CN101795579A - 无蛋白配方 - Google Patents

无蛋白配方 Download PDF

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CN101795579A
CN101795579A CN200780053668A CN200780053668A CN101795579A CN 101795579 A CN101795579 A CN 101795579A CN 200780053668 A CN200780053668 A CN 200780053668A CN 200780053668 A CN200780053668 A CN 200780053668A CN 101795579 A CN101795579 A CN 101795579A
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carbohydrate
amino acid
indigestible
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简·伊丽莎白·兰福德
伊恩·苏利文
凯瑟琳·特蕾莎·迪林
桑德拉·海伦·吉芬
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SHS International Ltd
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Abstract

本发明涉及包含作为唯一蛋白质来源的游离氨基酸、包括长链多不饱和脂肪酸的脂肪酸来源、包括可消化和不可消化的碳水化合物的碳水化合物来源、和无乳蛋白双歧杆菌的组合物用于治疗患有以下病症的人的用途：(a)绞痛、充血、流鼻涕、喘息、呕吐、腹泻、血便、便粘液、皮疹、湿疹、胃食道反流、嗜酸性食道炎或哮喘；(b)牛乳过敏和/或食物蛋白不耐受；和/或(c)感染，其中所述不可消化的碳水化合物选自无乳蛋白来源且总组合物基本无完整蛋白。

Description

无蛋白配方
发明领域
本发明涉及接受基于氨基酸的配方的婴儿的健康刺激。
发明背景
在优选的情况下，婴儿由母亲母乳喂养。然而，经常在婴儿中，在母乳喂养初期后，停止母乳喂养，且婴儿的饮食主要包括婴儿乳配方。
然而，在一小群婴儿中，母乳喂养或喂食常规婴儿配方引起有害反应，诸如疼痛和过敏反应。患有过敏的人群可能具有消化或代谢一些食物成分的困难，这然后导致胃肠和系统性过敏反应。过敏反应主要针对食物中的蛋白质组分。饮食的显著变化对于减少有害事件经常是必要的。
为了防止对蛋白质的过敏反应，婴儿食品由水解乳蛋白、氨基酸或非乳蛋白，例如大豆蛋白和不引起过敏反应的其他营养成分组成。
已知的包括氨基酸作为氮源的婴儿营养品是NeocateTM，其用于患有过敏、胃肠病症、湿疹、吸收不良或消化不良的患者。
在现有技术中，通常将不同营养来源的数量保持得很低，从而防止由于添加这些成分在配方中引入过敏原。然而，这具有以下缺点，即婴儿也不受益于所述添加的成分的有益作用。
WO2005039319公开synbiotics在包括采用水解产物形式的蛋白质的婴儿配方中的应用，由此减少过敏的风险(第11页，第35-37行)。
WO2006091103公开包含synbiotics的营养组合物，其用于治疗和预防免疫病症，包括过敏。公开了蛋白质水解产物和/或游离氨基酸减少过敏风险的用途。
本发明的目的是通过不在组合物中引入过敏原的条件下提供另外的营养益处而改进用于这种易受影响的患者群的饮食配方。
发明概述
本发明人已经认识到在含有多种游离氨基酸的无完整蛋白质的基本配方中，肠菌群如何形成是高度不可预测的。代替接受母乳的正常婴儿中的双歧杆菌(bifidobacteria)和乳杆菌(1actobacilli)优势菌群，许多其他的细菌菌种，包括潜在的致病菌种，可能在接受基于氨基酸的食物的婴儿的肠内盛行。
健康肠菌群的形成在所有婴儿中都特别重要，因为这些婴儿通过已经遭受受损的免疫功能，由此导致绞痛、充血、流鼻涕、喘息、呕吐、腹泻、血便、便粘液、皮疹、或湿疹。
本发明人已经认识到，健康菌群的形成在接受主要包含作为蛋白质来源的游离氨基酸的饮食的婴儿中是非常高度重要的。在不受理论限制的条件下，本发明人认为，良好的菌群，即富含双歧杆菌和乳杆菌的菌群，特别有益于(粘膜)免疫系统的成熟。良好的菌群预防过敏的形成或至少降低婴儿中过敏的严重性。因此，本发明人认识到有益菌群形成在这些婴儿中的关键作用。
不管关于所述易受影响的婴儿的饮食制剂配方的限制，本发明人发现可以将特定选择的饮食寡糖，优选果聚糖和/或果胶降解产物有益地加入到基础配方中，从而在不引起任何过敏性副作用的条件下刺激菌群形成。
乳来源的产物均不能用在该基础配方中，因为其可能引起向产物中添加乳过敏原。因此，按照本发明的益生(prebiotic)纤维小心地选自已知的益生纤维，从而防止将该纤维中存在的乳或其他完整和潜在过敏原性蛋白添加到非过敏性组合物中。
本发明人意外地发现在国际公认的过敏模型中，即当益生纤维与益生菌(优选双歧杆菌)组合时，存在关于防止过敏反应的协同作用。该协同作用不仅潜在地非常有益于婴儿，而且也有益于成年人。
附图简述
图1显示按照国际公认的小鼠疫苗模型测试的不同组合物的过敏反应。
图2证明TD1(短双歧杆菌(Bifidobacterium breve))和饮食纤维(OS)在小鼠酪蛋白过敏模型中的协同作用。
发明详述
按照本发明的一个优选实施方案包括包含作为唯一蛋白质来源的游离氨基酸、包括长链多不饱和脂肪酸的脂肪酸来源、包括可消化和不可消化的碳水化合物的碳水化合物来源、和无乳蛋白双歧杆菌(milk protein freeBifidobacteria)的组合物制备用于治疗患有以下病症的人的组合物的用途：
a.绞痛、充血、流鼻涕、喘息、呕吐、腹泻、血便、便粘液、皮疹、湿疹、胃食道反流、嗜酸性食道炎或哮喘；
b.牛乳过敏和/或食物蛋白不耐受；和/或
c.感染，
其中不可消化的碳水化合物选自无乳蛋白来源且总组合物基本无完整蛋白。
术语“唯一的蛋白质来源”在本文中意指所述组合物(优选)包含基于总蛋白质的至少99wt.％，优选至少99.5，更优选至少99.9wt.％的氨基酸。
本发明还提供组合物，其包含蛋白质成分、脂肪成分、可消化的碳水化合物成分、不可消化的碳水化合物和双歧杆菌，其中；
a)蛋白质成分包含基于总蛋白质的大于99wt.％游离氨基酸，并包含至少以下游离氨基酸：丙氨酸，精氨酸，天冬氨酸，半胱氨酸，甘氨酸，组氨酸，异亮氨酸，亮氨酸，赖氨酸，甲硫氨酸，脯氨酸，丝氨酸，苏氨酸，色氨酸，酪氨酸，缬氨酸和谷氨酰胺；
b)可消化的碳水化合物成分含有基于总可消化的碳水化合物的小于2wt.％的乳糖；
c)不可消化的碳水化合物包含具有平均DP为2-200的可溶性果聚糖和具有平均DP为2-200的可溶性半乳糖醛酸；和
d)脂肪成分包括基于总脂肪酸含量的0.1-5wt％LCPUFA。
如图1中所示，长链可溶性果聚糖(LFOS)与酸寡糖(AOS)(在本案中是果胶水解产物)的组合，在小鼠模型中测试时，与双歧杆菌一样良好地工作。然而，清楚地，如果寡糖与双歧杆菌组合，则强烈提高该作用。
在优选的实施方案中，营养组合物包括不可消化的纤维和双歧杆菌，因为该组合物在过敏性小鼠模型中提供最佳结果。(参见图1)。优选使用短双歧杆菌。
不可消化的碳水化合物
果聚糖是基于果糖的中性寡糖(＞50％的单糖单元是果糖)，优选菊粉，果聚糖和/或果寡糖，最优选具有平均DP为10-60的长链果寡糖(lcFOS)和具有平均DP为3-10的短链果寡糖(scFOS)的混合物。优选的实施方案包括比例为1∶9的lcFOS和scFOS的混合物，因为该比例更接近母乳中寡糖的组成，并已被证明有效刺激双歧杆菌在婴儿中的生长。
本方法优选包括施用一份食物(serving)，其包括0.05-25克不可消化的糖类，优选0.1-5克。本方法优选包括施用一份食物，其包括0.05-25克scFOS，优选0.1-5克scFOS。本方法优选包括施用0.05-25克不可消化的糖类/日，优选0.1-5克/日。
果胶降解产物
将果胶分成2个主要种类：特征为高于50％的甲氧基化程度的高甲氧基化果胶，和具有低于50％的甲氧基化程度的低甲氧基化果胶。用于本文中时，“甲氧基化程度”(也称为DE或“酯化程度”)意指聚半乳糖醛酸链中包含的自由羧酸基团的酯化(例如通过甲氧基化)程度。所述果胶优选由高甲氧基化果胶制备。
果胶优选特征在于高于20％，优选高于30％，甚至更优选高于50％的甲氧基化程度。
果胶用于本方法中时，具有平均聚合度(DP)为2-500，优选10-250和更优选20-50。当使用具有不同聚合度的果胶的混合物时，酸寡糖混合物的平均DP优选为3-1000，更优选3-250，甚至更优选3-50。发现寡糖的较低DP改善适口性，并且如果酸寡糖以液体形式施用，导致减小粘度的产物。
果胶优选以0.1-100克/日，优选0.4-50克/日，甚至更优选1-20克/日的量施用。
优选的实施方案包括处于50∶50-95∶5比例的果聚糖和果胶降解产物。优选所述比例是85∶15，因为这是如母乳中存在的中性寡糖和酸性寡糖的比例。
益生菌
适合用于本发明的益生菌在小鼠过敏模型中应该优选具有至少一种积极作用，如以下实施例中所述。益生菌还必须在实质上缺乏食物过敏原的条件下收获。这需要无完整蛋白的特殊程序或培养基，以制备益生菌。
因此优选的实施方案包括处于实质上缺乏完整食物蛋白或食物过敏原，特别是实质上缺乏乳蛋白的条件下的益生菌。
在优选的实施方案中，所述益生菌是双歧杆菌。甚至更优选地，所述益生菌是短双歧杆菌(Bifidobacterium breve)。双歧杆菌具有最强的耐受性，包括在所用的小鼠模型中的作用并因此是优选的。具体地，短双歧杆菌是高度有效的。
在另一个优选的实施方案中，所述双歧杆菌是无法存活的。这具有这样的优势，即产品的保存期变得更长且细菌的免疫调节活性变得不依赖于活双歧杆菌的数量。实验显示无法存活的细菌的免疫刺激作用是类似的且有时甚至优于活双歧杆菌的活性。
本发明组合物优选包括102-1013个双歧杆菌菌落形成单元(cfu)/克干重本发明组合物，优选102-1012cfu，更优选105-1010cfu，更优选104-5x109cfu/克干重本发明组合物。
氨基酸
氨基酸可以用在婴儿和幼儿的营养配方中。然而，除患有苯丙酮尿(PKU)和非PKU先天性代谢障碍的患者外，配方中的氨基酸组合物优选包括所有必需氨基酸，且优选最适于婴儿食品或婴儿营养。本发明人然后发现最佳氨基酸组合物应该尽可能接近母乳蛋白质组分的氨基酸组合物。这导致如表1中所示的优选氨基酸组合物(见下文)。
在优选的实施方案中，所述组合物包括基于总蛋白小于1wt.％的肽和基于总蛋白的大于99wt.％的游离氨基酸，其包括至少下列游离氨基酸：丙氨酸，精氨酸，天冬氨酸，半胱氨酸，甘氨酸，组氨酸，异亮氨酸，亮氨酸，赖氨酸，甲硫氨酸，脯氨酸，丝氨酸，苏氨酸，色氨酸，酪氨酸，缬氨酸和谷氨酰胺；
配方
按照本发明的配方包括作为氮源的游离氨基酸，脂肪(包括包含LCPUFA的脂肪混合物)和碳水化合物。根据法律要求加入维生素和矿物质。
本发明的组合物优选为婴儿提供营养，且包括脂质成分，蛋白质成分和碳水化合物成分。脂质成分优选提供5-50％的总热量，蛋白质成分优选提供5-50％的总热量，且碳水化合物成分优选提供15-90％的总热量。本发明的组合物优选用作婴儿配方，其中脂质成分提供35-50％的总热量，蛋白质成分提供7.5-12.5％的总热量，且碳水化合物成分提供40-55％的总热量。为了计算蛋白质成分的总热量％，需要采用由氨基酸提供的总能量。
LCPUFA
具有20和22个碳原子的LC-PUFA在本发明组合物中的含量优选不超过总脂肪含量的15wt.％，优选不超过总脂肪含量的10wt.％，甚至更优选不超过5wt.％。优选地，本发明的组合物包括总脂肪含量的至少0.1wt.％，优选至少0.25wt，更优选至少0.5wt.％，甚至更优选至少0.75wt.％具有20和22个碳原子的LC-PUFA。二十二碳六烯酸(DHA)含量优选不超过总脂肪的5wt.％，更优选不超过1wt.％，但至少为0.1wt％。由于发现花生四烯酸(AA)特别有效降低紧密连接渗透性，所以本发明的组合包括相对高的量，优选至少0.1wt.％，甚至更优选至少0.25wt.％，更优选至少0.5wt.％的总脂肪。AA含量优选不超过总脂肪的5wt.％，更优选不超过1wt.％。由AA的过度代谢可以导致炎症。因此，本发明的组合物优选包括AA和DHA，其中AA/DHA重量比优选高于0.25，优选高于0.5，甚至更优选高于1。该比例优选低于25。
LC-PUFA优选是非鱼来源的单细胞油，例如可获自Martek。
按照本发明的组合物的优选特征记述在表1-3中。
表1.按照本发明的组合物的氨基酸含量
Figure G2007800536680D00071
表2.过敏婴儿的营养婴儿配方
Figure G2007800536680D00072
表3.长链多不饱和(LCP)脂肪酸组合物的范围
Figure G2007800536680D00081
寡糖组合物中的优选范围是0.4-1.2g/100ml，其中85w％是scFOS和lcFOS且15w％是果胶水解产物。优选地，scFOS与lcFOS的比例是2-20，甚至更优选地，该比例是9。
按照本发明的无乳蛋白和过敏原的营养完整粉末配方(适合于用水稀释以形成肠喂养)的一个优选实施方案包括：
成分                              每100g粉末
蛋白质等价物(g)                   13
总氨基酸(g)                       15.5
总脂肪(g)                         23
向日葵油(g)                       4
分级椰油(g)                       7
菜籽油(Canola oil)(g)             4
高油酸向日葵油(g)                 6.6
ARASCOTM油(g)                     0.21
DHASCOTM油(g)                     0.11
碳水化合物：麦芽糖糊精(g)         49
益生菌(g)                         5.33
ScFOS(g)                          4.1
lcFOS(g)                          0.43
AOS(g)                            0.8
益生菌：短双歧杆菌(菌落形成单元； 1x1010
CFU)
其他维生素/矿物质/痕量元素        余量
以上配方提供约455kcal能量/100g粉末。
该配方可以用冷水、沸水稀释，以提供15％w/v的推荐浓度。
用途
优选地，所述组合物用于治疗患有以下疾病的婴儿(特别是具有特应性体质的婴儿)：
a.绞痛、充血、流鼻涕、喘息、呕吐、腹泻、血便、便粘液、皮疹、湿疹、胃食道反流、嗜酸性食道炎或哮喘；
b.牛乳过敏和/或食物蛋白不耐受；和/或
c.感染。
所述组合物还可以优选用于改善患有以上提到的症状的婴儿的大便特征。所述组合物特别为0-3岁的婴儿设计。在对氨基酸特征(见表1)进行一些调整的条件下，所述组合物也适合于3-10岁的婴儿。过敏婴儿经常患有腹泻，但也发生便秘。可以用于预防和治疗这些症状的优选组合物包括按照母乳的组成的纤维(其中scFOS/lcFOS比率是9∶1)，且另外存在果胶水解产物。
实施例
为了确定寡糖和益生短双歧杆菌(TD 1)的免疫刺激作用，在国际公认的小鼠疫苗模型(图1)中和在过敏模型(图2)中进行测试。
疫苗模型的材料和方法
小鼠
雌性6-和8-周龄C57BI/6JOIaHsd小鼠获自Harlan(Horst，荷兰)并保持在正常条件下，其具有12h黑暗和光亮周期，并自由接近食物和水。所有的实验均由独立的动物实验委员会(DEC Consult(DEC咨询)，Bilthoven，荷兰)的批准。
饮食和寡糖制剂
所有动物接受半纯化的基于AIN-93G的饮食(Research Diet Services(研究饮食服务).Wijk bij Duurstede，荷兰)。所有增补的寡糖产物被互换为等量的总碳水化合物，从而保持该参数相等。另外，该方法导致不同饮食中相当的总碳水化合物组成，从而确保肠菌群最小地受到对照和测试饮食参数，诸如肠经过时间和流体保留的差别的影响。将寡糖混合到AIN-93G饮食中并压成小片。
疫苗接种方法和DTH反应
疫苗接种实验利用来自2002/2003季的Influvac(SolvayPharmaceuticals(索尔韦药品)，Weesp，荷兰)进行。它是一种失活的流感病毒疫苗，其基于分离的血凝素(HA)和三种粘液病毒流感株的神经氨酸酶抗原，其剂量与30μg/mL HA/株(总共90μg/ml HA)等价。将油佐剂用于所有疫苗接种中(Stimune，以前称为Specol；Cedi-diagnostics(塞地-诊断学)，Lelystad，荷兰)。小鼠接受初次疫苗接种和加强疫苗接种，其由皮下(sc)注射总体积为100μL的疫苗和佐剂的1∶1混合物组成。加强疫苗接种在初次疫苗接种后21天时给予。该实验在加强疫苗接种后10天时结束。在初次和二级疫苗接种前和在实验结束时采血样(通过眼窝后穿刺获取)。所有实验中包括的阴性对照组(用“假组”表示)接受总体积为100μL的PBS和佐剂的1∶1混合物的注射。假组没有用于与增补组的统计学比较，而是仅起证明疫苗-诱导的反应的特异性的作用。在加强疫苗接种后9天时通过将25μL Influvacsc注射到两只耳朵的耳廓中来诱导DTH反应。在疫苗攻击前和其后24h，利用数字测微计(Mitutoyo Digimatic 293561，Veenendaal，荷兰)测量耳朵的厚度，重复2次。通过从攻击后24h时的数值减去基础耳厚度来计算DTH反应。
牛乳蛋白过敏模型的材料和方法
化学药品
酪蛋白和乳清获自DMV国际(DMV International)，Veghel，荷兰。
霍乱毒素购自Quadratech Diagnostics(Quadratech诊断)，埃普索姆，英国。PBS购自Cambrex Bio Science(Cambrex生物科学)，Verviers，比利时。Elisa包被缓冲液获自Sigma(西格玛)，Alphen aan den Rijn，荷兰。生物素标记的大鼠抗小鼠IgE购自BD Biosciences(BD生物科学)，Alphenaan den Rijn，荷兰。所有其他化学药品均获自Sigma-Aldrich-Chemie，Zwijndrecht，荷兰。
小鼠的口腔敏化和攻击
3-5周龄的无特定病原体的雌性C3H/HeOuJ小鼠(n＝4-6/组)购自Charles River Laboratories(查尔斯河实验室)(Maastricht，荷兰)，保持在无牛乳蛋白的小鼠食物上(Special Diets Services(特殊饮食服务)，Witham，艾塞克斯，英国)并饲养在Utrecht University(乌得勒支大学)动物设施中。动物护理和使用均按照荷兰动物实验委员会(Dutch Committee of AnimalExperiments)的指导方针进行。用具有霍乱毒素(CT，20μL/mL PBS)的均化酪蛋白(40mg/mL PBS)作为佐剂，使用钝针，胃内(i.g.)敏化小鼠。对照小鼠接受单独的CT或PBS。每周对小鼠进行加强，进行6周，最后一次敏化后一周时，用100mg酪蛋白i.g.攻击小鼠。
收集血液样品并在随后进行离心(15分钟，13500rpm.)。将血清保存在-70℃。i.g.攻击后半小时，通过脱颈椎处死小鼠。
过敏原特异性皮肤反应
在耳廓中注射特异性蛋白后，测量急性过敏原特异性皮肤反应。i.g.攻击前(t＝0)，分别在对照、酪蛋白敏化小鼠左耳中皮内(i.d.)注射20μL均化酪蛋白(在PBS中，0.5mg/mL)。在右耳中注射20μl PBS作为载体对照。CT和PBS小鼠也接受酪蛋白耳攻击，使用PBS注射作为对照。在攻击后0，1，4和24小时，利用数字测微计(Mitutoyo，Veenendaal，荷兰)测量耳朵厚度，重复2次。通过从在三个不同时间点(1，4和24h)时测量的数值中减去基础(0h)和对照(右耳)厚度来计算过敏原特异性耳肿胀。
测量血清免疫球蛋白和小鼠肥大细胞蛋白酶-1的水平
通过ELISA确定在处死的小鼠血清中总IgE浓度和酪蛋白或乳清特异性IgE，IgG1和lgG2a的水平。用处于包被缓冲液中的酪蛋白或处于PBS中的大鼠抗小鼠IgE(1μg/mL)在4℃包被Microlon板(Greiner，Alphen aanden Rijn，荷兰)18小时。用5％BSA洗涤和封闭板1小时。施加数个稀释度的血清样品，并在室温下温育2小时。洗涤板5次，与1μg生物素标记的大鼠抗小鼠IgE在室温下温育1个半小时。洗涤后，用辣根过氧化物酶(HRP)温育板1小时，洗涤并用邻苯二胺(OPD)显影。用4M H2SO4终止反应，并在Benchmark microplate reader(基准微板读数器)(Biorad，加利福尼亚，美国)上，在490nm处测量吸光度。小鼠肥大细胞蛋白酶-1(mMCP-1)的血清浓度如前述利用可商购的ELISA试剂盒(Moredun Scientific Ltd.(Moredun科学公司)，中洛锡安郡，英国)确定。
小鼠疫苗模型的结果显示在图1中，由该图清楚的是，TD1(＝短双歧杆菌)的组合在DTH反应上提供最强的作用，且显著优于单独的TD1或任何其他测试的组合。
小鼠酪蛋白过敏模型的结果显示在图2中，并且证明饮食纤维和TD1的组合协同地抑制针对酪蛋白的“变应原性”DTH反应。

Claims (16)

1.包含作为唯一蛋白质来源的游离氨基酸、包括长链多不饱和脂肪酸的脂肪酸来源、包括可消化和不可消化的碳水化合物的碳水化合物来源、和无乳蛋白双歧杆菌的组合物在制备用于治疗患有以下病症的人的组合物中的用途：
a.绞痛、充血、流鼻涕、喘息、呕吐、腹泻、血便、便粘液、皮疹、湿疹、胃食道反流、嗜酸性食道炎或哮喘；
b.牛乳过敏和/或食物蛋白不耐受；和/或
c.感染，
其中所述不可消化的碳水化合物选自无乳蛋白来源且总组合物基本无完整蛋白。
2.按照权利要求1的用途，其中所述人是年龄在0-36个月的婴儿。
3.包含作为唯一氨基酸来源的游离氨基酸、包括长链多不饱和脂肪酸的脂肪酸来源、包括可消化和不可消化的碳水化合物的碳水化合物来源、和无乳蛋白双歧杆菌的组合物在制备用于刺激具有特应性体质的婴儿的免疫系统成熟的组合物中的用途，其中所述不可消化的碳水化合物选自无乳蛋白来源且总组合物基本无完整蛋白。
4.按照权利要求1-3中任一项的用途，其中基于总蛋白的游离氨基酸包括至少以下游离氨基酸：丙氨酸，精氨酸，天冬氨酸，半胱氨酸，甘氨酸，组氨酸，异亮氨酸，亮氨酸，赖氨酸，甲硫氨酸，脯氨酸，丝氨酸，苏氨酸，色氨酸，酪氨酸，缬氨酸和谷氨酰胺。
5.按照权利要求1-4中任一项的组合物的用途，其中所述氨基酸构成总组合物的5-16en％，30-60en％脂肪，其中0.1-5en％LCPUFA和25-75en％可消化的碳水化合物。
6.按照权利要求5的用途，其中所述LCPUFA构成总组合物的0.2-1en％。
7.按照权利要求1-6中任一项的用途，其中所述不可消化的碳水化合物包括(i)具有平均聚合度为3-200的可溶性果聚糖和(ii)具有平均聚合度为3-200的可溶性半乳糖醛酸。
8.包含蛋白质成分、脂肪成分、可消化的碳水化合物成分、不可消化的碳水化合物和双歧杆菌的组合物，其中；
a)所述蛋白质成分包含基于总蛋白质的大于99wt.％的游离氨基酸，并包含至少以下游离氨基酸：丙氨酸，精氨酸，天冬氨酸，半胱氨酸，甘氨酸，组氨酸，异亮氨酸，亮氨酸，赖氨酸，甲硫氨酸，脯氨酸，丝氨酸，苏氨酸，色氨酸，酪氨酸，缬氨酸和谷氨酰胺；
b)所述可消化的碳水化合物成分含有基于总可消化的碳水化合物的小于2wt.％的乳糖；
c)所述不可消化的碳水化合物包含具有平均DP为2-200的可溶性果聚糖和具有平均DP为2-200的可溶性半乳糖醛酸；和
d)所述脂肪成分包括基于总脂肪酸含量的0.1-5wt％的LCPUFA。
9.按照权利要求8的组合物，其中：
所述脂肪成分包括基于总脂肪酸含量的0.2-1wt％的LCPUFA。
10.按照权利要求8或9的组合物，包含具有平均DP为2-200的不可消化、可溶性果聚糖和具有平均DP为2-200的不可消化、可溶性半乳糖醛酸。
11.按照权利要求8-10中任一项的组合物，包括短双歧杆菌(Bifidobacterium breve)。
12.按照权利要求8-11中任一项的组合物，包括花生四烯酸和/或二十二碳六烯酸。
13.按照权利要求8-12中任一项的组合物，其中所述不可消化的碳水化合物由长链FOS和短链FOS组成。
14.按照权利要求13的组合物，其中所述长链FOS具有平均DP为10-60且所述短链FOS具有平均DP为3-10。
15.按照权利要求8-14中任一项的组合物，其中所述产品是粉末或液体。
16.治疗患有以下病症的人的方法：
(a)绞痛、充血、流鼻涕、喘息、呕吐、腹泻、血便、便粘液、皮疹、湿疹、胃食道反流、嗜酸性食道炎或哮喘；
(b)牛乳过敏和/或食物蛋白不耐受；和/或
(c)感染，
所述方法包括向所述人施用包含作为唯一蛋白质来源的游离氨基酸、包括长链多不饱和脂肪酸的脂肪酸来源、包括可消化和不可消化的碳水化合物的碳水化合物来源、和无乳蛋白双歧杆菌的组合物，其中所述不可消化的碳水化合物选自无乳蛋白来源且总组合物基本无完整蛋白。
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CN106455657A (zh) * 2014-04-09 2017-02-22 雀巢产品技术援助有限公司 性别特异性合成营养组合物以及包含这类组合物的营养体系产品
CN107427553A (zh) * 2015-03-18 2017-12-01 N·V·努特里奇亚 通过β‑乳球蛋白衍生肽结合益生菌的给药来诱导口服耐受性的方法
CN108697141A (zh) * 2015-12-29 2018-10-23 N·V·努特里奇亚 含有不可消化寡糖和非复制型产乳酸细菌的营养配方物
CN107041546A (zh) * 2016-02-05 2017-08-15 上海他普亚贸易有限公司 一种氨基酸配方粉及其制备方法
CN112244097A (zh) * 2020-10-19 2021-01-22 湖南欧比佳营养食品有限公司 一种含有氨基酸及无乳糖的配方奶粉及其制备方法

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