CN1703149A - 包含共生菌物质的营养性配方制剂 - Google Patents
包含共生菌物质的营养性配方制剂 Download PDFInfo
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- CN1703149A CN1703149A CNA2003801011770A CN200380101177A CN1703149A CN 1703149 A CN1703149 A CN 1703149A CN A2003801011770 A CNA2003801011770 A CN A2003801011770A CN 200380101177 A CN200380101177 A CN 200380101177A CN 1703149 A CN1703149 A CN 1703149A
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- China
- Prior art keywords
- lactic acid
- bifidobacterium
- fos
- cfu
- sialyl lactose
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Abstract
提供包括低聚果糖、唾液酸乳糖和益生细菌的营养性组合物,其可用于消灭患者胃肠道中的致病微生物。
Description
发明领域
本发明涉及包含共生菌的营养性配方制剂和这种制剂在促进患者胃肠道中有益微生物生长并且抑制和消灭致病生物中的用途。更具体地说,本发明涉及包含与益生细菌的特定菌株组合的低聚果糖和唾液酸乳糖的营养性制剂。
发明背景
共生菌是″通过改善宿主胃肠道中活的微生物营养补充物的存活和植入而有利地影响宿主的益生菌和益生元的混合物″(Andersson etal.″Health effects of probiotics and prebiotics:Aliteraturereview on human studies.″Scand.J.Nutr.45:58-75(2001))。
益生元是通过有选择地刺激已经在结肠中建立的有限数目的细菌种属的生长和/或活性而有利地影响宿主,并因此有效地改善宿主健康的不会被消化的食品成分。(Gibson et al.,″Dietary modulation ofthe human colonic microbiota:Introducing the concept ofprebiotics.J.Nutrition 125:167-176(1995))。
低聚果糖是众所周知的益生元。低聚果糖经过小肠而没有被消化,再到达大肠。在大肠中,只通过有限范围的微生物来发酵低聚果糖,其中包括大多数种属的双歧杆菌,即对人体健康有益的细菌种属。(参见例如,Bouhnik et al,Bouhnik et al,″ShortChain Fructo-Oligosaccharide Administration Dose-DependentlyIncreases Fecal Bifidobacteria in Healthy Humans,″J.Nutrition,129:113-116(1999))。已知低聚果糖是双歧杆菌的特异性底物。(参见例如,Mitsuoka et al,″Effect of Fructo-oligosaccharides on Intestinal Microflora″,Die Nahrung,3,5-6:427-436(1987))。双歧杆菌产生作为其代谢副产物的短链脂肪酸,导致消化道pH的降低。
美国专利号5,849,324公开了通过肠内施用有效量的难消化的无氮低聚糖而减少中耳炎发生的方法。援引的特异性的低聚糖是果糖、木糖和半乳糖的低聚糖。
美国专利号5,827,526公开了通过肠内施用以预防为基础的有效量的难消化的无氮低聚糖而减少腹泻持续时间的方法。
美国专利号5,688,777公开了通过肠内施用有效量的难消化的无氮低聚糖而抑制艰难梭菌(Clostridium difficile)感染的方法。在感染的小鼠中,通过测量粪便集落形成单位(cfu),施用特异性的果糖低聚糖来减少或消灭艰难梭菌。
唾液酸乳糖是包括唾液酸和二糖乳糖的低聚糖。唾液酸是包含9个以上碳原子的氨基糖家族,其为神经氨酸的N-和O-取代的衍生物。最常见的唾液酸种类是N-乙酰神经氨酸。
唾液酸乳糖天然地存在于人乳以及其他哺乳动物的乳中。然而,与其他的哺乳动物种属相比,唾液酸乳糖以显著的高浓度存在于人乳中。乳中唾液酸乳糖的2个主要种类是3′-唾液酸乳糖和6′-唾液酸乳糖。这些种类天然地存在于人乳中,其相对比率为1∶3(3′∶6′)。
已知唾液酸乳糖具有针对特定致病细菌的抗-粘附特性。例如,唾液酸乳糖发挥
体外抑制霍乱毒素的作用(Idota et al.,″Inhibitionof Cholera Toxin by Human Milk Fractions andSialvllactose,″
Biosci.Biotech.Biochem.59:417-419)和幽门螺杆菌(Helicobacter pylori)(Simonet al.,″Inhibition ofHelicobacter pylori Binding to Gastrointestinal EpithelialCells by Sialic Acid-Containing Oligosaccharides,″Infectionand Immunity,750-757,(1997))。
考虑到其抗-粘附特性,唾液酸乳糖已经被用于处理许多医学状况。例如,美国专利号5,260,280公开了中和细菌肠毒素作用的包括含有唾液酸的低聚糖的组合物。美国专利号5,514,660、5,753,630和5,883,079公开了通过施用有效量的包含唾液酸的低聚糖,分别用于治疗或预防胃或十二指肠中的溃疡,或抑制幽门螺杆菌感染的方法。美国专利号5,620,965涉及通过施用有效量的某些低聚糖,用于抑制细菌幽门螺杆菌与胃或十二指肠细胞的结合的组合物。
美国专利号5,834,423描述了促进双歧杆菌增殖的唾液酸衍生物和利用有效量的某些唾液酸化的低聚糖作为抗腹泻试剂的用途。唾液酸化的低聚糖包括3′-唾液酸乳糖和6′-唾液酸乳糖。
WO2001060346公开了包括以协同方式作用来刺激有益的双歧杆菌生长的益生元物质低聚果糖和唾液酸乳糖的营养性组合物。
益生菌是对人体健康具有有益影响的活的微生物食品成分。(Salminen et al.,″Functional food science andgastrointestinal physiology and function.″Brit.J.Nutr.80(suppl.1):S147-S171(1998))。
大多数益生细菌通常是″乳酸细菌″,如此称呼是因为它们发酵碳水化合物成为乳酸。最经常研究的特异菌株包括乳杆菌属和双歧杆菌属的成员。(Sanders,″Probiotics.″Food Technol.53:67-77(1999))。
一些乳酸菌特异地产生乳酸作为其代谢的主要产物。一些乳酸菌主要产生左旋″L″-形式的乳酸[L(+)-乳酸],其它乳酸菌主要产生右旋″D″-形式的乳酸,而其它乳酸菌同时产生D-乳酸和L-乳酸。L(+)-乳酸是哺乳动物代谢的常见中间物。通过肝、肾和脑快速并且有效地氧化L(+)-乳酸。相比之下,哺乳动物组织不是很好地利用D(-)-乳酸,并且可能在人类婴儿中导致酸毒症。
干酪乳杆菌(Lactobacillus casei)种的菌株GG,一种通常称为″乳杆菌GG″或″LGG″的益生细菌,主要产生左旋L-形式的乳酸[L(+)-乳酸]。口服给药后,在婴幼儿的粪便中发现了LGG。(Sepp etal.,″Effect of administration of Lactobacillus casein strainGG on the gastrointestinal microbiota of newborns.″Microb.Ecol.Health Dis.6:309-314(1997);Sheen etal.,″Short Report:A placebo-controlled study ofLactobacillus GG colonization in one-to-three-year-oldPeruvian children.″Am.J.Trop.Med.Hyg.52:389-392(1995))。
包含LGG的乳制品显著地缩短幼儿腹泻的持续时间。(Kaila etal.,″Enhancement of the circulating antibody secreting cellresponse in human diarrhea by a human Lactobacillusstrain.″Pediatr.Res.32:141-144(1992);Isolauri et al.,″Thehuman Lactobacillus strain(Lactobacillus casei sp strainGG)promotes recovery from acute diarrhea in children.Pediatrics.88:90-97(1991))。
嗜酸乳杆菌(Lactobacillus acidophilus)产生近似相等量的D(-)-乳酸和L(+)-乳酸。含有嗜酸乳杆菌(菌株CRL730)和干酪乳杆菌(菌株CRL431)的发酵牛奶平均在4天中消除患有肠胃炎后综合症的婴儿的腹泻疾病。发酵牛奶使粪便的菌群恢复至主要的乳酸菌群。(Gonzalez et al.,″Biotherapeutic role of fermented milk.″Biotherapy.8:129-134(1995))。
美国专利号5,908,646公开了通过加入有效量的有益微生物,主要产生L(+)-乳酸的鼠李糖乳杆菌(L.rhamnosus)[干酪乳杆菌亚种鼠李糖]而抑制人食品中的梭菌种类的生长或活性的方法。
美国专利号5,902,578涉及包含有助于预防腹泻的人类肠道微生物的3种特异微生物的活细胞的组合物。具体地,3种微生物是路氏乳杆菌(Lactobacillus reuteri)、嗜酸乳杆菌和婴儿双歧杆菌(Bifidobacterium infantis)。腹泻可由抗生素治疗或病毒、细菌(例如大肠杆菌)或寄生虫的感染而引起。
美国专利号5,716,615涉及包含用于治疗胃肠机能紊乱的几个不同细菌的组合物。该微生物可选自冻干的乳杆菌种类,包括嗜酸乳杆菌、冻干的双歧杆菌种类、包括长双歧杆菌(B.Longum)、婴儿双歧杆菌和双歧双歧杆菌(B.bifidum)和嗜热链球菌(Streptococcusthermophilus)。
乳酸双歧杆菌是产生L(+)-乳酸的细菌。历史上,在文献中鉴定乳酸双歧杆菌(Bifidobacterium lactis)Bb-12为″双歧双歧杆菌″(Fukushima et al.,″Effect of a probiotic formula onintestinal immunoglobulin A production in healthychildren.″Int.J.Food Microb.42-39-44(1998))。
包含双歧双歧杆菌和嗜热链球菌的未发酵的婴儿配方食品减少急性腹泻和轮状病毒腹泻的发生。(Saavedra et al.,″Feeding ofBifidobacterium bifidum and Streptococcus thermophilus toinfants in hospital for prevention of diarrhoea and sheddingof rotavirus.″The Lancet.344:1046-49(1994))。
包含双歧双歧杆菌和嗜热链球菌的发酵的婴儿配方食品与未发酵的对照制剂相比,诱导肠中更普遍的双歧杆菌集群和更低的粪便pH。(Langhendries et al.,″Effect of a fermented infant formulacontaining viable Bifidobacteria on the fecal floracomposition and pH of healthy full-term infants.″J.Pediatr.Gastroenterol.Nutr.21:177-181(1995))。
包含双歧双歧杆菌和嗜热链球菌的未发酵的制剂支持营养不良的幼儿的追赶生长。包含2种细菌的基于乳品的制剂诱导肠的益生菌集群。(Haschke et al(1998))″临床试验证明改进型的配制品和成熟型的牛奶中益生菌菌株双歧杆菌Bb12的安全和效果.″Monatsschr.Kinderheilkd.146:S26-30(1998)。
WO2000010582公开了利用一种或多种产生乳酸的细菌的种属或菌株,优选为凝结芽孢杆菌(Bacillus coagulans)的菌株用于控制胃肠道病原体、包括控制抗生素-抗性的胃肠道病原体及其相关疾病的组合物和方法。
将包含益生菌双歧双歧杆菌(实际为乳酸双歧杆菌Bb12)和益生元乳-低聚糖的婴儿配方食品喂养给正常的婴儿产生更有利的粪便菌群,具有较少的梭菌和更多的双歧杆菌。(Fukushima et al.″Effectof follow-up formula containing Bifidobacteria(NAN BF)onfecal flora and fecal metabolites in healthychildren.″Bloscience Microflora.16:65-72(1997))。
美国专利号6,241,983公开了包含有益的人肠道微生物和促进胃肠道健康的食用纤维来源的组合物。更具体地说,该微生物可以选自乳杆菌和双歧杆菌种属。食用纤维的来源包括戊聚糖、β-葡聚糖、果胶和果胶多糖、甘露聚糖、阿拉伯聚糖和半乳聚糖、果糖低聚糖及其混合物。
美国专利号5,744,134要求保护包含有益的人肠内微生物和促进胃肠道健康的食用纤维来源的组合物。更具体地说,该微生物可以选自乳杆菌和双歧杆菌种属。食用纤维的来源是菊糖、果糖低聚糖、果胶、瓜耳豆胶及其混合物。
WO2001015714公开了用于增加全身免疫的组合物。该组合物包括一种或多种微量营养元素、一种或多种选自益生元、益生菌和共生菌的化合物、和以脂类为基础或以碳水化合物为基础的赋形剂。
WO2000033854描述了具有健康促进作用的、特别是用于预防和/或治疗消化道紊乱的制剂,其包含一种或多种益生菌和一种或多种不易消化的低聚糖。益生菌优选地选自例如乳杆菌或双歧杆菌种属的菌株,以及选自例如酵母种属菌株的酵母菌株。益生元可包括水解的角豆树胶、菊糖、阿拉伯半乳聚糖、阿糖基木聚糖、β-葡聚糖、L-阿拉伯糖、半乳甘露聚糖和葡糖甘露聚糖。
EP904784公开了具有健康促进作用的、特别是涉及预防和治疗胃肠道紊乱的营养性制剂,其包括有效量的下列每一种微生物的活细胞:主要产生左旋的L(+)-乳酸的双歧杆菌属、粪肠球菌(Enterococcus faecium)、和乳杆菌菌株。例证性的双歧杆菌种属包括婴儿双歧杆菌和乳酸双歧杆菌。
发明概述
本发明涉及包括低聚果糖、唾液酸乳糖和益生细菌的营养性组合物。本发明进一步指向抑制或消灭患者胃肠道中的致病生物的方法,包括对所述的患者肠内施用包括低聚果糖、唾液酸乳糖和益生细菌的组合物。
发明详述
本发明人已经发现低聚果糖、唾液酸乳糖和益生细菌的组合物消除致病细菌,特别是肠致病性大肠杆菌的肠内感染,因此可用于预防由肠致病性大肠杆菌导致的腹泻。优选用于本制剂的益生细菌包括嗜酸乳杆菌和乳酸双歧杆菌。
用于本组合物的唾液酸乳糖包括3′-唾液酸乳糖和6′-唾液酸乳糖。优选地,在此使用的唾液酸乳糖是3′-唾液酸乳糖。
可根据例如美国专利号5,575,916、5,714,075、5,278,299、5,374,541、和5,876,980中所描述的任何方法制备唾液酸乳糖。然而,本领域的技术人员可认识到任何其他合成和纯化唾液酸乳糖的方法都可用于制备本发明的组合物中所使用的唾液酸乳糖。
可通过任何已知的合成和/或分离方法制备对本发明有用的低聚果糖。对本发明有用的可商业购买形式的低聚果糖是可从Orafti S.A.,Tienen,比利时获得的Raftilose。
低聚果糖包括一系列天然存在于植物,例如洋葱和菊苣植物的根中的低聚糖。低聚果糖可从在许多植物,包括洋葱、韭菜、小麦、菊苣和菊芋中发现的天然存在的多聚果糖(菊糖)在工业上制备。菊苣是最通常使用的。可通过本领域已知的方法从这些植物回收足够数量的低聚果糖。天然存在的菊糖包括低聚果糖和果糖的高聚物。从例如菊苣的植物的菊糖衍生的低聚果糖包含多聚果糖链和具有末端葡萄糖单体的多聚果糖链。
低聚果糖可通过合成而不是提取方法来制备。可从蔗糖通过利用一种酶,β-呋喃果糖苷酶进行转果糖化的方式而合成低聚果糖,其中所述的酶将附加的果糖单体连接到蔗糖分子上。在这个方式中形成的低聚果糖包含连接至末端葡萄糖单体上的果糖单元。这种果糖低聚糖的实例是蔗果三糖(GF2)、霉菌赤藓醛糖(GF3)和呋喃果糖化的霉菌赤藓醛糖(GF4)。通过诸如这些方法制备的包括低聚糖混合物的低聚果糖是例如可从GTC Nutrition Company,Golden,CO,美国获得的NutraFlora。
对本发明有用的合适益生菌是双歧杆菌和乳杆菌。乳酸双歧杆菌BB1和嗜酸乳杆菌NCFM可从Rhodia公司获得。
本发明的营养性组合物可包括(或用水稀释后能够包括)0.1g/L至10g/L的低聚果糖、6mg/L至10g/L的唾液酸乳糖、每升106至1014集落形成单位(cfu)的乳杆菌、和106至1014cfu/L的双歧杆菌。优选地,本组合物包括(或用水稀释后能够包括)0.3g/L至6g/L的低聚果糖、60mg/L至1g/L的唾液酸乳糖、108至1012cfu/L的乳杆菌和108至1012cfu/L的双歧杆菌。更优选地,本制剂包括(或用水稀释后能够包括)1g/L至3g/L的低聚果糖、100mg/L至600g/L的唾液酸乳糖、109至1011cfu/L的乳杆菌、和109至1011cfu/L的双歧杆菌。以及甚至更优选地包括大约3g/L的低聚果糖、大约100mg/L的唾液酸乳糖、大约3×1010cfu/L的乳杆菌和大约3×1010cfu/L的双歧杆菌。
本发明的营养性组合物可以以多种营养性产品,例如婴儿配方食品、改进型的配制品、婴儿饮料、牛奶、酸奶、针对较年长儿童的基于水果的产品(例如果汁)、糖果、口香糖、锭剂、粉剂、片剂等的形式或与之结合的形式加以使用。优选地,该营养性组合物以婴儿配方食品的形式进行使用。当用作婴儿配方食品时,可能以料液或粉末的形式准备,再与水混合并且喂给婴儿。最优选地,将本制剂以粉末的形式加入婴儿配方食品中。
适用于本发明的婴儿配方食品应该包含全部维生素和认为在婴儿的每日饮食中必需的矿物质。这些维生素和矿物质应该以营养性显著的数量存在。可包括在将被加入本制剂的婴儿配方食品内的维生素、矿物质和其他营养的实例包括维生素A、复合维生素B、维生素C、维生素D、维生素E、维生素K、钙、镁、钠、钾、磷、铜、锌、氯化物、碘、硒、铁、烟酸、叶酸、泛酸、生物素、胆碱、肌醇和锰。
婴儿配方食品可包含本领域的技术人员能够认识到的一种或多种脂类来源。婴儿配方食品可进一步地包含已知具有有益效果的其他物质。这种物质的实例包括核苷酸、免疫球蛋白、多聚不饱和脂肪酸等。进一步参考下列非限制性的实施例对本发明加以说明。
实施例1
当用水稀释127.3克的所述婴儿配方食品至1升体积时,根据本发明的优选的婴儿配方食品提供下列营养:
营养
单位
每升
能量 Kcal 672
蛋白质 g 15
乳清∶酪蛋白比率 60-40
脂肪 g 36
碳水化合物,包括 g 72
低聚果糖 g 3.0
唾液酸乳糖 mg 100
嗜酸乳杆菌NCFM cfu 3×1010
乳酸双歧杆菌BB1 cfu 3×1010
维生素A RE 750
混合的天然类胡萝卜素 IU 400
维生素D mcg 10.6
维生素E IU 7.4
维生素K mcg 67.0
维生素B1(硫胺素) mcg 1000
维生素B2(核黄素) mcg 1500
维生素B6(吡哆醇) mcg 600
维生素B12(氰钴胺素) mcg 2.0
烟酸 mcg 9.0
叶酸 mcg 80
泛酸 mcg 3000
生物素 mcg 90
维生素C(抗坏血酸) mg 20
胆碱 mg 100
肌醇 mg 33
钙 mg 460
磷 mg 333
镁 mg 64
铁 mg 8.0
锌 mg 6.0
锰 mcg 50
铜 mcg 560
碘 mcg 100
钠 mg 160
钾 mg 650
氯化物 mg 433
硒 mcg 14
下列实验说明嗜酸乳杆菌和乳酸双歧杆菌消除肠致病性大肠杆菌的肠内感染的有效性。
实验
设计下列实验来评估嗜酸乳杆菌和乳酸双歧杆菌的组合作为预防由肠致病性大肠杆菌(″EPEC″)导致的腹泻的方法,其中用这种病原体有意感染猴子婴儿。
对恒河猴新生儿(黄褐色猕猴(Macaca mulatto))以唯一的方式喂养人化的婴儿配方食品(S26,可从Wyeth Nutrition获得)或来自出生的母乳。
在八(8)至九(9)周龄的开始,给予猴子109集落形成单位(cfu)的肠致病性大肠杆菌(EPEC)E2348/69。以通过胃插管法给予人化婴儿配方食品或母奶的方式施用EPEC。评估粪便稠度、食欲、体温和脱水。在EPEC给药的当天和在接种后的第3、6、和19或21天从每只猴子获得直肠擦抹物。
通过混合150克含有1010cfu/g的每种微生物的嗜酸乳杆菌NCFM(North Carolina Dairy Foundation的商标)和婴儿双歧杆菌BB1(都从Rhodia公司获得)的等量混合物来制备益生菌。将益生菌只掺入人化的配制品中。在研究结束前7天,将所有喂养配制品的猴子转变为补充有如上所述的益生菌混合物的配制品。以每种细菌为1.3×1010cfu/L的滴度喂养益生菌。
收集直肠擦抹物并如下所述进行微生物评估。
为了评估外源导入的致病和益生细菌的集群,发展了能够鉴定特异性的微生物种类的聚合酶链式反应(PCR)分析。设计只检测令人感兴趣的种类的引物以便排除属内的其他种类。从在LAC25平板上生长的两组粪便培养物的样品中分离DNA,一组为有氧生长的而第二组为无氧生长的。随后冷冻两组粪便培养物。如下进行PCR反应:94℃30秒,50℃1分钟,以及72℃1分钟,进行5个循环,然后立即为94℃30秒,56℃1分钟,以及72℃1分钟,进行30个循环。引入最终的延伸时间(72℃10分钟)以保证完全合成所有的DNA产物。通过琼脂糖凝胶电泳分离PCR产物,并且经透射目测观察。
通过16S核糖体的方法证实乳酸双歧杆菌和嗜酸乳杆菌的鉴定。从由菌落分离的基因组DNA对来自乳酸双歧杆菌和嗜酸乳杆菌的特定长度的16SrRNA基因区域进行PCR扩增。由于种属之间16SrRNA基因的同源性,从大肠杆菌(第005和531位)设计引物,其从令人感兴趣的种类特异地产生唯一长度的可区别产物。利用AmpliTaq FS DNA聚合酶和罗丹明染料终止剂进行16SrRNA扩增产物的循环测序,并且在ABIPrism 377DNA测序仪上电泳。利用PE/Applied生物系统DNA编辑和装配软件分析数据。将来自扩增产物的序列与序列数据库相比较并产生表现出种属水平相配的大于99%准确度的16SrRNA序列同源性。
根据这些鉴定设计引物对。参考公共的DNA数据库以确定适于独特PCR引物对的细菌DNA区域。乳酸双歧杆菌引物对靶向乳酸双歧杆菌的413bp区域,而嗜酸乳杆菌引物对靶向嗜酸乳杆菌的460bp区域。为了便于在琼脂糖凝胶上进行鉴定,通过添加GC-尾部来改进嗜酸乳杆菌的引物。
设计成特异地检测嗜酸乳杆菌的引物对针对鼠李糖乳杆菌、植物乳杆菌(L.plantarum)和鼠李糖乳杆菌GG是有效的。设计成能特异地检测乳酸双歧杆菌的引物对针对青春双歧杆菌(B.adolescentis)、婴儿双歧杆菌、和双歧双歧杆菌是有效的。在每种情况中只检测到令人感兴趣的种类。
也发展了PCR方法并用于确定动物体是否已经通过外源导入的肠致病性大肠杆菌(EPEC)E2348/69而具有集落菌。PCR方法包括在如上所述的PCR反应前从60个冷冻样品的每一种分离的DNA。根据公开的序列信息,设计能够特异性地检测编码EPEC的BFP蛋白质基因的326bp区域的EPEC PCR引物。被设计成能检测EPEC的EPEC引物针对肠产毒性大肠杆菌(ETEC)是有效的。只检测到EPEC。
通过PCR检查来自猴子的粪便擦抹样品中EPEC DNA的存在。在采取处理的第0天、感染当天,在任何样品中没有检测到EPEC。在处理的第3天(用EPEC感染后),所有的样品被测试为EPEC阳性。令人惊讶地,在研究的最后一天,在处理的第19或21天,在从喂养了补充有益生菌的配制品的猴子采集的任何粪便擦抹样品中没有检测到EPEC;而在来自哺母乳的猴子的所有粪便擦抹样品中检测到了EPEC。
表1说明PCR测定的结果。接种EPEC的猴子在单个EPEC接种后直到3周具有EPEC-阳性的擦抹物。这表明这些猴子中菌落的成功的集群化。而到研究结束时在EPEC接种和集落化之后,这些用补充有益生菌的配制品喂养的猴子具有EPEC-阴性的粪便擦抹物。相比之下,没有接收益生菌的哺乳猴子保持EPEC-阳性。
表1
喂养配制品的猴子 | ||||
动物ID | 天数 | EPEC | 乳酸双歧杆菌 | 嗜酸乳杆菌 |
47 | 0 | - | ND | ND |
3 | + | ND | ND | |
6 | + | - | - | |
19 | - | + | + | |
48 | 0 | - | ND | ND |
3 | - | ND | ND | |
6 | + | - | - | |
19 | - | + | - | |
40 | 0 | - | ND | ND |
3 | + | ND | ND | |
6 | + | - | - | |
19 | - | + | - | |
57 | 0 | - | ND | ND |
3 | + | ND | ND | |
6 | + | - | - | |
19 | - | + | + | |
63 | 0 | -/+ | ND | ND |
3 | + | ND | ND | |
6 | + | - | - | |
19 | - | + | + | |
91 | 0 | - | ND | ND |
3 | + | ND | ND | |
6 | + | - | - | |
19 | - | + | + | |
100 | 0 | - | ND | ND |
3 | + | ND | ND | |
6 | + | + | - | |
21 | - | + | - | |
105 | 0 | - | ND | ND |
3 | + | ND | ND | |
6 | + | + | - | |
21 | - | + | - | |
109 | 0 | - | ND | ND |
3 | + | ND | ND | |
6 | + | - | - | |
21 | - | + | - |
哺乳的猴子 | ||||
动物ID | 天数 | EPEC | 乳酸双歧杆菌 | 嗜酸乳杆菌 |
118 | 0 | - | ND | ND |
3 | + | ND | ND | |
6 | + | + | - | |
21 | + | - | + | |
108 | 0 | - | ND | ND |
3 | + | ND | ND | |
6 | + | + | - | |
21 | -/+ | + | - | |
54 | 0 | - | ND | ND |
3 | + | ND | ND | |
6 | + | + | - | |
21 | + | + | - |
ND=未进行;
-/+指示在重复试验中有变化的结果
在喂养了配制品的猴子中完成补充益生菌的方案后,通过如上所述的PCR分析确证益生菌(嗜酸乳杆菌NCFM和乳酸双歧杆菌BBI)在肠内的集群化。表1证明了在肠内施用人益生菌而在恒河猴幼儿中集群化。同时,从来自猴子胃肠道的分离物中没有检测到致病性的大肠杆菌。
实施例1的婴儿配方食品可类似地用于消灭来自猴子胃肠道的致病大肠杆菌。
本发明可以以其他特定的形式具体体现而不背离其精神和基本的特征,因此应该参考所附的权利要求书,而不是上述说明书来表明本
发明的范围。
Claims (12)
1.一种营养性组合物,包括低聚果糖、唾液酸乳糖和益生细菌。
2.如权利要求1中所述的营养性组合物,其中益生细菌是嗜酸乳杆菌和乳酸双歧杆菌。
3.如权利要求2中所述的营养性组合物,包括、或能够包括用水稀释后的0.1g/L至10g/L的低聚果糖、6mg/L至10g/L的唾液酸乳糖、106至1014cfu/L的嗜酸乳杆菌和106至1014cfu/L的乳酸双歧杆菌。
4.一种消灭患者胃肠道中的致病生物的方法,包括对所述的患者肠内施用包括低聚果糖、唾液酸乳糖和益生细菌的营养性组合物。
5.低聚果糖、唾液酸乳糖和益生细菌在制备用于消灭胃肠道中的致病生物的药物中的用途,该药物是用于肠内给药的营养性组合物的形式。
6.用作药物的如权利要求1中所述的营养性组合物。
7.如权利要求5中所述的用途,其中所述的药物是婴儿配方食品的形式。
8.如权利要求5或7中所述的用途,其中所述的益生细菌是嗜酸乳杆菌和乳酸双歧杆菌。
9.如权利要求8中的用途,其中所述的药物包括在用水稀释后或能够包括0.1g/L至10g/L的低聚果糖、6mg/L至10g/L的唾液酸乳糖、106至1014cfu/L的嗜酸乳杆菌和106至1014cfu/L的乳酸双歧杆菌。
10.如权利要求8中所述的用途,其中所述的药物包含或在用水稀释后能够包含0.3g/L至6g/L的低聚果糖、60mg/L至1g/L的唾液酸乳糖、108至1012cfu/L的嗜酸乳杆菌和108至1012cfu/L的乳酸双歧杆菌。
11.如权利要求8中所述的用途,其中所述的药物包括或在用水稀释后能够包括0.3g/L至6g/L的低聚果糖、60mg/L至1g/L的唾液酸乳糖、108至1012cfu/L的嗜酸乳杆菌和108至1012cfu/L的乳酸双歧杆菌。
12.低聚果糖、唾液酸乳糖、嗜酸乳杆菌和乳酸双歧杆菌细菌在制备用于预防由肠致病性大肠杆菌导致的腹泻的药物中的用途,该药物是用于肠内给药的婴儿配方食品的形式。
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OA (1) | OA13142A (zh) |
PL (1) | PL375071A1 (zh) |
WO (1) | WO2004032639A1 (zh) |
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-
2003
- 2003-10-08 AU AU2003282494A patent/AU2003282494A1/en not_active Abandoned
- 2003-10-08 MX MXPA05003597A patent/MXPA05003597A/es not_active Application Discontinuation
- 2003-10-08 WO PCT/US2003/031928 patent/WO2004032639A1/en not_active Application Discontinuation
- 2003-10-08 PL PL03375071A patent/PL375071A1/xx unknown
- 2003-10-08 BR BR0315209-0A patent/BR0315209A/pt not_active IP Right Cessation
- 2003-10-08 NZ NZ539862A patent/NZ539862A/en unknown
- 2003-10-08 CA CA002500366A patent/CA2500366A1/en not_active Abandoned
- 2003-10-08 EP EP03774686A patent/EP1549151A1/en not_active Withdrawn
- 2003-10-08 US US10/681,658 patent/US20040072794A1/en not_active Abandoned
- 2003-10-08 CN CNA2003801011770A patent/CN1703149A/zh active Pending
- 2003-10-08 OA OA1200500104A patent/OA13142A/en unknown
-
2005
- 2005-04-04 NO NO20051651A patent/NO20051651L/no not_active Application Discontinuation
- 2005-04-08 EC EC2005005725A patent/ECSP055725A/es unknown
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CN103369974A (zh) * | 2010-12-31 | 2013-10-23 | 雅培制药有限公司 | 包含人乳低聚糖和长链多不饱和脂肪酸的营养型制剂以及其用途 |
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CN110051676A (zh) * | 2010-12-31 | 2019-07-26 | 雅培制药有限公司 | 用于调节炎症的人乳寡糖 |
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US11524018B2 (en) | 2010-12-31 | 2022-12-13 | Abbott Laboratories | Nutritional formulations including human milk oligosaccharides and antioxidants and uses thereof |
US11633412B2 (en) | 2010-12-31 | 2023-04-25 | Abbott Laboratories | Nutritional formulations including human milk oligosaccharides and antioxidants and uses thereof |
US11654156B2 (en) | 2010-12-31 | 2023-05-23 | Abbott Laboratories | Nutritional formulations including human milk oligosaccharides and antioxidants and uses thereof |
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Also Published As
Publication number | Publication date |
---|---|
NO20051651L (no) | 2005-05-06 |
US20040072794A1 (en) | 2004-04-15 |
BR0315209A (pt) | 2005-08-16 |
WO2004032639A1 (en) | 2004-04-22 |
CA2500366A1 (en) | 2004-04-22 |
EP1549151A1 (en) | 2005-07-06 |
AU2003282494A1 (en) | 2004-05-04 |
NZ539862A (en) | 2006-05-26 |
ECSP055725A (es) | 2005-07-06 |
MXPA05003597A (es) | 2005-06-03 |
PL375071A1 (en) | 2005-11-14 |
OA13142A (en) | 2006-12-13 |
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