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CN1229115C - 含有益生素物质的营养配方 - Google Patents

含有益生素物质的营养配方 Download PDF

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CN1229115C
CN1229115C CNB01805191XA CN01805191A CN1229115C CN 1229115 C CN1229115 C CN 1229115C CN B01805191X A CNB01805191X A CN B01805191XA CN 01805191 A CN01805191 A CN 01805191A CN 1229115 C CN1229115 C CN 1229115C
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J·L·威尔逊
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Abstract

提供了一种包含寡聚果糖和唾液酸乳糖的营养组合物。

Description

含有益生素物质的营养配方
发明领域
本发明涉及含有益生素物质的营养配方以及这些配方在促进有益微生物的生长和抑制病原性有机体方面的应用。更具体地说,本发明涉及含有寡聚果糖和唾液酸乳糖的营养配方。
发明背景
寡聚果糖是一系列主要在蔬菜中发现的天然寡多糖,如洋葱和菊苣植物的根。寡聚果糖被认为是双歧杆菌的一种特定底物。(例如参见Mitsuoka等人,“寡聚果糖对肠微生物系统的作用(Effect of Fructo-oligosaccharides on Intestinal Microflora)”,Die Nahrung,3,5-6:427-436(1987))。
寡聚果糖通过小肠但不被消化,到达大肠。在大肠内,寡聚果糖只被有限范围的微生物发酵,该微生物包括大部分双歧杆菌种类,即有益人体健康的细菌种类。(参见Bouhnik等人,“短链寡聚果糖依赖服用剂量地增加健康人体中排泄的双歧杆菌(Short chain Fructo-oligosaccharides administration dose-dependently increases fecalbifidobacteria in healthy humans)”,J Nutrition,129:113-116)。
例如,寡聚果糖可以通过乳杆菌和双歧杆菌而有效地利用。已知在细菌的混合种群中,如存在于人结肠中的那些,寡聚果糖优先被双歧杆菌消耗。存在于该“混合种群”中的其它细菌或者不生长,或者生长被抑制。(例如参见Gibson等人,“用寡聚果糖和胰岛素选择性刺激人结肠中的双歧杆菌(Selective stimulation of bifidobacteria in thehuman colon,by oligofructose and insulin)”,Gastroenterol,108:975-982(1995))。
此外,已知双歧杆菌的代谢副产物是短链脂肪酸,导致在消化道中pH值的下降。该pH效应在临床上已经观察到,并且记录在Mitsuoka等人的“寡聚果糖对肠微生物系统的作用(Efiect of Fructo-oligosaccharides on Intestinal Microflora)”中,Die Nahrung,3,5-6:427-436(1987)。
唾液酸乳糖是在人乳汁以及其它哺乳动物乳汁中自然产生的寡多糖。但是与其它哺乳动物种类相比,人乳汁中唾液酸乳糖的存在浓度较高。
唾液酸乳糖的两种主要类型是3’-唾液酸乳糖和6’-唾液酸乳糖。这些种类以相对比例1∶3(3’∶6’)天然存在于人乳汁中。已知唾液酸乳糖对于特定的病原性细菌具有抗粘附性能。例如,已经提出唾液酸乳糖起抑制霍乱毒素(参见Idota等人,“人乳级分和唾液酸乳糖抑制霍乱毒素(Inhibition of cholera toxin by human milk fractions andsialyllactose)”,Biosci.Biotech.Biochem.59:417-419)以及幽门螺杆菌的作用(参见Simon等人,“含唾液酸的寡多糖抑制幽门螺杆菌结合到胃肠道上皮细胞”,Infection and Immunity,750-757,(1997))。考虑到其抗粘附性能,唾液酸乳糖已经用来处理许多医疗情况。例如,美国专利5514660和5753630描述了唾液酸乳糖在处理和抑制十二指肠溃疡的用途,美国专利5883079描述了在哺乳动物组织中唾液酸乳糖用来抑制幽门螺杆菌感染。
但是,这两种益生素物质,具体地说是寡聚果糖和唾液酸乳糖的组合使用以前从未描述过,因此可以看出有这种组合的需要。
发明概述
本发明涉及一种营养组合物,它可有效地增加有益的双歧杆菌并抑制病原性微生物结合到人体组织上。更具体地说,本发明涉及包含寡聚果糖和唾液酸乳糖的营养组合物。本发明进一步涉及一种增加双歧杆菌浓度并抑制病原性细菌结合到人体上的方法,包括肠内给药所述包含寡聚果糖和唾液酸乳糖的组合物。
附图简述
图1表示实施例1所述的双歧杆菌、梭菌和拟杆菌的生长。
图2表示实施例2所述的乳酸双歧杆菌的生长。
图3表示实施例3中所示的梭菌、拟杆菌和乳酸双歧杆菌的生长。
发明详述
用于本组合物的唾液酸乳糖包含3’-唾液酸乳糖和6’-唾液酸乳糖的混合物。优选此处使用的唾液酸乳糖是3’-唾液酸乳糖。用于本组合物的唾液酸乳糖可以按照下列文献描述的任何方法制备:例如美国专利5575916、5714075、5278299、5374541和5876980。但是本领域内技术人员应该理解,合成和纯化唾液酸乳糖的任何其它已知方法都可以用来制备用于本组合物的唾液酸乳糖。
本组合物的寡聚果糖组分可以由天然产生的聚果糖(菊糖)来制备,该聚果糖在许多植物中都可以找到,包括洋葱、韭菜、小麦、菊苣和朝鲜蓟。最常用的是菊苣。寡聚果糖可以采用本领域内的已知方法从这些植物中以充足的数量回收到。天然产生的菊糖包含寡聚果糖和果糖的高级聚合物。菊糖可以分离出来,因为它可溶于热水中。如果需要,天然产生的寡聚果糖可以分离出来,因为它还可溶于冷水中。任选地在除去天然产生的寡聚果糖之后,菊糖可以通过水解转化成寡聚果糖。通过采用菊糖酶,菊糖可以断裂为较小的链长。菊糖还可以通过化学水解降解为较小的链长。除了通过提取步骤之外,本组合物的寡聚果糖组分还可以通过合成来制备。寡聚果糖可以由蔗糖通过转果糖基化作用来合成,这需要借助一种酶,β-呋喃果糖苷酶来完成,它将附加的果糖单体连接到蔗糖分子上。以这种方式形成的寡聚果糖含有连接到末端葡萄糖单元上的果糖单元。衍生自从植物如菊苣中得到的菊糖的寡聚果糖含有果糖链和带有末端葡萄糖单元的果糖链。由这些方法制备的寡聚果糖是商品化的,出于本发明目的,寡聚果糖的优选形式是Raftilose(Orafti S.A.公司,Tienen,比利时)。此外,应该理解合成和/或分离寡聚果糖的任何已知方法都可适用于本发明。
本发明的营养组合物可以包含0.1g/L~10g/L寡聚果糖和6mg/L~10g/L唾液酸乳糖。优选本组合物含有0.3g/L~6g/L寡聚果糖和60mg/L~1g/L唾液酸乳糖,更优选1g/L~3g/L寡聚果糖和100mg/L~600mg/L唾液酸乳糖,甚至更优选约3g/L寡聚果糖和约100mg/L唾液酸乳糖。
本发明人已经发现,在本营养配方中寡聚果糖和唾液酸乳糖的组合产生一种协同的益生素效应,即益生素效应大于这些物质单独效应的加和。寡聚果糖和唾液酸乳糖的应用特别增加了消化道中有益细菌(双歧杆菌)的浓度,同时对病原性细菌没有效果(例如梭菌、拟杆菌、大肠杆菌等)。此外,尽管已知服用寡聚果糖会降低环境的pH值,但是已经发现寡聚果糖和唾液酸乳糖的组合会使pH值降低更多。消化道中pH值的降低导致环境不再有助于某些有机体的生长,具体地说是并非有益的或更加病原性的细菌,如大肠杆菌或拟杆菌。
本发明的营养组合物可用于与各种营养产品结合,如婴儿配方、改进型配方、儿童饮料、牛奶、酸奶、大龄儿童的水果产品(如果汁)、糖果、口香糖、止咳糖、粉剂、片剂等。优选将本组合物加入到婴儿配方中。婴儿配方可以是待哺育的液体或粉末形式,它可以和水混合,然后哺育给婴儿。最优选本配方以液体形式加入到婴儿配方中。
本发明适合使用的婴儿配方应当含有日常饮食中认为是必需的所有维生素和矿物质。这些维生素和矿物质应当以营养学显著的用量存在。可以包括在要加入本发明配方的婴儿配方中的维生素、矿物质和其它营养物的例子,包括维生素A、维生素B复合物、维生素C、维生素D、维生素E、维生素K、钙、镁、钠、钾、磷、铜、锌、氯、碘、铯、铁、烟酸、叶酸、泛酸、胆碱、生物素、肌醇和锰。
如本领域内技术人员所理解,婴儿配方可以含有一种或多种脂源。除了具有有益效果之外,婴儿配方可以进一步含有其它物质,如核苷酸、免疫球蛋白、聚不饱和脂肪酸等。
根据本发明优选的婴儿配方如下:
成分                   单位             每升
能源                    千卡              672
蛋白质                  g                 15
乳清∶酪蛋白比例                          60∶40
脂肪                    g                 36
碳水化合物              g                 72
寡聚果糖                g                 3.0
唾液酸乳糖              mg                100
维生素A                 RE                750
混合的天然胡萝卜素      IU                400
维生素D                 mcg               10.6
维生素F                 mg                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              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             90
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                      mg             433
铯                      mcg            14
参照以下实施例进一步描述本发明。
实施例1
每种微生物(梭菌、拟杆菌或乳酸双歧杆菌)的过夜培养物(PYG肉汤,37℃,厌氧)的等份接种物(A600=1.0)在恒速搅拌下分批培养生长(37℃,厌氧)。无碳水化合物的分批培养基(PYG)分别补充以葡萄糖(3.0g/L)、寡聚果糖(FOS,3.0g/L)、唾液酸乳糖(3’-或6’-唾液酸乳糖,100mg/L)、或寡聚果糖加唾液酸乳糖(分别为3.0g/L和100mg/L)。在各个时间点通过测定细菌在选择性琼脂上(双歧杆菌用BIM-25琼脂,梭菌和拟杆菌用Wilkens-Chalgren琼脂)的滴度来检测生长(见图1)。生长分析结果示于图1。
如图1所示,与葡萄糖相比,在生长培养基中用3’-唾液酸乳糖代替葡萄糖导致梭菌或拟杆菌基本不生长。但是,在寡聚果糖的存在下梭菌和婴儿双歧杆菌,而非拟杆菌,的生长类似于葡萄糖存在时的情况。寡聚果糖和唾液酸乳糖的组合对梭菌或拟杆菌的生长没有效果。但是对婴儿双歧杆菌的生长有显著效果,特别是在24小时的时间点。可以看出寡聚果糖和唾液酸乳糖的组合对婴儿双歧杆菌的生长有协同效果。
实施例2
乳酸双歧杆菌的过夜培养物(PYG肉汤,37℃,厌氧)的等份接种物(A600=1.0)在恒速搅拌下分批培养生长(37℃,厌氧)。无碳水化合物的分批培养基(PYG)分别补充以葡萄糖(3.0g/L)、寡聚果糖(3.0g/L)、或寡聚果糖(3.0g/L)加唾液酸乳糖(3’-或6’-唾液酸乳糖,100mg/L)。在各个时间点通过测定乳酸双歧杆菌在选择性琼脂上(BIM-25琼脂)的滴度来检测生长(见图2)。生长分析结果示于图2。
图2表明在寡聚果糖存在下乳酸双歧杆菌的生长明显优于葡萄糖存在下的生长。但是,在寡聚果糖和3’-或6’-唾液酸乳糖的组合存在下46小时,乳酸双歧杆菌的生长明显增强。
实施例3
双歧杆菌的一种代谢副产物是短链脂肪酸,它的存在降低了肠内的pH值。
图3表示在梭菌、拟杆菌和乳酸双歧杆菌的分批培养物接种后的不同时间的分析。每种微生物的过夜培养物(PYG肉汤,37℃,厌氧)的等份接种物(A600=1.0)在恒速搅拌下分批培养生长(37℃,厌氧)。如上所述补充无碳水化合物的分批培养基(PYG),在各个时间点检测培养基的pH值。pH值分析的结果示于图3。
图3中可以看出,在葡萄糖的存在下,所有三种结肠细菌都降低了pH值。在唾液酸乳糖单独存在时,在所有情况下pH值均升高。这与单独存在唾液酸乳糖时观察到的微生物生长较差是一致的。在寡聚果糖存在时,pH值降低,但在梭菌和婴儿双歧杆菌的分批培养物中降低的程度要比葡萄糖的小,而近似于在有葡萄糖的拟杆菌培养物中观察到的pH值变化。在本发明寡聚果糖和唾液酸乳糖的组合存在时,pH值降低到比用葡萄糖更大的程度。
但是,pH值的降低小于用葡萄糖(梭菌)或近似于葡萄糖pH值的变化(拟杆菌和乳酸双歧杆菌)。特别注意的是观察到,尽管在双歧杆菌培养物中单独使用寡聚果糖表现出pH值随时间的某些下降,但与只使用寡聚果糖的婴儿双歧杆菌培养物相比,唾液酸乳糖的存在急剧降低了pH值。因此,存在寡聚果糖和唾液酸乳糖的协同效应。
本发明可以其具体形式得到体现,而不背离其精神或其基本特征,并相应地应当参照所附的权利要求书,而非前述说明书来确定本
发明的范围。

Claims (13)

1.一种营养组合物,包含0.1g/L~10g/L寡聚果糖和6mg/L~10g/L唾液酸乳糖。
2.权利要求1的组合物,其中唾液酸乳糖是3’-唾液酸乳糖和6’-唾液酸乳糖的混合物。
3.权利要求1的组合物,其中唾液酸乳糖是3’-唾液酸乳糖。
4.权利要求1的组合物,其中唾液酸乳糖是6’-唾液酸乳糖。
5.权利要求1的营养组合物,包含0.3g/L~6g/L寡聚果糖和60mg/L~1g/L唾液酸乳糖。
6.权利要求5的营养组合物,包含1g/L~3g/L寡聚果糖和100mg/L~600mg/L唾液酸乳糖。
7.权利要求6的营养组合物,包含1.5g/L寡聚果糖和100mg/L唾液酸乳糖。
8.权利要求1的营养组合物,其中所述组合物呈液体形式。
9.权利要求1的营养组合物,其中所述组合物呈粉末形式。
10.权利要求1的营养组合物,进一步包含至少一种维生素A、维生素D、维生素E、和维生素B复合物。
11.权利要求1的营养组合物,进一步包含至少一种钙、镁、钠、钾、磷、铜、锌、碘、铯和铁。
12.权利要求1的营养组合物,它呈婴儿配方、改进型配方、儿童饮料、牛奶、酸奶、果汁、水果制饮料、糖果、口香糖、或止咳糖形式。
13.寡聚果糖和唾液酸乳糖用于制备一种在人体中增加双歧杆菌的数量并且抑制病原性细菌生长的营养组合物的用途,所述营养组合物包含0.1g/L~10g/L寡聚果糖和6mg/L~10g/L唾液酸乳糖。
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