CN110772519A - 青藤碱或其盐在制备降低血尿酸水平、防治尿酸性肾病的药品中的用途 - Google Patents
青藤碱或其盐在制备降低血尿酸水平、防治尿酸性肾病的药品中的用途 Download PDFInfo
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Abstract
本发明涉及青藤碱或其盐在制备降低血尿酸水平、防治尿酸性肾病的药品中的用途，属于医药领域。一方面，本发明提供了青藤碱或其盐在制备降低血尿酸水平的药品或保健品中的用途。另一方面，本发明还提供了青藤碱或其盐在制备预防和/或治疗尿酸性肾病的药品中的用途。动物实验证明，青藤碱能够大幅降低血尿酸水平，同时改善高尿酸血症小鼠肾小管扩张、坏死以及肾纤维化的程度。本发明的应用能够为临床治疗高尿酸血症及其导致的高尿酸肾病提供新的用药选择。
Description
技术领域
本发明涉及青藤碱或其盐在制备降低血尿酸水平、防治尿酸性肾病的药品中的用途，属于医药领域。
背景技术
高尿酸血症指正常嘌呤饮食情况下，非同日两次测定空腹血清尿酸水平男性≥416μmol/L(7mg/dl)，女性≥357μmol/L(6mg/dl)。近年来，国内外众多研究证实高尿酸血症与痛风、心血管疾病、代谢综合征、高血压及肾脏疾病的发生发展密切相关。高尿酸血症是慢性肾脏病(Chronic Kidney Disease，CKD)患病率增高的重要原因，并且是CKD进展的独立风险因素。研究表明，降低血尿酸水平可以延缓肾脏疾病进展。治疗高尿酸肾病重在预防、纠正高尿酸血症，降低血尿酸水平，防止尿酸盐沉积在肾脏。
青藤碱(Sinomenine)，CAS号为115-53-7，其结构式如下所示：
目前的研究表明，青藤碱具有独特的药理作用，可以用于炎症、自身免疫性疾病的治疗(参见：Wang Q,Li XK.Immunosuppressive and anti-inflammatory activities ofsinomenine[J].Int Immunopharmacol,2011,11(3):373-376.)，此外，还具有潜在的抗肿瘤及镇痛作用。
然而，迄今尚未见青藤碱具有降尿酸、防治尿酸性肾病作用的相关报道。
发明内容
本发明旨在至少解决现有技术中存在的技术问题之一。为此，本发明的目的在于提供青藤碱或其盐在制备降低血尿酸水平的药品或保健品中的用途。本发明的另一目的在于提供青藤碱或其盐在制备预防和/或治疗尿酸性肾病的药品中的用途。
本发明提供了青藤碱或其盐在制备降低血尿酸水平的药品或保健品中的用途。
本发明提供了青藤碱或其盐在制备预防和/或治疗尿酸性肾病的药品中的用途。
进一步地，所述的药品降低血肌酐水平。
进一步地，所述的药品降低血尿酸水平。
进一步地，所述的药品降低尿蛋白肌酐比。
进一步地，所述的药品改善肾小管扩张和/或坏死。
进一步地，所述的药品减少肾脏炎性细胞数量。
进一步地，所述的药品改善肾纤维化。
进一步地，所述的药品或保健品是以青藤碱或其盐为活性成分，加入可接受的辅料或者辅助性成分制备而成的制剂。
进一步地，所述的制剂为口服制剂或注射制剂。
本发明中，青藤碱的盐是指青藤碱与无机酸和/或碱、有机酸和/或碱形成的酸式和/或碱式盐，也包括两性离子盐(内盐)，还包括季铵盐，例如烷基铵盐。本发明所述的盐例如可以是青藤碱的盐酸盐、硫酸盐、枸橼酸盐、苯磺酸盐、氢溴酸盐、氢氟酸盐、磷酸盐、乙酸盐、丙酸盐、丁二酸盐、草酸盐、苹果酸盐、琥珀酸盐、富马酸盐、马来酸盐、酒石酸盐或三氟乙酸盐。
本发明提供了青藤碱或其盐在制备降低血尿酸水平、防治尿酸性肾病的药品中的用途。动物实验证明，青藤碱能够大幅降低血尿酸水平，同时改善高尿酸血症小鼠肾小管扩张、坏死以及肾纤维化的程度。本发明的应用能够为临床治疗高尿酸血症及其导致的高尿酸肾病提供新的用药选择。
附图说明
图1为实施例1中小鼠血尿酸水平检测结果图；
图2为实施例1中小鼠血肌酐水平检测结果图；
图3为实施例1中小鼠尿蛋白肌酐比检测结果图；
图4为实施例1中小鼠肾脏组织PAS染色图；
图5为实施例1中小鼠肾脏MASSON染色图。
具体实施方式
下面将结合实施例对本发明的方案进行解释。本领域技术人员将会理解，下面的实施例仅用于说明本发明，而不应视为限定本发明的范围。实施例中未注明具体技术或条件的，按照本领域内的文献所描述的技术或条件或者按照产品说明书进行。所用试剂或仪器未注明生产厂商者，均为可以通过市购获得的常规产品。
实施例1青藤碱降低血尿酸水平及防治尿酸性肾病的作用
实验动物：SPF级雄性C57BL/6J小鼠。实验前至少1周恒温环境下标准化实验日粮饲养，饮水不限。
动物分组：将小鼠60只分为5组：正常对照组12只、高尿酸肾病模型组12只、青藤碱低剂量治疗组(100mg/kg/d)12只、青藤碱高剂量治疗组(200mg/kg/d)12只、阳性对照别嘌呤醇(5mg/kg/d)12只。
造模方法：根据小鼠体质量以腺嘌呤100mg/kg、氧嗪酸钾1500mg/kg的比例，用蒸馏水将两者混合后制成终浓度为80g/L的混悬液，模型组每日早晚灌胃，连续3周，建立高尿酸血症肾损害动物模型。正常对照组动物每日早晚两次等剂量的蒸馏水灌胃。3周后处死小鼠，腹主动脉取血，留取肾脏组织。
实验方法：青藤碱和别嘌呤醇治疗组于造模后第1天开始采用口服给药方式给药，连续21天；模型组造模后在相同时间灌喂同等剂量生理盐水；正常对照组在相同时间灌喂同等剂量生理盐水。
小鼠血液样本在室温3000r/min离心15min后取血清测定生化指标；小鼠尿液标本在室温800g/min离心10min后取上层尿液测定生化指标。实验结果见图1～图3。对小鼠肾脏组织进行PAS染色，观察肾脏结构，实验结果见图4。采用MASSON染色观测肾脏纤维化情况，实验结果见图5。
从图1可以看出，青藤碱能够大幅降低血尿酸水平，且高剂量治疗组所能达到的效果优于降尿酸临床一线用药别嘌呤醇(与模型组比，*P<0.05，##P<0.01，###P<0.001)。
从图2可以看出，青藤碱降低血肌酐水平，效果与别嘌呤醇相当甚至更优，具有较好的肾功能保护作用(与模型组比，###P<0.001，****和####P<0.0001)。
从图3可以看出，青藤碱降低尿蛋白肌酐比，效果与别嘌呤醇相当甚至更优，具有改善肾功能的作用(与模型组比，#P<0.05，##P<0.01，****P<0.0001)。
从图4可以看出，正常对照组肾脏的PAS染色图片具有完整的肾脏结构。高尿酸肾脏病模型组在第21天时可见明显的肾小管变性、坏死，管状萎缩，以及炎性细胞浸润。使用高剂量青藤碱治疗21天后，能明显改善肾小管扩张和坏死，减轻肾脏炎性细胞侵入。
从图5可以看出，正常对照组肾脏的MASSON染色图片具有完整的肾脏结构。高尿酸肾脏病模型组在第21天时可见明显的肾小管变性、坏死，管状萎缩和纤维化；MASSON染色蓝色区域明显(蓝色区域表示纤维化病变的程度)。使用高剂量青藤碱治疗21天后，MASSON染色蓝色区域明显少于高尿酸肾脏病模型组，表明其可改善高尿酸引起的肾脏纤维化。
Claims (10)
1.青藤碱或其盐在制备降低血尿酸水平的药品或保健品中的用途。
2.青藤碱或其盐在制备预防和/或治疗尿酸性肾病的药品中的用途。
3.如权得要求2所述的用途，其特征是：所述的药品降低血肌酐水平。
4.如权得要求2所述的用途，其特征是：所述的药品降低血尿酸水平。
5.如权得要求2所述的用途，其特征是：所述的药品降低尿蛋白肌酐比。
6.如权得要求2所述的用途，其特征是：所述的药品改善肾小管扩张和/或坏死。
7.如权得要求2所述的用途，其特征是：所述的药品减少肾脏炎性细胞数量。
8.如权得要求2所述的用途，其特征是：所述的药品改善肾纤维化。
9.如权利要求1～8任意一项所述的用途，其特征是：所述的药品或保健品是以青藤碱或其盐为活性成分，加入可接受的辅料或者辅助性成分制备而成的制剂。
10.如权利要求9所述的用途，其特征是：所述的制剂为口服制剂或注射制剂。
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1142946A (zh) * | 1995-08-09 | 1997-02-19 | 白云山正清制药股份有限公司 | 青藤碱在制备治疗慢性肾炎药剂中的应用 |
| CN103070878A (zh) * | 2012-12-11 | 2013-05-01 | 上海浦东高星生物技术研究所 | 复方青藤片 |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1142946A (zh) * | 1995-08-09 | 1997-02-19 | 白云山正清制药股份有限公司 | 青藤碱在制备治疗慢性肾炎药剂中的应用 |
| CN103070878A (zh) * | 2012-12-11 | 2013-05-01 | 上海浦东高星生物技术研究所 | 复方青藤片 |
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