CN101460159A - 疲劳缓解剂 - Google Patents
疲劳缓解剂 Download PDFInfo
- Publication number
- CN101460159A CN101460159A CNA2007800210370A CN200780021037A CN101460159A CN 101460159 A CN101460159 A CN 101460159A CN A2007800210370 A CNA2007800210370 A CN A2007800210370A CN 200780021037 A CN200780021037 A CN 200780021037A CN 101460159 A CN101460159 A CN 101460159A
- Authority
- CN
- China
- Prior art keywords
- salt
- fatigue
- ornithine
- glutathion
- reducing agent
- 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.)
- Granted
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Abstract
对于疲劳者来说，期望缓解疲劳且创造出充实生活的药品、功能性食品等。即，本发明的目的在于提供疲劳缓解剂。根据本发明，能够提供含有鸟氨酸或其盐以及谷胱甘肽或其盐作为有效成分的疲劳缓解剂。
Description
技术领域
本发明涉及一种疲劳缓解剂，含有鸟氨酸或其盐以及谷胱甘肽或其盐作为有效成分。
背景技术
鸟氨酸主要在美国和日本被用作使生长激素分泌而增强肌肉合成、或者提高基础代谢而预防肥胖的食品原材料。另外，鸟氨酸在欧洲以L-鸟氨酸L-天冬氨酸盐的形式用作改善肝脏损伤的药品。
已知在与血中氨值上升相关的病态疲劳中，通过施用鸟氨酸或其盐降低血中氨值，从而病态疲劳恢复(专利文献1～3、非专利文献1)。而且，已知健康人通过摄取鸟氨酸，疲劳的自觉症状缓解(非专利文献2)。
但是，并不知道谷胱甘肽的缓解疲劳作用，也不知道通过使谷胱甘肽及其盐与鸟氨酸或其盐相配合能够得到协同的缓解疲劳效果。
专利文献1：日本特公昭42-7767号公报
专利文献2：日本特公昭46-3194号公报
专利文献3：日本特公昭41-8592号公报
非专利文献1：《Arzneim.-Forsch.(Drug Res.)》、1970年、第8卷、p1064-1067
非专利文献2：《食品与开发》、2005年、第40卷、第11号、p62-64
发明内容
对于疲劳者来说，期望缓解疲劳且创造出充实生活的药品、功能性食品等。即，本发明的目的在于提供疲劳缓解剂。
本发明涉及以下(1)～(3)：
(1)一种疲劳缓解剂，含有鸟氨酸或其盐以及谷胱甘肽或其盐作为有效成分。
(2)一种缓解疲劳的方法，包括将有效量的鸟氨酸或其盐以及谷胱甘肽或其盐施用于需要使用的对象。
(3)鸟氨酸或其盐以及谷胱甘肽或其盐在制造疲劳缓解剂中的的应用。
发明效果
根据本发明，能够提供含有鸟氨酸或其盐以及谷胱甘肽或其盐作为有效成分的、安全且有效的疲劳缓解剂。
附图说明
图1是示出饲养条件不同的大鼠的游泳时间的图。+、-表示是否与左栏的饲养条件相符。*表示危险率小于5％、有显著性差异。
具体实施方式
作为本发明中使用的鸟氨酸，可列举出L-鸟氨酸或D-鸟氨酸，但优选L-鸟氨酸。
本发明中使用的鸟氨酸可以是通过任何一种制造方法而制得的，作为L-鸟氨酸的制造方法，例如可以列举出化学合成法[Coll.Czechoslov.Chem.Commun.，24，1993(1959)]、发酵法(日本特开昭53-24096号公报、特开昭61-119194号公报)等方法。
而且，L-鸟氨酸和D-鸟氨酸也可以从シグマ—アルドリツチ公司等购入。
作为鸟氨酸的盐，例如可以列举出酸加成盐、金属盐、铵盐、有机胺加成盐、氨基酸加成盐等。
作为酸加成盐，例如可以列举出盐酸盐、硫酸盐、硝酸盐、磷酸盐等无机酸盐，醋酸盐、马来酸盐、富马酸盐、柠檬酸盐、苹果酸盐、乳酸盐、α-酮戊二酸盐、葡萄糖酸盐、辛酸盐等有机酸盐。
作为金属盐，可以列举出钠盐、钾盐等碱金属盐、镁盐、钙盐等碱土金属盐、铝盐、锌盐等。
作为铵盐，可以列举出铵、四甲基铵等盐。
作为有机胺加成盐，可以列举出吗啉、哌啶等的盐。
作为氨基酸加成盐，可以列举出甘氨酸、苯丙氨酸、赖氨酸、天冬氨酸和谷氨酸等的盐。
上述鸟氨酸的盐中，优选使用盐酸盐、柠檬酸盐、苹果酸盐、α-酮戊二酸盐、天冬氨酸盐，还可以使用其他的盐或适当配合使用2种以上的盐。
作为本发明中使用的谷胱甘肽，可以列举出还原型谷胱甘肽或氧化型谷胱甘肽。
还原型谷胱甘肽是表示具有γ-L-Glu-L-Cys-Gly结构的三肽，氧化型谷胱甘肽是表示2分子的还原型谷胱甘肽通过SS键结合的谷胱甘肽二肽。
本发明中使用的还原型谷胱甘肽和氧化型谷胱甘肽可以是由任何一种制造方法而制得的。作为还原型谷胱甘肽的制造方法，可以列举出从酵母等微生物的提取法[Methods in Enzymology，3，603(1957)]、化学合成法[Bull.Chem.Soc.Jpn.，53，2529(1980)]、酶法(日本特开昭61-74595)等方法，作为氧化型谷胱甘肽的制造方法，可以列举出[ActaBiochim.Pol.，17，175(1970)]等方法。另外，还原型谷胱甘肽和氧化型谷胱甘肽还可以购自シグマ—アルドリツチ公司等。
本发明的疲劳缓解剂可以单独含有还原型谷胱甘肽或氧化型谷胱甘肽中的任意一种，也可以同时含有还原型谷胱甘肽和氧化型谷胱甘肽
另外，本发明的疲劳缓解剂中含有的还原型谷胱甘肽和氧化型谷胱甘肽也可以以其盐的方式存在于该制剂中。作为还原型谷胱甘肽和氧化型谷胱甘肽的盐，可以列举出与上述鸟氨酸的盐相同的盐。
另外，在本发明中，还可以使用在机体内能够代谢为还原型谷胱甘肽的物质、例如N-乙酰半胱氨酸等来代替谷胱甘肽。
以重量比计，本发明的疲劳缓解剂中的鸟氨酸或其盐与谷胱甘肽或其盐的组成比为1:100～100:1，优选为1:50～50:1，特别优选为10:1～1:10。
另外，本发明的疲劳缓解剂可以以同一制剂中含有鸟氨酸或其盐和谷胱甘肽或其盐的方式进行制备，但也可以分别制造各自的制剂而作为试剂盒或套剂(set)方式的制剂(以下也仅称为试剂盒等)使用。
试剂盒等中含有的各制剂只要是各自单独地存在的方式，则可以以任意状态存在。例如，各制剂可分别包装，也可混合在同一容器内。
分别施用或摄取试剂盒等中含有的各制剂时，优选在各制剂中的有效成分在体内具有高效力的时间内给药。例如，每次施用或摄取，将全部制剂在8小时以内、优选2小时以内施用或摄取。
通过施用或摄取本发明的疲劳缓解剂，能够缓解疲劳。
作为疲劳，可以列举出生理疲劳和病态疲劳。
生理疲劳是指为了维持人类健康的防御反应。更具体来说，是指在工作、家务、闲暇的运动等日常活动中出现的疲劳，并不仅是肉体的疲劳，还包含精神的疲劳。
另一方面，病态疲劳是指作为伴随心脏病、支气管哮喘、肝炎、贫血、代谢性疾病、肌肉疾病、各种感染症、癌症等基础疾病的症状而出现的疲劳，以及慢性疲劳综合症、精神原因引起的抑郁症、由运动引起的过度训练综合症等的疲劳。
本发明的疲劳缓解剂能够用于缓解上述任意一种疲劳。
作为本发明的疲劳缓解剂，可以直接施用鸟氨酸或其盐以及谷胱甘肽或其盐，但通常优选以各种制剂的方式来提供。
制剂含有鸟氨酸或其盐以及谷胱甘肽或其盐作为有效成分，但也可以进一步含有任意的有效成分。而且，这些制剂可以将有效成分与药理学上可接受的1种或1种以上的载体一起混合，通过制剂学技术领域中熟知的任意方法进行制造。
制剂的给药方式优选使用缓解疲劳时最有效的方式，可以列举出口服给药或者例如静脉内、腹膜内或皮下给药等非口服给药，但优选口服给药。
作为给药剂型，例如可以是片剂、散剂、颗粒剂、丸剂、混悬剂、乳剂、浸出剂/煎剂、胶囊剂、糖浆剂、液体剂、酏剂、浸膏剂、酊剂以及流浸膏剂等口服制剂，注射剂、滴剂、膏剂、栓剂等非口服制剂中任意一种，但优选使用口服制剂。
适合口服给药的、例如如糖浆剂之类的液体制备物，可以通过添加水、蔗糖、山梨醇、果糖等糖类，聚乙二醇、丙二醇等二醇类，芝麻油、橄榄油、大豆油等油类，对羟基苯甲酸酯类等防腐剂，对羟基苯甲酸甲酯等对羟基苯甲酸衍生物、苯甲酸钠等保存剂，草莓香料、薄荷等香料类等来进行制剂。
另外，适合口服给药的、例如片剂、散剂和颗粒剂等，可以通过添加乳糖、白糖、葡萄糖、蔗糖、甘露醇、山梨醇等糖类，马铃薯、小麦、玉米等的淀粉，碳酸钙、硫酸钙、碳酸氢钠、氯化钠等无机物，结晶纤维素、甘草粉、龙胆粉等植物粉末等赋形剂，淀粉、琼脂、明胶粉、结晶纤维素、羧甲基纤维素钠、羧甲基纤维素钙、碳酸钾、碳酸氢钠、海藻酸钠等崩解剂，硬脂酸镁、滑石粉、氢化植物油、聚乙二醇、硅油等润滑剂，聚乙烯醇、羟丙基纤维素、甲基纤维素、乙基纤维素、羧甲基纤维素、明胶、淀粉糊液等粘合剂，脂肪酸酯等表面活性剂，甘油等增塑剂来进行制剂。
另外，还可以向适合口服给药的制剂中添加一般可以用于饮食品的添加剂，例如甜味剂、着色剂、保存剂、增粘稳定剂、氧化防止剂、发色剂、漂白剂、防霉剂、胶基、苦味剂、酶、光泽剂、酸味料、调味料、乳化剂、强化剂、制造用剂、香料、香辛料提取物等。
适合口服给药的制剂可以直接、或者以例如粉末食品、薄片状食品、瓶装食品、罐装食品、高压杀菌袋装食品、胶囊食品、片状食品、流动食品、健康饮料等方式，作为用于缓解疲劳的健康食品、功能性食品、营养补充食品、特定保健用食品等饮食品而使用。
适合非口服给药的、例如注射剂，优选由含有与受者的血液等渗的鸟氨酸或其盐及谷胱甘肽或其盐的灭菌水性制剂构成。例如，注射剂的情况，通过使用由盐溶液、葡萄糖溶液或盐溶液和葡萄糖溶液的混合物组成的载体等制备注射用溶液。
另外，在这些非口服制剂中，也可以添加选自在口服制剂中例示的防腐剂、保存剂、赋形剂、崩解剂、润滑剂、粘合剂、表面活性剂、增塑剂等中的1种或1种以上的辅助成分。
本发明的疲劳缓解剂中的鸟氨酸或其盐以及谷胱甘肽或其盐的浓度可以根据制剂的种类、施用该制剂所期待的效果等而适当地选择，但作为鸟氨酸或其盐以及谷胱甘肽或其盐，通常为0.1～100重量％，优选为0.5～70重量％，特别优选为1～50重量％。
将本发明的疲劳缓解剂施用于人时的给药量和给药次数，根据给药方式和被施用者的年龄、体重等而不同，但作为鸟氨酸或其盐以及谷胱甘肽或其盐，以成人每天通常为50mg～30g、优选为100mg～10g、特别优选为200mg～3g的方式，一天给药1次～数次。
给药周期没有特别限制，但通常为1天～1年，优选为1周～3个月。
另外，本发明的制剂除了能够应用于人，还能够应用于人之外的动物(以下简称为非人动物)。
作为非人动物，可以列举出哺乳类、鸟类、爬虫类、两栖类、鱼类等人以外的动物。
施用于非人动物时的给药量根据动物的年龄、种类、症状的性质或重症度而不同，但作为鸟氨酸或其盐以及谷胱甘肽或其盐，以1kg体重每天通常为1mg～600mg、优选为2mg～200mg、特别优选为4mg～60mg的方式，一天给药1次～数次。
给药周期没有特别限制，但通常为1天～1年，优选为1周～3个月。
下面示出研究鸟氨酸和谷胱甘肽的缓解疲劳效果的试验例。
试验例
将SD系雄性大鼠(7周龄、购自日本エスエルシ—)分为5组，驯化2天后，1组进行通常的地板饲养，剩下的4组进行5天水浸饲养。水浸饲养是指在塑料笼内装入水深1.5cm的水的状态下进行饲养。在该环境下，对于逃避水的大鼠来说不能得到充分的睡眠、不能采用休息姿势，精神上和肉体上总是处于不能休息的状态。已知当进行7天以上的水浸饲养后便开始出现死亡个体，进行5天水浸饲养后的大鼠可以说是实现疲劳困惫而过劳死的动物模型。
从水浸饲养的第1天开始，1天1次以10ml/kg体重口服给予蒸馏水、鸟氨酸(L-鸟氨酸盐酸盐、协和发酵工业公司制、给药量1000mg/kg体重)、还原型谷胱甘肽(谷胱甘肽(还原型)、协和发酵工业公司制、给药量800mg/kg体重)或鸟氨酸(给药量500mg/kg体重)和还原型谷胱甘肽(给药量400mg/kg体重)。
进行5天的水浸饲养后，使大鼠在载荷相当于体重的8％的重物的状态下游泳，测定直到鼻尖被水没过10秒以上的时间，用于评价疲劳度。
数值表示平均值±标准差(n＝4)，利用双侧分布的2样本t检验进行统计学上的显著性差异检验。
结果如图1所示。与地板饲养相比，水浸饲养时游泳时间缩短约20％，鸟氨酸给药组中可见游泳时间的恢复，但谷胱甘肽给药组中未见变化。而且，在鸟氨酸与谷胱甘肽的联合给药组中，尽管鸟氨酸的给药量为鸟氨酸给药组的一半，但是与鸟氨酸给药组相比游泳时间显著延长。
由以上的结果可知，通过在鸟氨酸的基础上配合使用谷胱甘肽，能够得到协同的缓解疲劳的效果。
下面示出本发明的实施例。
实施例1
含有鸟氨酸和谷胱甘肽的片剂的制造
将鸟氨酸盐酸盐76.2kg、还原型谷胱甘肽60.0kg、微晶纤维素36.0kg、蔗糖脂肪酸酯6.6kg、磷酸钙1.2kg及β-环糊精20.0kg混合。通过使用旋转式压缩成型机将得到的混合物压缩成型，制造直径8mm、250mg的片剂。
实施例2
含有鸟氨酸和谷胱甘肽的肠溶胶囊的制造
将通过混合搅拌由实施例1制备的混合物20kg和0.2kg的二氧化硅而得到的混合物投入胶囊填充机中，填充到明胶制2号硬胶囊20000粒中，从而得到硬胶囊。使用玉米醇溶蛋白溶液对所得硬胶囊的表面进行包衣，制造肠溶胶囊20000粒。
实施例3
含有鸟氨酸和谷胱甘肽的肠溶片剂的制造
使用虫胶溶液对由实施例1制备的片剂的表面进行包衣，制造肠溶片剂。
实施例4
含有鸟氨酸和谷胱甘肽的饮料的制造
在液温70℃下，将鸟氨酸盐酸盐0.64kg、氧化型谷胱甘肽0.6kg、赤藓糖醇3kg、柠檬酸0.05kg、人造甜味剂3g和香料0.06kg在50L的水中搅拌溶解，用柠檬酸将pH调至3.3后，采用板式杀菌进行灭菌后填充到瓶中，然后用巴氏杀菌机进行杀菌，从而制造饮料。
产业上的利用可能性
根据本发明，能够提供含有鸟氨酸或其盐以及谷胱甘肽或其盐作为有效成分的、安全且有效的疲劳缓解剂。
Claims (3)
1.一种疲劳缓解剂，含有鸟氨酸或其盐以及谷胱甘肽或其盐作为有效成分。
2.一种缓解疲劳的方法，包括将有效量的鸟氨酸或其盐以及谷胱甘肽或其盐施用于需要使用的对象。
3.鸟氨酸或其盐以及谷胱甘肽或其盐在制造疲劳缓解剂中的应用。
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| PCT/JP2007/061522 WO2007142286A1 (ja) | 2006-06-07 | 2007-06-07 | 疲労軽減剤 |
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| CN101460159B CN101460159B (zh) | 2011-11-23 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102526750A (zh) * | 2012-01-06 | 2012-07-04 | 安徽黄山胶囊股份有限公司 | 一种植物结肠溶空心胶囊 |
| CN102552457A (zh) * | 2010-12-24 | 2012-07-11 | 漆又毛 | 一种氨基酸和提取物组合物的药物用途 |
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| JPWO2009107660A1 (ja) * | 2008-02-25 | 2011-07-07 | 味の素株式会社 | 糖尿病又は肥満病の予防又は治療剤 |
| JP5997425B2 (ja) * | 2011-08-18 | 2016-09-28 | 協和発酵バイオ株式会社 | オルニチン含有組成物 |
| JP6469568B2 (ja) * | 2012-09-28 | 2019-02-13 | 協和発酵バイオ株式会社 | グルタチオンを含有する免疫増強剤 |
| JP2014159381A (ja) * | 2013-02-19 | 2014-09-04 | Kyowa Hakko Bio Co Ltd | オルニチン含有体組成改善用組成物 |
| JP6646369B2 (ja) * | 2015-06-25 | 2020-02-14 | 株式会社東洋新薬 | 抗疲労剤 |
| WO2017004396A1 (en) * | 2015-06-30 | 2017-01-05 | Nucorplabs, Inc. | Chewable composition to deliver gsh |
| US11291649B2 (en) * | 2017-06-07 | 2022-04-05 | Kao Corporation | Ammonia metabolism promoter |
| JP6829487B2 (ja) * | 2019-07-11 | 2021-02-10 | 株式会社東洋新薬 | 抗疲労剤 |
| JP2021020881A (ja) * | 2019-07-30 | 2021-02-18 | 三菱商事ライフサイエンス株式会社 | 疲労回復剤 |
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| GB1110392A (en) * | 1964-09-28 | 1968-04-18 | Yamanouchi Pharma Co Ltd | Composition containing glutathione and an amino acid or amino acids, and salts thereof |
| US3428025A (en) * | 1966-12-27 | 1969-02-18 | Xerox Corp | Xerographic development apparatus |
| ZA716628B (en) * | 1970-10-15 | 1972-06-28 | Richardson Merrell Spa | Composition and method for treatment of hepatic disease and mental fatigue |
| JPS5324096A (en) | 1976-08-19 | 1978-03-06 | Kyowa Hakko Kogyo Co Ltd | Preparation of l-ornithine by fermentation |
| JPS6174595A (ja) | 1984-09-21 | 1986-04-16 | Kyowa Hakko Kogyo Co Ltd | 物質の製造方法 |
| JPS61119194A (ja) | 1984-11-15 | 1986-06-06 | Kyowa Hakko Kogyo Co Ltd | 発酵法によるｌ−オルニチンの製造法 |
| DE69323731T2 (de) * | 1992-11-10 | 1999-07-22 | Otsuka Pharma Co Ltd | Futterzusammensetzung |
| JPH08275752A (ja) * | 1995-04-07 | 1996-10-22 | Riken Vitamin Co Ltd | ストレス改善食品 |
| JP2002338473A (ja) * | 2001-05-15 | 2002-11-27 | Yaizu Suisankagaku Industry Co Ltd | 抗疲労組成物 |
| US6855727B2 (en) * | 2000-12-04 | 2005-02-15 | Yaizu Suisankagaku Industry Co., Ltd. | Muscular fatigue-controlling composition and method for providing muscular fatigue-controlling effect |
| EP1381373B1 (en) * | 2001-04-25 | 2006-06-14 | Cobalz Limited | Medical compositions for use in the treatment or prevention of a functional vitamin b12 deficienfcy |
| DE10158498A1 (de) * | 2001-11-29 | 2003-07-24 | Becker Grubmueller Anuschka | Nahrungsergänzungspräparat |
| US20040001817A1 (en) * | 2002-05-14 | 2004-01-01 | Giampapa Vincent C. | Anti-aging nutritional supplement |
| US20040230257A1 (en) * | 2003-02-10 | 2004-11-18 | Ovokaitys Todd F. | Enhanced bioavailability of nutrients, pharmaceutical agents, and other bioactive substances through laser resonant homogenization or modification of molecular shape or crystalline form |
| ATE406886T1 (de) * | 2003-03-06 | 2008-09-15 | Kyowa Hakko Kogyo Kk | Tablette mit wasserabsorbierender aminosäure |
| CN101282721B (zh) * | 2005-10-04 | 2013-05-01 | 协和发酵生化株式会社 | 改善疲劳自觉症状用组合物 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102552457A (zh) * | 2010-12-24 | 2012-07-11 | 漆又毛 | 一种氨基酸和提取物组合物的药物用途 |
| CN102526750A (zh) * | 2012-01-06 | 2012-07-04 | 安徽黄山胶囊股份有限公司 | 一种植物结肠溶空心胶囊 |
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| EP2050444A4 (en) | 2009-06-03 |
| EP2050444B1 (en) | 2011-05-11 |
| JPWO2007142286A1 (ja) | 2009-10-29 |
| US20100137226A1 (en) | 2010-06-03 |
| JP5085541B2 (ja) | 2012-11-28 |
| ATE508740T1 (de) | 2011-05-15 |
| WO2007142286A1 (ja) | 2007-12-13 |
| EP2050444A1 (en) | 2009-04-22 |
| CN101460159B (zh) | 2011-11-23 |
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