CN100381119C - 治疗糖尿病的组合物 - Google Patents
治疗糖尿病的组合物 Download PDFInfo
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- CN100381119C CN100381119C CNB038047926A CN03804792A CN100381119C CN 100381119 C CN100381119 C CN 100381119C CN B038047926 A CNB038047926 A CN B038047926A CN 03804792 A CN03804792 A CN 03804792A CN 100381119 C CN100381119 C CN 100381119C
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- diabetes
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- coenzyme
- reduced coenzyme
- ubiquinone
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Abstract
本发明为患有糖尿病性高血糖症的患者和所谓的糖尿病预备军即葡萄糖耐量异常的人提供提高葡萄糖耐量的组合物。该组合物有助于控制血糖水平,预防糖尿病并发症,并因其高安全性而能长期给药。含有辅酶Q尤其是还原型辅酶Q10作为主要成分的组合物能提高糖尿病患者恶化的葡萄糖耐量,令人满意地控制血糖水平,并降低血液糖化血红蛋白水平。
Description
技术领域
本发明涉及含有辅酶Q的用于治疗糖尿病的组合物。
背景技术
糖尿病是最常见但很严重的生活习惯病之一。全世界有超过一百万的患者患糖尿病。并且,所谓的糖尿病预备军,即具有较高血糖水平的人的数量远远超过糖尿病患者的数量。糖尿病在世界范围内是一种严重的疾病。
已知有二种类型的糖尿病:胰岛素分泌不足引起的I型糖尿病(胰岛素依赖性糖尿病)和对胰岛素的敏感性降低引起的II型糖尿病(非胰岛素依赖性糖尿病)。大多数糖尿病患者患有II型糖尿病,其经常由不适当的生活习惯如过度饮食引起。
糖尿病的一个问题是缺乏表明高血糖的症状。因此,血糖水平经常处于长期得不到控制的状态,从而导致并发症(如视网膜病、肾病和动脉硬化)。例如,在日本,导致成人视力障碍最常见的病因是糖尿病性视网膜病。在日本,导致人工透析的慢性肾衰竭的第二种最常见病因是糖尿病性肾病。由于这些并发症的严重性,糖尿病治疗的首要目标是保持严格的血糖控制。
由于胰岛素分泌不足是I型糖尿病的病因,因此可通过胰岛素注射非常有效地控制I型糖尿病患者的血糖。但是,由于II型糖尿病患者对胰岛素的敏感性低,所以胰岛素注射对II型糖尿病患者不那么有效。对II型糖尿病患者的治疗包括饮食限制,其中限制过量饮食热量的摄取,并结合运动疗法以促进体内热量的消耗。但是,在很多情况下饮食控制难于继续。对于那些尽管采用饮食限制和运动疗法但仍没有表现出明显好转的患者来说,尝试通过施用糖尿病药物(磺酰脲类药物、双胍类药物等)来治疗。但是,这些药物存在以下严重问题。已知具有很长给药历史并且其第二代药物已从二十世纪70年代开始使用的磺酰脲类药物(SU药物)会导致由血糖水平过度降低产生的低血糖。另外,SU药物产生强烈的饥饿感,因而往往导致饮食限制失败。这常常导致血糖控制失败并促进肥胖。因此,医师必须严格控制施用存在这些问题的SU药物。双胍类药物(BG药物)也从二十世纪70年代就开始使用了。但是,不久后就报道了多例副作用,即乳酸酸中毒。尽管最近重新评价了BG药物的给药方法和有效性,但施用BG药物还需要医师的严格控制。
在这些情况下,已尝试开发新的口服糖尿病药物,例如已开发了α-葡萄糖苷酶抑制剂和胰岛素增敏剂。但是,这些药物历史短,因而这些药物能否被认可作为非常安全和有效的药物必须等待进一步的调查研究。事实上,已经因肝病副作用而停止了胰岛素增敏剂曲格列酮的开发。
如上所述,对于糖尿病患者而言,非常安全的口服糖尿病药很难得到。糖尿病的主要治疗仍是饮食限制;但是,在许多实际情况中,严格的饮食限制是困难的。尽管已为糖尿病患者开发了很多低热量食物,但是它们只能部分地有助于糖尿病治疗。此外,由于没有治疗糖尿病并发症特征的治疗药,所以目前通过严格控制血糖水平来预防并发症。因此,糖尿病的治疗期待能在饮食限制期间可安全给药的非常安全和有效的药物、有效的食物等。
辅酶Q为广泛存在于从细菌到哺乳动物各种生物机体内的必需成分,并已知可作为生物机体细胞中线粒体电子传递系统的成分。辅酶Q不仅通过在线粒体内的反复氧化和还原充当电子传递系统的传递成分,而且具有抗氧化作用。人辅酶Q的主要成分为辅酶Q10,其为侧链由10个重复单元组成的辅酶Q。
辅酶Q10的重要特征为高安全性。在大鼠中以1200mg/Kg的日剂量连续52周进行的慢性毒性试验报告没有毒性作用(K.D.Williams等,J.Agric.Food Chem.,47,3756-3763,1999)。
关于辅酶Q10,氧化型辅酶Q10在日本被广泛用作充血性心力衰竭药物,在欧洲和美国被广泛用作健康食品。尽管有报道提出氧化型辅酶Q10对糖尿病有疗效(Shimomura,Y.等,1981,Rinsho to Kenkyu,58,1349-1352),但氧化型辅酶Q10对糖尿病患者的疗效实际还不为人所知。还原型辅酶Q10为氧化型辅酶Q10的活化形式,在空气中通过氧化易转化成氧化型辅酶Q10。因此,在产品中还未使用还原型辅酶Q10。我们以前发现,与单独使用氧化型辅酶Q10相比,通过混合还原型辅酶Q10和氧化型辅酶Q10可提高总辅酶Q10的口服吸收性(特开平10-109933号公报)。但是,还原型辅酶Q10是否比氧化型辅酶Q10对疾病如糖尿病表现出更好的作用还不清楚。
发明概述
本发明的目的是提供能令人满意地控制糖尿病患者血糖水平的非常安全的口服组合物。
本发明人进行了大量研究并发现,通过使用非常安全的辅酶Q尤其是还原型辅酶Q能得到对糖尿病有效的组合物。
本发明涉及一种治疗糖尿病的组合物,该组合物包含式(1)所示的还原型辅酶Q作为有效成分:
(其中n表示1到12之间的整数)。
本发明还涉及一种治疗糖尿病的组合物,该组合物包含上述还原型辅酶Q和式(2)所示的氧化型辅酶Q作为有效成分:
(其中n表示1到12之间的整数)。
本发明还涉及其中辅酶Q为辅酶Q10的上述组合物;还含有糖尿病治疗药物的上述组合物;和其中糖尿病治疗药为磺酰脲类药物、磺胺类药物、双胍类药物、α-葡萄糖苷酶抑制剂、胰岛素增敏剂或胰岛素的上述组合物。
本发明还涉及含有上述治疗糖尿病的组合物的药物、功能性食品和动物饲料。
本发明还涉及控制血糖水平的方法和使用上述治疗糖尿病的组合物预防糖尿病并发症的方法。
发明详述
下面详细描述本发明。
辅酶Q用式(1):
(其中n表示1到12之间的整数),或式(2):
(其中n表示1到12之间的整数)来表示。式(1)所示的辅酶Q为还原型辅酶Q,式(2)所示的辅酶Q为氧化型辅酶Q。
对获得氧化型辅酶Q和还原型辅酶Q的方法没有特殊限制。这种方法的一个例子包括以下步骤:利用常规方法如合成、发酵或从天然物质中提取来制备辅酶Q,并浓缩通过色谱法得到的洗脱液中的氧化型辅酶Q级分或还原型辅酶Q级分。可通过常规方法制备氧化型辅酶Q。还原型辅酶Q可通过以下方法来制备:向上面得到的辅酶Q中加入常用还原剂如硼氢化钠或连二亚硫酸钠(保险粉),通过常规方法还原辅酶Q以制备还原型辅酶Q,并利用色谱法浓缩得到的还原型辅酶Q。可通过上述还原剂与常用高纯度辅酶Q的相互作用制备还原型辅酶Q。
如式(1)和(2)所示,本发明中使用的辅酶Q带有具有1至12个重复单元(式中的“n”)的侧链,尤其优选带有具有10个重复单元的侧链的辅酶Q,即辅酶Q10。
根据本发明的治疗糖尿病的组合物含有上述还原型辅酶Q作为有效成分或含有上述还原型辅酶Q和上述氧化型辅酶Q作为有效成分。
对得到治疗糖尿病的组合物的方法没有特殊限制。例如,可通过将上面制备的还原型辅酶Q或上面制备的还原型辅酶Q和氧化型辅酶Q溶解到合适的常用溶剂如异丙醇、丙酮或醚中,以便得到含有预定量的还原型辅酶Q的组合物。或者,可使用固体形式的还原型辅酶Q。或者,可将固体形式的还原型辅酶Q简单地与固体形式的氧化型辅酶Q混合。或者,可直接使用上述生产辅酶Q的方法中得到的氧化型辅酶Q和还原型辅酶Q的混合物。可通过控制上述常用高纯度辅酶Q的还原反应持续时间、还原剂的类型或还原剂的量直接制备本发明的组合物。
考虑到效果、成本等,根据本发明的治疗糖尿病的组合物优选含有组合物总量的0.001-20wt%、更优选0.01-10wt%的辅酶Q。
为获得更高的疗效,还原型辅酶Q含量优选为辅酶Q总量的至少60wt%,更优选至少为80wt%。
根据本发明的治疗糖尿病的组合物可另外含有治疗糖尿病的药物。治疗糖尿病的药物的例子包括磺酰脲类药物、磺胺类药物、双胍类药物、α-葡萄糖苷酶抑制剂、胰岛素增敏剂和胰岛素。
对治疗糖尿病的药物的含量没有特殊限制,可根据用途如药物、功能性食品和动物饲料等适当地确定。
例如,根据本发明的治疗糖尿病的组合物提高了葡萄糖耐量并有利于血糖水平的控制。因此,治疗糖尿病的组合物对预防糖尿病发作、治疗糖尿病和预防糖尿病并发症是有效的。
也可在控制血糖水平的方法中和预防糖尿病并发症的方法中使用本发明的治疗糖尿病的组合物。
例如,可在糖尿病药物、糖尿病人用功能性食品和食品原料和糖尿病动物患者用饲料中使用本发明的治疗糖尿病的上述组合物。这里,术语“功能性食品”是指不是药物但可口头服用以维持或改善健康的产品。功能性食品的例子包括口服增补剂、特定保健用食品、保健食品和食品添加物。
可在任何涉及到口服给药辅酶Q或口服给药辅酶Q和药物的应用中使用治疗糖尿病的组合物。
当本发明治疗糖尿病的组合物用作药物、功能性食品、动物饲料等时,对剂型没有特殊限制。例如,治疗糖尿病的组合物可用作粉剂、通过混合粘合剂制备的颗粒剂、通过用包衣剂包衣粉末颗粒制备的包衣粉剂或含有粉剂、颗粒剂或包衣粉剂的胶囊。治疗糖尿病的组合物可与天然油、油状高级脂肪酸、高级脂肪酸单酸甘油酯、表面活性剂或它们的混合物混合以制备含有所得油状混合物的软胶囊。这里,也可以使用主要由明胶或其它水溶性聚合物组成的物质。此外,术语“胶囊”包括微囊。
尤其是对于功能性食品应用,可将辅酶Q掺入到常规糖尿病人食品中。
治疗糖尿病的组合物优选含有防止还原型辅酶Q氧化的抗氧剂。但是,抗氧剂不是必需的,取决于剂型。抗氧剂的例子包括柠檬酸及其衍生物、维他命C及其衍生物、番茄红素、维他命A、类胡萝卜素、维他命B及其衍生物、类黄酮、多酚、谷胱甘肽、硒、硫代硫酸钠、维他命E及其衍生物、过氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶、谷胱甘肽-S-转移酶、谷胱甘肽还原酶、过氧化氢酶、抗坏血酸过氧化物酶和它们的混合物。
使用螯合剂也可以防止氧化。螯合剂的例子包括乙二胺四乙酸及其盐、乙二胺二乙酸及其盐、肟基二乙酸及其盐、羟乙基乙二胺四乙酸及其盐、二亚乙基三胺五乙酸及其盐、氨三乙酸及其盐、三亚乙基四胺六乙酸及其盐、二羧甲基谷氨酸四钠盐、二羟甲基甘氨酸、1,3-丙二胺四乙酸及其盐、1,3-二氨基-2-羟基丙烷四乙酸及其盐、葡萄糖酸钠、羟亚乙基二磷酸、nitrilotris(N[(-R-P(O)(OH)2)]3-)、膦酰基丁烷三羧酸和它们的混合物。
另外,上述抗氧剂可与螯合剂联合使用。
除上述还原型辅酶Q外,本发明治疗糖尿病的组合物还可根据常规方法含有适量药学上允许和食品卫生学上允许的物质。药学上允许和食品卫生学上允许的物质的例子包括但不限于赋形剂、崩解剂、润滑剂、粘合剂、包衣剂、着色剂、凝固抑制剂、吸收促进剂、增溶剂、稳定剂、保健食品原料、食品添加物原料和维他命。
赋形剂的例子包括但不限于蔗糖、乳糖、葡萄糖、玉米淀粉、甘露醇、结晶纤维素、磷酸钙和硫酸钙。
崩解剂的例子包括但不限于淀粉、琼脂、柠檬酸钙、碳酸钙、碳酸氢钠、糊精、结晶纤维素、羧甲基纤维素和黄蓍胶。
润滑剂的例子包括但不限于滑石粉、硬脂酸镁、聚乙二醇、二氧化硅和氢化植物油。
粘合剂的例子包括但不限于乙基纤维素、甲基纤维素、羟丙甲基纤维素、黄蓍胶、虫胶、明胶、阿拉伯胶、聚乙烯吡咯烷酮、聚乙烯醇、聚丙烯酸、聚甲基丙烯酸和山梨糖醇。
包衣剂的例子包括但不限于阿拉伯胶、欧巴代、夏枯草、蓖麻蜡、羧乙烯聚合物、羧甲纤维素、水合二氧化硅、硅酸镁、醋酸乙烯树脂、硬脂酸、鲸蜡醇和羟丙基甲基纤维素。
着色剂的例子包括但不限于允许加入到药物和食品中的物质。
凝固抑制剂的例子包括但不限于硬脂酸、滑石粉、轻质硅酸酐和水合二氧化硅。
吸收促进剂的例子包括但不限于表面活性剂如高级醇、高级脂肪酸和脂肪酸甘油酯。
增溶剂的例子包括但不限于有机酸如富马酸、琥珀酸和马来酸。
稳定剂的例子包括但不限于苯甲酸、苯甲酸钠和仲羟基苯甲酸乙酯。
保健食品原料的例子包括但不限于中国草药(如胃苓汤、温经汤、温清饮、黄耆建中汤、黄连解毒汤、黄连汤、葛根汤、加味归脾汤、加味逍遥散、甘麦大枣汤、桔梗汤、归脾汤、九味槟榔汤、荆芥连翘汤、桂皮加芍药大黄汤、桂皮加芍药汤、桂皮加龙骨牡蛎汤、桂枝汤、桂枝人参汤、桂枝茯苓丸、启脾汤、香苏散、五虎汤、五积散、牛车肾气丸、五淋散、柴陷汤、柴胡加龙骨牡蛎汤、柴胡桂皮干姜汤、柴胡桂枝汤、柴胡清肝汤、柴朴汤、柴苓汤、酸枣仁汤、滋阴降火汤、四逆散、四君子汤、四物汤、炙甘草汤、芍药甘草汤、十全大补汤、十味败毒汤、小建中汤、小柴胡汤、小青龙汤、消风散、辛夷清肺汤、神秘汤、真武汤、清上防风汤、清暑益气汤、清心莲子饮、清肺汤、疏经活血汤、大黄甘草汤、大黄牡丹皮汤、大建中汤、大柴胡汤、大柴胡汤去大黄、大承气汤、大防风汤、治大扑撲一方(ji-daboku-ippo)、调胃承气汤、钓藤散、肠痈汤、猪苓汤、猪苓汤合四物汤、通导散、桃核承气汤、当归饮子、当归建中汤、当归芍药散、当归汤、二陈汤、女神散、人参汤、人参养荣汤、排脓散及汤、麦门冬汤、八味地黄丸、半夏厚朴汤、半夏泻心汤、白虎加人参汤、茯苓饮、茯苓饮合半夏厚朴汤、平胃散、防已黄耆汤、防风通圣散、补中益气汤、麻黄汤、麻黄附子细辛汤、麻杏甘石汤、麻子仁丸、木防已汤、抑肝散、抑肝散加陈皮半夏、六君子汤、立效散、龙胆泻肝汤、苓甘姜味辛夏仁汤和六味丸等);茶(如绿茶、糙米茶、粉茶、煎茶、焙的茶、茉莉花茶、乌龙茶、红茶、黑茶、花茶、清茶和白茶);药草(如意大利欧芹(Italian parsley)、土木香(elecampane)、橄榄、薄荷(oregano)、刺菜蓟、春黄菊、咖哩植物、樟脑草、藏茴香、黑儿波(christmas rose)、绛三叶草(crimson clover)、矢车菊、普通锦葵(common mallow)、生菜地榆(salad burnet)、神圣亚麻(santolina)、桂皮、茉莉、甜菊(stevia)、鼠尾草(sage)、椴树(linden)、大叶天竺葵(scentedgeranium)、St.John′s植物(St.John′s wort)、肥皂草(soapwort)、黄精(Solomon’sseal)、百里香、艾菊、山萝卜(chervil)、细香葱、旱金莲、枣、罗勒(basil)、金银花(honeysuckle)、牛膝(hyssop)、亚麻、茴香、毛地黄、黑蜀葵(blackhollyhock)、法国万寿菊(French marigold)、石蚕(betony)、向日葵(heliotrope)、香柠檬(bergamot)、大麻叶(hemp agrimony)、芸香、金盏花(pot marigold)、琉璃苣(borage)、白夏至草(white horehound)、桃金娘(myrtle)、毛蕊花、甘牛至草(marjoram)、薄荷、西洋蓍草(yarrow)、熏衣草(lavender)、猪殃殃(lady′sbedstraw)、柠檬香草(lemongrass)、防臭木、蜜蜂花(lemon balm)、蔷薇(rose)、迷迭香、芝麻菜(rocket)、泡草莓(wild strawberry)、三色堇(wild pansy)和勿忘草(forgetmenot);蜂胶;银杏叶;青汁(green juice)以及它们的提取物。
食品添加物原料的例子包括但不限于氨基酸、金属离子、蛋白质、糖类、脂肪酸、酵母提取物、植物提取物、鱼提取物、水果和水果提取物。
维他命的例子包括但不限于维他命A、B、C、D和E。
在生产本发明治疗糖尿病的含有还原型辅酶Q的组合物的过程中,可根据用途如药物、保健食品、食品、动物药物或动物饲料来适当选择还原型辅酶Q的含量、剂型、贮存方法和贮存形式。
附图简述
图1为用含有辅酶Q10的饲料喂养4周的GK大鼠的葡萄糖耐量示意图。纵坐标表示血糖水平(mg/dl),横坐标表示葡萄糖负荷后经过的时间(分钟)。用4只大鼠的平均值±标准偏差作图。实心圆表示对照组;空心圆表示用还原型辅酶Q10(含有2%氧化型辅酶Q10)喂养的组;空心方框表示用氧化型辅酶Q10喂养的组。单星号和双星号代表相对于对照组显著性水平分别为5%和小于1%的显著差异(Dunnet试验)。
图2为用含有辅酶Q10的饲料喂养6周的GK大鼠的葡萄糖耐量示意图。纵坐标表示血糖水平(mg/dl),横坐标表示葡萄糖负荷后经过的时间(分钟)。用4只大鼠的平均值±标准偏差作图。实心圆表示对照组;空心圆表示用还原型辅酶Q10(含有2%氧化型辅酶Q10)喂养的组;空心方框表示用氧化型辅酶Q10喂养的组。单星号和双星号代表相对于对照组显著性水平分别为5%和小于1%的显著差异(Dunnet试验)。
发明的最佳实施方式
现在利用非限制性实施例详细描述本发明。
(实施例1)对患有II型糖尿病的模型大鼠的作用
使用患有II型糖尿病的模型GK大鼠(5周龄,雄性)检验还原型辅酶Q10和氧化型辅酶Q10对葡萄糖耐量的改善作用。用含有0.1wt%还原型辅酶Q10(含有2wt%氧化型辅酶Q10)的粉末状饲料或含有0.1wt%氧化型辅酶Q10的粉状饲料随意地喂养大鼠。为避免饲料混合物中的还原型辅酶Q10因氧化而减少,每隔2天用新饲料全部替换旧饲料。用不含辅酶Q10的粉末状饲料喂养对照组。在开始喂养饲料混合物4周和6周后进行葡萄糖耐量试验(每组中n=4)。在葡萄糖耐量试验中,以4ml/kg的剂量口服给药50%葡萄糖溶液,并在给药前和给药后30分钟、60分钟、90分钟和120分钟测量血糖水平。用简易血糖仪测定从尾静脉采集的血液中的血糖水平。结果示于图1和2。
图1显示了给药4周后葡萄糖耐量试验的结果。与对照组相比,用氧化型辅酶Q10喂养的组中血糖水平的增加在葡萄糖负荷30分钟后明显得到抑制。这个事实表明,葡萄糖耐量得到提高。与氧化型辅酶Q10组相比,用还原型辅酶Q10喂养的组中的血糖水平在从葡萄糖负荷30分钟后开始的全部测试时间内都急剧降低。这个事实表明,葡萄糖耐量得到进一步提高。
图2显示了给药6周后的结果。与4周后相比,用氧化型辅酶Q10喂养的组中的葡萄糖耐量表现出进一步的提高。与氧化型辅酶Q10相比,葡萄糖负荷后血糖水平的增加得到抑制。在全部测量时间内,用还原型辅酶Q10喂养的组中的血糖水平的增加得到强烈抑制。在全部测量点,血糖水平为200mg/dl或更低。这个事实表明,与给药4周后相比,葡萄糖耐量被提高到更高的程度。
这些结果表明,通过给药氧化型辅酶Q10可提高GK大鼠的葡萄糖耐量。此外,这些试验结果还表明,与给药氧化型辅酶Q10相比,通过给药还原型辅酶Q10可进一步提高GK大鼠的葡萄糖耐量。有趣的是,用氧化型辅酶Q10喂养的组在给药4周和6周后的葡萄糖耐量提高模式相同。尤其是葡萄糖负荷30分钟后血糖水平的提高得到抑制;但是,血糖水平保持增加直到葡萄糖负荷约1小时后,随后变得接近平稳,与对照组相比,在此期间未观察到大的差异。相反,用还原型辅酶Q10喂养的组在给药4周和6周后的葡萄糖耐量提高模式于负荷30分钟后达到峰值,并随时间而降低。用还原型辅酶Q10喂养的组在峰值30分钟后的血糖水平大大低于对照组的血糖水平。这个事实表明,葡萄糖耐量得到明显提高。令人惊奇地发现,由还原型辅酶Q10得到的葡萄糖耐量的提高模式不同于由氧化型辅酶Q10得到的模式。在以前的研究中,我们发现还原型辅酶Q10的口服吸收性不同于氧化型辅酶Q10的口服吸收性(特开平10-109933号公报)。这次我们发现,GK大鼠中的葡萄糖耐量提高模式在氧化型和还原型之间是不同的。仅仅吸收性的差异不能解释这种不同。因此可认为,在体内,还原型辅酶Q10有不同于氧化型辅酶Q10的作用。
(实施例2)对血液糖基化血红蛋白的作用
按照实施例1测量喂养12周的GK大鼠的血液糖化血红蛋白(血红蛋白Alc)水平。结果示于表1。用还原型辅酶Q10喂养的组中的血红蛋白Alc水平表现出明显的降低,即对照组血红蛋白Alc水平的约78%。相反,尽管用氧化型辅酶Q10喂养的组中的血红蛋白Alc水平表现出降低,即对照组血红蛋白Alc水平的约92%,但降低不明显,并小于用还原型辅酶Q10喂养的组得到的降低。糖化血红蛋白水平是临床上控制血糖水平的重要参数。用还原型辅酶Q10喂养的组表现出明显低水平的事实表明,GK大鼠的血糖水平通过施用这种物质得到令人满意的控制。用氧化型辅酶Q10喂养的组仅表现出轻微的降低,其不与用还原型辅酶Q10喂养的组得到的降低同样明显。这种关于糖化血红蛋白水平的结果大概归因于实施例1中所示的葡萄糖耐量的提高不足。
表1
GK大鼠的血红蛋白Alc水平
组 | 血红蛋白Alc水平(%) |
对照组 | 5.33±0.48(100) |
用还原型辅酶Q<sub>10</sub>喂养的组 | 4.17±0.15(78<sup>**</sup>) |
用氧化型辅酶Q<sub>10</sub>喂养的组 | 4.93±0.42(92) |
**显著不同于对照组,p<0.01(Student t-检验)。
工业适用性
本发明能提供有用的组合物,其用于在糖尿病患者和所谓糖尿病预备军即葡萄糖耐量异常的人中保持令人满意的血糖水平控制。本发明治疗糖尿病的组合物含有辅酶Q作为主要成分,并且非常安全,能长期给药并非常有用。此外,本发明能提供既用于治疗人类糖尿病又用于治疗宠物糖尿病的组合物。
Claims (9)
3.权利要求1或2所述的用途,其中辅酶Q为辅酶Q10。
4.权利要求1或2所述用途,其中所述组合物还包含糖尿病治疗药物。
5.权利要求4所述的用途,其中所述糖尿病治疗药物为磺酰脲类药物、磺胺类药物、双胍类药物、α-葡萄糖苷酶抑制剂、胰岛素增敏剂或胰岛素。
6.根据权利要求1或2的用途,其中所述组合物应用于治疗糖尿病的药物。
7.根据权利要求1或2的用途,其中所述组合物应用于治疗糖尿病的功能性食品。
8.根据权利要求1或2的用途,其中所述组合物应用于治疗糖尿病的动物饲料。
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JPS4910665B1 (zh) * | 1969-07-24 | 1974-03-12 | ||
US4959212A (en) * | 1988-06-22 | 1990-09-25 | Alexandra Stancesco | Oxidizing-energizing composition and method for the treatment of diabetes |
IT1284873B1 (it) * | 1996-07-26 | 1998-05-22 | Idi Farmaceutici Spa | Derivati stabili di ubichinolo procedimenti per la loro produzione e loro impiego farmaceutico |
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JP3742602B2 (ja) * | 2001-05-09 | 2006-02-08 | 株式会社カネカ | 還元型補酵素qの安定な溶液 |
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 |
EP1388340B1 (en) * | 2001-05-10 | 2010-09-08 | Kaneka Corporation | Compositions for transmucosal administration containing coenzyme q as the active ingredient |
US6506915B1 (en) * | 2001-06-14 | 2003-01-14 | Daniel David West | Synthesis of coenzyme Q10 ubiquinone |
JP3822479B2 (ja) * | 2001-10-10 | 2006-09-20 | 株式会社カネカ | 還元型補酵素q水溶液の安定化組成 |
TWI329513B (en) * | 2001-10-12 | 2010-09-01 | Kaneka Corp | Use of reduced coenzyme q for lessening oxidative stress |
JP2003135022A (ja) * | 2001-10-31 | 2003-05-13 | Crescendo Corporation | コエンザイムq10 |
-
2003
- 2003-03-19 TW TW092105985A patent/TW200304372A/zh unknown
- 2003-03-20 CN CNB038047926A patent/CN100381119C/zh not_active Expired - Lifetime
- 2003-03-20 KR KR1020047013560A patent/KR100591045B1/ko active IP Right Grant
- 2003-03-20 US US10/505,523 patent/US20050113459A1/en not_active Abandoned
- 2003-03-20 CA CA002476906A patent/CA2476906A1/en not_active Abandoned
- 2003-03-20 AU AU2003221136A patent/AU2003221136B2/en not_active Ceased
- 2003-03-20 EP EP03712784A patent/EP1493437A4/en not_active Withdrawn
- 2003-03-20 WO PCT/JP2003/003389 patent/WO2003077895A1/ja active IP Right Grant
- 2003-03-20 JP JP2003575948A patent/JP4653400B2/ja not_active Expired - Fee Related
Patent Citations (8)
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JPS4910665A (zh) * | 1972-03-31 | 1974-01-30 | ||
JPS5489036A (en) * | 1977-12-27 | 1979-07-14 | Eisai Co Ltd | Remedy and preventive for hypersensitivity to light |
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WO1993024650A1 (en) * | 1992-05-28 | 1993-12-09 | Monash University | Therapeutic compositions |
US6184255B1 (en) * | 1996-08-16 | 2001-02-06 | Kaneka Corporation | Pharmaceutical composition comprising coenzyme Q10 |
WO1998041113A2 (en) * | 1997-03-20 | 1998-09-24 | Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. | Medical food for diabetics |
EP0882450A2 (en) * | 1997-05-27 | 1998-12-09 | Kaneka Corporation | Cholesterol-lowering composition comprising coenzyme Q |
WO2001052822A1 (en) * | 2000-01-20 | 2001-07-26 | Chopra Raj K | Reduced form of coenzyme q in high bioavailability stable dosage forms and related applications |
Also Published As
Publication number | Publication date |
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US20050113459A1 (en) | 2005-05-26 |
TW200304372A (en) | 2003-10-01 |
KR20040091082A (ko) | 2004-10-27 |
AU2003221136A2 (en) | 2003-09-29 |
AU2003221136A1 (en) | 2003-09-29 |
CN1691939A (zh) | 2005-11-02 |
JPWO2003077895A1 (ja) | 2005-07-14 |
JP4653400B2 (ja) | 2011-03-16 |
AU2003221136B2 (en) | 2008-05-22 |
KR100591045B1 (ko) | 2006-06-19 |
EP1493437A4 (en) | 2010-08-11 |
CA2476906A1 (en) | 2003-09-25 |
WO2003077895A1 (fr) | 2003-09-25 |
EP1493437A1 (en) | 2005-01-05 |
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