CN101522185A - 抗抑郁剂 - Google Patents
抗抑郁剂 Download PDFInfo
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- CN101522185A CN101522185A CNA2007800371989A CN200780037198A CN101522185A CN 101522185 A CN101522185 A CN 101522185A CN A2007800371989 A CNA2007800371989 A CN A2007800371989A CN 200780037198 A CN200780037198 A CN 200780037198A CN 101522185 A CN101522185 A CN 101522185A
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- Prior art keywords
- amino acid
- antidepressant
- branched
- chain amino
- derivant
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Abstract
一种抗抑郁剂,含有选自支链氨基酸、其可药用的盐和它们的衍生物中的至少一种化合物作为有效成分。
Description
技术领域
本发明涉及含有支链氨基酸或其可药用的盐或它们的衍生物作为有效成分的抗抑郁剂。
背景技术
近年来,苦于抑郁症的人数增多。如果包括苦于没有表现出任何精神症状的所谓隐匿性抑郁症的患者,这种人的总数占有相当大的比例,而且据说每五个日本人中就有一人将在他们的一生中经历一次抑郁症。
目前,抑郁症的原因仍未确定,并不限于生物因素和性格因素。例如,当前社会环境的剧烈变化、弱者被抛弃的社会结构、单一的价值观排除异端的趋势与抑郁症患者增加有关。
抑郁症的治疗包括:首先是休息;其次是药物治疗;以及两者的组合。但是,大多数人现实上不允许去休息,因此他们实际上用抗抑郁剂来敷衍自己。
从包括丙咪嗪的被称为第一代的抗抑郁剂到包括最新的米那普仑的被称为第四代的抗抑郁剂,有各种抗抑郁剂。但是,这些抗抑郁剂可能引起例如口干、便秘、排尿障碍和无尿等副作用。此外,还担心与其它药物的相互作用。
同时,含有作为本发明的有效成分的支链氨基酸的已知药物的例子包括:通过口服摄取支链氨基酸来消除肌肉痛、肌肉劳损和肌强直的药物(参照专利文献1),和通过口服摄取支链氨基酸来在运动时维持瞬间或持久的肌肉力量的药物(参照专利文献2)。通过着眼于亮氨酸、异亮氨酸和缬氨酸等支链氨基酸具有器官特异性,因此主要用于肌肉和肝以外的肾等组织中的事实,发现支链氨基酸有助于改善肌肉痛和肌强直,或者运动时维持瞬间或持久的肌肉力量。并且,已知含有支链氨基酸的中枢神经系统的疲劳缓解剂(参照专利文献3)等。该文献阐明了中枢神经系统的疲劳的机理,同时证明了血脑屏障上的L-系统转运体的特异性抑制剂2-氨基二环[2,2,1]庚烷-2-甲酸(2-aminobicyclo[2,2,1]heptane-2-carboxylic acid)可以抑制中枢神经系统的疲劳,特别是在与亮氨酸、异亮氨酸或缬氨酸等支链氨基酸并用时,可以几乎完全抑制中枢神经系统的疲劳。此外,已知都含有支链氨基酸的脑细胞代谢改善组合物(参照专利文献7)和抗痴呆药(参照专利文献8)。但是,这些文献中未提及支链氨基酸具有抗抑郁作用。
已知的含有支链氨基酸的药物制剂包括:服药量少、风味和吞咽感优异的仅将支链氨基酸作为有效成分的药用胶冻剂(参照专利文献4);风味和饮用感得到改善,悬浮时可以保持优异的悬浮性的含有支链氨基酸、助悬剂和表面活性剂的药用干糖浆剂(参照专利文献5);和由于其优异的保存稳定性而在保存时保持不着色的支链氨基酸作为有效成分的咀嚼片剂(参照专利文献6)。但是,这些文献中都未记载抗抑郁作用。
专利文献1:日本特开2000-26289号公报
专利文献2:日本特开2000-26290号公报
专利文献3:国际公开第2002/034257号小册子
专利文献4:日本特开2003-221330号公报
专利文献5:日本特开2003-221329号公报
专利文献6:日本特开2003-221327号公报
专利文献7:日本特开平2-172915号公报
专利文献8:日本特开平3-275631号公报
发明内容
本发明的目的在于提供一种抗抑郁剂。
为了解决上述问题,本发明人进行了深入研究,结果发现支链氨基酸或其可药用的盐或它们的衍生物可以抑制抑郁症状,从而最终完成了本发明。
即,本发明涉及:
(1)一种抗抑郁剂,含有选自支链氨基酸、其可药用的盐和它们的衍生物中的至少一种化合物作为有效成分;
(2)根据上述(1)所述的抗抑郁剂,其中,支链氨基酸为选自L-缬氨酸、L-亮氨酸和L-异亮氨酸中的至少一种化合物;
(3)根据上述(2)所述的抗抑郁剂,其中,抗抑郁剂至少含有L-异亮氨酸;
(4)根据上述(3)所述的抗抑郁剂,其中,L-异亮氨酸、L-亮氨酸和L-缬氨酸的含有比例按照摩尔比换算为1:(0~3):(0~2);
(5)根据上述(1)~(4)中任意一项所述的抗抑郁剂,其中,抗抑郁剂进一步含有碳水化合物;
(6)根据上述(5)所述的抗抑郁剂,其中,碳水化合物为葡萄糖;以及
(7)根据上述(1)~(6)中任意一项所述的抗抑郁剂,抗抑郁剂为注射剂或颗粒的形式。
本发明还涉及:
(8)一种抑郁症的预防或治疗方法,包括向哺乳动物给予选自支链氨基酸、其可药用的盐和它们的衍生物中的至少一种化合物;
(9)选自支链氨基酸、其可药用的盐和它们的衍生物中的至少一种化合物在制备抗抑郁剂中的使用;以及
(10)选自支链氨基酸、其可药用的盐和它们的衍生物中的至少一种化合物作为抗抑郁剂的使用。
本发明还涉及:
(11)一种抑郁状态改善用食品组合物,含有选自支链氨基酸、其可药用的盐和它们的衍生物中的至少一种化合物作为有效成分。
根据本发明,由于支链氨基酸、特别是异亮氨酸具有抗抑郁作用,有可能改善抑郁状态或预防陷入抑郁状态。本发明的抗抑郁剂几乎没有由现有的抗抑郁剂引起的例如口干、便秘、排尿障碍和无尿等副作用,并且基本上没有与其它药物相互作用的危险。因此,本发明的抗抑郁剂具有高安全性,且可以持续给药。
附图说明
图1表示试验例1中大鼠从圆筒中出来所需的时间。图中,纵坐标表示时间。
具体实施方式
以下,对本发明的含有选自支链氨基酸、支链氨基酸的可药用的盐、和支链氨基酸或其可药用的盐的衍生物中的至少一种化合物作为有效成分的抗抑郁剂进行具体的说明。
本发明中使用的支链氨基酸只要满足日本药典的标准就不特别限定,该支链氨基酸的例子包括例如L-氨基酸、D-氨基酸、α-氨基酸、β-氨基酸、γ-氨基酸、天然氨基酸、合成氨基酸等任意支链氨基酸,优选为天然的L-氨基酸或α-氨基酸。本发明中使用的支链氨基酸的特别优选的例子包括L-缬氨酸、L-亮氨酸和L-异亮氨酸。上述支链氨基酸可以通过使用蛋白酶等水解来源于植物或来源于动物的蛋白质,或通过微生物发酵法来制备,或者可以为通过向有机酸中导入氨基得到的合成氨基酸等。
本发明中的支链氨基酸的可药用的盐为酸或碱的盐,对其不特别限定,其例子包括例如钠盐和钾盐等碱金属盐,钙盐等碱土金属盐,盐酸盐等无机酸盐和乙酸盐等有机酸盐,其中优选为盐酸盐。具体的例子包括L-缬氨酸盐酸盐、L-亮氨酸盐酸盐和L-异亮氨酸盐酸盐。
对本发明的抗抑郁剂中使用的支链氨基酸或其可药用的盐的衍生物不特别限定,其例子包括例如酯类和肽类。该酯类只要为例如甲酯、乙酯、丙酯和异丙酯等低级烷基酯就不特别限定。此情况下的低级烷基优选为含有1~6个碳原子的烷基。酯类的优选具体例子包括L-缬氨酸乙酯、L-亮氨酸乙酯和L-异亮氨酸乙酯。该肽类只要为例如二肽和三肽等寡肽就不特别限定,肽类的优选具体例子包括L-异亮氨酰基-L-亮氨酸、L-丙氨酰基-L-亮氨酸、L-亮氨酰基-L-丙氨酸和甘氨酰基-L-亮氨酸。因此,构成寡肽的支链氨基酸以外的氨基酸可以为包括L-氨基酸、D-氨基酸、α-氨基酸、β-氨基酸、γ-氨基酸、天然氨基酸、合成氨基酸等的任意氨基酸。
本发明的抗抑郁剂中,这些支链氨基酸或其可药用的盐或它们的衍生物可以单独使用,或其两种以上混合使用,但是优选至少含有L-异亮氨酸或其盐或其衍生物,特别优选至少含有L-异亮氨酸。
在本发明中,支链氨基酸或其可药用的盐或它们的衍生物使用两种以上时,对其混合比例不特别限定。具体地说,使用支链氨基酸或其可药用的盐或它们的衍生物,例如L-异亮氨酸、L-亮氨酸和/或L-缬氨酸时,这些化合物可以单独使用或两种以上混合使用,该化合物的混合比例按照摩尔比换算优选为L-异亮氨酸:L-亮氨酸:L-缬氨酸=约1:(0~3):(0~2),更优选为约1:(0~2.5):(0~1.5)。例如使用L-异亮氨酸、L-亮氨酸和/或L-缬氨酸的盐或其衍生物时,优选分别换算为L-异亮氨酸、L-亮氨酸或L-缬氨酸,以上述摩尔比使用。
本发明的抗抑郁剂优选进一步含有碳水化合物。该碳水化合物包括但不限于例如核糖、脱氧核糖、葡萄糖、果糖和半乳糖等单糖类;例如麦芽糖、海藻糖、蔗糖和乳糖等二糖类;以及例如直链淀粉、支链淀粉和糖原等多糖类。在碳水化合物中,较优选单糖类,并且由于可以用作生物体内的可即用能源,特别优选葡萄糖。
此时,对碳水化合物的含有比例不特别限定,但是换算为每摩尔支链氨基酸的葡萄糖,优选为例如约0.1~50摩尔。上述碳水化合物的含有比例换算为每摩尔支链氨基酸的葡萄糖,优选为约0.1~20摩尔,更优选为约0.2~10摩尔。
本发明的抗抑郁剂可以以含有可药用的添加物的药物的方式或含有食品卫生法上认可的添加物的食品的方式提供。
本发明的抗抑郁剂形成药物时,可以用作例如口服给药用固形制剂、口服给药用液体制剂或者肠胃外给药用注射剂(皮下注射、静脉内注射、肌肉内注射、腹腔内注射等)。口服给药用固形制剂包括例如片剂、丸剂、胶囊剂、散剂和颗粒剂。
可以在口服给药用固形制剂中使用的添加剂包括例如赋形剂、粘合剂、崩解剂、润滑剂、稳定剂和润湿剂。赋形剂包括但不限于蔗糖、乳糖、葡萄糖、淀粉和甘露醇。粘合剂包括但不限于阿拉伯胶、羧甲基纤维素、明胶、微晶纤维素、羟丙基纤维素、甲基纤维素和聚维酮。崩解剂包括但不限于羧甲基纤维素、淀粉、微晶纤维素和低取代羟丙基纤维素。润滑剂包括但不限于滑石、硬脂酸镁、硬脂酸钙和二氧化硅。稳定剂和润湿剂包括但不限于柠檬酸酐、月桂酸钠和甘油。这些添加剂可以单独使用或并用两种以上。口服给药用固形制剂可以根据常规方法,例如第14次修订版日本药典制剂总则中记载的方法等制备,例如将支链氨基酸、其盐或它们的衍生物与添加剂等混合,然后将该混合物制成药物制剂来得到。具体地说,颗粒剂优选可以如下制备:例如向支链氨基酸、其盐或它们的衍生物中加入上述赋形剂、粘合剂、崩解剂等并均匀捏合混合物后,将混合物通过压缩造粒、滚筒造粒、喷雾干燥造粒、挤压造粒、研磨造粒、流化造粒、搅拌造粒等制成粒状。片剂可以如下制备:例如,向支链氨基酸、其盐或它们的衍生物中加入上述赋形剂、粘合剂、崩解剂等并均匀捏合混合物后,直接进行压缩成型;或者由支链氨基酸、其盐或它们的衍生物与赋形剂、粘合剂、崩解剂等预备颗粒,然后,直接或者加入上述添加剂均匀地混合后形成颗粒,通过压缩成型制成片剂。颗粒剂或片剂在必要时可以通过适当的包衣剂(明胶、蔗糖、阿拉伯胶、巴西棕榈蜡等)或肠溶包衣剂(例如,乙酸邻苯二甲酸纤维素、甲基丙烯酸共聚物、羟丙基纤维素邻苯二甲酸酯、羧甲基乙基纤维素等)进行包衣。胶囊剂可以如下制备:向支链氨基酸、其盐或它们的衍生物中加入上述赋形剂、粘合剂、崩解剂等,均匀捏合混合物,可选地将混合物制成颗粒,可选地用包衣剂对颗粒进行包衣,然后将混合物、颗粒或已包衣的颗粒填充到胶囊中。
虽然对口服给药用固形制剂中的支链氨基酸、其盐或它们的衍生物的含有比例不特别限定,但是优选支链氨基酸的总量相对于全部固形制剂为约1~90质量%。
口服给药用液体制剂包括例如水剂、悬浮剂、乳剂、糖浆剂和酏剂。可以在这种液体制剂中使用的添加剂包括例如净化水、乙醇和它们的混合液等溶剂。该口服给药用液体制剂还可以含有例如助悬剂(例如,阿拉伯胶、琼脂、羧甲基纤维素、羟丙基纤维素等)、乳化剂(例如,聚山梨酯80、阿拉伯胶等)、调味物质(例如,单糖浆、蜂蜜、蔗糖、酒石酸等)、芳香物质(例如,水杨酸甲酯、小茴香油、橙油、薄荷醇等)、防腐剂(例如,苯甲酸、苯甲酸钠等)和缓冲剂(例如,柠檬酸、碳酸氢盐等)。这些添加剂可以单独使用或者并用两种以上。
可以用于肠胃外给药用注射剂的添加剂包括例如溶剂、稳定剂、增溶剂、助悬剂、表面活性剂、乳化剂、无痛剂、缓冲剂和防腐剂。溶剂包括但不限于注射用蒸馏水、生理盐水、例如芝麻油等植物油、乙醇、异丙醇、丙二醇、1,3-丁二醇和聚乙二醇。稳定剂和增溶剂包括但不限于谷氨酸、天冬氨酸和聚山梨酯80。助悬剂包括但不限于例如羧甲基纤维素钠和甲基纤维素等纤维素衍生物,和例如西黄蓍胶和阿拉伯胶等天然胶。表面活性剂包括但不限于脱水山梨糖醇脂肪酸酯、聚氧乙烯脱水山梨糖醇脂肪酸酯、聚氧乙烯脂肪酸酯、氢化蓖麻油的聚氧乙烯醚和卵磷脂。乳化剂包括但不限于硬脂酸聚烃氧基酯、聚桂醇、聚山梨酯80和阿拉伯胶。无痛剂包括但不限于氨基苯甲酸乙酯、肌醇、盐酸美普卡因、盐酸利多卡因、三氯叔丁醇、丙二醇和苯甲醇。缓冲剂包括但不限于柠檬酸或其盐、葡萄糖、磷酸或其盐和乙酸或其盐。防腐剂包括但不限于对羟基苯甲酸酯、苯扎氯铵和脱水山梨糖醇酸盐。这些添加剂可以单独使用或者并用两种以上。
注射剂可以根据常规方法,例如通过无菌操作法适当溶解支链氨基酸、其盐或它们的衍生物与添加剂等来进行制备。制备的注射剂被填充到安瓿、西林瓶(vial)、玻璃或聚乙烯制输液容器(包括袋)等中,然后进行灭菌。聚乙烯制输液容器(包括袋)可以例如与脱氧剂等一起包装于阻气性包装材料中。注射剂可以制成无菌的固形制剂,例如冻干制品,在正要使用前溶解于已灭菌或无菌的注射用蒸馏水或其它的溶剂中来使用。
虽然对支链氨基酸、其盐或它们的衍生物的含有比例不特别限定,但是在输液制剂的情况下,相对于注射剂整体,换算为游离支链氨基酸的总量优选为约0.1~10w/v%,更优选为约0.1~5w/v%,进一步优选为约0.5~3w/v%。
本发明的抗抑郁剂可以进一步含有例如维生素(例如,维生素A,维生素B1、B2、B6、B12,维生素C,维生素D,维生素E,烟酸,泛酸,叶酸,生物素,维生素F,维生素P,维生素Q,维生素U,胆碱,肌醇,对氨基苯甲酸等)和支链氨基酸以外的氨基酸(例如,赖氨酸,苯丙氨酸,蛋氨酸,苏氨酸,缬氨酸,组氨酸,色氨酸,丙氨酸,脯氨酸,精氨酸,谷氨酸,丝氨酸等)等营养素。
对含有本发明的抗抑郁剂的上述药物的给药量不特别限定,可以根据剂型、给药途径、患者的年龄和体重、疾病的严重程度等决定。换算为游离支链氨基酸,通常给药量为每日、每kg成人体重为可以约1~1000mg、优选为约1~500mg、更优选为约10~500mg、进一步优选为约50~300mg的范围之内,根据需要可以适当增减。该药物也可以每天分数次给药。
当本发明的抗抑郁剂为食品形式时,将支链氨基酸、其盐或它们的衍生物中的至少一种,优选至少将L-异亮氨酸与食品卫生法上认可的添加物或其它食品中使用的各种成分混合来制备食品或饮品。对所制备的食品的形式不特别限定,可以为例如片剂、胶囊剂、散剂、颗粒剂、口服给药用液体制剂、固体食品、膏状或果酱状的半流体食品、凝胶状食品和饮料等任何可能的食品形式。食品的具体例子包括例如,软饮料、果汁或乳酸菌饮料等饮料,果冻,糖果,饼干和曲奇。对该食品的制备方法不特别限定,可以使用此项技术中已知的任何方法。
上述食品除了支链氨基酸、其盐或它们的衍生物之外优选含有碳水化合物、膳食纤维等,更优选含有碳水化合物。碳水化合物的例子包括上述糖类,优选为单糖类、特别优选为葡萄糖。碳水化合物相对于支链氨基酸的含有比例与上述抗抑郁剂的情况相同。膳食纤维特别优选为难消化性糊精。
除了使用食品卫生法中认可的添加物(例如,羟丙甲基纤维素、微晶纤维素、酒石酸、甘露醇、糖精钠、甜菊、二甲基聚硅氧烷、对羟基苯甲酸酯等)来替代上述药物中的片剂、胶囊剂、散剂、颗粒剂或口服给药用液体制剂中的添加物之外,可以用与上述药物的制备方法同样的方式制备片剂、胶囊剂、散剂、颗粒剂或口服给药用液体制剂。
制备饮料时,根据需要可以含有例如,诸如香料、着色料、天然果汁、果肉、干酪和巧克力等调味物质和合成甜味剂等添加物。该添加物可以单独使用或者两种以上组合使用。
制备的膏状或果酱状的半流体食品、或者例如果冻等凝胶状食品,除了上述饮料中的成分之外,优选进一步含有一种或多种选自琼脂、明胶、角叉菜胶、结冷胶、黄原胶、刺槐豆胶、果胶、海藻酸钠、海藻酸钾和其它通常使用的多糖增稠剂中的凝胶化剂。相对于100质量份果冻,凝胶化剂的配比量为约2质量份以下,优选为约0.5~2质量份。
对这种食品中的支链氨基酸、其盐或它们的衍生物的含有比例不特别限定,但是优选换算为游离支链氨基酸的总量为约1~60质量%。换算为食品中游离支链氨基酸的总量,优选为约10~60质量%,更优选为约15~60质量%。
如此制备的食品可以用作改善抑郁状态的功能性食品。含有选自这种支链氨基酸、其可药用的盐或它们的衍生物中的至少一种化合物的抑郁状态改善用食品组合物也包括在本发明之内。优选在这种食品的包装等上提供其改善抑郁状态的效果的提示。
换算为游离支链氨基酸的上述食品的日摄取量优选为每成人(约60kg)约0.1~20g。换算为游离支链氨基酸的食品的日摄取量更优选为每成人(约60kg)约1~20g,进一步优选约为3~20g,特别优选约为5~20g。
通过向哺乳动物给予选自支链氨基酸、其可药用的盐和它们的衍生物中的至少一种化合物的有效量,可以预防、改善或治疗抑郁症。作为给药对象的哺乳动物,代表性地为人,优选的例子包括患有抑郁症的人,以及有可能陷入抑郁状态的人(患有隐匿性抑郁症的人,压力过大的人等)。预防包括例如,从有可能陷入抑郁状态发展成抑郁症的抑制,从健康状态发展成抑郁症的抑制。
含有向哺乳动物给予选自支链氨基酸、其可药用的盐和它们的衍生物中的至少一种化合物的预防或治疗抑郁症的方法也包括在本发明中。在本发明的预防或治疗抑郁症的方法中,优选制备含有选自支链氨基酸、其可药用的盐和它们的衍生物中的至少一种化合物作为有效成分的抗抑郁剂,并给予该抗抑郁剂。还优选制备含有选自支链氨基酸、其可药用的盐和它们的衍生物中的至少一种化合物的食品组合物,并使哺乳动物摄取该食品组合物。
选自支链氨基酸、其可药用的盐和它们的衍生物中的至少一种化合物在制备抗抑郁剂中的使用;以及选自支链氨基酸、其可药用的盐和它们的衍生物中的至少一种化合物作为抗抑郁剂的使用也包括在本发明中。使用选自支链氨基酸、其可药用的盐和它们的衍生物中的至少一种化合物制备的抗抑郁剂的优选方式与上述抗抑郁剂相同。
实施例
以下,参照制备例和试验例对本发明进行更具体的说明,但是本发明不被这些实施例所限定。
<制备例1>
将L-异亮氨酸300g溶解于注射用蒸馏水中。用氢氧化钠将该溶液的pH调节为6.50后,用注射用蒸馏水调至总体积为10L。将得到的溶液通过膜滤器过滤,以500mL/袋向聚乙烯制输液袋中填充、密封并在105℃下进行40分钟高压蒸气灭菌。将该袋与脱氧剂(三菱ガス化学制;商品名:エ—ジレス)一起用聚乙烯醇多层膜制成的阻气包装材料包装,得到注射剂。
<制备例2>
将L-异亮氨酸150g和L-缬氨酸150g溶解于注射用蒸馏水中。用氢氧化钠将该溶液的pH调节为6.50后,用注射用蒸馏水调至总体积为10L。将得到的溶液通过膜滤器过滤,以500mL/袋向聚乙烯制输液袋中填充、密封并在105℃下进行40分钟高压蒸气灭菌。将该袋与脱氧剂(三菱ガス化学制;商品名:エ—ジレス)一起用聚乙烯醇多层膜制成的阻气包装材料包装,得到注射剂。
<制备例3>
将L-异亮氨酸300g溶解于注射用蒸馏水中。用氢氧化钠将该溶液的pH调节为6.50后,用注射用蒸馏水调至总体积为10L并通过膜滤器过滤。
另一方面,将葡萄糖1000g溶解于注射用蒸馏水中。用注射用蒸馏水将该溶液的总体积调至10L并通过膜滤器过滤。
将这些溶液各自取500mL分别填充于聚乙烯制两室输液袋的不同室中,密封并在105℃下进行40分钟高压蒸气灭菌。将该袋与脱氧剂(三菱ガス化学制;商品名:エ—ジレス)一起用聚乙烯醇多层膜制的阻气包装材料包装,得到注射剂。
使用该注射剂时,挤压该袋的一室或者两室,从而将两室相连制成混合溶液,用作注射液。
<制备例4>
将L-丙氨酰基-L-亮氨酸1000g、L-异亮氨酸300g和L-缬氨酸240g溶解于注射用蒸馏水中。用氢氧化钠将该溶液的pH调节为6.50后,用注射用蒸馏水将总体积调至10L。将得到的溶液通过膜滤器过滤,以100mL/袋向聚乙烯制输液袋中填充、密封,并在105℃下进行40分钟高压蒸气灭菌。将该袋与脱氧剂(三菱ガス化学制;商品名:エ—ジレス)一起用聚乙烯醇多层膜制的阻气包装材料包装,得到注射剂。
<制备例5>
向10L净化水中加入并分散羟丙甲基纤维素120g和微晶纤维素羧甲基纤维素钠10g。向该分散液中加入并溶解酒石酸100g、甘露醇1000g、糖精钠10g、甜菊5g、二甲基聚硅氧烷40g、对羟基苯甲酸丙酯2g和对羟基苯甲酸甲酯5g。然后,向其中加入L-异亮氨酸950g、L-亮氨酸1900g和L-缬氨酸1150g,用均化器悬浮。该悬浮液用氢氧化钠将pH调节为6.5,进一步用均化器悬浮,制备均匀的悬浮液。
另一方面,向2L净化水中加入琼脂粉末40g、在约80℃下加温溶解。向得到的溶液中加入上述悬浮液6000g和菠萝香料40g,进行混合。以100g/容器的量向容器中填充得到的混合液,密封冷藏,制备果冻。
<制备例6>
将L-异亮氨酸500g、L-亮氨酸1000g、缬氨酸600g、柠檬酸酐100g和羟丙基纤维素50g均匀地混合,然后向混合物中添加蒸馏水300g进行造粒。
在60℃下干燥造粒产物2小时,并通过24目的筛得到颗粒。将得到的颗粒以4.5g/袋的量填充到铝层压粘性袋中,密封得到最终产品。
<试验例1>
口服给予支链氨基酸的抗抑郁作用
将10周龄SD大鼠分为两组(每组10只大鼠)。一组(对照组)在自由摄食(精制饲料AIN-76,日本农产工业株式会社制)和自由饮水下饲养6天。另一组(本发明组)在自由摄食(含有1质量%的L-异亮氨酸的精制饲料AIN-76)和自由饮水下饲养6天。使用这些受试动物,按照Gutman,D.A.等的防御性突然戒断试验方法(The Journal of Pharmacology andExperimental Therapeutics,304(2),874(2003)),对压力下的大鼠的抑郁状态改善作用进行试验。
即,将大鼠(每组各一只)从尾部开始放入直立的直径10cm、长20cm的黑色圆筒内,并立刻盖上盖子。10秒后,将圆筒放在由白色丙烯酸板构成的开阔区域(长100cm、宽100cm、高45cm),面向一个转角,距离该转角20cm的位置。立刻取下盖子,观察大鼠的行为5分钟,测定大鼠从圆筒出来所需的时间。
试验在隔音室中、在200勒(1x)的照度下进行,大鼠的行为从上方拍摄,并通过隔音室外的监视器进行观察。
统计处理通过双侧学生氏t检验进行。
结果如图1所示。与对照组相比,在本发明组从圆筒出来所需的时间显著短,这证明了L-异亮氨酸的抗抑郁效果。
使用L-亮氨酸或L-缬氨酸进行相同的试验,确认了具有与L-异亮氨酸相同的抗抑郁效果。
产业上的可利用性
本发明的抗抑郁剂可以改善抑郁状态或预防陷入抑郁状态,由于其安全性高、可以持续给药。因此,上述抗抑郁剂可用于药物或食品中。
Claims (11)
1、一种抗抑郁剂,含有选自支链氨基酸、其可药用的盐和它们的衍生物中的至少一种化合物作为有效成分。
2、根据权利要求1所述的抗抑郁剂,其中,支链氨基酸为选自L-缬氨酸、L-亮氨酸和L-异亮氨酸中的至少一种化合物。
3、根据权利要求2所述的抗抑郁剂,其中,抗抑郁剂至少含有L-异亮氨酸。
4、根据权利要求3所述的抗抑郁剂,其中,L-异亮氨酸、L-亮氨酸和L-缬氨酸的含有比例按照摩尔比换算为1∶(0~3)∶(0~2)。
5、根据权利要求1~4中任意一项所述的抗抑郁剂,其中,抗抑郁剂进一步含有碳水化合物。
6、根据权利要求5所述的抗抑郁剂,其中,碳水化合物为葡萄糖。
7、根据权利要求1~6中任意一项所述的抗抑郁剂,抗抑郁剂为注射剂或颗粒的形式。
8、一种抑郁症的预防或治疗方法,包括向哺乳动物给予选自支链氨基酸、其可药用的盐和它们的衍生物中的至少一种化合物。
9、选自支链氨基酸、其可药用的盐和它们的衍生物中的至少一种化合物在制备抗抑郁剂中的使用。
10、选自支链氨基酸、其可药用的盐和它们的衍生物中的至少一种化合物作为抗抑郁剂的使用。
11、一种抑郁状态改善用食品组合物,含有选自支链氨基酸、其可药用的盐和它们的衍生物中的至少一种化合物作为有效成分。
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US7635390B1 (en) * | 2000-01-14 | 2009-12-22 | Marctec, Llc | Joint replacement component having a modular articulating surface |
US7708741B1 (en) | 2001-08-28 | 2010-05-04 | Marctec, Llc | Method of preparing bones for knee replacement surgery |
CN116370448A (zh) * | 2017-04-26 | 2023-07-04 | 纳维托制药有限公司 | Sestrin-gator2相互作用的调节剂及其用途 |
WO2019172287A1 (ja) * | 2018-03-05 | 2019-09-12 | 味の素株式会社 | 認知機能の改善用組成物および不安様症状の改善用組成物、ならびに脳萎縮の抑制用組成物 |
WO2021087432A1 (en) | 2019-11-01 | 2021-05-06 | Navitor Pharmaceuticals, Inc. | Methods of treatment using an mtorc1 modulator |
Family Cites Families (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH02172915A (ja) | 1988-12-23 | 1990-07-04 | Ajinomoto Co Inc | 脳細胞代謝改善組成物 |
JPH03275631A (ja) | 1990-03-19 | 1991-12-06 | Ajinomoto Co Inc | 抗痴呆薬 |
JP3942207B2 (ja) | 1995-02-17 | 2007-07-11 | 武田薬品工業株式会社 | うつ性症状改善剤 |
JPH08238148A (ja) * | 1995-03-06 | 1996-09-17 | Unicom:Kk | 積木脚を備えた幼児用家具及びその構成部材 |
JP2000026289A (ja) | 1998-07-01 | 2000-01-25 | Crescendo Corporation:Kk | 分岐鎖アミノ酸による筋肉痛・筋肉のこり、はりへの効果 |
JP2000026290A (ja) | 1998-07-07 | 2000-01-25 | Crescendo Corporation:Kk | 分岐鎖アミノ酸による筋力維持 |
RU2151596C1 (ru) * | 1999-03-10 | 2000-06-27 | Казанский государственный университет им. В.И. Ульянова-Ленина | Композиция аминокислот с микроэлементами и кальцием, обладающая противоопухолевой, антидепрессивной и противоаритмической активностью |
WO2002034257A1 (fr) | 2000-10-27 | 2002-05-02 | Meiji Dairies Corporation | Agents de recuperation ou de prevention de la fatigue dans le systeme nerveux central et aliments de recuperation ou de prevention associes |
JP3341769B1 (ja) | 2002-01-25 | 2002-11-05 | 味の素株式会社 | 分岐鎖アミノ酸含有チュアブル剤 |
JP4281281B2 (ja) | 2002-01-30 | 2009-06-17 | 味の素株式会社 | 分岐鎖アミノ酸を含有するドライシロップ剤 |
JP3341770B1 (ja) | 2002-01-30 | 2002-11-05 | 味の素株式会社 | 分岐鎖アミノ酸を含有するゼリー剤 |
US7445807B2 (en) * | 2002-10-15 | 2008-11-04 | Western Holdings, Llc | Agglomerated granular protein-rich nutritional supplement |
GB0400031D0 (en) * | 2004-01-03 | 2004-02-04 | Univ Sheffield | Depression treatment |
US20070191287A1 (en) * | 2004-03-18 | 2007-08-16 | Michio Yamamura | D-ribose for improving depression-like symptoms |
JP2005336176A (ja) | 2004-04-28 | 2005-12-08 | Tanabe Seiyaku Co Ltd | 肉体疲労改善剤 |
WO2006077954A1 (ja) | 2005-01-21 | 2006-07-27 | Kyowa Hakko Kogyo Co., Ltd. | 神経疾患治療剤 |
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2007
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- 2007-10-10 KR KR20097006850A patent/KR20090077903A/ko not_active Application Discontinuation
- 2007-10-10 CN CN2007800371989A patent/CN101522185B/zh not_active Expired - Fee Related
- 2007-10-10 AT AT07829459T patent/ATE537822T1/de active
- 2007-10-10 WO PCT/JP2007/069721 patent/WO2008044691A1/ja active Application Filing
- 2007-10-10 US US12/444,144 patent/US9060979B2/en not_active Expired - Fee Related
- 2007-10-10 CA CA2664054A patent/CA2664054C/en active Active
- 2007-10-10 JP JP2008538731A patent/JP5266058B2/ja not_active Expired - Fee Related
- 2007-10-10 EP EP20070829459 patent/EP2077111B1/en not_active Not-in-force
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109689039A (zh) * | 2016-09-09 | 2019-04-26 | 味之素株式会社 | 用于预防或改善痴呆症或抑郁状态的组合物 |
CN109689039B (zh) * | 2016-09-09 | 2021-09-21 | 味之素株式会社 | 用于预防或改善痴呆症或抑郁状态的组合物 |
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US20100105774A1 (en) | 2010-04-29 |
TW200820983A (en) | 2008-05-16 |
JP5266058B2 (ja) | 2013-08-21 |
ATE537822T1 (de) | 2012-01-15 |
KR20090077903A (ko) | 2009-07-16 |
TWI397418B (zh) | 2013-06-01 |
EP2077111A4 (en) | 2010-03-24 |
US9060979B2 (en) | 2015-06-23 |
CN101522185B (zh) | 2012-07-11 |
EP2077111A1 (en) | 2009-07-08 |
CA2664054C (en) | 2015-05-26 |
WO2008044691A1 (fr) | 2008-04-17 |
EP2077111B1 (en) | 2011-12-21 |
CA2664054A1 (en) | 2008-04-17 |
JPWO2008044691A1 (ja) | 2010-02-12 |
AU2007305535A1 (en) | 2008-04-17 |
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