬肠胃炎胶囊的【处方】：飞扬草1.0-5.0份，火炭母0.2-3.0份，救必应0.1-1.0份，上述份指的是重量份。
上述飞扬肠胃炎胶囊的制备方法，其特征在于包括如下步骤：
按照处方量，取适量救必应打细粉；剩余救必应和另外二味药材加水煎煮二次，第一次8倍量水煎煮2小时，第2次加6倍量水煎煮1小时，合拼煎液，滤过，浓缩至相对密度1.25-1.30(70℃热测)的稠膏，加入所述适量救必应细粉及适量赋形剂、稳定剂或表面活性剂，混匀，制粒，装胶囊，即得成品。
本发明的另一实施方案提供一种药物组合物，该药物组合物按重量份计，包含飞扬草1.0-5.0份火炭母0.2-3.0份救必应0.1-1.0份。
本发明的另一实施方案提供上述药物组合物的制备方法，包括如下步骤：按照药物组合物三味药材的重量份，取适量救必应打细粉；剩余救必应和另外二味药材加水煎煮二次，第一次8倍量水煎煮2小时，第2次加6倍量水煎煮1小时，合拼煎液，滤过，浓缩至相对密度1.25-1.30(70℃热测)的稠膏，加入所述适量救必应细粉及适量赋形剂、稳定剂或表面活性剂，混匀，制粒，装胶囊，即得成品。
本发明所述的药物组合物可用于预防和/或治疗盆腔炎性后遗症。
与现有技术相比，本发明的优点在于：
(1)本发明将飞扬肠胃炎胶囊开发为预防和/或治疗盆腔炎性后遗症的药物，属于老药新用，扩大了飞扬肠胃炎胶囊的适应症；
(2)本发明发现单独使用飞扬草、火炭母、救必应成分对盆腔炎性后遗症的治疗效果不佳，但是采用三者组合(即飞扬肠胃炎胶囊)则显示出优于现有技术中的妇科千金胶囊的治疗效果，说明本发明飞扬肠胃炎胶囊中特定比例的飞扬草、火炭母、救必应之间产生了某种协同效应；
(3)本发明对飞扬肠胃炎胶囊在盆腔炎性后遗症的治疗中的使用剂量进行的探索，结果表明飞扬肠胃炎胶囊低、中剂量相比存在明显的量效关系，但中剂量、高剂量之间量效关系不明显，确定了飞扬肠胃炎胶囊的最佳使用剂量。
附图说明
图1飞扬肠胃炎胶囊对盆腔炎性后遗症大鼠子宫内膜病理变化影响(HE×200)，A：假手术组；B：模型组；C：飞扬肠胃炎胶囊低剂量组(0.6g/kg)；D：飞扬肠胃炎胶囊中剂量组(1.2g/kg)；E：飞扬肠胃炎胶囊高剂量组(2.4g/kg)；F：妇科千金胶囊组(1.2g/kg)。
图2飞扬肠胃炎胶囊对盆腔炎性后遗症大鼠子宫内膜NF-KB表达的影响(×200)，A：假手术组；B：模型组；C：飞扬肠胃炎胶囊低剂量组(0.6g/kg)；D：飞扬肠胃炎胶囊中剂量组(1.2g/kg)；E：飞扬肠胃炎胶囊高剂量组(2.4g/kg)；F：妇科千金胶囊组(1.2g/kg)。
图3飞扬肠胃炎胶囊对盆腔炎性后遗症大鼠子宫内膜Caspase-3表达的影响，A：假手术组；B：模型组；C：飞扬肠胃炎胶囊低剂量组(0.6g/kg)；D：飞扬肠胃炎胶囊中剂量组(1.2g/kg)；E：飞扬肠胃炎胶囊高剂量组(2.4g/kg)；F：妇科千金胶囊组(1.2g/kg)。
具体实施方式
为了便于对本发明的进一步理解，下面提供的实施例对其做了更详细的说明。但是这些实施例仅供更好的理解发明而并非用来限定本发明的范围或实施原则，本发明的实施方式不限于以下内容。
实验材料与方法
试验药物：飞扬肠胃炎胶囊(陕西君碧莎制药有限公司，批准文号：国药准字Z20080523，批号：20150909)；妇科千金胶囊(株洲千金药业股份有限公司，批准文号：国药准字Z20020024，批号：Z20020024)；莲芝消炎胶囊(惠州市九惠制药股份有限公司，批准文号：国药准字Z44020431)。
动物：SD大鼠120只，雌性，7～8周龄，体重210～250g，购于第四军医大学实验动物中心[SCXK(军)2012-0007]，适应性饲养一周，室内温度21～25℃，相对湿度40％～60％，自由饮水，人工控制光照昼夜12h，垫料一周更换两次。
试剂：苯酚(天津红岩试剂厂)、西黄蓍胶(上海金穗生物科技有限公司)、丙三醇(天津富宇精细化工有限公司)、IL-1βELISA检测试剂盒(联科生物)、TNF-αELISA检测试剂盒(联科生物)、NF-KB抗体(CST，美国)、Caspase-3抗体(CST，美国)。
仪器：MLS-3750高压蒸汽灭菌锅(日本三洋)、Centrifuge 5418R小型冷冻高速离心机(德国艾本德公司)、微量加样器(吉尔森公司)、25G平口针头。
实验方法：本实验对现有技术中盆腔炎性后遗症造模方法(“桂枝茯苓胶囊对大鼠慢性盆腔炎的影响”，孙兰，等，中药药理与临床，2013；29(04):21～24)进行优化。SD雌性大鼠100只，造模前12h禁食不禁水，造模日10％水合氯醛腹腔注射麻醉，为固定大鼠阴道以助于平口针头顺利从宫颈口进入子宫，故采用无菌小塑料管置入大鼠阴道，用25G平口针头朝大鼠右侧子宫推注0.1mL 15％苯酚胶浆(液化苯酚5mL，西黄蓍胶粉1g，丙三醇2mL，加蒸馏水至33.3mL)，大鼠倾斜放置3min防止胶体外漏，假手术组子宫内注入0.1mL无菌生理盐水，其余操作和模型组保持一致。造模后第16d对动物进行重新分组后灌胃给药，包括假手术组、模型组、飞扬肠胃炎胶囊低剂量组(0.6g/kg)、飞扬肠胃炎胶囊中剂量组(1.2g/kg)、飞扬肠胃炎胶囊高剂量组(2.4g/kg)、妇科千金胶囊组(1.2g/kg)、莲芝消炎胶囊组(1.2g/kg)、飞扬草组(1.2g/kg)、火炭母组(1.2g/kg)、救必应组(1.2g/kg)。假手术组、模型组给予等量生理盐水，其余给药组灌胃给予相应剂量药物，给药容量10mL/kg，给药周期30d。
最后一次给药24h后，10％水合氯醛腹腔注射麻醉大鼠，腹主动脉取血，4℃静置2h，3000rpm离心，10min，分离上层血清，保存于-80℃，用于IL-1β和TNF-α的检测。分离子宫，肉眼观察外观变化情况，如是否出现水肿、充血等，观察结束将右侧子宫剥离干净，置于10％甲醛溶液中固定，用于HE染色制作病理切片观察组织病理变化以及免疫组化检测子宫内膜NF-KB、Caspase-3表达情况。
统计学分析方法：实验数据以
表示，应用统计软件SPSS23.0对数据进行分析处理，方差齐则采用单因素方差分析法(One-Way ANOVA)进行多组间比较，方差不齐采用Tamhane’s T2检验，P＜0.05认为有统计学意义。
本发明飞扬草组是由飞扬草加水煎煮二次制备的，第一次8倍量水煎煮2小时，第2次加6倍量水煎煮1小时，合并煎液，滤过，浓缩后与及适量赋形剂、稳定剂或表面活性剂，混匀，制粒，装胶囊；火炭母组是由火炭母加水煎煮二次制备的，第一次8倍量水煎煮2小时，第2次加6倍量水煎煮1小时，合并煎液，滤过，浓缩后与及适量赋形剂、稳定剂或表面活性剂，混匀，制粒，装胶囊；救必应组由救必应加水煎煮二次制备的，第一次8倍量水煎煮2小时，第2次加6倍量水煎煮1小时，合并煎液，滤过，浓缩后与及适量赋形剂、稳定剂或表面活性剂，混匀，制粒，装胶囊。
实验结果
外观情况：模型组、莲芝消炎胶囊组、飞扬草组、火炭母组、救必应组大鼠子宫与假手术组相比可见明显肿胀、出血，部分子宫宫腔内有透明液体；假手术组大鼠两侧子宫外观无异常；飞扬肠胃炎胶囊中、高剂量组和妇科千金胶囊组，大鼠子宫炎症程度明显减轻；飞扬肠胃炎胶囊低剂量组的大鼠子宫与模型组相比外观症状有所改善。
HE病理结果：HE病理染色结果显示，假手术组子宫组织结构完整，单层柱状上皮细胞排列紧密；与假手术组比较，模型组、莲芝消炎胶囊组、飞扬草组、火炭母组、救必应组大鼠子宫大量炎性细胞浸润，部分细胞坏死，组织结构紊乱；飞扬肠胃炎胶囊中、高剂量组和妇科千金胶囊组与模型组比较，炎性细胞明显减少，只有少量浆细胞和嗜酸性粒细胞浸润，粘膜层组织结构完整；飞扬肠胃炎胶囊低剂量组与模型组比较，炎性细胞减少，但组织水肿、出血，内膜上皮轻度增生情况依然存在。结果表明，飞扬肠胃炎胶囊中、高剂量能够显著改善盆腔炎性后遗症大鼠子宫内膜组织发生的病理形态学改变，见图1，而单独使用莲芝消炎胶囊、飞扬草、火炭母或救必应对盆腔炎性后遗症大鼠子宫并无明显积极作用。
飞扬肠胃炎胶囊对盆腔炎性后遗症大鼠血清中IL-1β和TNF-α的影响：根据ELISA检测结果可知，与假手术组比较，模型组、莲芝消炎胶囊组、飞扬草组、火炭母组、救必应组大鼠血清中IL-1β水平显著升高；与模型组比较，飞扬肠胃炎胶囊中、高剂量组和妇科千金胶囊组IL-1β显著降低，飞扬肠胃炎胶囊低剂量组IL-1β含量降低；与假手术组比较，模型组、莲芝消炎胶囊组、飞扬草组、火炭母组、救必应组大鼠血清中TNF-α水平显著升高；与模型组比较，飞扬肠胃炎胶囊中、高剂量组和妇科千金胶囊组TNF-α显著降低，飞扬肠胃炎胶囊低剂量组TNF-α含量降低。结果表明，飞扬肠胃炎胶囊能够有效降低盆腔炎性后遗症大鼠血清中的IL-1β和TNF-α含量，且与低剂量相比，中、高剂量组效果更显著(表1)。
表1各实验组药物对盆腔炎性后遗症大鼠血清中IL-1β、TNF-α的影响(
n＝10)
注：与模型组比较：**P＜0.01；与飞扬肠胃炎胶囊低剂量组比较：ΔP＜0.05，ΔΔP＜0.01。
飞扬肠胃炎胶囊对盆腔炎性后遗症大鼠NF-KB和Caspase-3的影响：结果显示，与假手术组比较，模型组、莲芝消炎胶囊组、飞扬草组、火炭母组、救必应组子宫组织中NF-KB表达显著升高；与模型组比较，飞扬肠胃炎胶囊中、高剂量组和妇科千金胶囊组子宫组织中NF-KB表达明显降低，飞扬肠胃炎胶囊低剂量组子宫组织中NF-KB表达变化不明显。与假手术组比较，模型组、莲芝消炎胶囊组、飞扬草组、火炭母组、救必应组子宫组织中Caspase-3表达显著升高；与模型组比较，飞扬肠胃炎胶囊中、高剂量组和妇科千金胶囊组子宫组织中Caspase-3表达显著升高，飞扬肠胃炎胶囊低剂量组子宫组织中Caspase-3表达变化不明显。由此可知，飞扬肠胃炎胶囊中、高剂量能够有效抑制NF-KB的表达，同时促进Caspase-3的表达(表2，图2、3)。
表2各实验组药物对盆腔炎性后遗症大鼠组织中NF-KB、Caspase-3的影响(
n＝10)
注：与模型组比较：*P＜0.05，**P＜0.01；与飞扬肠胃炎胶囊低剂量组比较：ΔP＜0.05。
Claims (4)
1.飞扬肠胃炎胶囊在制备预防和/或治疗盆腔炎性后遗症药物中的应用，其特征在于所述飞扬肠胃炎胶囊的活性成分按重量份计，由飞扬草1.0-5.0份，火炭母0.2-3.0份，救必应0.1-1.0份组成。
2.权利要求1所述的应用，其特征在于其剂量为1.2−2.4 g/kg。
3.利要求1-2任一项所述的应用，其特征在于所述飞扬肠胃炎胶囊能有效降低盆腔炎性后遗症患者血清中的IL-1β和TNF-α含量。
4.权利要求1-2任一项所述的应用，其特征在于所述飞扬肠胃炎胶囊能有效抑制盆腔炎性后遗症患者子宫组织中NF-KB的表达，同时促进Caspase-3的表达。
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101007071A (zh) * | 2006-01-27 | 2007-08-01 | 刘晓 | 治疗急、慢性肠、胃炎及细菌性痢疾的中药及其制备工艺 |
| CN102178749A (zh) * | 2010-12-31 | 2011-09-14 | 史志辉 | 一种中药组合物及其制备方法 |
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Non-Patent Citations (1)
| Title |
|---|
| 高效液相色谱法测定飞扬肠胃炎片中槲皮素的含量;陈向前等;《海峡药学》;20091231;第21卷(第6期);第58-59页 * |
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