CN114098085B - 一种具有辅助改善记忆功能的功能性食品组合物及用途 - Google Patents
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Abstract
一种具有辅助改善记忆功能的功能性食品组合物,其特征在于该功能性食品由姜黄3000~5000重量份、山药5000~7000重量份、枸杞子1000~3000重量份、益智2000~4000重量份、黑芝麻1000~3000重量份、人参2000~4000重量份、桃仁2000~4000重量份、维生素A 0.3~0.6重量份、维生素B6 0.01~0.015重量份、维生素B12 0.005~0.007重量份、维生素C 0.1~0.3g重量份、维生素D 0.002~0.006重量份、维生素E 60~80重量份组成。将以上各原料药按照上述重量份配制,经过除杂、净化、晾干、粉碎、制粒或压片或其他工艺制成口服剂型。本发明根据中医药食同源理论及网络药理学大数据分析组方,安神益智、补益补气,具有改善记忆的功能。
Description
技术领域
本发明属于保健食品及医药技术领域,具体涉及一种具有辅助改善记忆功能的功能性食品组合物。
背景技术
记忆是人脑对经历过事物的识记、保持、再现或再认,它是进行思维、想象等高级心理活动的基础。人类的记忆过程与大脑皮层及海马密切相关,心理学认为记忆力分为短期记忆力、中期记忆力和长期记忆力,短期记忆力的实质是大脑实时生理反应的重现,而中期和长期的记忆力则与大脑细胞活动相关。大脑是高级神经活动的物质基础,在人体中扮演最为重要的角色。
记忆功能下降指多种原因导致的记忆力低于正常水平。随着时代的高速发展,生活节奏加快带来的弊病日益凸显:人口老龄化趋势难以逆转、中年人生活压力升高、青少年心理健康问题增加,以及发病率日趋上升的神经性疾病,以上因素都会导致记忆力下降。包括衰老,脑动脉硬化、脑中风、脑炎、老年痴呆,抑郁症,焦虑症,精神分裂症,甲状腺功能低下等多种神经性、精神性、代谢性疾病以及睡眠障碍,长期压力过大,用脑过度,抑郁、自卑、焦虑等持续不良心理状态这类常见原因。记忆力下降可谓是现代人普遍困扰的问题。
目前对于记忆力下降的患者主要是针对其诱发的上游病因对症治疗,但对于记忆功能下降本身,多数采用调整生活方式、调节情绪心态此类间接方法,或在饮食中添加有益于健脑的食品。而中国中医学自古以来就有“药食同源”(又称为“医食同源”)理论。这一理论认为:许多食物既是食物也是药物,食物和药物一样同样能够防治疾病。中医疗法讲求辨证施治,标本兼顾,而且具有疗效平稳、副作用少的特点,更适合用作辅助改善记忆。
记忆力减退的中医认知十分深远:《灵枢·本神》曰:“所以任物者谓之心,心有所忆谓之意,意之所存谓之志,因志而存变谓之思,因思而远慕谓之虑,因虑而处物谓之智。”这里的“忆、意、志、思、虑、智”就包括了含有学习记忆在内的一系列精神意识思维活动。目前市场上治疗记忆力减退的药物很多,但这些药物大部分都有一些不良反应,而且这些药物大都用以治疗神经损伤、脑损伤导致的记忆障碍,普通的记忆力下降人群无法使用。
发明内容
本发明的目的在于提供了一种由药食同源的中药材组成的辅助改善记忆功能的功能性食品组合物。
本发明的上述目的是通过以下技术方案予以实现的:一种具有辅助改善记忆功能的功能性食品组合物,由如下重量份数的各组分组成:
姜黄3000~5000份、山药5000~7000份、枸杞子1000~3000份、益智2000~4000份、黑芝麻1000~3000份、人参2000~4000份、桃仁2000~4000份、维生素A 0.3~0.6份、维生素B6 0.01~0.015份、维生素B12 0.005~0.007份、维生素C 0.1~0.3g份、维生素D0.002~0.006份、维生素E 60~80份。
其中,个组分的质量份优选如下:
组方1:姜黄3000份、山药6000份、枸杞2000份、益智仁4000份、黑芝麻2000份、人参4000份、桃仁2000份、维生素A0.4份、维生素B6 0.012份、维生素B12 0.006份、维生素C0.2g、维生素D 0.005份、维生素E 70份。
组分2:姜黄5000份、山药7000份、枸杞2000份、益智仁2000份、黑芝麻3000份、人参2000份、桃仁4000份、维生素A0.4份、维生素B6 0.012份、维生素B12 0.006份、维生素C0.2g、维生素D 0.005份、维生素E 70份。
所述改善记忆功能的功能性食品组合物,本发明可以加入辅料制成不同的剂型,优选片剂、颗粒剂、胶囊剂等,所用的辅料为一般药学上可接受的辅料。
本发明还提供一种辅助改善记忆功能的功能性食品组合物的制备方法,包括以下步骤:将所述各组分原料除杂、净化、晾干、粉碎,过120目筛,将粉末混匀后,再加入重量比例为50%的乳糖和重量比为34.5%的微晶纤维素,将其混合均匀,然后制粒、干燥;将将干燥后的混合颗粒按重量比加入0.5%的硬脂酸镁总混,制成所需的剂型。
本发明提供了所述组合物的制剂:本发明的保健食品组合物可以根据需要制备成任何适宜的口服制剂,包括片剂,胶囊剂,散剂,颗粒剂,冲剂,泡腾剂或袋泡剂等
本发明各组分功效如下:
姜黄,为姜科植物姜黄Curcuma longa L.的干燥根茎。味辛、苦,性温。归脾、肝经。破血行气,通经止痛。用于胸胁刺痛,胸痹心痛,痛经经闭,症瘕,风湿肩臂疼痛,跌扑肿痛。
山药,为薯蓣科植物薯蓣Dioscorea oppositifolia L.的干燥根茎。味甘,性平。归肺、脾、肾经。健脾,补肺,固肾,益精。用于脾虚食少,倦怠乏力,便溏泄泻,肺虚喘咳,肾虚遗精,带下尿频,内热消渴。
枸杞,为茄科植物宁夏枸杞LyciumbarbarumL.的成熟果实。味甘,性平。归肝、肾、肺经。滋补肝肾,益精明目。主治肝肾阴虚及早衰证。
益智仁,为姜科山姜属植物益智Alpinia oxyphylla Miq.的果实。味辛,性温;归脾、肾经。温脾止泻摄涎,暖肾缩尿固精。主治脾胃虚寒,呕吐,泄泻,腹中冷痛,口多唾涎,肾虚遗尿,尿频,遗精,白浊。
黑芝麻,为胡麻科芝麻属植物芝麻Sesamum indicum L.的黑色种子。味甘,性平;归肝、肾、大肠经。补益精血,润燥滑肠。主治须发早白,头晕眼花,妇女产后乳少,风痹,血虚津枯,肠燥便秘。
人参,为五加科人参属植物人参Panax ginseng C.A.Mey.的根。味甘、微苦,性微温;归肺、脾、心经。大补元气,补脾益肺,生津,安神益智。主治气虚欲脱,脉微欲绝,脾气不足,中气下陷,肺虚喘咳,气短乏力,津伤口渴,虚热消渴,失眠健忘,心悸怔忡,血虚萎黄,阳痿宫冷。
桃仁,为蔷薇科桃属植物桃Prunus persica(L.)Batsch或山桃Prunus davidiana(Carr.)Franch.的干燥成熟种子。味苦、甘,性平;归心、肝、大肠经。活血祛瘀,润肠通便,止咳平喘。主治经闭痛经,瘕瘕痞块,肺痈肠痈,跌扑损伤,肠燥便秘,咳嗽气喘。
维生素A具有促进生长、维持上皮组织如皮肤、结膜、角膜等正常功能的作用,并参与视紫红质的合成,增强视网膜感光力;参与体内许多氧化过程,尤其是不饱和脂肪酸的氧化。
维生素B6为人体内某些辅酶的组成成分,参与多种代谢反应,尤其是和氨基酸代谢有密切关系。功能有抗体的合成、消化系统中胃酸的制造、脂肪与蛋白质利用、维持钠/钾平衡(稳定神经系统)。
维生素B12可以促进甲基转移;参与制造骨髓红细胞,防止恶性贫血,防止大脑神经受到破坏;以辅酶的形式存在时可以增加叶酸的利用率,促进碳水化合物、脂肪和蛋白质的代谢;具有活化氨基酸的作用和促进核酸的生物合成;消除烦躁不安,集中注意力,增强记忆及平衡感。
维生素C为抗体及胶原形成,组织修补(包括某些氧化还原作用),苯丙氨酸、酪氨酸、叶酸的代谢,铁、碳水化合物的利用,脂肪、蛋白质的合成,维持免疫功能,羟化5-羟色胺,保持血管的完整,促进非血红素铁吸收等所必需,同时维生素C还具备有抗氧化,抗自由基的作用,为高效抗氧化剂。
维生素D主要功用是在体内转变为其活性形式后调节钙、磷代谢,促进肠内钙磷吸收和骨质钙化,维持血钙和血磷的平衡,此外还有促进皮肤细胞生长、分化及调节免疫功能的作用。
维生素E能促进生殖,它能促进性激素分泌,使男子精子活力和数量增加,还能够保护T淋巴细胞、保护红细胞,抗自由基氧化、抑制血小板聚集从而降低心肌梗死和脑梗塞的危险性。
上述7种药食同源的天然植物原料和6种维生素协同作用,可发挥辅助改善记忆功能的作用。
本发明与现有技术相比,具有如下优点:
本发明涉及功能性食品组合物:姜黄、山药、枸杞、益智仁、黑芝麻、人参、桃仁7种药食同源中药材与维生素A、维生素B6、维生素B12、维生素C、维生素D、维生素E这6种维生素共13种物质,能够起到改善记忆功能的作用还未见报道。本发明中涉及的中药材均为药食同源,整体味甘性平,不产生寒凉或湿热刺激,归经通达五脏六腑。
此外,本发明同时结合了传统中医药理论和网络药理学大数据分析得到辅助改善记忆组方,并通过广泛认可的动物行为学实验进行验证,具有显著作用,可长期服用。
附图说明
图1为四因素三水平正交表;
图2为实施例1中记忆获得障碍模型小鼠跳台实验的潜伏期;
图3为实施例1中记忆获得障碍模型小鼠跳台实验的错误次数;
图4为实施例1中记忆获得障碍模型小鼠避暗实验的潜伏期;
图5为实施例1中记忆获得障碍模型小鼠避暗实验的错误次数;
图6为实施例1中记忆再现障碍模型小鼠跳台实验的潜伏期;
图7为实施例1中记忆再现障碍模型小鼠跳台实验的错误次数;
图8为实施例1中记忆再现障碍模型小鼠避暗实验的潜伏期;
图9为实施例1中记忆再现障碍模型小鼠避暗实验的错误次数;
图10为本发明7味主药姜黄、山药、枸杞、益智仁、黑芝麻、人参、桃仁的成分-靶点网络图;其中最外圈代表靶点,椭圆形内部代表成分,菱形内部代表药材;
图11为本发明7味主药姜黄、山药、枸杞、益智仁、黑芝麻、人参、桃仁根据成分-靶点对应富集到与记忆相关的排名前20的生物过程气泡图;
图12为实施例3中小鼠跳台实验的潜伏期;
图13为实施例3中小鼠跳台实验的错误次数;
图14为实施例3中小鼠避暗实验的潜伏期;
图15为实施例3中小鼠避暗实验的错误次数;
图16为实施例3中小鼠水迷宫连续6天定位航行实验的逃逸潜伏期;
图17为实施例3中小鼠水迷宫连续6天定位航行实验的活动总距离;
图18为实施例3中小鼠水迷宫第七天空间探索实验的目标象限停留时间;
图19为实施例3中小鼠水迷宫第七天空间探索实验的穿越目标象限次数
图20为实施例4中小鼠跳台实验的潜伏期;
图21为实施例4中小鼠跳台实验的错误次数;
图22为实施例4中小鼠避暗实验的潜伏期;
图23为实施例4中小鼠避暗实验的错误次数。
具体实施方式
以下通过实施例形式,对本发明的上述内容再作进一步的详细说明,但不应将此理解为本发明上述主题的范围仅限于以下的实例,凡基于本发明上述内容所实现的技术均属于本发明的范围。
实施例1:
最优组方筛选实验。根据四因素三水平正交表设计各组分比例,筛选最优组方(见表1,图1)
组方1:枸杞3份、姜黄5份、山药5份、益智3份、黑芝麻1份、人参4份、桃仁2份。
组方2:枸杞2份、姜黄3份、山药7份、益智2份、黑芝麻3份、人参3份、桃仁2份。
组方3:枸杞3份、姜黄2份、山药6份、益智4份、黑芝麻2份、人参2份、桃仁4份。
组方4:枸杞2份、姜黄5份、山药7份、益智2份、黑芝麻3份、人参2份、桃仁4份。
组方5:枸杞2份、姜黄3份、山药6份、益智4份、黑芝麻2份、人参4份、桃仁2份。
组方6:枸杞2份、姜黄2份、山药5份、益智3份、黑芝麻1份、人参3份、桃仁2份。
组方7:枸杞2份、姜黄5份、山药6份、益智4份、黑芝麻2份、人参3份、桃仁2份。
组方8:枸杞2份、姜黄3份、山药5份、益智3份、黑芝麻1份、人参2份、桃仁4份。
组方9:枸杞2份、姜黄2份、山药7份、益智2份、黑芝麻3份、人参4份、桃仁2份。
所述组合物的制备方法为:分别称取适量各原料,除杂、净化、晾干、粉碎。过120目筛,将粉末混匀可用于实验。
表1本发明中药组分的四因素三水平正交设计表
1.记忆获得障碍模型小鼠分组、造模以及给药方式
选取5-6月龄,体重18-22g的雄性昆明种小鼠共110只,随机分为11组:空白组、模型组、组方1组、组方2组、组方3组、组方4组、组方5组、组方6组、组方7组、组方8组、组方9组,每组10只。按照人与小鼠体表面积换算等效给药:组方1-9组按相应比例给予3g/kg复方,空白组及模型组给予等剂量水,总计给药30天,期间摄食、饮水自由。实验第31天进行行为学训练,训练前10min除空白组外每只小鼠腹腔注射东莨菪碱5mg/kg,造成记忆获得障碍模型。
1.1、实验方法
1.1.1、跳台实验
在末次给药后次日进行训练。将小鼠放入反应箱中3min以适应环境,然后将小鼠放在反应箱内的铜栅上,并立刻接通36v交流电。训练一次后将小鼠放回,24h后进行重测验。将小鼠放置于平台上,观察3min,记录每只小鼠第一次跳下平台所需时间(即跳台潜伏期)以及小鼠3min内跳下平台的次数(即错误次数)。
1.1.2、避暗实验
在末次给药后次日进行训练。将小鼠背对洞口放入明室,当其进入暗室则会遭到电击。训练一次后将小鼠放回,24h后进行重测验。将小鼠放入明室,记录5min内每只小鼠进入暗室的时间(即避暗潜伏期)以及进入次数(即错误次数)。
1.2、实验结果
1.2.1、跳台实验结果
与空白组相比,模型组小鼠跳台潜伏期明显缩短(P<0.01),与模型组相比,组方1-7组均可延长小鼠跳台潜伏期(P<0.01)。与空白组相比,模型组小鼠错误次数明显增加(P<0.01);与模型组相比,组方1-7组均可减少小鼠错误次数(P<0.01或P<0.05),结果见表2、图2、图3。
注:与空白组相比,**P<0.01;与模型组相比,#P<0.05,##P<0.01
1.2.2、避暗实验结果
与空白组相比,模型组小鼠避暗潜伏期明显缩短(P<0.01),与模型组相比,组方2-8组均可延长小鼠避暗潜伏期(P<0.01或P<0.05)。与空白组相比,模型组小鼠错误次数明显增加(P<0.01);与模型组相比,组方1-9组均可减少小鼠错误次数(P<0.01或P<0.05),结果见表3、图4、图5。
注:与空白组相比,**P<0.01;与模型组相比,#P<0.05,##P<0.01
2.记忆再现障碍模型小鼠分组、造模以及给药方式
选取5-6月龄,体重18-22g的雄性昆明种小鼠共110只,随机分为11组:空白组、模型组、组方1组、组方2组、组方3组、组方4组、组方5组、组方6组、组方7组、组方8组、组方9组,每组10只。按照人与小鼠体表面积换算等效给药:组方1-9组按相应比例给予3g/kg复方,空白组及模型组给予等剂量水,总计给药30天,期间摄食、饮水自由。实验第31天进行行为学训练,训练前10min除空白组外每只小鼠灌胃30%乙醇10mL/kg,造成记忆再现障碍模型。
2.1、实验方法
2.1.1、跳台实验
在末次给药后次日进行训练。将小鼠放入反应箱中3min以适应环境,然后将小鼠放在反应箱内的铜栅上,并立刻接通36v交流电。训练一次后将小鼠放回,24h后进行重测验。将小鼠放置于平台上,观察3min,记录每只小鼠第一次跳下平台所需时间(即跳台潜伏期)以及小鼠3min内跳下平台的次数(即错误次数)。
2.1.2、避暗实验
在末次给药后次日进行训练。将小鼠背对洞口放入明室,当其进入暗室则会遭到电击。训练一次后将小鼠放回,24h后进行重测验。将小鼠放入明室,记录5min内每只小鼠进入暗室的时间(即避暗潜伏期)以及进入次数(即错误次数)。
2.2、实验结果
2.2.1、跳台实验结果
与空白组相比,模型组小鼠跳台潜伏期明显缩短(P<0.01),与模型组相比,组方1-6及8、9组均可延长小鼠跳台潜伏期(P<0.01或P<0.05)。与空白组相比,模型组小鼠错误次数明显增加(P<0.01);与模型组相比,组方1-7组均可减少小鼠错误次数(P<0.01或P<0.05),结果见表4、图6、图7。
注:与空白组相比,**P<0.01;与模型组相比,#P<0.05,##P<0.01
2.2.2、避暗实验结果
与空白组相比,模型组小鼠避暗潜伏期明显缩短(P<0.01),与模型组相比,组方1、2及4-9组均可延长小鼠避暗潜伏期(P<0.01或P<0.05)。与空白组相比,模型组小鼠错误次数明显增加(P<0.01);与模型组相比,组方1-9组均可减少小鼠错误次数(P<0.01或P<0.05),结果见表5、图8、图9。
注:与空白组相比,**P<0.01;与模型组相比,#P<0.05,##P<0.01
3.小结
记忆获得障碍模型小鼠和记忆再现障碍模型小鼠的两项行为学实验结果中,空白组与模型组均有显著性差异,表明东莨菪碱及30%乙醇均可造成小鼠空间记忆障碍。在记忆获得障碍模型中,与模型组相比,组方1-7均能不同程度的改善小鼠跳台潜伏期及错误次数、组方2-8均能不同程度改善小鼠避暗潜伏期及错误次数;在记忆再现障碍模型中,与模型组相比,组方1-6均能不同程度的改善小鼠跳台潜伏期及错误次数、组方1、2及4-9均能不同程度改善小鼠避暗潜伏期及错误次数。综合以上两种模型的行为学数据,组方5改善记忆作用最为明显,故选取组方5为最优组方,用于后期药效学实验。
实施例2:通过网络药理学和大数据分析进行组方
1.实验原理与方法
网络药理学主要通过系统生物学的研究方法,配合统计学的数学手段,将生物学网络与药物作用网络整合的新兴交叉学科。它能够通过网络获知药物对疾病的作用,使药物开发与疾病更好的贴合,使药物开发的成功率上升。中药的成分十分丰富,我们通过网络药理学和生物信息学大数据对中药进行系统研究,分析药物-成分、成分-靶点、靶点-疾病的相互作用,对本发明组合物中7味主药材的成分进行筛选,然后找到这些成分对应的靶点,并将这些靶点与记忆相关靶点取交集,然后将交集靶点对应的基因进行富集分析,为本发明组合物的开发和优化提供了理论支撑。
TCMSP数据库(http://sm.nwsuaf.edu.cn/lsp/tcmsp.php);
Uniprot数据库(http://www.uniprot.org/);
GeneCards数据库(https://www.genecards.org/);
DAVID数据库(https://david.ncifcrf.gov/summary.jsp)。
2.实验结果
本发明的7味主药材共筛选出109种成分,223个靶点,其中与记忆相关靶点取交集共计201个,占到筛选靶点的90%以上,见图2。GO富集分析的气泡图排名前20都与记忆的形成相关,从大数据生物信息学分析的角度。充分说明本发明组方的合理性和具有辅助改善记忆功能的潜在性,如表6、图10、图11所示。
表6气泡图中与记忆形成相关生物过程或通路条目名称
实施例3
最优组方辅助改善记忆作用的药效学评价
选用实施例1中筛选出的最优组方进行药效学评价,以确认其辅助改善记忆力的功效。
最优处方:一种辅助改善记忆功能的功能性食品组合物,由以下原料重量份数的组分组成:姜黄3000份、山药6000份、枸杞2000份、益智仁4000份、黑芝麻2000份、人参4000份、桃仁2000份、维生素A 0.4份、维生素B6 0.012份、维生素B12 0.006份、维生素C 0.2g、维生素D 0.005份、维生素E 70份
所述的组合物的制备方法为:分别称取适量各原料,除杂、净化、晾干、粉碎,过120目筛,将粉末混匀后可用于实验。
1.小鼠分组、造模以及给药方式
选取5-6月龄,体重18-22g的雄性昆明种小鼠共60只,随机分为6组:空白组、模型组、复方低剂量组、复方中剂量组、复方高剂量组、阳性药组,每组10只。按照人与小鼠体表面积换算等效给药:低剂量组1.5g/kg、中剂量组3g/kg、高剂量组6g/kg,阳性药组给予0.75mg/kg多奈哌齐,空白组及模型组给予等剂量水,总计给药30天,期间摄食、饮水自由。实验第31天进行行为学训练,训练前10min除空白组外每组小鼠腹腔注射东莨菪碱5mg/kg,造成记忆获得障碍模型。
2.实验方法
跳台实验
在末次给药后次日进行训练。将小鼠放入反应箱中3min以适应环境,然后将小鼠放在反应箱内的铜栅上,并立刻接通36v交流电。训练一次后将小鼠放回,24h后进行重测验。将小鼠放置于平台上,观察3min,记录每只小鼠第一次跳下平台所需时间(即跳台潜伏期)以及小鼠3min内跳下平台的次数(即错误次数)。
避暗实验
在末次给药后次日进行训练。将小鼠背对洞口放入明室,当其进入暗室则会遭到电击。训练一次后将小鼠放回,24h后进行重测验。将小鼠放入明室,记录5min内每只小鼠进入暗室的时间(即避暗潜伏期)以及进入次数(即错误次数)。
水迷宫实验
在末次给药后次日进行训练,训练期间每日一次持续给药。将小鼠头朝池壁放入水中,记录其60s内找到平台的时间(即潜伏期)以及在池中移动的总路程(即活动总距离)。如果这个时间超过60s,则使用金属棍引导小鼠找到平台,并使其在平台上停留10s。训练结束后将小鼠从池中捞出,放在电油汀上轻轻擦干毛发,然后放回笼内。每只动物每天训练4次,两次训练之间间隔15min,连续训练5d。
最后一次获得性训练结束后次日,将平台撤除进行空间探索实验。将小鼠由原先平台所在的象限的对侧放入水中,记录小鼠60s内在原先平台所在的象限游动的时间(即目标象限停留时间)和进入该象限的次数(即穿越目标象限次数)。
3.实验结果
3.1、跳台实验结果
与空白组相比,模型组小鼠跳台潜伏期明显缩短(P<0.01),与模型组相比,低、中、高剂量组及阳性对照组均可延长小鼠跳台潜伏期(P<0.05或P<0.01或P<0.001)。与空白组相比,模型组小鼠错误次数明显增加(P<0.0001);与模型组相比,中、高剂量组及阳性对照组均可减少小鼠错误次数(P<0.01或P<0.05),结果见表7、图12、图13。
注:与空白组相比,**P<0.01,****P<0.0001;与模型组相比,#P<0.05,##P<0.01,###p<0.001
3.2、避暗实验结果
与空白组相比,模型组小鼠避暗潜伏期明显缩短(P<0.0001),与模型组相比,中、高剂量组及阳性对照组均可延长小鼠避暗潜伏期(P<0.001或P<0.0001)。与空白组相比,模型组小鼠错误次数明显增加(P<0.0001);与模型组相比,低、中、高剂量组及阳性对照组均可减少小鼠错误次数(P<0.01或P<0.05),结果见表8、图14、图15。
注:与空白组相比,****P<0.0001;与模型组相比,##P<0.01,###p<0.001,####p<0.0001
3.3、水迷宫实验结果
在连续5天的定位航行实验中,随着训练时间的增加,空白组小鼠找到平台的潜伏期逐渐缩短,从第三天开始,与空白组相比,模型组小鼠找到平台的潜伏期明显延长(P<0.01或P<0.001):;与模型组相比,第二天中剂量组、阳性药组小鼠水迷宫潜伏期明显缩短(P<0.05);第三、四、五天低、中、高剂量组及阳性药组小鼠水迷宫潜伏期均明显缩短(P<0.05或P<0.01或P<0.001或P<0.0001),结果见表9、图16。
注:与空白组相比,**P<0.01,***P<0.001;与模型组相比,#P<0.05,##P<0.01,###p<0.001,####p<0.0001
在连续5天的定位航行实验中,随着训练时间的增加,空白组小鼠在池中活动的总距离逐渐缩短,从第三天开始,与空白组相比,模型组小鼠在池中活动的总距离明显延长(P<0.001):;与模型组相比,第二天中剂量组、阳性药组小鼠活动总距离明显缩短(P<0.05);第三、四、五天低、中、高剂量组及阳性药组小鼠活动总距离均明显缩短(P<0.05或P<0.01或P<0.001或P<0.0001),结果见表10、图17。
注:与空白组相比,***P<0.001;与模型组相比,#P<0.05,##P<0.01,###p<0.001,####p<0.0001
最后一天的空间探索实验结果表明,与空白组相比,模型组小鼠目标象限停留时间明显缩短(P<0.0001)且穿越目标象限次数明显减少(P<0.001);与模型组相比,低、中、高剂量组及阳性药组小鼠目标象限停留时间均明显增加(P<0.05或P<0.01)且穿越目标象限次数明显增加(P<0.01或P<0.001),结果见表11、图18、图19。
注:与空白组相比,***P<0.001,****P<0.0001;与模型组相比,#P<0.05,##P<0.01,###p<0.001
小结
三项行为学实验中,空白组与模型组相比均有显著差异,证明东莨菪碱可以造成小鼠空间记忆障碍;与模型组相比,跳台实验中最优组方的低、中、高剂量组均能明显延长记忆障碍模型小鼠潜伏期,中、高剂量组能够减少错误次数;避暗实验中最优组方的中、高剂量组能够明显延长记忆障碍模型小鼠潜伏期,低、中、高剂量组均能减少错误次数;水迷宫实验中训练期第三、四、五天,低、中、高剂量组潜伏期及活动总距离明显缩短,第七天撤走平台后低、中、高剂量组在目标象限停留时间及穿越目标象限次数明显增加。证明最优组方的三种剂量组对小鼠的获得性记忆障碍具有明显的改善作用。
实施例4最优组方拆方比较分析
为进一步验证最优组方的科学性和优效性,分别就最优组方中四种主药成分进行了成分替换,分别得到比较方1-4,用于与最优组方功效的对比。
最优组方:一种具有辅助改善记忆功能的功能性食品组合物,由如下重量份数的各组分组成:山药6000份、益智4000份、人参4000份、姜黄3000份、枸杞子2000份、黑芝麻2000份、桃仁2000份、维生素E 70份、维生素A 0.4份、维生素C 0.2g、维生素B6 0.012份、维生素B12 0.006份、维生素D 0.005份。
比较方1:一种具有辅助改善记忆功能的功能性食品组合物,由如下重量份数的各组分组成:当归6000份、益智4000份、人参4000份、姜黄3000份、枸杞子2000份、黑芝麻2000份、桃仁2000份、维生素E 70份、维生素A 0.4份、维生素C 0.2g、维生素B6 0.012份、维生素B12 0.006份、维生素D 0.005份。
比较方2:一种具有辅助改善记忆功能的功能性食品组合物,由如下重量份数的各组分组成:山药6000份、山茱萸4000份、人参4000份、姜黄3000份、枸杞子2000份、黑芝麻2000份、桃仁2000份、维生素E 70份、维生素A 0.4份、维生素C 0.2g、维生素B6 0.012份、维生素B12 0.006份、维生素D 0.005份。
比较方3:一种具有辅助改善记忆功能的功能性食品组合物,由如下重量份数的各组分组成:山药6000份、益智4000份、熟地黄4000份、姜黄3000份、枸杞子2000份、黑芝麻2000份、桃仁2000份、维生素E 70份、维生素A 0.4份、维生素C 0.2g、维生素B6 0.012份、维生素B12 0.006份、维生素D 0.005份。
比较方4:一种具有辅助改善记忆功能的功能性食品组合物,由如下重量份数的各组分组成:山药6000份、益智4000份、人参4000份、茯苓3000份、枸杞子2000份、黑芝麻2000份、桃仁2000份、维生素E 70份、维生素A 0.4份、维生素C 0.2g、维生素B6 0.012份、维生素B12 0.006份、维生素D 0.005份。
所述的组合物制备方法为:分别称取适量各原料,除杂、净化、晾干、粉碎、过120目筛,将粉末混匀后可用于实验。
1.小鼠分组、造模以及给药方式
选取5-6月龄,体重18-22g的雄性昆明种小鼠共80只,随机分为8组:空白组、模型组、最优组方组、比较方1组、比较方2组、比较方3组、比较方4组、阳性药组,每组10只。按照人与小鼠体表面积换算等效给药:比较方1-4组组按相应比例给予3g/kg复方,阳性药组给予0.75mg/kg多奈哌齐,空白组及模型组给予等剂量水,总计给药30天,期间摄食、饮水自由。实验第31天进行行为学训练,训练前10min除空白组外每组小鼠腹腔注射东莨菪碱5mg/kg,造成记忆获得障碍模型。
2.实验方法
跳台实验
在末次给药后次日进行训练。将小鼠放入反应箱中3min以适应环境,然后将小鼠放在反应箱内的铜栅上,并立刻接通36v交流电。训练一次后将小鼠放回,24h后进行重测验。将小鼠放置于平台上,观察3min,记录每只小鼠第一次跳下平台所需时间(即跳台潜伏期)以及小鼠3min内跳下平台的次数(即错误次数)。
避暗实验
在末次给药后次日进行训练。将小鼠背对洞口放入明室,当其进入暗室则会遭到电击。训练一次后将小鼠放回,24h后进行重测验。将小鼠放入明室,记录5min内每只小鼠进入暗室的时间(即避暗潜伏期)以及进入次数(即错误次数)。
实验结果
3.1、跳台实验结果
与空白组相比,模型组小鼠跳台潜伏期明显缩短(P<0.001或P<0.0001),与模型组相比,最优组方组可延长小鼠跳台潜伏期(P<0.001),比较方1-4组无显著性差异。与空白组相比,模型组小鼠错误次数明显增加(P<0.001);与模型组相比,最优组方组可减少小鼠错误次数(P<0.05),比较方1-4组无显著性差异。结果见表12、图20、图21。
注:与空白组相比,***P<0.001,****P<0.0001;与模型组相比,#P<0.05,###p<0.001
3.2、避暗实验结果
与空白组相比,模型组小鼠避暗潜伏期明显缩短(P<0.0001),与模型组相比,最优组方组可延长小鼠避暗潜伏期(P<0.001或P<0.0001),比较方1-4组无显著性差异。与空白组相比,模型组小鼠错误次数明显增加(P<0.0001);与模型组相比,最优组方组可减少小鼠错误次数(P<0.001),比较方1-4组无显著性差异,结果见表13、图22、图23。
注:与空白组相比,****P<0.0001;与模型组相比,###p<0.001,####p<0.0001
3.3、小结
两项行为学实验中,空白组与模型组相比均有显著差异,提示造模成功;与模型组相比,最优组方组能够明显延长记忆障碍小鼠跳台、避暗潜伏期及减少错误次数,而比较方1-4组均未能影响记忆障碍小鼠跳台、避暗潜伏期及错误次数。同时比较方1-4组的跳台、避暗潜伏期及错误次数与最优组方组相比均存在显著性差异,提示更换最优组方中主药任一成分均不能发挥显著功效,最优组方的药材配比即是最优配比,具有发挥功效的唯一重要性。
上述实施例只为说明本发明的技术构思及特点,其目的在于让熟悉此项技术的人士能够了解本发明的内容并据以实施,并不能以此限制本发明的保护范围。凡根据本发明精神实质所作的等效变化或修饰,都应涵盖在本发明的保护范围之内。
Claims (4)
1.一种具有辅助改善记忆功能的功能性食品组合物,其特征在于,所述功能性食品组合物的原料组成按照重量份计算为:姜黄3000~5000重量份、山药5000~7000重量份、枸杞子1000~3000重量份、益智2000~4000重量份、黑芝麻1000~3000重量份、人参2000~4000重量份、桃仁2000~4000重量份、维生素A 0.3~0.6重量份、维生素B6 0.01~0.015重量份、维生素B12 0.005~0.007重量份、维生素C 0.1~0.3g重量份、维生素D 0.002~0.006重量份、维生素E 60~80重量份。
2.根据权利要求1所述的具有辅助改善记忆功能的功能性食品组合物的制备方法,其特征在于,包括如下步骤:
(1)按重量份数称取姜黄、山药、枸杞、益智、黑芝麻、人参、桃仁、维生素A、维生素B6、维生素B12、维生素C、维生素D、维生素E,分别除杂、净化、晾干、粉碎、过120目筛,得各药材粉末;
(2)按比例分别称取(1)步骤所得的药材粉末,再加入重量比例为50%的乳糖和重量比为34.5%的微晶纤维素后混合均匀,然后制粒、干燥;
(3)将(2)步骤干燥后的混合颗粒按重量比加入0.5%的硬脂酸镁总混,制成颗粒剂,或最后压片制成片剂。
3.根据权利要求1或2所述的辅助改善记忆功能的功能性食品组合物,其特征在于,根据需要制成任何适宜的口服制剂,包括片剂,胶囊剂,散剂,颗粒剂,泡腾剂或袋泡剂。
4.一种如权利要求1所述的具有辅助改善记忆功能的功能性食品组合物在制备功能性食品中的用途。
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CN107432473A (zh) * | 2017-09-21 | 2017-12-05 | 珠海霍普金斯医药研究院股份有限公司 | 一种用于预防老年痴呆的功能食品 |
CN109276688A (zh) * | 2018-11-28 | 2019-01-29 | 宁波大学 | 一种用于老年痴呆症的中药组合物 |
RU2719728C1 (ru) * | 2019-06-17 | 2020-04-22 | Боисджони Тохириён | Специализированный пищевой продукт для улучшения процессов запоминания и воспроизведения и способ его получения |
CN113017086A (zh) * | 2021-03-26 | 2021-06-25 | 宁波大学医学院附属医院 | 一种改善脑认知功能、促进机体康复的食品及制备方法 |
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