CN113940971A - 一种治疗睡眠障碍的中药颗粒剂及其制备方法 - Google Patents
一种治疗睡眠障碍的中药颗粒剂及其制备方法 Download PDFInfo
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Abstract
本发明揭示了一种治疗睡眠障碍的中药颗粒剂及其制备方法,其由如下重量份数的原料制成:五味子550~650份;酸枣仁520~560份;百合330~360份;丹参320~360份;石菖蒲320~360份;沙棘280~320份;缬草230~270份;大枣230~270份。本发明能够有效的治疗失眠障碍,且具有补血滋阴功效,无毒副作用和成瘾性弊端,制作成本低。
Description
【技术领域】
本发明属于中药技术领域,特别是涉及一种治疗睡眠障碍的中药颗粒剂及其制备方法。
【背景技术】
随着社会进步,生活和工作节奏加快,竞争日趋激烈,精神压力增大,导致神经调节障碍失眠人群在不断增加。“晚上睡不着,白天不想起”已成为困扰许多年轻人的问题之一。数据显示,我国超3亿人存在睡眠障碍,在这些失眠人群中,以90后、95后、00后为代表的年轻人睡眠问题最为突出。
睡眠时间短,尤其是深度睡眠不够、入睡困难、早醒等是失眠的不同表现形式。神经衰弱、机体调节功能差、生活规律絮乱、慢性疾病等都可以成为发病原因。由于长期失眠也可以诱发高血压、糖尿病、精神分裂、焦虑、抑郁、狂躁及人体免疫功能下降。失眠的人患心脏病比正常人高出两到三倍。现代都市几乎成为失眠人群的发源地,如上海就有87.76%的人失眠,北京更高。近年来,不但老年人、中年人失眠患病率上升,90后已成为失眠大军。医学上称失眠为慢性自杀,除了对工作和生活带来严重影响,甚至会危及生命。
对本病要全身调整,精神调节,生活调养,环境改善,减少刺激,使之达到兴奋和抑制,协调阴阳平衡。
药物治疗早期已经应用巴比妥类、安定类、三唑仓等品种,由于它们存在依赖性及不良反应,已被佐匹克隆、扎来普隆等逐步代替,市场上的安定、刺五加、利培酮、唑吡坦等品种常见销售。
祖国医学对本病有独特的认识,认为和精血不足、心血劳损、思虑过度等造成的心肾不交、心脾血亏、肝郁不调等有关。相比现代医学在认识上更贴近人们的生理。在治疗上,中医更能坚持整体调节、腑腑调节以达阴阳平衡,而且中药可克服西药的弊端,无毒副作用和成瘾依赖性,更偏重于人体功能恢复。中药古方中有朱砂安神丸、归脾丸、白子仁养心丸、天王补心丹等早已应用临床。现代对本病研发的品种除百合枣仁胶丸、敖东安神丸等外,品种数量较少,效果一般。
为了发扬祖国医药学优势,满足3亿多失眠人群的大市场,让患者有挑选的余地,研发治疗失眠的高效中药品种是形势的需要,也是中医工作者义不容辞的责任。
【发明内容】
本发明的主要目的之一在于提供一种治疗睡眠障碍的中药颗粒剂,能够有效的治疗失眠障碍,且具有补血滋阴功效,无毒副作用和成瘾性弊端,制作成本低。
本发明通过如下技术方案实现上述目的:一种治疗睡眠障碍的中药颗粒剂,其由如下重量份数的原料制成:
五味子550~650份;
酸枣仁520~560份;
百合330~360份;
丹参320~360份;
石菖蒲320~360份;
沙棘280~320份;
缬草230~270份;
大枣230~270份。
进一步的,还包括以下辅料:
甘露醇320~360份;
糊精130~170份;
甜菊甙1~10份;
环状糊精包结物β-CD8~16份。
本发明还提供了一种治疗睡眠障碍的中药颗粒剂制备方法,其包括以下步骤:
S1)以五味子为原料制备五味子药液A;
S2)以石菖蒲和缬草为原料制备得到挥发油B、药渣C、药液D;
S3)用挥发油B和环糊精包结物β-CD制备得到挥发油包结物;
S4)以酸枣仁、百合、丹参、大枣、药渣C为原料水煎煮得到前液,然后放入药液D和沙棘汁,浓缩得到药液E;
S5)将药液E与五味子药液A合在一起,浓缩后真空干燥得到浸膏粉,然后加入辅料制粒;
S6)所述制粒干燥后再加入步骤S3)所得的挥发油包结物,混合形成颗粒成品。
进一步的,所述步骤S1)包括将550~650份五味子烘干捣碎,过筛,然后采用乙醇回流提取法得到五味子乙醇液,然后回收乙醇得到五味子药液A。
进一步的,所述乙醇回流提取法中,乙醇回流两次,乙醇浓度为60%~80%,每次回流乙醇溶剂用量6~8倍量,每次回流时间为1~2h。
进一步的,所述步骤S2)包括将320~360份石菖蒲与230~270份缬草,粉成细粒,加入8~12倍量水,蒸馏6~8h,提取得到所述挥发油,获取蒸馏后的水溶液为所述药液D,剩下的药渣为所述药渣C。
进一步的,所述步骤S3)包括称取8~16份环糊精包结物β-CD,加入蒸馏水,水浴溶解,在搅拌下加入1:1的乙醇与所述挥发油,加塞,继续恒温下搅拌,置冷箱中冷藏抽滤,依次用适量蒸馏水、无水乙醇洗涤,抽干,减压真空干燥至恒重,得到白色粉末状的所述挥发油包结物。
进一步的,所述步骤S4)包括将酸枣仁、百合、丹参、大枣、药渣C共同煎煮,煎煮2次,每次加水量6~12倍,60%~80%醇沉;合并两次煎煮后的药液,静置,取上清液,然后加入药液D和沙棘汁,共同煎煮至相对密度1.10g/ml(80℃测),加入乙醇使含醇量达到60%~80%,静置12~24h,回收乙醇,得到药液E。
进一步的,所述步骤S5)中采用减压蒸发浓缩工艺,水浴浓缩,浓缩温度为60~80℃,五味子药液A加入后浓缩至半量时,予以静置后过滤,滤液继续浓缩至相对密度为1.38~1.40g/ml(60~65℃测)的稠膏,然后真空干燥得到浸膏粉。
进一步的,所述步骤S5)中的辅料包括320~360份甘露醇、130~170份糊精及1~10份甜菊甙。
与现有技术相比,本发明一种治疗睡眠障碍的中药颗粒剂及其制备方法的有益效果在于:在治疗失眠方面具有良好的效果,且没有依赖性和副作用,在治疗失眠的同时,具有滋阴补血、全身调节的全面优势,且不会影响白天的自主活动。具体的,本中药颗粒剂组方中五味子、酸枣仁从药理分析、动物实验及临床应用,都证实能夠调节神经,改变睡眠障碍和提高睡眠质量;百合配合大枣协助丹参有效控制心悸不安,心血不足,提高睡眠质量;组方中尤其是缬草具有镇静作用,加强大脑皮层抑制过程,降低反射兴奋,它与五味子合用,是睡眠的增效剂;与酸枣仁合用可治疗心悸不安,失眠多梦;与石菖蒲合用可醒脑益心,消除忧虑,心情愉悦,促进入睡;组方中沙棘含多种营养成分,可促进全身细胞代谢,其所含黄酮类对植物神经紊乱有明显调节作用,对神经紧张或刺激引起的睡眠障碍可予以改善;沙棘配五味子、酸栆仁酸甘化阴,有益于治疗临床最常见肝血不足造成的失眠,沙棘配丹参能活血安神,沙棘对肠胃功能失调出现的睡眠障碍也有改善功效。
【附图说明】
图1为本发明实施例的工艺流程示意图。
【具体实施方式】
实施例一:
本实施例为一种治疗睡眠障碍的中药颗粒剂,其由如下重量份数的原料制成:
五味子550~650份;
酸枣仁520~560份;
百合330~360份;
丹参320~360份;
石菖蒲320~360份;
沙棘280~320份;
缬草230~270份;
大枣230~270份。
为了将本中药制作成颗粒,在睡前采用冲剂形式服用,本实施例一种治疗睡眠障碍的中药颗粒剂还包括以下辅料:
甘露醇320~360份;
糊精130~170份;
甜菊甙1~10份;
β-CD(环状糊精包结物)8~16份。
请参照图1,本实施例还提供了一种治疗睡眠障碍中药的制备方法,其包括以下步骤:
S1)以五味子为原料制备五味子药液A;
S2)以石菖蒲和缬草为原料制备得到挥发油B、药渣C、药液D;
S3)用挥发油B和环糊精包结物β-CD制备得到挥发油包结物;
S4)以酸枣仁、百合、丹参、大枣、药渣C为原料水煎煮得到前液,然后放入药液D和沙棘汁,制备得到药液E;
S5)将药液E与五味子药液A合在一起,经过真空干燥得到浸膏粉,然后加入辅料制粒;
S6)干燥后再加入步骤S3)所得的挥发油包结物,混合形成颗粒成品。
本实施例组方中药味成分较为复杂,其中,五味子主含脂溶性木脂素类化合物及三萜类成分等。据资料报道,五味子仁的乙醇提取物对中枢神经系统有一定的抑制作用,从该提取物中分离出七种联苯双烯类成分,尤其五味子醇甲和五味子醇乙更为明显,因木脂素类化合物在乙醇中溶解度较好,故用乙醇提取。
具体的,步骤S1)具体包括:将五味子烘干捣碎,过筛,然后采用乙醇回流提取法得到五味子乙醇液,然后回收乙醇得到五味子药液A。其中乙醇回流两次,乙醇浓度为60%~80%,每次回流乙醇溶剂用量6~8倍量,每次回流时间为1~2h。
本实施例对五味子按照上述方法进行了提取率与干膏率的计算,其中,采用乙醇回流两次的方法,以五味子醇甲含量和干膏率为检测指标,以乙醇浓度、溶剂用量以及回流时间为变量进行实施例的设计,如表1所示。
表1
检测方法:
本实施例将五味子药材烘干,用铜冲钵捣碎,过8目筛,称取20.0g,采用相应的方法回流,提取过滤,滤液合并,用相应浓度的乙醇稀释至400ml。精密移取5.0ml至10.0ml容量瓶中,甲醇定容,摇匀,微孔滤膜过滤,得供试液,剩余溶液回收乙醇,水浴挥干,真空干燥,得干膏,计算干膏率,结果如表2所示。
所述供试液采用药典方法检测五味子醇甲含量,固定相:C18柱,流动相:甲醇:水=65:35,流速:1ml/min,检测波长:250nm,计算提取率,结果如表2所示。
表2
本实施例经过对表2中的结果进行了方差分析,发现所选的各因素的各水平对干膏率无显著性影响,而A乙醇浓度和B溶剂用量两个因素对五味子醇甲的提取率有显著性影响,因此,在进行五味子药液A制备时,优选浓度为80%的乙醇回流两次,每次8倍溶剂用量,每次回流1.5h。
采用80%的乙醇回流两次,每次8倍溶剂用量,每次回流1.5h工艺参数,制备五味子药液A,对制备过程中五味子醇甲含量以及提取率进行了检测,其检测结果如表3所示。
表3
项目指标 | 五味子药材 | 乙醇回流液 | 回收乙醇后的浸膏 | 制剂 |
五味子醇甲含量(%) | 0.6474 | 0.5064 | 0.4297 | 0.3520 |
提取率(%) | 100 | 78.22 | 61.82 | 54.37 |
所述步骤S2)包括将石菖蒲与缬草,粉成细粒,浸泡2~4h,加入8~12倍水,蒸馏6~8h,提取得到挥发油,获取蒸馏后的水溶液为药液D,剩下的药渣为药渣C。
所述步骤S3)包括称取8~16份β-CD,加入蒸馏水,60℃水浴溶解,降至50℃,在搅拌下加入1:1的乙醇与挥发油液,加塞,继续恒温下搅拌2h,转速1000r/min,置冷箱中冷藏24h抽滤,依次用适量蒸馏水、无水乙醇洗涤,抽干,在45℃减压真空干燥至恒重,得到白色粉末,即挥发油包结物。
所述步骤S4)包括将酸枣仁、百合、丹参、大枣、药渣C共同煎煮,煎煮2次,每次加水量6~12倍,60%~80%醇沉;合并两次煎煮后的药液,静置,取上清液,然后加入药液D和沙棘汁,共同煎煮至相对密度1.10g/ml(80℃测),加入乙醇使含醇量达到60%~80%,静置24h,回收乙醇,得到药液E。
所述步骤S5)中采用减压蒸发浓缩工艺,制剂所含的各类有效成分性质较稳定,受热不易裂解,为了减少损失,保证在短时间低温度下进行浓缩,水浴浓缩温度为60~80℃,优选为70℃。五味子乙醇回收后的药液A可见少量沉淀,故在浓缩至半量时,予以静置后过滤,滤液继续浓缩至相对密度为1.38~1.40g/ml(60~65℃测)的稠膏,然后真空干燥得到浸膏粉,然后加入甘露醇、糊精和甜菊甙,制成颗粒成品。
为了验证本中药的有效性,采用如下三个实施例制备得到本中药。
实施例1:取600份五味子烘干粉碎后,用80%乙醇,每次8倍量回流两次,每次回流1.5h,回收乙醇得到五味子药液A;将351份石菖蒲、249份缬草粉碎,加12倍量水,蒸馏7h,收集挥发油;蒸馏后的药液D另器收集,并得到药渣C备用;取12份β-CD,加入蒸馏水水浴溶解,在搅拌下加入1:1的乙醇与挥发油,搅拌均匀,静置冷藏抽滤,然后依次用适量蒸馏水、无水乙醇洗涤,抽干,真空干燥至恒重,得到挥发油包结物;与549份酸枣仁、351份百合、351份丹参、249份大枣(碎)加水共煎煮两次,分别为9倍量水2h,9倍量水1h,合并两次煎煮液,过滤,将滤液与药液D合并,加入含有300份沙棘的沙棘汁共煎浓缩至相对密度1.10g/ml(80℃测),放冷至室温,加乙醇使含醇量达70%,搅匀,静置24h,取上清液,回收乙醇后,加入五味子药液A,浓缩至相对密度1.38~1.40g/ml(60~65℃测)的稠膏,真空干燥,得浸膏粉,加入350份甘露醇、150份糊精、8份甜菊甙以及适量乙醇制粒,干燥后再加入挥发油包结物,混匀,整粒,分装。
实施例2:取550份五味子烘干粉碎后,用60%乙醇,每次6倍量回流两次,每次回流1h,回收乙醇得到五味子药液A;将320份石菖蒲、230份缬草粉碎,加8倍量水,蒸馏6h,收集挥发油;蒸馏后的药液D另器收集,并得到药渣C备用;取8份β-CD,加入蒸馏水水浴溶解,在搅拌下加入1:1的乙醇与挥发油,搅拌均匀,静置冷藏抽滤,然后依次用适量蒸馏水、无水乙醇洗涤,抽干,真空干燥至恒重,得到挥发油包结物;与520份酸枣仁、330份百合、320份丹参、230份大枣(碎)加水共煎煮两次,分别为6倍量水1h,6倍量水0.5h,合并两次煎煮液,过滤,将滤液与药液D合并,加入含有300份沙棘的沙棘汁共煎浓缩至相对密度1.10g/ml(80℃测),放冷至室温,加乙醇使含醇量达60%,搅匀,静置12h,取上清液,回收乙醇后,加入五味子药液A,浓缩至相对密度1.38~1.40g/ml(60~65℃测)的稠膏,真空干燥,得浸膏粉,加入320份甘露醇、130份糊精、1份甜菊甙以及适量乙醇制粒,干燥后再加入挥发油包结物,混匀,整粒,分装。
实施例3:取650份五味子烘干粉碎后,用70%乙醇,每次7倍量回流两次,每次回流2h,回收乙醇得到五味子药液A;将360份石菖蒲、270份缬草粉碎,加10倍量水,蒸馏8h,收集挥发油;蒸馏后的药液D另器收集,并得到药渣C备用;取16份β-CD,加入蒸馏水水浴溶解,在搅拌下加入1:1的乙醇与挥发油,搅拌均匀,静置冷藏抽滤,然后依次用适量蒸馏水、无水乙醇洗涤,抽干,真空干燥至恒重,得到挥发油包结物;与560份酸枣仁、360份百合、360份丹参、270份大枣(碎)加水共煎煮两次,分别为12倍量水2h,12倍量水2h,合并两次煎煮液,过滤,将滤液与药液D合并,加入含有300份沙棘的沙棘汁共煎浓缩至相对密度1.10g/ml(80℃测),放冷至室温,加乙醇使含醇量达80%,搅匀,静置18h,取上清液,回收乙醇后,加入五味子药液A,浓缩至相对密度1.38~1.40g/ml(60~65℃测)的稠膏,真空干燥,得浸膏粉,加入360份甘露醇、170份糊精、10份甜菊甙以及适量乙醇制粒,干燥后再加入挥发油包结物,混匀,整粒,分装。
然后本申请人将上述各实施例制备的中药送入中国中医研究院基础所与市面上的药剂进行对照实验,具体实验内容如下:
一、本中药对阴虚小鼠血浆cAMP水平的影响
实验方法:取小鼠140只,雄性体重20~24g随机分为7组,每组20只。①空白组:给予生理盐水,给予给药组等体积的生理盐水;②模型对照组;③实施例1药剂:剂量44.1g/Kg;④实施例2药剂:剂量22.1g/Kg;⑤实施例3药剂:剂量11.1g/Kg;⑥天王补心丸组:剂量11.8g/Kg;⑦六味地黄丸组:剂量13.0ml//Kg。
每日给小鼠皮下注射甲状腺0.4mg/只,给药组同时灌服上述剂量的药物,连续6天,第7天取血0.5~1.0ml,按I125-cAMP试剂盒说明测定,并对实验数据进行组件统计学处理,结果如表4所示。
表4
组别 | 剂量 | 动物数(只) | 血浆cAMP(pmol/ml) | P值 |
空白对照 | 20 | 373.05±21.59 | ||
模型对照 | 20 | 594.56±40.88 | ||
实施例1 | 44.1g/Kg | 20 | 502.59±22.13 | <0.01 |
实施例2 | 22.1g/Kg | 20 | 502.38±32.36 | <0.01 |
实施例3 | 11.1g/Kg | 20 | 514.92±30.38 | <0.01 |
天王补心丸 | 11.8g/Kg | 20 | 506.86±19.61 | <0.01 |
六味地黄丸 | 13.0ml//Kg | 20 | 477.41±25.18 | <0.01 |
结果表明,模型对照组cAMP水平明显上升,表明造模成功。实施例1-3给药组均能不同程度地降低阴虚小鼠血浆cAMP水平,因此,验证了本实施例中药有滋阴作用。
二、本中药对血虚小鼠的补血作用
实验方法:取小鼠100只,雄性各半,体重18~22g随机分为5组,每组20只。①模型对照组:给予给药组等体积的生理盐水;②实施例1药剂:剂量44.1g/Kg;③实施例2药剂:剂量22.1g/Kg;④实施例3药剂:剂量11.1g/Kg;⑤复方阿胶浆组:剂量15.6ml/Kg。
用75%究竟擦拭鼠尾部使血管充血,减去尾尖端0.25~0.30cm,使小鼠失血0.5ml,测定各鼠血红蛋白(Hb)含量和红细胞(RBC)数。各鼠按照上述剂量分别灌胃相应药物,连续7天,第8天眼眶取血测定各鼠血红蛋白(Hb)含量和红细胞(RBC)数,结果如表5所示。
表5
组别 | 剂量 | 动物数(只) | Hb(g/l) | RBC(×10<sup>12</sup>/l) | P值 |
模型药前 | 20 | 145.05±9.73 | 8.16±0.68 | ||
模型对照 | 20 | 112.65±7.92 | 6.01±0.46 | ||
实施例1 | 44.1g/Kg | 20 | 126.30±8.74 | 6.74±0.88 | <0.01 |
实施例2 | 22.1g/Kg | 20 | 125.55±9.34 | 6.71±0.56 | <0.01 |
实施例3 | 11.1g/Kg | 20 | 120.60±8.04 | 6.59±0.58 | <0.01 |
复方阿胶 | 15.6ml/Kg | 20 | 131.70±9.40 | 7.15±0.60 | <0.01 |
结果表明,模型对照组第8天时血红蛋白(Hb)含量和红细胞(RBC)数较模型组第1次取血时明显降低,表明造模成功。实施例1-3给药组均能不同程度地升高血虚模型小鼠血红蛋白(Hb)含量和红细胞(RBC)数,因此,验证了本实施例中药有补血作用。
三、本中药对小鼠自主活动的影响
实验方法:将70只小鼠于实验前称重,随机分为7组。①空白对照组:给予大剂量组等体积的生理盐水;②实施例1药剂:剂量44.1g/Kg;③实施例2药剂:剂量22.1g/Kg;④实施例3药剂:剂量11.1g/Kg;⑤天王补心丸组:剂量11.8ml/Kg;⑥安神补脑液组:13ml/Kg;⑦安定组:1.3mg/Kg。
将小动物自主活动检测装置与MP-100生理实验信号采集分析系统相连,首先记录各组小鼠灌胃前25min内自主活动次数,然后记录灌胃1h后25min内的自主活动次数。每个装置内放1只小鼠,每次检测前让动物在装置内适应5min。
实验结果:对每组小鼠给药前及灌胃后25min内自主活动次数的差,用组间T检验进行显著性检验,结果如表6所示。
表6
组别 | 剂量 | 动物数(只) | 活动次数差(后-前)(X±SD) |
生理盐水 | 10 | -154.40±164.21 | |
实施例1 | 44.1g/Kg | 10 | -161.20±196.08 |
实施例2 | 22.1g/Kg | 10 | -132.80±131.51 |
实施例3 | 11.1g/Kg | 10 | -78.30±103.95 |
天王补心丸组 | 11.7gKg | 10 | -50.10±31.90 |
安神补脑液组 | 13.0ml/Kg | 10 | -126.80±116.78 |
舒乐安定组 | 1.3mg/Kg | 10 | -93±67.62 |
从表6中可见,实施例1与生理盐水对照组相比,对小鼠自主活动有微弱的抑制作用,但没有统计学意义;其他各组与生理盐水对照组相比,对小鼠自主活动有增加的趋势,但同样没有统计学意义。结果表明,本实施例中药对小鼠的自主活动没有影响。
四、本中药对戊巴比妥钠小鼠睡眠时间的影响
实验方法:将140只小鼠于实验前称重,随机分为7组。①空白对照组:给予大剂量组等体积的生理盐水;②实施例1药剂:剂量44.1g/Kg;③实施例2药剂:剂量22.1g/Kg;④实施例3药剂:剂量11.1g/Kg;⑤天王补心丸组:剂量11.8ml/Kg;⑥安神补脑液组:13ml/Kg;⑦安定组:1.3mg/Kg。
各组按剂量口服灌胃60min后,腹腔注射阈剂量戊巴比妥钠(43.75mg/Kg),观察各组实验动物,以翻正反射消失为入睡时间,从翻正反射消失至恢复翻正反射时间为睡眠持续时间,记录每只小鼠的睡眠时间。
实验结果:所获各组实验数据采用组间T检验进行统计学处理,结果如表7所示。
表7
组别 | 剂量 | 动物数(只) | 睡眠时间(min)(X±SD) | P值 |
空白对照组 | 20 | 70.50±18.30 | ||
实施例1 | 44.1g/Kg | 20 | 105.75±45.72 | <0.01 |
实施例2 | 22.1g/Kg | 20 | 98.30±36.18 | <0.01 |
实施例3 | 11.1g/Kg | 20 | 82.65±29.94 | <0.01 |
天王补心丸组 | 11.7gKg | 20 | 92.50±31.84 | <0.01 |
安神补脑液组 | 13.0ml/Kg | 20 | 84.40±36.53 | <0.01 |
舒乐安定组 | 1.3mg/Kg | 20 | 113.05±31.98 | <0.01 |
从表7中可见,实施例1-3均能明显延长戊巴比妥钠阈剂量小鼠的睡眠时间,本实施例中大剂量、中剂量与对照组相比差异非常显著。实验结果表明,本实施例中药有协同戊巴比妥钠的作用,具有催眠作用和镇静作用,即对中枢神经系统有抑制作用,有安神之功效。
五、本中药对戊巴比妥钠小鼠入睡个数的影响
实验方法:将140只小鼠于实验前称重,随机分为7组。①空白对照组:给予大剂量组等体积的生理盐水;②实施例1药剂:剂量44.1g/Kg;③实施例2药剂:剂量22.1g/Kg;④实施例3药剂:剂量11.1g/Kg;⑤天王补心丸组:剂量11.8ml/Kg;⑥安神补脑液组:13ml/Kg;⑦安定组:1.3mg/Kg。
各组按剂量口服灌胃60min后,腹腔注射阈剂量戊巴比妥钠(31.25mg/Kg),空白对照组只腹腔注射阈剂量戊巴比妥钠。观察各组实验动物,以小鼠翻正反射消失1min以上为入睡指标,记录每组小鼠的入睡情况。
实验结果:所获各组实验数据采用组x2检验进行统计学处理,结果如表8所示。
表8
组别 | 剂量 | 动物数(只) | 入睡动物数(只) | P值 |
空白对照组 | 20 | 2 | ||
实施例1 | 44.1g/Kg | 20 | 19 | <0.01 |
实施例2 | 22.1g/Kg | 20 | 18 | <0.01 |
实施例3 | 11.1g/Kg | 20 | 10 | <0.05 |
天王补心丸组 | 11.7gKg | 20 | 7 | >0.05 |
安神补脑液组 | 13.0ml/Kg | 20 | 6 | >0.05 |
舒乐安定组 | 1.3mg/Kg | 20 | 20 | <0.01 |
从表8中可见,实施例1-3均能明显使入睡小鼠数量增加,与对照组相比差异显著或非常显著。实验结果表明,本实施例中药有协同戊巴比妥钠的作用,具有安神之功效。
本实施例一种治疗睡眠障碍的中药颗粒剂及其制备方法的有益效果在于:在治疗失眠方面具有良好的效果,且没有依赖性和副作用,在治疗失眠的同时,具有滋阴补血、全身调节的全面优势,且不会影响白天的自主活动。具体的,本中药颗粒剂组方中五味子、酸枣仁从药理分析、动物实验及临床应用,都证实能夠调节神经,改变睡眠障碍和提高睡眠质量;百合配合大枣协助丹参有效控制心悸不安,心血不足,提高睡眠质量;组方中尤其是缬草具有镇静作用,加强大脑皮层抑制过程,降低反射兴奋,它与五味子合用,是睡眠的增效剂;与酸枣仁合用可治疗心悸不安,失眠多梦;与石菖蒲合用可醒脑益心,消除忧虑,心情愉悦,促进入睡;组方中沙棘含多种营养成分,可促进全身细胞代谢,其所含黄酮类对植物神经紊乱有明显调节作用,对神经紧张或刺激引起的睡眠障碍可予以改善;沙棘配五味子、酸栆仁酸甘化阴,有益于治疗临床最常见肝血不足造成的失眠,沙棘配丹参能活血安神,沙棘对肠胃功能失调出现的睡眠障碍也有改善功效。
以上所述的仅是本发明的一些实施方式。对于本领域的普通技术人员来说,在不脱离本发明创造构思的前提下,还可以做出若干变形和改进,这些都属于本发明的保护范围。
Claims (10)
1.一种治疗睡眠障碍的中药颗粒剂,其特征在于:其由如下重量份数的原料制成:
五味子550~650份;
酸枣仁520~560份;
百合330~360份;
丹参320~360份;
石菖蒲320~360份;
沙棘280~320份;
缬草230~270份;
大枣230~270份。
2.如权利要求1所述的治疗睡眠障碍的中药颗粒剂,其特征在于:还包括以下辅料:
甘露醇320~360份;
糊精130~170份;
甜菊甙1~10份;
环状糊精包结物β-CD8~16份。
3.一种治疗睡眠障碍的中药颗粒剂制备方法,其特征在于:其包括以下步骤:
S1)以五味子为原料制备五味子药液A;
S2)以石菖蒲和缬草为原料制备得到挥发油B、药渣C、药液D;
S3)用挥发油B和环糊精包结物β-CD制备得到挥发油包结物;
S4)以酸枣仁、百合、丹参、大枣、药渣C为原料水煎煮得到前液,然后放入药液D和沙棘汁,浓缩得到药液E;
S5)将药液E与五味子药液A合在一起,浓缩后真空干燥得到浸膏粉,然后加入辅料制粒;
S6)所述制粒干燥后再加入步骤S3)所得的挥发油包结物,混合形成颗粒成品。
4.如权利要求3所述的治疗睡眠障碍的中药颗粒剂制备方法,其特征在于:所述步骤S1)包括将550~650份五味子烘干捣碎,过筛,然后采用乙醇回流提取法得到五味子乙醇液,然后回收乙醇得到五味子药液A。
5.如权利要求4所述的治疗睡眠障碍的中药颗粒剂制备方法,其特征在于:所述乙醇回流提取法中,乙醇回流两次,乙醇浓度为60%~80%,每次回流乙醇溶剂用量6~8倍量,每次回流时间为1~2h。
6.如权利要求3所述的治疗睡眠障碍的中药颗粒剂制备方法,其特征在于:所述步骤S2)包括将320~360份石菖蒲与230~270份缬草,粉成细粒,加入8~12倍量水,蒸馏6~8h,提取得到所述挥发油,获取蒸馏后的水溶液为所述药液D,剩下的药渣为所述药渣C。
7.如权利要求3所述的治疗睡眠障碍的中药颗粒剂制备方法,其特征在于:所述步骤S3)包括称取8~16份环糊精包结物β-CD,加入蒸馏水,水浴溶解,在搅拌下加入1:1的乙醇与所述挥发油,加塞,继续恒温下搅拌,置冷箱中冷藏抽滤,依次用适量蒸馏水、无水乙醇洗涤,抽干,减压真空干燥至恒重,得到白色粉末状的所述挥发油包结物。
8.如权利要求3所述的治疗睡眠障碍的中药颗粒剂制备方法,其特征在于:所述步骤S4)包括将酸枣仁、百合、丹参、大枣、药渣C共同煎煮,煎煮2次,每次加水量6~12倍,60%~80%醇沉;合并两次煎煮后的药液,静置,取上清液,然后加入药液D和沙棘汁,共同煎煮至相对密度1.10g/ml(80℃测),加入乙醇使含醇量达到60%~80%,静置12~24h,回收乙醇,得到药液E。
9.如权利要求3所述的治疗睡眠障碍的中药颗粒剂制备方法,其特征在于:所述步骤S5)中采用减压蒸发浓缩工艺,水浴浓缩,浓缩温度为60~80℃,五味子药液A加入后浓缩至半量时,予以静置后过滤,滤液继续浓缩至相对密度为1.38~1.40g/ml(60~65℃测)的稠膏,然后真空干燥得到浸膏粉。
10.如权利要求3所述的治疗睡眠障碍的中药颗粒剂制备方法,其特征在于:所述步骤S5)中的辅料包括320~360份甘露醇、130~170份糊精及1~10份甜菊甙。
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