CN101695374A - 包括碱性鞘磷脂酶的用作饮食制剂、食品添加剂或药物制剂的组合物 - Google Patents
包括碱性鞘磷脂酶的用作饮食制剂、食品添加剂或药物制剂的组合物 Download PDFInfo
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- CN101695374A CN101695374A CN200910129862A CN200910129862A CN101695374A CN 101695374 A CN101695374 A CN 101695374A CN 200910129862 A CN200910129862 A CN 200910129862A CN 200910129862 A CN200910129862 A CN 200910129862A CN 101695374 A CN101695374 A CN 101695374A
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- lactobacillus
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- bifidobacterium
- illness
- bacterium
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Abstract
本发明涉及一种取决于使用者，可以作为营养、饮食或严格地治疗性制剂的，包括作为其活性物质的能够预防或治疗包括癌性过程、肠的炎性过程、高胆固醇血症和幽门螺杆菌感染的各种病理条件的碱性鞘磷脂酶的组合物。
Description
本发明涉及碱性鞘磷脂酶用于制备旨在营养、饮食或严格地治疗性用途的组合物的用途，和用这种方法制造的组合物。
因此，取决于此组合物所面向的特定个体，根据它们是否旨在充当合适的基料或预防性治疗或者充当治疗性制剂，这些组合物可以是如下形式并可充当合适的食品添加剂(food supplement)、饮食基料或药物制剂。
到目前为止已经鉴定了三种不同类型的鞘磷脂酶(SMase)。
有一种酸性鞘磷脂酶，它是一种溶酶体酶(具有最适pH 4.5-5)，其缺乏引起尼曼氏病，有一种中性鞘磷脂酶，具有最适pH 7.5，它的两种同工型已被描述。这些同工型之一定位在细胞膜并且依赖于镁，而另一种被容纳于细胞浆并且不依赖于阳离子。酸性鞘磷脂酶和中性鞘磷脂酶都在许多组织和细胞中被发现，是普遍存在的酶，涉及许多细胞功能。
第三种类型被称为碱性鞘磷脂酶，因为它主要在pH 9有活性。它不依赖于镁，并且在肠刷状缘中和在胆汁中都有发现。碱性鞘磷脂酶不存在于胃、十二指肠或胰腺，但是在肠，特别是在空肠的远端被发现。在结肠和直肠也观察到一个显著的碱性鞘磷脂酶活性。还在胆汁中发现了高水平的碱性鞘磷脂酶活性，但是，这似乎是人类特有的。鞘磷脂酶的这个双重来源使得人类与其它生物相比较，在水解通过饮食引进的鞘磷脂(SM)方面非常有效。迄今为止，认为碱性鞘磷脂酶不能由肠的细菌产生，因为在常规动物和无菌动物之间没有发现差异(参见R.D.Duan，斯堪的纳维亚胃肠学杂志(Scand.J.Gastroenterology)，33(1998)pp.673-683)。
除了存在于肠和存在于胆汁中的碱性鞘磷脂酶之外，已知没有其它碱性鞘磷脂酶可以用来生产旨在营养、饮食或严格地治疗性用途的组合 物。而且，酸性和中性鞘磷脂酶由于他们的不同特征而不能被使用(参见下表)。
表
就美容和皮肤学而言，鞘磷脂酶的用途已经公知。
日本专利No.63 216,813描述了含有鞘磷脂酶并且旨在抵消存在于皮肤中的这种酶随着衰老生理性减少以及促进其转化成神经酰胺而神经酰胺又对表皮有增加水分之作用的美容组合物。
国际专利申请PCT WO 98/22.082描述了鞘磷脂酶用于制备适合于治疗诸如皮炎、牛皮癣、鱼鳞癣和相似情形的病症的组合物。进一步地，此PCT申请描述了从革兰氏阴性细菌、革兰氏阳性细菌和乳酸细菌的菌株制备鞘磷脂酶，具有清晰的优越于先前所公知的使用诸如脑和肝的高等动物器官作为启始材料的过程的优点。
令人惊讶地是，现在已经发现一些细菌拥有高水平的碱性鞘磷脂酶，并且，他们的摄取可以有益于宿主。这些细菌可能与其它诸如乳酸细菌的细菌、与SM和/或与含有SM的食物组合，活着或以提取物的形式摄取，只要这些有酶活性。
因此，本发明的目的之一是提供一种包括足以在需要它的个体中发挥饮食、营养或治疗性作用的量的碱性鞘磷脂酶的饮食、营养或药物组合物。
特别地，此组合物适合于预防和/或治疗与肠发育有关的病症、癌性过程、免疫应答的病症、肠及其相关结构的炎性和凋亡过程、与胆固醇 合成有关的病症、由胃肠道表面的疏水特性所引起的病症、胃肠道的变应性病症、涉及消化过程的病症、炎性肠疾病、息肉病、特别是家族性息肉病、高胆固醇血症、幽门螺杆菌感染、新生儿生长的病症、与肠内稳态有关的病症以及中枢和外周神经系统的病症。
本组合物对在小儿科食物和/或肠内营养中使用也是有用的。在小儿科食物中，本组合物可以，例如，总的来说，与人造奶、炼乳、豆奶、奶粉、部分人源化奶(umanized milk)以及婴儿食品组合给食。
此组合物优选地含有细菌来源的碱性鞘磷脂酶，并且从革兰氏阴性细菌、革兰氏阳性细菌和乳酸细菌当中，或从其混合物中选择含有碱性鞘磷脂酶的细菌。
更加特别地，此组合物的碱性鞘磷脂酶从乳酸细菌获得，并且这些选自嗜酸乳杆菌(Lactobacillus acidophilus)、短乳杆菌(Lactobacillus brevis)、布赫内氏乳杆菌(Lactobacillus buchneri)、干酪乳杆菌(Lactobacillus casei)、链状乳杆菌(Lactobacilluscatenaforme)、纤维二糖乳杆菌(Lactobacillus cellobiosus)、卷曲乳杆菌(Lactobacillus crispatus)、弯曲乳杆菌(Lactobacilluscurvatus)、戴尔布吕克氏乳杆菌(Lactobacillus delbrueckii)、发酵乳杆菌(Lactobacillus fermentum)、詹氏乳杆菌(Lactobacillusjensenii)、莱希曼氏乳杆菌(Lactobacillus leichmannii)、小乳杆菌(Lactobacillus minutus)、植物乳杆菌(Lactobacillus plantarum)、罗氏乳杆菌(Lactobacillus rogosae)、唾液乳杆菌(Lactobacillussalivarius)、青春双歧杆菌(Bifidobacterium adolescentis)、角双歧杆菌(Lactobacillus angulatum)、双歧双歧杆菌(Bifidobacteriumbifidum)、短双歧杆菌(Bifidobacterium breve)、链状双歧杆菌(Bifidobacterium catenulatum)、齿双歧杆菌(Bifidobacteriumdentium)、埃氏双歧杆菌(Bifidobacterium eriksonii)、婴儿双歧杆菌(Bifidobacterium infantis)、长双歧杆菌(Bifidobacteriumlongum)、植物双歧杆菌(Bifidobacterium plantarum)、假链状双歧杆菌(Bifidobacterium pseudocatenulatum)、假长双歧杆菌 (Bifidobacterium pseudolongum)、乳链球菌(Streptococcus lactis)、棉子糖乳链球菌(Streptococcus raffinolactis)、嗜热链球菌(Streptococcus thermophilus)。
在这些乳酸细菌当中特别优选的菌株是根据布达佩斯条约于1998年2月6日在德国Braunschweig德国微生物和细胞培养物保藏中心(DSM)(“Deutsche Sammlung von Mikroorganismen und Zellkul turen GmbH”)以保藏号No.DSM 11,988申报的短乳杆菌CD2(Lactobacillus brevisCD2)菌株，或其突变体或衍生物。
根据本发明的一个优选实施方案，乳酸细菌作为活的、冻干的或超声处理过的细菌用于此组合物。
此组合物优先地含有每克组合物1×102到1×1013菌落形成单位(CFU)的乳酸细菌。
一种特别优选的组合物每克组合物含有200×109嗜热链球菌(Streptococcus thermophilus)，150×109双歧杆菌(Bifidobacteria)和4×109嗜酸乳杆菌(Lactobacillus acidophilus)。
根据本发明的组合物还可以含有胆汁酸，特别是熊去氧胆酸、果胶、鞘磷脂或其复合物、含有鞘磷脂的药物或食物、精氨酸脱亚胺酶(deiminase)、脂肪酸、多不饱和脂肪酸、非发酵的糖、特别是乳果糖、胆固醇抑制剂、神经酰胺酶抑制剂、蛋白酶抑制剂、免疫调节剂、抗致癌剂、维生素、生长因子、表面活性剂、谷物、纤维、乳化剂、稳定剂、脂类、抗氧化剂、防腐剂、自由基中和剂和/或血管保护剂。
本发明的组合物可以作为食品添加剂经口给食或者作为药物经口或非经胃肠给药。
本发明还涉及碱性鞘磷脂酶用于制备适合于预防和/或治疗与肠发育有关的病症、癌性过程、免疫应答的病症、肠及其相关结构的炎性和凋亡过程、与胆固醇合成有关的病症、由胃肠道表面的疏水特性所引起的病症、胃肠道的变应性病症、涉及消化过程的病症、炎性肠病、息肉病、特别是家族性息肉病、高胆固醇血症、幽门螺杆菌感染、新生儿生长的病症、与肠内稳态有关的病症以及中枢和外周神经系统的病症的饮 食、营养或药物组合物的用途。
此组合物还对在小儿科食物和/或肠内营养中使用有用。在小儿科食物中，此组合物一般可以，例如，与人造奶、炼乳、豆奶、奶粉、部分人源化的奶(umanized milk)和婴儿食品组合给食。
所使用的碱性磷脂酶优选地是细菌来源的，并且含有它的细菌从革兰氏阴性细菌、革兰氏炎性细菌和乳酸细菌当中或从其混合物中选择。
更加特别地，所使用的乳酸细菌选自嗜酸乳杆菌(Lactobacillusacidophilus)、短乳杆菌(Lactobacillus brevis)、布赫内氏乳杆菌(Lactobacillus buchneri)、干酪乳杆菌(Lactobacillus casei)、链状乳杆菌(Lactobacillus catenaforme)、纤维二糖乳杆菌(Lactobacillus cellobiosus)、卷曲乳杆菌(Lactobacilluscrispatus)、弯曲乳杆菌(Lactobacillus curvatus)、戴尔布吕克氏乳杆菌(Lactobacillus delbrueckii)、发酵乳杆菌(Lactobacillusfermentum)、詹氏乳杆菌(Lactobacillus jensenii)、莱希曼氏乳杆菌(Lactobacillus leichmannii)、小乳杆菌(Lactobacillus minutus)、植物乳杆菌(Lactobacillus plantarum)、罗氏乳杆菌(Lactobacillusrogosae)、唾液乳杆菌(Lactobacillus salivarius)、青春双歧杆菌(Bifidobacterium adolescentis)、角双歧杆菌(Lactobacillusangulatum)、双歧双歧杆菌(Bifidobacterium bifidum)、短双歧杆菌(Bifidobacterium breve)、链状双歧杆菌(Bifidobacteriumcatenulatum)、齿双歧杆菌(Bifidobacterium dentium)、埃氏双歧杆菌(Bifidobacterium eriksonii)、婴儿双歧杆菌(Bifidobacteriuminfantis)、长双歧杆菌(Bifidobacterium longum)、植物双歧杆菌(Bifidobacterium plantarum)、假链状双歧杆菌(Bifidobacteriumpseudocatenulatum)、假长双歧杆菌(Bifidobacterium pseudolongum)、乳链球菌(Streptococcus lactis)、棉子糖乳链球菌(Streptococcusraffinolactis)、嗜热链球菌(Streptococcus thermophilus)。
在这些乳酸细菌当中特别优选的菌株是根据布达佩斯条约于1998年2月6日在德国Braunschweig德国微生物和细胞培养物保藏中心(DSM) (“Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH”)以保藏号No.DSM 11,988保藏的短乳杆菌CD2(Lactobacillus brevisCD2)菌株或其突变体或衍生物。
根据本发明的一个优选实施方案，乳酸细菌作为活的、冻干的或超声处理过的细菌使用于此组合物。
使用的组合物优选地每克组合物含有1×102到1×1013CFU的乳酸细菌。
一个特别优选的组合物每克组合物含有200×109嗜热链球菌，150×109双歧杆菌和4×109嗜酸乳杆菌。
进行以下实验以确认在根据本发明的细菌中碱性鞘磷脂酶的存在及效率。这些实验涉及碱性鞘磷脂酶-负责人皮肤中神经酰胺之形成的酶-的检测。
方法
乳酸细菌中和肠活组织检查材料中酸性、中性和碱性鞘磷脂酶的分析
将10mg冻干的嗜热链球菌细菌悬浮于500μl的一种含有50mMTris-HCl，pH 7.4，10mM MgCl2，2mM EDTA，5mM DTT，0.1mM Na3Vo4，0.1mM Na2MoO4，30mM磷酸对硝基苯酯，10mM β-磷酸甘油，750mM ATP，1μM PMSF，10μM亮肽素，10μM抑肽素(购自希格玛化学公司(SigmaChemical Co.))和0.2％Triton X-100(为了分析中性SMase的活性)或500μl的0.2％Triton X-100(为了分析酸性SMase的活性)的缓冲液。为了分析碱性鞘磷脂酶活性，将细菌和(匀浆的)肠的活组织检查材料悬浮在含有5mM MgCl2，0.15M KCl，50mM KH2PO4，1mM PMSF和1mM苯甲脒(pH 7.4)的0.25M蔗糖缓冲液中。此后使用一台Vibracell超声仪(美国康涅狄格州丹伯利，声学材料公司(Sonic and MaterialsInc.，Danbury，CT))通过超声对以这种方法制备的样品进行裂解(持续30分钟，其中10-sec“开”时间段与10-sec“关”时间段交替)。此后将超声过的样品在4℃以14,000rpm离心30分钟，去除上清，并用美国加利福尼亚州伯乐公司(Bio-Rad Laboratories，(Richmond，CA))的一种试剂盒确定了蛋白的浓度。
为了确定中性SMase，将100μg的样品在一种含有50mM Tris-HCl，1mM MgCl2，pH 7.4，和2.25μl的[N-甲基-14碳]-鞘磷脂(SM)(0.2μCi/ml，比活：56.6mCi/mmol，Amersham)的缓冲液(终体积：50μl)中在37℃温育2小时。
为了确定酸性鞘磷脂酶，将100μg的细菌裂解物在37℃在一种含有250mM乙酸钠，1mM EDTA，pH 5.0，和2.25μl的[N-甲基-14C]-SM的缓冲液中(终体积：50μl)温育2小时。
为了分析碱性SMase，将这些样品加入375μl的Tris-EDTA缓冲液中(pH 9)至终体积为0.4ml，含有50mM Tris，0.5M NaCl，2mM EDTA和一种TC∶TDC∶GC∶GCDC摩尔比为3∶2∶1.8∶1的3mM胆汁盐的混合物。胆汁盐的这种混合物被发现对碱性SMase具有最高的刺激效应。向缓冲液中加入EDTA用来抑制Mg++-依赖性的最适pH为7.5的中性SMase的活性。14C-SM被溶解在乙醇中，在氮气中干燥并悬浮在含有3％TritonX-100和3mM胆汁盐的混合物的分析缓冲液。
通过加入2ml的氯仿和甲醇2∶1混合物终止反应。提取磷脂并在TLC板上分析，而SM的水解通过放射自显影和液体闪烁计数定量。存在于超声过的细菌中和肠活组织检查材料中的SMase表示成每小时每毫克蛋白被水解的SM的皮摩尔数。
来自嗜热链球菌的SMase的活性
图1说明超声过的乳酸细菌中鞘磷脂酶的活性水平。没有发现由酸性SMase引起的活性，但是，在所使用的实验条件下(各种pH值和具有以及没有MgCl2)在被测试的细菌样品中中性和碱性SMase都观察到了明显的水平。
在肠的活组织检查材料中发现的碱性鞘磷脂酶
图2说明，肠的活组织检查材料中的SMase活性的分析显示了依赖 于胆汁盐类型的碱性SMase的一个高活性水平，这在缺少胆汁盐时不能被检测到。在一位患局限性回肠炎的患者的组织中的酶活性的水平显示了比对照样品更低的碱性SMase水平。
嗜热链球菌对肠的碱性SMase的作用
如图3所示，在确定肠SMase所使用的实验条件下嗜热链球菌的样品中SMase活性的分析，说明了此细菌酶不受胆汁盐之存在或不存在的影响。进一步地，当同时测定细菌SMase活性和肠SMase活性时，SM的水解加和性地提高。用根据布达佩斯条约于1998年2月6日在德国Braunschweig德国微生物和细胞培养物保藏中心(DSM)(“DeutscheSammlung von Mikroorganismen und Zellkulturen GmbH”)以保藏号No.DSM 11，988保藏的短乳杆菌CD2(Lactobaillus brevis CD2)菌株或其突变体或衍生物获得了相似的结果(没有显示)。
附图说明
图1显示了在嗜热链球菌中发现的SMase活性。
图2显示了在肠的活组织检查中发现的碱性SMase。
图3显示了嗜热链球菌对肠碱性SMase的作用。
本申请还公开了如下内容：
1.饮食、营养或药物组合物，其特征在于它包括足以在需要它的个体中发挥饮食、营养或治疗性效应的量的碱性鞘磷脂酶。
2.根据项目1的组合物，适合于预防和/或治疗与肠发育有关的病症、癌性过程、免疫应答的病症、肠及其相关结构的炎性和凋亡过程、与胆固醇合成有关的病症、由胃肠道表面的疏水特性引起的病症，胃肠道的变应性病症、涉及消化过程的病症，炎性肠疾病、息肉病、特别是家族性息肉病、高胆固醇血症、幽门螺杆菌感染、新生儿生长的病症、与肠内稳态有关的疾病以及中枢和外周神经系统的病症。
3.根据项目1或2的组合物，适合在小儿科饮食中使用。
4.根据项目1或2的组合物，适合在肠内营养中使用。
5.根据项目3的组合物，其特征在于此组合物一般与人造奶、炼乳、豆奶、奶粉、部分人源化的奶和婴儿食品联合给食。
6.根据在先项目中任何一项的组合物，其特征在于此碱性磷脂酶是细菌来源的，并且该含有此碱性磷脂酶的细菌从革兰氏阳性细菌、革兰氏阴性细菌和乳酸细菌或从其混合物中选择。
7.根据项目6的组合物，其特征在于乳酸细菌选自嗜酸乳杆菌、短乳杆菌、布赫内氏乳杆菌、干酪乳杆菌、链状乳杆菌、纤维二糖乳杆菌、卷曲乳杆菌、弯曲乳杆菌、戴尔布吕克氏乳杆菌、发酵乳杆菌、詹氏乳杆菌、莱希曼氏乳杆菌、小乳杆菌、植物乳杆菌、罗氏乳杆菌、唾液乳杆菌、青春双歧杆菌、角双歧杆菌、双歧双歧杆菌、短双歧杆菌、链状双歧杆菌、齿双歧杆菌、埃氏双歧杆菌、婴儿双歧杆菌、长双歧杆菌、植物双歧杆菌、假链状双歧杆菌、假长双歧杆菌、乳链球菌、棉子糖乳链球菌、嗜热链球菌。
8.根据项目7的组合物，其特征在于使用根据布达佩斯条约于1998年2月6日在德国Braunschweig德国微生物和细胞培养物保藏中心(DSM)(“Deutsche Sammlung von Mikroorganismen und ZellkulturenGmbH”)以保藏号No.DSM 11,988保藏的短乳杆菌CD2菌株或其突变体或衍生物。
9.根据在先项目中任何一项的组合物，其特征在于此乳酸细菌作为活的、冻干的或者超声处理过的细菌在此组合物中使用。
10.根据在先项目中任何一项的组合物，其特征在于它每克组合物含有1×102到1×1013CFU的乳酸细菌。
11.根据项目7到9中任何一项的组合物，其特征在于它每克组合物含有200×109嗜热链球菌，150×109双歧杆菌和4×109嗜酸乳杆菌。
12.根据在先项目中任何一项的组合物，其特征在于它还含有胆汁酸，特别是熊去氧胆酸、果胶、鞘磷脂或其复合物、含有鞘磷脂的药物或食物、精氨酸脱亚胺酶、脂肪酸、多不饱和脂肪酸、非发酵的糖、特别是乳果糖、胆固醇抑制剂、神经酰胺酶抑制剂、蛋白酶抑制剂、免疫调剂剂、抗致癌剂、维生素、生长因子、表面活性剂、谷物、纤维、乳化剂、稳定剂、脂类、抗氧化剂、防腐剂、自由基中和剂和/或血管保护剂。
13.根据在先项目中任何一项的组合物，它可以作为食品添加剂经口给食。
14.根据在先项目中任何一项的组合物，它可以作为药物经口或非经胃肠给药。
15.碱性鞘磷脂酶用于制备适合于预防和/或治疗与肠发育有关的病症、癌性过程、免疫应答的病症、肠及其相关结构的炎性和凋亡过程、与胆固醇合成有关的病症、由胃肠道表面的疏水特性引起的病症、胃肠道的变应性病症、涉及消化过程病症、炎性肠疾病炎性肠疾病、息肉病、特别是家族性息肉病、高胆固醇血症、幽门螺杆菌感染、新生儿生长的病症、与肠内稳态有关的疾病以及中枢和外周神经系统的病症的饮食、营养或药物组合物的用途。
16.根据项目15的用途，在小儿科饮食方面。
17.根据项目15的用途，在肠内营养方面。
18.根据项目16的用途，在其特征在于此组合物一般与人造奶、炼乳、豆奶、奶粉，部分人源化的奶以及婴儿食物组合给食。
19.根据项目15至18中任何一项的用途，其中碱性鞘磷脂酶是细菌来源的，并且该含有它的细菌从革兰氏阳性细菌、革兰氏阴性细菌和乳酸细菌或从其混合物中选择。
20.根据项目19的用途，其特征在于此乳酸细菌选自嗜酸乳杆菌、短乳杆菌、布赫内氏乳杆菌、干酪乳杆菌、链状乳杆菌、纤维二糖乳杆菌、卷曲乳杆菌、弯曲乳杆菌、戴尔布吕克氏乳杆菌、发酵乳杆菌、詹氏乳杆菌、莱希曼氏乳杆菌、小乳杆菌、植物乳杆菌、罗氏乳杆菌、唾液乳杆菌、青春双歧杆菌、角双歧杆菌、双歧双歧杆菌、短双歧杆菌、链状双歧杆菌、齿双歧杆菌、埃氏双歧杆菌、婴儿双歧杆菌、长双歧杆菌、植物双歧杆菌、假链状双歧杆菌、假长双歧杆菌、乳链球菌、棉子糖乳链球菌、嗜热链球菌。
21.根据项目20的用途，其特征在于使用根据布达佩斯条约于1998年2月6日在德国Braunschweig德国微生物和细胞培养物保藏中心(DSM)(“Deutsche Sammlung von Mikroorganismen und ZellkulturenGmbH”)以保藏号No.DSM 11,988保藏的短乳杆菌CD2菌株或其突变体或衍生物。
22.根据项目15到21中任何一项的用途，其特征在于此乳酸细菌作为活的、冻干的或超声处理过的细菌在此组合物中使用。
23.根据项目15到21中任何一项的用途，其特征在于每克组合物使用1×102到1×1013CFU的乳酸细菌。
24.根据项目15到21中任何一项的用途，其特征在于每克组合物使用200×109嗜热链球菌，150×109双歧杆菌和4×109嗜酸乳杆菌。
Claims (10)
1.饮食、营养或药物组合物，其特征在于它包括足以在需要它的个体中发挥饮食、营养或治疗性效应的量的碱性鞘磷脂酶。
2.根据权利要求1的组合物，适合于预防和/或治疗与肠发育有关的病症、癌性过程、免疫应答的病症、肠及其相关结构的炎性和凋亡过程、与胆固醇合成有关的病症、由胃肠道表面的疏水特性引起的病症，胃肠道的变应性病症、涉及消化过程的病症，炎性肠疾病、息肉病、特别是家族性息肉病、高胆固醇血症、幽门螺杆菌感染、新生儿生长的病症、与肠内稳态有关的疾病以及中枢和外周神经系统的病症。
3.根据权利要求1或2的组合物，适合在小儿科饮食中使用。
4.根据权利要求1或2的组合物，适合在肠内营养中使用。
5.根据权利要求3的组合物，其特征在于此组合物一般与人造奶、炼乳、豆奶、奶粉、部分人源化的奶和婴儿食品联合给食。
6.根据在先权利要求中任何一项的组合物，其特征在于此碱性磷脂酶是细菌来源的，并且该含有此碱性磷脂酶的细菌从革兰氏阳性细菌、革兰氏阴性细菌和乳酸细菌或从其混合物中选择。
7.根据权利要求6的组合物，其特征在于乳酸细菌选自嗜酸乳杆菌、短乳杆菌、布赫内氏乳杆菌、干酪乳杆菌、链状乳杆菌、纤维二糖乳杆菌、卷曲乳杆菌、弯曲乳杆菌、戴尔布吕克氏乳杆菌、发酵乳杆菌、詹氏乳杆菌、莱希曼氏乳杆菌、小乳杆菌、植物乳杆菌、罗氏乳杆菌、唾液乳杆菌、青春双歧杆菌、角双歧杆菌、双歧双歧杆菌、短双歧杆菌、链状双歧杆菌、齿双歧杆菌、埃氏双歧杆菌、婴儿双歧杆菌、长双歧杆菌、植物双歧杆菌、假链状双歧杆菌、假长双歧杆菌、乳链球菌、棉子糖乳链球菌、嗜热链球菌。
8.根据权利要求7的组合物，其特征在于使用根据布达佩斯条约于1998年2月6日在德国Braunschweig德国微生物和细胞培养物保藏中心(DSM)(“Deutsche Sammlung von Mikroorganismen und ZellkulturenGmbH”)以保藏号No.DSM 11，988保藏的短乳杆菌CD2菌株或其突变体或衍生物。
9.根据在先权利要求中任何一项的组合物，其特征在于此乳酸细菌作为活的、冻干的或者超声处理过的细菌在此组合物中使用。
10.根据在先权利要求中任何一项的组合物，其特征在于它每克组合物含有1×102到1×1013CFU的乳酸细菌。
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| CN00808645A CN1354672A (zh) | 1999-06-09 | 2000-06-07 | 包括碱性鞘磷脂酶的用作饮食制剂、食品添加剂或药物制剂的组合物 |
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| CNA2008100823554A Pending CN101352234A (zh) | 1999-06-09 | 2000-06-07 | 包括碱性鞘磷脂酶的用作饮食制剂、食品添加剂或药物制剂的组合物 |
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| KR100868777B1 (ko) * | 2007-03-15 | 2008-11-17 | 재단법인서울대학교산학협력재단 | Ｒｓ３ 유형의 저항 전분에 대해 분해능이 있는비피도박테리움 아도레스센티스를 유효성분으로 함유하는것을 특징으로 하는 식품 조성물 |
| WO2009130349A1 (es) | 2008-04-22 | 2009-10-29 | Corporación Alimentaria Peñasanta (Capsa) | Obtención de una nueva cepa de bifidobacterium bifidum con actividad frente a la infección por helicobacter pylori |
| KR101364695B1 (ko) * | 2011-06-29 | 2014-02-19 | 가천대학교 산학협력단 | 헬리코박터 파이로리의 생육을 저해하는 타락 유래 젖산균 |
| MX2015005165A (es) * | 2012-10-25 | 2015-10-29 | Gervais Danone Sa | Cepas de streptococcus thermophilus para tratar infeccion por helicobacter pylori. |
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| TW201630596A (zh) * | 2015-01-06 | 2016-09-01 | Meiji Co Ltd | 鞘脂質吸收促進劑 |
| CN109069555B (zh) * | 2016-04-13 | 2022-07-26 | 株式会社明治 | 面向新生儿的用于改善脑功能的组合物 |
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| US5716615A (en) * | 1992-02-10 | 1998-02-10 | Renata Maria Anna Cavaliere Vesely | Dietary and pharmaceutical compositions containing lyophilized lactic bacteria, their preparation and use |
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| WO1998022082A1 (en) * | 1996-11-22 | 1998-05-28 | Cavaliere Widow Vesely Renata | Sphingomyelinase compositions and use thereof |
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| WO2012168854A1 (en) | 2011-06-08 | 2012-12-13 | Pri, S. A. | Synergistic combination for the treatment of type 2 diabetes mellitus |
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