CN115487239A - 一种治疗失眠伴焦虑抑郁的药物组合物及其制备方法 - Google Patents
一种治疗失眠伴焦虑抑郁的药物组合物及其制备方法 Download PDFInfo
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Abstract
本发明提供一种治疗失眠伴焦虑抑郁的药物组合物及其制备方法,属于药物组合物技术领域。该组合物按照重量份数计,包括以下原料:人参15‑30份、五味子15‑30份、柴胡15‑25份、白芍15‑25份、黄芩15‑25份、远志15‑25份、炒酸枣仁15‑25份、茯神15‑25份、合欢花10‑20份、煅龙骨10‑20份、煅牡蛎10‑20份、炙甘草5‑10份。本发明的中药组合物具有宁心安神,有效地改善患者入睡困难、易醒、醒后难以入睡等情况,减轻焦虑抑郁状态,疏肝解郁,使患者睡眠周期紊乱恢复正常,从而治愈失眠伴焦虑抑郁。
Description
技术领域
本发明属于药物组合物技术领域,具体涉及一种治疗失眠伴焦虑抑郁的药物组合物及其制备方法。
背景技术
失眠是指入睡困难或多梦易醒,导致睡眠质量差、睡眠时间短进而表现出日间疲劳、思睡、注意力不集中的一种主观症状。长期睡眠不足可导致免疫力下降、白天精神不振、乏力,出现工作效率低、学习成绩差,严重时可出现一系列生理和心理疾病。最新流行病学调查显示全球有30-35%的人群遭受不同程度睡眠障碍的困扰,在我国睡眠障碍的问题更为严重,发病率高达45%。随着社会压力的增加、生活节奏的加快、越来越多的失眠患者兼现不同程度的焦虑抑郁状态。因西药副作用大且易耐药,临床中大多数失眠伴焦虑抑郁状态的患者不愿长期选择西药治疗,而目前因有效治疗失眠伴焦虑抑郁的药物非常稀缺,现有药物治疗失眠,副作用大、起效慢,疗程长,总有效率低,对伴有焦虑、抑郁的患者几乎无效。
发明内容
本发明的目的是为了解决现有的药物组合物治疗失眠,副作用大、起效慢,疗程长,且对伴有焦虑、抑郁的患者几乎无效的技术问题,而提供一种治疗失眠伴焦虑抑郁的药物组合物及其制备方法。
本发明首先公开一种治疗失眠伴焦虑抑郁的药物组合物,按照重量份数计,包括以下原料:人参15-30份、五味子15-30份、柴胡15-25份、白芍15-25份、黄芩15-25份、远志15-25份、炒酸枣仁15-25份、茯神15-25份、合欢花10-20份、煅龙骨10-20份、煅牡蛎10-20份、炙甘草5-10份。
优选的是,所述的种治疗失眠伴焦虑抑郁的药物组合物,按照重量份数计,包括以下原料:人参20-25份、五味子20-25份、柴胡18-22份、白芍18-22份、黄芩18-22份、远志18-22份、炒酸枣仁18-22份、茯神18-22份、合欢花12-18份、煅龙骨12-18份、煅牡蛎12-18份、炙甘草6-8份。
优选的是,所述的治疗失眠伴焦虑抑郁的药物组合物的剂型为颗粒剂。
本发明的一种治疗失眠伴焦虑抑郁的药物组合物,其中每个原料的药性和药理如下:
人参:味甘,微苦,平。归脾、肺、心经。大补元气,补五脏,安精神,定魂魄,止惊悸,安神益智。迄今为止,已从人参中分离鉴定了46中人参皂苷,目前,对人参皂苷单体化合物的研究多集中在Rg1、Rb1、Rb2、Re等含量较高的成分,如人参皂苷Rb类具有中枢镇静作用,其中Rb1和Rb2表现为中枢神经抑制,人参皂苷Rg1则表现为中枢神经兴奋,人参皂苷Rb1和Rg1具有益智和抗衰老功能,人参皂苷Re是抗心律失常的有效成分。Rb1、Rb2、Rc混合皂苷具有安定效用;人参水浸剂5g/Kg腹腔注射能明显减少小鼠的自发活动。
五味子:味酸、甘,温。归肺、心、肾经。补肾宁心,养心血、镇惊,宁心、安神。五味子素有广泛的中枢抑制作用,并且有安定作用的特点。五味子醇提取物5mg/kg、10mg/kg灌胃可减少小鼠自发活动,协同戊巴比妥钠对小鼠的睡眠作用,对抗***酸引起的小鼠兴奋,对抗咖啡因、烟碱引起的小鼠惊厥。五味子素10~100mg/kg腹腔注射,随剂量的增加而减少小鼠自发活动, 10mg/kg腹腔注射对抗咖啡因、***酸引起的小鼠兴奋;60~120mg/kg腹腔注射明显延长小鼠巴比妥钠及戊巴比妥钠引起的小鼠睡眠时间;对抗电休克、戊四唑等引起的惊厥。五味子素有广泛的中枢抑制作用,并且有安定作用的特点。
柴胡:气味苦、平,无毒。主心腹肠胃中结气,饮食积聚,寒热邪气,推陈致新。久服轻身、明目、益精。柴胡其成分主要含柴胡皂苷,甾醇,挥发油 (柴胡醇、丁香酚等),脂肪酸(油酸、亚麻油酸、棕榈酸、硬脂酸等)和多糖等。柴胡皂苷具有抗炎作用,对多种致炎剂所致踝关节肿和***增生性炎症均有抑制作用。柴胡皂甙300mg/k,柴胡g腹腔注射,可抑制角叉菜胶、5- 羟色胺、组胺引起的大鼠足跖肿胀,抑制大鼠棉球肉芽肿,同时可使肾上腺肥大,胸腺萎缩。
黄芩:性味苦、寒,归肺经、胆经、脾经、大肠经和小肠经。主清热燥湿、泻火解毒、止血安胎等。黄芩的主要成分包括:黄酮类成分,此外还含有挥发油、苯乙醇昔类、瑙醇、氨基酸、生物碱和微量元素等。黄酮类具有消炎止痛的作用,可抑制多种***增生性疾病。氨基酸、生物碱和微量元素是人体必要的营养物质,相关研究表明黄芩具有除燥热、解心烦等作用,尤其是对睡眠剥夺的大鼠,腹腔注射黄芩素,具有一定的缩短失眠大鼠睡眠潜伏期,延长睡眠时间等作用。
白芍:苦,酸,微寒。归肝,脾经。具有补血,敛阴柔肝,缓急止痛等作用。白芍具有扩张冠状动脉,降低血压作用(d-儿茶精和没食子酸乙酯有抗血栓和抗血小板聚集作用);白芍对四氯化碳、黄曲霉毒素B1.D-半乳糖胺所致肝损伤有明显保护作用;白芍对肠管和在位胃运动有抑制作用,能显著对抗催产素引起的子宫收缩;白芍能抑制小鼠扭体、嘶叫、热板反应,对***抑制扭体反应有协同作用,并能对抗戊四唑所致惊厥等作用。
远志:味苦、辛、温。归心、肾、肺经。《本草正》:“远志,功专心肾,故可镇心止惊,安梦,壮阳益精,强志助力,以其气升,同冉申、甘草能举陷摄精、交接水火”。远志:大鼠口服远志提取物后,在血和胆汁中发现了能延长小鼠戊巴比妥钠睡眠时间的活性物质3,4,5一三甲氧基肉桂酸(TMCA)、甲基一3,4,5一三甲氧基肉桂酸(MTMCA)和对甲氧基肉桂酸(PMCA),提示远志水提物中含有TMCA的天然前提药物。进一步对远志中的活性成分3,4,5-三甲氧基肉桂酸(TMCA)进行研究,在大鼠脑室内注射促肾上腺皮质激素释放激素可增加蓝斑内的去甲肾上腺素含量,该作用可被脑室内注射TMCA而抑制,提示TMCA 可能是通过抑制蓝斑中的去甲肾上腺素的含量而起到镇静作用。远志皂苷E、F、 G等可非竞争性地抑制CAMP磷酸二酯酶,其与婴粟碱相当。
酸枣仁:味甘、酸、平。归肝、胆、心经。养肝、宁心、安神。《别录》:“主烦心不得眠,……虚汗烦渴,补中,益肝气,坚筋骨,助阴气,令人肥健。”《本草拾遗》:“睡多生使,不得睡炒熟。”王好古:“治胆虚不眠,寒也,炒服;治胆实多睡,热也,生用。”《本草汇言》:“敛气安神,荣筋养髓,和胃运脾”。酸枣仁煎剂给大白鼠口服或腹腔注射均表现镇静及嗜眠,无论白天或黑夜,酸枣仁均能表现上述作用。小白鼠口服时与巴比妥类药物表现为协同作用。
茯神:镇静作用。实验动物用茯神10~20g/kg灌胃后,进入安静欲睡状态,但无睡眠现象;对于苯甲酸钠咖啡因兴奋之小鼠,以茯神煎剂5g/kg作腹腔注射,能使其镇静,镇静率为90%,镇静指数3.11;若改用20g/kg灌胃,则镇静率为85.7%,镇静指数1.64。
合欢花:煎水,口服,能显著减少小鼠的自发活动及被动活动,有类似于巴比妥类药物的中枢抑制作用,能够延长戊巴比妥钠、***钠所导致的小鼠麻醉时间,促使阈值下剂量的戊巴比妥钠、异戊巴比妥钠引起得小鼠麻醉,一次给药或着连续给药3天都有显著效果。合欢花水煎剂给家兔口服却未见脑电有改变,也没有抗戊四氮所导致小鼠惊厥作用。
龙骨:实验表明:20%龙骨混悬液20ml/kg给小鼠灌服,能显著增加戊巴比妥钠的催眠率。
牡蛎:牡蛎壳粉末有镇静作用,可抑制小鼠惊厥反应。
本发明还提供一种治疗失眠伴焦虑抑郁的药物组合物的制备方法,包括:
步骤一:将五味子加入溶剂提取,过滤减压浓缩,粉碎,得到五味子粉末;
步骤二:将柴胡、白芍、黄芩、远志、炒酸枣仁、茯神、炙甘草七味药加水煎煮,合并煎液,滤过,滤液浓缩至50℃下相对密度为1.10-1.20,加乙醇使含醇量达50%,搅拌,静置过夜,滤过,滤液回收乙醇,浓缩至相对密度为 1.25-1.30的清膏;
步骤三:将合欢花、煅龙骨、煅牡蛎三味药加水煎煮,滤过,提取药液,药渣加入水,二次煎煮,将药渣经挤压回收药液后,合并药液,得到提取液;
步骤四:将五味子粉末、步骤二的清膏、步骤三的提取液和人参粉混合均匀,减压干燥,得到治疗失眠伴焦虑抑郁的药物组合物。
优选的是,所述的步骤一的溶剂为乙醇。
优选的是,所述的步骤一的提取温度为80℃,每次提取时间为30分钟,提取次数为2次。
优选的是,所述的步骤二的煎煮次数为2次,每次1.5h。
优选的是,所述的步骤三第一次煎煮的时间为60分钟,第二次煎煮时间为 30分钟。
优选的是,所述的步骤四减压干燥的温度为80℃。
本发明的有益效果
本发明提供一种治疗失眠伴焦虑抑郁的药物组合物及其制备方法,该配方中,人参甘温,善入脾胃经而大补元气,五味子味酸,甘、温,益气生津、养心安神,两药配伍,相须为用,为甘温补气生津安神的重要配伍,共为君药;远志味辛,安神定志,酸枣仁养心安神、茯神解郁安神、柴胡升发阳气、白芍柔肝养血、黄芩平抑肝阳六药共奏共疏肝解郁、宁心安神之功为臣药;合欢皮、龙骨、牡蛎共奏疏肝解郁、潜阳安神之效共用为佐药;甘草益气和中,调和诸药为使药。
本发明中药各组分共奏宁心安神、疏肝解郁、益气养阴之功,具有宁心安神,有效地改善患者入睡困难、易醒、醒后难以入睡等情况,减轻焦虑抑郁状态,疏肝解郁,使患者睡眠周期紊乱恢复正常,从而治愈失眠伴焦虑抑郁。本发明全部采用中草药组方,科学配比,无西药长期应用产生的毒副作用。
附图说明
图1为发明实施例1-3的中药颗粒对失眠模型大鼠海马病理形态学的HE染色(×200)照片;
图2为发明实施例1-3及对比例1的中药颗粒对失眠模型大鼠海马病理形态学的电镜照片(×2000)。
具体实施方式
下面结合具体实施例对本发明做进一步详细的说明。
实施例1
一种治疗失眠伴焦虑抑郁的中药组合物颗粒剂,原料组成及重量份数为:
人参23份、五味子23份、远志18份、茯神18份、柴胡18份、白芍18份、黄芩18份、炒酸枣仁18份、合欢花13份、煅龙骨13份、煅牡蛎13份、炙甘草7份。
一种治疗失眠伴焦虑抑郁的中药组合物颗粒剂的制备方法,包括:
将人参粉碎成细粉;
五味子加乙醇加热提取2次,提取温度为80℃,每次提取时间为30分钟过滤,减压回收乙醇并干燥浓缩,粉碎成细粉备用;
将柴胡、白芍、黄芩、远志、炒酸枣仁、茯神、炙甘草七味药加水煎煮2次,每次1.5小时,合并煎液。滤过,滤液浓缩至相对密度为1.10-1.20(50℃),加乙醇使含醇量达50%,搅拌,静置过夜,滤过,滤液回收乙醇,浓缩至相对密度为1.25-1.30的清膏;
将合欢花、煅龙骨、煅牡蛎、三味药加水煎煮60分钟,滤过,提取药液,药渣加入水,二次煎煮30分钟,将药渣经挤压回收药液后,合并药液,得到提取液;
将人参粉,五味子细粉,清膏和提取液混匀,80℃减压干燥,粉碎成细粉,加淀粉及糊精适量,混匀,以乙醇为润湿剂制成颗粒,40℃低温干燥。
实施例2
一种治疗失眠伴焦虑抑郁的中药组合物颗粒剂,原料组成及重量份数为:
人参20份、五味子20份、远志15份、茯神15份、柴胡15份、白芍15份、黄芩15份、炒酸枣仁15份、合欢花10份、煅龙骨10份、煅牡蛎10份、甘草5份。
按照实施例1的方法制备得到治疗失眠伴焦虑抑郁的中药组合物颗粒剂。
实施例3
一种治疗失眠伴焦虑抑郁的中药组合物颗粒剂,原料组成及重量份数为:
人参25份、五味子25份、远志20份、茯神20份、柴胡20份、白芍20份、黄芩20份、炒酸枣仁20份、合欢花15份、煅龙骨15份、煅牡蛎15份、甘草8份。
按照实施例1的方法制备得到治疗失眠伴焦虑抑郁的中药组合物颗粒剂。
对比例1
一种治疗失眠伴焦虑抑郁的中药组合物颗粒剂,原料组成及重量份数为:
人参35份、五味子35份、远志30份、茯神30份、柴胡30份、白芍25份、黄芩30份、炒酸枣仁份30份、合欢花25份、煅龙骨25份、煅牡蛎25份、甘草15份。
按照实施例1的方法制备得到中药组合物颗粒剂。
一、动物实验
通过动物实验来说明本发明中的中药颗粒的治疗效果,用实施例1至实施例 3制成的中药组合物颗粒剂治疗失眠模型大鼠,并将其分别记为实施例1中药组合物颗粒剂、实施例2中药组合物颗粒剂、实施例3中药组合物颗粒剂,经测试,与对照样品相比较如下所示:
1、造模及模型评价
1.1 100只Wister大鼠,健康,雄性,SPF级,2月龄,体重(200±20) g,长春中医药大学提供[动物许可证:SCXK(吉)-2021-002]。
1.2模型复制采用国内外公认的腹腔注射对氯丙氨酸(PCPA)复制模型法建立失眠大鼠模型,将100只大鼠适应性饲养7天后,称量体质量,随机分成空白组(15只),造模组(85只),将0.9%生理盐水中加入碳酸氢钠片调成弱碱性(PH:7.0-8.0)水溶液,将PCPA研磨成细粉按照1ml/100mg配制成混悬液备用,临用前用自动平衡离心机震荡摇匀;每日上午8:00-8:30根据大鼠体质量(400mg/kg)对造模组大鼠进行腹腔注射,空白组给予腹腔注射等剂量弱碱性生理盐水,连续注射2天后大鼠出现昼夜节律混乱,白昼与夜间皆活动不断。
1.3行为学观察第二次腹腔注射(PCPA)12h后,空白组和造模组根据大鼠体质量腹腔注射戊巴比妥钠(按照50ug/mL配比,溶于0.9%生理盐水中,给药剂量35mg/kg,此剂量为预实验测得引起大鼠睡眠的最小阈剂量),将大鼠仰卧位放置于平板上,若大鼠在60s内不翻动,则为翻正反射消失,可视为大鼠入睡,以翻正实验恢复为觉醒。给药与翻正反射消失的时间为睡眠潜伏期(SL);继续记录时间直至大鼠自动翻动身体且在60s内不再将身体翻转过去的时间为睡眠持续时间(ST)。比较空白组与模型组之间(SL与ST)的差异,进行统计分析,P<0.05,有统计学意义,造模成功。(见表1)记录各组大鼠睡眠潜伏期(SL)及睡眠持续时间(ST)
与空白组比较,模型组大鼠SL延长,ST缩短,有统计学意义(P<0.05)。 (见表1)
(注:与模型组组比较:*P<0.05)
2、治疗后行为学数据对比
2.1实验药品
长春中医药大学附属医院提供中药颗粒,由低、中、高剂量组组成,每组中药剂量分别为4、8、12g生药,其分别对应临床剂量的5、20、50倍,每毫升相当生药3.6g。将药物放在冰箱备用,临用时加蒸馏水配制为生药。
将造模成功的大鼠分为空白组、模型组、对照药品(枣仁安神胶囊)组、实施例1中药颗粒剂组、实施例2中药颗粒剂组、实施例3中药颗粒剂组,每组各 15只大鼠。每日给及灌胃给药治疗(空白组组除外),模型组给予等量蒸馏水 (lml/100mg),每天定时定量灌胃给药。
2.2各组大鼠SL与ST的变化
治疗后各组间SL比较:与空白组比较,模型组、对照药品(枣仁安神胶囊) 组、实施例1中药颗粒剂组、实施例2中药颗粒剂组、实施例3中药颗粒剂组大鼠SL延长,差异有统计学意义(P<0.05);与模型组比较,对照药品(枣仁安神胶囊)组、实施例1中药颗粒剂组、实施例2中药颗粒剂组、实施例3中药颗粒剂组大鼠SL缩短,具有统计学意义(P<0.05);与对照药品(枣仁安神胶囊)组比较,实施例1中药颗粒剂组、实施例2中药颗粒剂组、实施例3中药颗粒剂组大鼠SL延长,差异有统计学意义(P<0.05);大鼠SL缩短,具有统计学意义(P<0.05)。
治疗后各组间ST比较:与空白组比较,模型组、对照药品(枣仁安神胶囊) 组、实施例1中药颗粒剂组、实施例2中药颗粒剂组、实施例3中药颗粒剂组大鼠ST缩短,差异有统计学意义(P<0.05);与模型组比较,对照药品(枣仁安神胶囊)组、实施例1中药颗粒剂组、实施例2中药颗粒剂组、实施例3中药颗粒剂组大鼠ST均延长,差异具有统计学意义(P<0.05);与对照药品(枣仁安神胶囊)组比较,实施例1中药颗粒剂组、实施例2中药颗粒剂组、实施例3中药颗粒剂组大鼠大鼠ST延长,具有统计学意义(P<0.05)。(见表2)
(注:与空白组比较*P<0.05;与模型组比较:#P<0.05;与对照药品(枣仁安神胶囊)组比较△P<0.05)。
上述实验结果说明:本发明中药颗粒剂(安神舒郁颗粒)能增加失眠模型大鼠的睡眠时间,缩短失眠模型大鼠的睡眠潜伏期,且疗效优于枣仁安神胶囊。
二、本发明的中药颗粒剂对失眠模型大鼠大脑海马病理学的影响
本研究通过光学显微镜及***(吉林大学基础医学院完成观察),在镜下观察苏木精-伊红(HE)染色海马细微结构变化观测各剂量中药颗粒对失眠模型大鼠海马病理形态学的影响。
1HE染色结果
空白组:神经元排列整齐紧密,层次清晰,细胞数量多,胞质均红染,核大而圆,核仁清晰。(见图1中的A)
模型组:大鼠海马神经细胞分布少,核仁小,染色深,神经胶质细胞核染色深,核仁缩小。(见图1中的B)
实施例1、2、3中药颗粒剂及枣仁安神组:海马神经排列较整齐,胞质较均匀,其中枣仁安神组海马神经元变大(实施例1、2、3中药颗粒剂及枣仁安神组对应见图1中的C、D、E、F)。
2电镜观察结果
空白组:细胞核膜清晰,染色质分布均匀,线粒体结构清晰,粗面内质网丰富。(见图2中的A)。
模型组:大鼠海马神经核膜模糊不清,粗面内质网少,细胞形态空化,线粒体少,溶酶体增多,基质空化。(见图2中的B)。
对照药品(枣仁安神胶囊)组:海马神经核膜欠清晰,染色质分布不均,线粒体结构模糊,异染色质大量聚集。(见图2中的C)
实施例1、2、3中药颗粒剂:海马神经核膜欠清晰,染色质分布较均,线粒体结构清晰,异染色质少量聚集。(见图2中的D、E、F)。
通过上述实验及结果可以说明:实施中药颗粒剂(安神舒郁颗粒)能改善失眠模型大鼠海马神经病理组织学及超微结构,对脑组织有一定的保护作用。
三、临床实验
下面通过临床资料来说明本发明中的中药颗粒的治疗效果,用实施例1至对比例1制成的中药组合物颗粒剂治疗失眠患者,并将其分别记为实施例1中药组合物颗粒剂、实施例2中药组合物颗粒剂、实施例3中药组合物颗粒剂、对比例1 中药组合物颗粒剂,经测试,与对照样品相比较如下所示:
1、病例选择:作为治疗失眠的中药颗粒剂,选择确诊的失眠患者200例,随机分为5组,每组40例。并进行临床观察,失眠患者的年龄在30-70岁不等。
2、药物选择:
在5组失眠患者中选择4组分别使用实施例1-4中的中药颗粒剂,每次1袋,3 次/d,一个月为一疗程,使用3个疗程,剩余一组为样品对照组使用对照样品,每次6粒,3次/d,1个月为1个疗程,使用3个疗程。
疗效判定:
临床痊愈:失眠症状基本消失,夜间总睡眠时间达6小时以上或睡眠时间恢复正常,醒后精力充沛,睡眠深沉,匹兹堡睡眠指数量表(PSQI)总减分值大于5分。
显效:睡眠症状明显改善,睡眠时间较前增加3小时以上,睡眠明显好转,深度增加,匹兹堡睡眠指数量表(PSQI)总减分值3至5分。
有效:失眠症状有好转,睡眠维持时间较前增加不到3小时,症状有所减轻,匹兹堡睡眠指数量表(PSQI)总减分值1至2分。
无效:失眠无明显好转或反而加重,匹兹堡睡眠指数量表(PSQI)总减分值0分。
治疗结果
表3:为失眠患者使用中药颗粒剂和对照样品(枣仁安神胶囊)的治疗情况
以上结果显示,使用了本发明中的中药颗粒剂的治愈例数、见效例数和有效率明显高于样品对照组。可见,本发明中的实施例1中药颗粒剂至实施例3中药颗粒剂对于失眠患者具有较好的疗效,治愈率更高,治愈效果更好。
需要说明的是,对照样品可以在市面上购买。对照样品是一种用于治疗失眠的中药胶囊剂,规格为0.3g×12粒×3/盒,该中药胶囊剂主要成分为枣仁皂苷提取物。
四、典型病例举例:
(1)王先生,1969年生,吉林省长春市人,2013年3月初诊。患者5年来,入睡困难、多梦易醒、急躁、易怒,两胁胀满,头晕,口干、舌红、苔薄黄腻、脉弦略数。辅助检查:PSQI评分为13分。中医诊断:肝郁化火型不寐。口服本发明中的中药颗粒剂,每次12g,3次/d。治疗一月,入睡困难等症状较前好转,PSQI评分为10分,6疗程后,临床症状消失,PSQI评分为7分,随访至2020年2月未复发。
(2)金女士,1976年生,吉林省松原市人,2006年11月初诊。患者2年来,睡眠浅、多梦易醒、心情抑郁、舌质淡红、苔薄黄腻、脉沉弦。辅助检查:PSQI 评分为15分。中医诊断:肝气郁滞型不寐。口服本发明中的中药颗粒剂,每次 12g,3次/d。治疗一月,多梦易醒等症状较前减轻,PSQI评分为12分,4疗程后,临床症状消失,PSQI评分为8分,随访至2016年未复发。
(3)李先生,1977年生,吉林省长春市人,2014年6月初诊。患者1年来,睡眠差,易醒,醒后难以入睡,食欲不振,内心烦闷,大便粘腻,自述睡眠质量受心情影响大,舌质红,苔黄厚腻,脉弦滑。辅助检查:PSQI评分为15分。中医诊断:痰火扰心型不寐。口服本发明中的中药颗粒剂,每次12g,3次/d。治疗一月,睡眠差减轻,PSQI评分为12分;3疗程后,临床症状消失,PSQI评分为7分,随访至2020年未复发。
(4)翟女士,1971年生,黑龙江省哈尔滨市人,2007年6月初诊。患者3年来,睡眠差,易醒,多梦,心悸、纳差、溏便,舌质淡,苔薄白,脉沉细。辅助检查:PSQI评分为12分。中医诊断:心脾两虚型不寐。口服本发明中的中药颗粒剂,每次12g,3次/d。治疗一月,多梦易醒等症状较前减轻,PSQI评分为9 分;5疗程后,临床症状消失,PSQI评分为7分。随访至2015年未复发。
(5)李先生,1974年生,辽宁省沈阳市人,2013年10月初诊。患者2年来,睡眠差,易醒,尿频,腰痛,舌质淡红,苔黄微腻,脉沉弦。辅助检查:PSQI 评分为13分。中医诊断:心肾不交型不寐。口服本发明中的中药颗粒剂,每次 12g,3次/d。治疗一月,睡眠差、尿频等症状较前好转,PSQI评分为10分;3疗程后,临床症状消失,PSQI评分为7分,随访至2018年未复发。
本发明全部采用中草药组方,科学配比,无西药长期应用产生的毒副作用;制得的新药具有突破古方、组合精纯、安全有效、工艺先进、服用携带方便、生物利用度高的优点,因此极具市场竞争力。
Claims (9)
1.一种治疗失眠伴焦虑抑郁的药物组合物,其特征在于,按照重量份数计,包括以下原料:人参15-30份、五味子15-30份、柴胡15-25份、白芍15-25份、黄芩15-25份、远志15-25份、炒酸枣仁15-25份、茯神15-25份、合欢花10-20份、煅龙骨10-20份、煅牡蛎10-20份、炙甘草5-10份。
2.根据权利要求1所述的一种治疗失眠伴焦虑抑郁的药物组合物,其特征在于,所述的种治疗失眠伴焦虑抑郁的药物组合物,按照重量份数计,包括以下原料:人参20-25份、五味子20-25份、柴胡18-22份、白芍18-22份、黄芩18-22份、远志18-22份、炒酸枣仁18-22份、茯神18-22份、合欢花12-18份、煅龙骨12-18份、煅牡蛎12-18份、炙甘草6-8份。
3.根据权利要求1或2所述的一种治疗失眠伴焦虑抑郁的药物组合物,其特征在于,所述的治疗失眠伴焦虑抑郁的药物组合物的剂型为颗粒剂。
4.根据权利要求1所述的一种治疗失眠伴焦虑抑郁的药物组合物的制备方法,其特征在于,包括:
步骤一:将五味子加入溶剂提取,过滤减压浓缩,粉碎,得到五味子粉末;
步骤二:将柴胡、白芍、黄芩、远志、炒酸枣仁、茯神、炙甘草七味药加水煎煮,合并煎液,滤过,滤液浓缩至50℃下相对密度为1.10-1.20,加乙醇使含醇量达50%,搅拌,静置过夜,滤过,滤液回收乙醇,浓缩至相对密度为1.25-1.30的清膏;
步骤三:将合欢花、煅龙骨、煅牡蛎三味药加水煎煮,滤过,提取药液,药渣加入水,二次煎煮,将药渣经挤压回收药液后,合并药液,得到提取液;
步骤四:将五味子粉末、步骤二的清膏、步骤三的提取液和人参粉混合均匀,减压干燥,得到治疗失眠伴焦虑抑郁的药物组合物。
5.根据权利要求1所述的一种治疗失眠伴焦虑抑郁的药物组合物的制备方法,其特征在于,所述的步骤一的溶剂为乙醇。
6.根据权利要求1所述的一种治疗失眠伴焦虑抑郁的药物组合物的制备方法,其特征在于,所述的步骤一的提取温度为80℃,每次提取时间为30分钟,提取次数为2次。
7.根据权利要求1所述的一种治疗失眠伴焦虑抑郁的药物组合物的制备方法,其特征在于,所述的步骤二的煎煮次数为2次,每次1.5h。
8.根据权利要求1所述的一种治疗失眠伴焦虑抑郁的药物组合物的制备方法,其特征在于,所述的步骤三第一次煎煮的时间为60分钟,第二次煎煮时间为30分钟。
9.根据权利要求1所述的一种治疗失眠伴焦虑抑郁的药物组合物的制备方法,其特征在于,所述的步骤四减压干燥的温度为80℃。
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