CN104224835A - 用于降低血中的糖、丙二醛修饰ldl、同型半胱氨酸和/或c反应蛋白的组合物 - Google Patents
用于降低血中的糖、丙二醛修饰ldl、同型半胱氨酸和/或c反应蛋白的组合物 Download PDFInfo
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- CN104224835A CN104224835A CN201410443133.6A CN201410443133A CN104224835A CN 104224835 A CN104224835 A CN 104224835A CN 201410443133 A CN201410443133 A CN 201410443133A CN 104224835 A CN104224835 A CN 104224835A
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Abstract
本发明提供一种用于降低血中的糖、丙二醛修饰LDL、同型半胱氨酸及C反应蛋白的全部检测值的组合物,其中,每一给药单位含有维生素B1210±2μg、维生素B65±1mg、叶酸800±160μg、锌10±2mg、硒50±10μg、维生素C 500±100mg、维生素E 20±4mg、铬30±6μg、维生素B23±0.6mg、维生素B13±0.6mg、烟酸15±3mg、泛酸10±2mg、按视黄醇当量计的维生素A 300±60μg、维生素D35±1μg、生物素50±10μg、半乳寡聚糖2±0.4g、钾40±8mg、钙80±16mg、镁3±0.6mg及磷7.5±1.5mg,能量为46±9.2千卡。
Description
本申请是申请人于2008年10月23日提交的申请号为200880112375.X(PCT/JP2008/069244)、发明名称为“用于降低血中的糖、丙二醛修饰LDL、同型半胱氨酸和/或C反应蛋白的组合物”的申请的分案申请。
技术领域
本发明涉及用于降低血中的糖、丙二醛修饰LDL(MDA-LDL)、同型半胱氨酸和/或C反应蛋白(CRP)的组合物。
背景技术
糖尿病、高脂血症、高血压病等疾病,认为除遗传因素、应激和病原体等外部因素以外,与不适当的饮食生活、运动不足、吸烟、过度饮酒等生活习惯叠加而发病,被称为生活习惯病(非专利文献1)。随着生活习惯的改变和老年人的增加,生活习惯病的患者、潜在患者也增加,需要实施综合的生活习惯病对策。日本厚生劳动省以改善生活习惯为目标,将“首先运动、其次饮食、严格禁烟、最后药物”作为口号,开始强化其解决对策(非专利文献2)。作为针对生活习惯病的运动疗法,在健身俱乐部等运动设施中,有氧运动的效果受到关注,采纳走步、游泳等作为运动习惯的人数逐渐增多,另外,据报道不仅通过运动指导,而且通过与营养管理师协作进行营养管理,也许也能取得预防、改善生活习惯病的显著效果。
生活习惯病,定义为“其发病、进展与饮食习惯、运动习惯、休息、吸烟、饮酒等生活习惯有关的疾病群”,作为代表性的疾病,有龋齿、牙周病、骨质疏松症、酒精性肝疾病、肥胖症、痛风(高尿酸血症)、高血压病、糖尿病、高脂血症、心脏病、脑卒中、癌症等。作为生活习惯病所伴有的病理状态,已知有“动脉硬化”。
餐后高血糖的持续被推测是由于随着糖化蛋白的亢进、蛋白激酶C的活化,引起氧化应激,由该氧化应激引起血管障碍。
氧化应激被认为引起血管构成细胞或单核细胞、血小板等血细胞的活化,促进炎症性细胞因子分泌和氧化LDL(MDA-LDL)分泌,从而使血管障碍不断进展、恶化。此时发生的炎症使作为炎症标记物的CRP值也升高。认为这些一系列的反应与动脉硬化的发病、进展相关(非专利文献3)。
同型半胱氨酸是存在于血液中的氨基酸。近年来,同型半胱氨酸与动脉硬化的关联受到关注。粥样动脉硬化中,单核细胞与由于动脉的内皮细胞损伤而分泌的趋化因子反应而粘附浸润在内皮细胞上,在内膜中单核细胞分化为巨噬细胞,摄取血中的胆固醇而使内膜肥大化,并且巨噬细胞也崩解而成为粥状。如果同型半胱氨酸在血中蓄积,则同型半胱氨酸会发生自身氧化,氧化过程中产生的氧自由基等使内皮细胞发生障碍,从而容易产生动脉硬化(非专利文献4)。动脉硬化已知也是糖尿病的合并症,认为动脉硬化与糖尿病有密切的关系。
非专利文献1:“生活習慣病予防と運動·栄養管理”石井恵子ほか臨床栄養Vol.108No.22006.2(“生活习惯病预防与运动、营养管理”,石井惠子等,临床营养,108卷,第2期,2006年2月)
非专利文献2:“生活習慣病に対する心身医学的アプロ一チ”山中隆夫ほか日本心身医学会Vol.46No.42006.4(“对于生活习惯病的心身医学疗法”,山中隆夫等,日本心身医学会,46卷,第4期,2006年4月)
非专利文献3:“医学のあゆみ”,Vol.218,No1,2006.7.1山岸昌一(“医学的进展”,218卷,第1期,2006年7月1日,山岸昌一)
非专利文献4:“医学のあゆみ”,202(10):789-793,2002.(“医学的进展”,202(10),789-793页,2002年)
发明内容
本发明的目的在于,提供用于降低血中的糖、丙二醛修饰LDL、同型半胱氨酸和/或C反应蛋白的组合物。
本发明人等让生活习惯病的患者及潜在患者摄取含有下述(a)及(b)的成分的组合物来确认其有用性,结果发现,对于降低血中的糖、丙二醛修饰LDL、同型半胱氨酸及C反应蛋白有效,从而完成了本发明。
(a)从由维生素B12、维生素B6及叶酸组成的组中选择的至少一种成分
(b)从由锌、硒及抗氧化维生素组成的组中选择的至少一种成分
本发明的主旨如下所述。
(1)一种组合物,其中,含有下述(a)及(b)的成分,并且用于降低血中的从由糖、丙二醛修饰LDL、同型半胱氨酸及C反应蛋白组成的组中选择的至少一种。
(a)从由维生素B12、维生素B6及叶酸组成的组中选择的至少一种成分
(b)从由锌、硒及抗氧化维生素组成的组中选择的至少一种成分
(2)如(1)所述的组合物,其中,还含有α-硫辛酸和/或铬。
(3)如(2)所述的组合物,其中,含有维生素B12、维生素B6、叶酸、锌、硒、维生素C、维生素E、α-硫辛酸、铬、维生素B2、维生素B1、烟酸、泛酸、维生素A、维生素D3及生物素。
(4)如(3)所述的组合物,其中,每一给药单位含有维生素B1210±2μg、维生素B65±1mg、叶酸800±160μg、锌10±2mg、硒50±10μg、维生素C 500±100mg、维生素E 20±4mg、α-硫辛酸30±6mg、铬30±6μg、维生素B23±0.6mg、维生素B13±0.6mg、烟酸15±3mg、泛酸10±2mg、维生素A(视黄醇当量)300±60μg、维生素D35±1μg及生物素50±10μg,能量为46±9.2千卡(kcal)。
(5)如(1)~(4)中任一项所述的组合物,其中,还含有半乳寡聚糖、钾、钙、镁及磷。
(6)如(5)所述的组合物,其中,每一给药单位含有半乳寡聚糖2±0.4g、钾40±8mg、钙80±16mg、镁3±0.6mg及磷7.5±1.5mg。
(7)如(1)~(6)中任一项所述的组合物,其分散在可服用的液体中。
(8)如(7)所述的组合物,其中,每一给药单位的容量为125±25mL。
(9)如(1)~(8)中任一项所述的组合物,其用于治疗和/或预防生活习惯病。
(10)如(9)所述的组合物,其中,生活习惯病为糖尿病、动脉硬化或代谢综合征。
(11)如(1)~(10)中任一项所述的组合物,其用于对生活习惯病的患者或潜在患者给药。
(12)一种降低血中的从由糖、丙二醛修饰LDL、同型半胱氨酸及C反应蛋白组成的组中选择的至少一种的方法,其中,包括对受试者给药对于降低血中的从由糖、丙二醛修饰LDL、同型半胱氨酸及C反应蛋白组成的组中选择的至少一种有效的量的下述(a)及(b)的成分。
(a)从由维生素B12、维生素B6及叶酸组成的组中选择的至少一种成分
(b)从由锌、硒及抗氧化维生素组成的组中选择的至少一种成分
(13)一种治疗和/或预防生活习惯病的方法,其中,包括对受试者给药对于生活习惯病的治疗和/或预防有效的量的下述(a)及(b)的成分。
(a)从由维生素B12、维生素B6及叶酸组成的组中选择的至少一种成分
(b)从由锌、硒及抗氧化维生素组成的组中选择的至少一种成分
(14)如(13)所述的方法,其中,生活习惯病为糖尿病、动脉硬化或代谢综合征。
(15)下述(a)及(b)的成分的应用,用于制造降低血中的从由糖、丙二醛修饰LDL、同型半胱氨酸及C反应蛋白组成的组中选择的至少一种的组合物。
(a)从由维生素B12、维生素B6及叶酸组成的组中选择的至少一种成分
(b)从由锌、硒及抗氧化维生素组成的组中选择的至少一种成分
(16)下述(a)及(b)的成分的应用,用于制造治疗和/或预防生活习惯病的组合物。
(a)从由维生素B12、维生素B6及叶酸组成的组中选择的至少一种成分
(b)从由锌、硒及抗氧化维生素组成的组中选择的至少一种成分
(17)如(16)所述的应用,其中,生活习惯病为糖尿病、动脉硬化或代谢综合征。
根据本发明,提供用于降低血中的糖、丙二醛修饰LDL、同型半胱氨酸和/或C反应蛋白的组合物。
本说明书包括作为本申请的优先权基础的日本专利申请、日本特愿2007-277140的说明书和/或附图中记载的内容。
附图说明
图1表示空腹血糖值的结果。圆形标记为给药组、三角标记为非给药组,将各自与第0个月的差以各组的平均值作图。与第0个月的差异显著性检验(t检验)的结果中,*表示p<0.05,**表示p<0.01,示出有显著差异。在给药组的第3个月时,相对于第0个月可见显著(p<0.01)的减少。
图2表示丙二醛修饰LDL的结果。圆形标记为给药组、三角标记为非给药组,将各自与第0个月的差以各组的平均值作图。与第0个月的差异显著性检验(t检验)的结果中,*表示p<0.05,**表示p<0.01,示出有显著差异。在给药组的第2个月时,相对于第0个月可见显著(p<0.01)的减少。
图3表示总同型半胱氨酸的结果。圆形标记为给药组、三角标记为非给药组,将各自与第0个月的差以各组的平均值作图。与第0个月的差异显著性检验(t检验)的结果中,*表示p<0.05,**表示p<0.01,示出有显著差异。在给药组的第2个月及第3个月时,相对于第0个月可见显著(p<0.01)的减少。
图4表示C反应蛋白(CRP)的结果。圆形标记为给药组、三角标记为非给药组,将各自与第0个月的差以各组的平均值作图。与第0个月的差异显著性检验(t检验)的结果中,*表示p<0.05,**表示p<0.01,示出有显著差异。在给药组的第1个月及第2个月时,相对于第0个月可见显著(p<0.05)的减少,在第3个月时,相对于第0个月可见显著(p<0.01)的减少。
具体实施方式
以下,对本发明的实施方式进行更具体的说明。
本发明提供一种组合物,其中,含有下述(a)及(b)的成分,并且用于降低血中的从由糖、丙二醛修饰LDL、同型半胱氨酸及C反应蛋白组成的组中选择的至少一种。
(a)从由维生素B12、维生素B6及叶酸组成的组中选择的至少一种成分
(b)从由锌、硒及抗氧化维生素组成的组中选择的至少一种成分
维生素B12、维生素B6及叶酸是参与同型半胱氨酸代谢的成分。这些参与同型半胱氨酸代谢的成分被认为活化从蛋氨酸至半胱氨酸的代谢过程,有助于降低血中的同型半胱氨酸量。本发明的组合物也可以单独含有维生素B6、维生素B12或叶酸的任意一种,但优选组合含有上述三种成分的多种成分,最优选组合含有上述所有三种成分。
本发明的组合物,以每一给药单位计,例如,含有维生素B121.1~50.0μg、优选5.0~15.0μg,含有维生素B61.6mg~60.0mg、优选3.0~8.0mg,含有叶酸200μg~1.1mg、优选600~1000μg。
锌、硒及抗氧化维生素是参与除去活性氧的成分组。活性氧被认为与血管内皮障碍有关,参与除去活性氧的上述成分对于改善血管内皮障碍发挥重要的作用。硒是作为抗氧化酶的谷胱甘肽过氧化物酶的构成物质,锌是作为抗氧化酶的超氧化物歧化酶的构成物质。维生素E、维生素C等抗氧化维生素有还原型和氧化型两型,通过接受活性氧带有的自由基,自身被氧化,从而显示除去活性氧的功能。本发明的组合物也可以单独含有锌、硒或抗氧化维生素的任意一种,但优选组合含有上述成分的多种成分。作为抗氧化维生素的例子,例如可以列举维生素C、维生素E、维生素A,但不限于这些。维生素族的摄取量因饮食的内容而异,特别是在需要限制饮食的糖尿病患者或其潜在患者中有不足的倾向。因此,本发明的组合物优选组合含有多种抗氧化维生素。
本发明的组合物,以每一给药单位计,例如,含有锌1.2~30mg、优选9~12mg,含有硒10~250μg、优选30~60μg。另外,在使用维生素C、维生素E、维生素A作为抗氧化维生素的情况下,以每一给药单位计,例如,含有维生素C 100mg~2000mg、优选300mg~1000mg,含有维生素E 3mg~600mg、优选5mg~300mg,含有维生素A(视黄醇当量)10μg~3000μg、优选100~550μg。
本发明的组合物还可以含有α-硫辛酸和/或铬。
α-硫辛酸参与糖代谢的促进。认为其刺激细胞内存在的葡萄糖转运体(GLUT-4)在细胞膜上的动员,使肌肉或肌细胞中胰岛素引起的糖摄入大幅度增加。
α-硫辛酸的含量,例如以每一给药单位计,20~1000mg是适当的,更优选25~100mg。
铬通过提高胰岛素受体结合能力,提高胰岛素受体数量、胰岛素受体激酶活性而使胰岛素敏感性增强。
铬的含量例如以每一给药单位计,5~50μg是适当的,更优选10~40μg。
另外,本发明的组合物除上述成分以外还可以含有其它成分。例如,可以含有在上述普通饮食中容易不足的钙、促进钙吸收的维生素D(例如维生素D3)等。另外,作为参与上述同型半胱氨酸代谢的维生素、抗氧化维生素例示的维生素以外的维生素(例如维生素B2、维生素B1、烟酸、泛酸),也是本发明的组合物中适合含有的成分的例子。还可以含有生物素、半乳寡聚糖、钾、镁、磷。通过含有这些物质,也可以防止糖尿病饮食等进行限制的饮食中的成分缺乏。另外,还可以添加β-胡萝卜素、铁、辅酶Q10等。β-胡萝卜素是维生素A的前体物质。从消化道吸收,以需要的量才转化成维生素A,因此不必担心维生素A的过量摄取。其作用与维生素A显示同样的作用。铁也是血红蛋白的构成成分,因此不足时可能导致贫血。通过配合铁,可以期待预防、防止、改善贫血症状的效果。辅酶Q10具有强抗氧化作用,因此可以期待氧化应激引起的疾病的预防、防止效果。另外,它是参与ATP产生的成分,因此通过补充也可以期待使营养素代谢顺利进行的效果。
本发明的组合物中,例如,以每一给药单位计,维生素B2的含量为0.5~20mg是适当的,优选1~10mg;维生素B1的含量为0.5~10mg是适当的,优选1.0~5.0mg;烟酸的含量为1~100mg是适当的,优选5~50mg;泛酸的含量为1~100mg是适当的,优选5~50mg;维生素D3的含量为1~10μg是适当的,优选2~8μg;生物素的含量为1~200μg是适当的,优选10~100μg;β-胡萝卜素的含量为0.1~100mg是适当的,优选1.0~50mg;铁的含量为0.5~50mg是适当的,优选1.0~30mg;辅酶Q10的含量为1.0~1000mg是适当的,优选2~100mg。
另外,本发明的组合物中,例如,以每一给药单位计,半乳寡聚糖的含量为0.1~20g是适当的,优选1~10g;钾的含量为10~1000mg是适当的,优选15~500mg;钙的含量为1~2300mg是适当的,优选10~600mg;镁的含量为0.1~10mg是适当的,优选1~5mg;磷的含量为1~3500mg是适当的,优选5~1050mg。
本发明的组合物的能量的量,以每一给药单位计,5~200千卡是适当的,优选20~150千卡。另外,就一般成分而言,例如,以每一给药单位计,蛋白质的含量设定为0.4±0.08g左右或0.7±0.14g左右、碳水化合物的含量设定为11.1±2.22g左右或21.2±4.24g左右、钠的含量设定为30±6mg左右即可。
本发明的组合物可以通过本领域技术人员公知的方法制备。例如,可以将上述各成分混合,按照粉末、颗粒、片剂、液剂等剂型来制备。对于经口摄取困难的患者,液剂可以经管给药,因此是更优选的剂型。
在以液剂形式制备本发明的组合物的情况下,用于分散或溶解组合物的液体,只要是通常服用的液体且不会减弱各成分对生物体的作用则没有特别限制,例如可以使用水、生理盐水等。为了改善经口给药的味觉,可以使用果汁。作为果汁,可以列举蓝莓汁、葡萄汁、葡萄柚汁、柠檬汁、柑桔汁、胡萝卜汁、苹果汁、菠萝汁,从能够缓和维生素C、维生素B族的酸味、气味的观点考虑,更优选蓝莓汁或葡萄汁。液剂的情况下,每一给药单位的容量为10~250ml是适当的,优选50~200ml,更优选125±25mL。另外,液剂情况下的水分含量,例如以每一给药单位计,可以设定为116±23.2g左右或110±22g左右。
本发明的组合物的成分表(125mL中)的例子如下表1所示。
[表1]
如上所述制备的组合物是所致的降低血中的糖、丙二醛修饰LDL、总同型半胱氨酸和/或C反应蛋白的效果,可以通过如下方法确认:对生活习惯病(例如糖尿病、动脉硬化、代谢综合征等)的患者或潜在患者、或者生活习惯病的疾病模型动物给予该组合物,采集给药前后的血液并测定血中的糖(例如空腹血糖值)、丙二醛修饰LDL、总同型半胱氨酸和/或C反应蛋白的值,观察给药前后的测定值的变化,由此来确认。或者,也可以将给予该组合物的组的测定值与给予安慰剂(例如市售的饮料)的组(对照组)的测定值进行比较。
血中的糖的值可以通过酶法、即使用葡萄糖脱氢酶(GDH)将葡萄糖转化为D-葡萄糖-δ-内酯,在340nm处计测NAD+(P)→NAD(P)H的变化来测定。
血中的丙二醛修饰LDL的值可以通过使用了丙二醛修饰LDL单克隆抗体和抗ApoB(载脂蛋白B)单克隆抗体的夹心ELISA法来测定。
血中的总同型半胱氨酸的值可以通过高效液相色谱(HPLC)法来定量测定。
血中的C反应蛋白的值可以通过胶乳免疫比浊法测定,即,使吸附有抗CRP抗体的胶乳粒子与样品反应,由于抗原-抗体反应而引起凝集反应,因此,测定其在572nm的吸光度变化,由此来测定。
糖、丙二醛修饰LDL、总同型半胱氨酸及C反应蛋白如上所述与生活习惯病有关,因此,血中的糖、丙二醛修饰LDL、总同型半胱氨酸及C反应蛋白的值可以作为生活习惯病的治疗和/或预防效果的指标。例如,空腹血糖值的基准值为70~109mg/dl,空腹血糖值超过110mg/dl时,追加餐后血糖值、75g OGTT 2小时值、糖化蛋白等的检查,进行糖尿病的判断。另外,丙二醛修饰LDL的参考基准值为58.8±17.9U/L,得到冠状动脉疾病患者(113.4±49.1U/L)与对照组(85.2±22.5U/L)相比为高值的报道(参考1)。总同型半胱氨酸的基准值为3.7~13.5nmol/ml,有血浆总同型半胱氨酸值为15nmol/ml以上时与低于15nmol/ml的患者相比冠状动脉疾病的死亡率增高的报道(参考2)。用于判断有无感染的C反应蛋白的基准值为0.30mg/dl以下。CRP通常作为感染症等炎症的指标使用,但近年来,开发了高灵敏度CRP作为慢性动脉硬化性疾病的指标,设定0.1mg/dl为冠状动脉疾病的截止值(参考3)。
参考1:“MDA-LDL测定系の開発およびその臨床的評価”第13回生物試料分析科学回大会实方和宏他(“MDA-LDL测定系统的开发及其临床评价”第13次生物试样分析科学大会,实方和宏等)
参考2:“Plasma homocysteine levels and mortality in patients withcoronary artery disease.”N Engl J Med/337巻,4号,230-6,1997NygardO et.(“血浆同型半胱氨酸水平与冠状动脉疾病患者的死亡率”,新英格兰医学杂志,337卷,第4期,230-236页,1997年,Nygard O等)
参考3:“高感度CRP(high sensitive C-reactive protein:hs-CRP)”Thrombosis and Circulation Vol.12No.42004,高橋伯夫(“高灵敏度CRP(高灵敏度C反应蛋白,hs-CRP)”,血栓与循环,12卷,第4期,2004年,高桥伯夫)
因此,本发明的组合物可以用于生活习惯病的治疗和/或预防。将本发明的组合物对生活习惯病的患者或潜在患者给药即可。将本发明的组合物以一天一个给药单位的给药量对生活习惯病的患者或潜在患者给药即可。给药可以经口或经管进行。
实施例
以下,通过实施例具体地说明本发明。另外,这些实施例只是用于说明本发明,并不限定本发明的范围。
[制备例1]组合物的制备
作为组合物,制备在含有蓝莓提取液的汁液中含有各种成分的组合物。一支(125ml)该组合物中含有:维生素A 300μg、维生素B13.0mg、维生素B23.0mg、维生素B65.0mg、维生素B1210μg、维生素C 500mg、烟酸15mg、叶酸800μg、维生素D35.0μg、维生素E 20mg、生物素50μg、泛酸10mg、锌10mg、钙80mg、磷7.5mg、钠30mg、钾40mg、硒50μg、铬30μg、α-硫辛酸30mg、半乳寡聚糖2g。
[实施例1]组合物的有用性
目的:以生活习惯病的患者或潜在患者、并进行运动疗法的患者为对象,让他们摄取制备例1制备的组合物,以确认其有用性。
对象患者:茨城县内的医院门诊就诊者中的生活习惯病的患者或潜在患者、并进行运动疗法的患者(无论年龄、性别,但是没有消化道通过障碍的患者)。进行本试验时,对患者充分说明试验的内容,取得患者本人的由自由意志决定的对试验的书面同意。
试验方法:以取得同意的患者为对象,让他们每天饮用一支制备例1制备的组合物(125mL/支),在给药开始时、1个月后、2个月后、3个月后进行采血。评价项目除给药前后的身体测量以外,还有血压、血液生化学检查、营养学指标、活性氧显现量、最大氧摄取量、动脉硬化度(CAVI)、尿常规检查、自觉症状。试验期间中的药剂的服用按通常进行,并避免使用含有大量维生素、微量元素的补给品。另外,让他们自由摄取饮食。
分组:设置制备例1制备的组合物的摄取组(给药组)和非摄取组(非给药组)两组,通过“信封法”随机进行分组。非摄取组摄取作为对照的不含维生素和微量营养素的、46千卡、125ml蓝莓汁(Nutri公司制,比较试验用)。
给药前后的评价项目:
1)血液检查
白蛋白、红细胞数、血色素量、红细胞压积、白细胞量、淋巴细胞量、血小板数、总蛋白、空腹血糖值、HbAlc、总胆固醇、HDL胆固醇、LDL胆固醇、甘油三酯、总胆红素、直接胆红素、AST、ALT、γ-GTP、Al-P、LDH、胆碱酯酶、BUN、肌酐、尿酸、Na、K、Ca、Cl、CRP、脂联素、ADMA、氧化LDL、总同型半胱氨酸
2)特别检查
活性氧显现量、最大氧摄取量、动脉硬化度(CAVI)
3)尿常规检查
蛋白、糖、尿胆原
4)身体检查
BMI(体重、身高)、体温、血压、脉搏
5)自觉症状
食欲、腹涨感、呕吐、腹泻、便秘等
评价日程:请他们每天确认自觉症状、组合物服用情况,并通过日记进行记录。对需要进行采血、采尿的评价测定前值,每个月合计进行4次。体重在采血日测定。
安全性的确保:试验负责医师在受试者参加试验的过程中进行必要且适当的观察、检查,留意确保受试者的安全性。另外,为了从伦理的、科学的观点客观地评价本试验的有效性、安全性信息,接受伦理委员会的审议。
病例数:各组20例(合计40例)
试验期间:2006年7月~2007年8月
结束基准:
1)结束:在试验开始后3个月结束。
2)中止:以下的情况下中止试验。重新开始试验取决于主治医师的判断。
(1)发现严重的有害现象/有害反应的情况下
(2)患者或家属有中止愿望的情况下
(3)其它的负责医师判断应当中止试验的情况下
结果:结果如图1~4所示。空腹血糖值、丙二醛修饰LDL、总同型半胱氨酸及C反应蛋白(CRP),在组合物的摄取组与非摄取组之间可见显著差异。
其它评价项目在组合物的摄取组与非摄取组之间未见显著差异。
本说明书中引用的所有发行物、专利及专利申请作为参考原样引入本说明书中。
工业上的可利用性
本发明的组合物可以用于降低血中的糖、丙二醛修饰LDL、总同型半胱氨酸和/或C反应蛋白,对于生活习惯病的治疗和/或预防有用。
Claims (10)
1.一种组合物,其用于降低血中的糖、丙二醛修饰LDL、同型半胱氨酸及C反应蛋白的全部检测值,每一给药单位含有维生素B1210±2μg、维生素B65±1mg、叶酸800±160μg、锌10±2mg、硒50±10μg、维生素C 500±100mg、维生素E 20±4mg、铬30±6μg、维生素B23±0.6mg、维生素B13±0.6mg、烟酸15±3mg、泛酸10±2mg、按视黄醇当量计的维生素A 300±60μg、维生素D35±1μg、生物素50±10μg、半乳寡聚糖2±0.4g、钾40±8mg、钙80±16mg、镁3±0.6mg及磷7.5±1.5mg,能量为46±9.2千卡。
2.如权利要求1所述的组合物,其分散在可服用的液体中。
3.如权利要求2所述的组合物,其中,每一给药单位的容量为125±25mL。
4.如权利要求1所述的组合物,其用于治疗和/或预防生活习惯病。
5.如权利要求4所述的组合物,其中,生活习惯病为糖尿病、动脉硬化或代谢综合征。
6.如权利要求1所述的组合物,其用于对生活习惯病的患者或潜在患者给药。
7.如权利要求1所述的组合物,其中,每一给药单位含有辅酶Q10 15±3mg。
8.权利要求1所述的组合物在制造降低血中的糖、丙二醛修饰LDL、同型半胱氨酸及C反应蛋白的全部检测值的药物中的应用。
9.权利要求1所述的组合物在制造治疗和/或预防生活习惯病的药物中的应用。
10.如权利要求9所述的应用,其中,生活习惯病为糖尿病、动脉硬化或代谢综合征。
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Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1686547A (zh) * | 2005-03-30 | 2005-10-26 | 淮北市辉克药业有限公司 | 长期使用的治疗糖尿病的复方制剂 |
JP2007106703A (ja) * | 2005-10-14 | 2007-04-26 | Nutri Kk | 血管障害の予防および治療組成物 |
Family Cites Families (26)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4927850A (en) * | 1988-04-08 | 1990-05-22 | Bayless Robert K | Antioxidant compositions and methods for ameliorating inflammatory symptoms of respiratory disease |
EP0730862A1 (en) * | 1990-05-16 | 1996-09-11 | Zbigniew Walaszek | Formulation containing glucaric acid for the prevention or treatment of non-cancerous cellular hyperproliferation and dietary supplement |
US5569670A (en) | 1992-06-05 | 1996-10-29 | Asta Medica Aktiengesellschaft | Combination medications containing alpha-lipoic acid and related |
DE4218572A1 (de) | 1992-06-05 | 1993-12-09 | Asta Medica Ag | Synergistische Kombination von Arzneimitteln enthaltend als Wirkstoff alpha-Liponsäure, Dihydroliponsäure, deren Metaboliten sowie die oxidierten und reduzierten Enantiomere der alpha-Liponsäure wie die R-alpha-Liponsäure oder S-alpha-Liponsäure sowie Metaboliten der alpha-Liponsäure mit den Vitaminen A, B1-6, B12, C und E |
ZA936723B (en) | 1992-09-14 | 1995-08-14 | Vesta Med Pty Ltd | Pharmaceutical preparations for lowering homocysteine levels |
IL121112A (en) | 1997-06-19 | 2005-11-20 | Lycored Natural Prod Ind Ltd | Synergistic pharmaceutical or dietary compositionscomprising lycopene and vitamin e for preventing ldl oxidation |
AU8031998A (en) | 1997-06-19 | 1999-01-04 | Bianca Fuhrman | Synergistic compositions for lycopene and vitamin e for the prevention of ldl o xidation |
US6274170B1 (en) | 1999-02-18 | 2001-08-14 | Richard Heibel | Compounds for cardiovascular treatment comprising multi-vitamin and anti-platelet aggregating agents and methods for making and using the same |
GB9916536D0 (en) * | 1999-07-14 | 1999-09-15 | Scarista Limited | Nutritional or pharmaceutical compositions |
US6261606B1 (en) | 1999-09-14 | 2001-07-17 | Natural Compounds, Ltd. | Naturally extracted and synthetic hypoglycemic or hypolipidemic compositions |
US6361800B1 (en) | 2000-04-13 | 2002-03-26 | Cooper Concepts, Inc. | Multi-vitamin and mineral supplement |
AU2001253294A1 (en) * | 2000-04-14 | 2001-10-30 | Mars, Incorporated | Compositions and methods for improving vascular health |
US7208180B2 (en) * | 2000-05-08 | 2007-04-24 | N.V. Nutricia | Method and preparation for the preventing and/or treating vascular disorders and secondary disorders associated therewith |
US20040037892A1 (en) * | 2001-11-19 | 2004-02-26 | Adrianne Bendich | Dietary composition containing conjugated linoleic acid and calcium for improved health |
JP2004515508A (ja) * | 2000-12-16 | 2004-05-27 | アベンティス・ファーマ・ドイチユラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | 化合物の健康促進組成物 |
IT1320180B1 (it) * | 2000-12-29 | 2003-11-26 | Hunza Di Marazzita Maria Carme | Preparazioni nutrizionali e terapeutiche dotate di attivita'antiossidante ed in grado di controllare gli eccessi ponderali e |
JP2002348244A (ja) | 2001-05-23 | 2002-12-04 | Fancl Corp | 抗糖尿病組成物 |
CH696628A5 (de) | 2002-02-26 | 2007-08-31 | Eprova Ag | Verwendung von Folaten zur Herstellung einer Zubereitung geeignet zur Vorbeugung und Behandlung von Entzündungen und entzündungsassoziierter Krankheiten, im Speziellen zur Beeinflussung der |
CA2520955C (en) | 2003-03-31 | 2009-11-24 | Council Of Scientific And Industrial Research | A process for preparation of hypoglycemic foods and formulations thereof |
US20060116334A1 (en) | 2004-12-01 | 2006-06-01 | Curt Hendrix | Folate based composition for treatment of the cardiovascular system |
JP4818637B2 (ja) | 2005-05-02 | 2011-11-16 | 日本メナード化粧品株式会社 | 低密度リポタンパク質(ldl)酸化抑制剤 |
MX2008002701A (es) | 2005-08-26 | 2008-03-18 | Nestec Sa | Nutricion para pacientes obesos. |
ATE509624T1 (de) | 2005-12-23 | 2011-06-15 | Nutricia Nv | Zusammensetzung enthaltend mehrfach ungesättigte fettsäuren, proteine, mangan und/oder molybden und nukleotide/nukleoside, zur behandlung von demenz |
DE202006014588U1 (de) * | 2006-09-20 | 2006-12-14 | Orthomol Pharmazeutische Vertriebs Gmbh | Carotinoide-enthaltendes Produkt |
US20080102137A1 (en) * | 2006-10-31 | 2008-05-01 | Guffey Manning V R | Composition and method for etiological treatment and prevention of diseases and/or complications associated with chronic glucose metabolism destabilization |
US20080318883A1 (en) | 2007-06-19 | 2008-12-25 | Elson Corporation | Anti-aging supplement |
-
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Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1686547A (zh) * | 2005-03-30 | 2005-10-26 | 淮北市辉克药业有限公司 | 长期使用的治疗糖尿病的复方制剂 |
JP2007106703A (ja) * | 2005-10-14 | 2007-04-26 | Nutri Kk | 血管障害の予防および治療組成物 |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111239292A (zh) * | 2019-10-24 | 2020-06-05 | 丁芬 | 同时检测多种脂溶性维生素和同型半胱氨酸的方法 |
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