CN101443010A - 脑功能改善剂及含有该改善剂的功能性食品 - Google Patents
脑功能改善剂及含有该改善剂的功能性食品 Download PDFInfo
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- CN101443010A CN101443010A CNA2007800169944A CN200780016994A CN101443010A CN 101443010 A CN101443010 A CN 101443010A CN A2007800169944 A CNA2007800169944 A CN A2007800169944A CN 200780016994 A CN200780016994 A CN 200780016994A CN 101443010 A CN101443010 A CN 101443010A
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- brain function
- improving agent
- functional food
- salt
- improving
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Abstract
提供了具有改善学习和记忆能力的作用的脑功能改善剂，和含有该功能改善剂的功能性食品。包含单独或与辅酶Q10组合的吡咯并喹啉醌类或其盐的制品和含有该制品的功能性食品可以改善因各种因素造成的脑功能障碍而衰减的学习和记忆能力。
Description
技术领域
本发明涉及至少包含通式(1)所示的吡咯并喹啉醌或其盐作为活性成分的脑功能改善剂，和含有该改善剂的功能性食品。此外，本发明涉及包含通式(1)所示的吡咯并喹啉醌或其盐及辅酶Q10作为活性成分的脑功能改善剂，和含有该改善剂的功能性食品。由于它们具有改善衰减的学习和记忆能力的作用，这类脑功能改善剂和功能性食品在改善由血管或器质性的损害引起的脑功能衰减方面非常有用。
在该式中，R1、R2和R3相同或不同，并代表氢原子、烷基、链烯基、苄基、炔丙基(プロパギル)或烷氧基羰基烷基。
背景技术
近年来，总人口中的中老年人百分比快速增长。伴随着这种增长，学习和记忆能力随老化而衰减和由疾病引起的痴呆的增加变成问题。疾病引起的痴呆包括以阿尔茨海默氏症为代表的脑变性疾病、由脑梗死和脑出血引起的脑血管障碍、脑瘤、头部外伤、传染病、代谢病等等。特别地，随着老龄化社会的发展，阿尔茨海默氏症的患者数量显著增加。据说，阿尔茨海默氏症患者在日本占痴呆患者的大约30％，在美国占40至60％。该疾病的特征在于短期记忆或远期记忆的急性障碍、人格障碍等等，并且从医疗费用和看护角度看已经引起严重的社会问题。
该疾病与脑组织的萎缩、损失等以及乙酰胆碱(其是神经递质)含量降低有关。该疾病的特征进一步包括在大脑皮层和海马中观察到的老年斑和神经原纤维缠结，并在存在于老年斑中心的淀粉状β蛋白质和作为神经原纤维缠结的结构蛋白质的τ蛋白质上研究其病因学机理。已经基于这种病因学机理开发治疗剂，并已经开发出乙酰胆碱酯酶抑制剂及类似物。但是，它们迄今还称不上成功。换言之，发作后的恢复常常是困难的，当前的疗法必须依靠延迟疾病的进展，如对症疗法。
同时，随着近来在对食物成分功能的研究中的进展，已经发现对脑功能有作用的成分，并在食物中积极探索预防该疾病并抑制该疾病进展的功能(例如，参见专利文献1至3)。二十二碳六烯酸(DHA)、银杏叶提取物和类似物已知为激活脑功能的食物材料。但是，它们的作用不足，并且需要开发更有效的食物材料。
专利文献1：日本专利公开(Kokai)No.H07-017855。
专利文献2：日本专利公开(Kokai)No.H07-143862。
专利文献3：日本专利No.3195594。
发明内容
本发明的一个目的在于提供具有改善因血管或非血管原因而受损的脑功能的作用的制品，和含有这种制品的功能性食品。
本发明人已经对吡咯并喹啉醌类或其盐的生物活性进行了各种研究。结果发现，这些化合物的口服给药具有显著改善实验动物的学习和记忆能力的作用，此外，其与辅酶Q10的联用表现出协同效应。由此完成本发明。
具体而言，如下列条目1至4中所述，本发明涉及具有脑功能改善作用，如改善衰减的学习和记忆能力的制品和功能性食品，其特征在于包含吡咯并喹啉醌或其盐，和如果需要，包含辅酶Q10。具体而言，本发明涉及改善因老化和痴呆症如阿尔茨海默氏症而衰减的学习和记忆能力的脑功能改善剂，和含有该改善剂的功能性食品。
1.至少包含通式1所示的吡咯并喹啉醌类或其盐的脑功能改善剂：
其中R1、R2和R3相同或不同，并代表氢原子、烷基、链烯基、苄基、炔丙基或烷氧基羰基烷基。
2.根据上述条目1的脑功能改善剂，进一步包含辅酶Q10。
3.根据上述条目1或2的脑功能改善剂，其可用于改善衰减的学习和记忆能力。
4.包含根据上述条目1至3任一项的脑功能改善剂的功能性食品。
本发明涉及包含吡咯并喹啉醌类或其盐、或与辅酶Q10一起的吡咯并喹啉醌类或其盐作为活性成分并具有脑功能改善作用如衰减的学习和记忆能力改善作用等的脑功能改善剂，并涉及含有该功能改善剂的功能性食品。具体而言，本发明涉及改善由老化和痴呆症如阿尔茨海默氏症引起的学习和记忆能力衰减的脑功能改善剂，和含有该改善剂的功能性食品。
附图说明
图1是显示实施例1中观察到的在记忆与学习能力改善速度方面的作用的图。
图2是显示实施例2中观察到的在记忆保持能力方面的作用的图。
具体实施方式
本发明涉及包含吡咯并喹啉醌类或其盐、或辅酶Q10及吡咯并喹啉醌或其盐作为活性成分的脑功能改善剂，和含有该改善剂的功能性食品。
1979年，作为甲醇同化细菌中甲醇脱氢酶的辅酶，发现了吡咯并喹啉醌。除细菌外，它们也在如大豆、蚕豆、青椒、马铃薯、欧芹和菠菜的食用植物和如醋、茶、可可、纳豆和豆腐等的加工食品中检出。
可以通过有机化学合成法(例如，JACS，第103卷，第5599-5600页(1981))、发酵法(例如，日本专利公开(Kokai)No.H01-218597)或类似方法制造吡咯并喹啉醌类及其盐。
吡咯并喹啉醌类及其盐的实例包括通式(1)所示的吡咯并喹啉醌类及其盐，例如碱金属盐，如钠盐和钾盐，以及碱土金属盐，如镁盐和钙盐，但不限于此。
传统上，已经为医疗用途通过静脉注射或腹腔内给药评价过吡咯并喹啉醌类及其盐。但是，这些给药途径不方便，它们是侵入性的并容易造成不良药物反应这样严重的问题。在这些情况下，它们的作用尚未在没有不良药物反应的情况下展现，并且尚未确实地评测它们的功效。但是，本发明人已经意外地发现，这些化合物的口服摄入以其极小的摄入量表现出脑功能改善作用，如衰减的学习和记忆能力的改善，并且其摄入量的有效范围极宽，同时即使在其高摄入量下也未发生不良药物反应。这些发现表明，吡咯并喹啉醌类及其盐可以用作为功能性食品的安全材料。
通式(1)所示的吡咯并喹啉醌或其盐单独使用，或与辅酶Q10组合使用，并也可以与其它功能性食品材料组合使用。可组合使用的功能性食品材料的实例包括L-肉碱、α-硫辛酸、用作食品的维生素(如维生素B族、维生素C和维生素E)、氨基酸、类胡萝卜素(如虾青素、α-胡萝卜素和β-胡萝卜素)、ω3脂肪酸(如二十二碳六烯酸和二十碳五烯酸)、ω6脂肪酸(如花生四烯酸)等等，但不限于这些实例。
此外，包含通式(1)所示的吡咯并喹啉醌类或其盐和任选的辅酶Q10的本发明的脑功能改善剂可以以食品和饮品的形式使用，包括饮料、糖浆、各种医院饮食、营养补充剂和日常饮食时的食品和饮品，以及片剂、胶囊和颗粒。可用作制品中的液体试剂的添加剂的实例包括水、糖类(如果糖和葡萄糖)、油类(如花生油、大豆油和橄榄油)、以及二醇类(如聚乙二醇和聚丙二醇)。固体制品如片剂、胶囊和颗粒所用的赋形剂的实例包括乳糖、蔗糖和甘露醇。润滑剂的实例包括高岭土、滑石和硬脂酸镁。崩解剂的实例包括淀粉和藻酸钠。粘合剂的实例包括聚乙烯醇、纤维素和明胶。表面活性剂的实例包括脂肪酸酯。增塑剂的实例包括甘油和类似物。但是，实例不限于上述实例。
实施例
下面，通过下列实施例更具体地解释本发明。但是，本发明不限于这些实施例。
实施例1
用单独含有0.02％吡咯并喹啉醌二钠盐(PQQ·2Na)或0.3％辅酶Q10(CoQ10)或含有这两者的饲料或不含这些化合物的饲料饲养雄性Wistar大鼠(9周大)。从饲养21天后12周大的年龄开始，每组9只动物接受使用Morris水迷宫(Morris water maze)的学习与记忆能力测试。具体而言，将圆形水池(直径150厘米，深度45厘米)底部用白线分成四个象限。在象限之一的中心放置圆形平台，以使其隐藏在水下。让每只大鼠从没有平台的其它三个象限的不同位置开始游泳，并测量直到其到达平台的时间。该测试每天一次，总计20天。通过下列方程式计算学习率：
学习率(％)＝100-(第X次试验时大鼠到达平台的平均时间/第一次实验时大鼠到达平台的平均时间)×100
在上述水迷宫测试中，在添加PQQ·2Na的治疗组和不使用PQQ·2Na的治疗组中，学习率都随着试验次数的提高而提高。但是，添加PQQ·2Na的治疗组的提高率在统计学上显著更高，由此证实PQQ·2Na改善了记忆和学习能力。结果显示在图1中。
实施例2
用单独含有0.02％ PQQ·2Na或0.3％ CoQ 10或含有这两者的饲料或不含这些化合物的饲料饲养雄性Wistar大鼠(9周大)。从饲养21天后12周大的年龄开始，通过与实施例1中相同的使用Morris水迷宫的训练，让每组9只动物记忆平台的位置。水池底部用白线分成四个象限。在象限之一的中心放置平台。已经记住平台位置的动物经受氧化应激(Oxidative Stress)(在100％氧气下48小时)。随后，让该动物在已移除平台的水迷宫中游60秒，并测量在原先放置平台的象限中的停留时间。通过下列方程式计算记忆保持率：
记忆保持率(％)＝(经受氧化应激后9天内的平均停留时间/即将经受氧化应激前的平均停留时间)×100
结果显示在图2中。在PQQ·2Na+CoQ10治疗的组中，平均记忆保持率最高，接下来是单独用PQQ·2Na治疗的组。此外，当PQQ·2Na与CoQ10联用时，在平均记忆保持率方面观察到显著的协同效应。
Claims (4)
1.脑功能改善剂，其特征在于至少包含下列通式(1)所示的吡咯并喹啉醌类或其盐：
其中R1、R2和R3相同或不同，代表氢原子、烷基、链烯基、苄基、炔丙基或烷氧基羰基烷基。
2.根据权利要求1的脑功能改善剂，其中，进一步包含辅酶Q10。
3.根据权利要求1或2的脑功能改善剂，其可用于改善衰减的学习和记能力。
4.功能性食品，其中包含根据权利要求1至3任一项的脑功能改善剂。
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| JP2003026567A (ja) * | 2001-05-10 | 2003-01-29 | Kanegafuchi Chem Ind Co Ltd | 補酵素ｑを有効成分とする粘膜投与用組成物 |
| WO2004010924A2 (en) * | 2002-04-04 | 2004-02-05 | Children's Medical Center Corporation | Pyrroloquinoline quinone drugs as a neuroprotectant and methods of use thereof |
| JP2005082523A (ja) * | 2003-09-08 | 2005-03-31 | Toru Hasegawa | 神経変性疾患特にアルツハイマー病及びパーキンソン病の根本治療薬 |
| CN1933824A (zh) * | 2004-03-23 | 2007-03-21 | 株式会社钟化 | 血中持续性辅酶q组合物 |
| JP2005325086A (ja) * | 2004-05-17 | 2005-11-24 | Asahi Kasei Pharma Kk | 睡眠障害予防及び／又は治療剤、機能性食品又は化粧料 |
| KR20070057218A (ko) * | 2004-08-30 | 2007-06-04 | 가부시키가이샤 가네카 | 미토콘드리아 활성화제 |
| JP2006069958A (ja) * | 2004-09-02 | 2006-03-16 | Bio Igaku Kenkyusho Kk | 老化防止剤 |
-
2007
- 2007-03-29 CN CNA2007800169944A patent/CN101443010A/zh active Pending
- 2007-03-29 CA CA002649315A patent/CA2649315A1/en not_active Abandoned
- 2007-03-29 JP JP2007534943A patent/JPWO2007119588A1/ja active Pending
- 2007-03-29 US US12/226,222 patent/US20090192312A1/en not_active Abandoned
- 2007-03-29 EP EP07740307A patent/EP2011498A4/en not_active Withdrawn
- 2007-03-29 WO PCT/JP2007/056869 patent/WO2007119588A1/ja active Application Filing
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101757624B (zh) * | 2009-12-24 | 2012-04-18 | 上海医学生命科学研究中心有限公司 | 一种预防和治疗老年痴呆症的组合物 |
| CN113348019A (zh) * | 2019-01-28 | 2021-09-03 | 三得利控股株式会社 | 食欲素受体拮抗抑制用组合物 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP2011498A1 (en) | 2009-01-07 |
| EP2011498A4 (en) | 2009-11-11 |
| CA2649315A1 (en) | 2007-10-25 |
| WO2007119588A1 (ja) | 2007-10-25 |
| JPWO2007119588A1 (ja) | 2009-08-27 |
| US20090192312A1 (en) | 2009-07-30 |
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