CN114712454A - 药物组合物在制备用于治疗心血管疾病的药物中的应用 - Google Patents
药物组合物在制备用于治疗心血管疾病的药物中的应用 Download PDFInfo
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Abstract
本发明公开了药物组合物在制备用于治疗心血管疾病的药物中的应用,涉及生物医药技术领域,按重量份数计,所述药物组合物的主料包括110~150份黄连、160~190份乌梅、110~150份麦冬、110~150份地黄、1~20份阿胶、110~150份黄芪、110~150份山药、110~150份玄参以及110~150份苍术,本发明发现采用上述主料制备获得的药物组合物能够用于治疗或改善心血管疾病,有效降低心肌组织炎症因子的水平,为心血管疾病的治疗和研究提供了一种新的途径。
Description
技术领域
本发明涉及生物医药技术领域,具体而言,涉及药物组合物在制备用于治疗心血管疾病的药物中的应用。
背景技术
心血管疾病(Cardiovascular diseases,CVD)是威胁人类健康、影响生活质量和造成社会经济损失的全球性公共卫生问题,仅在2015年,心血管疾病引起的死亡率占全世界全因死亡率的33.33%,其终生风险超过60%。
心血管疾病是具有不同病理生理机制的复杂实体,氧化应激、炎症、自噬、线粒体损伤等被视为潜在的常见病理机制。虽然药物管理起到一定的治疗和控制作用,其预后仍然不佳且发病率居高不下,亟需安全、有效的新药开发,以减轻CVD的负担,缓解CVD对医学提出的严峻挑战。
鉴于此,特提出本发明。
发明内容
本发明的目的在于提供药物组合物在制备用于治疗心血管疾病的药物中的应用。
本发明是这样实现的:
本发明实施例提供了一种药物组合物在制备用于治疗或改善心血管疾病中的应用,按重量份数计,所述药物组合物的主料包括以下组分:110~150份黄连、160~190份乌梅、110~150份麦冬、110~150份地黄、1~20份阿胶、110~150份黄芪、110~150份山药、110~150份玄参以及110~150份苍术。
本发明具有以下有益效果:
本申请发明人发现,按重量份数计,主料包括110~150份黄连、160~190份乌梅、110~150份麦冬、110~150份地黄、1~20份阿胶、110~150份黄芪、110~150份山药、110~150份玄参以及110~150份苍术的药物组合物能够用于治疗或改善心血管疾病,其能够有效降低心肌组织炎症因子的水平,为心血管疾病的治疗和研究提供了一种新的途径。
附图说明
为了更清楚地说明本发明实施例的技术方案,下面将对实施例中所需要使用的附图作简单地介绍,应当理解,以下附图仅示出了本发明的某些实施例,因此不应被看作是对范围的限定,对于本领域普通技术人员来讲,在不付出创造性劳动的前提下,还可以根据这些附图获得其他相关的附图。
图1为实施例1中连梅颗粒的制备流程图;
图2为实施例1中连梅颗粒中药-化学成分网络图;
图3为实施例1中连梅颗粒靶向心血管疾病的核心子网络;
图4为实施例1中连梅颗粒药物-成分-靶点-疾病拓扑结构分析网络图;
图5为实施例1中香草素与MIF蛋白分子对接示意图;
图6为实施例1中槲皮素与MIF蛋白分子对接示意图;
图7为实施例1中香草素、槲皮素与TLR9蛋白分子对接示意图;
图8为实施例1中连梅颗粒核心网络靶点基因本体GO富集分析条形图;
图9为实施例1中连梅颗粒核心网络靶点Kegg通路富集气泡图。
具体实施方式
为使本发明实施例的目的、技术方案和优点更加清楚,下面将对本发明实施例中的技术方案进行清楚、完整地描述。实施例中未注明具体条件者,按照常规条件或制造商建议的条件进行。所用试剂或仪器未注明生产厂商者,均为可以通过市售购买获得的常规产品。
首先,本发明实施例提供了一种药物组合物在制备用于治疗或改善心血管疾病中的应用,按重量份数计,所述药物组合物的主料包括以下组分:110~150份黄连、160~190份乌梅、110~150份麦冬、110~150份地黄、1~20份阿胶、110~150份黄芪、110~150份山药、110~150份玄参以及110~150份苍术。
连梅颗粒由黄连、黄芪、乌梅、山药、麦冬、玄参、生地、苍术、阿胶9味中药组成,以乌梅和黄连为君药,臣药为黄芪和苍术,麦冬、生地和阿胶为佐药,山药和玄参为使药,补气引经。研究表明,连梅颗粒对CVD(心血管疾病)具有一定的治疗作用,可通过抗氧化起到抗动脉粥样硬化的作用,还可以降低心肌组织炎症因子水平。
连梅颗粒的药物组成中,黄连的主要成分黄连碱在体外和体内均对CVD具有改善作用,可抑制H9c2心肌细胞自噬、凋亡,改善心梗模型大鼠心肌氧化水平和线粒体呼吸功能障碍;黄连具有抗动脉粥样硬化、降脂、降血糖和缓解肝脂肪变性作用,作为心血管保护剂具有巨大的潜力。
黄芪的活性成分黄芪甲苷可通过AMPK信号通路,PI3K/Akt/mTOR信号通路等发挥抗氧化,抗炎,抗凋亡、增强免疫力作用,还可改善高血压患者的心脏结构,左心室收缩功能和左心室舒张功能,表现出强大的心血管保护作用。
乌梅中的齐墩果酸、5-羟甲基糠醛、熊果酸等成分、山药皂苷元、总甾体皂苷、麦冬多糖、玄参环烯醚萜从苷以及生地黄甲醇提取物等均具有抗炎、抗氧化、降血脂和血糖、强心、抗心律失常、抗高血压和抗心肌缺血再灌注损伤等多种药理作用。
本发明在“君-臣-佐-使”的基础上,通过网络拓扑结构分析发现,连梅颗粒的10种重要的活性成分主要来自于黄连、黄芪、玄参、苍术、生地、山药、乌梅,其中,5种来源于黄连、7种来源于黄芪,4种来自于苍术和乌梅,该四味药均为连梅颗粒的君药和臣药,其靶点集占连梅颗粒核心靶点集83.33%(80/96)的靶点,而乌梅、黄连、黄芪、苍术为主要成分药物,连梅颗粒发挥药效主要是以君药和臣药协同,与中医理论相符。
连梅颗粒的重要活性成分包括黄酮类(槲皮素和鼠李糖苷)、酚酸类(香草酸)、酚类(丁香酚)、内酯类(对香豆酸)以及苯丙酸类(阿魏酸)等。黄酮类化合物,尤其是对心脏有益,具有扩张冠状血管、改善心肌供血量、降低血脂等方面的作用,具有重要的药用价值。
槲皮素可通过抑制LDL氧化,舒张血管,减少粘附分子和降低炎症因子水平,保护内皮功能,预防氧化和炎性损伤以及防止血小板的凝集。槲皮素被称为II型结合位点配体,巨噬细胞移动抑制因子(MIF)的酶活性对低浓度的槲皮素具有相对较高的敏感性,使得槲皮素成为该细胞因子的作用位点。MIF的缺乏可抑制Th1衍生细胞因子的TNF-α和IFN-γ的上调,并增加了作为Th2衍生细胞因子的IL-4的水平,而在MIF缺乏的小鼠中,槲皮素反而抑制HSP40和70表达的上调并加重炎症的进展。
鼠李糖苷属于黄酮苷,研究发现其可抑制氧化氢诱导的氧化损伤和凋亡,还进一步抑制脂质过氧化和apoA-I聚集来抑制HDL氧化和糖基化,对动脉粥样硬化的保护作用。除此之外,鼠李糖苷等提取混合物可减少DNA片段化,通过调控MAPK途径抑制炎症因子iNOS,MMP-9,COX-2,TNF-α等的表达,抑制TLR4介导的NF-κB活化减轻炎症进展过程。
体内和体外实验均证明,香草酸、丁香酚、对香豆酸、阿魏酸等均可发货保护缺氧/复氧细胞模型氧化损伤和线粒体功能损伤、炎症、抗血栓形成、抑制心室重塑过程和调节免疫力的作用。
经一系列创造性的研究,本发明人发现按照上述组分以及配比制备获得的药物组合物能够有效的改善或治疗心血管疾病,可明显降低心肌组织炎症因子水平、抑制巨噬细胞泡沫化,为心血管疾病的治疗和研究提供了一种新的途径和方向。
具体地,药物组合物中,黄连的重量份可以为:110、115、120、125、130、135、140、145和150份种的任意份数;乌梅的重量份可以为:160、165、170、175、180、185和190份种的任意份数;麦冬的重量份可以为:110、115、120、125、130、135、140、145和150份种的任意份数;地黄的重量份可以为:110、115、120、125、130、135、140、145和150份种的任意份数;阿胶的重量份可以为:1、2、4、6、8、10、12、14、16、18和20中的任意份数;黄芪的重量份可以为:110、115、120、125、130、135、140、145和150份种的任意份数;山药的重量份可以为:110、115、120、125、130、135、140、145和150份种的任意份数;玄参的重量份可以为:110、115、120、125、130、135、140、145和150份种的任意份数;苍术的重量份可以为:110、115、120、125、130、135、140、145和150份种的任意份数。
优选地,所述心血管疾病选自:高血压、心力衰竭、心肌梗塞、心肌再灌注损伤、脑缺血、冠状动脉疾病和房颤中的至少一种。
优选地,按重量份数计,所述药物组合物的主料包括以下组分:120~150份黄连、160~190份乌梅、120~150份麦冬、120~150份地黄、1~20份阿胶、120~150份黄芪、120~150份山药、120~150份玄参以及120~150份苍术。在上述范围内,制备获得的药物组合物能更有效地发挥其治疗心血管疾病地药效。
优选地,所述药物组合物还包括辅料;所述辅料的组分选自糊精和乳糖中的至少一种。
优选地,按上述重量份数计,所述药物组合物中,每1份主料,对应包括1~3份糊精以及1~3份乳糖。
具体地,每一份主料可对应1份、2份或3份糊精和乳糖,优选为2份。
优选地,当所述药物组合物包括辅料且所述辅料包括糊精和乳糖时,所述药物组合物的制备方法如下:将除阿胶以外的主料按照上述重量份数进行混合,获得混合物;
将所述混合物煎煮和减压压缩,获得浸膏;
将所述浸膏压缩干燥和粉碎,获得干膏粉;
将所述干膏粉与阿胶、糊精以及乳糖混合后,造粒干燥,获得最终产物。
在一些实施例中,不对煎煮的次数和具体操作进行限定,只要采用上述原料进行制备并将其用于制备治疗心血管疾病的药物中即属于本申请的保护范围内。
优选地,按照以下方式制备获得药物,疗效更好。具体地,所述煎煮的具体步骤如下:
将所述混合物与8~10倍重量的水混合,煎煮0.5~1.5小时,获得第一滤液和第一滤渣;
将第一滤渣与8~10倍重量的水混合,煎煮0.5~1.5小时,获得第二滤液和第二滤渣;
将第二滤渣与8~10倍重量的水混合,煎煮0.5~1.5小时,获得第三滤液和第三滤渣;
每次煎煮的时间均可以为0.5小时、0.7小时、0.9小时、1小时、1.3小时和1.5小时中的任意时间;每次煎煮时,添加水的重量可以为混合物或滤渣的8倍、9倍或10倍。
将所述第一滤液、第二滤液和第三滤液合并后减压浓缩,获得所述浸膏。
优选地,所述减压浓缩的条件为70~90℃。在一些实施例中,减压浓缩的时间可以为70℃、75℃、80℃、85℃、90℃中的任意温度。
优选地,将所述阿胶与所述干膏粉混合前,所述制备方法包括将阿胶与糊精按1:(0.5~3)的质量比混合后粉碎,获得阿胶粉用于后续与所述干膏粉混合。
优选地,所述干膏粉、阿胶、糊精以及乳糖的混合比为:(0.8~1.2):(0.8~1.2):(1.8~2.2):(1.8~2.2),优选为1:1:2:2。
优选地,所述药物的类型可选自:液体剂型、固体剂型、半固体剂型和气体剂型中的至少一种。
其中,液体剂型的药物可以为溶液剂或注射剂等,固体剂型的药物可为颗粒、片剂或胶囊;半固体剂型可为软膏或凝胶等,气体剂型可以为气雾剂或喷雾剂。
以下结合实施例对本发明的特征和性能作进一步的详细描述。
实施例1
本发明提供了一种连梅颗粒(药物组合物),其包括以下主料:黄连133.3g、乌梅177.8g、麦冬133.3g、地黄133.3g、阿胶11.1g、黄芪133.3g、山药133.3g、玄参133.3g以及苍术133.3g;共计1122g,制成1000g。
请参照图1,上述连梅颗粒的制备过程具体如下:
将除阿胶外的八味药材混合后加10倍重量的水,煎煮1小时,获得第一滤液和第一滤渣;将第一滤渣与10倍重量的水混合,煎煮1小时,获得第二滤液和第二滤渣;将第二滤渣与10倍重量的水混合,煎煮1小时,获得第三滤液和第三滤渣;合并第一滤液、第二滤液以及第三滤液过滤后,于80℃下减压浓缩成相对密度为1.25~1.30的稠膏(60℃测);将获得的稠膏于80℃下减压干燥,粉碎成细粉,作为干膏粉,备用;
将阿胶与1倍量的糊精混合后粉碎成细粉,作为阿胶粉,备用;
将上述获得的干膏粉、阿胶粉、糊精以及乳糖混合(混合比为1:1:2:2),加90%乙醇湿法制粒,并于60℃下干燥,制成颗粒1000g,分装,记得。1、连梅颗粒的成分收集与筛选。
连梅颗粒由黄连、黄芪、乌梅、山药、麦冬、玄参、生地、苍术、阿胶9味中药组成,通过中药系统药理数据库(TCMSP、ymMap、ETCM数据库以及TCM@taiwan数据库)搜集整理连梅颗粒中的主要化合物成分,利用Pubchem数据库核对成分结构并进行化学名称的规范,并获取候选化合物的Canonical SMILES号。再通过SwissADME平台预测候选化合物的口服生物利用度和类药性,最后,5种类药性预测(Lipinski、Ghose、Veber、Egan、Muegge)结果中有2个及2个以上为“Yes”,即可最终筛选为活性化合物。由于这种筛选剔除了一些不符合条件的但却有广泛药理学作用的化合物,如黄芪甲苷以及哈巴苷等,为了提高预测结果可信度,进一步通过相关文献/收集连梅颗粒入血成分,建立连梅颗粒活性化合物数据集。
从连梅颗粒中搜集到了669个满足条件的成分。由图2网络图所示,连梅颗粒成分中单味中药可对应3个以上的化学成分,而不同的单位中药也包含相同的化学成分,连梅颗粒中,化学活性成分Sitogluside、Vanillic Acid、Arginine、Campesterol和Uridine等至少对应3个或以上中药(如表1所示)。
表1连梅颗粒药物-成分靶点对应表
2、连梅颗粒靶点预测
基于DrugBank,Pubchem数据库,检索连梅颗粒活性化合物的对应靶点,经DrugBank,Pubchem未找到对应靶标的化合物,通过TargetNet平台,利用活性成分的Canonical SMILES号,预测成分的潜在靶点,设置参数AUC≥0.7,Fingerprint type:ECFP4fingerprint,收集Prob=1的靶点,同时利用UniProt数据库剔除非人源的靶点,最后形成连梅颗粒的潜在靶点群。
在以上步骤中搜集到连梅颗粒669个化学成分,通过SwissADME平台根据候选化合物的口服生物利用度和类药性筛选出具有化学活性成分380个,其中,黄连55个、黄芪72个、乌梅33个、山药66个、麦冬35个、玄参52个、生地46个、苍术48个、阿胶3个,并成功通过TargetNet平台成功预测其作用靶点6608个,其中,黄连919个、黄芪1417个、乌梅784个、山药990个、麦冬325个、玄参949个、生地552个、苍术622个、阿胶50个,通过Uniprot标准化人源后并除重总共得到连梅颗粒283个靶点。
3、心血管疾病靶点收集
应用TTD数据库、DisGeNET数据库、GeneCards以“Cardiovascular Disease”为检索词搜集CVD靶点。在疾病靶点的整合中,靶点的Score值越大,说明该靶点与疾病的关系越密切。故在DisGeNET数据库和GeneCards数据库中选取分数高于平均值的靶点,删除重复冗杂的基因,合并3个数据库所获得的数据作为CVD相关靶点。
CVD靶点一共收集到1795个,其中TTD数据库33个,DisGeNET数据库486个、GeneCards数据库1275个。在疾病靶点的整合中,删除重复冗杂的基因,合并3个数据库获得的1557个CVD相关靶点。
4、连梅颗粒靶向心血管疾病的核心子网络。
以高质量全基因组HINT数据库获得的人类疾病基因作为背景网络,利用Cytoscape3.7.0软件分别构建连梅颗粒成分预测靶点和心血管疾病靶点PPI网络,通过Merge插件,提取连梅颗粒PPI网络和心血管疾病PPI网络的交集,形成连梅颗粒靶向心血管疾病的核心子网络。
连梅颗粒靶向心血管疾病的核心子网络见图3和表2,提取连梅颗粒人类心血管疾病靶点96个。
表2连梅颗粒靶向心血管疾病的核心子网络部分靶点
5、连梅颗粒靶向心血管疾病病种的获取。
将筛选的96个连梅颗粒核心靶点通过CTD数据库,参数设置为精准预测,成功预测连梅颗粒具有潜在治疗作用的心血管疾病93种,去除重复后剩余93种为连梅颗粒具有治疗潜在性的心血管疾病,结果见表3。
表3连梅颗粒靶向心血管疾病部分病种
6、网络构建和分析
利用Cytoscape3.7.0软件,将连梅颗粒9味中药成分、380个化学活性成分、96个靶向人类心血管疾病靶点、93种潜在治疗作用的心血管疾病构建连梅颗粒的药物-成分-靶点-疾病网络,根据节点连接度(degree)、节点紧密度(closeness)和节点介度(betweenness)对核心子网络进行分析,筛选连梅颗粒的关键活性成分、关键靶点、以及主要的心血管疾病病种。结果图4所示,连梅颗粒的药物-成分-靶点-疾病网络584个节点,4327条边。根据Degree值调节其形状大小,Degree值越大,颜色越深、形状越大;经网络拓扑结构分析,连接度排在前9名的活性成分为Vanillic acid(香草酸)、Quercetin(槲皮素)、Ferulic acid(阿魏酸)、P-Coumaric Acid(对香豆酸)、Caffeate(咖啡因)、Acetic acid(醋酸)、Rhamnocitrin(鼠李糖苷)、Furfural(糠醛)以及Eugenol(丁香酚),它们是连梅颗粒中的重要活性成分。
香草酸和槲皮素的Degree值在所有重要活性成分中排名最高。连梅颗粒靶点网络和心血管疾病靶点网络Degree值排在前10的靶点为MIF、TLR9、MAOA、ABCG2、AHR、MAOB、RELA、FOLH1、ESR2、ESR1,靶点MIF和TLR9为网络中Degree值最高的靶点,连梅颗粒靶向心血管疾病靶点网络显示,网络Degree值排在前面的疾病为Hypertension(高血压)、Heartfailure(心力衰竭)、Myocardial Infarction(心肌梗塞)、Myocardial ReperfusionInjury(心肌再灌注损伤)、Atherosclerosis(动脉硬化)、Brain Ischemia(脑缺血)、Coronary Artery Diseases(冠状动脉疾病)、Atrial Fibrillation(房颤),其中,高血压、心力衰竭、心肌梗塞和心肌再灌注损伤Degree值排名较前,如表4所示。
表4连梅颗粒Degree值前10的成分、靶点和疾病种类
因此,初步预测,连梅颗粒活性成分香草酸和槲皮素可能通过MIF、TLR9靶蛋白起到治疗心血管疾病的作用,其治疗心血管疾病包括高血压、心力衰竭、心肌梗塞、心肌再灌注损伤等(图4)。
7、分子对接验证关键化合物与关键靶点的相互作用关系。
通过分子对接方法对分析甄选出的关键化合物和关键靶点的相互作用进行计算机预测和验证。从PDB数据库(https://www.rcsb.org/)和Pubchem数据库(https://pubchem.ncbi.nlm.nih.gov/)分别下载关键蛋白MIF(PDB ID:6B1K)、TLR9(Conformer3D_CID_54760476)蛋白的蛋白结构。通过软件PyMOL,在命令框中输入“remove solvent”,对蛋白进行去水处理,根据PDB有关该蛋白的说明,去除蛋白上携带的离子及小分子等。随后利用AutoDockTools1.5.6软件,通过“add hydrogen”对蛋白进行加氢、计算电荷等处理,保存为pdbqt格式。从Pubchem数据库中下载关键化合物香草酸(Pubchem CID:8468)、槲皮素(Pubchem CID:5280343)的化学结构,保存为*mol2格式。利用Chembio3D Ultra软件,点击“Calculations”,选择适合小分子化合物的MM2力场,对小分子化合物进行能量最小化处理。通过软件Autodock Vina 1.1.2进行分子与蛋白对接,选取结合能(Binding energy)数值最小的构象,通过PyMOL进行分析作图。
基于网络拓扑结构分析可知,香草酸和槲皮素和MIF、TLR9蛋白分别是拓扑结构分析网络的主要成分和靶点,如图5、图6、图7和表5,分子对接结果示,香草素通过1个氢键与MIF蛋白的残基ASN6形成相互作用关系,槲皮素通过5个氢键与MIF蛋白的残基ASN6、SER60形成相互作用关系,香草酸与MIF、槲皮素与MIF蛋白结合相对紧密,而TLR9与香草素、槲皮素的结合能分别为-3.9、-2.8,结合能水平较低。
表5连梅颗粒活性成分香草酸、槲皮素和MIF、TLR9蛋白对接结果
8、连梅颗粒核心网络靶点基因本体GO富集分析。
对连梅颗粒96个核心网络靶点进行基因本体GO和KEGG通路富集分析,选择P<0.05的生物过程、分子功能、细胞组分三个模块前15个富集Score绘制条形图(图8)。在生物学过程中(Biological process,BP),从RNA聚合酶II启动子转录的正调控、信号转导、DNA转录、RNA聚合酶II启动子的转录起始、蛋白水解、DNA转录的正调控,对药物的反应、积极调控细胞增殖、RNA聚合酶II启动子转录的负调控、类固醇激素介导的信号通路、凋亡过程的负调控、氧化还原过程、炎症反应、细胞对脂多糖的反应、细胞增殖的负调控;在细胞组成中(Cellular component,CC),主要涉及细胞表面、质膜、细胞外空间、细胞外泌体、细胞质的核周区域、核染色质、核质、顶质膜、质膜的组成部分、轴突、细胞外区域、血小板α颗粒管腔和受体复合体;在分子功能中(Molecular function,MF),主要涉及蛋白质结合、锌离子结合、蛋白质均二聚活性、DNA结合、受体结合、转录因子活性,序列特异性DNA结合、类固醇激素受体活性、酶结合、序列特异性DNA结合、ATP结合、药物结合、相同的蛋白质结合、RNA聚合酶II转录因子活性、丝氨酸型内肽酶活性、蛋白激酶结合等。
9、连梅颗粒核心网络靶点Kegg通路富集分析。
对连梅颗粒96个核心网络靶点进行Kegg通路富集分析,共获得74条通路,以P<0.05,基因数≥3为度,显著富集的通路有56条,与心血管相关的通路20条,见图9。结果显示,核心子网络的靶点涉及的疾病通路为心肌能量代谢通路。与心肌能量代谢通路信号有4条,分别为cAMP信号通路、钙信号通路、PPAR信号通路、病毒性心肌炎信号通路;与神经-免疫调节系统相关的通路有3条,分别是神经活性配体-受体相互作用、B细胞受体信号传导途径、T细胞受体信号传导途径;与信号转导的通路有3条,分别为HIF-1信号通路,PI3K/AKT信号通路,cGMP-PKG信号通路;与炎症信号通路有4条,分别为雌激素信号通路、TNF信号通路、花生四烯酸代谢通路、Toll样受体信号通路;与肾素-血管紧张素系统的通路有2条,分别为胰岛素抵抗、肾素-血管紧张素系统途径;与细胞增殖的信号通路有3条,分别为Ras信号通路、Rap1信号通路、VEGF信号通路;与细胞生长和死亡的通路有1条,为细胞凋亡通路。
以上所述仅为本发明的优选实施例而已,并不用于限制本发明,对于本领域的技术人员来说,本发明可以有各种更改和变化。凡在本发明的精神和原则之内,所作的任何修改、等同替换、改进等,均应包含在本发明的保护范围之内。
Claims (10)
1.药物组合物在制备用于治疗或改善心血管疾病中的应用,其特征在于,按重量份数计,所述药物组合物的主料包括以下组分:110~150份黄连、160~190份乌梅、110~150份麦冬、110~150份地黄、1~20份阿胶、110~150份黄芪、110~150份山药、110~150份玄参以及110~150份苍术。
2.根据权利要求1所述的药物组合物在制备用于治疗或改善心血管疾病中的应用,其特征在于,所述心血管疾病选自:高血压、心力衰竭、心肌梗塞、心肌再灌注损伤、脑缺血、冠状动脉疾病和房颤中的至少一种。
3.根据权利要求1所述的药物组合物在制备用于治疗或改善心血管疾病中的应用,其特征在于,按重量份数计,所述药物组合物的主料包括以下组分:120~150份黄连、160~190份乌梅、120~150份麦冬、120~150份地黄、1~20份阿胶、120~150份黄芪、120~150份山药、120~150份玄参以及120~150份苍术。
4.根据权利要求3所述的药物组合物在制备用于治疗或改善心血管疾病中的应用,其特征在于,所述药物组合物还包括辅料;所述辅料的组分选自糊精和乳糖中的至少一种;
优选地,按重量份数计,所述药物组合物中,每1份主料,对应包括1~3份糊精以及1~3份乳糖。
5.根据权利要求1~4任一项所述的药物组合物在制备用于治疗或改善心血管疾病中的应用,其特征在于,当所述药物组合物包括辅料且所述辅料包括糊精和乳糖时,所述药物组合物的制备方法如下:将除阿胶以外的主料按照重量份数进行混合,获得混合物;
煎煮所述混合物,减压压缩后,获得浸膏;
干燥所述浸膏压缩干燥,粉碎后,获得干膏粉;
将所述干膏粉与阿胶、糊精以及乳糖混合后,造粒干燥,获得最终产物。
6.根据权利要求5所述的药物组合物在制备用于治疗或改善心血管疾病中的应用,其特征在于,所述煎煮的具体步骤如下:
将所述混合物与8~10倍重量的水混合,煎煮0.5~1.5小时,获得第一滤液和第一滤渣;
将第一滤渣与8~10倍重量的水混合,煎煮0.5~1.5小时,获得第二滤液和第二滤渣;
将第二滤渣与8~10倍重量的水混合,煎煮0.5~1.5小时,获得第三滤液和第三滤渣;
将所述第一滤液、第二滤液和第三滤液合并后减压浓缩,获得所述浸膏。
7.根据权利要求5所述的药物组合物在制备用于治疗或改善心血管疾病中的应用,其特征在于,所述减压浓缩的条件为:70~90℃。
8.根据权利要求5所述的药物组合物在制备用于治疗或改善心血管疾病中的应用,其特征在于,将所述阿胶与干膏粉、糊精以及乳糖混合前,所述制备方法包括将阿胶与糊精按1:(0.5~3)的质量比混合后粉碎,获得阿胶粉,以用于后续与所述干膏粉混合。
9.根据权利要求5所述的药物组合物在制备用于治疗或改善心血管疾病中的应用,其特征在于,所述干膏粉、阿胶、糊精以及乳糖的混合比为:(0.8~1.2):(0.8~1.2):(1.8~2.2):(1.8~2.2)。
10.根据权利要求1所述的药物组合物在制备用于治疗或改善心血管疾病中的应用,其特征在于,所述药物的类型可选自:液体剂型、固体剂型、半固体剂型和气体剂型中的至少一种。
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