CN103988988B - 减少伴侣动物年龄相关性精神活动衰退的组合物和方法 - Google Patents
减少伴侣动物年龄相关性精神活动衰退的组合物和方法 Download PDFInfo
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- CN103988988B CN103988988B CN201410115999.4A CN201410115999A CN103988988B CN 103988988 B CN103988988 B CN 103988988B CN 201410115999 A CN201410115999 A CN 201410115999A CN 103988988 B CN103988988 B CN 103988988B
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- methionine
- acid
- weight
- cysteine
- sulphur
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Abstract
本发明公开了包含含硫抗氧化剂的猫科动物食用组合物。该组合物改善至少一种行为特征,该行为特征显示预防或减少年龄相关性意识能力衰退。本发明也公开了通过供给猫科动物该食用组合物来预防这种衰退的方法。
Description
本申请是申请日为2004年7月2日、申请号为200480019132.3、发明名称为“减少伴侣动物年龄相关性精神活动衰退的组合物和方法”的发明专利申请的分案申请。
相关申请的交叉参考
本申请要求2003年7月3日提交的美国申请号为10/613,604的权益,该申请已于2004年7月1日转换成临时申请(顺序号未知),有相同的提交日期2003年7月3日,该申请通过引用而整体结合到本文中。
发明领域
本发明涉及伴侣动物食用组合物,详细来讲,本发明涉及用于降低如老化相关性精神活动衰退的伴侣动物食用组合物和方法。
发明背景
伴侣动物如狗和猫在有关思考、学习和记忆的精神活动中可能遭受年龄相关性衰退(Houpt,K.A.,Cognitive Dysfunction in Geriatric Cats(老年猫的认知功能障碍),August J.R.ed,Consultations in Feline Internal Medicine第4版,W.B.Saunders,Philadelphia,PA2001,pp.583-591)。另外,在与意识能力改变有关的衰老猫中可以明显观察到行为改变和身体改变。对被认为是导致这种能力减弱的各种可能原因方面已经取得进展,然而目前仍没有获得有效的治疗方法。
发明概述
因此,本文中发明人成功地发现一种或多种含硫抗氧化剂特别是含硫氨基酸在猫食物中存在,可抑制即预防或逆转衰老猫意识能力的衰退。给猫喂包含一种或多种含硫的其他抗氧化剂的食用组合物可以显著增强猫的身体活动。
因此,在各种实施方案中,本发明可包括用于减弱猫科动物意识能力衰退的方法。减弱意识能力的衰退包括预防和逆转存在的意识能力衰退状态中之一或两者。该方法包括供给猫科动物一种食用组合物,该食用组合物包含至少一种含硫抗氧化剂特别是至少一种含硫氨基酸。该食用组合物还可包含至少一种ω-3脂肪酸和其它选自维生素E、维生素C、左卡尼汀(1-carnitine)及其混合物的抗氧化剂。喂这种食物可预防或逆转伴侣动物的精神颓废,这是因为任何一种或多种或所有含硫抗氧化剂或含硫氨基酸、ω-3脂肪酸和其它抗氧化剂存在的量可以表示意识能力衰退减弱的方式单独或一起改变至少一种行为特征。
在各种实施方案中,本发明也可包括猫科动物食用组合物。该组合物可包含至少一种含硫抗氧化剂特别是至少一种含硫氨基酸。该食用组合物还可包含至少一种ω-3脂肪酸和至少两种选自维生素E、维生素C和左卡尼汀的其它抗氧化剂。喂这种食物可预防或逆转伴侣动物的精神颓废,这是因为任何一种或多种或所有含硫抗氧化剂或含硫氨基酸、ω-3脂肪酸和其它抗氧化剂存在的量可以表示意识能力衰退减弱的方式单独或一起改变至少一种行为特征。
在各种实施方案中,本发明方法和组合物中的含硫氨基酸或抗氧化剂可包括一种或多种选自以下的含硫氨基酸:半胱氨酸、蛋氨酸、牛磺酸、谷胱甘肽、s-腺苷蛋氨酸、n-乙酰基半胱氨酸、胱硫醚、磺基丙氨酸、半胱亚磺酸、胱氨酸、蛋氨酸砜、蛋氨酸亚砜、甜菜碱、蛋氨酸的甲基羟基类似物及其混合物或所述含硫氨基酸的甲基酯如蛋氨酸甲酯。特别是,含硫氨基酸或抗氧化剂可以为浓度为如约0.8% 重量至约2.0%重量的蛋氨酸;浓度为如约0.2%重量至约0.7%重量的半胱氨酸或浓度为约1.0%重量至约2.2%重量的半胱氨酸和蛋氨酸混合物。在各种但并非所有的实施方案中,含硫抗氧化剂可为除硫辛酸外的含硫抗氧化剂。
在各种实施方案中,作为减弱意识能力衰退的指征而测量的改变行为特征可以为无目的游动减少、不适当排泄减少、过度发声减少、主动运动(initiating play)增多、睡眠减少、呜呜声减少、注意力集中下降、蜷坐减少和/或身体活动增加。
在各种实施方案中,ω-3脂肪酸可为二十二碳六烯酸、二十碳五烯酸、α-亚麻酸或其组合,浓度至少为约50ppm,其它抗氧化剂可为浓度至少为约500ppm的维生素E、浓度至少为约50ppm的维生素C和浓度至少为约100ppm(以干物质计)的左卡尼汀。
伴侣猫食物符合至少1年龄猫的日常营养要求。
发明详述
喂给衰老伴侣猫的食物可为如表1中所示的供给成年猫的标准普通食物。
表1
成分 | 指标 |
蛋白质(干物质的%) | ≥30 |
脂肪(干物质的%) | ≥10 |
磷(干物质的%) | ≥0.5 |
钠(干物质的%) | ≥0.2 |
类似的食物可供给大于约1年龄的成年猫和约7年龄或以上的老猫。
向伴侣猫食物中加入足量的含硫抗氧化剂、特别是含硫氨基酸可 导致行为上有显著且确实改变,具体表现为老龄猫全身活动增加或预防大于1年龄的成年猫食用食物后出现身体活动减少的现象。术语“老龄”通常指至少7年龄的猫。
随着年龄的增长出现的意识能力降低可以许多方式表现。例如,在猫中可表现为定向力障碍、居处变脏、睡眠-觉醒方式改变、与家庭成员和宠物间的交互作用减少、发声过多和身体活动减少。
给予本发明的食物可以增加衰老猫的身体活动。尽管本发明食用组合物可用于预防或逆转年龄相关性精神活动衰退,但也可预防或逆转非衰老原因如神经变性疾病导致的精神活动衰退。
食物中的抗氧化剂或其前体可定义为“食物中显著减少活性组分如活性氧组分和活性氮组分对正常人类生理机能的不利影响的物质”。(Dietary Reference Intakes ofVitamin C,Vitamin E,Selenium,and Carotenoids(维生素C、维生素E、硒和类胡萝卜素的食物参考摄入量),Food and Nutrition Board Institute of Medicine,NationalAcademy Press,Washington,D.C.,2000年4月,p.42,所述参考文献通过引用而整体结合到本文中)。
在自然界中可发现许多抗氧化剂,这些抗氧化剂中许多为含硫抗氧化剂。例如,不受任何理论的作用机理束缚,认为由于其包含可氧化的硫且有螯合能力,所以含硫氨基酸蛋氨酸具有自由基清除活性。蛋氨酸也可用作其他抗氧化剂化合物的前体,例如半胱氨酸。如另一个实例,含硫氨基酸半胱氨酸也包含可氧化的硫,该氨基酸可用作抗氧化剂谷胱甘肽的前体。在再一个含硫抗氧化剂的实例中,认为磺酸基氨基酸牛磺酸通过与吞噬作用过程中产生的过量次氯酸盐反应形成N-氯牛磺酸而用作抗氧化剂。含硫抗氧化剂的具体非限定性实例包括含硫氨基酸如半胱氨酸、蛋氨酸牛磺酸、谷胱甘肽、s-腺苷蛋氨酸、n-乙酰基半胱氨酸、胱硫醚、磺基丙氨酸、半胱亚磺酸、胱氨酸、蛋氨酸砜蛋氨酸亚砜、甜菜碱、蛋氨酸的甲基羟基类似物、除上述所列氨基酸外的含硫氨基酸、氨基酸的甲基酯如蛋氨酸甲酯,和包括其他 显示上述性质的含硫物质。
本发明的含硫抗氧化剂或含硫氨基酸可以为自然存在的或合成的物质。在各种实施方案中,含硫抗氧化剂包括除硫辛酸外的抗氧化剂。
其他抗氧化剂也可存在于本发明的食用组合物中。这些抗氧化剂包括维生素E、维生素C和左卡尼汀。此外,也可存在ω-3脂肪酸。维生素E可以生育酚或生育酚与其各种衍生物例如酯如维生素E醋酸酯、琥珀酸酯、棕榈酸酯等的混合物形式给予。优选α形式,但可包括β、γ和δ形式。优选d型,但可接受外消旋混合物。被宠物摄取后,这些形式物质和衍生物会表现类似维生素E活性的作用。在该食物中维生素C可以抗坏血酸和它的各种衍生物形式给予,如磷酸钙盐、胆甾醇盐、2-单磷酸盐等,被宠物摄取后,这些物质会表现类似维生素C活性的作用。上述维生素可以为任何形式如液体、半固体、固体和热稳定形式。在该食物中可使用左卡尼汀,也可使用卡尼汀的各种衍生物例如盐如盐酸盐、延胡索酸盐和琥珀酸盐以及乙酰基化卡尼汀等。在天然资源如鱼油或植物物质中可发现ω-3脂肪酸。自然中发现的ω-3脂肪酸包括二十碳五烯酸(EPA)、二十二碳六烯酸(DHA)和α-亚麻酸(ALA)。
本发明的食用组合物可以为湿猫食、半湿猫食、干猫食和猫零食(treats)形式。湿猫食的水分含量通常大于约65%。半湿猫食的水分含量一般在约20%至约65%之间,且可包括湿润剂、山梨酸钾和防止微生物生长(细菌和霉菌)的其他成分。干猫食(粗磨)的水分含量通常低于约10%,且干猫食的处理一般包括挤出、干燥和/或加热烘焙。猫零食一般可为半湿可咀嚼零食;许多形式的干零食;可咀嚼骨或烘焙、挤出或捣碎的零食;糖果零食;或本领域技术人员已知的其他类型零食。
所有成分以占该食物的%重量(以干物质计)表示,它们在营养平衡食物中给予的数量以活性物质本身计算,即以游离物质测量。采用的最大量不应该产生毒性。
蛋氨酸可存在于本发明食用组合物中的浓度为至少约0.8%重量、至少约0.9%重量、至少约1.0%重量、至少约1.1%重量,最高达约1.5%或以上。半胱氨酸可存在于本发明食用组合物中的浓度为至少约0.2%重量、至少约0.3%重量、至少约0.4%重量、至少约0.5%,最高达约0.7%或以上。以硫氨基酸计,蛋氨酸和半胱氨酸的组合也可存在的总浓度为至少约1.0%重量、至少约1.2%重量、至少约1.4%重量、至少约1.5%重量、至少约1.6%重量,最高达约2.2%重量。
以重量计,维生素E可存在的浓度为至少约100ppm,至少约150ppm、至少约300ppm、至少约500ppm,最高达最大无毒浓度。以重量计,维生素E的最大浓度可最高达约1,000ppm、最高达约1,500ppm、最高达约2,000ppm或以上。
以重量计,维生素C可存在的浓度为至少约50ppm、至少约75ppm、至少约100ppm、至少约200ppm,最高达最大无毒浓度。以重量计,维生素C的最大浓度可最高达约500ppm、最高达约600ppm或以上。
在各种实施方案中,本发明食用组合物也可包含左卡尼汀,以重量计,其浓度为至少约100ppm、至少约200ppm或至少约500ppm,最高达最大无毒浓度。以重量计,左卡尼汀的最大浓度可最高达约4,000ppm、最高达约5,000ppm、最高达约6,000或以上。
ω-3脂肪酸可存在于食用组合物中的浓度为至少约0.05%重量、至少约0.1%重量、至少约0.2%重量、至少约0.3%重量,最高达最大无毒浓度。一般地,一种或多种ω-3脂肪酸可存在于该食物中的ω-3脂肪酸总浓度为约0.3%重量、约0.4%重量或约0.5%重量或以上。
如需要也可存在其他物质。这些物质和它们的量如下所示:
可使用约1-15ppm的β-胡萝卜素。
可使用约0.1最高达约5ppm的硒。
可使用至少约5ppm的黄体素。
可使用至少约25ppm的生育三烯酚(Tocotrienols)。
可使用至少约25ppm的辅酶Q10。
可使用至少约25ppm的大豆异黄酮。
可使用至少50ppm的银杏提取物或1%的食物。
实施例
该研究举例说明食物对衰老相关性精神衰退指征性行为特征的影响,该食物包含增加量的蛋氨酸和半胱氨酸以及增加量的维生素E、维生素C、左卡尼汀和ω-3脂肪酸、二十二碳六烯酸、二十碳五烯酸和α-亚麻酸。
将老龄猫编入3个不同兽医院的试验地点。将约10年龄的老猫进行身体健康、临床血液检查(clinical bloodwork)(评估肝脏、甲状腺、肾脏、内分泌和其他健康指标)和泌尿道健康的筛选。要求猫在身体和其他评估方面没有明显的健康问题。然后询问拥有者以评估他们的猫在22项行为特征中与其8年龄时相比的行为改变。
有四十六(46)只猫符合健康要求并被登记进行研究。将猫随机分成试验组或对照食物组,喂分配的食物30天后通过调查表重新评估。不告知拥有者和监督该试验的兽医所分配食物的特征。食用组合物如下表2中所示。
表2
猫试验制剂和对照制剂中主要营养成分的浓度(%重量,以干物质计)
分析物 | 试验组 | 对照组 |
蛋白质 | 33.5 | 32.8 |
脂肪 | 18.1 | 19.8 |
钙 | 1.02 | 0.909 |
磷 | 0.66 | 0.65 |
镁 | 0.069 | 0.067 |
牛磺酸 | 0.2161 | 0.1946 |
维生素E(IU/kg) | 1178 | 114 |
维生素C(ppm) | 175 | <10 |
卡尼汀(ppm) | 562 | 15 |
二十二碳六烯酸 | 0.123 | 0.026 |
二十碳五烯酸 | 0.11 | 0.024 |
α-亚麻酸 | 0.279 | 0.119 |
蛋氨酸 | 1.29 | 0.932 |
半胱氨酸 | 0.61 | 0.475 |
蛋氨酸+半胱氨酸 | 1.902 | 1.407 |
为了比较组间和组内的差异,经统计学分析评价46只入编猫的基础数据和30天的数据。基础数据显示对于研究开始询问的所有问题,组间没有显著差异。然而,要求拥有者将他们的猫与8年龄时比较时,发现22项当前行为评估中的9项有显著差异(表3)。
表3
与8年龄猫对比的基础数据
问题 | 显著变化 |
无目的游动 | 更多 |
不适当排泄 | 更多 |
过度发声 | 更多 |
主动运动 | 更少 |
睡眠 | 更多 |
呜呜声 | 更多 |
注意力集中 | 更多 |
蜷坐 | 更多 |
活动 | 更少 |
当研究中30天喂养时间点结束时,结果分析显示,接受试验食物组相对于接受对照食物组的评估值,在一项行为评估中显著增加,活动增加。结合基础数据,结果显示拥有者注意到在食物改变的30天内,类似于年幼动物的活动增加。本说明书中所引用的所有参考文献通过引用而整体结合到本文中。本文中对这些参考文献的讨论仅用于总结作者的观点,并不认为任何参考文献构成有关专利性的先有技术。申请人保留对所引用参考文献的准确性和相关性提出异议的权利。
Claims (11)
1.至少一种含硫抗氧化剂、至少一种ω-3脂肪酸和选自维生素E、维生素C、左卡尼汀及其混合物的其他抗氧化剂在制备食用组合物中的用途,所述食用组合物用于减少猫科动物的心智能力衰退,其中所述含硫抗氧化剂、ω-3脂肪酸和其它抗氧化剂在该食用组合物中存在的量以表现出减少老化相关性心智能力衰退的方式一起改变至少一种行为特征,其中所述至少一种含硫抗氧化剂为蛋氨酸以及一种或多种选自以下的组份:(i)半胱氨酸、牛磺酸、谷胱甘肽、s-腺苷蛋氨酸、n-乙酰基半胱氨酸、胱硫醚、磺基丙氨酸、半胱亚磺酸、胱氨酸、蛋氨酸砜、蛋氨酸亚砜、甜菜碱、蛋氨酸甲基羟基类似物或其混合物或(ii)蛋氨酸、半胱氨酸、牛磺酸、谷胱甘肽、s-腺苷蛋氨酸、n-乙酰基半胱氨酸、胱硫醚、磺基丙氨酸、半胱亚磺酸、胱氨酸、蛋氨酸砜、蛋氨酸亚砜、甜菜碱、蛋氨酸甲基羟基类似物中一种或多种的甲酯,其中所述至少一种改变的行为特征为身体活动增加,其中所述蛋氨酸存在的浓度为0.8%重量至1.5%重量,所述半胱氨酸存在的量为0.2%重量至0.7%重量,所述其它抗氧化剂包含浓度为至少500ppm的维生素E、浓度为至少50ppm的维生素C和浓度为至少100ppm的左卡尼汀。
2.权利要求1的用途,其中所述甲酯是蛋氨酸甲酯。
3.权利要求1的用途,其中所述至少一种含硫抗氧化剂包含半胱氨酸。
4.权利要求1的用途,其中所述半胱氨酸和蛋氨酸的混合物存在的总量为1.0%重量至2.2%重量。
5.权利要求1的用途,其中所述至少一种ω-3脂肪酸选自二十二碳六烯酸、二十碳五烯酸、α-亚麻酸及其组合。
6.权利要求1的用途,其中所述ω-3脂肪酸在所述食用组合物中存在的浓度为至少0.05ppm。
7.一种猫科动物食用组合物,所述组合物包含至少一种含硫抗氧化剂、至少一种ω-3脂肪酸和至少两种选自维生素E、维生素C和左卡尼汀的其它抗氧化剂,其中所述含硫抗氧化剂、ω-3脂肪酸和其它抗氧化剂在该食用组合物中存在的量以表现出减少老化相关性心智能力衰退的方式一起改变至少一种行为特征,其中所述ω-3脂肪酸在该食用组合物中存在的浓度为至少50 ppm,其中所述至少一种含硫抗氧化剂为蛋氨酸以及一种或多种选自以下的组份:(i)半胱氨酸、牛磺酸、谷胱甘肽、s-腺苷蛋氨酸、n-乙酰基半胱氨酸、胱硫醚、磺基丙氨酸、半胱亚磺酸、胱氨酸、蛋氨酸砜、蛋氨酸亚砜、甜菜碱、蛋氨酸甲基羟基类似物或其混合物或(ii)蛋氨酸、半胱氨酸、牛磺酸、谷胱甘肽、s-腺苷蛋氨酸、n-乙酰基半胱氨酸、胱硫醚、磺基丙氨酸、半胱亚磺酸、胱氨酸、蛋氨酸砜、蛋氨酸亚砜、甜菜碱、蛋氨酸甲基羟基类似物中一种或多种的甲酯,其中所述至少一种改变的行为特征为身体活动增加,其中所述蛋氨酸存在的浓度为0.8%重量至1.5%重量,所述半胱氨酸存在的量为0.2%重量至0.7%重量,所述其它抗氧化剂包含浓度为至少500ppm的维生素E、浓度为至少50ppm的维生素C和浓度为至少100ppm的左卡尼汀。
8.权利要求7的组合物,其中所述甲酯是蛋氨酸甲酯。
9.权利要求7的组合物,其中所述至少一种含硫抗氧化剂包含半胱氨酸。
10.权利要求9的组合物,其中所述半胱氨酸和蛋氨酸的混合物存在的总量为1.0%重量至2.2%重量。
11.权利要求7的组合物,其中所述至少一种ω-3脂肪酸选自二十二碳六烯酸、二十碳五烯酸、α-亚麻酸及其组合。
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