CN106880628B - 一种治疗肝损伤的药物组合物 - Google Patents
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Abstract
本发明涉及一种治疗肝损伤的药物组合物，所述药物组合物包含下式的化合物或其药学上可接受的盐、和药学上可以接受的载体：本发明药物能有效减轻免疫性肝损伤的症状，保肝护肝，为免疫性肝损伤患者带来极大的健康效益。
Description
技术领域
本发明涉及医药领域，具体的说，本发明涉及一种治疗肝损伤的药物组合物。
背景技术
免疫性肝损伤(包括自身免疫性肝炎)是由于患者肝脏的免疫耐受性减退，引起的一种不能自然痊愈的肝炎。关于自身免疫性肝炎的发病机制，最新观点认为，机体在易感性基因的作用下，受环境因素、药物或感染因子的诱导而发病，由于产生肝细胞膜自身靶抗原，机体免疫功能失调，以及肝脏本身免疫耐受性减退，导致肝损伤。目前对免疫性肝损伤的临床治疗还缺乏特效的药物，迫切需要研制新药进行治疗。
发明内容
本发明的目的在于提供一种治疗肝损伤的药物组合物。
为了实现本发明的目的，本发明提供一种治疗肝损伤的药物组合物，所述药物组合物包含下式的化合物或其药学上可接受的盐、和药学上可以接受的载体：
优选地，所述药物组合物可以制成丸剂、颗粒剂、胶囊剂或片剂。
本发明还提供化合物在制备治疗肝损伤的药物中的用途，所述化合物具有下列结构：
本发明药物能有效减轻免疫性肝损伤的症状，保肝护肝，为免疫性肝损伤患者带来极大的健康效益。
附图说明
图1是本发明药物对肝组织病理学的影响。
A正常组；B模型组；C阳性对照组；D低剂量组；E中剂量组；F高剂量组
具体实施方式
下面结合本发明药物对刀豆蛋白A所致免疫性肝损伤小鼠的肝脏指数、脾脏指数、肝脏组织病理学变化，对免疫性肝损伤小鼠血清中ALT、AST、NO含量的影响，对免疫性肝损伤小鼠肝脏匀浆中SOD、MDA水平的影响对本发明做进一步的详细说明，所述是对本发明的解释而不是限定。
实验例1本发明药物的表征
1H-NMR(CDCl3,TMS)δ(ppm):1.66-1.76(m,1H)、2.03-2.14(m,1H)、2.56-2.67(m,1H)、3.21-3.25(m,2H)、3.47-3.54(m,2H)、3.59-3.64(m,1H)、3.74-3.81(m,1H)、3.86-3.95(m,2H)、4.31-4.36(m,2H)、7.10-7.14(m,2H)、7.32-7.37(m,1H)、7.41-7.46(m,1H)、7.69-7.85(m,4H)、8.14-8.20(m,2H)、8.52-8.54(m,1H).
实验例2本发明药物对于免疫性肝损伤的治疗效果
将实验动物随机均分为正常组、模型组、阳性对照组、本发明药物高、中、低剂量组，每组20只。正常组与模型组小鼠每天灌胃生理盐水20mL·kg-1；阳性对照组小鼠灌胃0.02g·kg-1阳性对照药物联苯双酯；本发明药物高、中、低剂量组分别灌胃0.04g·kg-1、0.02g·kg-1、0.01g·kg-1本发明药物。每天一次，共给药8d，末次给药1h后，除正常组外，其余各组小鼠均一次性尾静脉注射刀豆蛋白A 30mg·kg-1。禁食不禁水8h后称量小鼠体重，摘眼球采血，分离血清，测定ALT(谷氨转氨酶)、AST(谷草转氨酶)、NO水平；摘眼球取血后，脱颈处死，取肝脏、脾脏，计算脏器系数(脏器质量/体重×100％)；取部分肝脏组织制备成10％的肝匀浆，3000r·min-1离心10～15min，取上清液，测定SOD(超氧化物歧化酶)、MDA(丙二醛)含量。
取上述肝脏组织(肝左叶)置于10％甲醛溶液(PBS配制)固定，HE染色，镜检。
统计学处理
数据用SPSS17.0软件进行方差分析及独立样本t检验，结果用差表示，P<0.05为具有统计学意义。
本发明药物对刀豆蛋白A致免疫性肝损伤小鼠肝脾指数的影响
与正常组比较，模型组小鼠的肝脏、脾脏指数明显升高(P<0.01)，提示造模成功；与模型组比较，本发明药物各组均能显著降低小鼠肝脾脏器指数，其中高剂量组与模型组比较具有极显著差异(P<0.01)。见下表。
注:与模型组比较1)P<0.05，2)P<0.01。
本发明药物对刀豆蛋白A致免疫性肝损伤小鼠血清中ALT、AST、NO含量的影响结果见下表。
注:与模型组比较1)P<0.05，2)P<0.01。
与正常组比较，模型组小鼠血清中ALT、AST及NO含量显著升高(P<0.01)，说明造模成功。与模型组比较，本发明药物各组小鼠血清中ALT、AST及NO含量均显著性降低(P<0.01,P<0.05)。其中高剂量组药效最佳，说明本发明药物不仅对小鼠起到了保肝降酶的作用，并且在肝脏发生病变时能迅速调节免疫，减少炎症介质等毒害物质的释放，从而减轻肝脏炎性细胞的浸润。
本发明药物对刀豆蛋白A致免疫性肝损伤小鼠肝脏匀浆中SOD、MDA水平的影响结果见下表。
注:与模型组比较1)P<0.05，2)P<0.01。
模型组小鼠肝匀浆中SOD活性较正常组显著降低(P<0.01)；MDA含量显著升高(P<0.01)，说明造模成功。本发明药物各组均能显著升高免疫性肝损伤小鼠肝脏匀浆SOD活性，降低小鼠肝脏匀浆中MDA含量(P<0.01，P<0.05)，具有清除氧自由基、增强机体抗氧化的能力，从而保护肝细胞生物膜，避免或减少肝细胞核固缩或崩解。
本发明药物对肝组织病理学影响
光镜下正常组小鼠肝组织结构完整，肝细胞以中央静脉为中心向四周呈条索状、放射状整齐排列，肝小叶结构完整，肝细胞分界清，细胞核1～2个，呈圆形、类圆形，位于细胞中央，胞质丰富，肝窦排列规则，汇管区清晰。模型组小鼠肝小叶结构基本清晰，肝窦扩张充血，肝细胞胞质内有空泡状的物质，将肝细胞的细胞核挤压到细胞一侧；肝细胞结构不清晰，细胞核浓缩深染，胞浆分界不清，呈蛋白样的均质红染。本发明药物各组小鼠肝组织结构完整，病变主要以肝细胞水肿、脂肪、坏死为主，肝细胞损伤程度较模型组明显减轻。高剂量组肝细胞水肿与炎性浸润较阳性对照组轻。低、中剂量组肝细胞损伤程度明显较高剂量组重。见图1。
Claims (3)
1.一种治疗免疫性肝损伤的药物组合物，其特征在于，所述药物组合物包含下式的化合物或其药学上可接受的盐、和药学上可以接受的载体：
2.根据权利要求1所述的治疗免疫性肝损伤的药物组合物，其特征在于，所述药物组合物制成丸剂、颗粒剂、胶囊剂或片剂。
3.化合物在制备治疗免疫性肝损伤的药物中的用途，其特征在于，所述化合物具有下列结构：
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