CN103269697A - 半胱氨酸和食物摄入 - Google Patents
半胱氨酸和食物摄入 Download PDFInfo
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- CN103269697A CN103269697A CN2011800614347A CN201180061434A CN103269697A CN 103269697 A CN103269697 A CN 103269697A CN 2011800614347 A CN2011800614347 A CN 2011800614347A CN 201180061434 A CN201180061434 A CN 201180061434A CN 103269697 A CN103269697 A CN 103269697A
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Abstract
本发明涉及营养领域；特别是涉及预防和/或治疗营养不良。本发明的一个实施方案涉及富含半胱氨酸的营养组合物，其用于治疗和/或预防营养不良和与其相关的障碍。该组合物可以特别但不唯一地用于老年人群。
Description
本发明涉及营养领域；特别是涉及预防和/或治疗营养不良。本发明的一个实施方案涉及富含半胱氨酸的营养组合物，其用于治疗或预防营养不良和与其相关的障碍。该组合物可以特别但不唯一地用于老年人群。
厌食是食欲感觉减退。对于食欲减退存在很多可能的原因，其中一些可以表现出严重的临床病症，或造成显著的风险。厌食通常是其它疾病的后果。在这些情况下，营养不良是个显著的问题，因为它会延缓恢复过程，甚至可能阻碍完全恢复。
厌食通常出现在老年人群中。尽管随着年龄的增长而出现体内脂肪的增加和肥胖，但是食物摄入随着寿命增加而线性减少。这可以通过随着年龄的增长而减少的体力活动和改变的代谢得以解释。老化相关的厌食可以存在实质性的不良反应。食欲和食物摄入的年龄相关的生理学降低被称为“老龄化的厌食”。老龄化的“生理学”厌食和体重减轻诱发病理学的体重减轻和营养不良。这种生理学厌食是例如由食物摄入的改变的激素和神经递质调节引起的。老人中显著的体重减轻促使发病率和升高的死亡率，对生活质量产生负面影响，并且引起虚弱。
目前，厌食通常通过施用多种药物来治疗，其中某些可能具有不希望的副作用。
因此，本领域需要天然的途经来治疗和/或预防营养不良和与其相关的障碍，而没有不希望的副作用，特别是在老年人中。理想地，这应当通过组合物来实现，所述的组合物是每个人可获得的，受到消费者喜爱并且可以每天使用。
本发明人已经解决了这个需求。
因此，本发明的目的是改善技术水平并且为本领域提供实现本发明目的的组合物。
本发明人惊讶地发现他们可以通过独立权利要求的主题来实现该目的。从属权利要求进一步发展本发明的想法。
特别地，本发明人发现半胱氨酸可以例如用作组合物的部分，用于肠内营养或食物产品，以维持或改善食物摄入，例如在老年人中。
本发明人发现半胱氨酸表现出抗厌食的特性，例如抗老龄化相关的厌食特性。对于补充丙氨酸的膳食(对照膳食)，没有观察到这种作用。据发明人所知，这是半胱氨酸对食物摄入的有益作用的首次描述。因此，提供富含半胱氨酸的膳食或向食物产品中添加例如高于正常需要量的半胱氨酸，将消除例如老年人中出现的食物消耗的减少。还存在很多健康相关的病症与厌食相关，例如化疗、感染、神经性厌食或应激病症。半胱氨酸在此还可以用于治疗或预防厌食和相关的病症。因此，例如，半胱氨酸还可以用于临床产品以控制食物摄入。
因此，本发明的一个实施方案是富含半胱氨酸的营养组合物。
“富含”半胱氨酸意指向营养组合物中添加半胱氨酸或以增加每克天然半胱氨酸含量的方式处理食物组合物。如果组合物含有超过推荐的每日摄入(RDI)的半胱氨酸，组合物即被进一步认为“富含”半胱氨酸。半胱氨酸的推荐的每日摄入为：婴儿(0-12个月)45mg/kg体重；儿童(1-17岁)22mg/kg体重；以及成年人(>18岁)10mg/kg体重。
半胱氨酸还可以以半胱氨酸前体形式提供，所述的半胱氨酸前体选自蛋白质或肽水解物或肽中结合的半胱氨酸，例如γ-谷氨酰基-半胱氨酸，或肽的其它形式，例如γ-谷氨酰基-半胱氨酸酯，混合的二硫化物，例如L-半胱氨酸-谷胱甘肽半胱氨酸前药，N-乙酰基-半胱氨酸(游离形式，酰胺或酯形式)，S-烯丙基-半胱氨酸，S-甲基-半胱氨酸，S-乙基-半胱氨酸，S-丙基-半胱氨酸，TCA(噻唑烷羧酸(thiazelidineScarboxylic acid))，OTC(L-2-氧代噻唑烷-4-羧酸酯)，布西拉明(bucillamine)谷胱甘肽和谷胱甘肽酯(一甲酯、一乙酯、二乙酯、异丙酯)，谷胱甘肽前药，S-乙酰基-谷胱甘肽，S-苯基乙酸酯-谷胱甘肽和S-羟基-甲基巯基L-半胱氨酸。
本发明的组合物可以用于治疗和/或预防营养不良和/或与其相关的障碍。
本发明还涉及半胱氨酸在制备用于治疗和/或预防营养不良和/或与其相关的障碍的组合物中的用途。
本发明的组合物可以另外地或选择性地用于增加食物摄入。
它还可以用于降低饱满感和/或饱食。
值得注意的是，本发明人发现施用本发明组合物使得食物摄入显著增加。因此，本发明组合物还可以用于增加食欲。
本发明组合物能增加食欲以及摄入食物的总量。
因此，例如通过施用本发明组合物可以治疗任何与营养不良相关的障碍。例如，与营养不良相关的障碍可以选自厌食、神经性厌食、恶病质、与食物摄入减少相关的炎性疾病或其组合。
轻度炎症出现是发生例如与老龄化相关的homeosteny的一个重要参数。年龄相关的轻度炎症可以导致死亡率和发病率升高，例如体重减轻。本发明提供了新的营养策略，以平衡例如老年人中可能出现的轻度炎症的副作用。
在本发明的一个实施方案中，组合物可以被施用于老年人。
如果在其出生国内年龄超过平均预期寿命的前一半，优选如果在其出生国内年龄超过平均预期寿命的前三分之二，更优选如果在其出生国内年龄超过平均预期寿命的前四分之三，最优选如果在其出生国内年龄超过平均预期寿命的前五分之四，这样的个体被认为是“老年人”或“年老的”。
例如，本发明组合物可以被施用于年龄至少50岁、至少60岁、至少70岁或至少80岁的人。
本发明组合物还可以被施用于宠物，例如年老的宠物。
本发明组合物可以用于治疗或预防年龄相关的食物摄入减少。
本发明组合物通常包含蛋白质成分、脂质成分和碳水化合物成分。
蛋白质成分可以包含至少3.0重量-%、至少4重量-%、至少5重量-%、至少7重量-%或至少10重量-%的半胱氨酸。
在个体遭受胃肠道功能损伤时，优选例如所用的至少部分蛋白质源是预先水解的。
对于相同的原因，可以优选使用含有MCT(中链甘油三酯)的脂质源。MCTs具有易于被机体吸收的优点。
在本发明的范围内，半胱氨酸通常可以以日剂量范围为约0.03至0.15g/kg体重、例如0.05至0.12g/kg体重施用。
为了实现该日剂量，组合物可以含有至少2g/kg干重、至少4g/kg干重、至少6g/kg干重、至少8g/kg干重或至少10g/kg干重的量的半胱氨酸。
任何来源的半胱氨酸可以用于本发明的范围内。化学纯的半胱氨酸具有可获得高纯度和浓度的优点，从而提供非常准确的剂量。
然而，半胱氨酸还可以由天然来源提供。例如，半胱氨酸可以由动物来源，例如猪肉、灌肠用碎猪肉、鸡肉、火鸡肉、鸭肉、午餐肉、蛋、乳、乳蛋白质、乳清蛋白质、乳清干酪(ricotta)、农家干酪和/或酸乳；和/或由素食来源，例如红胡椒、大蒜、洋葱、绿花椰菜、包子甘蓝、燕麦、格兰诺拉麦(granola)和/或麦胚提供。
这些天然来源产生天然且有效的食物组合物，而没有添加人工制备的化合物。还可以满足具体的膳食需求，例如对于素食者或绝对素食者。
本发明组合物可以具有至少0.5kcal/g干重的热密度。具有整体低食物摄入的某些人对于消化高热量食物有问题。对于这些人，优选低热量配方。否则，如果消耗更高热密度的食物，增加食物摄入具有更显著的作用。因此，本发明组合物还可以具有至少0.8kcal/g干重、至少1.0kcal/g干重、至少1.5kcal/g干重或至少2.0kcal/g干重的热密度。
通常，组合物的约10至40%热量可以来自蛋白质。由于特别是老年人群通常遭受蛋白质摄入不足，可以优选组合物的约20至40%热量来自蛋白质。
组合物还可以包含组合物的约15至45%热量来自脂质，和/或组合物的约20至70%热量来自碳水化合物。
组合物可以是人或动物消耗可接受的任何类型的组合物。例如，组合物可以选自食物产品、宠物食物产品、饮料、药物、营养配方、临床营养用组合物、通过添加水重构的营养粉末、果汁或乳、营养食品、食物添加剂、食物补充剂、乳制品或凝胶。
食物添加剂或药物可以是例如片剂、胶囊剂、锭剂或液体形式。
组合物可以进一步包含保护性水胶体(例如树胶、蛋白质、改性淀粉)、粘合剂、薄膜形成剂、包囊剂/物质、壁/壳物质、基质化合物、包衣剂、乳化剂、表面活性剂、增溶剂(油、脂肪、蜡、卵磷脂等)、吸附剂、载体、填充剂、共化合物、分散剂、润湿剂、加工助剂(溶剂)、流动剂、掩味剂、增重剂、成胶剂、凝胶形成剂、抗氧化剂和抗微生物剂。
它们还可以包含常规的药物添加剂和佐剂、赋形剂和稀释剂，包括但不限于水、任何来源的明胶、植物胶、木素磺酸盐(ligninsulfonate)、滑石粉、糖、淀粉、阿拉伯胶、植物油、聚亚烷基二醇、矫味剂、防腐剂、稳定剂、乳化剂、缓冲剂、润滑剂、着色剂、润湿剂、填充剂等。
组合物可以口服施用、肠内施用或非肠道施用。
通常优选口服施用，因为它易于在家实施，并且因此其可在私人环境中使用本发明主题。每个人可以轻易地获得并且使用本发明组合物，任选在咨询医护人员之后。
在住院条件下，营养不良和食欲缺乏通常是一个严重的问题，其可以导致恢复过程延缓。对于不愿或不能口服消耗食物的人，肠内施用本发明组合物可以是优选的选择，例如作为管饲配方。
如果不能或不推荐口服和/或肠内施用，可以使用非肠道施用。因此，本发明组合物还可以是适合非肠道施用的形式。这类组合物通常不包含例如碳水化合物源。
组合物可以作为膳食或以膳食范围施用。
组合物还可以例如在用餐前一小时或在用餐过程中施用。这样它可以用作例如功能性食欲增进剂。
本领域技术人员将认识到，他们可以自由地组合本文描述的本发明的所有特征，而没有脱离所公开的本发明的范围。特别是，为本发明的用途所描述的特征可以适用于本发明的组合物，反之亦然。
根据以下实施例和附图，本发明的进一步的优点和特征是显而易见的。
图1概述了试验设计。
图2显示了喂食丙氨酸(A)和半胱氨酸(C)膳食的老年大鼠的Kaplan-Meier存活曲线。对数秩(log-rank)检验=0.054，P=0.816。
图3显示了半胱氨酸补充对体重的作用。重复测量的两因素方差分析：时间(T)：P<0.0001，膳食(D)：P=0.915，TxD：P=0.137。没有共享共有字母的a至h时间点显著不同(Fisher’s PLSD，P<0.05)。
图4显示了半胱氨酸补充对食物摄入的作用。重复测量的两因素方差分析：时间(T)：P<0.0001，膳食(D)：P=0.0002，TxD：P=0.0001。没有共享共有字母的a至i时间点显著不同(Fisher’s PLSD，P<0.05)。
实施例：
在无非特异性病原体动物房(Unité de Nutrition Comparée,INRATheix)出生和喂养的同龄雄性Wistar大鼠用于研究。当大鼠18个月龄时，它们每月称重，以评估它们的体重变化，并且采集血样，以便定量炎性标志物(急性期蛋白质：α2-巨球蛋白和纤维蛋白原)。在21个月龄时，将大鼠分为体重、体重减轻和炎性状态匹配的两组。给大鼠喂食补充的膳食，从21个月龄开始，并且持续14周。半胱氨酸膳食存在于每kg补充4.0g L-半胱氨酸(Sigma)的商品化粒状膳食A04(SAFE/UAR,Scientific AnimalFood and Engineering,Villemoisson-sur-Orge,法国)，并且对照膳食每kg补充2.9g L-丙氨酸(Jerafrance)(等氮膳食)。试验膳食配制在UnitéPréparation Aliments Expérimentaux,INRA Jouy-en-Josas中。表1呈现了商品化(未补充的)膳食的氨基酸组成。
表1.商品化膳食(A04)的氨基酸组成
| 氨基酸 | 蛋白质含量(g/100g) | 商品化膳食中的含量(g/kg) |
| 天冬氨酸 | 7.5 | 12.22 |
| 苏氨酸 | 3.5 | 5.70 |
| 丝氨酸 | 3.9 | 6.41 |
| 谷氨酸 | 20.3 | 33.15 |
| 脯氨酸 | 7.4 | 12.03 |
| 甘氨酸 | 5.2 | 8.53 |
| 丙氨酸 | 4.6 | 7.52 |
| 缬氨酸 | 4.3 | 6.98 |
| 半胱氨酸 | 1.74 | 2.84 |
| 甲硫氨酸 | 2.00 | 3.26 |
| 异亮氨酸 | 3.4 | 5.58 |
| 亮氨酸 | 7.1 | 11.61 |
| 酪氨酸 | 3.2 | 5.29 |
| 苯丙氨酸 | 4.4 | 7.18 |
| 赖氨酸 | 4.5 | 7.29 |
| 组氨酸 | 2.3 | 3.69 |
| 精氨酸 | 5.6 | 9.17 |
| 总计 | 91.1 | 148.46 |
1-死亡率
存活曲线是通过Kaplan-Meier方法产生(图2)并且通过对数秩检验比较，以分析半胱氨酸补充对死亡率的作用。
半胱氨酸补充没有改变死亡率。
2-体重
体重(图3)随时间而降低，并且在补充7周时体重与初值存在显著不同。体重在试验结束时加速降低，因为两组最后一周的体重不同于各自先前的数值。
3-食物摄入
食物摄入(图4)随时间而降低，并且丙氨酸膳食更低。时间和膳食之间显著的相互作用表明半胱氨酸能够钝化与老化相关的食物摄入降低。事实上，丙氨酸组食物摄入每周显著降低0.96%(显著的线性回归r=0.88，P<0.0001)，而半胱氨酸组没有变化(r=0.20，P=0.50)。
消耗4g半胱氨酸补充的膳食钝化了当大鼠为约22.5个月龄时出现的食物摄入降低，这意味着半胱氨酸显示出抗老化相关的厌食特性。
4-体重，骨骼肌和器官重量
如表3所示，补充半胱氨酸的大鼠比对照大鼠表现出更高的肝重量。
表3.半胱氨酸补充对机体、骨骼肌和器官重量的作用
BW：体重。
Claims (15)
1.半胱氨酸，其用于治疗和/或预防营养不良和/或与其相关的障碍。
2.用于权利要求1的用途的半胱氨酸，其中半胱氨酸是以半胱氨酸前体形式提供的，所述的半胱氨酸前体选自蛋白质或肽水解物或肽中结合的半胱氨酸，例如γ-谷氨酰基-半胱氨酸，或肽的其它形式，例如γ-谷氨酰基-半胱氨酸酯，混合的二硫化物，例如L-半胱氨酸-谷胱甘肽半胱氨酸前药，N-乙酰基-半胱氨酸(游离形式，酰胺或酯形式)，S-烯丙基-半胱氨酸，S-甲基-半胱氨酸，S-乙基-半胱氨酸，S-丙基-半胱氨酸，TCA(噻唑烷羧酸)，OTC(L-2-氧代噻唑烷-4-羧酸酯)和S-羟基-甲基巯基L-半胱氨酸。
3.用于上述权利要求之一的用途的半胱氨酸，其用于增加食物摄入，和/或降低饱满感和/或饱食。
4.用于上述权利要求之一的用途的半胱氨酸，其用于增加食欲。
5.用于权利要求1的用途的半胱氨酸，其中与营养不良相关的障碍选自厌食、神经性厌食、恶病质、与食物摄入减少相关的炎性疾病或其组合。
6.用于上述权利要求之一的用途的半胱氨酸，其施用于老年个体。
7.用于上述权利要求之一的用途的半胱氨酸，其用于治疗和/或预防年龄相关的食物摄入减少。
8.用于上述权利要求之一的用途的半胱氨酸，其中半胱氨酸是以营养组合物的形式提供的。
9.用于上述权利要求之一的用途的半胱氨酸，其中营养组合物包含含有至少3.0重量-%半胱氨酸的蛋白质成分，和/或其中半胱氨酸以约0.03至0.15g/kg体重范围的日剂量施用。
10.用于上述权利要求之一的用途的半胱氨酸，其中营养组合物是口服施用、肠内施用或非肠道施用，并且其中营养组合物是在用餐前一小时内、在用餐过程中施用，或作为膳食替代物施用。
11.营养组合物，该营养组合物包含至少3.0重量-%的半胱氨酸，优选至少4.0重量-%的半胱氨酸，更优选至少5.0重量-%的半胱氨酸。
12.权利要求11的营养组合物，其中营养组合物具有至少0.5kcal/g的热密度。
13.权利要求11或12的营养组合物，其中营养组合物包含约10至40%的营养组合物的热量来自蛋白质。
14.权利要求11至13之一的营养组合物，其中营养组合物包含约15至45%的营养组合物的热量来自脂质，和/或约20至70%的营养组合物的热量来自碳水化合物。
15.权利要求11至14之一的营养组合物，其中营养组合物选自食物产品、宠物食物产品、饮料、药物、营养配方、临床营养用组合物、通过添加水重构的营养粉末、果汁或乳、营养食品、食物添加剂、食物补充剂、乳制品或凝胶。
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| EP10188399A EP2444083A1 (en) | 2010-10-21 | 2010-10-21 | Cysteine and food intake |
| PCT/EP2011/068231 WO2012052463A1 (en) | 2010-10-21 | 2011-10-19 | Cysteine and food intake |
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| EP3668499A1 (en) | 2017-08-14 | 2020-06-24 | Axcella Health Inc. | Amino acid compositions for the treatment of liver disease |
| WO2019101700A1 (en) * | 2017-11-21 | 2019-05-31 | Nestec S.A. | Compositions and methods using oleuropein or curcumin for muscle quality and/or muscle mass |
| CN112839643A (zh) | 2018-06-20 | 2021-05-25 | 胺细拉健康公司 | 用于治疗肌肉中脂肪浸润的组合物及方法 |
| WO2020163188A1 (en) * | 2019-02-08 | 2020-08-13 | Imbria Pharmaceuticals, Inc. | Compositions containing n-acetylcysteine conjugated to a tca cycle intermediate |
| WO2021079987A1 (ja) * | 2019-10-25 | 2021-04-29 | 味の素株式会社 | 筋質向上剤 |
| WO2024068302A1 (en) | 2022-09-30 | 2024-04-04 | Evonik Operations Gmbh | Probiotic composition for the treatment of malnutrition |
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| Publication number | Publication date |
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| US20130225486A1 (en) | 2013-08-29 |
| AU2011317627A1 (en) | 2013-05-23 |
| US9233090B2 (en) | 2016-01-12 |
| RU2013123062A (ru) | 2014-11-27 |
| CA2815109C (en) | 2020-03-24 |
| WO2012052463A1 (en) | 2012-04-26 |
| BR112013009709A2 (pt) | 2016-07-19 |
| SG189935A1 (en) | 2013-06-28 |
| JP2014504261A (ja) | 2014-02-20 |
| MX2013004371A (es) | 2013-08-27 |
| DK2629769T3 (en) | 2018-01-02 |
| JP6160832B2 (ja) | 2017-07-12 |
| CA2815109A1 (en) | 2012-04-26 |
| EP2629769B1 (en) | 2017-10-04 |
| EP2629769A1 (en) | 2013-08-28 |
| PH12013500761A1 (en) | 2017-08-23 |
| ES2654344T3 (es) | 2018-02-13 |
| EP2444083A1 (en) | 2012-04-25 |
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| AU2011317627B2 (en) | 2016-06-02 |
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