CN102933210A - 觉醒时间延长剂 - Google Patents
觉醒时间延长剂 Download PDFInfo
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- CN102933210A CN102933210A CN2011800152193A CN201180015219A CN102933210A CN 102933210 A CN102933210 A CN 102933210A CN 2011800152193 A CN2011800152193 A CN 2011800152193A CN 201180015219 A CN201180015219 A CN 201180015219A CN 102933210 A CN102933210 A CN 102933210A
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- awakening time
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- carotene
- time lengthening
- phylloxanthin
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Abstract
本发明提供安全且获得简单、即便与其它的食材或原材料组合也不会产生风味上的问题的适于饮食品或药品用途的具有延长觉醒时间的作用的饮食品、药品原材料。本发明发现了陆地动物、陆地植物或微生物来源的胡萝卜素氧化衍生物具有缩短睡眠时间、延长觉醒时间的作用。
Description
技术领域
本发明涉及以陆地动物、陆地植物或微生物来源的胡萝卜素氧化衍生物为有效成分的觉醒时间延长剂。
背景技术
类胡萝卜素是8个类异戊二烯单元结合而成的烃类胡萝卜素的统称。类胡萝卜素作为天然色素分布在植物、微生物、动物中,包括如β-胡萝卜素等那样以维生素A原的形式具有生理作用的物质、如藏花素、藏花酸等那样的生药有效成分、以及含有这些物质的作为食品的着色料重要的物质。另外,在植物和光合成细菌中,作为光能传递中的辅助酶而为人所知(非专利文献1)。另外最近,在类胡萝卜素中,就鱼贝类或海藻等海洋生物中含有的类胡萝卜素即所谓的海洋类胡萝卜素而言,发现了很多新的作用。
例如,作为羊栖菜或裙带菜等海藻中所含的脂溶性物质之一的岩藻黄质可举出抗肥胖作用(非专利文献2)和中性脂肪的吸收抑制作用(专利文献1)等。
另外发现了,例如在虾、蟹等甲壳类中含有的用作红色色素的虾青素具有生物体内的抗氧化作用(专利文献3)、具有肝功能改善效果(专利文献4)等。而且还发现了虾青素具有改善肌肉损伤或疾病的效果(专利文献2)。
另一方面,作为类胡萝卜素的一种的叶黄素是存在于植物的叶、花、果实或蛋黄等中的色素。叶黄素一直以来作为着色用的食品添加物使用,但由于具有基于抗氧化作用的抑制眼睛疲劳或白内障/老年性黄斑变性等的效果,因而近年来作为功能性食品原材料而备受关注。例如,在专利文献5中公开了配合有叶黄素的眼睛疲劳用组合物。在专利文献6中公开了配合有叶黄素的用于处置黄斑变性的营养辅助剂。
然而,随着生活样式的多样化,在不规律的生活和压力大的现代社会中,基于体内生物钟的睡眠-觉醒的节奏或平衡被打乱、以睡眠障碍为代表的与生理节律障碍有关的疾病迅速地增加。另外,在老年人中,一般睡眠变浅、多见途中觉醒、易于发生睡眠障碍。睡眠障碍的原因多种多样,作为其原因之一,据说活动时间内的运动量少与入睡差有关。因此,需要支持在活动时间可以活跃地活动、结果获得高质量睡眠的生活节奏的原材料。
作为解决这些问题的手段,专利文献7公开了以作为类胡萝卜素之一种的虾青素和/或其酯作为有效成分的昼夜节律正常化组合物。专利文献7所记载的发明中,虾青素通过提高褪黑激素在生物体内的利用率而具有有效地调节昼夜节律的作用,在大鼠实验中是基于通过虾青素使作为大鼠睡眠时间带的光亮期的活动比率降低的作用。即,专利文献7记载的昼夜节律正常化组合物是对睡眠造成影响的组合物。
但是,专利文献7记载的昼夜节律正常化组合物由于是对睡眠时间造成影响的组合物,因而对于以活动时间内的运动量少为原因的入睡差而言还留有是否能够改善的疑问。进而,专利文献7记载的作为昼夜节律正常化组合物的虾青素属于海洋类胡萝卜素,在例如适用于乳制品等饮食品中时,来自原材料的特殊气味成为问题,在风味的方面留有问题。
现有技术文献
专利文献
专利文献1:日本特开2009-173597号公报
专利文献2:日本特表2001-514215号公报
专利文献3:日本特开平2-49091号公报
专利文献4:日本特开平9-124470号公报
专利文献5:日本特开2007-308396号公报
专利文献6:日本专利第3672554号公报
专利文献7:国际公开公报WO01/087291
非专利文献
非专利文献1:天然物化学修订第4版、145页、南光堂
非专利文献2:H.Maeda et al.,Biochemical and Biophysical ResearchCommunication,332(2005)392-397
发明内容
发明要解决的技术问题
本发明鉴于上述情况而完成,本发明要解决的技术问题在于提供安全且获得简单、即便与其它食材或原材料组合也不会产生风味问题的觉醒时间延长剂,另外同时提供使用了上述觉醒时间延长剂的饮食品、食品组合物、药品组合物。
用于解决技术问题的手段
鉴于上述现有的问题,本发明人等进行了深入研究,结果在陆地动物、陆地植物或微生物来源的胡萝卜素氧化衍生物中发现了延长觉醒时间的作用。
即,本发明涉及下述[1]~[24]。
[1]一种觉醒时间延长剂,其以陆地动物、陆地植物或微生物来源的胡萝卜素氧化衍生物为有效成分。
[2]上述[1]所述的觉醒时间延长剂,其中,所述的陆地动物、陆地植物或微生物来源的胡萝卜素氧化衍生物含有羟基、羰基、醚基中的至少1个。
[3]上述[1]或[2]所述的觉醒时间延长剂,其中,所述的陆地动物、陆地植物或微生物来源的胡萝卜素氧化衍生物以叶黄素(lutein)、玉米黄质(zeaxanthin)、藏花素(crocin)、球形烯(spheroidene)、堇菜黄质(violaxanthin)、圆红酵母素醛(torularhodinaldehyde)、圆红酵母素(torularhodin)、辣椒红(capsanthin)、藏红酸(crocetin)、胭脂树橙(bixin)、玄参红酸(azafrin)、β-胡萝卜酮(β-carotenone)、花菱草类胡萝卜素(eschscholtzxanthin)、紫杉紫素(rhodoxanthin)、癸异戊二烯黄素(decaprenoxanthin)中的至少1种以上作为有效成分。
[4]上述[1]~[3]任一项所述的觉醒时间延长剂,其中,所述的陆地动物、陆地植物或微生物来源的胡萝卜素氧化衍生物的有效量为0.1~1500mg/60kg体重。
[5]一种用于延长觉醒时间的药品组合物,其是配合0.01~95质量%的上述[1]~[4]任一项所述的觉醒时间延长剂而成的。
[6]一种用于延长觉醒时间的饮食品,其是配合0.0001~10质量%的上述[1]~[4]任一项所述的觉醒时间延长剂而成的。
[7]一种延长觉醒时间的方法,其包含向对象投予药学有效量的陆地动物、陆地植物或微生物来源的胡萝卜素氧化衍生物的工序。
[8]上述[7]所述的方法,其中,所述的陆地动物、陆地植物或微生物来源的胡萝卜素氧化衍生物含有羟基、羰基、醚基中的至少1个。
[9]上述[7]或[8]所述的方法,其中,所述的陆地动物、陆地植物或微生物来源的胡萝卜素氧化衍生物以叶黄素、玉米黄质、藏花素、球形烯、堇菜黄质、圆红酵母素醛、圆红酵母素、辣椒红、藏红酸、胭脂树橙、玄参红酸、β-胡萝卜酮、花菱草类胡萝卜素、紫杉紫素、癸异戊二烯黄素中的至少1种以上作为有效成分。
[10]上述[7]~[9]任一项所述的方法,其中,所述的陆地动物、陆地植物或微生物来源的胡萝卜素氧化衍生物的有效量为0.1~1500mg/60kg体重。
[11]一种制造对觉醒时间的延长有效的药品组合物的方法,其包含配合0.01~95质量%的上述[1]~[4]任一项所述的觉醒时间延长剂的工序。
[12]一种制造对觉醒时间的延长有效的饮食品的方法,其包含添加0.0001~10质量%的上述[1]~[4]任一项所述的觉醒时间延长剂的工序。
[13]陆地动物、陆地植物或微生物来源的胡萝卜素氧化衍生物在觉醒时间延长剂的制造中的用途。
[14]上述[13]所述的用途,其中,所述的陆地动物、陆地植物或微生物来源的胡萝卜素氧化衍生物含有羟基、羰基、醚基中的至少1个。
[15]上述[13]或[14]所述的用途,其中,所述的陆地动物、陆地植物或微生物来源的胡萝卜素氧化衍生物以叶黄素、玉米黄质、藏花素、球形烯、堇菜黄质、圆红酵母素醛、圆红酵母素、辣椒红、藏红酸、胭脂树橙、玄参红酸、β-胡萝卜酮、花菱草类胡萝卜素、紫杉紫素、癸异戊二烯黄素中的至少1种以上作为有效成分。
[16]上述[13]~[15]任一项所述的用途,其中,所述的陆地动物、陆地植物或微生物来源的胡萝卜素氧化衍生物的有效量为0.1~1500mg/60kg体重。
[17]上述[1]~[4]任一项所述的觉醒时间延长剂在对觉醒时间的延长有效的药品组合物的制造中的用途。
[18]上述[1]~[4]任一项所述的觉醒时间延长剂在对觉醒时间的延长有效的饮食品的制造中的用途。
[19]用于在觉醒时间延长中使用的陆地动物、陆地植物或微生物来源的胡萝卜素氧化衍生物。
[20]上述[19]所述的胡萝卜素氧化衍生物,其含有羟基、羰基、醚基中的至少1个。
[21]上述[19]或[20]所述的胡萝卜素氧化衍生物,其以叶黄素、玉米黄质、藏花素、球形烯、堇菜黄质、圆红酵母素醛、圆红酵母素、辣椒红、藏红酸、胭脂树橙、玄参红酸、β-胡萝卜酮、花菱草类胡萝卜素、紫杉紫素、癸异戊二烯黄素中的至少1种以上作为有效成分。
[22]上述[19]~[21]任一项所述的胡萝卜素氧化衍生物,其中,用于在觉醒时间的延长中使用的有效量为0.1~1500mg/60kg体重。
[23]上述[1]~[4]任一项所述的觉醒时间延长剂,其用于在对于觉醒时间的延长有效的药品组合物的制造中使用。
[24]上述[1]~[4]任一项所述的觉醒时间延长剂,其用于在对于觉醒时间的延长有效的饮食品的制造中使用。
发明效果
本发明的觉醒时间延长剂作为用于缩短睡眠时间、延长觉醒时间的饮食品、药品是有用的。而且,配合有本发明的觉醒时间延长剂的具有觉醒作用的饮食品/饮食品原材料或者药品/药品原材料是以陆地动物、陆地植物或微生物来源的胡萝卜素氧化衍生物作为有效成分的,由于食用经验丰富、副作用少,因而安全性高。而且,原材料来源的特殊气味与以往相比少很多,在风味方面也优异。另外,通过摄取、服用或投予本发明的觉醒时间延长剂,例如可以更长时间地度过白天的觉醒时间、活跃地活动,从而在睡眠时间带可获得优质的睡眠。
附图说明
图1为表示不同大鼠个体在橄榄油投予时和叶黄素投予时的暗期内的觉醒时间的图。
图2为表示不同大鼠个体在橄榄油投予时和叶黄素投予时的暗期内的Non-REM睡眠时间的图。
图3为表示不同大鼠个体在橄榄油投予时和叶黄素投予时的暗期内的REM睡眠时间的图。
图4为在各个大鼠中用平均值表示以橄榄油投予时的暗期内的觉醒时间、Non-REM睡眠时间、REM睡眠时间为基准的叶黄素投予时的暗期内的觉醒时间、Non-REM睡眠时间、REM睡眠时间的增减的图。图中的(*)表示与橄榄油投予时相比、叶黄素投予时在显著水平为10%以下具有显著性差异(p<0.1,t检验);*表示与橄榄油投予时相比、叶黄素投予时在显著水平为5%以下具有显著性差异(p<0.05,t检验)。
具体实施方式
以下详细地说明本发明,但本发明并非限定于以下所述的各个方式。
本发明中的陆地动物、陆地植物或微生物来源的胡萝卜素氧化衍生物只要是含有类胡萝卜素的例如蔬菜、果实、微生物等来源的胡萝卜素氧化衍生物,则无特别限定。本发明的胡萝卜素氧化衍生物可以含有羟基、羰基、醚基中的至少1个。
作为本发明的胡萝卜素氧化衍生物的一个例子,举出叶黄素进行以下说明。
叶黄素(lutein)丰富地含有在蔬菜、水果、植物中。是特别在羽衣甘蓝、球芽甘蓝、菠菜、西兰花等绿黄色蔬菜或金盏花等黄色的花等植物界中广泛存在的类胡萝卜素之一。其中,在菊科的金盏花的花瓣中高浓度地含有,一直以来作为饲料用于家禽类的蛋黄的着色强化用途,近年来还作为有效利用了其鲜明黄色的食品着色料而使用。而且,还已知叶黄素会改善老年性黄斑变性或白内障等眼疾病。叶黄素的CAS No.是127-40-2,另外叶黄素的别名还称为(3R,3'R,6'R)-β,ε-胡萝卜素-3,3'-二醇((3R,3'R,6'R)-β,ε-carotene-3,3'-diol)、(3R,3'R,6'R)-3,3'-二羟基-β,ε-胡萝卜素((3R,3'R,6'R)-3,3'-Dihydroxy-β,ε-carotene),或者还称为狭义的胡萝卜醇(Xanthophyll)。叶黄素属于胡萝卜素的醇衍生物,市售的有Lutein 20S(含叶黄素20质量%,协和发酵生物)等。Lutein 20S是含有20%的金盏花的花瓣来源的叶黄素的红褐色热软化性糊料。
叶黄素的提取除了在室温或经加热的状态下使上述植物或微生物含浸在溶剂中或者使用索氏(Soxhlet)提取器等提取器具进行的溶剂提取之外,还可利用:使用水蒸气蒸馏等蒸馏法进行提取的方法;使二氧化碳形成超临界状态进行的超临界提取法;或者进行压榨获得提取物的压榨法;进行冷冻干燥并向其中添加蒸馏水后除去残渣而获得上清的方法等。另外,还可使用果汁等直接经过喷雾干燥等处理后的物质。
作为上述提取中使用的提取溶剂,极性溶剂、非极性溶剂的任一种均可使用,还可将它们混合后使用。例如可举出水;甲醇、乙醇、丙醇、丁醇等醇类;乙二醇、丙二醇、丁二醇等多元醇类;丙酮、甲乙酮等酮类;乙酸甲酯、乙酸乙酯等酯类;四氢呋喃、二乙基醚等链状及环状醚类;聚乙二醇等聚醚类;二氯甲烷、氯仿、四氯化碳等卤代烃类;己烷、环己烷、石油醚等烃类;苯、甲苯等芳香族烃类;吡啶类;超临界二氧化碳;油脂、蜡、其它油等,这些物质可单独使用或者组合2种以上使用,还可改变溶剂反复进行。其中优选使用水、乙醇、丙二醇、丁二醇等,更优选使用水和乙醇的混合液。
另外,作为提取物的分离纯化手段,例如可举出对提取物进行活性炭处理、液液分配、柱色谱法、液相色谱法、凝胶过滤、精密蒸馏等。
除了叶黄素之外,作为本发明的胡萝卜素氧化衍生物的例子,还包含作为属于胡萝卜素的醇衍生物(玉米黄质等)、苷(藏花素等)、醚衍生物(球形烯等)、环氧化物衍生物(堇菜黄质等)、醛衍生物(圆红酵母素醛等)和羧酸衍生物(圆红酵母素等)以及阿朴类胡萝卜素(藏红酸、胭脂树橙、玄参红酸等)、裂环类胡萝卜素(β-胡萝卜酮等)、退类胡萝卜素(花菱草类胡萝卜素、紫杉紫素等)、高级类胡萝卜素(癸异戊二烯黄素等)的胡萝卜素氧化衍生物、且为陆地动物、陆地植物或微生物来源的物质。作为其例子,可以举出:
玉米黄质(zeaxanthin,也称为(3R,3'R)-β,β-胡萝卜素-3,3'-二醇,CAS No.为144-68-3,分布在玉米种子、锦灯笼的果实等中,可由Fluka、EXTRASYNTHESE S.A.等获得)、
藏花素(crocin,也称为8,8'-二阿朴-ψ,ψ-胡萝卜素-8,8'-二元酸双(6-O-β-D-吡喃葡萄糖基-β-D-吡喃葡萄糖基)酯,CAS No.为42553-65-1,分布在藏红花的柱头、栀子花的果实等中,可由Sigma、EXTRASYNTHESES.A.等获得)、
球形烯(spheroidene,也称为3,4-二脱氢-1,2,7',8'-四氢-1-甲氧基-ψ,ψ-胡萝卜素,CAS No.为13836-61-8,分布在球形红假单胞菌(细菌)等中)、
堇菜黄质(violaxanthin,也称为5α,6α:5'α,6'α-双羟基-5,5',6,6'-四氢-β,β-胡萝卜素-3β,3β'-二醇,CAS No.为126-29-4,分布在三色堇的花瓣等以及多数的绿叶或果实中,可由CaroteNature等获得)、
圆红酵母素醛(也称为torularhodinaldehyde,分布在红酵母属的酵母等中)、
圆红酵母素(torularhodin,也称为3',4'-二脱氢-β,ψ-caroten-16'-羧酸,CAS No.为514-92-1,分布在红酵母属的酵母等中,可由CaroteNature等获得)、
藏红酸(crocetin,也称为8,8'-二阿朴-ψ,ψ-胡萝卜素-8,8'-二元酸,CASNo.为27876-94-4,分布在藏红花的柱头等中,可由EXTRASYNTHESE S.A.等获得)、
胭脂树橙(bixin,也称为(9Z)-6,6'-二阿朴-ψ,ψ-胡萝卜素-6,6'-二元酸6-甲基酯,CAS No.为6983-79-5,分布在胭脂树的果实等中,可由CaroteNature、ChromaDex,Inc.等获得)、
玄参红酸(azafrin,也称为(5R,6R)-5,6-二氢-5,6-二羟基-10'-阿朴-β,ψ-胡萝卜酸,CAS No.为507-61-9,分布在玄参科植物的树干/树根等中)、
β-胡萝卜酮(β-carotenone,也称为5,6,5',6'-二裂环-β,β-caroten-5,6,5',6'-四酮,分布在九里香(Murraya exotica)等中,可由CaroteNature等获得)、
花菱草类胡萝卜素(eschscholtzxanthin,也称为(3S,3'S)-4',5'-二脱氢-4,5'-退-β,β-胡萝卜素-3,3'-二醇,CAS No.为472-73-1,分布在花菱草的花瓣等中)、
紫杉紫素(rhodoxanthin,也称为4',5'-二脱氢-4,5'-退-β,β-胡萝卜素-3,3'-二酮,CAS No.为116-30-3,分布在紫杉的果实等中,可由CaroteNature等获得)、
癸异戊二烯黄素(decaprenoxanthin,也称为(2R,2'R,6R,6'R)-2,2'-双[(E)-4-羟基-3-甲基-2-丁烯基]-ε,ε-胡萝卜素,CAS No.为28368-06-1,分布在脱氢黄杆菌(细菌)、冰状节杆菌(细菌)等中),但并非限定于这些例子。
本发明的觉醒时间延长剂中使用的陆地动物、陆地植物或微生物来源的胡萝卜素氧化衍生物可以直接使用通过上述示例过的方法获得的提取液或分离出的级分,还可适当用溶剂稀释制成稀释液后使用、或者制成浓缩浸膏或干燥粉末、或制备成糊状。
本发明的觉醒时间延长剂具有延长觉醒时间的作用。
另一方面,本发明的觉醒时间延长剂具有缩短睡眠时间的作用。
本发明的陆地动物、陆地植物或微生物来源的胡萝卜素氧化衍生物如后述实施例所示,具有缩短睡眠时间、延长觉醒时间的作用。因此,本发明的陆地动物、陆地植物或微生物来源的胡萝卜素氧化衍生物不仅可作为觉醒时间延长剂使用,还可作为睡眠时间缩短剂使用。进而,还可将本发明的觉醒时间延长剂与其它的添加剂或饮食品原材料组合来用于制造对觉醒时间的延长有效的药品(或也称作药品组合物。以下相同)或饮食品。
本发明的药品或饮食品还可称作“延长觉醒时间的药品组合物或饮食品”、“为了延长觉醒时间而使用的药品组合物或饮食品”、“缩短睡眠时间的药品组合物或饮食品”或者“用于缩短睡眠时间而使用的药品组合物或饮食品”。
本发明的觉醒时间延长剂可以作为发挥延长觉醒时间的作用的、人或动物用的药品、准药品(医药部外品)、食品、功能性食品、病患用食品、特定保健用食品的添加剂来使用。另外,本发明可作为显示延长觉醒时间的人或动物用的药品、准药品、食品、功能性食品、病患用食品、特定保健用食品来应用。进而,不仅可以用于对进行驾驶操作的人员、辅助驾驶操作的人员、医疗服务人员或施工操作人员等因会对本人或他人的生命造成威胁而不允许在操作中睡着的人员;在通常为睡眠的时间带(例如夜间)内进行工作的人员、运动不足者或中老年者、卧床修养人员来进行处置,还可以用于对包括运动员在内的所有人进行处置。
本发明的觉醒时间延长剂例如通过更长时间地度过白天的觉醒时间、能够活跃地进行活动,从而在睡眠时间带中可获得优质的睡眠。另外,由于能够进一步延长觉醒时间,因而可以预防老年人或长期疗养者的长卧不起、延长要求处于觉醒状态的人员的觉醒状态,能够自在地安排生活节奏。
另外,本发明中,在以治疗或预防目的使用觉醒时间延长剂时,优选向对象投予本发明的觉醒时间延长剂。作为本发明的觉醒时间延长剂的投予对象,不仅限于进行驾驶操作的人员、辅助驾驶操作的人员、医疗服务人员或施工操作人员等因会对本人或他人的生命造成威胁而不允许在操作中睡着的人员、在通常为睡眠的时间带(例如夜间)内进行工作的人员、运动不足者或中老年者、卧床修养人员,还可例示出包括运动员在内的所有人,但并非限定于这些例子。
作为将本发明的觉醒时间延长剂作为药品、准药品使用时的投予形态,例如可举出利用片剂、胶囊剂、颗粒剂、散剂、糖浆剂等的经口投予或利用注射剂、栓剂、吸入剂、经皮吸收剂、外用剂等的非经口投予。另外,在制备这些各种剂型的制剂时,可以单独使用本发明的胡萝卜素氧化衍生物(例如叶黄素),或者可以适当组合其它药学上可允许的赋形剂、结合剂、增量剂、崩解剂、表面活性剂、润滑剂、分散剂、缓冲剂、保存剂、矫味剂、香料、覆膜剂、载体、稀释剂等后使用。另外,在这些投予形态中,优选的形态为经口投予,例如在制备经口用液体制剂时,可以添加矫味剂、缓冲剂、稳定化剂等利用常规方法进行制造。
本发明的对觉醒时间延长有效的饮食品的分类或种类并无限定,可以是功能性饮食品、特定保健用饮食品、健康饮食品、看护用饮食品,还可以是点心、乳酸菌饮料、奶酪或酸奶等乳制品、调味料等。对于饮食品的形状也无限定,可以制成固体、液态、流食状、果冻状、软糖状、片状、颗粒状、胶囊状等通常可流通的所有饮食品形状。上述饮食品的制造可通过本领域技术人员的常规方法进行,只要不妨碍本发明的陆地动物、陆地植物或微生物来源的胡萝卜素氧化衍生物的觉醒时间延长作用,则还可添加糖类、蛋白质、脂质、食物纤维、维生素类、生物体所需微量金属(硫酸锰、硫酸锌、氯化镁、碳酸钾等)、香料以及其它的配合物。
另外,配合本发明的觉醒时间延长剂而成的饮食品具体地可通过在各种饮食品、饮食品组合物(例如牛奶、乳饮料、清凉饮料、发酵乳、酸奶、奶酪、面包、饼干、椒盐饼干、披萨、配方奶粉、流食、病患用食品、幼儿用奶粉等食品、哺乳妇用奶粉等食品、营养食品等)中添加以本发明的陆地动物、陆地植物或微生物来源的胡萝卜素氧化衍生物为有效成分的觉醒时间延长剂来制造。另外,还可摄取配合有这些觉醒时间延长剂的饮食品。
本发明的觉醒时间延长剂在这些饮食品或饮食品组合物中的配合量根据其使用形态而有所不同,以本发明的觉醒时间延长剂为叶黄素的情况为一例时,如下所述。在为食品的形态时,通常优选为0.0001~10质量%、更优选为0.001~5质量%、特别优选为0.002~2质量%。在为饮料时,优选为0.001~0.5质量%、更优选为0.005~0.25质量%、特别优选为0.01~0.1质量%。在为药片等食品片剂和/或胶囊剂时,叶黄素优选含有0.1~95质量%、更优选含有1~90质量%、特别优选含有5~50质量%。此外,对于其性状,可以是通常使用的饮食品的状态,例如固体状(粉末、颗粒状等)、糊状、液态、悬浮状或凝胶状的任一种。
在为除上述以外的药品、例如片剂、颗粒剂、胶囊剂等经口用固形制剂、内服液剂、糖浆剂等经口用液体制剂时,如果是叶黄素,通常优选为0.01~95质量%、更优选为5~90质量%、特别优选为10~50质量%。
对于其它成分也无特别限定,当将本发明的以陆地动物、陆地植物或微生物来源的胡萝卜素氧化衍生物为有效成分的觉醒时间延长剂作为饮食品或食品组合物使用时,可以使用水、蛋白质、糖类、脂质、维生素类、矿物质类、有机酸、有机碱、果汁、香料类等作为主成分。作为蛋白质,例如可举出全脂奶粉、脱脂奶粉、部分脱脂奶粉、酪蛋白、乳清粉、乳清蛋白、乳清蛋白浓缩物、乳清蛋白分离物、α-酪蛋白、β-酪蛋白、κ-酪蛋白、β-乳球蛋白、α-乳白蛋白、乳铁蛋白、大豆蛋白、鸡蛋蛋白质、肉蛋白等动植物性蛋白质、它们的水解物;黄油、乳清矿物质、奶油、乳清、非蛋白态氮、唾液酸、磷脂、乳糖等各种乳来源成分等。作为糖类,可举出一般的糖类、加工淀粉(除了糊精之外,还有可溶性淀粉、英国淀粉、氧化淀粉、淀粉酯、淀粉醚等)、食物纤维等。作为脂质,例如可举出猪油、鱼油等、它们的分离油、氢化油、酯交换油等动物性油脂;棕榈油、红花油、玉米油、菜籽油、椰子油、它们的分离油、氢化油、酯交换油等的植物性油脂等。作为维生素类,例如可举出维生素A、胡萝卜素类、维生素B群、维生素C、维生素D群、维生素E、维生素K群、维生素P、维生素Q、烟酸、尼克酸、泛酸、生物素、肌醇、胆碱、叶酸等,作为矿物质类,例如可举出钙、钾、镁、钠、铜、铁、锰、锌、硒、乳清矿物质等。作为有机酸,例如可举出苹果酸、柠檬酸、乳酸、酒石酸等。这些成分可单独使用,还可组合2种以上使用,还可使用合成品和/或大量含有它们的食品。
本发明的觉醒延长剂的有效摄取量(投予量)优选每日为0.1~1500mg/60kg体重、更优选为1~1200mg/60kg体重、特别优选为5~1000mg/60kg体重。
另外,本说明书中引用的全部现有技术文献作为参照纳入本说明书中。
实施例
以下举出实验例、实施例说明本发明,但本发明并非限定于此。另外,本说明书中,%在没有明确说明时是表示质量%。
[实验例1]
<暗期的评价>
在戊巴比妥麻醉下对10周龄的雄性SD大鼠8只将头部切开,在头盖骨的头顶部埋入脑波发射装置(Data Science公司)。之后,通常地饲养3周,将一般状态没有问题的大鼠用于实验。分为对照组(3只)和叶黄素投予组(3只)这2组。将作为20%叶黄素的Lutein 20S(含叶黄素20质量%,协和发酵生物,含20%的金盏花花瓣来源的叶黄素的红褐色热软化性糊料)悬浮在橄榄油中,在16点时以80mg/kg(按叶黄素换算计为16mg/kg)的投予量经口投予给大鼠。对照组在同时间经口投予橄榄油。之后,在包括作为大鼠活动时间带的暗期(19点~次日7点)的前后2小时在内的从17点到次日9点为止的16小时内,利用遥测系统测定大鼠的脑波。所得的脑波数据使用专用的解析软件(Somnologica Science,Medcare公司)进行解析,研究测定时间内的觉醒、Non-REM睡眠、REM睡眠的变化(Biological& Pharmaceutical Bulletin,Vol.30,No.10,2007,p.1895-1897)。
在1周以上的停药期间后,将属于对照组的大鼠作为叶黄素投予组利用与上述相同的方法投予叶黄素,将属于叶黄素投予组的大鼠作为对照组投予橄榄油,进行与上述相同的测定。
将不同大鼠个体的暗期内的觉醒时间、Non-REM睡眠时间、REM睡眠时间分别示于图1、图2、图3。就觉醒时间而言,如图1所示,与作为对照的橄榄油投予相比,通过叶黄素投予,绝大多数的个体的觉醒时间有所延长,平均来说,橄榄油投予下的觉醒时间为368分钟、而叶黄素投予下的觉醒时间为387分钟,可见觉醒时间的延长倾向。就Non-REM睡眠时间而言,如图2所示,与作为对照的橄榄油投予相比,通过经口投予叶黄素,绝大多数的个体的Non-REM睡眠时间缩短,平均来说,橄榄油投予下的Non-REM睡眠时间为249分钟、而叶黄素投予下的Non-REM睡眠时间为229分钟,可见Non-REM睡眠时间的缩短倾向。另外,就REM睡眠时间而言,如图3所示,平均来说,橄榄油投予组的Non-REM睡眠时间为101分钟、而叶黄素投予组为102分钟,未见差异。
取图1~图3所示的不同个体中的叶黄素投予时的各测定项目的值减去橄榄油投予时的各测定项目的值的差值,将各个值的平均值示于图4。由图4可知,通过投予叶黄素,与橄榄油投予时相比,显示了觉醒时间延长约20分的倾向(p<0.10),相反地,与橄榄油投予时相比,Non-REM睡眠时间显著性地缩短了约20分钟(p<0.05)。
产业上的利用可能性
本发明的以陆地动物、陆地植物或微生物来源的胡萝卜素氧化衍生物为有效成分的觉醒时间延长剂可以延长觉醒时间。另外,本发明的觉醒时间延长剂可以以各种形态提供,由于原材料来源的特殊气味少,因而可以简单地利用,可作为延长觉醒时间的饮食品或药品提供。进而,本发明由于对人体的安全性也没有问题,因而可以简单且有效地利用其优异的效果,其利用价值很高。
Claims (6)
1.一种觉醒时间延长剂,其以陆地动物、陆地植物或微生物来源的胡萝卜素氧化衍生物作为有效成分。
2.根据权利要求1所述的觉醒时间延长剂,其中,所述的陆地动物、陆地植物或微生物来源的胡萝卜素氧化衍生物含有羟基、羰基、醚基中的至少1个。
3.根据权利要求1或2所述的觉醒时间延长剂,其中,所述的陆地动物、陆地植物或微生物来源的胡萝卜素氧化衍生物以叶黄素、玉米黄质、藏花素、球形烯、堇菜黄质、圆红酵母素醛、圆红酵母素、辣椒红、藏红酸、胭脂树橙、玄参红酸、β-胡萝卜酮、花菱草类胡萝卜素、紫杉紫素、癸异戊二烯黄素中的至少1种以上作为有效成分。
4.根据权利要求1~3任一项所述的觉醒时间延长剂,其中,所述的陆地动物、陆地植物或微生物来源的胡萝卜素氧化衍生物的有效量为0.1~1500mg/60kg体重。
5.一种用于延长觉醒时间的药品组合物,其是配合0.01~95质量%的权利要求1~4任一项所述的觉醒时间延长剂而成的。
6.一种用于延长觉醒时间的饮食品,其是配合0.0001~10质量%的权利要求1~4任一项所述的觉醒时间延长剂而成的。
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