CN109288939A - 一种治疗心脑血管疾病的药物及其制备方法 - Google Patents
一种治疗心脑血管疾病的药物及其制备方法 Download PDFInfo
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Abstract
本发明提供一种治疗心脑血管疾病的药物,由下述质量份的原料制成:藏红花全花60‑80份、红景天50‑250份、苏木100‑200份、当归100‑300份、胆南星50‑150份、川芎150‑250份、黄芪200‑400份、地龙100‑200份、怀牛膝100‑200份。制备方法如下:1)将黄芪、地龙、苏木、怀牛膝加水煎煮提取三次,合并提取液,过滤、浓缩成膏,烘干、粉碎;2)将川芎、当归、红景天用乙醇水溶液提取三次,合并提取液、浓缩成稠膏,烘干、粉碎;3)将胆南星烘干后与藏红花全花混合、粉碎;然后将上述药粉混匀,装入胶囊,即得。本发明通过对处方和制备工艺的改进,提高了晶珠双红活血胶囊的药效。
Description
技术领域
本发明属于中药领域,具体涉及一种治疗心脑血管疾病的藏药新药-晶珠双红活血胶囊及其制备方法。
背景技术
心脑血管疾病是心脏血管和脑血管的疾病统称。目前心脑血管疾病已经跃居我国发病率高、致残率高、死亡率高、复发率高、医疗费用高、并发症多(常称“五高一多”)的疾病。心脑血管疾病主要指冠心病、心肌梗死、脑血栓、高血压等11种疾病,它是由高血压、高血脂、高血糖、高粘血症、血小板功能增强、动脉硬化、体内自由基含量增高及微循环障碍所引起;血脂在血管壁上越积越多,造成动脉血管粥样硬化,导致血管管腔狭小,血液流动受阻,营养成分和氧等物质不能顺畅的输送到身体所需部位,二氧化碳等废物也不能被充分的带走,同时导致血管管壁变薄、脆化、失去弹性。
晶珠双红活血胶囊是一种能治疗心脑血管疾病的药物。原有的制备方法为:黄芪、地龙、苏木、怀牛膝水提三次,合并三次提取液,过滤、浓缩、烘干、粉碎;川芎、当归、红景天用70%乙醇回流提取三次、合并三次提取液、减压回收乙醇,浓缩成膏、烘干、粉碎。胆南星烘干后与藏红花混合、粉碎,将三种药粉按比例混匀,加辅料、灌装胶囊。
晶珠双红活血胶囊的首药为藏红花。藏红花为鸢尾科番红花属草本植物,主产于伊朗、印度等地,经西藏传入我国。藏红花的传统药用部位为干燥柱头,具有活血化瘀、凉血解毒等功效,但藏红花柱头的产量极低,其仅占整朵花质量的7.4%,也就是说,为获得1kg藏红花柱头,需要使用13.5kg藏红花全花。目前,采摘了柱头的藏红花被全部丢弃,造成了极大的资源浪费。研究表明,藏红花的非柱头部位富含黄酮类、酚酸类、苷类等多种化学成分,具有良好的抗氧化活性,对血脂、血压、心脏平滑肌收缩和血小板聚集均有明显调节作用。为了提高对藏红花的综合利用,并优化晶珠双红活血胶囊的疗效,需要改变藏红花的用药部位,并对原有的药材配比进行调整。
此外,在原有的制备工艺中,无论是水煎煮还是乙醇提取,其有效成分的溶出均未达到理想水平,限制了药效发挥,因此需要分别对水煎煮和乙醇提取的工艺条件进行优化,以提高有效成分的溶出率。因此,研制一种能克服上述缺陷的新的制备晶珠双红活血胶囊的方法具有重要的现实意义。
发明内容
本发明的目的是提供一种治疗心脑血管疾病的藏药新药-晶珠双红活血胶囊及其制备方法。
本发明所提供的治疗心脑血管疾病的藏药新药-晶珠双红活血胶囊,由下述质量份的原料制成:藏红花全花60-80份、红景天50-250份、苏木100-200份、当归100-300 份、胆南星50-150份、川芎150-250份、黄芪200-400份、地龙100-200份、怀牛膝100-200份。
优选后,所述晶珠双红活血胶囊由下述质量份的原料制成:藏红花全花70份、红景天200份、苏木150份、当归200份、胆南星50份、川芎200份、黄芪300份、地龙150份、怀牛膝150份。
其中,藏红花全花的优选质量分数为70份,这样既能保持其柱头部位的含量不低于原配方,又能充分利用非柱头部位。
本发明所提供的晶珠双红活血胶囊的制备方法,包括下述步骤:
1)将所述黄芪、地龙、苏木、怀牛膝加水煎煮提取三次,合并三次提取液,过滤、浓缩成稠膏,烘干、粉碎,得药粉1;
2)将所述川芎、当归、红景天用体积分数为70%的乙醇水溶液提取三次,合并三次提取液、浓缩成稠膏,烘干、粉碎,得药粉2;
3)将所述胆南星烘干后与所述藏红花全花混合、粉碎,得药粉3;
4)将所述药粉1、药粉2、药粉3混匀,装入胶囊,即得。
上述步骤1)—3)的顺序可以任意调换或同时进行。
其中,步骤1)中所述煎煮提取前需加水浸泡,所述加水量为黄芪、地龙、苏木、怀牛膝体积的10倍,浸泡时间为120分钟。
所述煎煮提取的条件如下:三次煎煮加水量依次为所述黄芪、地龙、苏木、怀牛膝体积的10倍、7倍、4倍;三次煎煮的时间依次为4小时、2小时、1小时。
步骤2)中,用乙醇提取前需用体积分数为70%的乙醇水溶液浸泡,所述70%的乙醇水溶液的用量为川芎、当归、红景天体积的6倍,浸泡时间60分钟。
所述提取的条件如下:第一次提取加入的乙醇水溶液的质量为药材质量的6倍,提取3小时;第二次提取加入的乙醇水溶液的质量为药材质量的4倍,提取2小时;第三次提取加入的乙醇水溶液的质量为药材质量的4倍,提取1小时。
步骤1)和步骤2)中,所述浓缩成膏具体是将提取液浓缩至相对密度为1.30~1.35(50℃)的稠膏。
制成上述胶囊的各原料药是按照质量份作为配比,在生产时可按照相应的比例增大或减少,如大规模生产可以以公斤或以吨为单位,小规模生产也可以以克为单位,重量可以增大或减小,但各组成之间的原料药质量配比比例不变。
上述方法制备得到的晶珠双红活血胶囊也属于本发明的保护范围。
本发明通过对现有处方及制备工艺进行改进,创造性地解决了藏红花综合利用问题,同时使用喷雾干燥法对药材提取物稠膏进行干燥,增加了有效成分的收率,从而提高了晶珠双红活血胶囊的药效。
药效试验证实,按照本发明方法制备的晶珠双红活血胶囊,具有活血祛瘀,镇心安神、调和气血,调和隆、赤巴、培根平衡功能;适用于综合性木布病蔓延至心脏(冠状动脉硬化、冠心病、缺血性心脏病、心绞痛)及蔓延至头部(高血压、脑血栓、中风后遗症)疾病的治疗与预防。与现有的晶珠心脑通胶囊相比,治愈率更高、见效更快。
具体实施方式
下面通过具体实施例对本发明进行说明,但本发明并不局限于此。
下述实施例中所使用的实验方法如无特殊说明,均为常规方法;下述实施例中所用的试剂、材料等,如无特殊说明,均可从商业途径得到。
下述实施例中所用的材料、试剂等,如无特殊说明,均可从商业途径得到。
下述实施例中所用的藏红花、红景天、苏木、当归、胆南星、川芎、黄芪、地龙、怀牛膝均符合《中国药典》(2015年版)一部正文各药材项下的有关规定。投料前,通过鉴定,各味药材实物与名称相符,质量符合标准。
实施例1、考察不同水提工艺条件对活性成分的影响
处方组成如下:
藏红花全花70g、红景天200g、苏木150g、当归200g、胆南星50g、川芎200 g、黄芪300g、地龙150g、怀牛膝150g。
制备方法如下:
1)将处方量的黄芪、地龙、苏木、怀牛膝加水煎煮提取三次,合并三次提取液,过滤、浓缩至相对密度为1.30~1.35(50℃)的稠膏,90℃烘干、粉碎,得药粉1;
2)将处方量的川芎、当归、红景天(用量为川芎、当归、红景天体积的6倍)浸泡60分钟,然后用体积分数为70%的乙醇水溶液提取三次(第一次加6倍体积乙醇提取3小时,第二次加4倍体积乙醇提取2小时、第三次加4倍体积乙醇提取1小时),合并提取液、浓缩至相对密度为1.30~1.35(50℃)的稠膏,90℃烘干、粉碎、过80 目筛,得药粉2;
3)将处方量的胆南星烘干后与藏红花全花混合、粉碎,得药粉3;
4)将所述药粉1、药粉2、药粉3混匀,灌装成1000粒胶囊,即得。
上述步骤1)中,通过三因素(浸泡时间、加水量、提取时间)、三水平设计正交试验,以黄芪甲苷收率为考察指标,正交因素及水平见表1,正交试验结果见表2。
表1晶珠双红活血胶囊水煎煮工艺因素及水平
(注:第二次和第三次提取时间的优化未显示)
表2晶珠双红活血胶囊水煎煮工艺正交试验结果
序号 | A | B | C | 黄芪甲苷收率(mg/g) |
1 | 1 | 1 | 1 | 0.849 |
2 | 2 | 2 | 2 | 0.961 |
3 | 3 | 3 | 3 | 1.075 |
4 | 1 | 2 | 3 | 0.877 |
5 | 2 | 3 | 1 | 0.983 |
6 | 3 | 1 | 2 | 0.879 |
7 | 1 | 3 | 2 | 0.974 |
8 | 2 | 1 | 3 | 1.136 |
9 | 3 | 2 | 1 | 0.988 |
K1 | 2.700 | 2.864 | 2.815 | |
K2 | 3.080 | 2.826 | 2.814 | |
K3 | 2.942 | 3.032 | 3.088 | |
R | 0.380 | 0.206 | 0.274 |
由表2可见,当水煎煮工艺条件为A2B3C3时,黄芪甲苷收率高于其他工艺条件,因此最佳工艺条件为:10倍量体积的水,浸泡120分钟,水煎煮三次,第一次提取时间4小时。以同样方法进行优化,得出第二次加7倍量体积的水提取2小时,第三次加4倍量体积的水提取1小时。
实施例2、考察不同醇提工艺条件对活性成分的影响
处方组成同实施例1。
制备方法如下:
1)将处方量的黄芪、地龙、苏木、怀牛膝加水煎煮提取三次(加10倍量体积的水,浸泡120分钟,三次煎煮加水量依次为所述黄芪、地龙、苏木、怀牛膝体积的10 倍、7倍、4倍;三次煎煮的时间依次为4小时、2小时、1小时。),合并三次提取液,过滤、浓缩至相对密度为1.30~1.35(50℃)的稠膏,90℃烘干、粉碎,得药粉1;
2)将处方量的川芎、当归、红景天用乙醇水溶液提取三次,合并提取液、浓缩至相对密度为1.30~1.35(50℃)的稠膏,90℃烘干、粉碎、过80目筛,得药粉2;
3)将处方量的胆南星烘干后与藏红花全花混合、粉碎,得药粉3;
4)将所述药粉1、药粉2、药粉3混匀,灌装成1000粒胶囊,即得。
上述步骤2)中,通过三因素(乙醇浓度、加乙醇量、提取时间)、三水平设计正交试验,以红景天苷提取率为考察指标,正交因素及水平见表3。
表3晶珠双红活血胶囊乙醇提取工艺因素及水平
表4晶珠双红活血胶囊乙醇提取工艺正交试验结果
由表4可见,当乙醇提取工艺条件为A2B1C3时,红景天苷提取率达到最大,因此乙醇提取的最佳工艺条件为:乙醇浓度70%,加6倍体积的70%乙醇,第一次提取时间3小时。以同样方法进行优化,得出第二次加4倍体积的70%乙醇提取2小时,第三次加4倍体积的70%乙醇提取1小时。
实施例3、藏红花不同部位入药后的药效比较
根据藏红花的不同用药部位,分别制备以下两种晶珠双红活血胶囊制剂,观察其对大鼠心肌缺血再灌注损伤的保护作用。
(1)A制剂:藏红花全花70g、红景天200g、苏木150g、当归200g、胆南星 50g、川芎200g、黄芪300g、地龙150g、怀牛膝150g,按照上述实施例1方法进行制备。
(2)B制剂:藏红花柱头5g、红景天200g、苏木150g、当归200g、胆南星 50g、川芎200g、黄芪300g、地龙150g、怀牛膝150g,按照上述实施例1方法进行制备。
结果如表5所示。ATP/ADP:A制剂组显著高于B制剂组,同时A制剂、B制剂两组均显著高于模型组;Na+/K+-ATPase:A制剂组显著高于B制剂组,同时A制剂、 B制剂两组均显著高于模型组;乳酸脱氢酶(LDH):A制剂组显著高于B制剂组和模型组,B制剂组与模型组无显著差异。该结果表明,以藏红花全花入药制备的晶珠双红活血胶囊,对大鼠心肌缺血再灌注损伤的保护作用强于以藏红花柱头入药制备的晶珠双红活血胶囊,推测藏红花非柱头部位的活性成分是导致这一差异的原因之一,但尚需进一步深入开展药理研究。
表5使用藏红花不同部位入药的晶珠双红活血胶囊制剂对大鼠心肌缺血再灌注的影响
注:*,与B组相比,P<0.05;#,与模型组相比,P<0.05
实施例4、最佳工艺条件制备晶珠双红活血胶囊
处方组成同实施例1。
制备方法如下:
1)将处方量的黄芪、地龙、苏木、怀牛膝加水煎煮提取三次(加10倍量体积的水,浸泡120分钟,三次煎煮加水量依次为所述黄芪、地龙、苏木、怀牛膝体积的10 倍、7倍、4倍;三次煎煮的时间依次为4小时、2小时、1小时。),合并三次提取液,过滤、浓缩至相对密度为1.30~1.35(50℃)的稠膏,90℃烘干、粉碎,得药粉1;
2)将处方量的川芎、当归、红景天用体积分数为70%的乙醇水溶液提取三次(加 6倍量体积的70%的乙醇水溶液,浸泡60分钟;三次提取乙醇水溶液用量依次为所述川芎、当归、红景天体积的6倍、4倍、4倍;三次提取的时间依次为3小时、2小时、 1小时。),合并提取液、浓缩至相对密度为1.30~1.35(50℃)的稠膏,90℃烘干、粉碎、过80目筛,得药粉2;
3)将处方量的胆南星烘干后与藏红花全花混合、粉碎,得药粉3;
4)将所述药粉1、药粉2、药粉3混匀,加辅料、灌装成1000粒胶囊,即得。
对比例、
处方组成同实施例1。
采用三种方式提取,方中黄芪、地龙、苏木、怀牛膝水提三次(三次煎煮加水量依次为所述黄芪、地龙、苏木、怀牛膝体积的5倍、5倍、5倍;三次煎煮的时间依次为2小时、2小时、2小时。),合并三次提取液,过滤、浓缩、烘干、粉碎;川芎、当归、红景天70%乙醇回流提取三次(第一次加6倍体积乙醇提取2小时,第二次加6 倍体积乙醇提取2小时、第三次加6倍体积乙醇提取2小时)、合并三次提取液、减压回收乙醇,浓缩成膏、烘干、粉碎;胆南星烘干后与藏红花混合、粉碎,将三种药粉按比例混匀,加辅料、灌装成1000粒胶囊,即得本发明产品。
实施例5、药效试验
下面对使用本发明实施例4制备方法与对比例方法制备的晶珠双红活血胶囊各5个批号进行比较,评价二者在活性成分含量及临床疗效上的差异。
1、活性成分含量的比较以红景天苷、黄芪甲苷、藏红花苷Ⅰ/Ⅱ为评价指标,使用高效液相色谱测量各活性成分的溶出量,结果如表6所示。
表6采用不同方法制备的晶珠双红活血胶囊的活性成分比较
由表6可见,采用本发明的制备方法,晶珠双红活血胶囊中的活性成分红景天苷、黄芪甲苷以及藏红花苷Ⅰ/Ⅱ的溶出量均明显高于原有的制备方法,差别具有统计学意义(P均<0.05)。
2、临床效果
缺血性心脑血管疾病是由于脂质代谢异常,使血脂沉积于血管内壁,引起冠状动脉及脑血管血液循环障碍所致。晶珠双红活血胶囊具有益气活血、祛瘀通脉的功能,可用于气虚血瘀引起的胸痹及中风,以及冠心病、心绞痛、脑栓塞恢复期等心脑血管疾病属上述证候者。北京晶珠中医医院对此进行了初步观察。
本观察共纳入缺血性心脑血管疾病及高脂血症门诊患者94例,随机分为A组和 B组。A组48例,其中男26例,女20例,年龄34-82岁,病程1-16年;其中冠心病 21例,脑血栓10例,高脂血症17例。B组46例,其中男24例,女22例,年龄35-80 岁,病程1-18年;其中冠心病19例,脑血栓12例,高脂血症15例。冠心病患者均有不同程度的胸闷、胸痛、气短、乏力和心悸等症状,心电图检查均有心肌缺血、ST 段下移和肌酸磷酸激酶(CPK)的改变,符合冠心病诊断标准。脑血栓患者均有不同程度的头晕、语言不利、肢体障碍、智力或记忆力下降,且脑部CT显示不同部位存在不同程度的斑块,符合脑血栓的诊断标准。高脂血症患者均有头晕乏力、胸闷、嗜睡的症状。全部患者均在正常饮食条件下,在2周内2次检查空腹血清总胆固醇(TC) ≥60mmol/L,或甘油三酯(TG)≥1.54mmol/L。
A组患者接受采用本发明方法制备的晶珠双红活血胶囊治疗,B组患者接受采用原方法制备的晶珠双红活血胶囊治疗。两组给药方式均为一次4粒,一日3次,口服,3个月为一个疗程。在治疗期间每15天复查一次心电图,疗程结束时复查TC、TG和 CPK,随访2个疗程。
两组的临床疗效比较如表7所示,治疗前后实验室检查结果如表8所示。其中A 组的总有效率为89.6%,显著高于B组(78.3%,P<0.05)。在实验室检查结果方面, A、B两组治疗后与治疗前相比,TC、TG和CPK水平均显著下降(P均<0.05),而A 组治疗后的TC和CPK水平显著低于B组治疗后(P均<0.05)。综上表明,采用本发明方法制备的晶珠双红活血胶囊,对缺血性心脑血管疾病的综合疗效优于采用原方法制备的晶珠双红活血胶囊。
表7A、B两组患者临床疗效比较
表8A、B两组患者治疗前后实验室检查结果比较
注:*,与本组治疗前比较,P<0.05;#:与B组治疗后比较,P<0.05。
Claims (8)
1.一种治疗心脑血管疾病的药物,由下述质量份的原料制成:藏红花全花60-80份、红景天50-250份、苏木100-200份、当归100-300份、胆南星50-150份、川芎150-250份、黄芪200-400份、地龙100-200份、怀牛膝100-200份。
2.根据权利要求1所述的药物,其特征在于:所述由下述质量份的原料制成:藏红花全花70份、红景天200份、苏木150份、当归200份、胆南星50份、川芎200份、黄芪300份、地龙150份、怀牛膝150份。
3.制备权利要求1或2所述药物的方法,包括下述步骤:
1)将所述黄芪、地龙、苏木、怀牛膝加水煎煮提取三次,合并三次提取液,过滤、浓缩成稠膏,烘干、粉碎,得药粉1;
2)将所述川芎、当归、红景天用体积分数为70%的乙醇水溶液提取三次,合并三次提取液、浓缩成稠膏,烘干、粉碎,得药粉2;
3)将所述胆南星烘干后与所述藏红花混合、粉碎,得药粉3;
4)将所述药粉1、药粉2、药粉3混匀,装入胶囊,即得。
上述步骤1)—3)的顺序可以任意调换或同时进行。
4.根据权利要求3所述的方法,其特征在于:所述步骤1)中,所述煎煮提取的条件如下:三次煎煮加水量依次为所述黄芪、地龙、苏木、怀牛膝体积的10倍、7倍、4倍;三次煎煮的时间依次为4小时、2小时、1小时。
5.根据权利要求3或4所述的方法,其特征在于:所述步骤1)中,所述煎煮提取前需加水浸泡,所述加水量为黄芪、地龙、苏木、怀牛膝体积的10倍,浸泡120分钟。
6.根据权利要求3-5中任一项所述的方法,其特征在于:所述步骤2)中,所述提取的条件如下:第一次提取加入的乙醇水溶液的质量为药材质量的6倍,提取3小时;第二次提取加入的乙醇水溶液的质量为药材质量的4倍,提取2小时;第三次提取加入的乙醇水溶液的质量为药材质量的4倍,提取1小时。
7.根据权利要求3-6中任一项所述的方法,其特征在于:所述步骤2)中,用乙醇提取前需用体积分数为70%的乙醇水溶液浸泡,所述体积分数为70%的乙醇水溶液的用量为川芎、当归、红景天体积的6倍,浸泡时间为60分钟。
8.根据权利要求3-7中任一项所述的方法,其特征在于:所述步骤1)和步骤2)中,所述浓缩成稠膏具体是将提取液浓缩至相对密度为1.30~1.35(50℃)的稠膏。
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