CN116570645A - 一种用于防治血管性痴呆的药物组合物 - Google Patents
一种用于防治血管性痴呆的药物组合物 Download PDFInfo
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- CN116570645A CN116570645A CN202310840582.3A CN202310840582A CN116570645A CN 116570645 A CN116570645 A CN 116570645A CN 202310840582 A CN202310840582 A CN 202310840582A CN 116570645 A CN116570645 A CN 116570645A
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Classifications
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- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/537—Salvia (sage)
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Abstract
本发明属于神经系统疾病治疗领域，具体涉及一种用于防治血管性痴呆的药物组合物。所述组合物含有丹参总酚酸80‑110份，洋川芎内酯类0.2‑5份，水蛭胺类5‑20份，毛冬青总皂苷30‑50份，蟾毒灵0.05‑0.5份，麝香酮0.01‑0.5份、人参总皂苷10‑20份、胆酸1‑5份、芦丁30‑40份。本发明提供的拆方组合物具有良好的防治血管性痴呆的作用，该组合物可以是由各组分单体混合制备得到，也可以是对中药提取单体组分得到的，各组分在治疗血管性痴呆方面具有较好的协同作用。
Description
技术领域
本发明属于神经系统疾病治疗领域，具体涉及一种用于防治血管性痴呆的药物组合物。
背景技术
血管性痴呆(Vascular Dementia,VD)是由缺血性、出血性及急慢性缺血缺氧性脑血管性疾病引起的脑功能损伤后产生的，以高级神经认知功能障碍为主的临床综合征，发病机制复杂且诱因较多。除常见的卒中，炎症、感染及氧化损伤等亦可增加血管性痴呆的风险。研究表明，炎症反应参与了VD的发生，在脑血管疾病及随后继发的神经损伤中起重要作用，VD 的发病机制复杂且诱因较多，目前临床治疗药物虽能不同程度地改善症状，但并未取得重大突破。
血栓心脉宁是由丹参、川芎、麝香等十味中药加工制成的中成药，具有芳香开窍、益气活血、散瘀止痛的功效，临床上主要用于冠心病、心绞痛等疾病的治疗。其药味多成分复杂，给药物作用物质基础研究带来了诸多不利，且在血管性痴呆方面的药效还有待进一步提高。拆方研究，精确简化组分配伍，对药效作用机理的阐述具有重要的意义，且如何拆方，达到更高的药效，是复杂处方亟待解决的课题。
发明内容
为克服现有技术的不足，本发明提供一种用于防治血管性痴呆的药物组合物。
本发明的目的是通过以下技术方案予以实现的：
一种用于防治血管性痴呆的组合物，所述组合物由如下重量份数的组分组成：丹参总酚酸80-110份，洋川芎内酯类0.2-5份，水蛭胺类5-20份，毛冬青总皂苷30-50份，蟾毒灵0.05-0.5份，麝香酮0.01-0.5份、人参总皂苷10-20份、胆酸1-5份和芦丁30-40份。
优选地，所述丹参总酚酸包括质量比为5-10:20-40:1-5的丹参素、丹酚酸B和迷迭香酸。
优选地，所述洋川芎内酯类选自洋川芎内酯A。
优选地，所述水蛭胺类包括质量比为1-5:1-5的水蛭胺C和水蛭胺A。
优选地，所述毛冬青总皂苷包括质量比为10-15:1的异绿原酸A和毛冬青皂苷B2。
优选地，所述人参总皂苷选自人参皂苷Rb、人参皂苷Rg3、人参皂苷Re中的一种或几种。
优选地，所述人参总皂苷选自人参皂苷Re。
上述组合物的制备方法，包括如下步骤：将丹参总酚酸，洋川芎内酯类，水蛭胺类，毛冬青总皂苷，蟾毒灵，麝香酮、人参皂苷、胆酸和芦丁直接混合或用溶剂分散后即得。
本发明的再一目的是提供上述的组合物在制备防治血管性痴呆方面的产品中的应用。
本发明的有益效果：
（1）本发明提供的拆方组合物具有良好的防治血管性痴呆的作用，该组合物可以是由各组分单体混合制备得到，也可以是对中药提取单体组分得到的，各组分在治疗血管性痴呆方面具有较好的协同作用。
（2）本发明提供的组合物中，异绿原酸A和毛冬青皂苷B2具有较好的协同增效作用，能有效活血开窍、祛风止痛，能有效提高机体血清AchE、5-HT的水平，降低脑组织中TNF-α、IL-1β的水平。
（3）本发明研究特定组成的丹参总酚酸、洋川芎内酯A、水蛭胺类、特定组成的毛冬青总皂苷、蟾毒灵、麝香酮和人参皂苷Re成分，对Ach E、5-HT、TNF-α、IL-1β的影响，清楚而透彻的研究了较好治疗血管性痴呆的活性成分组合物及其机理，弥补了中药组分复杂、药效不明确的缺陷。
具体实施方式
下面结合实施例对本发明技术方案作进一步说明。
实施例1
本实施例用于防治血管性痴呆的药物组合物，按重量份数计，所述组合物由如下组分组成，具体见表1。
制备方法为将上述表格中的各组分按照相应的重量份数混合，即得用于防治血管性痴呆的组合物。
实施例2
本实施例用于防治血管性痴呆的药物组合物，按重量份数计，所述组合物由如下组分组成，具体见表2。
制备方法为将上述表格中的各组分按照相应的重量份数混合，得用于防治血管性痴呆的组合物。
实施例3
本实施例用于防治血管性痴呆的药物组合物，按重量份数计，所述组合物由如下组分组成，具体见表3。
制备方法为将上述表格中的各组分按照相应的重量份数混合，即得用于防治血管性痴呆的组合物。
实施例4
本实施例用于防治血管性痴呆的药物组合物，按重量份数计，所述组合物由如下组分组成，具体见表4。
制备方法为将上述表格中的各组分按照相应的重量份数混合，即得用于防治血管性痴呆的组合物。
对比例1
组合物各单体如下表5。
制备方法为将上述表格中的各组分按照相应的重量份数混合，即得。
对比例2
组合物各单体如下表6。
制备方法为将上述表格中的各组分按照相应的重量份数混合，即得。
对比例3
组合物各单体如下表7。
制备方法为将上述表格中的各组分按照相应的重量份数混合，即得。
试验例1 本发明组合物防治血管性痴呆的药效试验
一、材料和方法
实验材料1.1 实验动物
成年SD大鼠120只，雄性，SPF级，体重220 ± 20 g。购自长春市亿斯实验动物技术有限责任公司，动物生产合格证号：SCXK（吉）-2020-0002。
适应性饲养7天后进入实验期。
1.2 实验药物
受试药物：
血栓心脉宁片，由吉林华康药业股份有限公司提供，批准文号：国药准字Z20030145，批号221003。
对比例1-3、实施例1-4的药物按上述相应的对比例和实施例制备，由吉林华康药业股份有限公司提供。
空白对照：蒸馏水，自制。
1.3 实验试剂
5-HT酶联免疫检测试剂盒、Ach E检测试剂盒、TNF-α检测试剂盒、IL-1β ELISA检测试剂盒均购于上海酶联生物科技有限公司。
2.方法
2.1动物分组
适应性喂养7天后，将120只SPF级成年雄性SD大鼠随机分为12组，每组10只。分别为空白对照组、模型对照组、血栓心脉宁组、对比例1-3组、实施例1高剂量组、实施例1中剂量组、实施例1低剂量组、实施例2-4组。
2.2给药剂量
灌胃给药，1次/d/只，其中，血栓心脉宁组1000mg/kg，实施例1-高剂量组给药80mg/kg，实施例1-中剂量组给药40mg/kg，实施例1-低剂量组给药20mg/kg，其余实施例2-4组和对比例1-3各组给药量与实施例1-中剂量组一致，空白对照组、模型对照组灌胃给予等量蒸馏水。
2.3造模方法
采用“永久性双侧颈总动脉闭塞”来建立血管性痴呆大鼠模型，除空白对照组外，其余各组大鼠使用戊巴比妥钠经腹腔注射麻醉后仰卧位，剃除颈部毛发并进行皮肤消毒。从颈部正中处进行切口，钝性分离双侧颈总动脉(CCA)后用手术缝合线将其永久性结扎。缝合切口后再行局部消毒，小心放回笼内（每笼一只待其完全清醒）。空白对照组大鼠不剥离、不阻断CCA，其余方法相同。手术后的大鼠均放回原笼继续饲养。建模手术结束后第7天，进行灌胃给药，所有实验组连续灌胃28天。
2.4 Morris水迷宫测试
将各组大鼠在正式训练前一天分别放入水中自由游泳2min，使其熟悉水迷宫环境，然后再对各组大鼠正式进行Morris水迷宫测试。定位航行实验历时4天，在实验周期内每日固定时间段训练4次，然后在计算的时候取4次实验的平均值作为大鼠在当日内的潜伏期。训练开始时，将平台置于某一象限，4次训练即将大鼠分别从四个不同的象限放入水中，然后采集这只大鼠在2min内找到并爬上平台所用的时间，即为逃避潜伏期。在站台上稳定10s算找到站台，否则继续记录，如果大鼠在2min内未找到平台，需将其牵引到平台，并停留60s，这时潜伏期记为2min。
2.5大鼠血清Ach E、5-HT活性测定，大鼠脑组织TNF-α、IL-1β含量测定
水迷宫实验后，快速处死大鼠，分别取血清、完整脑组织。大脑组织在冰浴条件下采用机械组织匀浆器制备10%匀浆，按测试指标的要求分装后于-20℃冰箱保存。测定时按照试剂盒说明书要求分别测定血清中Ach E、5-HT以及脑组织中TNF-α、IL-1β 含量。
3.统计学分析
实验数据采用SPSS22.0软件进行统计分析，计量资料以平均值±标准差(Mean ±SD)表示，组间差异采用单因素方差分析，p<0.05为显著性差异。
二、结果
对大鼠上台潜伏期比较的影响结果如下表8所示。
对大鼠血清Ach E、5-HT的影响结果如下表9所示。
对大鼠脑组织TNF-α、IL-1β 的影响结果见表10所示。
结果表明，组合物高、中剂量组，相比于阳性药血栓心脉宁，对血管痴呆性大鼠模型具有明显的提高机体血清Ach E、5-HT的作用，组合物低中高剂量组相比于阳性药血栓心脉宁，能明显降低大鼠水迷宫上台潜伏期，降低大鼠脑组织TNF-α的水平，具有良好的治疗血管性痴呆的作用。
上述详细说明是针对本发明其中之一可行实施例的具体说明，该实施例并非用以限制本发明的专利范围，凡未脱离本发明所为的等效实施或变更，均应包含于本发明技术方案的范围内。
Claims (8)
1.一种用于防治血管性痴呆的药物组合物，其特征在于，所述组合物由如下重量份数的组分组成：丹参总酚酸80-110份，洋川芎内酯类0.2-5份，水蛭胺类5-20份，毛冬青总皂苷30-50份，蟾毒灵0.05-0.5份，麝香酮0.01-0.5份、人参总皂苷10-20份、胆酸1-5份和芦丁30-40份。
2.根据权利要求1所述的组合物，其特征在于，所述丹参总酚酸包括质量比为5-10:20-40:1-5的丹参素、丹酚酸B和迷迭香酸。
3.根据权利要求1所述的组合物，其特征在于，所述洋川芎内酯类选自洋川芎内酯A。
4.根据权利要求1所述的组合物，其特征在于，所述水蛭胺类包括质量比为1-5:1-5的水蛭胺C和水蛭胺A。
5.根据权利要求1所述的组合物，其特征在于，所述毛冬青总皂苷包括质量比为10-15:1的异绿原酸A和毛冬青皂苷B2。
6.根据权利要求1所述的组合物，其特征在于，所述人参总皂苷选自人参皂苷Rb、人参皂苷Rg3、人参皂苷Re中的一种或几种。
7.根据权利要求1所述的组合物，其特征在于，所述人参总皂苷选自人参皂苷Re。
8.一种权利要求1-7任一项所述的组合物在制备防治血管性痴呆药物中的应用。
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| CN102507842A (zh) * | 2011-11-13 | 2012-06-20 | 吉林华康药业股份有限公司 | 一种血栓心脉宁片的检测方法 |
| CN103006768A (zh) * | 2012-12-21 | 2013-04-03 | 吉林华康药业股份有限公司 | 血栓心脉宁在制备治疗血管性痴呆的药物中的应用 |
| CN110201118A (zh) * | 2019-06-10 | 2019-09-06 | 吉林修正药业新药开发有限公司 | 一种中药组合物在制备治疗或预防血管性老年痴呆药物中的应用 |
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| CN102507842A (zh) * | 2011-11-13 | 2012-06-20 | 吉林华康药业股份有限公司 | 一种血栓心脉宁片的检测方法 |
| CN103006768A (zh) * | 2012-12-21 | 2013-04-03 | 吉林华康药业股份有限公司 | 血栓心脉宁在制备治疗血管性痴呆的药物中的应用 |
| CN110201118A (zh) * | 2019-06-10 | 2019-09-06 | 吉林修正药业新药开发有限公司 | 一种中药组合物在制备治疗或预防血管性老年痴呆药物中的应用 |
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