CN115025126A - 地龙在制备预防和/或治疗脂肪肝的药物中的用途 - Google Patents
地龙在制备预防和/或治疗脂肪肝的药物中的用途 Download PDFInfo
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Abstract
本发明属于医药技术领域,具体涉及一种地龙在制备预防和/或治疗脂肪肝的药物中的用途。本发明首次发现了地龙药材,或其炮制品,或其提取物在制备预防和/或治疗脂肪肝的药物中的用途。动物实验证明,从地龙药材中提取的地龙总蛋白提取物对脂肪肝具有很好的治疗效果,在相关药物的制备中具有很好的应用前景。
Description
技术领域
本发明属于医药技术领域,具体涉及一种地龙在制备预防和/或治疗脂肪肝的药物中的用途。
背景技术
脂肪肝是指由于各种原因引起的肝细胞内脂肪堆积过多的病变。脂肪性肝病正严重威胁国人的健康,成为仅次于病毒性肝炎的第二大肝病,已被公认为隐蔽性肝硬化的常见原因。
脂肪肝的治疗方法主要是消除病因。到目前为止,西药尚无防治脂肪肝的有效药物,以中药长期调理性的治疗最好。中药中以制何首乌和山楂最好,这两种药能降低血脂,防止胆固醇在肝内沉积。西药常选用保护肝细胞、去脂药物及抗氧化剂等,如维生素B、C、E、卵磷脂、熊去氧胆酸、水飞蓟素、肌苷、辅酶A、还原型谷胱甘肽、牛磺酸、肉毒碱乳清酸盐、肝泰乐,以及某些降脂药物(例如:肝旨清)等等。上述药物虽然很多,但大多仍需要进一步验证其疗效以及安全性。因此,开发新的脂肪肝治疗药物仍然是本领域的重要研究课题。
地龙(Geosaurus),为环节动物门钜蚓科动物参环毛蚓Pheretimaas pergillum(EPerrier)、通俗环毛蚓P vulgarisChen、威廉环毛蚓Pguillelmi(Michaelsen)或栉肓毛蚓PpectiniferaMichaelsen的干燥体。前一种习称“广地龙”,后三种习称“泸地龙”,主产于广西、广东、福建。地龙含有胶原酶、纤溶酶、蚓激酶、核酸、微量元素等多种成分,被广泛用于药物中。其性寒、味咸,清热定惊,痛经活络、平喘利尿;用于脑血栓、脑梗塞、冠心病、中风,关节麻痹,肢体麻木,半身不遂,高血压症等病症。
地龙总蛋白是从中药材地龙中提取得到的蛋白质复合物。地龙中的蛋白质已被证明具有活血化瘀、溶栓降压、抗肿瘤、平喘止咳和消炎止痛等功效(袁渊等,地龙活性蛋白药理学作用研究进展)。
现有技术文献(复方地龙胶囊治疗脂肪肝60例临床观察,doi:10.3969/j.issn.1003-5699.2003.03.014)公开了地龙药材制成的复方药物对脂肪肝具有疗效。但是其并没有进一步探讨地龙药材单方对脂肪肝的治疗效果。除此之外,对于地龙药材以及地龙中的蛋白质对脂肪肝的功效,尚未有任何文献报道。
发明内容
针对现有技术中的问题,本发明提供地龙在制备预防和/或治疗脂肪肝的药物中的用途,目的在于为脂肪肝的治疗提供更多的临床选择。
地龙药材,或其炮制品,或其提取物在制备预防和/或治疗脂肪肝的药物中的用途。
优选的,所述药物用于预防和/或治疗肥胖性脂肪肝。
优选的,所述药物用于降低血液中转氨酶的含量。
优选的,所述药物用于降低血液和/或肝脏组织中胆固醇和/或甘油三酯的含量。
优选的,所述提取物是地龙总蛋白提取物。
优选的,所述地龙总蛋白提取物按照如下方法制备得到:
步骤1,将地龙加入以水为溶剂的pH 6.1~6.9的缓冲溶液,冷浸提取;
步骤2,取上清液,醇沉,分离出沉淀,即得。
优选的,步骤1中,所述冷浸提取的条件为在0~4℃冷浸12~24h。
优选的,步骤2中,所述醇沉的过程是向所述上清液中加入乙醇,直至乙醇的体积分数为70~80%。
本发明还提供一种用于预防和/或治疗脂肪肝的地龙总蛋白提取物,它按照如下方法制备得到:
步骤1,将地龙加入以水为溶剂的pH 6.1~6.9的缓冲溶液,冷浸提取;
步骤2,取上清液,醇沉,分离出沉淀,即得。
优选的,步骤1中,所述冷浸提取的条件为在0~4℃冷浸12~24h;
和/或,步骤2中,所述醇沉的过程是向所述上清液中加入乙醇,直至乙醇的体积分数为70~80%。
本发明发现了地龙药材的一种新的功效,并提供了一种新的地龙总蛋白提取物。动物实验发现,地龙总蛋白提取物对高脂饮食诱导的脂肪肝动物模型具有很好的治疗效果。其能够有效抑制高脂饮食引起的体重上升,并且能减轻肝脏重量,降低肝脏指数,减轻肝脏的病理变化。同时,其能够有效降低血清和肝脏组织中的胆固醇(TC)和甘油三酯(TG)的含量,以及血清中ALT(谷丙转氨酶)和AST(谷草转氨酶)的含量。以上实验结果表明,本发明的地龙总蛋白提取物对脂肪肝具有很好的治疗效果,在相关药物的制备中具有很好的应用前景。
显然,根据本发明的上述内容,按照本领域的普通技术知识和惯用手段,在不脱离本发明上述基本技术思想前提下,还可以做出其它多种形式的修改、替换或变更。
以下通过实施例形式的具体实施方式,对本发明的上述内容再作进一步的详细说明。但不应将此理解为本发明上述主题的范围仅限于以下的实例。凡基于本发明上述内容所实现的技术均属于本发明的范围。
附图说明
图1为地龙总蛋白降低高脂喂养小鼠体重的实验结果(*P<0.05,**P<0.01,vs.模型组,n=10);
图2为地龙总蛋白降低高脂喂养小鼠肝脏指数的实验结果(*P<0.05,**P<0.01,vs.模型组,n=10);
图3为地龙总蛋白改善高脂喂养小鼠肝脏脂肪变性的实验结果;
图4为地龙总蛋白降低高脂喂养小鼠血清TC的检测结果(*P<0.05,**P<0.01,vs.模型组,n=10);
图5为地龙总蛋白降低高脂喂养小鼠血清TG的检测结果(**P<0.01,vs.模型组,n=10);
图6为地龙总蛋白降低高脂喂养小鼠肝脏组织TC的检测结果(**P<0.01,vs.模型组,n=10);
图7为地龙总蛋白降低高脂喂养小鼠肝脏组织TG的检测结果(**P<0.01,vs.模型组,n=10);
图8为地龙总蛋白降低高脂喂养小鼠血清AST的检测结果(**P<0.01,vs.模型组,n=10);
图9为地龙总蛋白降低高脂喂养小鼠血清ALT的检测结果(**P<0.01,vs.模型组,n=10)。
具体实施方式
以下实施例和实验例中,未具体说明的试剂和材料均为市售品。
实施例1地龙总蛋白提取物
本实施例的地龙总蛋白提取物制备方法如下:
称取50g地龙粗粉加入pH 6.8的磷酸盐缓冲溶液500mL,于4℃冷浸24h,3000rpm离心15min,取上清液,加无水乙醇至体积分数为75%,4℃静置12h,10000rpm离心15min,收集沉淀物,沉淀物用无水乙醇洗涤3次,于40℃减压干燥,称重,即得。
下面通过实验对本发明的有益效果作进一步的说明。
实验例1地龙总蛋白提取物对脂肪肝动物模型的治疗效果
一、实验方法
1.地龙总蛋白提取物的制备
与实施例1相同。
2.动物实验分组方法及给药方法
将40只雄性C57BL/6小鼠随机分为:正常组、模型组、地龙蛋白低剂量组(1g/kg),地龙蛋白高剂量组(2g/kg),每组10只。
高脂致脂肪肝模型建立方法如下:小鼠适应性喂养2周后,将小鼠随机分为2组:正常组、模型组、地龙蛋白低剂量组(1g/kg),地龙蛋白高剂量组(2g/kg)。正常组小鼠喂正常饲料(成都达硕公司标准化动物饲料);其余3组以高脂饲料(组成见表1)喂养10周,建立非酒精性脂肪肝模型。高脂饲料喂养10周后,模型组、地龙蛋白(高、低剂量组)分别灌胃给与1%羧甲基纤维素钠(CMC-Na)和地龙蛋白(1g/kg、2g/kg,地龙蛋白以1%CMC-Na混悬)。干预8周后,称重,腹腔注射无巴比妥麻醉(45mg/kg,ip),眼球取血、处死。
表1高脂饲料配方
(1)肝脏指数的测定
处死后,取全部肝脏,称重,将肝脏置于离心管内,标记,放在装有干冰的泡沫盒内,80℃冰箱保存,待用。根据记录的小鼠体重、计算肝指数。
(2)肝脏病理切片
取新鲜肝脏组织,10%中性甲醛固定24h,然后经过脱水、透明、浸蜡、包埋等步骤制作石蜡切片,切片厚度4μm,油红染色后,观察肝脏脂质情况。
(3)血清和肝脏组织生化指标测定
摘眼球取血后静置1h,4℃,3000rpm,离心10min,分离血清,-80℃保存,采用试剂盒检测血样本中总胆固醇(TC)和甘油三酯(TG)、ALT(谷丙转氨酶)和AST(谷草转氨酶)。
取肝组织,冰上以Tris-HCl进行组织匀浆,匀浆液在4℃用10000rpm离心10min,收集上清液,采用试剂盒检测肝脏TC、TG水平。
二、实验结果
各组小鼠体重如图1所示,可以看到,高脂饲料喂养会导致小鼠体重显著升高,而采用地龙总蛋白提取物干预后能够显著抑制高脂引起的体重上升。
各组小鼠肝脏指数如图2所示,高脂饲料喂养会导致小鼠肝脏显著指数升高,而采用地龙总蛋白提取物干预后能减轻肝脏重量,降低肝脏指数。
各组小鼠肝脏脂肪变性状况如图3所示,可以看到高脂饲料喂养会导致小鼠肝脏脂质堆积。地龙总蛋白提取物干预后,能减轻肝脏病理变化,减轻肝脏脂肪变性,油红染色后,可见地龙总蛋白干预组,脂滴空泡减少,细胞肿胀也有较大改善。
各组小鼠的血清中TC和TG的含量,肝脏组织中TC和TG的含量,以及血清中AST和ALT含量如图4-9所示。从图中可以看到,高脂饮食喂养的小鼠血清和肝脏组织中TC和TG的含量升高,血清中AST和ALT的含量升高。
通过上述实施例和实验例可以看到,从地龙药材中提取得到的地龙总蛋白提取物能够有效抑制高脂饮食引起的体重上升,减轻肝脏重量,降低肝脏指数,减轻肝脏的病理变化。同时,其能够有效降低血清和肝脏组织中的TC和TG的含量,以及血清中ALT和AST的含量。由此可见,地龙对脂肪肝具有很好的治疗效果,且具有降血脂的功效,在相关药物的制备中具有很好的应用前景。
Claims (10)
1.地龙药材,或其炮制品,或其提取物在制备预防和/或治疗脂肪肝的药物中的用途。
2.按照权利要求1所述的用途,其特征在于:所述药物用于预防和/或治疗肥胖性脂肪肝。
3.按照权利要求1所述的用途,其特征在于:所述药物用于降低血液中转氨酶的含量。
4.按照权利要求1所述的用途,其特征在于:所述药物用于降低血液和/或肝脏组织中胆固醇和/或甘油三酯的含量。
5.按照权利要求1所述的用途,其特征在于:所述提取物是地龙总蛋白提取物。
6.按照权利要求5所述的用途,其特征在于:所述地龙总蛋白提取物按照如下方法制备得到:
步骤1,将地龙加入以水为溶剂的pH 6.1~6.9的缓冲溶液,冷浸提取;
步骤2,取上清液,醇沉,分离出沉淀,即得。
7.按照权利要求6所述的用途,其特征在于:步骤1中,所述冷浸提取的条件为在0~4℃冷浸12~24h。
8.按照权利要求6所述的用途,其特征在于:步骤2中,所述醇沉的过程是向所述上清液中加入乙醇,直至乙醇的体积分数为70~80%。
9.一种用于预防和/或治疗脂肪肝的地龙总蛋白提取物,其特征在于:它按照如下方法制备得到:
步骤1,将地龙加入以水为溶剂的pH 6.1~6.9的缓冲溶液,冷浸提取;
步骤2,取上清液,醇沉,分离出沉淀,即得。
10.按照权利要求9所述的地龙总蛋白提取物,其特征在于:步骤1中,所述冷浸提取的条件为在0~4℃冷浸12~24h;
和/或,步骤2中,所述醇沉的过程是向所述上清液中加入乙醇,直至乙醇的体积分数为70~80%。
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101607990A (zh) * | 2009-07-03 | 2009-12-23 | 山东大学威海分校 | 一种蚯蚓活性蛋白及其提取方法与应用 |
CN103211150A (zh) * | 2013-05-17 | 2013-07-24 | 胡凯 | 一种含活性地龙蛋白的多肽食品 |
CN104173383A (zh) * | 2014-08-18 | 2014-12-03 | 倪春辉 | 蚯蚓提取物的药物用途 |
US20170296607A1 (en) * | 2014-10-13 | 2017-10-19 | Korea Institute Of Oriental Medicine | Composition including extract of dolichos lablab linne as active ingredient for preventing or ameliorating non-alcoholic fatty liver disease |
-
2022
- 2022-06-23 CN CN202210718779.5A patent/CN115025126A/zh active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101607990A (zh) * | 2009-07-03 | 2009-12-23 | 山东大学威海分校 | 一种蚯蚓活性蛋白及其提取方法与应用 |
CN103211150A (zh) * | 2013-05-17 | 2013-07-24 | 胡凯 | 一种含活性地龙蛋白的多肽食品 |
CN104173383A (zh) * | 2014-08-18 | 2014-12-03 | 倪春辉 | 蚯蚓提取物的药物用途 |
US20170296607A1 (en) * | 2014-10-13 | 2017-10-19 | Korea Institute Of Oriental Medicine | Composition including extract of dolichos lablab linne as active ingredient for preventing or ameliorating non-alcoholic fatty liver disease |
Non-Patent Citations (3)
Title |
---|
刘亚明等: "中药地龙的活性成分及药理作用研究进展", 山西中医, vol. 27, no. 3, pages 44 - 45 * |
袁渊等: "地龙活性蛋白对实验性高脂血症大鼠的调脂作用及其机制", 中国医院药学杂志, vol. 38, no. 3, pages 239 - 241 * |
郭朋: "复方地龙胶囊治疗脂肪肝60例临床观察", 吉林中医药, vol. 23, no. 3, pages 17 * |
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