CN101909636A - 包含n-乙酰基乳糖胺的寡糖用于使新生儿免疫应答成熟的应用 - Google Patents
包含n-乙酰基乳糖胺的寡糖用于使新生儿免疫应答成熟的应用 Download PDFInfo
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- CN101909636A CN101909636A CN2008801240700A CN200880124070A CN101909636A CN 101909636 A CN101909636 A CN 101909636A CN 2008801240700 A CN2008801240700 A CN 2008801240700A CN 200880124070 A CN200880124070 A CN 200880124070A CN 101909636 A CN101909636 A CN 101909636A
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Abstract
本发明涉及选自乳糖-N-四糖、乳糖-N-新四糖、乳糖-N-六糖、乳糖-N-新六糖、乳糖-对-N-六糖、乳糖-对-N-新六糖、乳糖-N-八糖、乳糖-N-新八糖、异-乳糖-N-八糖、乳糖-对-N-八糖和乳糖-N-十糖的寡糖在制备用于婴儿的药物和用于婴儿的治疗性营养组合物中的应用，所述药物和治疗性营养组合物用于调节新生儿的免疫应答。本发明还涉及所述寡糖用于调节新生儿的免疫系统以在所述婴儿生命的最初数周促进可与在那些人乳喂养的婴儿中所发现的有益的肠内微生物群相比拟的有益的肠内微生物群的发展的应用，及所述寡糖用于在婴儿中降低随后出现变态反应的风险的应用。
Description
发明领域
本发明涉及通过训练免疫系统以避免不适当的免疫应答来使新生儿免疫应答成熟。
发明背景
即将出生前婴儿的胃肠道被认为是无菌的。在正常出生过程中，其遇到来自母亲消化道、皮肤和母体环境的细菌并且开始菌群定植。2-4周龄的健康的母乳喂养的婴儿的粪便微生物群(其可作为该年龄组的最佳微生物群)主要包括双歧杆菌属(Bifidobacteria)菌种及一些乳杆菌属(Lactobacilli)菌种和更少量的拟杆菌属(Bacteroides)菌种诸如脆弱拟杆菌(Bacteroides fragilis)，而潜在病原体诸如梭菌属(Clostridia)除外。在大约2岁完成断奶后，开始建立与成人模式相似的消化道微生物群模式。
定植的早期是适应消化道新环境的关键时期，其以高浓度提供了大多数的已鉴定的先天性免疫受体的配体，诸如脂多糖类。因此在此期间必须密集地调节和训练消化道先天性免疫识别以避免不适当的刺激。
在小鼠中，出生的几小时内肠内上皮细胞对外源性细菌的复合物诸如内毒素应答，以获得Toll样受体耐受从而促进随后的微生物定植和稳定的宿主微生物内稳态的发展(Lotz等人，2006)。假定相似的出生后进程也在人类新生儿中发生。允许定植发生所需要的促炎反应的下调的功能障碍可导致在定植过程中肠的炎症和紊乱发展。这又可引起宿主和微生物之间的长期斗争，其伴随短期的对健康的负面影响，而且还可能是长期的在消化道局部以及甚至全身性的负面影响。
已显示：这种延迟的或不适当的定植就婴儿以后的发育而言可具有特定的后果。例如，Fantuzzi等人提出全身性轻度炎症和亚最佳消化道微生物群可与后来的肥胖的发展有关(Fantuzzi G.“Adipose tissue，adipokines，and inflammation”(“脂肪组织、脂肪因子和炎症”)J Allergy Clin Immunol.2005；115：911-919)。
简言之，越来越多证据的涌现表明生命早期建立适当的肠内微生物群可能是以后的健康发育中的一个重要的因素。此外，不适当的肠内微生物群可能伴随着消化道内的局部炎症和低水平的全身性炎症，其对整体健康有其自身的不利影响。
对所有的婴儿都推荐母乳喂养。除各种大量营养素之外，已知人乳包含许多生物活性营养素，即广义上被归类为蛋白质、碳水化合物或脂肪但在其提供热量之外还具有特定功能的化合物。所述生物活性营养素的一大类别是人乳寡糖，这是一组以不同的量存在于人乳中的超过100种的寡糖，但例如在牛奶中其数量或种类与人乳中不同。这些各种各样的寡糖的数量和功能仍然在研究解释中，尽管其中某些被已经被认为与例如降低病原体附着宿主上皮细胞的能力有关。
然而，在一些情况下由于医学原因母乳喂养不充足或不成功或母亲选择不进行母乳喂养。为这些情况开发了婴儿配方产品。绝大多数的婴儿配方产品是基于牛奶的，如上所述，其在多样性或含量方面不像人乳那样富含功能性碳水化合物。
发明概述
发明人惊奇地发现对新生儿施用具有键合于一、二和/或多价的N-乙酰基乳糖胺结构的乳糖的结构的寡糖对免疫系统的训练特别有效，其在新生儿期肠内微生物群的建立期间促进下调不适当的促炎应答，从而同样能下调不适当的免疫应答。
因此，在第一个方面，本发明提供了选自乳糖-N-四糖(lacto-N-tetraose)、乳糖-N-新四糖(lacto-N-neotetraose)、乳糖-N-六糖(lacto-N-hexaose)、乳糖-N-新六糖(lacto-N-neohexaose)、乳糖-对-N-六糖(para-lacto-N-hexaose)、乳糖-对-N-新六糖(para-lacto-N-neohexaose)、乳糖-N-八糖(lacto-N-octaose)、乳糖-N-新八糖(lacto-N-neooctaose)、异-乳糖-N-八糖(iso-lacto-N-octaose)、乳糖-对-N-八糖(para-lacto-N-octaose)和乳糖-N-十糖(lacto-N-decaose)的寡糖在制备用于婴儿的药物和用于婴儿的治疗性营养组合物中的应用，所述药物和治疗性营养组合物用于使新生儿中免疫应答成熟。
第二个方面，本发明提供了选自乳糖-N-四糖、乳糖-N-新四糖、乳糖-N-六糖、乳糖-N-新六糖、乳糖-对-N-六糖、乳糖-对-N-新六糖、乳糖-N-八糖、乳糖-N-新八糖、异-乳糖-N-八糖、乳糖-对-N-八糖和乳糖-N-十糖的寡糖在制备用于婴儿的药物和用于婴儿的治疗性营养组合物中的应用，所述药物和治疗性营养组合物用于调节新生儿的免疫系统以在婴儿生命的最初数周促进可与在那些人乳喂养的婴儿中所发现的有益的肠内微生物群相比拟的有益的肠内微生物群的发展。
第三个方面，本发明提供了选自乳糖-N-四糖、乳糖-N-新四糖、乳糖-N-六糖、乳糖-N-新六糖、乳糖-对-N-六糖、乳糖-对-N-新六糖、乳糖-N-八糖、乳糖-N-新八糖、异-乳糖-N-八糖、乳糖-对-N-八糖和乳糖-N-十糖的寡糖在制备用于施用于新生儿的药物和治疗性营养组合物中的应用，所述药物和治疗性营养组合物用于在所述婴儿中降低随后出现变态反应的风险。
本发明还涉及在新生儿中促进免疫应答成熟的方法，所述方法通过对有需要的新生儿施用治疗有效量的选自以下的寡糖实现：乳糖-N-四糖、乳糖-N-新四糖、乳糖-N-六糖、乳糖-N-新六糖、乳糖-对-N-六糖、乳糖-对-N-新六糖、乳糖-N-八糖、乳糖-N-新八糖、异-乳糖-N-八糖、乳糖-对-N-八糖和乳糖-N-十糖。
本发明进一步涉及在婴儿生命的最初数周促进可与在那些人乳喂养的婴儿中所发现的有益的肠内微生物群相比拟的有益的肠内微生物群的发展的方法，所述方法通过对有需要的新生儿施用治疗有效量的选自以下的寡糖实现：乳糖-N-四糖、乳糖-N-新四糖、乳糖-N-六糖、乳糖-N-新六糖、乳糖-对-N-六糖、乳糖-对-N-新六糖、乳糖-N-八糖、乳糖-N-新八糖、异-乳糖-N-八糖、乳糖-对-N-八糖和乳糖-N-十糖。
最后，本发明还涉及在婴儿中降低随后出现变态反应的风险的方法，所述方法通过对有需要的新生儿施用治疗有效量的选自以下的寡糖实现：乳糖-N-四糖、乳糖-N-新四糖、乳糖-N-六糖、乳糖-N-新六糖、乳糖-对-N-六糖、乳糖-对-N-新六糖、乳糖-N-八糖、乳糖-N-新八糖、异-乳糖-N-八糖、乳糖-对-N-八糖和乳糖-N-十糖。
不希望受理论束缚，本发明人相信在肠腔的具有键合于一、二和/或多价N-乙酰基乳糖胺结构的乳糖的结构的寡糖可作为促炎因子的“诱饵”，阻止它们与其天然配体相结合，并由此缓解促炎应答。具体而言，半乳凝素-3是一个涉及多种促炎反应诸如嗜中性粒细胞(例如IL8)活化的可溶的β-半乳糖苷-结合蛋白。嗜中性粒细胞作为募集到感染部位的主要的吞噬性白细胞参与先天性免疫应答。半乳凝素-3能由消化道上皮释放以活化免疫系统。
对半乳凝素-3缺失小鼠(gal-/-)的研究显示半乳凝素-3调节对病原体的先天性和适应性免疫应答的调节作用(Bernardes等人，2006)。与野生型对照相比，在相似的病原体负荷下，gal-/-小鼠显示出低得多的炎症应答、对消化道粘膜固有层的较低的白细胞浸润且没有消化道坏死。因而能得出以下结论：半乳凝素-3的缺乏导致较弱的炎症应答。
末端为半乳糖β-1，4N-乙酰葡糖胺诸如乳糖-N-新四糖的聚糖类结合半乳凝素-3。如之前对半乳凝素-9的研究所显示，游离的半乳凝素-结合聚糖类能干扰半乳凝素与标靶配体结合，由此改变靶标配体行为(Ohtsubo等人，2005)。聚合的N-乙酰基乳糖胺单元越多，对半乳凝素-3的亲和力越高且诱饵功能越强。
此外，通过树突细胞产生较多的IL12和IFN-γ证明了gal3-/-小鼠显示较高的Th1应答(Bernardes等人，2006)。辅助T细胞在适应性免疫中起关键作用。Th1细胞对细胞-介导的免疫应答非常重要，且Th2细胞促进体液免疫。Th1和Th2应答是相反-调节的，即Th1细胞产生的细胞因子抑制Th2功能，且反之亦然。已显示向Th2-偏倚的免疫应答对成功妊娠的维持起决定作用，且其还在出生及生命的最初几个月中占据优势。出生后对微生物抗原的暴露优选地引起Th1应答，已提出其在新生儿中抗衡Th2-极化的细胞因子的产生。在早期的Th1应答不充分的情况下，Th2-型细胞因子(IL-4、IL-5和IL-13)的生成进一步持续，导致IgE生成并因而导致变应性疾病。得出的结论是：上文所述的诱饵活性还有助于使得免疫系统偏向于Th1应答，由此训练免疫系统并降低生命早期出现变态反应的风险。
发明详述
在本说明书中，下文术语具有以下含义：
“可与在那些人乳喂养的婴儿中所发现的有益的肠内微生物群相比拟的有益的肠内微生物群”是指主要包括双歧杆菌属和乳杆菌属菌种的可观群体而不包括如拟杆菌属、梭菌属和链球菌属(Streptococci)的菌种的可观群体的肠内微生物；
“新生儿”是指在生命的最初两个月的婴儿。
除非另有说明，所有提及的百分比为以重量计的百分比。
本发明涉及选自以下的寡糖的应用：乳糖-N-四糖、乳糖-N-新四糖、乳糖-N-六糖、乳糖-N-新六糖、乳糖-对-N-六糖、乳糖-对-N-新六糖、乳糖-N-八糖、乳糖-N-新八糖、异-乳糖-N-八糖、乳糖-对-N-八糖和乳糖-N-十糖。优选的寡糖是乳糖-N-四糖(LNT)和乳糖-N-新四糖(LNnT)。LNT和LNnT可通过使用糖基转移酶将糖单元由供体部分酶促转移至受体部分而化学合成，如例如在US专利5,288,637中所述。或者，LNT和LNnT可通过将游离的或结合于寡糖(例如乳果糖)的己酮糖类(例如果糖)化学转化为N-乙酰己糖胺或含寡糖的N-乙酰己糖胺，如Wrodnigg，T.M.；Stutz，A.E.(1999)Angew.Chem.Int.Ed.38：827-828中所述。然后可将该方式制备的N-乙酰基乳糖胺转移至作为受体部分的乳糖。
治疗性营养组合物优选为包含选自以下的寡糖的婴儿配方产品：乳糖-N-四糖、乳糖-N-新四糖、乳糖-N-六糖、乳糖-N-新六糖、乳糖-对-N-六糖、乳糖-对-N-新六糖、乳糖-N-八糖、乳糖-N-新八糖、异-乳糖-N-八糖、乳糖-对-N-八糖和乳糖-N-十糖，其含量基于干重为0.1至3g/100g组合物。
依据本发明使用的婴儿配方产品可包含不超过2.0g/100千卡、优选1.8至2.0g/100千卡的量的蛋白质源。认为蛋白质的种类对于本发明不是至关重要的，只要满足必需氨基酸含量的最小要求并且确保良好的生长即可，但是优选以重量计50％以上的蛋白质源是乳清。因此，可使用基于乳清、酪蛋白及其混合物的蛋白质源，以及基于大豆的蛋白质源。当涉及乳清蛋白时，该蛋白质源可基于酸性乳清或甜乳清或其混合物，并且可以以任何期望的比例包含α-乳清蛋白和β-乳球蛋白。
蛋白质可以是完整的蛋白质或经水解的蛋白质，或完整的和经水解的蛋白质的混合物。可能希望提供部分水解的蛋白质(水解程度在2至20％)，例如对于认为有发生牛奶变态反应风险的婴儿而言。如果需要经水解的蛋白质，根据需要进行水解操作，这是本领域已知的。例如，可通过在一个或多个步骤中酶促水解乳清片段来制备乳清蛋白水解物。如果用作起始材料的乳清片段基本上不含乳糖，那么发现该蛋白质在水解过程中受到少得多的赖氨酸阻断。这使得赖氨酸阻断的程度能够从以总赖氨酸的重量计大约15％减少至以赖氨酸重量计少于大约10％；例如以赖氨酸重量计大约7％，这极大地提高了蛋白质源的营养价值。
婴儿配方产品可包含碳水化合物源。尽管优选的碳水化合物源是乳糖，但是可以使用在婴儿配方产品中常规存在的任何碳水化合物源诸如乳糖、蔗糖、麦芽糖糊精、淀粉及其混合物。优选地，碳水化合物源提供配方产品总能量的35至65％。
婴儿配方产品可包含脂质源。脂质源可以是适合用于婴儿配方产品的任何脂质或脂肪。优选的脂肪源包括棕榈油酸甘油酯、高油酸向日葵油和高油酸红花油。也可加入必需脂肪酸亚油酸和α-亚麻酸，同样可加入少量的包含大量预制的花生四烯酸和二十二碳六烯酸的油，例如鱼油或微生物油。总之，脂肪含量优选例如提供配方产品总能量的30至55％。脂肪源优选具有的n-6比n-3脂肪酸的比率为大约5∶1至大约15∶1，例如大约8∶1至大约10∶1。
婴儿配方产品还可包含认为在日常饮食中是必需的所有维生素和矿物质，并且以营养显著的量包含之。已确定了某些维生素和矿物质的最小需要量。任选存在于婴儿配方产品中的矿物质、维生素和其他营养素的实例包括维生素A、维生素B1、维生素B2、维生素B6、维生素B12、维生素E、维生素K、维生素C、维生素D、叶酸、肌醇、烟酸、生物素、泛酸、胆碱、钙、磷、碘、铁、镁、铜、锌、锰、氯化物、钾、钠、硒、铬、钼、牛磺酸和L-肉碱。通常以盐的形式加入矿物质。特定矿物质和其他维生素的存在和量将根据预期婴儿群体而变化。
如果需要，婴儿配方产品可包含乳化剂和稳定剂，如大豆卵磷脂、甘油单酯和甘油二酯的柠檬酸酯等。
婴儿配方产品优选还包含0.3至10％的量的至少一种益生元。益生元是不可消化的食物成分，通过选择性刺激一种或有限数量的结肠中细菌的生长和/或活性有益地作用于宿主，并因而改善宿主健康。该成分不可消化的意思是其在胃或小肠中不被破坏和吸收，且因而完整的到达结肠，在这里它们被有益的细菌选择性地发酵。益生元的实例包括某些寡糖，诸如低聚果糖(FOS)和半乳寡聚糖(GOS)。可以使用益生元的组合，诸如90％GOS与10％短链低聚果糖(诸如商品名为的产品)或10％菊粉(诸如商品名为
的产品)而。特别优选的益生元的组合是70％短链低聚果糖和30％菊粉。
婴儿配方产品还可包含至少一种益生菌株。益生菌是一种微生物细胞制剂或微生物细胞的组分，对宿主的健康或良好状态具有有益的作用。适合的益生菌株包括可从芬兰的Valio Oy获得的商标为LGG的鼠李糖乳杆菌(Lactobacillus rhamnosus)ATCC 53103、鼠李糖乳杆菌CGMCC 1.3724和副干酪乳杆菌(Lactobacillus paracasei)CNCM I-2116、BioGaia A.B销售的商标为Reuteri的罗伊氏乳杆菌(Lactobacillus reuteri)菌株、新西兰BLIS技术有限公司销售的称为K12的唾液链球菌(Streptococcus salivarius)DSM 13084、尤其是丹麦的Christian Hansen公司销售的商标为Bb 12的乳双歧杆菌(Bifidobacterium lactis)CNCM I-3446、日本的Morinaga乳业有限公司销售的商标为BB536的长双歧杆菌(Bifidobacterium longum)ATCC BAA-999、Rhodia销售的商标为Bb-03的短双歧杆菌(Bifidobacterium breve)菌株、Morinaga销售的商标为M-16V的短双歧杆菌菌株、Procter&Gamble公司销售的商标为Bifantis的婴儿双歧杆菌(Bifidobacterium infantis)菌株和Institut Rosell(Lallemand)销售的商标为R0070的短双歧杆菌菌株，其量为10e3至10e12cfu/g粉末，更优选为10e7至10e12cfu/g粉末。
婴儿配方产品可任选包含具有有益作用的其他物质，诸如乳铁蛋白、核苷酸、核苷等。
婴儿配方产品可以以任何合适的方式制备。例如，可通过以适当的比例将蛋白质、碳水化合物源以及脂肪源混合在一起而制备。如果使用乳化剂，则可在此时加入。维生素和矿物质可在此时加入但通常稍后加入以避免热降解。任何亲脂性维生素、乳化剂等可在搅拌前溶解于脂肪源中。然后可将水、优选已进行反渗透的水加入混合以形成液体混合物。水的适宜温度为约50℃至约80℃以利于成分的分散。可使用商购可得的液化器以形成液体混合物。如果最终产物将是液体形式，在该时期加入N-乙酰基乳糖胺和/或包含N-乙酰基乳糖胺的寡糖。如果最终产物将是粉末形式，如果需要则在该时期同样可加入寡糖。然后将液体混合物(例如分两个阶段)匀化。
然后可将液体混合物热处理以降低细菌载量(load)，例如通过快速加热液体混合物至约80℃至大约150℃的温度范围约5秒至约5分钟来进行。这可通过蒸汽注射、高压釜或通过热交换器进行；例如板式热交换器。
然后，可将液体混合物冷却至约60℃至约85℃；例如通过瞬时冷却法进行。然后可将液体混合物再次匀化，例如分两个阶段，第一阶段约10MPa至约30MPa，第二阶段约2MPa至约10MPa。然后可将匀化的混合物进一步冷却以加入任何热敏感成分，诸如维生素和矿物质。此时适宜地调节匀化混合物的pH和固体成分。
将匀化的混合物转移至合适的干燥装置诸如喷雾干燥器或冷冻干燥器并转化成粉末。该粉末的含水量应小于约5％重量。如果使用寡糖时，则可在此时与益生细菌菌株通过干燥-混合而加入。
如果优选液体产物，可将匀化的化合物灭菌，然后无菌填装于适合的容器中，或可首先填装于容器中然后杀菌。
在另一个实施方案中，所述组合物可以是包含足以达到期望作用的量的选自以下的寡糖的补充剂：乳糖-N-四糖、乳糖-N-新四糖、乳糖-N-六糖、乳糖-N-新六糖、乳糖-对-N-六糖、乳糖-对-N-新六糖、乳糖-N-八糖、乳糖-N-新八糖、异-乳糖-N-八糖、乳糖-对-N-八糖和乳糖-N-十糖。优选地寡糖的日剂量是0.1至3g。包含在补充剂中的寡糖的量将依据如何施用该补充剂而选择。例如，如果补充剂每天施用两次，各补充剂可包含0.05至1.5g寡糖。补充剂应当是适于施用于新生儿的形式，且只包含那些适于该年龄组的辅助剂和赋形剂。
本发明参照下面的实施例进一步说明：
实施例1
下面提供本发明中所使用的适合的婴儿配方产品的组合物的实例。
| 营养成分 | 每100千卡 | 每升 |
| 能量(千卡) | 100 | 670 |
| 蛋白质(g) | 1.83 | 12.3 |
| 脂肪(g) | 5.3 | 35.7 |
| 亚油酸(g) | 0.79 | 5.3 |
| α-亚麻酸(mg) | 101 | 675 |
| 乳糖(g) | 11.2 | 74.7 |
| 矿物质(g) | 0.37 | 2.5 |
| Na(mg) | 23 | 150 |
| K(mg) | 89 | 590 |
| Cl(mg) | 64 | 430 |
| Ca(mg) | 62 | 410 |
| P(mg) | 31 | 210 |
| Mg(mg) | 7 | 50 |
| Mn(μg) | 8 | 50 |
| Se(μg) | 2 | 13 |
| 维生素A(μg RE) | 105 | 700 |
| 维生素D(μg) | 1.5 | 10 |
| 维生素E(mg TE) | 0.8 | 5.4 |
| 维生素K1(μg) | 8 | 54 |
| 维生素C(mg) | 10 | 67 |
| 维生素B1(mg) | 0.07 | 0.47 |
| 维生素B2(mg) | 0.15 | 1.0 |
| 烟酸(mg) | 1 | 6.7 |
| 维生素B6(mg) | 0.075 | 0.50 |
| 叶酸(μg) | 9 | 60 |
| 泛酸(mg) | 0.45 | 3 |
| 维生素B12(μg) | 0.3 | 2 |
| 生物素(μg) | 2.2 | 15 |
| 胆碱(mg) | 10 | 67 |
| Fe(mg) | 1.2 | 8 |
| I(μg) | 15 | 100 |
| Cu(mg) | 0.06 | 0.4 |
| Zn(mg) | 0.75 | 5 |
| LNnT | 37 | 250 |
Claims (10)
1.选自乳糖-N-四糖、乳糖-N-新四糖、乳糖-N-六糖、乳糖-N-新六糖、乳糖-对-N-六糖、乳糖-对-N-新六糖、乳糖-N-八糖、乳糖-N-新八糖、异-乳糖-N-八糖、乳糖-对-N-八糖和乳糖-N-十糖的寡糖在制备用于婴儿的药物和用于婴儿的治疗性营养组合物中的应用，所述药物和治疗性营养组合物用于使新生儿中免疫应答成熟。
2.选自乳糖-N-四糖、乳糖-N-新四糖、乳糖-N-六糖、乳糖-N-新六糖、乳糖-对-N-六糖、乳糖-对-N-新六糖、乳糖-N-八糖、乳糖-N-新八糖、异-乳糖-N-八糖、乳糖-对-N-八糖和乳糖-N-十糖的寡糖在制备用于婴儿的药物和用于婴儿的治疗性营养组合物中的应用，所述药物和治疗性营养组合物用于调节新生儿的免疫系统以在所述婴儿生命的最初数周促进可与在那些人乳喂养的婴儿中所发现的有益的肠内微生物群相比拟的有益的肠内微生物群的发展。
3.选自乳糖-N-四糖、乳糖-N-新四糖、乳糖-N-六糖、乳糖-N-新六糖、乳糖-对-N-六糖、乳糖-对-N-新六糖、乳糖-N-八糖、乳糖-N-新八糖、异-乳糖-N-八糖、乳糖-对-N-八糖和乳糖-N-十糖的寡糖在制备用于施用于新生儿的药物和治疗性营养组合物中的应用，所述药物和治疗性营养组合物用于在所述婴儿中降低随后出现变态反应的风险。
4.权利要求1、2或3的应用，其中寡糖是乳糖-N-四糖或乳糖-N-新四糖。
5.前述权利要求中任意一项的应用，其中治疗性营养组合物是婴儿配方产品。
6.权利要求5的应用，其中每100g婴儿配方产品包含0.1至3g的选自以下的寡糖：乳糖-N-四糖、乳糖-N-新四糖、乳糖-N-六糖、乳糖-N-新六糖、乳糖-对-N-六糖、乳糖-对-N-新六糖、乳糖-N-八糖、乳糖-N-新八糖、异-乳糖-N-八糖、乳糖-对-N-八糖和乳糖-N-十糖。
7.权利要求5或6的应用，其中婴儿配方产品还包含益生菌株，其量基于干重为10e3至10e12cfu/g配方产品。
8.权利要求5至7中任意一项的应用，其中婴儿配方产品还包含占配方产品重量的0.3至10％的量的至少一种益生元。
9.权利要求1至4中任意一项的应用，其中药物是补充剂，其日剂量包含0.1至3g选自以下的寡糖：乳糖-N-四糖、乳糖-N-新四糖、乳糖-N-六糖、乳糖-N-新六糖、乳糖-对-N-六糖、乳糖-对-N-新六糖、乳糖-N-八糖、乳糖-N-新八糖、异-乳糖-N-八糖、乳糖-对-N-八糖和乳糖-N-十糖。
10.前述权利要求中任意一项的应用，其中药物或治疗性营养组合物在分娩后立即施用于婴儿，并在其后施用至少两个月。
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103889240A (zh) * | 2011-10-18 | 2014-06-25 | 雀巢产品技术援助有限公司 | 用于增加胰岛素敏感性和/或降低胰岛素抵抗性的组合物 |
| CN104023560A (zh) * | 2011-08-29 | 2014-09-03 | 雅培制药有限公司 | 用于预防胃肠道损伤和/或促进胃肠道愈合的人乳寡糖 |
| CN107847509A (zh) * | 2015-08-04 | 2018-03-27 | 雀巢产品技术援助有限公司 | 用于诱导与母乳喂养的婴儿的肠道微生物群接近的肠道微生物群的具有2FL和LNnT的营养组合物 |
| CN107955082A (zh) * | 2017-12-11 | 2018-04-24 | 江南大学 | 幽门螺旋杆菌脂多糖外核心八糖的制备方法 |
| CN109414447A (zh) * | 2016-06-24 | 2019-03-01 | 格礼卡姆股份公司 | 包括hmo的组合物、其制备和用于预防和/或治疗病毒和/或细菌感染的用途 |
| CN110301646A (zh) * | 2012-03-27 | 2019-10-08 | 雅培制药有限公司 | 用于使用人乳寡糖调节细胞介导的免疫的方法 |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2465508A1 (en) * | 2010-11-23 | 2012-06-20 | Nestec S.A. | Composition comprising hydrolysed proteins and oligosaccharides for treating skin diseases |
| EP2454948A1 (en) | 2010-11-23 | 2012-05-23 | Nestec S.A. | Oligosaccharide mixture and food product comprising this mixture, especially infant formula |
| EP2465509A1 (en) * | 2010-11-23 | 2012-06-20 | Nestec S.A. | Oligosaccharide composition for treating acute respiratory tract infections |
| US8802650B2 (en) | 2010-12-31 | 2014-08-12 | Abbott Laboratories | Methods of using human milk oligosaccharides for improving airway respiratory health |
| NZ612455A (en) * | 2010-12-31 | 2015-02-27 | Abbott Lab | Human milk oligosaccharides to promote growth of beneficial bacteria |
| MX355424B (es) | 2010-12-31 | 2018-04-18 | Abbott Lab | Oligosacáridos de leche humana para modular la inflamación. |
| CA2822497C (en) | 2010-12-31 | 2020-07-28 | Abbott Laboratories | Methods for reducing the incidence of oxidative stress using human milk oligosaccharides, vitamin c and anti-inflammatory agents |
| SG191392A1 (en) | 2010-12-31 | 2013-08-30 | Abbott Lab | Methods for decreasing the incidence of necrotizing enterocolitis in infants, toddlers, or children using human milk oligosaccharides |
| NZ612472A (en) | 2010-12-31 | 2015-02-27 | Abbott Lab | Nutritional compositions comprising human milk oligosaccharides and nucleotides and uses thereof for treating and/or preventing enteric viral infection |
| US8703737B2 (en) | 2010-12-31 | 2014-04-22 | Abbott Laboratories | Nutritional formulations including human milk oligosaccharides and antioxidants and uses thereof |
| AU2012273206B2 (en) | 2011-06-20 | 2015-09-24 | H.J. Heinz Company Brands Llc | Probiotic compositions and methods |
| MY182335A (en) | 2011-07-22 | 2021-01-19 | Abbott Lab | Galactooligosaccharides for preventing injury and/or promoting healing of the gastrointestinal tract |
| EP2798069B1 (en) * | 2011-12-15 | 2017-03-29 | Washington University | Porcine knob xenotype chimeric adenoviral vector for dendritic cell infection |
| MX2016013064A (es) * | 2014-04-08 | 2017-01-26 | Abbott Lab | Metodos para mejorar las respuestas inmune innata y/o deteccion de patogenos de la mucosa mediante oligosacaridos de la leche humana. |
| EP3264920B1 (en) * | 2015-03-05 | 2020-12-16 | Société des Produits Nestlé S.A. | Compositions for use in the prevention or treatment of otitis or bronchitis in infants or young children |
| CN109562117A (zh) | 2016-08-04 | 2019-04-02 | 雀巢产品技术援助有限公司 | 具有2FL和LNnT的营养组合物，用于通过作用于肠道微生物群生态失调来预防和/或治疗非轮状病毒腹泻 |
| JP2023545766A (ja) | 2020-10-16 | 2023-10-31 | ソシエテ・デ・プロデュイ・ネスレ・エス・アー | 乳児又は低年齢の小児用フォーミュラ |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE462134B (sv) * | 1987-10-22 | 1990-05-14 | Biocarb Ab | Livsmedel innehaallande lacto-n-tetraos och foerfarande foer dess framstaellning |
| EP0481038B1 (en) * | 1990-04-16 | 2002-10-02 | The Trustees Of The University Of Pennsylvania | Saccharide compositions, methods and apparatus for their synthesis |
| US6204431B1 (en) * | 1994-03-09 | 2001-03-20 | Abbott Laboratories | Transgenic non-human mammals expressing heterologous glycosyltransferase DNA sequences produce oligosaccharides and glycoproteins in their milk |
| US5906982A (en) * | 1997-03-31 | 1999-05-25 | Abbott Laboratories | Nutritional formulations containing Lacto-N-neoTetraose |
| US6045854A (en) * | 1997-03-31 | 2000-04-04 | Abbott Laboraties | Nutritional formulations containing oligosaccharides |
| DE19958985A1 (de) * | 1999-12-07 | 2001-06-13 | Nutricia Nv | Oligosaccharidmischung |
| 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 |
| FI20010118A (fi) * | 2001-01-19 | 2002-07-20 | Carbion Oy | Uudet helicobacter pylori reseptorit ja niiden käyttö |
| DE10147100A1 (de) * | 2001-09-25 | 2003-04-17 | Numico Res B V | Antiinfektive Kohlenhydrate |
| JP5219329B2 (ja) * | 2002-06-28 | 2013-06-26 | ネステク、リミテッド | 下痢の予防又は治療用の医薬組成物 |
| CA2530437C (en) * | 2003-06-23 | 2011-11-15 | Nestec S.A. | Nutritional formula for optimal gut barrier function |
| ES1056525Y (es) * | 2004-01-13 | 2004-07-16 | Perez Alfredo Pineiro | Halador de tres rodillos para redes y aparejos de pesca. |
| US7303745B2 (en) * | 2005-04-15 | 2007-12-04 | Bristol-Myers Squibb Company | Method for preventing or treating the development of respiratory allergies |
| EP1714660A1 (en) * | 2005-04-21 | 2006-10-25 | N.V. Nutricia | Uronic acid and probiotics |
| RU2462252C2 (ru) * | 2006-03-10 | 2012-09-27 | Н.В. Нютрисиа | Применение неусвояемых сахаридов для лучшей адаптации младенцев после рождения |
| ES2362210T3 (es) * | 2006-03-13 | 2011-06-29 | Glycom A/S | Derivados de lactosamina novedosos. |
| US8197872B2 (en) * | 2007-05-17 | 2012-06-12 | The Regents Of The University Of California | Human milk oligosaccharides to promote growth of beneficial gut bacteria |
-
2008
- 2008-11-07 PT PT88484662T patent/PT2217246E/pt unknown
- 2008-11-07 AU AU2008324105A patent/AU2008324105B2/en active Active
- 2008-11-07 MY MYPI2010002042A patent/MY159076A/en unknown
- 2008-11-07 WO PCT/EP2008/065143 patent/WO2009060073A1/en active Application Filing
- 2008-11-07 PL PL08848466T patent/PL2217246T3/pl unknown
- 2008-11-07 RU RU2010123176/15A patent/RU2486904C2/ru active
- 2008-11-07 EP EP08848466.2A patent/EP2217246B1/en not_active Revoked
- 2008-11-07 CN CN2008801240700A patent/CN101909636A/zh active Pending
- 2008-11-07 US US12/741,997 patent/US20100233198A1/en not_active Abandoned
- 2008-11-07 SG SG2012081311A patent/SG185948A1/en unknown
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- 2008-11-07 CA CA2705014A patent/CA2705014A1/en not_active Abandoned
- 2008-11-07 ES ES08848466.2T patent/ES2528469T3/es active Active
- 2008-11-07 MX MX2010005132A patent/MX2010005132A/es active IP Right Grant
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2010
- 2010-06-07 ZA ZA2010/04053A patent/ZA201004053B/en unknown
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104023560A (zh) * | 2011-08-29 | 2014-09-03 | 雅培制药有限公司 | 用于预防胃肠道损伤和/或促进胃肠道愈合的人乳寡糖 |
| CN103889240A (zh) * | 2011-10-18 | 2014-06-25 | 雀巢产品技术援助有限公司 | 用于增加胰岛素敏感性和/或降低胰岛素抵抗性的组合物 |
| CN103889240B (zh) * | 2011-10-18 | 2016-09-14 | 雀巢产品技术援助有限公司 | 用于增加胰岛素敏感性和/或降低胰岛素抵抗性的组合物 |
| CN110301646A (zh) * | 2012-03-27 | 2019-10-08 | 雅培制药有限公司 | 用于使用人乳寡糖调节细胞介导的免疫的方法 |
| CN107847509A (zh) * | 2015-08-04 | 2018-03-27 | 雀巢产品技术援助有限公司 | 用于诱导与母乳喂养的婴儿的肠道微生物群接近的肠道微生物群的具有2FL和LNnT的营养组合物 |
| CN107847509B (zh) * | 2015-08-04 | 2021-06-01 | 雀巢产品有限公司 | 具有2FL和LNnT的营养组合物 |
| CN109414447A (zh) * | 2016-06-24 | 2019-03-01 | 格礼卡姆股份公司 | 包括hmo的组合物、其制备和用于预防和/或治疗病毒和/或细菌感染的用途 |
| CN107955082A (zh) * | 2017-12-11 | 2018-04-24 | 江南大学 | 幽门螺旋杆菌脂多糖外核心八糖的制备方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| BRPI0820175B1 (pt) | 2019-02-12 |
| BRPI0820175B8 (pt) | 2022-11-22 |
| PL2217246T3 (pl) | 2015-06-30 |
| BRPI0820175A2 (pt) | 2015-06-16 |
| AU2008324105B2 (en) | 2014-01-30 |
| ZA201004053B (en) | 2016-08-31 |
| EP2217246A1 (en) | 2010-08-18 |
| MY159076A (en) | 2016-12-15 |
| SG185948A1 (en) | 2012-12-28 |
| RU2486904C2 (ru) | 2013-07-10 |
| EP2217246B1 (en) | 2014-12-17 |
| RU2010123176A (ru) | 2011-12-20 |
| CA2705014A1 (en) | 2009-05-14 |
| AU2008324105A1 (en) | 2009-05-14 |
| WO2009060073A1 (en) | 2009-05-14 |
| US20100233198A1 (en) | 2010-09-16 |
| ES2528469T3 (es) | 2015-02-10 |
| PT2217246E (pt) | 2015-02-10 |
| MX2010005132A (es) | 2010-06-02 |
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