CN103717217A - 脑内血清素增加剂 - Google Patents
脑内血清素增加剂 Download PDFInfo
- Publication number
- CN103717217A CN103717217A CN201280036642.6A CN201280036642A CN103717217A CN 103717217 A CN103717217 A CN 103717217A CN 201280036642 A CN201280036642 A CN 201280036642A CN 103717217 A CN103717217 A CN 103717217A
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- CN
- China
- Prior art keywords
- brain
- epicatechin
- serotonin
- flos camelliae
- camelliae japonicae
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Abstract
本发明提供通过口服摄取发挥增加脑内血清素作用的组合物。该组合物是含有表儿茶素的脑内血清素增加剂,所述表儿茶素如下所述获得:对山茶叶进行蒸煮、干燥从而获得干燥的山茶叶,将用蒸馏水或乙醇提取得到的干燥的山茶叶而得的提取物加载于离子交换树脂柱,对20%乙醇洗脱液进行浓缩干燥。
Description
技术领域
本发明涉及造成脑内血清素增加的制剂以及含有所述制剂的饮食品。
背景技术
血清素(5-羟色胺;5-HT)是一种具有生理活性的胺,属于吲哚胺类。在人体中约存在10mg,其中2%存在于中枢神经系统,已知是一种重要的神经递质。中缝核(日文:縫線核)等从脑干向大脑、脊髓广泛映射的中枢血清素激活途径(日文:中枢セロトニン作動性経路),介由其众多的受体亚型,与情绪和心情、睡眠和清醒、食欲、运动、体温以及认知的调节相关(非专利文献1、2)。
脑内神经递质血清素是与精神稳定相关的物质,5-HT的增加具有减轻精神压力的效果。与精神压力特别有关系的有5-HT、γ-氨基丁酸(GABA)、多巴胺(DA)以及去甲肾上腺素(NA)(非专利文献3),如果5-HT不足,会造成情绪不稳定、入睡和睡醒变差等精神不稳定状态。一般认为随着醒来5-HT会增加,5-HT增加的话则能使脑激活,导致轻松状态,引发精神上的积极性,使心情平静(非专利文献4)。
例如抑郁症发病时脑内与情绪和睡眠相关中枢的单胺神经细胞发生NA和5-HT的缺乏,其结果是化学上的传递不足,被认为会导致生理和心理两方面的抑郁症状(非专利文献5)。特别认为5-HT是与抑郁相关的主要因素(非专利文献6),已知自杀者的脑中5-HT浓度下降(非专利文献7)。由此认为如果能增加5-HT,能提高早晨、日间的轻松感,平静情绪,缓和精神压力,被认为与抑郁的改善相关。
至今为止报告的有血清素释放促进作用、血清素再吸收阻断作用等增加脑内血清素作用的原材料有羽衣甘蓝、蜂胶或其提取物(专利文献11)、N-甲氧基苯甲酰-γ-氨基丁酸或对甲氧基苯甲酸(专利文献12)、甘氨酸(非专利文献9)、贯叶连翘(日文:セントジョーンズワート)(非专利文献10)等,作为药物也有选择性血清素再摄取抑制剂(SSRI),但有时会伴有食欲不振、体重增加或减少、性欲异常等副作用,作为血清素增加原材料的选择之一,要求原材料具有稳定性和安全性。
表儿茶素即3,3’,4’,5,7-五羟基黄烷是儿茶素类黄酮之一,在树皮和树干中广泛存在,在儿茶钩藤(黑儿茶;日文:ガンビア)、槟榔子等中含量特别高。而且,结构上2位和3位的碳为不对称碳,因此同一化学结构可有4种结构。这些结构可区分为(-)-儿茶素、(+)-儿茶素、(-)-表儿茶素、(+)-表儿茶素。此处所指表儿茶素为(-)-表儿茶素,已知具有多种生理作用。例如,至今为止公开的有:胰脏β细胞保护剂(专利文献1)、认知功能改善用方法及组合物(专利文献2)、透明质酸酶活性阻断剂(专利文献3)、抗氧化剂及其制造方法以及含有该抗氧化剂的饮食品(专利文献4)、美白用皮肤外用剂(专利文献5)、双歧菌繁殖促进剂(专利文献6)、可用于血管类健康改善的热处理过的可可制品(专利文献7)、脂连蛋白分泌促进组合物及含有该组合物的饮食品(专利文献8)、除臭剂组合物(专利文献9)、类胰蛋白酶活性阻断剂及其应用(专利文献10)等。
对于脑或5-HT,在用微透析法进行的脑灌注试验中可知,儿茶素类对大鼠脑的海马体有增加释放5-HT作用,特别是表儿茶素与表儿茶素没食子酸酯和(+)-儿茶素等其他的儿茶素类相比,有约100倍以上的增加作用。另外,儿茶素经口服投药也观察到了5-HT的释放(非专利文献8)。另外在对突触体进行分离培养的试验体系中,有报告认为表儿茶素对有助于血清素调节的血清素的摄取有阻断效果(非专利文献11)。但是,这些研究未对表儿茶素口服摄取的情况进行评价,另外,由于表儿茶素通过肠道吸收会与硫酸结合或与葡萄糖醛酸结合,不以表儿茶素的状态迁移到脑内,非专利文献11的结果没有对作用到血清素的是否为结合体作出判断。
另外,作为含有表儿茶素的原材料,有绿茶叶、可可豆、葡萄籽、苹果皮、大豆、蚕豆、山茶叶等。
现有技术文献
专利文献
专利文献1:日本特开2008-7452号公报
专利文献2:日本特表2009-539991号公报
专利文献3:日本特开平06-9391号公报
专利文献4:日本特开2007-254508号公报
专利文献5:日本特开平10-120546号公报
专利文献6:日本特开2006-298821号公报
专利文献7:日本特表2009-501161号公报
专利文献8:日本特开2006-131512号公报
专利文献9:日本特开平09-38183号公报
专利文献10:日本特开2007-186457号公报
专利文献11:日本特开2003-300892号公报
专利文献12:日本特开2002-154956号公报
非专利文献
非专利文献1:Annuals New York Academy of Science,600,9-35,1990
非专利文献2:Pharmacology Biochemistry and Behavior,54,129-141,1996
非专利文献3:《新バイオサイエンスシリーズストレス探求-分子レベルで見ると-》,科学同人,京都,81-91,1994
非专利文献4:《セロトニン欠乏脳-キレる脳·欝の脳を鍛え直す-》,日本放送出版协会,东京,49-56,2003
非专利文献5:《うつ病の科学と健康-一般医のための-》,朝仓书店,东京,15-20,1987
非专利文献6:Journal of Pharmacy and Pharmacology,57,651-656,2005
非专利文献7:The British Journal of Psychiatry,113(505),1407-1411,1967
非专利文献8:日本营养粮食学会要点集,2D-13p,2008
非专利文献9:Psychiatry and Clinical Neurosciences,65,142-149,2011
非专利文献10:British Journal of Pharmacology,142,414-418,2004
非专利文献11:Phytomedicine,14,396-402,2007
发明内容
发明所要解决的技术问题
提供通过口服摄取发挥增加脑内血清素作用的组合物。
解决技术问题所采用的技术方案
如上所述,现有技术中,完全未对口服摄取表儿茶素后的情况进行研讨。于是,本发明详细研讨了口服摄取表儿茶素的情况脑内血清素是否增加。其结果是,确认通过仅在大鼠的胃内投入表儿茶素进行单一口服摄取,其脑内血清素增加。另外,发现了作为表儿茶素的原材料的山茶叶,并确认了将其提取物中的表儿茶素浓缩后的组合物能够增加脑内血清素。总之,本发明的解决方法是通过口服摄取含表儿茶素物质、特别是山茶叶提取物能发挥增加脑内血清素的作用。
即,本发明的目的是增加脑内血清素的量,研究的结果是发现通过仅通过胃内给予表儿茶素进行单一口服摄取,其脑内血清素增加。另外,确立了从山茶叶获得不含其他儿茶素而只含高含量表儿茶素的组合物的制备方法,发现其对脑内血清素的增加作用。
发明的效果
确立了能通过口服摄取表儿茶素有效增加脑内血清素,并且从山茶叶获得不含其他儿茶素而只含高含量表儿茶素的组合物的制备方法。
附图说明
图1是表示由给予表儿茶素所得到的5-HT释放量的图。
图2是表示由给予儿茶素混合物所得到的5-HT释放量的图。
具体实施方式
本发明涉及含有表儿茶素的脑内血清素增加剂。
另外,本发明涉及以从山茶叶中提取表儿茶素为特征的含有高表儿茶素组分的脑内血清素增加剂。
并且,本发明涉及由山茶叶获得表儿茶素的制备方法,该方法的特征是:蒸煮山茶叶、干燥处理获得干燥的山茶叶、使获得的干燥山茶叶的蒸馏水或乙醇提取物加载于离子交换树脂柱、通过对20%乙醇洗脱液进行浓缩干燥获得表儿茶素富集的组分。
还有,本发明涉及含有含表儿茶素的脑内血清素增加剂的食品。
本发明涉及口服摄取后能发挥使脑内血清素水平上升效果的组合物。血清素是与心情和清醒相关的脑内神经递质,一般认为可以使心情轻松,提高注意力。因此,可提高血清素水平的组合物可给予调整心情、提高注意力的效果,可期待作为点心和健康食品的功能性原材料使用。
还有,本发明提供上述含有含表儿茶素的脑内血清素增加剂的饮食品。饮食品包括生鲜食品、肉、鱼等动物性食品,谷物、蔬菜等植物性食品,乳制品、面包、即食食品等加工食品,点心类等嗜好食品,甜味剂、调味剂等烹饪调味用材料,保健食品,特殊用途食品,水、清凉饮料水、酒精饮料、茶等饮料,食品加工材料,食品添加剂等。
实施例
[实施例1]
表儿茶素的脑内血清素释放促进效果试验
(试验动物)
本试验使用Wistar系雄性大鼠(270~310g,8~10周龄)。大鼠在约24℃室温和45~50%湿度的环境下,明暗循环12小时饲养。另外饲养中饲料和水均自由摄取。
(试剂类)
本试验使用的试剂是:(-)-表儿茶素[EC(和光(Wako),大阪),纯度98%以上]及儿茶素混合物[Mix(和光,大阪),儿茶素类占85%以上;含有(-)-表没食子儿茶素没食子酸酯(以下称EGCG)约36.2%、(-)-表没食子儿茶素(以下称EGC)约23.2%、(-)-表儿茶素没食子酸酯(以下称ECG)约10.6%、EC约7.4%、(+)-儿茶素(以下称CA)约2.4%、(-)-没食子儿茶素约5.7%、(-)-没食子儿茶素没食子酸酯约1.6%等],分别配制为1mg/kg、10mg/kg、50mg/kg、100mg/kg,各试剂在0.5ml或1ml的生理盐水(0.9%NaCl)中溶解,将各溶液用灌胃器(日文:経口ゾンデ)直接向大鼠胃内给药。另外,作为对照组使用等量的生理盐水。此处各给药组每组使用大鼠4~5只。
(试验方法)
将大鼠用戊巴比妥钠麻醉,以Paxinos和Watson脑地图为参考埋入导向套管。确认导向套管完全固定后,插入虚拟套管(日文:ダミーカニューレ)。在大鼠恢复后,用戊巴比妥钠麻醉,在导向套管中插入透析用探针,灌流(灌流速度1μl/分钟)透析液(标准林格氏液)。每20分钟通过高速液相色谱仪测定透析液中5-HT量。60分钟后,在大鼠胃中投入EC或儿茶素混合物,继续测定直至观察到5-HT的最大释放量。数据一律以平均值(mean)±标准差(SD)表示,统计处理使用统计分析软件SPSS17.0J,使用Mann-Whitney检验(非成对和非参数)及单因素方差分析,危险率不满5%则判断为有显著差异。
(结果)
上述脑内5-HT释放促进效果试验所得的结果如图1和2所示。
由图1可以判明,给予EC的时候,5-HT的释放量为:给予1mg/kg时110±16%、给予10mg/kg时133±10%、给予50mg/kg时513±535%、给予100mg/kg时987±643%,5-HT的释放量随EC的浓度增加(图1)。给予1mg/kg、10mg/kgEC时5-HT的释放量没有大的差异。另外,给予最大浓度100mg/kg EC的时候,5-HT的释放量与给予1mg/kg、10mg/kg EC相比时有显著增加。
另一方面,如图2所示,给予儿茶素混合物(Mix)的时候,5-HT的释放量为:给予1mg/kg时113±12%、给予10mg/kg时135±17%、给予50mg/kg时148±39%、给予100mg/kg时227±112%,5-HT的释放量有随儿茶素混合物的浓度增加的倾向。
比较给予1mg/kg和10mg/kg儿茶素混合物时5-HT的释放量,显示了相同程度的增加,并且发现EC和儿茶素混合物均给予10mg/kg的水平时从脑部海马体释放的5-HT的释放量的浓度没有大幅度的增加。
进一步,比较给予1mg/kg EC和100mg/kg EC时,5-HT的释放量有约9倍的差异。与此相对,给予1mg/kg儿茶素混合物和100mg/kg儿茶素混合物时,儿茶素浓度差为100倍但5-HT的释放量的差约为2倍。
并且,结果显示给予EC50mg/kg和100mg/kg时,5-HT的释放量的增加与给予儿茶素混合物50mg/kg和100mg/kg时相比约高4~5倍。
根据上述,确认了口服摄取中与给予儿茶素混合物相比,给予表儿茶素能使脑内血清素有显著的增加。
[实施例2]
由山茶叶制备表儿茶素富集的组合物-1
将山茶(Camellia japonica)的叶5.477kg在沸水浴中进行5分钟蒸煮处理后热风干燥,得到干燥的山茶叶1.89kg。在干燥山茶叶中加入18.9L蒸馏水,在室温下静置提取4小时。过滤除去不溶物,将滤液加载于装填了Diaion HP-20(三菱化学株式会社制)3L的柱,依次用6L蒸馏水、6L10%乙醇、6L20%乙醇洗脱。将20%乙醇洗脱液减压浓缩,进行冷冻干燥,得到23.52g表儿茶素富集的组分(表儿茶素含有率24.7%)。
[实施例3]
由山茶叶制备表儿茶素富集的组合物-2
将山茶叶151.64g在沸水浴中进行5分钟蒸煮处理后热风干燥,得到干燥的山茶叶58.48g。在干燥山茶叶中加入1.175L蒸馏水,室温下静置提取过夜。过滤除去不溶物后,对滤液进行冷冻干燥,得到山茶叶水提取物12.18g。山茶叶水提取物的表儿茶素含有率为3.12%。将10g得到的山茶叶水提取物溶解于1L蒸馏水中,加载于装填了Diaion HP-20(三菱化学株式会社制)250mL的柱,依次用1L蒸馏水、1L10%乙醇、1L20%乙醇洗脱。将20%乙醇洗脱液减压浓缩,进行冷冻干燥,得到0.932g表儿茶素富集的组分(表儿茶素含有率32.94%)。
[实施例4]
由山茶叶制备表儿茶素富集的组合物-3
将山茶叶90.12g在沸水浴中进行5分钟蒸煮处理后热风干燥,得到干燥的山茶叶34.50g。在干燥山茶叶中加入690mL70%乙醇,在室温下静置提取过夜。过滤除去不溶物后,对滤液进行减压浓缩,冷冻干燥,得到山茶叶70%乙醇提取物6.58g。山茶叶70%乙醇提取物中表儿茶素含有率为6.75%。将1g得到的山茶叶70%乙醇提取物溶解于1L蒸馏水中,加载于装填了Diaion HP-20(三菱化学株式会社制)250mL的柱,依次用1L蒸馏水、1L10%乙醇、1L20%乙醇洗脱。将20%乙醇洗脱液减压浓缩,进行冷冻干燥,得到0.12g表儿茶素富集的组分(表儿茶素含有率44.09%)。
[实施例5]
表儿茶素富集组分的脑内5-HT释放促进效果试验
以实施例2中得到的表儿茶素富集组分作为试样,使用与实施例1相同的方法验证对脑内5-HT水平的影响效果,确认表儿茶素富集组分通过口服给药能够增加脑内5-HT水平。
[实施例6]
用常规方法制造含有本发明的表儿茶素富集组分的脑内血清素增加剂的巧克力、含片、口香糖、糖果、软糖、饮料。以下所示为它们的配方。并且,本发明的范围不受这些限制。
产业上利用的可能性
含有山茶叶提取物的脑内血清素增加剂可适用于多种制品。
本申请要求基于2011年7月27日提出申请的日本专利申请号2011-164454的优先权,引用其内容作为本申请的一部分。
Claims (4)
1.含有表儿茶素的脑内血清素增加剂。
2.如权利要求1所述的脑内血清素增加剂,其特征在于,上述表儿茶素是由山茶叶提取的表儿茶素富集的组分。
3.由山茶叶制备表儿茶素富集的组分的方法,其特征在于,蒸煮并干燥山茶叶从而获得干燥的山茶叶,将用蒸馏水或乙醇提取得到的干燥的山茶叶而得的提取物加载于离子交换树脂柱,通过对20%乙醇洗脱液进行浓缩干燥获得表儿茶素富集的组分。
4.含有脑内血清素增加剂的食品,所述脑内血清素增加剂含有表儿茶素。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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JP2011-164454 | 2011-07-27 | ||
JP2011164454A JP2013028546A (ja) | 2011-07-27 | 2011-07-27 | 脳内セロトニン増加剤 |
PCT/JP2012/004706 WO2013014921A1 (ja) | 2011-07-27 | 2012-07-24 | 脳内セロトニン増加剤 |
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CN103717217A true CN103717217A (zh) | 2014-04-09 |
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CN201280036642.6A Pending CN103717217A (zh) | 2011-07-27 | 2012-07-24 | 脑内血清素增加剂 |
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JP (1) | JP2013028546A (zh) |
KR (1) | KR20140058541A (zh) |
CN (1) | CN103717217A (zh) |
TW (1) | TW201322990A (zh) |
WO (1) | WO2013014921A1 (zh) |
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WO2024036223A1 (en) * | 2022-08-10 | 2024-02-15 | Epirium Bio Inc. | Epicatechin inhibiting atp hydrolysis |
Citations (2)
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JP2002080363A (ja) * | 2000-08-31 | 2002-03-19 | Meiji Seika Kaisha Ltd | 抗ストレス組成物 |
US20100055219A1 (en) * | 2006-03-15 | 2010-03-04 | Tropical Technology Center Ltd. | Antiinflammatory agent |
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2011
- 2011-07-27 JP JP2011164454A patent/JP2013028546A/ja active Pending
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2012
- 2012-07-24 KR KR1020147002945A patent/KR20140058541A/ko not_active Application Discontinuation
- 2012-07-24 WO PCT/JP2012/004706 patent/WO2013014921A1/ja active Application Filing
- 2012-07-24 CN CN201280036642.6A patent/CN103717217A/zh active Pending
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JP2002080363A (ja) * | 2000-08-31 | 2002-03-19 | Meiji Seika Kaisha Ltd | 抗ストレス組成物 |
US20100055219A1 (en) * | 2006-03-15 | 2010-03-04 | Tropical Technology Center Ltd. | Antiinflammatory agent |
Also Published As
Publication number | Publication date |
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TW201322990A (zh) | 2013-06-16 |
JP2013028546A (ja) | 2013-02-07 |
WO2013014921A1 (ja) | 2013-01-31 |
KR20140058541A (ko) | 2014-05-14 |
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