CN101888793A - 具有高能含量的营养配方 - Google Patents
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- CN101888793A CN101888793A CN2008801164957A CN200880116495A CN101888793A CN 101888793 A CN101888793 A CN 101888793A CN 2008801164957 A CN2008801164957 A CN 2008801164957A CN 200880116495 A CN200880116495 A CN 200880116495A CN 101888793 A CN101888793 A CN 101888793A
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Abstract
本发明涉及用于治疗和/或预防婴儿生长缓慢，特别是用于促进患儿的追赶生长的高能配方。
Description
发明领域
患病的婴儿通常表现出能够用额外的高能营养修正的生长缓慢(faltering growth)模式。本发明涉及促进这类婴儿的追赶生长(catch-upgrowth)，而不会对肠屏障功能产生通常与高能组合物(energy densecomposition)有关的不良副作用的组合物。
发明背景
在生命的第一年，由于高基础合成代谢要求，儿童(婴儿)对能量和营养限制是特别敏感的。每单位体重的能量和营养需求在生命的前4至6个月最高，并且需求逐渐下降直至青少年发育陡增。
现在有相当的证据表明，婴儿期的主要生长驱动力是充分的营养。在随后的儿童期和青春期中，诸如生长激素、甲状腺素和皮质醇的体液因子起到重要的多的作用，但是仍然要求充分的营养。
要求营养支持的婴儿代表了独特的挑战，这不仅是因为婴儿生长、发育和器官成熟的高营养需求，还因为婴儿不大的身体储备(bodyreserves)。婴儿全部营养，特别是能量的身体储备都比成人要小，并且在急性和慢性疾病中，这些资源会快速地消耗。满足能量要求的组织损耗在婴儿中比在更大的儿童和成人快得多，这使得婴儿对饥饿的影响特别易感。已经确立的是，成人有约70天的足够身体储备，而相比之下，早产的婴儿的身体储备为4天，足月的婴儿的身体储备为31天。
在急性和慢性疾病期间，婴儿具有特殊的营养需求，并且经常患有生长缓慢。因此，这类婴儿需要额外的营养来补偿在疾病期间发生的生长不足。通常通过提供额外的能量来实现这个目的。由于婴儿不饮用大的体积，所以通过浓饮料代乳品(formula)来提供能量，该浓饮料代乳品通常含有至少0.9kcal/ml的能量。
WO 2007/039596公开了这样的组合物，该组合物包含益生菌、益生元纤维(prebiotic fiber)和LC-PUFA作为活性成分来促进受到物理压力或心理压力的年幼哺乳动物的追赶生长。
WO 2006/091103公开了包含益生菌和益生元纤维作为活性成分的组合物以用于治疗和/或预防胃肠病症、免疫病症和/或内分泌病症。
WO 2007/073193公开了向婴儿给予的组合物，该组合物包含脂质和尿苷的混合物作为活性组分以用于预防长大后的肥胖。
WO 2007/046699公开了包含LC-PUFA和/或核苷酸的组合物以用于发展通过剖腹产分娩的婴儿的肠菌群。
本发明的目的是提供适于促进婴儿，优选0至18个月年龄组的婴儿的最佳追赶生长的配方，所述婴儿患有疾病引起的生长缓慢，同时减少通常与高能组合物有关的胃肠症状。
发明概述
本发明人认识到，为了在生病期间或生病后治疗或预防生长缓慢，需要对喂养婴儿的现行做法进行改进。特别地认识到，高能配方导致肠功能不良，特别是由于营养摄取的降低、屏障功能的降低和/或不期望的细菌生长的增加引起的肠功能不良。
通常，婴儿营养具有约0.7kcal/ml的能密度。本发明这组的患者需要增加的能密度。本发明人认识到，由于并非所有营养物质(例如，蛋白质)都是易于吸收的，所以增加的能密度可以导致肠道内不期望的细菌生长的增加。本发明人发现，通过在现有的高能组合物中包含核苷酸、LC-PUFA和不易消化的低聚糖的协同作用混合物可以降低副作用，该不易消化的低聚糖即难消化的碳水化合物。本发明人还认识到向患儿给予活细菌是无益的。
因此，本发明提供了促进婴儿的追赶生长的营养配方，该营养配方包含脂质来源，该脂质来源含有组合物中脂肪酸的至少0.1wt％的量的长链多不饱和脂肪酸(LC-PUFA)、基于组合物干重的至少0.1wt％的量的难消化的碳水化合物(益生元纤维)以及基于组合物干重的至少1.10-4wt％的量的核苷酸。
本发明特别的优势在于，其提供了能够促进追赶生长，特别是患儿的追赶生长的组合物，该组合物通过改善肠内吸收以改善蛋白质的摄入并同时改善营养成分的摄取来促进追赶生长，特别是患儿的追赶生长。还借助核苷酸的存在，通过婴儿(全身)免疫系统的维持中的协同作用，这最终使得胃肠症状降低，从而支持发育上(developmentally)合适的喂养行为并增强生活质量。
发明详述
在一实施方案中，本发明涉及包含蛋白质、脂肪、可消化的碳水化合物和难消化的碳水化合物以及核苷酸的组合物在制备用于治疗和/或预防婴儿生长缓慢的高能含量组合物中的用途，其中该组合物具有
a.至少0.9kcal/ml并优选低于2.0kcal/ml的能密度；和
b.提供总热量的至少9.5％的蛋白质组分；和
c.基于总脂肪酸的至少0.1wt％的长链多不饱和脂肪酸；和
d.基于组合物干重的至少0.1wt％的难消化的碳水化合物；和
e.基于组合物干重的至少1.10-4wt％的核苷酸。
在一实施方案中，本发明涉及治疗和/或预防婴儿生长缓慢的方法，所述方法包括向所述婴儿给予如本文所定义的高能含量组合物。
在一实施方案中，本发明涉及如本文所定义的组合物在治疗和/或预防婴儿生长缓慢中的用途。在一实施方案中，该用途是用于促进患儿的追赶生长。
在一实施方案中，所述组合物具有至少0.9kcal/ml并低于1.8kcal/ml、优选至少0.9kcal/ml并低于1.5kcal/ml的能密度。在一实施方案中，所述组合物具有至少0.9kcal/ml并低于1.2kcal/ml的能密度。
难消化碳水化合物
难消化的碳水化合物优选自低聚果糖、低聚半乳糖、唾液酸低聚糖、低聚木糖、菊粉、阿拉伯树胶、瓜耳胶、抗性淀粉、乳源性(milk-derived)低聚糖及上述的混合物。难消化的碳水化合物优选自低聚果糖、菊粉、阿拉伯树胶和低聚半乳糖。优选地，本发明的组合物包含低聚半乳糖。这些碳水化合物对刺激双歧杆菌(Bifdocateria)和乳酸杆菌(Lactobacilli)的生长特别有效。优选地，本发明的组合物包含(i)低聚半乳糖和(ii)低聚果糖和/或菊粉。优选地，低聚半乳糖：(低聚果糖和/或菊粉)的重量比为25∶1至1∶25。合适的低聚半乳糖可以商购自Borculo Domo Ingredients，并且商标名为Vivinal GOS 10。合适的低聚果糖可以商购自Orafti S。优选地，难消化的碳水化合物的总量为基于组合物干重的至少0.1wt％。
本发明优选地包括给予包含0.05克至25克、优选0.1克至5克的难消化的碳水化合物的食物(serving)。本发明优选地包括给予包含0.05克至25克低聚半乳糖、优选0.1克至5克低聚半乳糖的食物。本发明优选地包括每日给予0.05克至25克难消化的碳水化合物，优选每日给予0.1克至5克难消化的碳水化合物。本发明优选地包括每日给予0.05克至25克低聚半乳糖，优选每日给予0.1克至5克低聚半乳糖。
优选地，本发明的难消化的碳水化合物具有至少2单糖单位的聚合度(DP)，并且在肠内不能被存在于人上消化道(小肠及胃)的酸或消化酶的作用消化或者只是被部分地消化，但是可以通过人肠菌群而发酵。术语单糖单位是指具有闭环结构的单位，优选己糖，例如吡喃糖或呋喃糖形式。低聚糖的平均聚合度通常低于60单糖单位，优选低于40单糖单位，甚至更优选低于20单糖单位。
根据另一实施方案，本发明的组合物的至少一种难消化的碳水化合物选自果聚糖、低聚果糖、难消化的糊精、低聚半乳糖(包括反式低聚半乳糖)、低聚木糖、低聚阿拉伯糖、低聚葡萄糖、低聚甘露糖、低聚岩藻糖、酸性低聚糖(例如，糖醛酸低聚糖，如果胶水解物)及上述的混合物。优选地，本发明的组合物包括至少一种，优选至少两种选自低聚果糖或菊粉、低聚半乳糖及果胶和/或果胶水解物的难消化的碳水化合物。
根据另一优选实施方案，本发明的组合物包含至少一种选自低聚果糖、菊粉、阿拉伯树胶和低聚半乳糖及果胶水解物的难消化的碳水化合物。优选地，至少70％的果胶水解物的聚合度为2至50。优选地，果胶水解物的平均分子量为1kD至20kD，优选为4kD至10kD。可以通过如US 5,472,952中所述的方法来确定平均分子量。
当以即食液态形式存在时，本发明的组合物优选地包含每升0.1克至100克、更优选每升0.5克至50克、甚至更优选每升1克至25克难消化的碳水化合物。由于过度的发酵，过高的难消化的碳水化合物含量可能引起不适，而非常低的含量则可能导致不足的粘液层。
在存在至少两种不同的难消化的碳水化合物的情况下，重量比优选为1至10，更优选为1至5。最佳地，这些重量比刺激肠内不同部位的不同类型粘蛋白的产生。
优选地，包含在本发明的组合物中难消化的碳水化合物的量超过基于该组合物总干重的0.1wt.％、优选超过0.2wt.％、更优选超过0.5wt.％、并且甚至更优选超过1wt.％。本发明的组合物优选地具有低于20-wt.％、更优选低于10-wt.％、甚至更优选低于5-wt.％的难消化的碳水化合物含量。
长链多不饱和脂肪酸
本发明的组合物优选地包含长链多不饱和脂肪酸(LC-PUFA)。LC-PUFA是这样的脂肪酸，其中酰基链的长度为20至24个碳原子(优选20或22个碳原子)，并且其中酰基链在酰基链中的所述碳原子之间包含至少两个不饱和键。更优选地，本发明的组合物包含至少一种选自二十碳五烯酸(EPA，20:5 n3)、二十二碳六烯酸(DHA，22:6 n3)、花生四烯酸(ARA，20:4 n6)和二十二碳五烯酸(DPA，22:5 n3)的LC-PUFA。EPA、DHA和ARA被发现有效地降低肠的紧密连接的通透性。降低的紧密连接的通透性减少了感染发生和/或减少了细菌(内或外)毒素的通道(passage)。因此在本发明的组合物中掺入LC-PUFA，优选EPA、DHA、DPA和/或ARA，改善了肠屏障的完整性，这对于患儿是最为重要的，因为这些婴儿具有较少发展的肠菌群并因此具有成熟较慢的肠屏障。LC-PUFA还具有抗炎效果，并促进产乳酸细菌附着到粘膜表面，以此刺激健康菌群的发展。
由于低浓度的ARA、DHA、DPA和/或EPA已经有效地降低紧密连接的通透性，所以在本发明的组合物中，该组合物优选地是营养组合物，LC-PUFA的含量优选不超过总脂肪含量的5wt.％，优选不超过总脂肪含量的2.5wt.％，甚至更优选不超过总脂肪含量的1wt.％。优选地，本发明的组合物包含占总脂肪含量至少0.1wt.％、优选至少0.25wt.％、更优选至少0.5wt.％、甚至更优选至少0.75wt.％的LC-PUFA。由于同样的原因，EPA含量优选不超过总脂肪的1wt.％，更优选不超过总脂肪的0.5wt.％，但优选总脂肪的至少0.02wt.％，更优选总脂肪的至少0.05wt.％。DHA含量优选不超过总脂肪的1wt.％，更优选不超过总脂肪的0.5wt.％，但至少是总脂肪的0.1wt.％。由于发现ARA特别有效地降低紧密连接的通透性，所以本发明的组合物包括相对高的量的ARA，优选总脂肪的至少0.1wt.％、甚至更优选总脂肪的至少0.25wt.％、最优选总脂肪的至少0.35wt.％的ARA。ARA含量优选不超过总脂肪的1wt.％。当本发明的肠道组合物包含ARA时，有利地添加EPA和DHA以平衡ARA的作用，例如降低ARA代谢产物的潜在促炎作用。ARA的过量代谢产物可能引起炎症。因此，本发明的组合物优选地包含ARA、EPA和DHA，其中ARA/DHA的重量比优选地高于0.5，优选高于0.7，甚至更优选高于1。ARA/DHA的比率优选低于10。ARA/EPA的重量比优选为1至100，更优选为5至20。
n6∶n3的比率优选为1∶2至8∶1，更优选为4∶1至8∶1。LC-PUFA的来源可以是例如卵脂质(egg lipid)、真菌油(fungal oil)、低EPA鱼油或藻类油。
重要地，亚油酸(C18:2 n6)与α亚麻酸(C18:3 n-3)的比率优选为4至6，更优选为4.5至5.5。该比率将提供用于治疗肠屏障功能，并因此用于诱导健康追赶生长的最佳脂肪混合物。
核苷酸
向本发明的组合物中添加核苷酸和/或核苷进一步改善了肠粘膜屏障功能，特别是由于其抑制和/或减少了细菌移位的发生并降低了肠损伤。因此，本发明的组合物还包含干配方(dry formula)总重的至少1.10-4wt％的核苷和/或核苷酸，优选1mg至500mg，甚至更优选5mg至100mg。有利地，本发明的组合物包含核苷酸和/或核苷，因为在与LC-PUFA和难消化的碳水化合物组合时，这些组分出乎意料地以被认为是协同作用的方式改善肠屏障功能、免疫系统和/或肠菌群。
更优选地，所述组合物包含核苷酸。核苷酸优选为一磷酸核苷酸、二磷酸核苷酸或三磷酸核苷酸形式，更优选一磷酸核苷酸。核苷酸优选为核糖核苷酸或脱氧核糖核苷酸，更优选核糖核苷酸。核苷酸可以是单体、二聚体或聚合物(包括RNA和DNA)。核苷酸优选作为游离酸或以盐、更优选单钠盐的形式存在。向本发明的组合物中掺入核苷酸改善了肠屏障的完整性和/或成熟，这对于患儿是最为重要的，因为这些婴儿具有较少发展的肠菌群并因此具有成熟较慢的肠屏障，肠屏障的完整性或成熟度对于这些婴儿而言是最为重要的。优选地，所述组合物包含选自5’-一磷酸胞苷(CMP)、5’-一磷酸尿苷(UMP)、5’-一磷酸腺苷(AMP)、5’-一磷酸鸟苷(GMP)和5’-一磷酸肌苷(IMP)的一种或多种，更优选选自CMP、UMP、AMP、GMP和IMP的至少3种。增加的核苷酸多样性可以进一步改善屏障完整性。
优选地，所述组合物每100克本发明的组合物干重包含5mg至100mg、更优选5mg至50mg、最优选10mg至25mg的核苷酸。核苷酸还刺激免疫系统，由此增强抗诸如大肠杆菌(E.coli)的高负荷(high load)肠病原体的保护。
优选地，本发明的组合物每100g组合物干重包含1mg至20mg、更优选3mg至12.5mg的CMP。优选地，所述组合物每100g组合物干重中包含1mg至20mg、更优选2mg至9mg的UMP。优选地，本发明的组合物每100g本发明的组合物干重包含0.5mg至15mg、更优选1.5mg至8mg的AMP。优选地，所述组合物每100g组合物干重包含0.2mg至10mg、更优选0.6mg至3mg的GMP。优选地，本发明的组合物每100g组合物干重包含0.5mg至10mg、更优选1.3mg至5mg的IMP。
因此，本发明的优选组合物包含核苷酸、蛋白质、脂肪酸、可消化的碳水化合物和难消化的碳水化合物，并具有
a.0.95kcal/ml至1.15kcal/ml的能密度；和
b.提供总热量的至少9.5％、优选10能量％至12能量％的蛋白质组分；
c.基于组合物中总脂肪酸的0.1wt％至0.5wt％的长链多不饱和脂肪酸；
d.基于组合物干重的0.2wt％至0.4wt％的难消化的碳水化合物；和
e.基于组合物干重的至少1.10-4wt％、优选基于组合物干重的2.10-4wt％至4.10-4wt％的量的选自5’-一磷酸胞苷(CMP)、5’-一磷酸尿苷(UMP)、5’-一磷酸腺苷(AMP)、5’-一磷酸鸟苷(GMP)和5’-一磷酸肌苷(IMP)的至少3种核苷酸。
常量营养物
本发明的组合物优选地向婴儿提供营养，并包含脂质组分、蛋白质组分和碳水化合物组分。脂质组分优选地提供总热量的5％至50％，蛋白质组分优选地提供总热量的9.5％至50％，碳水化合物组分优选地提供总热量的15％至90％。本发明的组合物优选地用作婴儿代乳品，其中脂质组分提供总热量的35％至50％，蛋白质组分提供总热量的10％至12.5％，碳水化合物组分提供总热量的40％至55％。为了计算蛋白质组分在总热量中的％，需要考虑由蛋白质、肽和氨基酸提供的总能量。
本发明的组合物中所用的蛋白质组分优选地包括选自非人动物蛋白(如乳蛋白、肉蛋白和卵蛋白)、植物蛋白(如大豆蛋白、小麦蛋白、稻米蛋白、马铃薯蛋白和豌豆蛋白)、游离氨基酸及上述的混合物的至少一种。特别优选牛乳来源的氮源，特别是牛乳蛋白蛋白质，如酪蛋白和乳清蛋白。优选地，蛋白质组分包括完整的蛋白质，更优选完整的牛乳清蛋白和/或完整的牛酪蛋白。
优选地，本发明的组合物不是哺乳动物乳汁，优选不是人乳。优选地，本发明的组合物不含人乳蛋白。
容积渗克分子浓度是决定胃肠耐受性的重要因素。为了改善胃肠耐受性，组合物的容积渗克分子浓度优选不超过350mOsmol/升，更优选低于300mOsmol/升。如果将组合物用作管饲(tube feed)，则容积渗克分子浓度优选低于300mOsmol/升，甚至更优选低于250mOsmol/升，因为管饲的婴儿对具有较高容积渗克分子浓度的喂食更为敏感。
患儿通常患有降低的肠屏障功能。为了预防不良胃肠感染，本发明的化合物优选不包含活益生菌。
应用
本发明的组合物旨在向患儿提供营养和/或治疗和/或预防婴儿的生长缓慢。本发明的组合物特别适于向患有囊性纤维化、心脏病症、创伤、癌症和/或瘫痪的婴儿，或者接受过或将要接受手术的婴儿给予。优选通过胃肠管(gastrointestinal tube)给予本发明的组合物。优选地，以100ml至1000ml的每日剂量给予本发明的组合物。优选地，向0至18个月大的婴儿给予所述组合物。在一实施方案中，本发明的组合物不包含活细菌。
给予包含LC-PUFA、难消化的低聚糖和核苷酸的本发明的组合物使得(医院)致病微生物移位减少，该致病微生物如大肠杆菌(Eschericiacoli)，属于气单胞菌属(Aeromonas)、克雷白杆菌属(Klebsiella)、肠杆菌属(Enterobacter)、假单胞菌属(Pseudomonas)、变形杆菌属(Proteus)和不动杆菌属(Acinetobacter)的其它革兰氏阴性物种，及诸如肠球菌(Enterococcus)、葡萄球菌(Staphylococcus)、链球菌(Streptococcus)、芽孢杆菌(Bacillus)和梭状芽孢杆菌(Clostridium)的革兰氏阳性物种，病毒和/或真菌，优选大肠杆菌(大肠杆菌(E.coli))。因此，本发明的组合物优选地用于治疗和/或预防患儿或患有生长缓慢的婴儿的感染和/或腹泻的方法，所述方法包括向通过剖腹产分娩的婴儿给予本发明的组合物。在优选实施方案中，将本发明的组合物用于治疗和/或预防大肠杆菌、气单胞菌、克雷白杆菌、肠杆菌和/或假单胞菌引起的感染，更优选大肠杆菌引起的感染。
通过利用本发明的组合物改善了胃肠耐受性。因此，本发明的化合物优选地用于改善患儿对肠道喂养代乳品(enteral fed formula)的胃肠耐受性。
实施例
下列非限定性实施例进一步对本发明进行说明。
实施例1：营养组合物-Infatrini
具有1kcal/ml的能密度并适于诱导0至18个月大的患者的追赶生长的组合物
g/100ml
蛋白质 10.4能量％ 2.6
碳水化合物 41.1能量％ 10.3
脂肪 48.6能量％ 5.4
纤维 0.8
核苷酸 2.8.10-3(CMP、UMP、AMP、GMP、IMP)
根据欧盟指令(EC directive)FSMP 1999/21的维生素/矿物质
组分单位 每100ml 每100kcal
蛋白质(相当)，总g数 2.60 2.61
-氮(蛋白质)g 0.41 0.41
-动物蛋白g 2.60 2.61
·乳清蛋白g 1.56 1.57
·酪蛋白g 1.04 1.04
碳水化合物g 10.3 10.3
-糖g 5.69 5.71
·葡萄糖g 0.28 0.28
·乳糖g 5.16 5.18
·麦芽糖g 0.24 0.24
-多糖g 4.42 4.43
脂肪g 5.36 5.38
-植物性g 5.24 5.26
-动物性g 0.12 0.12
·其中的乳g 0.08 0.08
-饱和g 2.05 2.05
·其中的MCT g
-单不饱和g 2.33 2.34
-多不饱和g 0.99 0.99
膳食纤维g 0.800 0.803
-可溶的g 0.80 0.80
湿度/水分g 84.9 85.2
核苷酸**mg 2.80 2.81
-5’-一磷酸胞苷 0.93 0.94
-5’-一磷酸尿苷 0.47 0.47
-5’-一磷酸腺苷 0.78 0.78
-5’-一磷酸鸟苷 0.23 0.23
-5’-一磷酸肌苷 0.39 0.39
容积渗克分子浓度：290mOsmol/升
实施例2：用包含EPA、DHA和ARA的脂肪酸混合物降低肠紧密连接
的通透性
在Transwell滤器(Corning，Costar BV，The Netherlands)上培养肠上皮细胞系T84(ATCC、USA)的单层细胞(MC)，这允许进行粘膜和浆膜取样以及刺激人肠上皮细胞。融合(confluency)后两周，在使用或不用多不饱和脂肪酸ARA、DHA、GLA、EPA或对照棕榈酸(10μM或100μM，粘膜隔(mucosal compartment)，Sigma，St.Louis，USA)的IL-4(2ng/ml、浆膜隔(serosal compartment)，Sigma，USA)的存在下，孵育单层细胞。在IL-4孵育之前，将细胞用ARA、DHA、EPA或棕榈酸预孵育48hr。将PUFA和棕榈酸与IL-4的共培养继续另外的48hr；同时每24hr更换培养基和添加剂。通过测量跨上皮电阻(TER)和跨上皮通透性来确定上皮屏障功能。
表1给出了ARA、DHA、EPA和棕榈酸(100μM)对IL-4介导的屏障破坏的影响的结果。表1显示LC-PUFA的ARA、DHA和EPA抑制由IL-4引起的通量增加。相比之下，与对照相比，棕榈酸具有不良的影响和减少的屏障破坏。这些结果表明了ARA、DHA和EPA在临床和婴儿营养配方中预防或减少IL-4介导的屏障破坏的有利用途。这些结果进一步支持了本发明的脂肪酸和难消化的低聚糖的组合的协同效果。
表1
| 成分(LC-PUFA) | IL-4通量 | IL-4TER |
| 对照 | 582 | 374 |
| 棕榈酸 | 777 | 321 |
| DHA | 271 | 547 |
| ARA | 218 | 636 |
| EPA | 228 | 539 |
图1给出了各种FA(棕榈酸、DHA、GLA和AA)对IL-4介导的屏障破坏(通量)的取决于时间和剂量(10μM和100μM)的保护效果。图1显示了，如通过减少的4kD葡聚糖通量所反映的，ARA、DHA和GLA抗IL-4介导的屏障破坏的保护作用。这些结果表明了ARA、DHA和GLA在临床和婴儿营养配方中预防或减少例如如在食物过敏或牛乳过敏中所发生的IL-4介导的屏障破坏的有利用途。这些结果进一步支持了本发明的脂肪酸和难消化碳水化合物的组合的协同效果。
Claims (7)
1.包含蛋白质、脂肪、可消化的碳水化合物和难消化的碳水化合物以及核苷酸的组合物在制备用于治疗和/或预防婴儿生长缓慢的高能含量组合物中的用途，其中所述组合物具有
a.至少0.9kcal/ml并优选低于2.0kcal/ml的能密度；和
b.提供总热量的至少9.5％的蛋白质组分；和
c.基于总脂肪酸的至少0.1wt％的长链多不饱和脂肪酸；和
d.基于所述组合物干重的至少0.1wt％的难消化的碳水化合物；和
e.基于所述组合物干重的至少1.10-4wt％的核苷酸。
2.如权利要求1所述的用途，其中以管饲给予所述组合物。
3.如权利要求1或2所述的用途，其中所述婴儿患有胃肠不耐受、囊性纤维化、心脏病症、创伤、癌症和/或瘫痪，或者接受过或将要接受手术。
4.如前述权利要求中任一项所述的用途，其中所述难消化的碳水化合物选自低聚果糖、低聚半乳糖、唾液酸低聚糖、低聚木糖、菊粉、阿拉伯树胶、瓜耳胶、抗性淀粉、乳源性低聚糖、果胶及上述的混合物。
5.如前述权利要求中任一项所述的用途，其中所述组合物包含选自5’-一磷酸胞苷(CMP)、5’-一磷酸尿苷(UMP)、5’-一磷酸腺苷(AMP)、5’-一磷酸鸟苷(GMP)和5’-一磷酸肌苷(IMP)的至少3种核苷酸。
6.如前述权利要求中任一项所述的用途，其中所述高能含量组合物用于促进患儿的追赶生长。
7.营养组合物，其包含蛋白质、脂肪酸、可消化的碳水化合物和难消化的碳水化合物以及核苷酸，其中所述组合物具有
a.0.95kcal/ml至1.15kcal/ml的能密度；和
b.提供总热量的至少9.5％的蛋白质组分；
c.基于所述组合物中总脂肪酸的0.1wt％至0.5wt％的长链多不饱和脂肪酸；
d.基于所述组合物干重的0.2wt％至0.4wt％的难消化的碳水化合物；和
e.基于所述组合物干重的至少1.10-4wt％的量的选自5’-一磷酸胞苷(CMP)、5’-一磷酸尿苷(UMP)、5’-一磷酸腺苷(AMP)、5’-一磷酸鸟苷(GMP)和5’-一磷酸肌苷(IMP)的至少3种核苷酸。
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| CN201410818358.5A CN104585749B (zh) | 2007-09-17 | 2008-09-17 | 具有高能含量的营养配方 |
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| NL2007000230 | 2007-09-17 | ||
| NLPCT/NL2007/000230 | 2007-09-17 | ||
| PCT/NL2008/050607 WO2009038458A1 (en) | 2007-09-17 | 2008-09-17 | Nutritional formulation with high energy content |
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| CN201410818358.5A Division CN104585749B (zh) | 2007-09-17 | 2008-09-17 | 具有高能含量的营养配方 |
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| CN101888793B CN101888793B (zh) | 2015-01-14 |
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| CN200880116495.7A Active CN101888793B (zh) | 2007-09-17 | 2008-09-17 | 具有高能含量的营养配方 |
| CN201410818358.5A Active CN104585749B (zh) | 2007-09-17 | 2008-09-17 | 具有高能含量的营养配方 |
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| CN201410818358.5A Active CN104585749B (zh) | 2007-09-17 | 2008-09-17 | 具有高能含量的营养配方 |
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| Country | Link |
|---|---|
| US (1) | US20100261642A1 (zh) |
| EP (3) | EP3263120A1 (zh) |
| CN (2) | CN101888793B (zh) |
| AT (1) | ATE536105T1 (zh) |
| BR (1) | BRPI0816993A2 (zh) |
| DK (1) | DK2190304T3 (zh) |
| ES (1) | ES2377565T3 (zh) |
| MX (1) | MX2010002978A (zh) |
| PL (1) | PL2190304T3 (zh) |
| PT (1) | PT2190304E (zh) |
| RU (1) | RU2486772C2 (zh) |
| SI (1) | SI2190304T1 (zh) |
| WO (1) | WO2009038458A1 (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105324039A (zh) * | 2013-04-17 | 2016-02-10 | N·V·努特里奇亚 | 用于在苯丙酮酸尿症中改善脑功能的营养组合物 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010134800A1 (en) * | 2009-05-19 | 2010-11-25 | N.V. Nutricia | Human milk fortifier with high protein and long chain poly unsaturated fatty acids for improving body adipose tissue distribution |
| CN102481009A (zh) * | 2009-08-13 | 2012-05-30 | 雀巢产品技术援助有限公司 | 包含外源性核苷酸的营养组合物 |
| CA2778647A1 (en) * | 2009-11-25 | 2011-06-03 | Nestec S.A. | Nutritional compositions including a high protein component and exogenous nucleotides |
| BR112012027427A2 (pt) * | 2010-04-26 | 2015-09-15 | Nestec Sa | composições nutritivas e métodos para a mudança da nutrição parenteral para a nutrição enteral |
| EP2404507A1 (en) * | 2010-07-08 | 2012-01-11 | Nestec S.A. | Array of age-tailored nutritional formula with optimum fat content |
| US20130064923A1 (en) * | 2011-09-13 | 2013-03-14 | Agropur Cooperative | Liquid Milk Beverage For Toddlers |
| MX2018015187A (es) * | 2016-08-04 | 2019-04-24 | Nestec Sa | Composiciones nutricionales con 2fl y lnnt para su uso en la prevencion y/o tratamiento de la diarrea no causada por rotavirus mediante la accion en la disbiosis de la microbiota intestinal. |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5472952A (en) | 1993-03-18 | 1995-12-05 | Bristol-Myers Squibb Company | Partially hydrolyzed pectin in nutritional compositions |
| US5438042B1 (en) * | 1993-10-08 | 1997-08-26 | Sandoz Nutrition Ltd | Enteral nutritional composition having amino acid profile |
| EP1062873A1 (en) * | 1999-12-13 | 2000-12-27 | N.V. Nutricia | Improved infant formula, protein hydrolysate for use in such an infant formula, and method for producing such a hydrolysate |
| DE10057290B4 (de) * | 2000-11-17 | 2004-01-08 | Fresenius Kabi Deutschland Gmbh | Enteral zu verabreichendes Supplement zur parenteralen Ernährung oder partiellen enteralen/oralen Ernährung bei kritisch Kranken, chronisch Kranken und Mangelernährten |
| EP1549158B1 (en) * | 2002-10-10 | 2009-01-07 | Wyeth | Infant formula containing nucleotides |
| US7867541B2 (en) * | 2003-04-14 | 2011-01-11 | Mead Johnson Nutrition Company | Compositions and methods of formulation for enteral formulas containing sialic acid |
| US8252769B2 (en) * | 2004-06-22 | 2012-08-28 | N. V. Nutricia | Intestinal barrier integrity |
| EP1634599A1 (en) * | 2004-08-20 | 2006-03-15 | N.V. Nutricia | Iimmune stimulatory infant nutrition |
| DK1855550T3 (da) | 2005-02-28 | 2012-01-16 | Nutricia Nv | Næringspræparat med probiotika |
| DE602006011195D1 (de) | 2005-10-05 | 2010-01-28 | Nestec Sa | Verwendung einer nährstoffformulierung zur förderung des aufholwachstums |
| EP1776877A1 (en) | 2005-10-21 | 2007-04-25 | N.V. Nutricia | Method for stimulating the intestinal flora |
| PL1962823T3 (pl) * | 2005-12-23 | 2015-08-31 | Nutricia Nv | Kompozycja zawierająca wielonienasycone kwasy tłuszczowe, białka i mangan i/lub molibden do poprawy składu błony komórkowej |
| ATE509624T1 (de) * | 2005-12-23 | 2011-06-15 | Nutricia Nv | Zusammensetzung enthaltend mehrfach ungesättigte fettsäuren, proteine, mangan und/oder molybden und nukleotide/nukleoside, zur behandlung von demenz |
| PT1981358E (pt) * | 2006-01-31 | 2010-08-24 | Nestec Sa | Composição nutricional para bebés com baixo peso após o nascimento |
| US20080003330A1 (en) * | 2006-06-30 | 2008-01-03 | Ricardo Rueda | Infant formulas for early brain development |
| US20080089981A1 (en) * | 2006-10-17 | 2008-04-17 | N.V. Nutricia | Ketogenic diet |
-
2008
- 2008-09-17 EP EP17171310.0A patent/EP3263120A1/en not_active Withdrawn
- 2008-09-17 PT PT08831921T patent/PT2190304E/pt unknown
- 2008-09-17 SI SI200830553T patent/SI2190304T1/sl unknown
- 2008-09-17 PL PL08831921T patent/PL2190304T3/pl unknown
- 2008-09-17 US US12/678,243 patent/US20100261642A1/en not_active Abandoned
- 2008-09-17 EP EP08831921A patent/EP2190304B1/en not_active Revoked
- 2008-09-17 RU RU2010115277/13A patent/RU2486772C2/ru active
- 2008-09-17 BR BRPI0816993-4A2A patent/BRPI0816993A2/pt not_active Application Discontinuation
- 2008-09-17 CN CN200880116495.7A patent/CN101888793B/zh active Active
- 2008-09-17 AT AT08831921T patent/ATE536105T1/de active
- 2008-09-17 EP EP11192130.0A patent/EP2428125B1/en active Active
- 2008-09-17 MX MX2010002978A patent/MX2010002978A/es active IP Right Grant
- 2008-09-17 DK DK08831921.5T patent/DK2190304T3/da active
- 2008-09-17 ES ES08831921T patent/ES2377565T3/es active Active
- 2008-09-17 CN CN201410818358.5A patent/CN104585749B/zh active Active
- 2008-09-17 WO PCT/NL2008/050607 patent/WO2009038458A1/en active Application Filing
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105324039A (zh) * | 2013-04-17 | 2016-02-10 | N·V·努特里奇亚 | 用于在苯丙酮酸尿症中改善脑功能的营养组合物 |
Also Published As
| Publication number | Publication date |
|---|---|
| RU2486772C2 (ru) | 2013-07-10 |
| BRPI0816993A2 (pt) | 2014-10-07 |
| EP2190304A1 (en) | 2010-06-02 |
| MX2010002978A (es) | 2010-06-09 |
| EP2428125A2 (en) | 2012-03-14 |
| EP2190304B1 (en) | 2011-12-07 |
| CN104585749B (zh) | 2018-12-28 |
| EP2428125A3 (en) | 2014-08-27 |
| CN104585749A (zh) | 2015-05-06 |
| ATE536105T1 (de) | 2011-12-15 |
| DK2190304T3 (da) | 2012-03-12 |
| ES2377565T3 (es) | 2012-03-28 |
| EP2428125B1 (en) | 2017-05-17 |
| US20100261642A1 (en) | 2010-10-14 |
| PT2190304E (pt) | 2012-03-20 |
| PL2190304T3 (pl) | 2012-04-30 |
| RU2010115277A (ru) | 2011-10-27 |
| EP3263120A1 (en) | 2018-01-03 |
| WO2009038458A1 (en) | 2009-03-26 |
| CN101888793B (zh) | 2015-01-14 |
| SI2190304T1 (sl) | 2012-04-30 |
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