CN101686711A - 增强猫科动物的免疫系统的组合物和方法 - Google Patents
增强猫科动物的免疫系统的组合物和方法 Download PDFInfo
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Abstract
公开了可用于增进成长中的动物的免疫系统发育的组合物和方法。
Description
对相关申请的交叉引用
本申请要求2007年2月22日提交的美国临时申请No.60/891,171的优先权，其内容经此引用并入本文。
发明领域
本发明涉及增强哺乳动物的免疫系统的组合物和方法。
发明背景
市售宠物食品，例如猫食包括针对许多不同的营养需求专门配制的组合物。这些包括，例如，为不同品种类型、大小和身体状况设计的配方。它们也包括针对动物在其生命周期不同阶段的营养需求设计的配方。尽管这类宠物食品配方可得，但是，需要开发针对动物健康的其它方面的配方和方法。
宠物始终暴露在病原体中。无法响应这些病原体可能造成慢性疾病和死亡。对病原体的响应可能受到动物饮食的抑制，以致阻碍充足的免疫响应。因此，需要增强动物对病原体激发的免疫响应的组合物和方法。
通过使用疫苗，已极大降低猫的许多传染病的发病率。疫苗不是100％有效，因为针对特定疾病接种疫苗的一些猫会无法对该疾病免疫。因此，需要开发提高疫苗效力和增强猫科动物在受到抗原激发时的免疫响应的组合物和方法。
发明概述
在某些方面中，本发明涉及可用于增强免疫系统或动物在受到抗原激发时的免疫响应的组合物。
本发明包括组合物1.0，可用于增强动物的免疫功能的宠物食品组合物，其包含：
大约200至大约1200IU/kg维生素E；
大约50至大约500ppm维生素C；
大约0.1％至大约0.7％EPA；和
大约0.1％至大约0.7％DHA。
本发明还包括下列组合物：
1.1包含大约0.1％至大约0.5％DHA，例如大约0.2％至大约0.5％，例如大约0.2，大约0.3％或大约0.4％的组合物1.0；
1.2包含大约200至大约1200IU/kg维生素E，例如大约500IU/kg至大约1100IU/kg，大约700，大约800，大约900或大约1000IU/kg的组合物1.0或1.1；
1.3包含大约50至大约500ppm维生素C，例如大约100至大约400ppm维生素C，例如大约150，大约175，大约200或大约225ppm的任何前述组合物；
1.4包含大约100ppm至大约500ppm肉毒碱，例如大约200，大约300或大约400ppm的任何前述组合物；
1.5包含大约2.5g/1000kcal至大约7g/1000kcal赖氨酸的任何前述组合物；
1.6包含大约2400ppm至大约7500ppm胆碱，例如大约3000，大约4000，大约4500，大约4600，大约4625，大约4650，大约4700，大约5000或大约6000ppm的任何前述组合物；
1.7包含大约0.1％至大约0.6％EPA，例如大约0.2％，大约0.3％，大约0.4％或大约0.5％的任何前述组合物；
1.8包含大约50ppm至大约200ppm锰的任何前述组合物；
1.9包含大约0.5％至大约1.6％蛋氨酸，例如0.8％至大约1.6％蛋氨酸，例如大约1.3或大约1.4％蛋氨酸的任何前述组合物。
1.10任何前述组合物，进一步包含：
0至大约90重量％碳水化合物；
大约5重量％至大约70重量％蛋白质；
大约2重量％至大约50重量％脂肪；
大约0.1重量％至大约20重量％总膳食纤维；
0至大约15重量％，优选大约2重量％至大约8重量％的维生素、矿物质和其它营养素，以支持动物营养需求的各种(varying)百分比存在。
1.11包含大约5重量％至大约55重量％碳水化合物的组合物1.10；
1.12包含大约20重量％至大约60重量％蛋白质，例如大约30至大约55％的组合物1.10或1.11；
1.13包含大约5重量％至大约40重量％脂肪，例如至少大约8％或大约9％至大约40％脂肪的任一组合物1.10-1.12；
1.14包含大约1重量％至大约11重量％总膳食纤维的任一组合物1.10-1.13；
1.15包含大约1000至大约4000ppm牛磺酸的任何前述组合物；
1.16包含大约0.5％至大约6％亚油酸，例如大约2.5％至大约5％的任何前述组合物；
1.17包含大约1％至大约3％总n-3脂肪酸，例如大约1.3％，大约1.4％，大约1.5％或大约1.6％的任何前述组合物；
1.18包含大约1％至大约6％总n-6脂肪酸，例如大约3％至大约5％，大约3.5％或大约4％的任何前述组合物。
本发明的组合物可以是湿、干或半干的食品。
本发明包括方法2.0——增进猫科动物的神经发育的方法，包括对该猫科动物施用任一组合物1.0-1.18。
本发明还包括下列方法：
2.1方法2.0，其中该猫科动物是幼猫。
2.2方法2.0或2.1，其中该猫科动物由在妊娠过程中喂饲任一组合物1.0-1.15的母猫生出。
2.3方法2.2，其中该幼猫在子宫内。
2.4方法2.2，其中母猫在妊娠之前喂饲任一组合物1.0-1.18。
2.5方法2.2或2.4，其中母猫在大部分妊娠持续期间喂饲任一组合物1.0-1.18。
2.6任一方法2.2-2.5，其中母猫在妊娠之前和在妊娠过程中喂饲基本由任一组合物1.0-1.18组成的组合物。
2.7任一前述方法，其中该幼猫在断奶前，例如仍在哺乳期的同时喂饲任一组合物1.0-1.18。
2.8任一前述方法，其中该幼猫在断奶后喂饲任一组合物1.0-1.18。
2.9方法2.8，其中该幼猫喂饲由任一组合物1.0-1.18组成的食品组合物。
2.10任一前述方法，其中向该动物施用有效量的组合物。
2.11任一前述方法，其中向该动物施用该组合物有效时间。
参照下列实例的详述理解本发明的其它特征和优点。
发明详述
本文所述的本发明预计不限于所述的具体方法、规程和试剂，因为这些可变。还要理解的是，本文所用的术语仅用于描述具体实施方案，而不是要以任何方式限制本发明的范围。
除非另行指明，本文所用的所有技术和科学术语具有本发明所属领域的普通技术人员一般理解的相同含义。此外，本文引用的所有参考文献全文经此引用并入本文。在本公开中的定义和引用的参考文献中的定义冲突的情况下，以本公开为准。
除非文中清楚地另行指明，本文和所附权利要求中所用的单数形式“一”和“该”包括复数对象。
本发明涉及任何动物，优选哺乳动物，更优选伴侣动物。术语“伴侣动物”是指与人亲密生活在一起的任何动物，并包括，但不限于，任何品种的犬科动物和猫科动物。但是，本文中设想，饮食可受人控制的任何动物都可获益于喂饲本文公开的配方。这些动物可以包括，例如驯养农畜(例如，牛、马、猪等)以及圈养，例如在动物园等中的非驯养动物。该动物优选是猫科动物，幼猫或成年猫。
本文所用的“有效...的量”或用于实现特定结果的“有效量”和类似术语是指可有效实现特别需要的生物学结果的本文所述的化合物、材料或组合物的量。本文设想的这类结果包括，例如，在子宫内发育的同时和/或在其出生后的成长期(例如，到出生后6个月，9个月，12个月或15个月)，动物的神经发育、骨和关节健康、免疫功能的增进和/或健康身体构成的增进。可以例如通过在该动物在子宫内或在哺乳期的同时向所述动物的母亲施用本发明的组合物以及通过在其成长期间向该动物直接施用来实现这种有效活性。
如本文所用，在如本文所述的成长中的动物中，特定生物学过程或身体状况的“增进”是指与对照动物相比，成长中的动物的生物学过程或身体状况的改善。这类过程或状况的改善可以由本领域技术人员确定。可以通过检验响应疫苗接种的抗体滴度并与对照动物进行比较来确定动物的免疫功能，其中与对照动物相比抗体滴度的提高表明适应性免疫功能的增进。
本文所用的“成长中的动物的发育的增进”或“增进的发育”和类似术语是指成长中的动物的一种或多种生物学过程和/或身体状况，包括但不限于，对生物体的成长和发育而言重要的生物学过程，包括但不限于，本文所述的生物学过程，例如骨和关节健康、神经和免疫系统发育和体重增加(例如瘦肌肉量而非脂肪组织的增加)的总体改善。
动物的“成长”生命阶段是指从出生或断奶(大约8周大)到大约1岁的期间。
本文所用的术语“幼猫”是指未成熟的猫科动物，通常在出生和12个月之间。
本文所用的“必需氨基酸”是指不能由生物体重新合成并因此必须在饮食中提供的那些氨基酸。本领域技术人员理解的是，必需氨基酸根据生物体的代谢随物种而变。例如，通常理解的是，对狗和猫(和人)而言，必需氨基酸是苯基丙氨酸、亮氨酸、蛋氨酸、赖氨酸、异亮氨酸、缬氨酸、苏氨酸、色氨酸、组氨酸和精氨酸。此外，牛磺酸，尽管在技术上不是氨基酸而是半胱氨酸衍生物，是猫必需的。平衡膳食可提供所有的必需氨基酸，但某些必需氨基酸更重要，因为缺乏其中之一的饮食会限制其它必需氨基酸的效用，即使所述其它必需氨基酸足量存在。
如本领域技术人员理解的那样，“限制氨基酸”是指如果在饮食中的存在量不足则会造成其它必需氨基酸的效用受限(即使所述其它必需氨基酸原本以足够大的量存在)的氨基酸。赖氨酸是本文公开的组合物中的限制必需氨基酸。因此，相对于被确定为在影响所需生物结果方面至关重要的赖氨酸的量，定量调配或“平衡”其余的必需氨基酸。本文所用的“平衡氨基酸”是指必需氨基酸赖氨酸与确保最佳动物成长和发育所需的能量的关系。
本文所用的“必需营养素”是指正常人体运行所需的不能由身体合成的营养素。必需营养素的类别包括维生素、膳食矿物质、脂肪酸和氨基酸。本领域技术人员理解的是，被认为必需的营养素根据生物体的代谢随物种而变。例如，对狗和猫而言，必需营养素包括维生素A、D、E、K、B1、B6、B12、核黄素、烟酸、泛酸、叶酸、钙、磷、镁、钠、钾、氯、铁、铜、锌、锰、硒和碘。胆碱，通常被视为B族复合维生素，可以包含在半必需营养素中。
肉毒碱，也称作L-肉毒碱(左卡尼汀)是由氨基酸赖氨酸和蛋氨酸合成的季铵化合物，并负责脂肪酸从细胞溶胶传输到线粒体。
各种动物，如哺乳动物和猫科动物的免疫响应是本领域中公知的。免疫响应通常是生物体内的预防疾病的机制，例如通过确认和杀灭病原体和肿瘤细胞。免疫响应可分成各种响应类型，例如体液或细胞介导的响应，以及先天和适应性响应。因此，免疫响应可以是体液先天响应、细胞介导的先天响应、细胞介导的适应性响应和细胞介导的适应性响应及其组合。公知的是，当动物例如受病原体激发时，这些响应可同时出现。例如，先天体液免疫响应的补体级联可补充T和B细胞，它们构成细胞介导的适应免疫性的基础，并且可通过适应性免疫系统补充补体。
不受任何理论或特定作用模式限制，本发明基于令人惊讶的发现，即动物饮食可增强动物对抗原，例如病原体或疫苗的免疫响应。将某些成分添加到宠物食品组合物中并向动物施用这些组合物可以增强成长中的动物的免疫系统。另外，将某些成分添加到宠物食品组合物中并向妊娠中的母畜施用这些组合物可以增强其后代的免疫系统。
本发明设想，可以增强或扩大猫科动物对许多抗原，包括病原体和疫苗的免疫响应。可以针对许多疾病或状况对猫科动物接种疫苗，包括猫传染性粒细胞缺乏症、猫疱疹病毒-1、猫杯状病毒、猫白血病病毒、狂犬病、衣原体病、猫传染性腹膜炎、支气管败血性博德特氏菌感染(bordetella bronchiseptica infection)、皮肤真菌病、贾第虫病等。因此，本发明设想了建立例如对病原体的增强的适应性体液免疫的改进的方法，包括本发明的方法和用病原体的疫苗免疫接种动物以抵抗该病原体。动物的增强的免疫功能可被表征为是在抗原激发时表现出比对照动物高的抗体或细胞介导响应的免疫响应。
如本文设想的那样，本发明的组合物包含营养上完全和平衡的动物饲料组合物。在营养素和成分中，这类组合物包括推荐的健康量的蛋白质、碳水化合物和脂肪。“营养上完全和平衡的动物饲料组合物”以及适用于动物饲料组合物的营养素和成分及它们的推荐量是本领域技术人员熟悉的(参见，例如，National Research Council，2006NutritionalRequirements for Dogs and Cats，National Academy Press，Washington D.C.或the Official Publication of the Association of American Feed ControlOfficials，Inc.Nutrient Requirements for Dogs and Cats 2006)。
本文中设想，本文中公开的组合物也可以以本领域技术人员熟悉的量和组合包含抗氧化剂、添加剂、稳定剂、增稠剂、食用香料、适口性增强剂和着色剂。“抗氧化剂”是指能够与自由基反应或降低自由基的生成和中和自由基的物质。实例包括，但不限于，β胡萝卜素、硒、辅酶Q10(泛醌)、叶黄素、生育三烯酚类、大豆异黄酮、S-腺苷甲硫氨酸、谷胱甘肽、牛磺酸、N-乙酰半胱氨酸、维生素E、维生素D、维生素C、黄烷类、花色素和硫辛酸。
尽管设想了任何稠度或含湿量的食品，但本发明的组合物优选可以例如是湿、半干或干的动物食品组合物。“湿”食品是指在罐头或箔袋中出售并具有大约70至大约90％含湿量的食品。“干”食品是指具有大约5至大约15％含湿量的组合物，并通常以小碎粒或粗粒形式制造。半干组合物是指具有大约15％至大约70％湿度的组合物。如美国专利6,517,877中所述，本文中还设想了具有中等湿稠度的组合物和可能包含各种稠度的组分以及可能具有超过一种稠度的组分的组合物，例如，软的耐嚼的肉状粒子以及具有外部谷类组分和内部奶油组分的粗粒。
下列实施例进一步例证本发明且不是要限制本发明。如通篇所用，范围用于简述在该范围内的各个和每个值。可以选择该范围内的任何值作为该范围的界限。要理解的是，当描述配方时，如本领域中常见的那样，它们可以以其成分描述，尽管这些成分在其制造、储存和使用时可能在实际配方中彼此反应，且所述配方旨在涵盖这些产物。
下列实施例进一步描述和验证本发明范围内的示例性实施方案。这些实施例仅用于举例说明而不应被视为本发明的限制，因为可以在不背离其精神和范围的情况下作出许多变动。除本文所示和所述的那些外，本发明的各种修改是本领域技术人员显而易见的且旨在落在所附权利要求内。
实施例1
在下文中公开用于增进成长中的动物的发育的配方。考虑“理想蛋白质概念”(Baker和Czarnecki-Maulden，1991Annu.Rev.Nutr.11：239-63)来开发这些组合物。
针对“成长”生命期开发食品。这些食品包括针对犬科动物成长和猫科动物成长的配方。这些食品的最低营养素推荐以及原型食品的目标值列在下表1中。
表1.幼猫配方的关键营养素
| 营养素 | 目标值 | 最小值 | 最大值 |
| 蛋白质，％ | 45.5 | 30 | 55 |
| 蛋氨酸，％ | 1.4 | 0.8 | 1.5 |
| 锰，ppm | 90 | 50 | 200 |
| DHA，％ | 0.21 | 0.1 | 0.5 |
| EPA，％ | 0.31 | 0.1 | 0.7 |
| 胆碱，ppm | 4880 | 2500 | 7500 |
| 牛磺酸，ppm | 2380 | 1000 | 4000 |
| 亚油酸，％ | 3.8 | 2.5 | 6 |
| 总n-3脂肪酸，％ | 1.35 | 1 | 3 |
| 维生素E，IU/kg | 900 | 200 | 1200 |
| 维生素C，ppm | 90 | 50 | 500 |
| 赖氨酸，g/1000kcal | 4 | 2.5 | 7 |
实施例2
该研究使用四种食品，实验配方X、商品A、商品A1和商品B。食品组成列在表2中。商品A、A1和B食品可获自商业来源。商品A和A1是相同品牌的食品，但在不同批次中制成。
表2向母猫和幼猫喂饲的食品的分析营养素
| 营养素 | 配方X | 商品A | 商品A1 | 商品B |
| 粗蛋白质，％ | 41.63 | 41.2 | 36.09 | 35.47 |
| 脂肪，％ | 23.15 | 14.47 | 12.43 | 22.94 |
| Ca，％ | 1.23 | 1.12 | 1.50 | 1.06 |
| P，％ | 1.11 | 1.11 | 1.19 | 0.96 |
| DHA，％ | 0.22 | 0.06 | 0.04 | ＜0.01 |
| EPA，％ | 0.32 | 0.06 | 0.04 | ＜0.01 |
| 亚油酸，％ | 3.79 | 1.59 | 1.96 | 1.37 |
| 总n-3脂肪酸，％ | 1.47 | 0.34 | 0.25 | 0.53 |
| 总n-6脂肪酸，％ | 3.86 | 1.88 | 1.91 | 1.44 |
| 牛磺酸，％ | 0.24 | 0.17 | 0.23 | 0.20 |
| 蛋氨酸，％ | 1.3 | 0.76 | 0.62 | 0.99 |
| 胱氨酸，％ | 0.49 | 0.51 | 0.44 | 0.35 |
| 锰，ppm | 78 | 63 | 77 | 56 |
| 维生素E，IU/kg | 914 | 35 | 76 | 138 |
| 维生素C，ppm | 183 | -- | -- | -- |
| 胆碱，ppm | 4624 | 3010 | 2807 | 3331 |
在受孕之前，向19只母猫喂饲配方X或商品A至少2周。母猫集中饲养直至经由触诊确认怀孕，然后转移到产科住处。喂饲商品A的母猫生下32只幼猫，喂饲配方X的母猫生下16只幼猫。在幼猫出生后，用相同食品喂养母猫生下的幼猫直至幼猫断奶。
在断奶后，将喂饲商品A的母猫生下的32只幼猫如下划分：16只幼猫喂饲商品A1；16只幼猫喂饲商品B。在断奶后，喂饲配方X的母猫生下的16只幼猫保持用配方X喂养。
将这48只幼猫接种狂犬病疫苗，并在疫苗接种之前和在疫苗接种后1、2、4、8和16周测定抗狂犬病抗体滴度。
结果列在表3中。来自喂饲配方X的母猫并继续喂饲配方X的幼猫具有通过对狂犬病疫苗接种的提高的抗体滴度测得的显著改进的免疫响应。当向妊娠和哺乳期的母猫和向断奶后生长过程中的幼猫喂饲配方X时，幼猫的抗体滴度显著提高。
表3-响应狂犬病疫苗接种的幼猫平均抗体滴度
| 接种前 | 1周 | 2周 | 4周 | 8周 | 16周 | |
| 商品A母猫-商品A1幼猫 | 0.1 | 0.1 | 22.0 | 43.3 | 47.5 | 25.0 |
| 商品A母猫-商品B幼猫 | 0.1 | 0.2 | 23.4 | 47.0 | 52.8 | 12.5 |
| 配方X母猫-配方X幼猫 | 0.1 | 0.2 | 26.4 | 62.4 | 63.9 | 37.2 |
Claims (21)
1.宠物食品组合物，其包含：
大约200至大约1200IU/kg维生素E；
大约50至大约500ppm维生素C；
大约0.1％至大约0.9％EPA；和
大约0.1％至大约0.7％DHA。
2.权利要求1的组合物，其包含大约0.2％至大约0.5％DHA。
3.权利要求1或2的组合物，其包含大约200至大约1200IU/kg维生素E。
4.任一前述组合物，其包含大约50至大约500ppm维生素C。
5.任一前述组合物，其包含大约100ppm至大约500ppm肉毒碱。
6.任一前述组合物，其包含大约2400ppm至大约7500ppm胆碱。
7.任一前述组合物，其包含大约0.1％至0.6％EPA。
8.任一前述组合物，其包含大约50ppm至大约200ppm锰。
9.任一前述组合物，其包含大约0.5％至大约1.6％蛋氨酸。
10.任一前述组合物，其进一步包含：
0至大约90重量％碳水化合物；
大约5重量％至大约70重量％蛋白质；
大约2重量％至大约50重量％脂肪；
大约0.1重量％至大约20重量％总膳食纤维；
0至大约15重量％的维生素、矿物质和其它营养素，以支持动物营养需求的各种百分比存在。
11.增强猫科动物对抗原的免疫响应的方法，包括向所述猫科动物施用权利要求1-10任一项的组合物。
12.权利要求11的方法，其中所述猫科动物是幼猫。
13.权利要求11或12的方法，其中所述猫科动物由在妊娠过程中喂饲权利要求1-10任一项的组合物的母猫生出。
14.权利要求13的方法，其中所述母猫在妊娠之前喂饲权利要求1-10任一项的组合物。
15.权利要求12-14任一项的方法，其中所述幼猫在断奶前喂饲权利要求1-10任一项的组合物。
16.权利要求12-15任一项的方法，其中所述幼猫在断奶后喂饲由权利要求1-10任一项的组合物组成的组合物。
17.权利要求11-16任一项的方法，其中所述免疫响应是体液免疫响应。
18.权利要求11-17任一项的方法，其中所述免疫响应是适应性体液免疫响应。
19.权利要求18的方法，其中所述适应性体液免疫响应包括对抗抗原的抗体的生成和释放。
20.权利要求11-19任一项的方法，其中所述抗原在疫苗中呈递。
21.权利要求20的方法，其中疫苗选自猫传染性粒细胞缺乏症、猫疱疹病毒-1、猫杯状病毒、猫白血病病毒、狂犬病、衣原体病、猫传染性腹膜炎、支气管败血性博德特氏菌感染、皮肤真菌病和贾第虫病。
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