CN103989695B - 一种治疗支气管哮喘的药物组合物及其应用 - Google Patents
一种治疗支气管哮喘的药物组合物及其应用 Download PDFInfo
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Abstract
本发明公开了一种治疗支气管哮喘的药物组合物及其应用，该药物组合物含有莫诺苷和醋酸地塞米松，其中莫诺苷与醋酸地塞米松的重量比为60-360：1。本发明最重要的优点是协同平喘，改善支气管哮喘大鼠的肺功能，降低气道反应性，从而达到治愈支气管哮喘的目的。
Description
技术领域
本发明属于医药技术领域，具体涉及一种治疗支气管哮喘的药物组合物及其应用。
背景技术
支气管哮喘（简称哮喘）是一种以嗜酸性粒细胞、T淋巴细胞、肥大细胞以及巨噬细胞等细胞和一系列细胞因子参与为特征的慢性气道炎症性疾病，严重威害着公众健康，其主要的病理特征是急慢性气道炎症、平滑肌功能紊乱和气道重塑，据WHO预计，每年有1500万人因哮喘失去劳动能力，占全球疾病负担的1%，全球每年因哮喘死亡的人数达25万人，患者及社会为控制哮喘付出了巨额的花费，给社会带来了很大的经济负担，因此，对于哮喘的发病机制及其防治的研究，一直是各国医学家关注的热点。
目前，治疗哮喘的化学药品主要有糖皮质激素、β2受体激动药和黄嘌呤类等药物，虽疗效确切可靠，但不良反应较大。糖皮质激素疗效显著，但作用广泛，长期大剂量使用易引起多种严重不良反应；β2受体激动药是哮喘急性发作的常用药，黄嘌呤类药物适用于各型哮喘，但它们在发挥治疗作用的同时可兴奋心脏，甚至引起心律失常。同时，近二十年来尽管已经采取包括吸入糖皮质激素在内的综合抗炎治疗方案，但流行病学调查发现哮喘的发病率、死亡率并没有随之而降低（苏奎国,姜良铎,郭勇英,等.桑苏饮对哮喘模型大鼠气道重塑及肺组织上皮细胞ICAM-1表达的影响[J].山东中医药大学学报,2010,34(4):354-357.），仍然迫切需要去寻找新的方法来防治哮喘。
莫诺苷是从中药山茱萸中提取得到的水溶性的环烯醚萜类化合物，文献报道山茱萸水提物具有降血糖、免疫抑制、抗炎、抗休克、强心、抗心律失常、抗疲劳、抗衰老和增强记忆力等作用。然而，通过检索国内外的现有技术发现，在治疗支气管哮喘方面，尚未见有以莫诺苷或将莫诺苷与醋酸地塞米松联用作为主要活性成分的治疗药物。
发明内容
本发明的目的之一是提供一种作用全面、毒副作用低的治疗支气管哮喘的药物组合物。本发明药物含有特定比例的莫诺苷和醋酸地塞米松，两药合用可协同改善支气管哮喘患者的肺功能，降低气道反应性，改善哮喘气道重塑，其治疗效果明显优于相同剂量的单方。
为了实现本发明的目的，发明人通过大量试验研究并不懈探索，最终获得了如下技术方案：
一种治疗支气管哮喘的药物组合物，其中所述的药物组合物含有莫诺苷和醋酸地塞米松。
优选地，如上所述的治疗支气管哮喘的药物组合物，其中莫诺苷与醋酸地塞米松的重量比为60-360：1。
进一步优选地，如上所述的治疗支气管哮喘的药物组合物，其中莫诺苷与醋酸地塞米松的重量比为150-200：1。
再进一步优选地，如上所述的治疗支气管哮喘的药物组合物，其中莫诺苷与醋酸地塞米松的重量比为180：1。
本发明所述治疗支气管哮喘的药物组合物为口服制剂。优选地，所述的口服制剂包括片剂、胶囊剂、颗粒剂。
按照本发明所提供的药物组合物制备成的药物制剂中，每一制剂单位含有莫诺苷的有效量为18mg-72mg，含有醋酸地塞米松的有效量为0.1mg-0.4mg。进一步优选的本发明所提供的药物组合物制备成的药物制剂中，每一制剂单位含有莫诺苷的有效量为54mg，含有醋酸地塞米松的有效量为0.3mg。对于本领域的技术人员来说，给药频次是可以依据病情状况、年龄等因素综合考虑后确定的。
本发明人采用卵白蛋白(OVA)致敏和激发建立大鼠哮喘模型，通过统计试验数据发现，莫诺苷和醋酸地塞米松合用可协同改善支气管哮喘大鼠的肺功能，降低气道反应性，改善哮喘气道重塑，其治疗效果明显优于相同剂量的单方。因此，本发明的目的之二是提供一种新的药物组合物用于制备治疗支气管哮喘的药物中的用途；即：莫诺苷与醋酸地塞米松组成的组合物作为活性成分在制备治疗支气管哮喘的药物中的应用。
与现有技术相比，本发明涉及的药物组合物具有如下优点和显著的进步：
（1）本发明最重要的优点是协同平喘，改善支气管哮喘大鼠的肺功能，降低气道反应性，从而达到治愈支气管哮喘的目的。
（2）相同疗效的情况下，减少了莫诺苷及醋酸地塞米松使用的剂量，从而降低了地塞米松的毒副作用，增加了用药的安全性和患者的依从性。
具体实施方式
以下是本发明的具体实施例，对本发明的技术方案做进一步作描述，但是本发明的保护范围并不限于这些实施例。凡是不背离本发明构思的改变或等同替代均包括在本发明的保护范围之内。
清洁级SD大鼠60只，雌雄各半，体质量180~220g。所有大鼠随机分为正常对照组、模型对照组、地塞米松组、莫诺苷组、复方组，每组12只。采用卵白蛋白（OVA）致敏法制备支气管哮喘动物模型。除正常对照组外，其他四组动物第1、2、3日用含OVA10mg、A1(OH)3干粉100mg的生理盐水混悬液lmL腹腔注射致敏，第8日重复致敏1次，第l5日开始超声雾化1%0VA进行激发，约30min/次，于每日早上8-9时进行。直至大鼠出现哮喘样发作，共4周。雾化时见大鼠出现烦躁不安、打喷嚏、大小便失禁、抓耳朵、紫绀等症状，说明哮喘模型复制成功。第5周起各组大鼠分别按如下剂量灌胃给予相应的受试物：
正常对照组：等体积生理盐水；
模型对照组：等体积生理盐水；
莫诺苷组：莫诺苷90mg/kg；
地塞米松组：醋酸地塞米松0.5mg/kg；
复方组：莫诺苷90mg/kg+地塞米松0.5mg/kg。
各组大鼠每日给药1次，共灌胃30d。末次给药后1h，使用美国Buxco公司的整体体积描记系统测定肺功能：大鼠放入流量型整体体积描记箱，每个箱内放置1只大鼠，每轮测量4只大鼠，将大鼠直接放进一个密闭的腔内，大鼠能自由活动，无须麻醉，呼吸接近自然，观察并让动物在腔内适应5～10min。首先用0.4％磷酸组胺-2％氯化乙酰胆碱(1：2)进行激发，激发剂经雾化系统进入每个放置大鼠的整体体积描记箱，每个整体体积描记箱内雾化50μL，雾化器的雾化时间为1min。传感器记录小鼠呼吸时引起的体描箱内压力变化，由放大器处理后，信号传输给系统，由计算机计算出大鼠的呼吸频率、每分钟通气量、吸气流量峰值、呼气流量峰值及增强呼吸间歇。结果参见表1、表2、表3。
表1各组大鼠气道反应性比较
与模型组比较，★P＜0.05，★★P＜0.01；与莫诺苷组比较，■P＜0.05，■■P＜0.01；与地塞米松组比较，●P＜0.05，●●P＜0.01。
表2各组大鼠呼吸频率和每分钟通气量值比较
与模型组比较，★P＜0.05，★★P＜0.01；与莫诺苷组比较，■P＜0.05，■■P＜0.01；
与地塞米松组比较，●P＜0.05，●●P＜0.01。
表3各组大鼠吸气流量峰值和呼气流量峰值比较
与模型组比较，★P＜0.05，★★P＜0.01；与莫诺苷组比较，■P＜0.05，■■P＜0.01；
与地塞米松组比较，●P＜0.05，●●P＜0.01。
Claims (3)
1.一种治疗支气管哮喘的药物组合物，其特征在于：所述的药物组合物含有莫诺苷和醋酸地塞米松，莫诺苷与醋酸地塞米松的重量比为180：1。
2.根据权利要求1所述治疗支气管哮喘的药物组合物，其特征在于：所述的药物组合物为口服制剂。
3.根据权利要求2所述治疗支气管哮喘的药物组合物，其特征在于：所述的口服制剂包括片剂、胶囊剂、颗粒剂。
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| CN106727641A (zh) * | 2016-12-07 | 2017-05-31 | 郑州仁宏医药科技有限公司 | 一种治疗支气管炎的药物及其制备方法 |
| CN106511363A (zh) * | 2016-12-07 | 2017-03-22 | 郑州仁宏医药科技有限公司 | 一种治疗支气管炎的西药组合及其制备方法 |
| CN110151768A (zh) * | 2019-05-08 | 2019-08-23 | 西安交通大学 | 一种具有抗哮喘活性的药物组合物及其应用 |
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| CN1709423A (zh) * | 2005-06-06 | 2005-12-21 | 广东医学院 | 糖皮质激素与中药组成的防治哮喘及慢阻肺的药物制剂 |
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