CN117599151B - 益心舒片联合活性肽预防和/或治疗慢性心力衰竭的用途 - Google Patents
益心舒片联合活性肽预防和/或治疗慢性心力衰竭的用途 Download PDFInfo
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Abstract
本发明的目的在于提供一种益心舒片联合活性肽预防和/或治疗慢性心力衰竭的用途，尤其是用于预防和/或治压力负荷诱导的心肌肥厚和心力衰竭，如肾性高血压诱导的慢性心力衰竭，大幅度降低了死亡率，在可接受范围内降低血压，可以有效改善心脏功能，减缓心脏重塑进程，减慢进入心力衰竭阶段的速度。
Description
技术领域
本发明涉及医药生物领域，具体涉及益心舒片联合活性肽预防和/或治疗慢性心力衰竭的用途。
背景技术
益心舒丸(微丸)出于金元时代李杲(字明之，晚号东垣老人)所著的《内外伤辨惑论》(生脉饮同出于此论)。由人参、麦冬、五味子组成。
方中人参补脾益气以生津为主，辅以麦冬养阴清热以生津，五味子敛肺止汗而生津，共成益气养阴，生津止渴，固表止汗之功，为治热伤气阴的常用方剂。在此基础上加入了丹参，黄芪，川芎及山楂四味药，方中人参大补元气以生津，丹参活血化瘀以复脉，共为本方主药，为君；黄芪益气补虚，麦冬养阴生津，川芎活血行气，辅助两君药益气活血，共为臣药，五味子补益心气，山楂降脂活血，共为佐药。诸药合方，共建益气复脉，活血化瘀，养阴生津之功效。用于气阴两虚，心悸脉结代，胸闷不舒、胸痛及冠心病、心绞痛见有上述症状者。
益心舒的作用已经被临床验证，但是也存在药效显著性等方面的问题。因此，临床中开始进行联合用药，有文献报道了心绞痛、早搏、动脉硬化方面的联合用药，也有慢性心力衰竭方面的报道(参考吕杰等，益心舒片联合曲美他嗪治疗对慢性心力衰竭心功能参数及Adropin蛋白水平的影响，中国临床保健杂志，第06期，第70-73页，2019；朱改针等，伊伐布雷定联合益心舒片对稳定型心绞痛患者血管内皮细胞功能的影响，中西医结合研究，第04期，第10-12页，2020；张昊洲，益心舒片联合尼可地尔治疗冠心病心绞痛患者的临床疗效，中国药物与临床，第05期，第96-98页，2020；孙政，益心舒片联合炙甘草汤与西药治疗频发性室性早搏临床研究，新中医，第15期，第87-90页，2020.08.05；薛仁洪，美益康益心舒片治疗稳定性心绞痛的临床疗效及对动脉硬化程度的影响，中国处方药，第02期，第68-69页，2020)。
具有活性的多肽称为活性肽，又称生物活性肽或生物活性多肽。活性肽在人的生长发育，新陈代谢，疾病以及衰老，死亡的过程中起着关键作用。活性肽是人体中最重要的活性物质。正是因为它在体内分泌量的增多或减少，才使人类有了幼年，童年，成年，老年直到死亡的周期。而注射活性肽便打破了生命的这一周期，从而达到延长生命，有效减缓衰老的神奇效果。因此，活性肽变成科学家炙手可热的研究对象。通过生物信息学结合计算机模拟，考虑了脑钠肽，肌钙蛋白，肌红蛋白等常见的蛋白，也考虑了WWP1、NAT10、Apo O等新发现的相关基因，得到了得分最高的活性肽MFGHVQAAMF。
因此，本发明提出了将益心舒片联合活性肽预防和/或治疗慢性心力衰竭的用途。尤其是用于预防和/或治压力负荷诱导的心肌肥厚和心力衰竭，如肾性高血压诱导的慢性心力衰竭，大幅度降低了死亡率，在可接受范围内降低血压，可以有效改善心脏功能，减缓心脏重塑进程，减慢进入心力衰竭阶段的速度。
发明内容
本发明提供一种益心舒片联合活性肽在制备用于预防和/或治疗慢性心力衰竭的药物中的用途，所述益心舒片含有人参、麦冬、五味子、黄芪、丹参、川芎、山楂以及药用辅料，所述活性肽的氨基酸序列为MFGHVQAAMF。
其中慢性心力衰竭是肾脏疾病导致的肾性高血压诱导的；
其中预防和/或治疗慢性心力衰竭包括降低死亡率；
其中预防和/或治疗慢性心力衰竭包括降低肾性高血压的血压；
其中预防和/或治疗慢性心力衰竭包括改善心脏功能；
其中预防和/或治疗慢性心力衰竭包括减缓心脏重塑进程；
其中预防和/或治疗慢性心力衰竭包括减慢进入心力衰竭阶段的速度；
其中预防和/或治疗慢性心力衰竭包括改善心肌肥厚；
其中预防和/或治疗慢性心力衰竭包括改善慢性心力衰竭相关的呼吸症状；
其中预防和/或治疗慢性心力衰竭包括心脏收缩舒张功能。
本发明的有益效果是：本发明提出了将益心舒片联合活性肽预防和/或治疗慢性心力衰竭的用途。尤其是用于预防和/或治压力负荷诱导的心肌肥厚和心力衰竭，如肾性高血压诱导的慢性心力衰竭，大幅度降低了死亡率，在可接受范围内降低血压，可以有效改善心脏功能，减缓心脏重塑进程，减慢进入心力衰竭阶段的速度。
具体实施方式
下面结合实施例对本发明的实施方式作更进一步的说明。
实施例1：动物实验
取发育整齐、生长性能一致、体重为150-200g左右的血压正常的SD大鼠90只，使其自由摄食及饮水。适应性喂养一周后，根据血压对大鼠进行随机分组，分为空白(30只，其中15只进行假手术，由于假手术不影响大鼠功能，后续结果都计入空白组)和需要做手术的组(60只)，做两肾一夹手术，术后2周将其分为模型对照组(15只)，50mg/kg益心舒片(15只)，50mg/kg活性肽(15只)，25mg/kg益心舒片联合25mg/kg活性肽(15只)，灌胃给药或者给水一天一次，术前8小时禁食不禁水。培养第20周处死压力负荷诱导的心肌肥厚及心力衰竭模型大鼠。
血压及心率测试结果：第2/6/12/16周，采用智能无创血压计检测监测大鼠麻醉状态下右前肢血压变化，得到心率(Heart rate HR，单位次/分)，收缩压(SBP，单位mmHg)，舒张压(DBP，单位mmHg)，各组心率变化无规律。结果见表1和2，取整数。
表1SBP测量结果
表2DBP测量结果
结果显示，活性肽在可接受范围内降低血压，无过山车式波动，尤其是益心舒片联合活性肽显示协同降压作用，且作用效果优于单独使用。
收缩舒张功能：第14周采用彩色多普勒超声实时心脏影像测定EF和FS，并观察心脏形态，结果见表3，取整数。
表3EF和FS测量结果
结果显示，益心舒片和活性肽可以有效改善心脏功能，尤其是益心舒片联合活性肽显示协同改善心脏收缩舒张功能作用，且作用效果优于单独使用。
血流动力学测试结果：第20周采用生物机能实验系统测定，测完处死，心率(Heartrate HR，单位次/分)，收缩压(SBP，单位mmHg)，舒张压(DBP，单位mmHg)，左室发展压LVDP＝LVSP-LVEDP，单位mmHg、左室压力变化最大上升速率(+dP/dtmax)、左室压力变化最大下降速率(-dP/dtmax)，结果取整数，见表4。各组心率变化无规律。
表4血流动力学测试结果
结果显示，益心舒片和活性肽可以有效改善心脏功能，减缓心脏重塑进程，减慢进入心力衰竭阶段的速度，尤其是益心舒片联合活性肽显示协同改善心脏收缩舒张功能作用，且作用效果优于单独使用。
BNP的含量：采用试剂盒测定各组实验动物心脏中血清BNP的含量，结果取整数，见表6。
表6血清BNP的含量
| BNP(ng/ml) | |
| 空白组 | 17±1 |
| 模型对照组 | 38±4 |
| 益心舒片 | 26±3 |
| 活性肽 | 23±2 |
| 益心舒片联合活性肽 | 20±2 |
死亡率：记录整个过程中各组动物死亡情况，结果见表7。
表7各组动物死亡情况
结果显示，益心舒片和活性肽可以有效降低了死亡率，尤其是益心舒片联合活性肽显示协同大幅度降低了死亡率，这对心衰患者至关重要。
以上实施例仅用以说明本发明的技术方案，而非对其限制；尽管参照前述实施例对本发明进行了详细的说明，本领域的普通技术人员应当理解：其依然可以对前述各实施例所记载的技术方案进行修改，或者对其中部分技术特征进行等同替换；而这些修改或者替换，并不使相应技术方案的本质脱离本发明各实施例技术方案的精神和范围。
Claims (5)
1.益心舒片联合活性肽在制备用于预防和/或治疗慢性心力衰竭的药物中的用途，所述益心舒片含有人参、麦冬、五味子、黄芪、丹参、川芎、山楂以及药用辅料，所述活性肽的氨基酸序列为MFGHVQAAMF，其中慢性心力衰竭是肾脏疾病导致的肾性高血压诱导的。
2.根据权利要求1所述益心舒片联合活性肽在制备用于预防和/或治疗慢性心力衰竭的药物中的用途，其中预防和/或治疗慢性心力衰竭包括降低死亡率。
3.根据权利要求1所述益心舒片联合活性肽在制备用于预防和/或治疗慢性心力衰竭的药物中的用途，其中预防和/或治疗慢性心力衰竭包括降低肾性高血压的血压。
4.根据权利要求1所述益心舒片联合活性肽在制备用于预防和/或治疗慢性心力衰竭的药物中的用途，其中预防和/或治疗慢性心力衰竭包括改善心肌肥厚。
5.根据权利要求1所述益心舒片联合活性肽在制备用于预防和/或治疗慢性心力衰竭的药物中的用途，其中预防和/或治疗慢性心力衰竭包括心脏收缩舒张功能。
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