CN101662956A - 羟基酪醇和含有羟基酪醇的橄榄提取物/浓缩物的新颖用途 - Google Patents
羟基酪醇和含有羟基酪醇的橄榄提取物/浓缩物的新颖用途 Download PDFInfo
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- CN101662956A CN101662956A CN200880012549A CN200880012549A CN101662956A CN 101662956 A CN101662956 A CN 101662956A CN 200880012549 A CN200880012549 A CN 200880012549A CN 200880012549 A CN200880012549 A CN 200880012549A CN 101662956 A CN101662956 A CN 101662956A
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Abstract
本发明涉及羟基酪醇(包含羟基酪醇的组合物)作为生命延长剂的用途。本发明还另外涉及的组合物基本上不包含白藜芦醇,并且优选地被经口施用给动物。本发明还涉及生命延长方法。“生命延长”在本发明的上下文中表示:与未处理的情况相比降低在某年龄死亡的风险;提高存活更久(长寿)的可能性;和/或延长不依赖于医疗护理的寿命。
Description
本发明涉及羟基酪醇(包含羟基酪醇的组合物)作为生命延长剂(lifeprolonging agent)的用途。本发明还涉及的组合物基本上不包含白藜芦醇,并且被经口施用给动物。本发明还涉及生命延长方法。“生命延长”在本发明的上下文中表示:与未处理的情况相比降低在某年龄死亡的风险;提高存活更久(长寿)的可能性,即与未处理的情况相比提高平均生命预期(life expectancy);和/或延长不依赖于医疗护理的寿命。
因此,羟基酪醇能够使人存活更久;延长人的生命;使人愉快地衰老和/或消耗其生命期。
寿命(longevity)是人生命的长度(生命预期)。多种因素对个体的寿命有所贡献。生命预期中的重要因素包括性别、遗传因素、健康护理情况、卫生状况、饮食、锻炼、生活方式和犯罪率。
活到较老的年龄一直为人们所期盼。有许多机构致力于探寻衰老的原因、防止衰老的途径、和逆转衰老的途径。这表明非常需要提高存活更久的机会的手段。
由American Journal of Clinical Nutrition 2006(Feb),83(2),484S-487S:″The different paths to 100.Perls TT.″已知以下内容:
基于人群的研究表明约90%的百岁老人在92岁的平均年龄时具有生活自理能力(functionally independent)。因此,为了达到极老的年龄,出现了一种更加可能的观点:个体越老,他或她就曾经越健康。因此,百岁老人可能代表一种抵抗年龄相关疾病和更慢衰老的模型。目前在美国,每10000个人中有1个为100岁龄或更老。然而,该比率在迅速改变,并且很可能大部分工业化的国家会很快经历该比率的两倍,即每5000人中一个百岁老人。存活至极老年龄的能力似乎是遗传因素、环境、生活方式和运气的复杂组合的结果。理解非常老的人的遗传特性,和鉴定寿命(或死亡率)的分子驱动物,是一种潜在地有力的途径,可用于发现调节衰老和疾病易感性的生物通路,并用于开发会允许更多人群在良好健康下衰老的预防剂和治疗剂。
我们惊讶地发现,在低等生物的模型Drosophila Melanogaster(果蝇)中,羟基酪醇能够提高生命预期。Drosophila已在老年学研究中广泛用作模型生物,用于研究能够延长生命期的处理。其具有允许有效研究制品对寿命影响的短生命周期,但是却含有复杂的器官和内分泌系统。
优选地,羟基酪醇是组合物中唯一的活性生命延长成分。
羟基酪醇(3,4-二羟基苯乙醇)可以是合成来源的,或可与其他水溶性多酚(例如酪醇和橄榄苦苷)一起从橄榄叶、橄榄果实和橄榄油生产中的植被水(vegetation water)提取获得。
因此,术语“羟基酪醇”还包括含有羟基酪醇的任何植物材料或提取物,特别是以植物材料或提取物的总重为基础,以至少1.5重量%的量,优选地以至少30重量%的量,更优选地以至少40重量%的量,最优选地以至少50重量%的量含有羟基酪醇的那些。本发明上下文中使用的术语“植物材料”表示植物的任何部分。
在本发明的其他实施方案中,可使用羟基酪醇衍生物例如酯和生理学/药学可接受的盐来代替羟基酪醇。还可以使用羟基酪醇和羟基酪醇衍生物的混合物。
衍生物可以是例如酯。羟基酪醇的优选的酯是例如乙酸酯或葡糖苷酸(gucuronide)缀合物。羟基酪醇酯的最优选的例子是橄榄苦苷。
涉及从橄榄叶中提取橄榄苦苷和/或羟基酪醇的参考文献的例子是WO02/18310、US 2002/0198415、WO2004/005228、US 6,416,808和US2002/0058078,它们公开了下述方法:将橄榄植被水酸水解2到12个月,直至存在的橄榄苦苷中至少90%被转化。从橄榄、橄榄果肉、橄榄油和橄榄研磨沸水中提取酚类化合物的方法由Usana Inc.专利US 6,361,803和WO01/45514和US 2002/0004077描述。EP-A 1582512描述了从橄榄叶中提取羟基酪醇。从去核橄榄的植被水中获得羟基酪醇和/或橄榄苦苷的方法公开于US 2004/0039066A1中第[0080]-[0091]段。
可特别地根据US 6,416,808(第4栏第37行到第7栏第27行);WO2004/005228;US 6,936,287;US 2005-103711;US 2003-108651;US2002-198415;US 6,165,475;JP 2001-252054;JP 2000-319161;WO01/45514(Usana)US 6,358,542(特别见第4栏第1行到第9栏第50行和实施例1-5和11-13)US 6,361,803(特别见第3栏第64行到第9栏第47行和实施例1-5和11-13);和WO 2006/084658中公开的方法之一制造植被水。
优选地如US 6,416,808(第4栏第37行到第7栏第27行)中所公开的内容来制造植被水。
还可使用植被水浓缩物代替羟基酪醇;然而优选使用纯度至少为1.5重量%,优选地至少为30重量%,更优选地至少为50重量%的羟基酪醇。
一种特别合适的植被水浓缩物是例如可商业得自CreAgri,Hayward,美国的″6%″,″6%″含有以6%总重为基础5到8重量%的蛋白质,45到68重量%的碳水化合物,17到30重量%的脂肪,8到15重量%的灰分和最少6重量%的水溶性单酚和多酚(其中约2.5重量%的羟基酪醇)。
也可使用均可商业得自CreAgri,Hayward,美国的″2%″和″9%″,以及可商业得自Glanbia and Indena(Milan,Italy)的一下产品:含有20到35重量%羟基酪醇和4到6重量%酪醇的OLIVACTIVTM;总酚含量≥30重量%(通过UV测量),羟基酪醇量≥1.5重量%(通过HPLC测量),毛蕊花糖苷(verbascoside)量≥5.0重量%(通过HPLC测量)的OLEASELECTTM;和每kg含有22到24g羟基酪醇和5.0到6.5g酪醇的粉末OLIVE(OLEA)DRY。
其他合适的产品是可商业得自Seppic的Prolivols,其含有35重量%的多酚,特别是20mg羟基酪醇(每g Prolivols)和3mg酪醇(每gProlivols);以及Olive Braun Standard 500(来自obipektin):每kg含1.0到2.2g羟基酪醇和0.2到0.7g酪醇的粉末;Olivex橄榄多酚液体P10(来自Albert Isliker):每kg含2.0到3.5g羟基酪醇和0.2到1.0g酪醇的液体;Olivex橄榄多酚(来自Albert Isliker):每kg含22到23g羟基酪醇和6.5到8.0g酪醇的粉末;和Olive Polyphenols NLT(来自LalilabInc.),其含有2.0到6重量%的羟基酪醇和0.7到1.1重量%的酪醇。
在合适的可商业获得的植被水浓缩物中,羟基酪醇的量在每kg植被水浓缩物总重1.0到220g的范围内变化。酪醇的量优选地在每kg植被水浓缩物总重0.2到45g的范围内变化。羟基酪醇与酪醇的重量比例优选地在100∶10和100∶40之间,更优选地在100∶18和100∶35之间。
植被水在商业上也称作“橄榄汁”,其干燥的制品也可称作“橄榄汁粉末”或“橄榄汁制剂”。
“基本不含白藜芦醇”是指组合物中白藜芦醇的量以组合物的总重为基础≤1重量%,优选地≤0.5重量%,更优选地≤0.1重量%。其还表示不有意地向组合物中添加白藜芦醇。白藜芦醇仅可作为从植物或植物果实(例如橄榄)中获得的羟基酪醇提取物/浓缩物的副产物存在于组合物中。
优选地,组合物被经口施用给动物,这表示组合物是可以被动物食用或饮用或通过口/颌(jaw)放入动物胃中的任何形式。
因此,组合物优选地选自饮食补剂、食物添加剂、功能性食物、饲料添加剂、功能性饲料、食物预混物、饲料预混物和饮料。
饮食补剂形式的例子是片剂、丸剂、颗粒剂、锭剂、胶囊、即食饮品和泡腾配制物。
食物/饲料添加剂的例子是为用于消耗在食物/饲料的制造期间或其制备期间添加进食物/饲料中的任何组合物/配制物。
功能性食物的例子是乳制品(酸乳)、谷物棒和烘焙物品例如蛋糕、曲奇和面包。也包括临床营养品。
功能性饲料(包括宠物食品组合物)的例子包括旨在提供必需饮食需求的饲料,以及所有的零食(例如狗饼干)或其他饲料补剂。包含根据本发明的组合物的动物饲料可以是干燥组合物(例如粗粉(kibble))、半湿润组合物、湿润组合物或其任何组合的形式。替代地或另外,动物饲料是补剂例如肉汁(gravy)、饮用水、酸乳、粉末、悬浮液、咀嚼物、调剂物(例如饼干)或任何其他递送形式。
食物预混物的例子是用于制造乳制品、谷物棒和烘焙物(例如蛋糕和曲奇)和汤的预混物。
本发明的另一方面涉及饲料添加剂或添加剂组合物,例如要被添加进一种或多种可食用饲料物质或成分中,例如用于制备饲料组合物或用于补充现存的饲料以形成饲料组合物。
所谓的预混物是本发明的动物饲料添加剂的例子。预混物表示一种或多种微量成分(micro-ingredient)与稀释剂和/或载体的优选地均一的混合物。预混物被用于促进微量成分在更大混合物中的均一分散。
预混物可以是颗粒或团块的形式。
在一个具体的实施方案中,羟基酪醇在被添加进饲料中的形式下或被包含在饲料添加剂中时,是充分确定的。术语“充分确定的”表示羟基酪醇制剂至少为30%纯净。在另一具体的实施方案中,充分确定的羟基酪醇制剂为至少50%、60%、70%、80%、85%、88%、90%、92%、94%或至少95%纯净。
通常,脂溶性和水溶性维生素,以及痕量矿物质形成用于添加进饲料中的所谓预混物的一部分,而主要矿物质则通常被独立地添加进饲料中。
另外,任选的饲料添加剂成分是着色剂,例如类胡萝卜素如β-胡萝卜素、虾青素和叶黄素;芳香化合物;稳定剂;抗微生物肽;产活性氧的物类;和/或至少一种选自以下的酶:植酸酶(EC 3.1.3.8或3.1.3.26);木聚糖酶(EC 3.2.1.8);半乳聚糖酶(EC 3.2.1.89);α-半乳糖苷酶(EC 3.2.1.22);蛋白酶(EC 3.4.)、磷脂酶A1(EC 3.1.1.32);磷脂酶A2(EC 3.1.1.4);溶血磷脂酶(EC 3.1.1.5);磷脂酶C(EC 3.1.4.3);磷脂酶D(EC 3.1.4.4);淀粉酶,例如α-淀粉酶(EC 3.2.1.1);和/或β-葡聚糖酶(EC 3.2.1.4或EC3.2.1.6)。
饮料包括无醇饮品和含酒精的饮品,以及要添加进饮用水和液体食品中的液体制剂。无醇饮品为例如方便饮品、软饮、运动饮品或一般性运动饮料、果汁(如例如橙汁、苹果汁和葡萄汁);蔬菜汁(如番茄汁);思慕雪、柠檬水、功能性水、接近水的饮品(即具有低卡路里含量的基于水的饮品)、茶和基于乳的饮品。含酒精的饮品特别是啤酒。液体食品为例如汤和乳制品(例如麦芯饮品)。
根据本发明的饮食组合物可还含有保护性水胶体、粘合剂、成膜剂、包封剂/材料、壁/壳材料、基质化合物、包衣、乳化剂、表面活性剂、增溶剂(油、脂肪、蜡、卵磷脂等等)、吸附剂、载体、填充剂、辅助化合物、分散剂、湿润剂、加工助剂(溶剂)、流动剂、遮味剂、增重剂、啫喱化剂(jellyfying agents)、凝胶形成剂、抗氧化剂和抗微生物剂。
也可以替代饮食补剂使用并被本发明涵盖的是药物组合物或OTC(非处方)制剂。
除了可药用的载体和具有上文给出的优选的纯度(和其他优选级)的羟基酪醇(衍生物)以外,根据本发明的药物组合物可还含有常规的药物添加剂和佐剂、赋形剂或稀释剂,包括但不限于水、任何来源的明胶、植物胶、硫酸木质素、滑石、糖、淀粉、阿拉伯胶、植物油、聚亚烷基二醇、调味剂、防腐剂、稳定剂、乳化剂、缓冲剂、润滑剂、着色剂、湿润剂、填充剂等等。载体材料可以是适用于口施用的有机或无机惰性载体。
根据本发明的饮食补剂和药物组合物可以是适用于对动物体(优选地对人体)口施用的任何盖仑形式(galenic form),例如固体形式如片剂、丸剂、颗粒剂、锭剂、胶囊和泡腾配制物如粉末和片剂,或液体形式如溶液、乳液或悬浮液,如例如饮料、糊剂和油悬浮液。糊剂可以被填充进硬壳或软壳胶囊中。饮食和药物组合物可以是受控(延迟)释放配制物的形式。
根据本发明,这类组合物被用于延长动物的生命。
因此,本发明还涉及(具有上文给出的形式和优选级的)被施用给动物(优选人)的包含羟基酪醇的组合物,所述组合物用于延长所述动物(优选人)的生命,其中所述组合物基本不包含白藜芦醇。优选地,所述组合物经口施用。
另外,本发明通过对动物施用有效量羟基酪醇或有效量包含羟基酪醇的组合物来延长所述动物生命的方法,其中所述组合物基本上不包含白藜芦醇。
动物在本发明的上下文中包括人并包括哺乳动物、鱼和鸟。优选的“动物”是人、宠物动物和农业动物以及骆驼和大象,其中人是特别优选的。
宠物动物的例子是狗、猫、鸟、观赏鱼(toy fish)、荷兰猪、仓鼠、兔子和雪貂。农业动物的例子是鱼、猪、马、反刍动物(牛、绵羊和山羊)和家禽。
“延长动物的生命”在本发明的上下文中表示与未处理情况相比降低在某年龄死亡的风险;提高存活更久(长寿)的可能性,即与未处理情况相比提高平均生命预期;和/或延长不依赖于医疗护理的寿命。
本发明还包括的其他定义由Hermann Brenner和Volker Amdt在Experimental Gerontoloy 2004,39,679-686:″Epidemiology in aging research″中给出。
计算生命预期的起点是人群成员的年龄分组死亡率(age-specific deathrates)。例如,如果一组人中10%在其90岁生日存活并在其91岁生日前死亡,则在90岁的年龄分组死亡率为10%。
然后使用这些数值计算生命表(life table),可以根据所述表计算存活到每个年龄的概率。在保险精算符号(actuarial notation)中,从年龄x存活到年龄x+n的概率被表示为npx,在年龄x期间(即在年龄x和x+1之间)死亡的概率被表示为qx。
然后通过合计存活至每个年龄的概率,计算年龄x时的生命预期(表示为ex)。这是对存活总年数的预期值(应当将其视为他们庆祝的生日数)。
因为年龄被取整至最后一个生日,人们在其最后一个生日后平均再生存半年,所以对生命预期加上半年来计算总生命预期。
生命预期根据其定义是一种算术平均值。还可以通过将生存曲线从年龄到正无穷大积分计算生命预期(最大生命期,有时称作“ω”)。当然,对于已消失的同龄组(例如所有在1850年出生的人)而言,可以通过将死亡年龄平均来简单地计算生命预期。对于有一些存活者的同龄组而言,通过使用近几年的死亡率经验估计生命预期。
注意在该计算中没有对未来生命预期的预期改变进行修正(allowance)。通常引用生命预期图表时,它们已经如此计算而未针对预期的未来改变进行修正。这表示引用的生命预期图表通常不适用于计算具体年龄的任何给定个体预期能够存活多久,因为它们有效地假设目前的死亡率会被“冻结”并且在未来不会改变。相反,生命预期图表可以被认为是概括人群目前健康状态的一种有用的统计值。存在一些模型用于说明死亡率的进化(例如Ronald D.Lee和Lawrence Carter在Journal of the AmericanStatistical Association 1992(September),87,659-671:″Modeling andForecasting the Time Series of U.S.Mortality″中公开的Lee-Carter模型)。
果蝇用于测定其他物种(包括人)寿命的用途在例如Browner WS,Kahn AJ,Ziv E,Reiner AP,Oshima J,Cawthon RM,Hsueh WC和CummingsSR的American Journal of Medicine 2004,117(11),851-860:′The genetics ofhuman longevity″中公开。该科技文章的作者发现,“在模型生物例如小鼠、果蝇和蠕虫中影响衰老和寿命的许多基因具有人同系物”。
果蝇寿命模型对饮食限制(DR)阳性应答。已知饮食限制在大量衰老模型(例如酵母、线虫、果蝇和小鼠)中提高寿命/生命期,所述饮食限制通过无营养不良的低营养(undemutrition)实现,即受限制的饮食含有避免任何必需营养素缺乏并维持动物体功能的足量的蛋白质、脂肪、维生素和矿物质。典型地,饮食-限制研究中的测试生物比其自由-进食的副本消耗少30%到50%卡路里的饮食。这些受限制的饮食含有维持动物体功能的足量的蛋白质、脂肪、维生素和矿物质。DR一致地提高若干种哺乳动物(小鼠、大鼠、荷兰猪)的生命期。最近的数据提出,饮食限制可延长猴子的生命期,并可能延长人的生命期。最后,大量研究显示涉及调节生命期的通路在进化中和物种间(从线虫变化到人)是保守的。对涉及生命期调节的关键分子通路例如胰岛素信号转导通路而言就是这样,所述通路从单细胞酵母到哺乳动物是保守的。胰岛素信号转导通路已经显示在不同物种的生命期调节以及生长和尺寸中起关键作用。这种保守表明,某些影响生命期的生理学过程在物种间是保守的,并有力地说明提高简单动物寿命的处理很可能对于哺乳动物寿命是重要的。因此,Drosophila已成为一种公认的鉴定能够延长人寿命的化合物的模型。
用于人(70kg人)的羟基酪醇每日剂量可以为至少0.1mg。其可从5到500mg变化,优选地从15到100mg变化。
对哺乳动物而言,羟基酪醇的优选的剂量从0.28到1.9mg/(kg代谢体重)变化,其中对哺乳动物而言
“代谢体重”[以kg计]=(体重[以kg计])0.75
这表示例如对70kg的人而言,优选的每日剂量应在6.77和45.98mg之间变化,对20kg的狗而言,优选的每日剂量应在2.23和15.1mg之间变化。
本发明接着通过以下的非限制性实施例进一步阐述。
实施例
实施例1
软明胶胶囊
通过常规工序来制备提供下述剂量的软明胶胶囊,所述剂量为每粒胶囊50mg羟基酪醇。合适的每日剂量为1到5粒胶囊。
其它成分:甘油。水、明胶、植物油
实施例2
硬明胶胶囊
通过常规工序来制备提供下述剂量的硬明胶胶囊,所述剂量为每粒胶囊75mg羟基酪醇。合适的每日剂量为1到5粒胶囊。
其它成分:
填料:适量的乳糖或纤维素或纤维素衍生物
润滑剂:如果需要的话,硬脂酸镁(0.5%)
实施例3
片剂
通过常规工序来制备片剂,每片提供100mg羟基酪醇作为活性成分,和微晶纤维素、二氧化硅(SiO2)、硬脂酸镁、交羧甲基纤维素钠总计500mg作为赋形剂。
实施例4
软饮
可如下制备含有羟基酪醇的软饮:
混合果汁浓缩物和水溶性香料而不掺入空气。将色素溶于去离子水中。将抗坏血酸和柠檬酸溶于水中。将苯甲酸钠溶于水中。果胶在搅拌下被添加并在煮沸时溶解。冷却溶液。预混合橙油和油溶性香料。将F下提到的活性成分搅拌进A的果汁浓缩物混合物中。
为了制备软饮,将所有的组分A-F混合在一起后使用Turrax和随后使用高压匀化器(p1=200bar,p2=50bar)匀化。
实施例5
使用Drosophila的生命延长实验
使用Drosophila melanogaster(Oregon野生株系)进行生命期研究。将果蝇在12:12小时的光/暗循环中于25℃的温度和65%的相对湿度下进行培养。用含170g玉米粉、15g琼脂、15g酵母、10ml 100%丙酸、130g蔗糖和2000ml水的标准培养基饲喂果蝇。
生命期研究
将一天龄的Drosophila转移至含2ml饮食培养基的塑料管(25x100mm)中,所述饮食培养基每3天更换。一只管中放置每种性别的10只果蝇。从第15天开始在饮食中为Drosophila提供羟基酪醇。每3天对Drosophila计数直至所有果蝇死亡。在实验结束时,在校正由于操作造成的总损失后计算存活率(Phillips JP,Campbell SD,Michaud D,Charbonneau M,HillikerAJ,Proc Natl Acad Sci U S A.1989,86(8),2761-2765:″Null mutation ofcopper/zinc superoxide dismutase in Drosophila confers hypersensitivity toparaquat and reduced longevity.″)。根据Cui X,Dai XG,Li WB,Zhang BL,Fang YZ in Am.J.Chin.Med.1999,27(3-4),407-413:″Effects of lu-duo-weicapsule on prolonging life span of housefly and Drosophila melanogaster.″所述方法计算平均生命期。
结果
在饮食中以1、5、10、20和50mg/100g的浓度测试羟基酪醇。所有的浓度都延长了雄性Drosophila的生命期,在5mg/100g饮食下观察到最好的效果(11.5%)。
对照 | 羟基酪醇1mg/100g | 羟基酪醇5mg/100g | 羟基酪醇10mg/100g | 羟基酪醇20mg/100g | 羟基酪醇50mg/100g | |
Drosophila总数 | 299 | 264 | 253 | 290 | 300 | 300 |
平均生命期(天) | 69.42 | 75.14 | 77.44 | 72.12 | 74.26 | 72.21 |
STDEV(天) | 17.83 | 34.71 | 19.23 | 20.53 | 17.16 | 18.71 |
相对于对照生命期的增长百分数 | 8.23 | 11.55 | 3.89 | 6.97 | 4.02 |
Claims (10)
1.包含羟基酪醇的组合物作为生命延长剂的用途,其中所述组合物基本不含白藜芦醇。
2.根据权利要求1的用途,其中羟基酪醇是所述组合物中唯一的活性生命延长成分。
3.根据权利要求1或2的用途,其中所述组合物被经口施用给动物。
4.根据权利要求3的用途,其中所述组合物选自饮食补剂、食物添加剂、功能性食物、食物预混物、饲料添加剂、功能性饲料、饲料预混物和饮料。
5.包含羟基酪醇的用于动物的组合物,所述组合物用于与未用所述组合物处理的动物相比降低在某年龄死亡的风险;用于提高存活更久(长寿)的可能性,即与未用所述组合物处理的动物相比提高平均生命预期;和/或延长不依赖于医疗护理的寿命,其中所述组合物基本不含白藜芦醇。
6.根据权利要求5的组合物,其中所述组合物被经口施用给所述动物。
7.根据权利要求6的组合物,其中所述组合物是饮食补剂、食物添加剂、功能性食物、饲料添加剂、功能性饲料或饮料的形式。
8.根据权利要求5到7中任一项的组合物,其中所述动物是人。
9.通过对动物施用有效量羟基酪醇或有效量包含羟基酪醇的组合物来延长所述动物生命的方法,其中所述组合物基本不含白藜芦醇。
10.通过对所述动物施用有效量的羟基酪醇或有效量的含羟基酪醇的组合物,来降低在某年龄死亡的风险;提高存活更久(长寿)的可能性,即提高平均生命预期;和/或延长不依赖于医疗护理的寿命的方法,其中所述组合物基本不含白藜芦醇。
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JP2001181632A (ja) * | 1999-10-14 | 2001-07-03 | Nisshin Oil Mills Ltd:The | 抗酸化剤 |
US7713569B2 (en) * | 2000-09-01 | 2010-05-11 | Creagri, Inc. | Hydroxytyrosol-rich composition from olive vegetation water and method of use thereof |
JP3820218B2 (ja) * | 2000-09-01 | 2006-09-13 | クレアグリ, インコーポレイテッド | 植物水からヒドロキシチロソール富化組成物を得る方法 |
JP2002153238A (ja) * | 2000-11-21 | 2002-05-28 | Nippon Shinyaku Co Ltd | 食品、飼料及び医薬組成物 |
EP1482909B1 (en) * | 2002-02-13 | 2018-07-04 | Creagri, Inc. | Method and composition for treatment of inflammation |
GB0314294D0 (en) * | 2003-06-19 | 2003-07-23 | Natraceutical Sa | Olive powder |
-
2007
- 2007-04-18 EP EP07007874A patent/EP1982603A1/en not_active Ceased
-
2008
- 2008-04-17 JP JP2010503410A patent/JP2010524441A/ja not_active Withdrawn
- 2008-04-17 CN CN200880012549A patent/CN101662956A/zh active Pending
- 2008-04-17 WO PCT/EP2008/003088 patent/WO2008128703A1/en active Application Filing
- 2008-04-17 US US12/596,481 patent/US20100113612A1/en not_active Abandoned
- 2008-04-17 EP EP08735304A patent/EP2134196A1/en not_active Withdrawn
- 2008-04-17 KR KR1020097021543A patent/KR20100015610A/ko not_active Application Discontinuation
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112076242A (zh) * | 2019-06-13 | 2020-12-15 | 上海交通大学 | 一种橄榄叶提取物新用途 |
Also Published As
Publication number | Publication date |
---|---|
EP1982603A1 (en) | 2008-10-22 |
KR20100015610A (ko) | 2010-02-12 |
US20100113612A1 (en) | 2010-05-06 |
JP2010524441A (ja) | 2010-07-22 |
EP2134196A1 (en) | 2009-12-23 |
WO2008128703A1 (en) | 2008-10-30 |
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