CN108685961A - 一种改善学习记忆组合物及制剂,其制备方法及应用 - Google Patents
一种改善学习记忆组合物及制剂,其制备方法及应用 Download PDFInfo
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Abstract
本发明公开了一种显著改善学习型记忆组合物,其组成包含姜黄素、雨生红球藻脂溶性抽提物、元宝枫籽油和芹菜籽油,本发明配方组成物质理化性质相似、成分及功能不同、作用机理各异,通过多靶点协同作用达到显著提高学习记忆的技术效果,且对人体无毒副作用,可以广泛用于制备改善学习记忆和预防治疗老年痴呆的药物和保健品,本发明还提供了一种包含上述组合物的软胶囊及其制备方法,其制备方法简单,适于工业化生产。
Description
技术领域
本发明涉及一种改善学习记忆组合物及制剂,其制备方法和应用,属于医药保健品领域。
背景技术
学习和记忆能力是人类赖以生存所必不可缺少的重要脑功能,学习和记忆力下降会严重影响其生活和社会适应能力,大大降低其生活质量和社会存在感。记忆能力的下降甚至退化与人体健康状况、大脑生理老化、大脑创伤以及病理性变化等有着密切的关系。除此之外,经济、社会飞速发展所带来的压力也会导致不同年龄阶层的人出现记忆紊乱,从而影响正常生活。有资料表明,约5%~15%的老年人有不同程度的痴呆症状,严重者给社会和家庭带来很大精神和经济负担。且不少年轻人群由于生活工作压力巨大,出现学习记忆力减退的现象也越来越多。
目前众多研究者已从不同角度提出了记忆力衰退的发病机制学说,如胆碱功能低下假说、基因突变假说、淀粉样蛋白假说、炎症或免疫假说、氧化应激及兴奋性毒性假说、凋亡假说等。然而,医学研究表明,对于老年痴呆症至今还没有特效药物和治疗方法。因此研究开发具有改善学习记忆功能的医药保健品,具有重要的经济和社会应用价值。
发明内容
本发明的目的在于提供一种具有改善学习记忆组合物及制剂,其制备方法和应用。
本发明的目的之一是通过以下技术方案实现的。
一种改善学习记忆能力组合物,按重量份计包含以下组分:姜黄素0.3-2份、雨生红球藻脂溶性抽提物1-3份、元宝枫籽油10-30份、芹菜籽油1-3份。
优选地,上述改善学习记忆能力组合物,按重量份计包含以下组分:姜黄素0.5-1份、雨生红球藻脂溶性抽提物1.2-2份、元宝枫籽油15-20份、芹菜籽油1.5-2份。
上述雨生红球藻脂溶性抽提物制备方法为:新鲜雨生红球藻置高压均质机中破壁,收集藻渣,用CO2超临界萃取4h,温度75℃,压力40MPa,CO2流速25L/h,收集脂溶性抽提物,所得脂溶性抽提物中虾青素含量≥5%。
上述元宝枫籽油制备方法为:元宝枫种仁加热至85~90℃蒸炒40min,选用95型螺旋榨油机物理压榨,得元宝枫籽油,所述元宝枫籽油中神经酸的含量≥5%。
上述芹菜籽油可以直接购买市售样品,或者自行制备,其制备方法为:芹菜籽用烘箱干燥处理后粉碎,过60目筛备用。称取一定量过筛后样品置于圆底烧瓶,加入9倍量蒸馏水,浸泡23h,加热沸腾产生过热水蒸气在常压下蒸馏8h,同时在溶剂瓶中加入适量乙醚,50℃水浴加热,同步循环萃取蒸馏出芹菜籽油,收集油水混合液,加入适量无水硫酸钠干燥除去水分,过滤,滤液旋转蒸发除去溶剂,得淡黄绿色芹菜籽油。
本发明组合物中的姜黄素具有抗炎症、抗氧化、免疫调节、抑制aβ蛋白聚集等作用;元宝枫籽油含有功能性脂肪酸神经酸,是世界科学家公认的、能修复疏通受损大脑神经通路神经纤维并促使神经细胞再生的双效神奇物质,它的缺乏,将会引起脑中风后遗症、老年痴呆、脑瘫、脑萎缩、记忆力减退、失眠健忘等脑疾病;雨生红球藻脂溶性抽提物中主要成分虾青素是世界上最强的天然抗氧化剂之一,抗氧化活性超过现有的抗氧化剂。而芹菜籽油能改善局灶性脑缺血大脑损伤程度,同时对神经细胞也有一定的保护作用。四者联合应用从不同的方面发挥作用,能够有效改善学习记忆力、老年痴呆症等症状。且组合物中四种成分均可用于保健食品,可长期使用,安全无毒。
综上所述,本发明组合物可应用于制备具有改善学习记忆,抗阿尔兹海默病等药品、保健食品、特殊功能性食品等。
本发明还提供了一种改善学习记忆能力软胶囊,其由胶囊内容物、胶皮组成。其中,胶囊内容物由权利要求1-2所述改善学习记忆组合物、0种或几种药学可接受辅料基质组成;胶皮由明胶、甘油、水、药学可接受的遮光剂、药学可接受的着色剂中的1种或几种组成。
所述药学上接受辅料基质为稀释剂、防腐剂、助悬剂等,稀释剂可为聚乙二醇、丙二醇、聚山梨酯、甘油、花生油、玉米油、豆油等,防腐剂选自苯甲酸、山梨酸、三氯叔丁醇、苯甲醇、对羟基苯甲酸甲酯等;助悬剂选自蜂蜡、氢化植物油、氢化蓖麻油、阿拉伯胶、大豆卵磷脂、可可油、辛酸丙二醇酯、辛酸甘油酯、羧甲基纤维素、羟丙基纤维素、羟乙基甲基纤维素等。
所述遮光剂可为二氧化钛、氧化铁或炭黑,所述着色剂可为氧化铁红、苋菜红、胭脂红、柠檬黄或靛蓝等。
其制备方法包含以下步骤:
(1)胶囊内容物制备:按内容物处方量称取各组分,置于洁净容器搅拌混合30min,置胶体磨中研磨2~3次,抽真空脱泡(真空度-0.06~-0.08Mpa)出料,静置2小时,观察混合物均以透明、无气泡,即得胶囊内容物。
(2)溶胶:按胶皮处方量称取明胶、甘油、水,将甘油和水置溶胶罐中加热至40~50℃,投入明胶并升温至70~80℃,搅拌30min,使之完全熔融,加入遮光剂或着色剂,保温1h,抽真空脱泡,观察胶液透明无气泡后过100目筛,60±5℃保温,得胶液。
(3)压丸、定型、洗丸、干燥、捡丸、包装即得。
附图说明
图1、图2为组合物对东莨菪碱诱导记忆获得性障碍小鼠避暗试验行为的影响
图3为组合物对东莨菪碱诱导记忆获得性障碍小鼠脑组织乙酰胆碱酯酶活性的影响
图4为组合物对东莨菪碱诱导记忆获得性障碍小鼠脑组织超氧化物歧化酶活性影响
图5为组合物对东莨菪碱诱导记忆获得性障碍小鼠脑组织丙二醛含量影响
具体实施方式
为了更好的理解本发明,下面通过具体实施例对本发明作进一步说明,但不以任何方式对本发明加以限制,基于本发明教导所作的任何变化或替换,均属本发明保护范围。
下面实施例中所用样品,姜黄素、芹菜籽油直接购买市售样品,雨生红球藻脂溶性抽提物和元宝枫籽油为自制样品,其制备方法见实施例1和2
实施例1雨生红球藻脂溶性抽提物制备
取新鲜雨生红球藻2kg,置高压均质机中破壁,收集藻渣,后用CO2超临界萃取4h,温度75℃,压力40MPa,CO2流速25L/h,收集脂溶性抽提物,制得雨生红球藻脂溶性抽提物550g,其中虾青素含量6%。
实施例2元宝枫籽油制备
取元宝枫种仁4kg,加热至85~90℃蒸炒40min,用95型螺旋榨油机物理压榨,得元宝枫籽油1.4kg,其中神经酸含量为6%。
实施例3组合物软胶囊制备
胶囊内容物处方:组合物198g(其中:姜黄素3g、雨生红球藻脂溶性抽提物30g、元宝枫籽油150g、芹菜籽油15g);辅料基质40g(包含:聚乙二醇400、大豆卵磷脂)。
软胶囊制备:(制成1000粒)
(1)胶囊内容物制备:按内容物处方量称取各组分,置于洁净容器搅拌混合30min,置胶体磨中研磨2~3次,抽真空脱泡(真空度-0.06~-0.08Mpa)出料,静置2小时,观察混合物均以透明、无气泡,即得胶囊内容物。
(2)溶胶:称取明胶200g、甘油100g、水200g,将甘油和水置溶胶罐中加热至40~50℃,投入明胶并升温至70~80℃,搅拌30min,使之完全熔融,加入遮光剂二氧化钛,保温1h,抽真空脱泡,观察胶液透明无气泡后过100目筛,60±5℃保温,得胶液。
(3)压丸、定型、洗丸、干燥、捡丸、包装即得。
实施例4组合物软胶囊制备
胶囊内容物处方:组合物350g(其中:姜黄素20g、雨生红球藻脂溶性抽提物10g、元宝枫籽油300g、芹菜籽油20g)。
软胶囊制备:(制成1000粒)
(1)胶囊内容物制备:按内容物处方量称取各组分,置于洁净容器搅拌混合30min,置胶体磨中研磨2~3次,抽真空脱泡(真空度-0.06~-0.08Mpa)出料,静置2小时,观察混合物均以透明、无气泡,即得胶囊内容物。
(2)溶胶:称取明胶200g、甘油120g、水200g,将甘油和水置溶胶罐中加热至40~50℃,投入明胶并升温至70~80℃,搅拌30min,使之完全熔融,加入遮光剂二氧化钛,保温1h,抽真空脱泡,观察胶液透明无气泡后过100目筛,60±5℃保温,得胶液。
(3)压丸、定型、洗丸、干燥、捡丸、包装即得。
实施例5组合物软胶囊制备
胶囊内容物处方:组合物252g(姜黄素10g、雨生红球藻脂溶性抽提物12g、元宝枫籽油200g份、芹菜籽油30g);辅料基质45g(包含:玉米油、苯甲酸)。
软胶囊制备:(制成1000粒)
(1)胶囊内容物制备:按内容物处方量称取各组分,置于洁净容器搅拌混合30min,置胶体磨中研磨2~3次,抽真空脱泡(真空度-0.06~-0.08Mpa)出料,静置2小时,观察混合物均以透明、无气泡,即得胶囊内容物。
(2)溶胶:称取明胶200g、甘油80g、水190g,将甘油和水置溶胶罐中加热至40~50℃,投入明胶并升温至70~80℃,搅拌30min,使之完全熔融,加入着色剂胭脂红,保温1h,抽真空脱泡,观察胶液透明无气泡后过100目筛,60±5℃保温,得胶液。
(3)压丸、定型、洗丸、干燥、捡丸、包装即得。
实施例6组合物软胶囊制备
胶囊内容物处方:组合物135g(姜黄素5g、雨生红球藻脂溶性抽提物20g、元宝枫籽油100g、芹菜籽油10g);辅料基质22g(包含:聚山梨酯、丙二醇、大豆卵磷脂、山梨酸)。
软胶囊制备:(制成1000粒)
(1)胶囊内容物制备:按内容物处方量称取各组分,置于洁净容器搅拌混合30min,置胶体磨中研磨2~3次,抽真空脱泡(真空度-0.06~-0.08Mpa)出料,静置2小时,观察混合物均以透明、无气泡,即得胶囊内容物。
(2)溶胶:称取明胶200g、甘油120、水220g,将甘油和水置溶胶罐中加热至40~50℃,投入明胶并升温至70~80℃,搅拌30min,使之完全熔融,加入二氧化钛和氧化铁红,保温1h,抽真空脱泡,观察胶液透明无气泡后过100目筛,60±5℃保温,得胶液。
(3)压丸、定型、洗丸、干燥、捡丸、包装即得。
实施例7组合物软胶囊制备
胶囊内容物处方:组合物252g(姜黄素10g、雨生红球藻脂溶性抽提物12g、元宝枫籽油200g、芹菜籽油30g);辅料基质35g(包含:甘油、蜂蜡、对羟基苯甲酸乙酯)。
软胶囊制备:(制成1000粒)
(1)胶囊内容物制备:按内容物处方量称取各组分,置于洁净容器搅拌混合30min,置胶体磨中研磨2~3次,抽真空脱泡(真空度-0.06~-0.08Mpa)出料,静置2小时,观察混合物均以透明、无气泡,即得胶囊内容物。
(2)溶胶:称取明胶200g、甘油100g、水200g,将甘油和水置溶胶罐中加热至40~50℃,投入明胶并升温至70~80℃,搅拌30min,使之完全熔融,加入着色剂芹菜红,保温1h,抽真空脱泡,观察胶液透明无气泡后过100目筛,60±5℃保温,得胶液。
(3)压丸、定型、洗丸、干燥、捡丸、包装即得。
实施例8组合物软胶囊制备
胶囊内容物处方:组合物185g(姜黄素5g、雨生红球藻脂溶性抽提物15g、元宝枫籽150g、芹菜籽油15g)、辅料基质22g(包括:花生油、蜂蜡)。
软胶囊制备:(制成1000粒)
(1)胶囊内容物制备:按内容物处方量称取各组分,置于洁净容器搅拌混合30min,置胶体磨中研磨2~3次,抽真空脱泡(真空度-0.06~-0.08Mpa)出料,静置2小时,观察混合物均以透明、无气泡,即得胶囊内容物。
(2)溶胶:称取明胶200g、甘油110g、水200g,将甘油和水置溶胶罐中加热至40~50℃,投入明胶并升温至70~80℃,搅拌30min,使之完全熔融,加入遮光剂二氧化钛,保温1h,抽真空脱泡,观察胶液透明无气泡后过100目筛,60±5℃保温,得胶液。
(3)压丸、定型、洗丸、干燥、捡丸、包装即得。
下面通过动物实验例1来说明本发明组合物的药理效果
试验例1
实验动物:SPF级雄性KM小鼠,体重20-25g,饲养环境:室温(23±2)℃,相对湿度50%-60%,12/12h明暗交替,自由饮食、摄水。小鼠于实验前7d置于实验室适应环境。
实验动物分组及处理:
将48只KM小鼠随机分成4组,模型+组合物组、模型+脑复康组、模型组和空白对照组。模型组和空白对照组均以等量的生理盐水灌胃,阳性对照组给西药脑复康0.3g/kg,组合物组给予实施例4制备软胶囊内容物0.35g/kg,各组均按10ml/kg/b.w.灌胃给药(空白组和模型组灌胃等量生理盐水),每天一次,连续28d。在最后一次给药1h后,除空白组腹腔注射生理盐水外,其他组均腹腔注射东莨菪碱(3mg/kg/b.w.)制备小鼠学习记忆障碍模型,并于注射20min后进行避暗试验。
避暗试验:
该试验分为习得测试(Acquisition trial)和记忆保持测试(Retention trial)两部分。小鼠灌胃第26天起,连续2d在同一时间将小鼠放入避暗仪中适应5min。第28天腹腔注射东莨菪碱20min后开始习得测试,将小鼠背对拱门放入明箱后,给暗室不锈钢栅栏通以0.3mA电流持续5min,由于小鼠具有趋暗的习性会由明室向暗室探索,小鼠一进入暗室即受电击,其正确反应是回到明室,记录小鼠第1次进入暗室的时间即为避暗潜伏期,步入潜伏期大于5min者弃去不用,5min内小鼠进入暗室的次数即为穿梭次数,作为习得成绩;24h后对小鼠进行记忆保持测试,记录小鼠5min内的潜伏期及进入暗室的次数(即穿梭次数),作为记忆成绩,5min内未进入暗室的小鼠其潜伏期按300s计,穿梭次数计0次。
小鼠血浆、脑组织内生化指标检测:
行为学试验结束后,乙醚麻醉小鼠,摘眼球取血,全血离心后取血清;脱颈椎处死小鼠,迅速于冰上断头取脑,加9倍体积(m/V)的冰生理盐水进行匀浆。4℃离心(3000r/min,10min),取上清液,即为10%组织匀浆。分别按照试剂盒说明书测定脑组织匀浆中乙酰胆碱酯酶活性、过氧化物歧化酶活性和丙二醛活性,采用考马斯亮兰法测定组织蛋白含量。
实验结果:
1.小鼠避暗试验行为表现
试验结果见图1、图2,由图1、图2可知,在习得测试时,各组间潜伏期与穿梭次数均无显著性差异(P>0.05)。在记忆保持测试时,与空白组相比,模型组潜伏期显著缩短,穿梭次数显著增加,表明腹腔注射东莨菪碱使小鼠产生学习记忆障碍。与模型组相比,组合物组和阳性对照组潜伏期显著延长,穿梭次数减少,表明组合物能显著改善痴呆小鼠学习记忆的能力。
2.小鼠脑组织乙酰胆碱酯酶活性
实验结果见图3,从图可以看出与空白组对比,模型组乙酰胆碱酯酶活性显著升高,组合物组和阳性对照组和模型组比较乙酰胆碱酯酶活性均显著降低,说明本发明组合物能够抑制东莨菪碱诱发的胆碱酯酶活性的升高。
3.小鼠脑组织超氧化物歧化酶活性和丙二醛含量
超氧化物歧化酶活性(SOD)是机体内唯一直接特异性地能够使细胞损伤减少的物质,众多研究认为自由基与老年性痴呆症有重要关系,丙二醛(MDA)活性的高低不仅能分析出体内氧自由基水平的高低程度,还能分析出细胞损伤的程度。所以,在测定生化指标时经常同时检测MDA和SOD的活性,机体清除氧自由基能力的高低可以通过SOD活性测定来反映,机体受自由基侵袭的严重度可以通过MDA活性测定来反映。实验结果见图4和图5,结果显示,和对照组比较,模型组小鼠超氧化物歧化酶活性降低,丙二醛含量升高,表明东莨菪碱损伤小鼠清除自由基能力。组合物组和阳性对照组与模型组比较,超氧化物歧化酶活性升高,丙二醛含量降低,表明本发明组合物能提高机体清除自由基能力。与空白组相比,组合物组和阳性对照组超氧化物歧化酶活性,丙二醛活性基本恢复正常水平,说明本发明组合物能够较好的增强东莨菪碱致衰小鼠脑组织中抗氧化酶活力,减少氧化产物含量,从而减轻组织过氧化损伤。
Claims (5)
1.一种改善学习记忆的组合物,其特征在于,所述组合物按重量份计包含以下成分:姜黄素0.3-2份、雨生红球藻脂溶性抽提物1-3份、元宝枫籽油10-30份、芹菜籽油1-3份。
2.如权利要求1所述改善学习记忆的组合物,其特征在于,按重量份计包含以下组分:姜黄素0.5-1份、雨生红球藻脂溶性抽提物1.2-2份、元宝枫籽油15-20份、芹菜籽油1.5-2份。
3.权利要求1-2所述改善学习记忆组合物,在制备具有改善学习记忆,抗阿尔兹海默病等药品、保健食品、特殊功能性食品等方面的应用。
4.一种改善学习记忆软胶囊,其特征在于其由胶囊内容物、胶皮组成,其中,胶囊内容物由权利要求1-2所述改善学习记忆组合物、0种或几种药学可接受辅料基质组成,胶皮由明胶、甘油、水、药学可接受的遮光剂、药学可接受的着色剂中的1种或几种组成。
5.如权利要求4所述改善学习记忆能力软胶囊,其特征在于其制备方法包含以下步骤:
(1)胶囊内容物制备:按内容物处方量称取各组分,置于洁净容器搅拌混合30min,置胶体磨中研磨2~3次,抽真空脱泡,出料,静置2小时,观察混合物均一透明、无气泡,即得胶囊内容物;
(2)溶胶:按处方量称取胶皮配方组成物质,置溶胶罐中加热至70~80℃,搅拌30min使之完全熔融,加入遮光剂或着色剂,保温1h,抽真空脱泡,观察胶液透明无气泡后过100目筛,60±5℃保温,得胶液;
(3)压丸、定型、洗丸、干燥、捡丸、包装即得。
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