CN112890200A - 用于促进低体重婴幼儿生长追赶的一种营养组合物 - Google Patents
用于促进低体重婴幼儿生长追赶的一种营养组合物 Download PDFInfo
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- CN112890200A CN112890200A CN202110250196.XA CN202110250196A CN112890200A CN 112890200 A CN112890200 A CN 112890200A CN 202110250196 A CN202110250196 A CN 202110250196A CN 112890200 A CN112890200 A CN 112890200A
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- lactobacillus
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Abstract
本发明涉及一种包含骨桥蛋白(OPN)和乳低聚糖的营养组合物，所述营养组合物至少包含高浓度骨桥蛋白、一种唾液酸化低聚糖和至少一种N‑乙酰化低聚糖，所述营养组合物可用于婴幼儿的生长追赶及健康生长。
Description
技术领域
本发明涉及包含骨桥蛋白和特定母乳低聚糖的一种营养组合物，所述营养组合物至少包含高浓度骨桥蛋白、一种唾液酸化低聚糖和至少一种N-乙酰化低聚糖，用于婴幼儿的生长追赶及健康生长。
背景技术
追赶生长是指因病理因素导致生长迟缓的婴幼儿在消除病理因素后产生生长加速的现象，最佳时期为出生后第一年。低体重出生儿易发生生长追赶。低出生体重儿是指新生儿分娩时体重＜2500g。目前发现新生儿低出生体重主要受到非遗传因素影响，包括胎儿宫内发育情况和妊娠时间等。孕前营养不良，若孕期不注意营养补充，继续保持孕前饮食习惯和饮食结构，可引发贫血或营养不良程度，导致胎儿宫内发育迟缓，影响胎儿生长速度，导致新生儿低体重的发生。羊水过少，妊娠期高血压也会导致新生儿低体重的发生。低出生体重儿如果后期生长追赶不达标也可能会对后期神经系统及心理行为的发育产生影响，也可能使成年期身高低于同龄人平均身高，另外可能还会增加胰岛素抵抗及冠心病的发生风险及增加成年期相关疾病的发生风险。
出生后的早期营养对婴儿最佳生长发育以及长期健康影响起着至关重要的作用。对母乳喂养的婴儿来说，在生命最初几个月里，母乳是唯一的营养来源。世界卫生组织建议应该在生命的最初六个月完全母乳喂养,母乳是一个复杂的营养液，包含高浓度的乳糖、脂肪、蛋白质和母乳低聚糖(HMO,human milk oligosaccharides)。HMO作为母乳中第三大营养物质，有超过200种结构。HMOs的核心结构包括葡萄糖(Glc)，半乳糖(Gal)，n-乙酰氨基葡萄糖(GlcNAc)，并进一步修饰岩藻糖基(Fuc)和/或n-乙酰神经氨酸(Neu5Ac，唾液酸)。根据唾液酸的存在与否，HMOs可分为中性和酸性两类。大多数HMOs在胃肠道运输过程中没有被消化，因此完整地到达大肠，能够促进婴幼儿早期肠道微生物群的发育和成熟，如促进双歧杆菌的生长和定植。除了调节微生物,HMO还对婴儿有非常多的益处,包括调节上皮细胞免疫反应和肠道细胞增殖和成熟,维持上皮屏障功能,保护胃肠道对细菌和病毒的病原体。此外，还有一些研究证实HMO可以进入系统循环对宿主系统性免疫成熟发挥作用，并参与大脑发育。
骨桥蛋白(OPN,osteopontin)是母乳中重要的免疫刺激因子之一，可促进婴儿免疫系统成熟,保护母乳喂养的婴儿免受病原体感染。研究表明,OPN在肥胖者体内脂肪组织中的表达明显上调,且主要由脂肪组织巨噬细胞所分泌.它可通过介导巨噬细胞的趋化和增强单核细胞趋化蛋白(MCP)-1的作用来促进巨噬细胞在脂肪组织中的蓄积,还可引起肥胖相关的脂肪组织炎性反应因子的增加,在肥胖、胰岛素抵抗的发生过程中起重要作用。然而OPN对于肥胖的调节作用目前公开的研究结果较少，特别是对于婴幼儿的体重的影响尚无报道。
发明内容
令人惊喜地发现，与用传统营养组合物喂养的婴儿相比，包含OPN和特定母乳低聚糖的营养组合物可协同提高低体重出生婴幼儿的生长速度，以获得更接近于母乳喂养婴儿所获得的效果。
因此，本发明提供了一种包含OPN和特定母乳低聚糖的营养组合物，所述特定母乳低聚糖至少包含一种唾液酸化低聚糖和至少一种N-乙酰化低聚糖。
在一个具体实施方案中，所述特定母乳低聚糖至少包含LDFT(乳糖二岩藻四糖)、3'SL(3’唾液乳糖)、LNT(乳-N-新四糖)、2-FL(2-岩藻糖基乳糖)和LNnT(乳糖-N-新四糖)中的两种或多种。
在一个具体实施方案中，所述营养组合物至少包含OPN、LDFT(乳糖二岩藻四糖)、3'-SL(3'-唾液酸乳糖)、2’-FL(2’-岩藻糖基乳糖)和LNnT(乳糖-N-新四糖)中的两种或多种。在一个具体实施方案中，所述营养组合物中骨桥蛋白(OPN)与总低聚糖的质量比例是1:20-200。
在一个具体实施方案中，所述营养组合物中唾液酸化低聚糖的含量为10-25wt％，更为优选的，所述唾液酸化低聚糖中包含的3'-唾液酸乳糖(3'-SL)占所述营养组合物总重量的10％-25％。
在一个具体实施方案中，所述营养组合物包含以重量百分比计35％-50％的岩藻糖基化的中性低聚糖，更为优选的，所述岩藻糖基化的中性低聚糖中包含的2’-岩藻糖基乳糖(2’-FL)占所述营养组合物总重量的25％-45％，乳糖二岩藻四糖(LDFT)占所述营养组合物总重量的10％～25％。
在一个具体实施方案中所述营养组合物包含5-35wt％的N-乙酰化低聚糖的中性低聚糖，更为优选的，所述N-乙酰化低聚糖的中性低聚糖中包含的乳糖-N-新四糖(LNnT)占所述营养组合物总重量的5％-35％。
在一个具体实施方案中，所述营养组合物为包含低聚糖的个性化营养组合物，所述低聚糖的浓度为每100g营养组合物中含有10-10000mg低聚糖。本发明的另一个目的涉及上述营养组合物的用途。
在一个具体实施方案中，所述营养组合物用于促进低体重婴幼儿的生长追赶，使其接近同年龄段的母乳喂养婴儿的生长速度。
附图说明
附图用来提供对本发明的进一步理解，并且构成说明书的一部分，与本发明的实施例一起用于解释本发明，并不构成对本发明的限制。在附图中：
图1 T1三个时期低体重与高体重组母乳低聚糖含量对比图；
图2 T2三个时期低体重与高体重组母乳低聚糖含量对比图；
图3 T3三个时期低体重与高体重组母乳低聚糖含量对比图。
具体实施方式
以下结合附图对本发明的优选实施例进行说明，应当理解，此处所描述的优选实施例仅用于说明和解释本发明，并不用于限定本发明。
实施例1母乳低聚糖特定种类与婴儿体重的关系1从医院招募28名婴儿志愿者，入选标准为健康、足月儿(胎龄≥37周)、阴道分娩；经过医学上证明是健康婴儿：无症状和无疾病体征。参加实验的婴儿母亲都将签定知情协议书，并保证在实验期间纯母乳喂养。
2通过在婴儿年龄第一个月T1(30d±2d),第二个月T2(60d±2d),第三个月T3(90d±2d)时收集妈妈母乳样本及测量婴儿的体重。将28名婴儿分为高体重组与低体重组进行分析，测三个时期妈妈母乳里22种母乳低聚糖含量，通过统计发现母乳低聚糖特定种类的含量与婴儿体重相关。
表1婴儿T1有显著差异母乳低聚糖种类含量
表2婴儿T2有显著差异母乳低聚糖种类含量
表3婴儿T3有显著差异母乳低聚糖种类含量
表4母乳中不同时期高低体重组中有显著差异种类HMO含量
由表1及附图1可得，在T1时期三种母乳低聚糖DSLNT,LSTc,LNT在低体重组与高体重组之间均有显著性差异(p＜0.05)，且三种母乳低聚糖在低体重组含量高于高体重组。由表2及附图2可得，在T2时期三种母乳低聚糖LDFT,3’-SL,LNT在低体重组与高体重组之间均有显著性差异(p＜0.05)，且其中LDFT和3’-SL在高体重组含量高于低体重组，LNT在低体重组种含量高于高体重组。由表3及附图3可得，在T3时期有四种母乳低聚糖LDFT,3’-SL,LSTc,LNT在低体重组与高体重组之间均有显著性差异(p＜0.05)，其中LDFT和3’-SL在高体重组种含量高于低体重组，LSTc和LNT在低体重组含量高于高体重组。综上可得，在高体重组中含量高的母乳低聚糖种类为LDFT和3’-SL，在低体重组中含量高的母乳低聚糖为DSLNT,LSTc和LNT。
实施例2母乳低聚糖对低体重婴儿的生长追赶作用
通过研究发现在高体重组中含量高的母乳低聚糖种类为LDFT和3’-SL，母乳低聚糖种类与婴儿体重存在相关。设想可以通过补充OPN和特定的母乳低聚糖实现低体重婴儿的生长追赶。于是设计以下配方，通过动物实验对母乳低聚糖的功效进行验证。
生长追赶验证配方分组如下：
组1：70mg LDFT+120mg 2’-FL+100mg LNnT
组2：70mg 3’-SL+120mg 2’-FL+100mg LNnT
组3：70mg LDFT+70mg 3’-SL+120mg 2’-FL+100mg LNnT
组4：6mg OPN+70mg LDFT+70mg 3’-SL+120mg 2’-FL+100mg LNnT对照组：120mg2’-FL+100mg LNnT
使用时用温生理盐水将上述组方调制为混合物溶液,使得低聚糖在溶液最终浓度为3.9g/L，使得OPN的在溶液最终浓度为65mg/L。
选择8周龄的C57小鼠，其中雌性小鼠20只，雄性小鼠10只，实验前适应性喂养一周后开始实验，雌雄小鼠按2：1比例随机合笼，观察雌鼠有无阴栓及体重有无明显增加，确定雌鼠怀孕后，在怀孕第11天分组：
正常饮食组：给与普通饲料并自由饮食；
限制饮食组：选出较多孕鼠入组，给与普通饲料并周期性给食。
分组结果显示，孕鼠孕后期限制饮食可有效降低仔鼠体重，正常饮食组仔鼠体重为1.21±0.02g,限制饮食组仔鼠体重为1.13±0.02g。
从正常饮食组雌鼠所产的雄性仔鼠中随机选出8只作为正常出生体重组，从限制饮食组雌鼠所产的雄性仔鼠中，按照体重小于正常饮食组仔鼠2个标准差的原则，选出40只作为低出生体重组。两组均母乳喂养至第21天。
在母乳喂养期间，将低出生体重组的40只仔鼠分为如下五组：
对照组(n＝8)：喂养母乳的同时，灌服对照组配方的营养组合物
实验组1(n＝8)：喂养母乳的同时，灌服组1配方的营养组合物
实验组2(n＝8)：喂养母乳的同时，灌服组2配方的营养组合物
实验组3(n＝8)：喂养母乳的同时，灌服组3配方的营养组合物
实验组4(n＝8)：喂养母乳的同时，灌服组4配方的营养组合物
母乳喂养至21天后断奶，从第22天开始至第36天：
正常出生体重组(n＝8):喂养普通饲料；
对照组(n＝8)：喂养普通饲料，同时灌服对照组配方的营养组合物
实验组1(n＝8)：喂养普通饲料，同时灌服组1配方的营养组合物
实验组2(n＝8)：喂养普通饲料，同时灌服组2配方的营养组合物
实验组3(n＝8)：喂养普通饲料，灌服组3配方的营养组合物
实验组4(n＝8)：喂养普通饲料，灌服组4配方的营养组合物
表5小鼠体重测量结果
结果如表5所示，3周龄时，实验组1，实验组2，实验组3和实验组4小鼠体重与对照组有显著性差异(p＜0.05)，且实验组4体重接近于正常出生体重组。5周龄时，实验组1，实验组2，实验组3和实验组4与对照组有显著性差异(p＜0.05)，实验组3与实验组1和实验组2有显著性差异，实验组4与实验组1，2，3均有显著性差异，且实验组4与正常出生体重组无显著性差异(p＞0.05)。
由上述结果可得断乳前，含LDFT+2’FL+LNnT营养组合物和含3’SL+2’FL+LNnT营养组合物，含LDFT+3’SL+2’FL+LNnT营养组合物，含OPN+LDFT+3’SL+2’FL+LNnT营养组合物有利于低出生体重小鼠体增长，断乳前低体重出生小鼠已经出现生长追赶，且含OPN+LDFT+3’SL+2’FL+LNnT组营养组合物喂养的低出生体重小鼠体重接近于正常出生体重组小鼠。OPN,LDFT及3’SL对低出生小鼠体重增长，生长追赶，促进小鼠健康发育有协同增效作用。5周龄时四个实验组的体重与对照组有显著性差异(p＜0.05)，且含OPN+LDFT+3’SL+2’FL+LNnT组营养组合物喂养的低出生体重小鼠体重与正常出生体重组无显著性差异(p＞0.05)，进一步说明OPN，LDFT和3’SL有利于低出生体重儿的生长追赶。因此，含有OPN，LDFT和3’SL的营养组合物可以协同促进低体重出生婴幼儿的生长追赶及健康生长。
显然，本领域的技术人员可以对本发明进行各种改动和变型而不脱离本发明的精神和范围。这样，倘若本发明的这些修改和变型属于本发明权利要求及其等同技术的范围之内，则本发明也意图包含这些改动和变型在内。
Claims (10)
1.一种包含OPN和特定母乳低聚糖的营养组合物，其特征在于，所述特定母乳低聚糖至少包含一种唾液酸化低聚糖、一种岩藻糖基化低聚糖和一种N-乙酰化低聚糖。
2.如权利要求1所述的营养组合物，其特征在于，所述唾液酸化低聚糖至少包括3'-唾液酸乳糖(3’-SL)和/或6'-唾液酸乳糖(6’-SL)，所述岩藻糖基化低聚糖包括乳糖二岩藻四糖(LDFT)和/或2’-岩藻糖基乳糖(2’-FL)，所述N-乙酰化低聚糖包括乳糖-N-新四糖(LNnT)。
3.如权利要求2所述的营养组合物，其特征在于，所述营养组合物包含如下含量的组分：
(1)以重量百分比计10％-25％的唾液酸化低聚糖，其中所述唾液酸化低聚糖中包含的3'-唾液酸乳糖(3'-SL)占所述营养组合物总重量的10％-25％；
(2)以重量百分比计35％-50％的岩藻糖基化中性低聚糖，其中所述岩藻糖基化中性低聚糖中包含的2’-岩藻糖基乳糖(2’-FL)占所述营养组合物总重量的25％-45％，乳糖二岩藻四糖(LDFT)占所述营养组合物总重量的10％～25％；
(3)以重量百分比计5％-35％的N-乙酰化中性低聚糖，其中所述N-乙酰化中性低聚糖中包含的乳糖-N-新四糖(LNnT)占所述营养组合物总重量的5％-35％。
4.根据权利要求2或3所述的营养组合物，其特征在于，所述营养组合物中总低聚糖的浓度为每100g营养组合物中含有10-10000mg低聚糖。
5.根据权利要求2或3所述的营养组合物，其特征在于，所述骨桥蛋白OPN与所述低聚糖的质量比例是1:20-200。
6.如权利要求1-5任一所述的营养组合物，其特征在于，所述组合物进一步包含益生元，所述益生元选自低聚果糖、菊粉、低聚木糖、聚葡萄糖或它们的任何组合。
7.如权利要求6所述的营养组合物，其特征在于，其还包含益生菌。
8.如权利要求7所述的营养组合物，其特征在于，所述益生菌是选自以下的益生菌菌株或它们的组合：嗜酸乳杆菌(Lactobacillus acidophilus)、唾液乳杆菌(Lactobacillussalivarius)、鼠李糖乳杆菌(Lactobacillus rhamnosus)、副干酪乳杆菌(Lactobacillusparacasei)、干酪乳杆菌(Lactobacil luscasei)、约氏乳杆菌(Lactobacillusjohnsonii)、植物乳杆菌(Lactobacillus plantarum)、发酵乳杆菌(Lactobacillusfermentum)、乳酸乳杆菌(Lactobacillus lactis)、德氏乳杆菌(Lactobacillusdelbrueckii)、瑞士乳杆菌(Lactobacillus helveticus)、保加利亚乳杆菌(Lactobacillus bulgari)、乳酸乳球菌(Lactococcus lactis)、二丁酮乳球菌(Lactococcus diacetylactis)、乳脂乳球菌(Lactococcus cremoris)、唾液链球菌(Streptococcus salivarius)、嗜热链球菌(Streptococcusthermophilus)、乳双歧杆菌(Bifidobacterium lactis)、动物双歧杆菌(Bifidobacterium animalis)、长双歧杆菌(Bifidobacterium longum)、短双歧杆菌(Bifidobacterium breve)、婴儿双歧杆菌(Bifidobacteriuminfantis)和青春双歧杆菌(Bifidobacterium adolescentis)。
9.如权利要求1-8任一所述的营养组合物，其特征在于，所述组合物为固体或液体制剂。
10.如权利要求1-9任一所述的营养组合物的用途，其特征在于，所述用途为用于婴幼儿的生长追赶。
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