CN101111239A - 用于减少体内脂肪的组合物 - Google Patents
用于减少体内脂肪的组合物 Download PDFInfo
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- CN101111239A CN101111239A CNA2005800472567A CN200580047256A CN101111239A CN 101111239 A CN101111239 A CN 101111239A CN A2005800472567 A CNA2005800472567 A CN A2005800472567A CN 200580047256 A CN200580047256 A CN 200580047256A CN 101111239 A CN101111239 A CN 101111239A
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- Prior art keywords
- body fat
- acid
- astaxanthin
- extract
- compositions
- Prior art date
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Abstract
高血压、胰岛素耐受、高血脂等生活方式病的病因主要是体内脂肪的增加。本发明的目的在于提供减少体内脂肪和抑制体内脂肪增加、对于体内脂肪引起的成人病的治疗和预防有效的用于减少体内脂肪的组合物;以及含有该组合物的药物和食品。[解决方法]本发明提供混合有(A)虾青素、(B)活性成分、吸附剂、增溶剂的一种以上的用于减少体内脂肪的组合物,或者混合(A)含有虾青素的红球藻提取物、(B)活性成分、吸附剂、增溶剂的一种以上的用于减少体内脂肪的组合物,以及含有这些组合物的药物和食品。
Description
技术领域
本发明涉及含有虾青素作为有效成分的用于减少体内脂肪的组合物、以及将红球藻粉碎、用溶剂提取得到的用于减少体内脂肪的组合物。通过将这些组合物以药物的形式给药、或作为饮食摄取,得到对于体内脂肪减少或肥胖或与其相伴的疾病的预防、改善和治疗有效的药物和食品。
背景技术
近年来,由于摄入高卡路里食物或生活方式的改变、运动不足、应激等原因,生活方式病增加,成为大的社会问题。特别是体内脂肪率增加导致的肥胖或体重超标成为占日本总人数两成以上的大问题。肥胖是指摄取的能量比消耗的能量过剩,脂肪组织超乎寻常地蓄积的身体状况,日本人中,是指成年男性的体内脂肪率为25%以上、女性为30%以上。肥胖会由于体内脂肪过多蓄积而引起高血压、心血管障碍、高血脂、动脉硬化、糖尿病等各种疾病,还会并发血管障碍、视力障碍、神经障碍、抵抗力降低等并发症。对于消除占生活方式病的最大原因的肥胖的方法进行了很多研究,已经开发并实施了饮食疗法、运动疗法、药物疗法等各种治疗方法。
通常,肥胖的治疗是采用饮食疗法或运动疗法,但在食物能量的摄取增加或劳动环境变化等的现代社会中,持续的卡路里摄取限制法(减肥)、或者需要有进行适当运动的时间或空间的运动疗法,这实际上很难进行。
作为肥胖的药物疗法,采用了通过脂肪组织的脂肪分解亢进等来促进能量消耗的方法;以及抑制由消化道吸收脂质、糖等或者抑制饮食等抑制能量摄取的方法等。但是,药物疗法必须适当地给药,过量摄取会妨碍必要的营养的摄取、或者使吸收的营养平衡失衡等副作用,或者必须有医生的处方,不容易使用。
人们需求来自天然、没有副作用的、作为食品可容易地摄取的减少体内脂肪的组合物,已知有藤黄果种皮提取物和含有酸橙果实的体内脂肪降低剂(专利文献1)、给予共轭亚油酸的方法(专利文献2)、给予维生素D3的方法(专利文献3)。
虾青素是与β-胡萝卜素相同的类胡萝卜素的一种,是分布于虾、蟹等甲壳类,鲑鱼、鲷鱼等鱼类,绿藻一红球藻等藻类,红发夫酵母等酵母类等天然、特别是广泛分布于海洋中、被广泛食用的红色色素,具有维生素E的约1000倍,β-胡萝卜素的约40倍的强的抗氧化作用。
作为虾青素所具有的其它功能特性,目前已有很多报道指出其具有抗炎症作用、抗动脉硬化作用、对糖尿病的作用、防止光学伤害的视网膜保护作用、昼夜节律调节作用、免疫激活作用、抗应激作用、提高***质量作用或抑制膀胱癌的诱发等。另外,关于对于运动的作用,报道有提高肌肉持续力的作用(专利文献4)、抑制运动中血液乳酸值升高的效果(非专利文献1)、运动后消除疲劳的效果(非专利文献2)。
但是,关于虾青素以及将红球藻粉碎、用溶剂提取得到的提取物会减少体内脂肪,以及抑制体内脂肪的增加,结果具有治疗或预防肥胖的效果尚未见报道。
专利文献1:日本特开第2001-321126号公报
专利文献2:日本特表平第10-508189号公报
专利文献3:日本特开平第3-3210156号公报
专利文献4:日本特表第2001-514215号公报
非专利文献1:临床医药、18(9)、1085~1100、2002年
非专利文献2:疲劳和休养的科学、18(1)、35~46、2003年
发明内容
发明所要解决的课题
本发明的目的在于提供具有减少体内脂肪的效果和抑制体内脂肪增加的效果的组合物,以及含有该组合物的药物或饮食。其目的还在于由此提供可以治疗、改善和预防由于体内脂肪过多导致的肥胖而产生的各种疾病,以及表现、维持因瘦身效果而导致的美好体型。
解决课题的方法
本发明人等为解决上述课题进行了深入的研究,结果发现:虾青素以及将红球藻粉碎、用溶剂提取的提取物显示减少体内脂肪、抑制增加的效果,从而完成了本发明。
即,本发明是
(1)用于减少体内脂肪的组合物,其含有虾青素作为有效成分。
(2)用于减少体内脂肪的组合物,其是将红球藻粉碎,用溶剂提取所得。
(3)用于减少体内脂肪的组合物,其是在(1)~(2)中任一项的组合物中混合活性成分、吸附剂、增溶剂的一种以上而得到的。
(4)体内脂肪减少剂,其含有(1)~(3)中任一项的组合物。
(5)用于减少体内脂肪的饮食,其含有(1)~(3)中任一项的组合物。
(6)减少体内脂肪的方法,其包含将(1)~(3)中任一项的组合物对人给药或摄取。
实施发明的最佳方式
本发明的含有虾青素作为有效成分的用于减少体内脂肪的组合物、以及将红球藻粉碎并用溶剂提取所得到的用于减少体内脂肪的组合物通过以药物或饮食的形式给药或摄取,可以无副作用地减少体内脂肪和抑制体内脂肪的增加,可以进行以体内脂肪过多、即肥胖为原因的疾病的治疗、改善和预防。
本发明中,“虾青素”是指来自天然的或由合成得到的虾青素。来自天然的虾青素例如有从虾、磷虾、蟹等甲壳类的甲壳、卵和内脏,各种鱼贝类的皮和卵,绿藻—红球藻等藻类,红发夫酵母等酵母类,海洋性细菌,侧金盏花和毛茛等种子植物中获得。来自天然的提取物和化学合成品均市场有售,可以容易地获得。
虾青素例如按照公知的方法,将红发夫酵母、红球藻、海洋性细菌等在适当的培养基上培养获得。从容易培养或提取、以最高浓度含有虾青素或产率高的角度考虑,优选绿藻—红球藻。
红球藻是属于团藻目衣藻科的绿藻类。通常是绿藻,因此叶绿素含量高,为绿色,通过两条鞭毛在水中游泳。但是,在营养源缺乏或温度变化等饥饿条件下形成休眠孢子,虾青素含量增高,变成红色的球形。本发明中,可以使用任何状态下的红球藻,但优选使用较多含有虾青素的休眠孢子状的红球藻。属于红球藻属的绿藻类例如还可以使用雨生红球藻(Haematococcus pluviaris)、湖泊红球藻(Haematococcus lacustris)、Haematococcus capensis、Haematococcusdroebakensis、Haematococcus zimbabwiensis,最优选雨生红球藻(Haematococcus pluviaris)。
红球藻类的培养方法优选没有其它微生物的混入、繁殖、其它夹杂物混入少的密闭型培养方法,例如在部分开放式的穹顶形状、圆锥状或圆筒形状的培养装置和装置内具有可自由移动的排气装置的培养基进行培养的方法(国际公开第99/50384号公报),或者在密闭型的培养槽内放入光源,由内部照射光进行培养的方法,以及使用密闭型圆筒形状或平板状或管状的培养层的方法,以及使用峰波长约为540nm以下波长的光进行照射培养的方法(日本特开2004-147641号公报)。
从含有本发明的虾青素的红球藻中获得提取物的方法有以下:(1)将红球藻干燥并粉碎,然后以二氧化碳作为提取溶剂进行超临界提取,除去二氧化碳,获得提取物的方法[超临界提取法]、(2)将红球藻粉碎并用溶剂提取,除去溶剂,获得提取物的方法[粉碎提取法]。
以下具体说明超临界提取法。将含有虾青素的红球藻干燥并粉碎,然后填充到提取层中,以超临界状态的二氧化碳作为提取剂提取,除去二氧化碳,得到提取物。超临界状态的物质具有与液体同样的提取能力,同时具有接近于气体的扩散能力,提取效率高,并且不会残留作为提取溶剂的提取剂,可容易地完全分离。例如可按照日本特开2004-41147号公报所记载的方法进行超临界提取。
使用二氧化碳作为提取剂时,超临界提取的条件通常是温度31~80℃、优选31~50℃,压力为7.38~40MPa、优选10~38MPa。这里,二氧化碳的超临界流体不仅限于超临界状态,即温度和压力在超过临界温度、临界压力的状态下的流体,也包含温度、压力两者均在临界点附近等的所谓的亚临界状态的流体。
为了提高提取能力,可以在二氧化碳的超临界流体中加入辅助溶剂,这样可以提高提取能力。辅助溶剂为甘油、乙醇、水等,优选甘油。辅助溶剂可以根据提取速度的变化进行增减。例如提取时间过长则提取速度下降,可以使超临界流体中的辅助溶剂的添加量增多。
可用于提取的红球藻可使用按照常规方法进行粉碎、干燥所得,例如按照WO2002/077105号小册子中所记载的方法进行粉碎、干燥得到粉末。可以以粉末状直接填充,也可以预先通过湿式法形成为颗粒状、球状等形状,然后填充。通过在粉体和/或成型体中预先混合上述辅助溶剂或提取促进剂,可以提高提取性。
提取促进剂是红球藻等藻类中所含的油脂类,通过预先添加同样的物质,可以促进成型体形成多孔质,增加与超临界流体的接触面积,从而提高提取性能。油脂类例如有碳原子数为8~12个的中链脂肪酸三甘油酯、菜籽油、玉米油、橄榄油等的一种以上,优选碳原子数为8~12的中链脂肪酸三甘油酯。
以下具体说明粉碎提取法。粉碎提取法是将红球藻进行粉碎,用有机溶剂提取内含物,除去有机溶剂,获得提取物的方法。红球藻的粉碎可在水或有机溶剂中进行。将红球藻用水粉碎时,通过喷雾干燥等方法进行干燥,除去水,然后用有机溶剂提取。特别优选将红球藻悬浮于有机溶剂中,然后通过粉碎机,将细胞粉碎,同时提取,除去固体物质,除去有机溶剂,获得提取物的方法。该方法有以下特征:无需对红球藻进行过多的加热,另外提取途径中不会暴露在空气中,因此可以抑制脂质或虾青素等提取物内的物质的氧化,在制造过程中极少生成杂质。例如有本申请人以前所申请的方法(日本特愿2004-253525)。
这里使用的红球藻可以使用湿粉末或干燥物。可以根据需要添加表面活性剂、抗氧化剂。表面活性剂例如有聚甘油脂肪酸酯、甘油脂肪酸酯、蔗糖脂肪酸酯、山梨糖醇酐脂肪酸酯、丙二醇脂肪酸酯。抗氧化剂有维生素E(生育酚)、维生素E衍生物、生育三烯酚、迷迭香提取物、维生素C、维生素C衍生物、谷胱甘肽、植酸、儿茶酸类、类黄酮类、β-胡萝卜素等。
可用于提取的有机溶剂例如为乙醇、甲醇等醇类,丙酮,醚,乙酸乙酯,己烷,苯,氯仿,二氯甲烷;优选乙醇、甲醇、丙酮、己烷,特别优选丙酮、乙醇、己烷。
本发明的含类胡萝卜素类天然物的粉碎方法可以是将含有类胡萝卜素类的天然物悬浮于有机溶剂中,用可使用有机溶剂的粉碎机例如高压匀浆器、超声波粉碎机、珠磨机等进行湿式粉碎,优选用珠磨机进行湿式粉碎。
作为珠磨机的粉碎条件,为了抑制提取物的劣化,可在短时间内进行,停留时间为1~30分钟,圆周速度为2~30m/秒,所使用的珠子的直径为0.2~5mm,粉碎时的温度为-10至50℃。
除去固体物质的处理方法可按照常规方法例如加压过滤、减压过滤、自然过滤等进行。
溶剂的除去方法可按照常规方法进行,例如通过减压浓缩机等从滤液中除去有机溶剂。为了抑制提取物的劣化,最好是无需过多加温,可在0~200℃、优选20~80℃下进行,一次的处理时间越短越好,可以以在0.5~20小时、优选0.5~10小时内可处理的量除去溶剂。为了进一步除去溶剂,可以通过分子蒸馏机或薄膜式离心旋转蒸发器等进一步使有机溶剂的浓度降低。
作为虾青素的使用形式,可以使用由上述方法得到的含有虾青素的红球藻的提取物以及含有它们的粉末或水溶液、或者红发夫酵母、绿藻红球藻、海洋性细菌等的干燥品以及它们的粉碎品。其中,从容易使用或虾青素含量高的角度考虑,优选使用红球藻的提取物。
虾青素是3,3’-二羟基-β,β-胡萝卜素-4,4’-二酮,具有立体异构性。具体来说,已知有(3R,3’R)-虾青素、(3R,3’S)-虾青素和(3S,3’S)-虾青素三种立体异构体。本发明可以使用其中任意一种。
已知虾青素未见有突变原性,是安全性高的化合物,广泛作为食品添加物使用(高桥二郎等:红球藻虾青素的毒性试验-Ames试验、大鼠单次给予毒性试验、大鼠90天反复口服给予毒性试验,临床医药,20:867~881,2004)。
在本发明的记载中,如没有特别说明,虾青素包含虾青素和/或其酯。虾青素的酯还包含单酯和/或二酯。
本发明的作为用于减少体内脂肪的组合物的虾青素可以使用虾青素的游离态、单酯、二酯的至少一种。二酯中,两个羟基被酯键保护,因此化学性和物理性方面比游离态或单酯的稳定性高,在本发明的组合物中难以被氧化分解。不过,摄入到生物体中时,由于生物体内的酶而迅速水解为虾青素,从而显示效果。
虾青素的单酯可以是:低级或高级饱和脂肪酸、或者低级或高级不饱和脂肪酸酯化而得到的酯类。上述低级或高级饱和脂肪酸、或者低级或高级不饱和脂肪酸的具体例子有:乙酸、月桂酸、肉豆蔻酸、十五烷酸、棕榈酸、棕榈烯酸、十七烷酸、反油酸、蓖麻酸、岩芹酸、异油酸、桐酸、石榴油酸、十八碳三烯-4-酮酸、十八碳四烯酸、顺式-9-二十碳烯酸、5-二十碳烯酸、5-廿二碳烯酸、鲸蜡烯酸、芥酸、5,13-廿二碳二烯酸、鲨油酸、癸烯酸、ステリング酸、十二碳烯酸、油酸、硬脂酸、二十碳五烯酸、廿二碳六烯酸、亚油酸、亚麻酸、花生油烯酸等。另外,虾青素的二酯可以是选自上述脂肪酸的相同或不同种的脂肪酸被酯化而得的二酯类。
虾青素的单酯有:甘氨酸、丙氨酸等氨基酸;乙酸、柠檬酸等一元或多元羧酸;磷酸、硫酸等无机酸;葡糖苷等糖;甘油糖脂肪酸、鞘氨醇糖脂肪酸等糖脂肪酸;甘油脂肪酸等脂肪酸;甘油磷酸等被酯化而得到的单酯类。在可以的情况下,也包含上述单酯类的盐。
虾青素的二酯有:选自上述低级饱和脂肪酸、高级饱和脂肪酸、低级不饱和脂肪酸、高级不饱和脂肪酸、氨基酸、一元或多元羧酸、无机酸、糖、糖脂肪酸、脂肪酸以及甘油磷酸的相同或不同的酸酯化而得到的二酯类。在可以的情况下,也包含上述二酯类的盐。甘油磷酸的二酯可以是甘油磷酸的饱和脂肪酸酯类、或者含有选自高级不饱和脂肪酸、不饱和脂肪酸或饱和脂肪酸的脂肪酸类的甘油磷酸酯类等。
为了提高本发明的虾青素和红球藻提取物的减少体内脂肪的效果,可以在虾青素或红球藻提取物中混合选自活性成分、吸附剂和增溶剂的一种以上。活性成分例如有维生素A类、类胡萝卜素类、维生素B类、维生素C类、维生素D类、维生素E类、生育三烯酚、谷胱甘肽以及它们的衍生物和它们的盐;α-硫辛酸、脱氧核糖核酸、核糖核酸、三磷酸腺苷、单磷酸腺苷、甘草酸(glycyrrhizin)、甘草酸(glycyrrhizic acid)、鸟嘌呤、黄嘌呤、α-或γ-亚麻酸、二十碳五烯酸、琥珀酸、***及其衍生物和它们的盐;天冬氨酸、乙醇酸、乳酸、苹果酸、柠檬酸、水杨酸等α-羟基酸及其它们的衍生物和它们的盐;血清除蛋白的提取物、脾脏提取物、胎盘提取物、鸡冠提取物、蜂王浆;酵母提取物、乳酸菌提取物、双歧杆菌提取物、灵芝提取物;胡萝卜提取物、獐牙菜提取物、迷迭香提取物、黄柏提取物、蒜提取物、扁柏酚、顶花防己碱、芦荟提取物、鼠尾草提取物、山金车提取物、洋甘菊提取物、白桦提取物、小连翘提取物、桉提取物、无患子提取物、旋覆花提取物、鸡血藤提取物、山扁豆提取物、桑白皮提取物、当归提取物、拳参提取物、苦参提取物、山楂提取物、白百合提取物、啤酒花提取物、多花蔷薇提取物、薏苡仁提取物;D-组分、糖原、二十八烷醇、蒜素、辅酶Q10、儿茶酸;半胱氨酸及其衍生物和它们的盐;肽;赖氨酸、烯丙基硫醚、生物素、泛酸、胶原、弹性蛋白、角蛋白及它们的衍生物和它们的盐类;透明质酸、硫酸软骨素、硫酸皮肤素、硫酸乙酰肝素、肝素、硫酸角质素;乳酸菌;铁、钼、钙、锌、硒、锰、铜、碘等矿物质类等。优选生育酚、生育三烯酚、α-硫辛酸、辅酶Q10及它们的衍生物。
可混合在本发明的用于减少体内脂肪的组合物中的吸附剂有:乳糖、蔗糖等糖类,山梨醇、甘露醇、木糖醇、赤藓醇、麦芽糖醇等糖醇类,硅铝酸镁、水滑石、水化铝酸镁、无水磷酸钙、碳酸钙、硅酸酐、二氧化硅、滑石粉等无机化合物,纤维素类、淀粉类、明胶、琼脂。本发明的组合物可以是将虾青素或红球藻提取物和/或活性剂、吸附剂进行干式制粒或湿式制粒制备,湿式制粒可按照常规方法例如喷雾干燥法、硫化床制粒法、混炼制粒法或冷冻干燥法等干燥制备。
可混合在本发明的用于减少体内脂肪的组合物中的增溶剂有:中链脂肪酸三甘油酯、食用油脂类、脂肪酸酯、甘油、乙二醇等。本发明的组合物可以按照常规方法,将虾青素或红球藻提取物和/或活性剂、增溶剂混合。可以使这些混合物吸附在上述吸附剂上制粒制备。这些吸附剂或增溶剂通过减少虾青素与空气接触的面积,可有效防止虾青素的氧化。还可以有效地保护其到达肠等吸收部位。
本发明的组合物中,相对于组合物的总量,可以含有0.001%~99.9%虾青素,优选含有0.01%~20%虾青素,更优选含有0.1%~10%虾青素。本发明的组合物中,相对于组合物的总量,可以含有含虾青素的红球藻提取物0.01~99.9%,优选0.1%~80%,更优选1%~50%。
相对于1重量份虾青素,活性成分为0.05~2重量份,优选0.1~1重量份;吸附剂为1~1000重量份,优选2~500重量份;增溶剂为0.05~2重量份,优选0.1~1重量份。相对于1重量份含有虾青素的红球藻提取物,活性成分含有0.01~1重量份,优选0.02~0.5重量份;吸附剂含有0.2~10重量份,优选0.5~5重量份;增溶剂含有0.2~20重量份,优选0.5~10重量份。
本发明的组合物的给药或摄取量换算成虾青素游离态的量,成人每天为0.2mg~100mg的服用量,优选0.5mg~20mg,口服给药或非口服给药。给药量根据所给药的人的年龄、体重、状态的程度、给药形式而不同。
本发明的减少体内脂肪的效果是指即使体重没有变化,也使体内脂肪减少、体内脂肪率降低的效果;以及抑制体内脂肪增加、抑制体脂肪率增加的效果。在给药或摄取本发明的体脂肪减少剂期间,通过定期进行较轻的运动,可以进一步提高体内脂肪减少效果。通过给药或摄取本发明的用于减少体内脂肪的组合物,可以抑制体内脂肪的增加,从而也具有防止肥胖的效果。
通过减少过量的体内脂肪,也对于因肥胖或体重超标而引起的疾病例如糖尿病、动脉硬化、高血压、癌症、高血脂、类风湿、高血尿酸症、变形性关节炎、痛风、脑卒中、缺血性心脏病、呼吸障碍、胰腺炎、肾炎、白内障、早老性痴呆、变应性疾病、老化、多汗症、缺血疾病、糖尿病的并发症—肾病或神经障碍或视网膜障碍的相关疾病的治疗、改善、预防有效。神经障碍中,对于突发性的耳聋、眼或面部异常(麻痹或疼痛)、直立性低血压、发汗异常、腹泻或便秘(消化器官症状)、排尿障碍、四肢疼痛、知觉异常、肌肉萎缩、坏疽的治疗、改善、预防有效。眼障碍中,对于白内障、单纯视网膜病、增生前视网膜病和增生视网膜病有效。在缺血性心脏病中,对于脑梗死、心肌梗死的治疗、改善、预防有效。
可提高本发明的体内脂肪减少效果的运动有行走、自行车、攀登、有氧运动、机械训练、水中有氧运动、水中行走等有氧运动,每周可进行2~4次,每次运动30分钟~2小时。
本发明的组合物可以混合在药物中,可以按照常规方法制成例如片剂、舌下片剂、丸剂、栓剂、散剂、粉剂、细粒剂、颗粒剂、胶囊剂、微胶囊剂、注射剂、乳剂、贴剂等形式的制剂。例如片剂可以与药理上可接受的载体均匀混合、制片,散剂、粉剂、颗粒剂可以将药物和载体通过干式制粒或湿式制粒制备,湿式制粒可通过常规方法例如喷雾干燥法、硫化床制粒法、混合制粒法或冷冻干燥法等干燥制备。还可根据需要,按照常规方法制成咀嚼片剂或口腔内快速崩解片剂。
散剂、粉剂、细粒剂、颗粒剂、片剂可使用乳糖、葡萄糖、蔗糖、甘露糖醇、硅铝酸镁、合成水滑石、无水磷酸氢钙等赋形剂,淀粉、海藻酸钠等崩解剂,硬脂酸镁、滑石粉等润滑剂,聚乙烯醇、羟丙基纤维素、明胶等粘结剂,脂肪酸酯等表面活性剂,甘油等增塑剂等制备。
以本发明的虾青素或其酯作为有效成分的组合物可按照常规方法,混合适当的山梨醇、甘露糖醇、木糖醇、赤藓醇、麦芽醇等糖醇,乳糖、蔗糖、麦芽糖等糖类,硅铝酸镁、水滑石、水化铝酸镁、无水磷酸钙、碳酸钙等无机赋形剂,淀粉、明胶、甲基纤维素、氯乙烯吡咯烷酮等粘结剂,或者淀粉、琼脂、交聚维酮、结晶纤维素等崩解剂,或者二氧化硅、滑石粉、硬脂酸镁、聚乙二醇等润滑剂,香料、甜味剂,制成各种制剂的形式。例如可以以片剂、口腔内快速崩解剂、胶囊、颗粒、细粒等固体给药形式,酏剂、糖浆剂和混悬液等液体给药形式给药。
为了抑制虾青素或其酯的分解或氧化,可以根据需要向上述组合物中添加具有抗氧化能力的物质作为稳定剂。例如可以添加选自维生素A、维生素B、维生素C、维生素E或这些的维生素衍生物,生育酚,半胱氨酸,谷胱甘肽,谷胱甘肽过氧化物酶,柠檬酸类,磷酸类,多酚类,核酸类,中药类,海草类,无机物等现有的抗氧化剂的一种或两种以上的混合物。为了改善虾青素单体或单酯的吸收,可以以微粉状态给药。
本发明的组合物可以根据需要再添加其它抗氧化剂。对抗氧化剂没有特别限定,只要具有抗氧化作用均可采用。例如可选择松香油、3,4-二脱氢松香油等维生素A类,维生素B,D-抗坏血酸、L-抗坏血酸等维生素C类,生育酚、生育三烯酚、乙酸维生素E、琥珀酸维生素E等维生素E类,磷酸维生素E类,辅酶Q,类黄酮,鞣酸,鞣花酸,多酚类,自由基抑制剂,过氧化氢分解剂、金属螯合剂,活性氧除去剂,含有α-胡萝卜素、β-胡萝卜素、γ-胡萝卜素和δ-胡萝卜素的胡萝卜素类,生育醌,以及它们的药学上可接受的盐,以及它们的混合物的一种或两种以上。
注射剂可以根据需要,在pH调节剂、缓冲剂、溶解剂、悬浮剂、等渗剂、稳定剂、防腐剂等存在下,按照常规方法,将有效成分制成制剂。
悬浮剂例如有:聚山梨酯80、甲基纤维素、羟乙基纤维素、羧甲基纤维素钠、聚氧乙烯山梨糖醇酐单月桂酸酯、***树胶、粉末黄蓍胶等。溶解剂例如有:聚山梨酯80、氢化聚氧乙烯蓖麻油、烟酰胺、聚氧乙烯山梨糖醇酐单月桂酸酯、聚乙二醇、蓖麻油脂肪酸乙酯等。稳定剂例如有:亚硫酸钠、偏亚硫酸钠等。防腐剂例如有:对羟基苯甲酸甲酯、对羟基苯甲酸乙酯、山梨酸、苯酚、甲酚、氯甲酚等。
本发明的药物中,本发明的组合物可以以0.01~99.9%重量、优选0.1~90%重量的量含有。可根据每天的给药量适当确定。
本发明的组合物可以混合在具有降低脂肪效果的饮食中。
饮食的形式可以是功能性食品、特殊保健用食品、辅助食品等健康食品或常规食品、饮料等。
作为常规食品、饮料的形式,可以是人造黄油、黄油、奶油酱汁、干酪、鲜奶油、起酥油、猪油、冰激淋、酸乳酪、乳制品、酱汁、肉制品、鱼制品、炸薯条、薯片、爆米花、撒在饭上的粉状食品、香口胶、巧克力、布丁、果冻、软糖、糖果、水果糖、焦糖、松糕、蛋糕、炸面饼圈、饼干、曲奇饼、椒盐饼干等,通心粉、意大利面条、色拉油、速溶汤粉、调味汁、蛋、蛋黄酱、豆酱等,或果汁饮料、清凉饮料、运动饮料等碳酸类饮料或非碳酸类饮料等,茶、咖啡、可可等非酒精类,或者利口酒、药用酒等酒精饮料等常规食品中的添加剂。
对于本发明的饮食,可以在功能性食品、特殊保健用食品、辅助食品等健康食品中,制成与上述药物同样的形式。可以与乳蛋白、大豆蛋白、卵清蛋白等,或者它们的分解产物——蛋清低聚肽、大豆水解物、氨基酸单体的混合物一起使用。还可以是混合有糖类、脂肪、微量元素、维生素类、乳化剂、香料等的自然流食、半消化营养食品和营养食品、口服液剂、胶囊剂、肠营养剂等加工产品。以口服液剂的形式提供时,为了达到营养平衡、使摄取时的风味良好,可以混合氨基酸、维生素类、矿物质类等营养添加物、甜味剂、香辛料、香料和色素等。
将本发明的组合物混合在饮食中时,可以与常规的饮食的原料一起混合,按照常规方法加工制备。本发明的组合物的混合量根据食品的形态等而不同,没有特别限定,通常为0.00001~10%重量,优选0.0001~5%重量,可制成仅含有发挥降低体内脂肪效果的必要的量。本发明的组合物的使用量可由本领域技术人员根据饮食的种类适当选择,以本发明的组合物中所含虾青素游离态的量为基准,成人每天摄取量为0.2~100mg,优选0.5~20mg。
使用本发明的食品作为营养辅助食品或功能性食品时,其形态可以是与上述药用制剂同样的形态。本发明的食品形态并不限于此。为了减少动物的脂肪量,可以将本发明的组合物作为饲料供给。
实施例1
为了进一步详细说明本发明,以下给出实施例,当然,本发明并不只限于该实施例。
[红球藻提取物的制备方法]
将80kg干燥未粉碎的红球藻粉末(AstaReal AB公司制备、虾青素含量3.7%)和2kg复合维生素E(理研维生素、E700)分散于120kg丙酮中,使用填充了85%1mm直径玻璃珠的防爆型珠磨试验机(ダイノミルKDL-25BC、WAB制造),一边适时冷却一边在室温下以圆盘圆周速度10m/秒、流速100kg/小时进行两次粉碎处理,同时提取含有类胡萝卜素的脂质组分。将粉碎悬浮液总量进行吸滤,回收提取滤液,再将过滤残余物用40kg丙酮漂洗三次,完全提取含有类胡萝卜素的脂质成分。在减压下(100托、45℃)从所得提取滤液的总量中馏去丙酮,换算成游离态,得到含有5.0%虾青素的红球藻提取物。这里使用的红球藻是在密闭体系的培养装置中培养的。
将该红球藻浓缩物制成按照游离态换算含有6mg虾青素的胶囊(含药胶囊),用于试验。使用同种形态的含有0mg虾青素的胶囊作为安慰剂胶囊(对照胶囊),用于试验。
[受试者和摄取方法]
将32名23~57岁健康女性受试者随机分成两组,每组16人,作为试验组和对照组。采用双盲法对试验组和对照组进行分发,受试者和试验实施者到试验结束为止均不了解各受试者属于哪一组。试验组给予含药胶囊,对照组给予安慰剂胶囊,分别为每天两粒,使其在晚饭后服用。服用期间(试验期间)为6周。对所有的受试者测定试验开始时(0周)、服用终止时(6周)的体内脂肪率和体重。体内脂肪率通过体重计[TBF-511、(株)タニタ制造]测定。
[试验期间的运动负荷]
受试者在试验期间负荷的运动是行走,运动量根据试验开始前最大心搏率法决定。对于最大摄氧量为40ml/kg体重/分钟以上的受试者,按照最大心搏率的60~70%连续行走40分钟;对于最大摄氧量为40ml/kg体重/分钟以下的受试者,按照最大心率的50~60%连续行走40分钟,行走每周实施三次。
所得测定值的比较是在各组的试验开始时和试验结束时,使用所对应的t检验,另外,组间比较是使用无对应的t检验进行。
[表1]平均体内脂肪率(%)的变化
试验前(%) | 试验后(%) | 体内脂肪变化率(%) | |
试验组对照组 | 27.6±3.226.6±3.1 | 26.6±2.926.8±3.6 | -3.60.8 |
A:p<0.05(t-检验,对照组对试验组)
[表2]平均体重(kg)的变化
试验前(kg) | 试验后(kg) | 体内脂肪变化率(%) | |
试验组对照组 | 55.7±5.454.1±6.3 | 55.5±5.154.4±6.3 | -0.40.68 |
A:p<0.05(t-检验,对照组对试验组)
表1表示平均体内脂肪率的变化,表2表示平均体重的变化。试验组、对照组均未见体重的显著变化。关于体内脂肪率,试验组由27.6%变化为26.6%,显示体内脂肪降低3.6%;对照组由26.6%变化为26.8%,未见显著差异。该结果显示,通过摄取虾青素,体内脂肪率降低。
[制造例1]片剂
将下述成分按照下述组成比(%重量),通过均匀干式法混合,制成粉末,然后制成每粒为300mg的片剂。
红球藻提取物 30mg
乳糖 70mg
淀粉 70mg
酪蛋白钠 6mg
明胶 6mg
纤维素 109mg
二氧化硅 3mg
蔗糖脂肪酸酯 6mg
红球藻提取物中,将虾青素换算为游离态,含有5%重量。
[制剂2]软胶囊剂
将红球藻提取物(含有5%重量虾青素)和食用油脂混合,按照常规方法填充到含有下述成分的软胶囊剂壳中,得到每粒为300mg的软胶囊。
内容物
红球藻提取物 20mg
食用油脂 150mg
剂壳
明胶 100mg
甘油 30mg
[制剂例3]口服液剂
混合下述成分,按照常规方法加入10kg水,制备口服液剂。
红球藻提取物水溶液* 25g
液体糖 4000g
DL-酒石酸钠 1g
柠檬酸 50g
维生素C 50g
维生素E 150g
环糊精 25g
氯化钾 5g
硫酸镁 2g
*按照日本特开2001-316601中实施例的方法制备的红球藻提取物水溶液(含有1%虾青素)
[制剂例4]长颗粒
混合下述成分,按照常规方法制粒,制备装有5g的长颗粒。
Astareal粉末* 5%
复合维生素B 1%
烟酸 0.1%
泛酸 0.1%
牛磺酸 10%
谷氨酸 1%
GABA 0.01%
天冬氨酸 0.05%
BCAA 0.5%
柠檬酸 10%
维生素C 10%
γ-谷维素粉末 0.15%
CMCNa 适量
糊精 适量
*含有1%重量虾青素的红球藻提取物的粉末
Claims (6)
1.用于减少体内脂肪的组合物,其含有虾青素作为有效成分。
2.用于减少体内脂肪的组合物,其是将红球藻粉碎并用溶剂提取所得。
3.用于减少体内脂肪的组合物,其是在权利要求1~2中任一项的组合物中混合活性成分、吸附剂、增溶剂的一种以上而得到的。
4.体内脂肪减少剂,其含有权利要求1~3中任一项的组合物。
5.用于减少体内脂肪的饮食,其含有权利要求1~3中任一项的组合物。
6.减少体内脂肪的方法,其包含将权利要求1~3中任一项的组合物对人给药或摄取。
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CN (1) | CN101111239A (zh) |
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WO (1) | WO2006059730A1 (zh) |
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CN105055368A (zh) * | 2015-09-23 | 2015-11-18 | 湖北雅仕达生物技术有限公司 | 促进胃肠道吸收虾青素的口服制品及制备方法 |
CN107456451A (zh) * | 2017-09-07 | 2017-12-12 | 集美大学 | 虾青素酯作为胰脂肪酶抑制剂的用途 |
CN108065392A (zh) * | 2017-12-05 | 2018-05-25 | 杭州鑫伟低碳技术研发有限公司 | 一种辅助治疗高血压、高血脂症状的组合物 |
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JP2007238441A (ja) * | 2004-12-03 | 2007-09-20 | Fuji Chem Ind Co Ltd | アスタキサンチンを有効成分とする体脂肪減少用組成物 |
JP5070040B2 (ja) * | 2005-03-31 | 2012-11-07 | 富士化学工業株式会社 | 血管不全改善剤 |
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JP5260996B2 (ja) * | 2008-03-25 | 2013-08-14 | 株式会社イムダイン | 発声改善剤 |
KR101322259B1 (ko) | 2008-10-27 | 2013-10-28 | 에스비아이 파마 가부시키가이샤 | 5-아미노레불린산 혹은 그의 유도체, 또는 그들 염을 유효성분으로 하는 성인병의 예방·개선제 |
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RU2551578C2 (ru) * | 2013-04-29 | 2015-05-27 | Сергей Константинович Панюшин | Сыпучий пищевой продукт |
EP3040069A4 (en) * | 2013-06-27 | 2017-04-12 | The Doshisha | Intestinal flora improving composition containing astaxanthin |
WO2016146803A1 (de) * | 2015-03-19 | 2016-09-22 | Basf Se | Astaxanthinzusammensetzungen (iii) |
CN107427029A (zh) * | 2015-03-19 | 2017-12-01 | 巴斯夫欧洲公司 | 虾青素组合物(i) |
JP6978103B2 (ja) * | 2015-07-01 | 2021-12-08 | 株式会社東洋新薬 | 網膜保護組成物 |
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IL113935A (en) * | 1995-05-31 | 1999-09-22 | Imi Tami Institute Research | Process for the recovery of carotenoid pigment from algae |
JPH10155459A (ja) * | 1996-11-27 | 1998-06-16 | Suntory Ltd | アスタキサンチン含有飲食物 |
SE513186C2 (sv) * | 1997-12-09 | 2000-07-24 | Astacarotene Ab | Sätt att öka produktionen av och förbättra kvaliteten hos sperma med användning av xantofyller |
SE9903619D0 (sv) * | 1999-10-07 | 1999-10-07 | Astacarotene Ab | Use and method of treatment |
JP4628557B2 (ja) * | 2001-02-07 | 2011-02-09 | 末人 山上 | 血行障害の改善作用を有する健康補助食品 |
US7064101B2 (en) * | 2001-03-22 | 2006-06-20 | Fuji Chemical Industry Co., Ltd. | Stable astaxanthin-containing powdery compositions and process for producing the same |
JP2003064360A (ja) * | 2001-08-28 | 2003-03-05 | Nissui Pharm Co Ltd | 抗酸化剤 |
US20030054070A1 (en) * | 2001-09-07 | 2003-03-20 | Aquasearch, Inc. | Edible solvent extraction of carotenoids from microorganisms |
JP5031156B2 (ja) * | 2001-09-20 | 2012-09-19 | カゴメ株式会社 | 抗肥満剤 |
JP2003335668A (ja) * | 2002-05-21 | 2003-11-25 | Fuji Chem Ind Co Ltd | 経口用美肌用剤 |
CN1708480B (zh) * | 2002-07-29 | 2010-12-15 | 卡达克斯药物公司 | 用于抑制和改善疾病的类胡萝卜素结构类似物 |
EP2653157B1 (en) * | 2004-02-04 | 2016-08-03 | Fuji Chemical Industry Co., Ltd. | Astaxanthin for improving muscle atrophy |
JP2007238441A (ja) * | 2004-12-03 | 2007-09-20 | Fuji Chem Ind Co Ltd | アスタキサンチンを有効成分とする体脂肪減少用組成物 |
-
2004
- 2004-12-03 JP JP2004382296A patent/JP2007238441A/ja active Pending
-
2005
- 2005-12-02 WO PCT/JP2005/022218 patent/WO2006059730A1/ja active Application Filing
- 2005-12-02 CN CNA2005800472567A patent/CN101111239A/zh active Pending
- 2005-12-02 US US11/792,211 patent/US20090047304A1/en not_active Abandoned
- 2005-12-02 EP EP05811785A patent/EP1829537A4/en not_active Withdrawn
- 2005-12-02 JP JP2006546657A patent/JP5165894B2/ja not_active Expired - Fee Related
- 2005-12-02 KR KR1020077012455A patent/KR101262686B1/ko active IP Right Grant
- 2005-12-02 RU RU2007125126/15A patent/RU2402342C2/ru active
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102150838A (zh) * | 2010-12-16 | 2011-08-17 | 北京康比特体育科技股份有限公司 | 一种减肥组合物,包含组合物的制剂及其制备方法 |
CN105055368A (zh) * | 2015-09-23 | 2015-11-18 | 湖北雅仕达生物技术有限公司 | 促进胃肠道吸收虾青素的口服制品及制备方法 |
CN107456451A (zh) * | 2017-09-07 | 2017-12-12 | 集美大学 | 虾青素酯作为胰脂肪酶抑制剂的用途 |
CN108065392A (zh) * | 2017-12-05 | 2018-05-25 | 杭州鑫伟低碳技术研发有限公司 | 一种辅助治疗高血压、高血脂症状的组合物 |
Also Published As
Publication number | Publication date |
---|---|
JP5165894B2 (ja) | 2013-03-21 |
RU2007125126A (ru) | 2009-01-10 |
EP1829537A4 (en) | 2012-06-06 |
EP1829537A1 (en) | 2007-09-05 |
WO2006059730A1 (ja) | 2006-06-08 |
RU2402342C2 (ru) | 2010-10-27 |
KR101262686B1 (ko) | 2013-05-15 |
JPWO2006059730A1 (ja) | 2008-06-05 |
KR20070109981A (ko) | 2007-11-15 |
JP2007238441A (ja) | 2007-09-20 |
US20090047304A1 (en) | 2009-02-19 |
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