CN107773609A - 一种具有改善睡眠功能的药物组合物及其制剂 - Google Patents
一种具有改善睡眠功能的药物组合物及其制剂 Download PDFInfo
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Abstract
本发明提供了一种改善睡眠的配方及其制剂工艺，所述配方为五味子酸枣仁混合提取物与γ‑氨基丁酸的组合物，并以五味子酸枣仁混合提取物、γ‑氨基丁酸为核心制成的口服片剂，其重量组成为：五味子酸枣仁混合提取物15‑35份、γ‑氨基丁酸6‑20份，轻质MgO 5‑15份，麦芽糊精5‑20份，羟丙基甲基纤维素1‑10份，羧甲基淀粉钠0.1‑1.5份，硬脂酸镁0.1‑1.2份。本配方及制剂具有养心补肝、宁心安神的功效，针对睡眠障碍有良好的治疗和保健作用。本发明具有疗效确切、无副作用、安全可靠的优点。
Description
技术领域：
本发明属中药制剂技术领域，具体涉及一种改善睡眠的药物组合物及其制剂。
背景技术：
人一生中有1/3的时间是在睡眠中度过的，睡眠是生命所必需的过程，是机体复原、整合和巩固记忆的重要环节，是健康不可缺少的组成部分。据世界卫生组织调查，27％以上的人有睡眠问题。世界睡眠日的一项万人问卷调查显示，国人中有45％存在着不同程度的睡眠障碍。
睡眠障碍主要体现为两种：一种就是睡眠中出现梦游、梦呓、夜惊、梦魇、磨牙、肌肉或肢体不自主跳动等睡眠中发作性异常。另外一种就是睡眠量的不正常。包括睡眠过多，其中有因各种脑病、内分泌障碍、代谢异常导致的嗜睡或昏睡，也有睡眠量不足，整夜睡眠时间少于5小时的表现。最典型的睡眠障碍是入睡困难和失眠。狭义的睡眠障碍多指睡眠不足、入睡困难、失眠、睡眠质量低等。
一旦睡眠出现问题，对机体健康损害极大。从短期效应来看，睡眠障碍直接影响的是第二天的工作与学习，精神萎靡，疲惫无力，情绪不稳，注意力不集中。从长远角度来讲，大多数患者长期失眠，越想睡越睡不着，越急越睡不着，易引发焦虑症；同时睡眠障碍可以是某些疾病的并发症状，失眠也可能导致机体的生理活动发生一系列改变，对机体其他系统的功能亦有影响。长期睡眠障碍可以导致许多神经、精神及亚健康症状。如烦躁、抑郁、警觉和活动能力下降，自主神经功能紊乱、消化功能障碍等；甚至会降低免疫机能，影响身体健康及工作效率，使生活质量下降。据调查，90％以上失眠的患者存在莫名的孤独感、挫败感，65％以上的失眠患者有抑郁症，并有自杀意向。因此，及时纠正睡眠障碍，保证现代人正常、高质量的睡眠是人们身心健康的关键。
发明内容：
本发明所要解决的技术问题是研制一种新型疗效确切、低毒、高效的改善睡眠的中药组合物及制剂，以解决现有技术中存在的问题。
本发明是通过如下技术方案实现的：
本发明所述的药物组合物由五味子、酸枣仁混合提取物，γ-氨基丁酸组成；各组分间的用量为：五味子酸枣仁混合提取物15-35份、γ-氨基丁酸6-20份；
作为优选，本发明的药物组合物中，五味子酸枣仁混合提取物20份、γ-氨基丁酸8份。
所述的五味子、酸枣仁混合提取物通过五味子、酸枣仁按重量比1：1混合后提取制备得到的。
所述的五味子酸枣仁提取物为醇提物，其总木质素含量以五味子乙素计不低于23.9mg/g，总皂苷含量以酸枣仁皂苷A计不低于2.5mg/g。
所述提取物通过如下方法提取：
取等量的五味子和酸枣仁药材，分别低温烘干、粉碎，过筛。称取一定量酸枣仁加入5-10倍量90％乙醇浸泡8-16h后，加入五味子，回流提取1-3次，1-2h/次，过滤，滤液合并，浓缩，微波干燥，得到混合提取物。
本发明所述的药物组合物可以与药学上可接受的载体制备临床上可接受的制剂，所述的制剂可以为片剂，胶囊剂、颗粒剂或口服液。
进一步地，本发明提供了一种五味子、酸枣仁混合提取物、γ-氨基丁酸为主药成分的口服片剂。其重量组成为：五味子酸枣仁混合提取物、γ-氨基丁酸、轻质氧化镁、麦芽糊精、羟丙基甲基纤维素、羧甲基纤维素钠、硬脂酸镁。其中，五味子酸枣仁混合提取物15-35份、γ-氨基丁酸6-20份，轻质MgO 5-15份，麦芽糊精5-20份，羟丙基甲基纤维素1-10份，羧甲基淀粉钠0.1-1.5份，硬脂酸镁0.1-1.2份。
称取五味子酸枣仁混合提取物，加入γ-氨基丁酸、轻质氧化镁、麦芽糊精、羟丙基甲基纤维素、羧甲基纤维素钠、硬脂酸镁，充分混合均匀，压片，包衣。
本发明的技术方案是基于目前非药物治疗失眠方法短期内无法达到理想效果，治疗失眠的常用药物苯二氮卓类，非苯二氮卓类，抗焦虑、抑郁剂类药物均有一定的依赖性，并可影响到正常的睡眠生理机制，而中药的多靶点、多途径作用机制对于复杂病因的失眠症有较强的优势。因此依据中医药理论，结合古代文献及当代报道，朱砂、琥珀、酸枣仁、夜交藤、远志、茯神、合欢皮、珍珠母、大枣、百合等一大批疗效较好的安神药材组成的复方如黄连阿胶汤、温胆汤、酸枣仁汤、安神颗粒等被应用于临床。本方所用药材包括：
五味子：五味子为木兰科植物五味子Schisandra chinensis(Turcz.)Baill.的干燥成熟果实，习称“北五味子”。《神农本草经》中记载：“五味子主治益气，咳逆上气，劳伤赢瘦，补不足，强阴，益男子精”。李时珍在《本草纲目》中说：“酸成人肝而补肾，辛苦人心而补肺，甘人中宫益脾胃”。其气味酸、温、无毒，具有敛肺滋肾、生津止汗、涩精止泻、宁心安神等功效，可用于治疗久嗽虚喘、梦遗滑精、遗尿尿频、久泻不止、自汗、盗汗、津伤口渴、短气脉虚、心悸失眠等。其应用已有2000多年的历史，一直为我国药典所收载。目前主要用于治疗神经衰弱、失眠等症。以往文献报道，五味子的煎剂、酊剂、片剂及五仁醇、木脂素类化学成分都能延长戊巴比妥钠所致小鼠睡眠时间，证明其具有改善睡眠作用。醇甲为五味子仁乙醇提取物中主要有效成分之一。
酸枣仁：酸枣仁为鼠李科植物酸枣Ziziphus jujube Mill.var.spinosa(Bunge)Hu ex H.F.Chow的干燥种子，别名枣仁、酸枣核。《神农本草经》列为上品。《本草纲目》列入木部类。现代《中药学》列入养心安神药类。酸枣仁味甘，性平，有养心补肝、宁心安神、敛汗、生津的功效。用于虚烦不眠，惊悸多梦，体虚多汗、津伤口渴。酸枣仁主要含三萜类、黄酮类、生物碱类等化学成分，已有文献报道黄酮类、皂苷类化合物为改善睡眠的主要有效成分。
γ-氨基丁酸(GABA)：GABA一直被认为与睡眠有关，一些药物的镇静促眠作用是因为它能增加以GABA受体的亲和力以加强GABA与识别位点的结合；也有一些药物能通过抑制GABA的分解以提高其在脑内的含量，也在一定程度上增加慢波睡眠时间。GABA合成神经元分布于脑干、间脑的核团内和投射神经元内。能产生丘脑-皮层纺锤波的丘脑网状核内神经元含有GABA，从而在丘脑皮层投射中起抑制作用。位于下丘脑和前脑基部的GABA神经元向前脑皮层投射，可能与在前脑纪录到的睡眠细胞有关。
本发明针对睡眠障碍的主要病因将上述药物进行组合得到了具有改善睡眠的药物配方。
本发明具有如下优点：(1)绿色天然；(2)疗效确切；(3)无副作用。
具体实施方式：
实施例1：取等量的五味子和酸枣仁药材，分别低温烘干、粉碎，过16目筛。称取一定量酸枣仁加入6倍量90％乙醇浸泡12h后，加入五味子，回流提取2次，1.5h/次，过滤，滤液合并，浓缩，微波干燥，得到混合提取物，备用。
实施例2：称取混合提取物200g，加入γ-氨基丁酸80g，充分混合均匀，得配方1。
实施例3：称取混合提取物150g，加入γ-氨基丁酸60g，充分混合均匀，得配方2。
实施例4：称取混合提取物250g，加入γ-氨基丁酸10g，充分混合均匀，得配方3。
实施例5：以配方1为核心药物组成，进行制剂处方筛选，按照表4配方制备的配方4。
(1)吸收剂的选择
按照提取工艺制得的浸膏由于含有较多的油脂类成分，直接与其他辅料混合制粒后出现物料流动性差、填充不均匀、下料困难、松片等现象，故尝试加入适量的无机盐如碳酸钙、氧化钙、氧化镁、氢氧化铝等吸附油脂后，再进行压片。以休止角及片剂的硬度为指标，设计了以下处方进行筛选，见表1。
表1吸收剂的考察结果
按表1设计的方案进行实验，实验方法如下：按表中规定的量称取原料和稀释剂，加入羧甲基淀粉钠和硬脂酸镁，混合均匀后压片。结果表明：使碳酸钙或氧化镁吸附油脂均可明显改善原料的可压性，且氧化镁更有助于增加片剂的硬度，而磷酸氢钙不利于改善原料的可压性。
(2)填充剂的选择
考察了不同用量的预胶化淀粉分别对压片的影响，以片剂的硬度和崩解时间为指标，设计了以下处方进行筛选，见表2。
表2填充剂的考察结果
按表2设计的方案进行实验，实验方法如下：按表中规定的量称取原料和辅料，混合均匀后压片。结果表明：以8g预胶化淀粉压得的片剂硬度适中、崩解较快。
(3)崩解剂的选择
从羧甲基纤维素钠、交联聚维酮等效果较好的崩解剂中进行筛选，设计了以下处方，见表3。
表3崩解剂的考察结果
按表3设计的方案进行实验，实验方法如下：按表中规定的量称取原料和混合均匀后压片。结果表明：加入羧甲基淀粉钠或交联聚维酮作为崩解剂时均使崩解时限符合相应的规定，综合考虑成本选择羧甲基淀粉钠作为本品的崩解剂。
(4)中试工艺的调整
按照前期小式研究确定的处方及制备工艺进行中式放大研究，崩解时限虽然合格，但硬度较低，包衣后的片剂边缘不整齐且麻片较多，因此改进了处方工艺见表4。
表4工艺调整后的处方
实施例6：各配方对改善睡眠的影响
分为8组，对照组及7个给药组。连续灌胃小鼠30d，0.5g/Kg，末次给样或蒸馏水15min后，各组小鼠腹腔注射50m g/kg戊巴比妥钠，注射量为0.2ml/20g，以翻正反射消失为指标，观察睡眠时间。见表5。
表5各配方对延长戊巴比妥钠睡眠时间的影响
*P<0.05与对照组比较，aP<0.05，与五味子提取物比较，bP<0.05，与酸枣仁提取物组比较，cP<0.05，与γ-氨基丁酸组比较。
Claims (10)
1.一种具有改善睡眠功能的药物组合物，其特征在于：该组合物是由五味子酸枣仁混合提取物、γ-氨基丁酸组成，其重量份数组成为：五味子酸枣仁混合提取物15-35份、γ-氨基丁酸6-20份。
2.根据权利要求1所述的具有改善睡眠功能的药物组合物，其特征在于：所述组合物由下述重量份数的原料配制而成：五味子酸枣仁混合提取物20份、γ-氨基丁酸8份。
3.根据权利要求1或2所述的具有改善睡眠功能的药物组合物，其特征在于：所述的五味子酸枣仁混合提取物是通过五味子、酸枣仁按重量比1：1混合后提取得到的。
4.根据权利要求1-3任何一项所述的具有改善睡眠功能的药物组合物，其特征在于：所述的五味子酸枣仁提取物为醇提物，其总木质素含量以五味子乙素计不低于23.9mg/g，总皂苷含量以酸枣仁皂苷A计不低于2.5mg/g。
5.权利要求1-4任何一项所述的制备方法，其特征在于，所述的五味子酸枣仁混合提取物通过如下方法提取：
取等量的五味子和酸枣仁药材，分别低温烘干、粉碎，过筛。称取一定量酸枣仁加入5-10倍量90％乙醇浸泡8-16h后，加入五味子，回流提取1-3次，1-2h/次，过滤，滤液合并，浓缩，微波干燥，得到混合提取物。
6.一种药物制剂，包含权利要求1-5任何一项所述的具有改善睡眠功能的药物组合物和药学上可接受的载体。
7.根据权利要求6所述的药物制剂，其特征在于，所述的制剂为片剂，胶囊剂、颗粒剂或口服液。
8.根据权利要求7所述的药物制剂，其特征在于，所述的片剂组方为：五味子酸枣仁混合提取物15-35份、γ-氨基丁酸6-20份，轻质MgO 5-15份，麦芽糊精5-20份，羟丙基甲基纤维素1-10份，羧甲基淀粉钠0.1-1.5份，硬脂酸镁0.1-1.2份。
9.如权利要求8所述的药物制剂的制备方法，其特征在于：
1)称取五味子酸枣仁混合提取物15-35份，加入γ-氨基丁酸6-20份充分混合均匀；
2)加入制剂常用的辅料混合均匀后压片。
10.权利要求1-5任何一项所述的具有改善睡眠功能的药物组合物或权利要求6-8任何一项所述的药物制剂在制备改善睡眠功能的保健食品或药物中的应用。
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106492048A (zh) * | 2017-01-03 | 2017-03-15 | 乐康珍品(北京)健康科技有限公司 | 一种促睡眠制剂及其制备方法 |
| CN109432220A (zh) * | 2018-12-28 | 2019-03-08 | 宋昕恬 | 参枣促眠片及其制备方法 |
| CN110584035A (zh) * | 2019-09-29 | 2019-12-20 | 厦门市养真保健食品有限公司 | 一种复方酸枣仁乌梅颗粒及制备方法 |
| CN114377109A (zh) * | 2022-01-18 | 2022-04-22 | 河北御芝林生物科技有限公司 | 一种安神助眠组合物及其制备方法和应用 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101450122A (zh) * | 2008-12-30 | 2009-06-10 | 南京中医药大学 | 一种治疗失眠的中药制剂和制备方法及其应用 |
| CN103054044A (zh) * | 2012-12-26 | 2013-04-24 | 北京康比特体育科技股份有限公司 | 一种改善睡眠的保健食品组合物 |
-
2016
- 2016-08-25 CN CN201610718471.5A patent/CN107773609A/zh active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101450122A (zh) * | 2008-12-30 | 2009-06-10 | 南京中医药大学 | 一种治疗失眠的中药制剂和制备方法及其应用 |
| CN103054044A (zh) * | 2012-12-26 | 2013-04-24 | 北京康比特体育科技股份有限公司 | 一种改善睡眠的保健食品组合物 |
Non-Patent Citations (1)
| Title |
|---|
| 尚迎辉: "酸枣仁汤治疗心肾不交型失眠100例临床观察", 《实用中医内科杂志》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106492048A (zh) * | 2017-01-03 | 2017-03-15 | 乐康珍品(北京)健康科技有限公司 | 一种促睡眠制剂及其制备方法 |
| CN109432220A (zh) * | 2018-12-28 | 2019-03-08 | 宋昕恬 | 参枣促眠片及其制备方法 |
| CN110584035A (zh) * | 2019-09-29 | 2019-12-20 | 厦门市养真保健食品有限公司 | 一种复方酸枣仁乌梅颗粒及制备方法 |
| CN114377109A (zh) * | 2022-01-18 | 2022-04-22 | 河北御芝林生物科技有限公司 | 一种安神助眠组合物及其制备方法和应用 |
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