CN104011199A - 双歧杆菌增殖促进剂 - Google Patents
双歧杆菌增殖促进剂 Download PDFInfo
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- CN104011199A CN104011199A CN201280063110.1A CN201280063110A CN104011199A CN 104011199 A CN104011199 A CN 104011199A CN 201280063110 A CN201280063110 A CN 201280063110A CN 104011199 A CN104011199 A CN 104011199A
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- bifidobacterium breve
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Abstract
将肽二聚体作为选自婴儿双歧杆菌和短双歧杆菌的细菌的增殖促进剂的有效成分,所述肽二聚体由具有序列号1所示的氨基酸序列的肽和具有序列号2~4的任意者所示的氨基酸序列的肽构成,并且各个肽中的半胱氨酸残基通过二硫键而结合。
Description
技术领域
本发明涉及双歧杆菌特别是婴儿双歧杆菌和短双歧杆菌的增殖促进剂。本发明的增殖促进剂可用作食品、饲料和药品。
背景技术
已知婴儿的肠内菌群以双歧杆菌(双歧杆菌属细菌)最占优势,可以认为这与维持婴儿的健康密切相关。在人的肠内生息的双歧杆菌的图谱(pattern)随着年龄的增长而改变,婴幼儿期主要由婴儿双歧杆菌和短双歧杆菌构成,成人期主要由长双歧杆菌和青春双歧杆菌构成(非专利文献1)。因此,开发促进双歧杆菌特别是婴儿双歧杆菌和短双歧杆菌增殖的食品对于维持婴儿健康是重要的课题。
作为双歧杆菌增殖促进因子,已知有乳蛋白质中的乳铁蛋白(非专利文献2),牛乳铁蛋白广泛应用于育儿用奶粉、补充剂(supplement)等中。
另外,作为酶消化乳蛋白质的肽,已知有酪蛋白糖巨肽(非专利文献3)、人乳铁蛋白肽(非专利文献4)。公开了人乳铁蛋白肽为对于两歧双歧杆菌的双歧因子(bifidogenic)(促进双歧杆菌成长的性质)(专利文献1)。然而,虽然两歧双歧杆菌在婴儿期也有检测出但并不是代表的菌种。
关于乳铁蛋白肽,公开了由牛乳铁蛋白的胃蛋白酶消化物生成的几种肽具有抗菌活性(非专利文献5),启示了用作自然食品的保存剂、医药、兽医学领域中的抗菌剂的可能性。然而,这些肽具有双歧杆菌增殖促进作用还不为人知。
作为短双歧杆菌的增殖促进剂,已知有N-乙酰神经氨酸和/或唾液乳糖(专利文献2);对于婴儿双歧杆菌和短双歧杆菌具有增殖促进效果的肽还不为人知。
现有技术文献
专利文献
专利文献1:日本特表2001-516570号
专利文献2:日本特开平7-267866号
非专利文献
非专利文献1:光冈知足、肠内细菌学杂志、19:179-192,2005
非专利文献2:Rahman,M.M.et.al.,Int.J.Food Sci.Tech.45:453-458,2010
非专利文献3:Azuma,N.et al.,Agric.Biol.Chem.48:2159-2162,1984
非专利文献4:Liepke,C.et al.,Eur.J.Biochem.269:712-718,2002
非专利文献5:Dionysius,D.A.et al.,J.Dairy Sci.80:667-674,1997
发明内容
发明要解决的问题
如上所述,具有两歧双歧杆菌的增殖促进作用的来源于乳蛋白质的肽是已知的,但是对于婴儿期重要的婴儿双歧杆菌和/或短双歧杆菌具有增殖促进作用的来源于乳蛋白质的肽还不为人知。
本发明的课题在于,提供以来源于乳蛋白质的肽作为有效成分的、婴儿双歧杆菌和/或短双歧杆菌的增殖促进剂。
用于解决问题的方案
本发明人等为了解决上述课题进行了深入研究,结果发现,作为抗菌肽而公开的肽(J.Dairy Sci.80:667-674,1997)之一及其类似肽对于双歧杆菌特别是婴儿双歧杆菌和短双歧杆菌具有增殖促进作用,至此完成本发明。
即,本发明为一种选自婴儿双歧杆菌和短双歧杆菌的细菌的增殖促进剂,含有肽二聚体作为有效成分,所述肽二聚体由具有序列号1所示的氨基酸序列的肽和具有序列号2~4的任意者所示的氨基酸序列的肽构成,并且各个肽中的半胱氨酸残基通过二硫键而结合。
另外,本发明提供一种选自婴儿双歧杆菌和短双歧杆菌的细菌的增殖促进用组合物,其包含前述增殖促进剂和选自婴儿双歧杆菌和短双歧杆菌的细菌。
作为优选的形式,本发明的组合物为药品。
另外,作为优选的形式,本发明的组合物为饮食品。
另外,本发明提供一种肽在用于促进选自婴儿双歧杆菌和短双歧杆菌的细菌的增殖中的应用,
前述肽为肽二聚体,由具有序列号1所示的氨基酸序列的肽和具有序列号2~4的任意者所示的氨基酸序列的肽构成,并且各个肽中的半胱氨酸残基通过二硫键而结合。
另外,本发明提供一种促进动物中的选自婴儿双歧杆菌和短双歧杆菌的细菌的增殖的方法,包括对该动物投与肽,
前述肽为肽二聚体,由具有序列号1所示的氨基酸序列的肽和具有序列号2~4的任意者所示的氨基酸序列的肽构成,并且各个肽中的半胱氨酸残基通过二硫键而结合。
具体实施方式
接着,对于本发明优选的实施方式详细地进行说明。其中,本发明不限定于以下优选的实施方式,可以在本发明的范围内自由地变更。需要说明的是,本说明书中对于百分率只要没有特别的限定,则为基于质量的表示方式。
作为本发明的增殖促进剂的有效成分的肽为肽二聚体,由具有序列号1所示的氨基酸序列的肽和具有序列号2~4的任意者所示的氨基酸序列的肽构成,并且各个肽中的半胱氨酸残基通过二硫键而结合。这些肽二聚体的结构如下述式(1)~(3)所示。式(1)的上段和下段的肽的氨基酸序列分别与序列号1和序列号2相当。式(2)的上段和下段的肽的氨基酸序列分别与序列号1和序列号3相当。式(3)的上段和下段的肽的氨基酸序列分别与序列号1和序列号4相当。本说明书中,将这些肽二聚体也记载为“活性肽”。活性肽也可以为上述肽二聚体的盐类。
活性肽具有双歧杆菌增殖促进作用,特别是对于婴儿双歧杆菌和短双歧杆菌选择性地具有显著的增殖促进作用。活性肽所具有的“增殖促进作用”意味着:摄取活性肽时与不摄取活性肽的情况相比较,肠内的婴儿双歧杆菌和/或短双歧杆菌的菌数多;或者用培养基培养婴儿双歧杆菌或短双歧杆菌时,包含活性肽的培养基比不包含活性肽的培养基的菌数多。
活性肽与已知对于两歧双歧杆菌具有增殖促进作用的具有下述式(4)的结构的来源于人乳铁蛋白的肽(Liepke,C.et al.,Eur.J.Biochem.269:712-718,2002)显示约50%的同源性,然而活性谱完全不同。即,活性肽与牛乳铁蛋白、式(4)所表示的来源于人乳铁蛋白的肽相比较,对于婴儿双歧杆菌和短双歧杆菌具有非常强的增殖促进作用;而对于两歧双歧杆菌,与牛乳铁蛋白、式(4)的来源于人乳铁蛋白的肽不同,几乎不具有增殖促进作用。需要说明的是,式(4)的来源于人乳铁蛋白的肽的氨基酸序列如序列号5所示。
活性肽可以如下制造:通过化学合成构成该肽的各个肽单体且使这些肽通过二硫键结合。肽的化学合成可以通过寡肽的合成中通常使用的液相法或固相法而进行。合成的肽根据需要被脱保护,去除未反应试剂、副产物等。这样的肽的合成可以通过使用市售的肽合成装置而进行。优选从上述合成(混合)物中分离并纯化目标的肽。肽的纯化可以通过与通常寡肽的纯化中使用的相同的手法例如适宜组合离子交换色谱、吸附色谱、反相色谱、分配色谱、凝胶过滤色谱等各种色谱,溶剂沉淀、盐析、两种液相间的分配等方法而进行。肽的纯化时,对于包含目标肽的级分,可以使它们通过二硫键结合而得到肽二聚体,对于该肽二聚体用实施例所述的方法以对于婴儿双歧杆菌或短双歧杆菌的增殖促进作用作为指标而确定;这些级分的活性成分可以通过质谱分析法或/和蛋白测序仪而鉴定。
另外,构成活性肽的肽单体还可以通过在适当的宿主细胞内使编码这些肽的重组DNA表达而制造。重组DNA的制作中所需要的载体和宿主可以使用通常蛋白质、肽的制造中所使用的物质。
为了使肽单体之间通过二硫键结合,例如,将肽单体的混合液置于适当的氧化条件中即可。适当的氧化条件可以通过以适当的比率混合二硫苏糖醇、还原型谷胱甘肽或胱氨酸等还原剂以及氧化型谷胱甘肽或半胱氨酸等氧化剂而设定。以二硫键结合的二聚体由于可以包含异二聚体和同二聚体,所以优选将具有式(1)、(2)或(3)的结构的异二聚体分离、纯化。目标的异二聚体的分离、生成可以用上述的各种色谱等方法进行。
活性肽可以直接地或者与制剂学允许的制剂载体组合而用作婴儿双歧杆菌和/或短双歧杆菌的增殖促进剂(以下,也记载为“本发明的药剂”。)。活性肽可以单独使用一种,也可以以2种或3种的混合物形式使用。
对于本发明的药剂的制剂形式没有特别的限定,可例示出:片剂(包括糖衣片、肠溶片、舌下片。)、散剂、胶囊剂(包括肠溶性胶囊、软胶囊。)、颗粒剂(包括包衣而成的颗粒。)、丸剂、含片剂、脂质体包埋剂、溶液剂或者它们的制剂学上能够允许的缓释制剂等。制剂化时,作为制剂载体可以使用通常的口服药剂中常用的赋形剂、粘合剂、崩解剂、润滑剂、稳定剂、矫味剂、稀释剂、表面活性剂、增溶剂等添加剂。另外,只要不有损本发明的效果,也可以组合活性肽、以及已知的或者将来预计可以出现的对于婴儿双歧杆菌和/或短双歧杆菌具有增殖促进作用的药剂或药品组合物。组合使用的药品组合物可以作为有效成分之一而包含在本发明的药剂中,也可以不包含在本发明的药剂中而是作为单独的药剂而组合商品化。
作为上述制剂中使用的载体和赋形剂,可例示出:乳糖、葡萄糖、白糖、甘露糖、马铃薯淀粉、玉米淀粉、碳酸钙、磷酸钙、硫酸钙、结晶纤维素、甘草末、龙胆末等;作为粘合剂,可例示出例如:淀粉、明胶、糖浆、聚乙烯醇、聚乙烯基醚、聚乙烯基吡咯烷酮、羟丙基纤维素、乙基纤维素、甲基纤维素、羧甲基纤维素等。
另外,作为崩解剂可例示出:淀粉、琼脂、明胶末、羧甲基纤维素钠、羧甲基纤维素钙、结晶纤维素、碳酸钙、碳酸氢钠和藻酸钠等。
进而,分别地,作为润滑剂可例示出:硬脂酸镁、氢化植物油和聚乙二醇等;作为着色剂,可例示出:药品中能够允许添加的红色2号、黄色4号和蓝色1号等。
片剂和颗粒剂可以根据需要用白糖、羟丙基纤维素、纯化虫胶、明胶、山梨糖醇、甘油、乙基纤维素、羟丙基纤维素、羟丙基甲基纤维素、聚乙烯基吡咯烷酮、纤维醋法酯、羟丙基甲基纤维素邻苯二甲酸酯、甲基丙烯酸甲酯和甲基丙烯酸聚合物等包衣。
本发明的一方式为活性肽在用于婴儿双歧杆菌和/或短双歧杆菌的增殖促进剂的制造中的使用。另外,本发明的其他的方式为婴儿双歧杆菌和/或短双歧杆菌的增殖促进中使用的活性肽。另外,本发明的其他方式为用于促进婴儿双歧杆菌和/或短双歧杆菌增殖的活性肽的使用。
另外,本发明的其他的方式为包括对动物投与活性肽的、促进该动物中的婴儿双歧杆菌和/或短双歧杆菌增殖的方法。作为动物,可列举出:人、牛、山羊、绵羊等,其中,优选为人或牛。
对于本发明的药剂中所包含的活性肽的量,没有特别的限定适宜选择即可,例如在制剂中为0.001~10质量%,优选为0.01~3质量%,特别优选为0.1~1质量%。本发明的药剂包含多种活性肽的情况下,前述肽的量为肽的总量。
本发明的药剂对于肠内菌群的改善、免疫调节、腹泻、便秘、肥胖、炎症性肠病等具有予防或治疗作用。
对于本发明的药剂的投与期间,没有特别的限定,可以根据投与对象的状态而适宜选择,例如为1次/3天~5次/1天。对于本发明药剂的投与量也可以根据投与对象的年龄、性别、状态、其他的条件等适宜选择;例如,以活性肽的量(多种的情况下为总量)计,基准优选设为10μg/kg/次~5000μg/kg/次、更优选设为50μg/kg/次~500μg/kg/次的范围。
投与对象优选为人特别是婴幼儿。另外,投与对象的肠内菌群中婴儿双歧杆菌和/或短双歧杆菌不是优势的情况下,例如是婴幼儿以外的情况下,优选与活性肽一起投与婴儿双歧杆菌和/或短双歧杆菌。活性肽以及婴儿双歧杆菌和/或短双歧杆菌可以在本发明的药剂中同时含有,也可以以单独药剂的形式组合。对于药剂中婴儿双歧杆菌和/或短双歧杆菌相对于活性肽的量,没有特别的限制,优选为10~105CFU(colony forming unit:菌落形成单位)/μg活性肽,更优选为102~104CFU/μg活性肽。
也可以在饮食品(饮料或食品)中含有本发明的药剂或作为其有效成分的活性肽。另外,作为在饮食品中含有活性肽或本发明的药剂作为有效成分的婴儿双歧杆菌和/或短双歧杆菌的增殖促进剂的一方式,也可以加工成对这些细菌具有增殖促进作用的饮食品。
作为饮食品,只要是不有损活性肽的效果而能够口服摄取的物质,对于形式、性状没有特别的限制,除了在饮食品中含有活性肽以外,也可以使用通常饮食品中应用的原料通过通常的方法而制造。
对于如上述的食品,无论是液状、糊状、固体、粉末等形式均可,除了果片、流食等之外,还可列举出例如:面包、通心粉、意大利实心面、面类、蛋糕粉、油炸粉、面包粉等小麦粉制品;方便面、杯面、蒸煮烹调食品、烹调罐头、微波食品、速食汤/炖品、即食味噌汁/汤,汤罐头,冻干食品以及除此之外的即食食品等即食食品类;农产品罐头、水果罐头、酱/果酱类、咸菜、煮豆类、农产品干货类、谷类(谷物加工品)等农产品加工品;水产罐头、鱼肉火腿/香肠、水产练制品、海鲜类、酱油煮过的海鲜等水产加工品;畜产罐头/糊类、畜肉火腿/香肠等畜产加工品;加工乳、乳饮料、酸奶类、乳酸菌饮料类、奶酪、冰淇淋类、调制奶粉类、奶油以及其他的乳制品等乳/乳制品;黄油、人造奶油类、植物油等油脂类;酱油、味增、酱汁类;西红柿加工调料、柑橘类、食醋类等基础调料;烹饪组合、咖喱素类、乳酪面粉糊类、调味汁类、面汤类、香料类以及其他的复合调料等复合调料/食品类;原材料冷冻食品、半烹调冷冻食品、烹调后冷冻食品等冷冻食品;饴糖、糖果、口香糖、巧克力、小甜饼干、饼干、蛋糕、馅饼、小菜、咸饼干、日式点心,大米糖果,豆糖果,甜点以及其他的点心等点心类;碳酸饮料、天然果汁、果汁饮料、加入了果汁的清凉饮料、果肉饮料、加入了果粒的水果饮料、蔬菜类饮料、豆乳、豆乳饮料、咖啡饮料、茶饮料、粉末饮料、浓缩饮料、运动饮料、营养饮料、醇饮料以及其他的嗜好饮料等嗜好饮料类;婴儿食品、鱼粉拌紫菜、茶泡饭等其他的市售食品等;育儿用调制奶粉;经肠营养食品;功能性食品(特定保健用食品、营养功能食品)等。
进而,作为在饲料中含有活性肽或本发明的药剂作为有效成分的双歧杆菌增殖促进剂的一方式,也可以加工成具有双歧杆菌增殖促进作用的饲料。
对于饲料的形式没有特别的制限,可以通过配合例如:玉米、小麦、大麦、黑麦、高粱等谷类;大豆油粕、菜籽油粕、椰子油粕、亚麻籽油粕等植物性油粕类;麸皮、麦糠、米糠、脱脂米糠等糠类;玉米麸质、玉米粉果酱等制造粕类;鱼粉、脱脂奶粉、乳清、黄油、牛油等动物性饲料类;圆酵母、啤酒酵母等酵母类;磷酸三钙、碳酸钙等矿物质饲料;油脂类;单独的氨基酸;糖类等而制造。对于饲料的形式,可列举出例如:宠物食品、家畜饲料、养鱼饲料等。
对于本发明的饮食品(包括饲料)中所含的活性肽的量,可以没有特别限定而适宜选择,例如:以活性肽的量(多种的情况下为总量)计,在饮食品中为0.00001~1质量%,优选为0.0001~0.1质量%,特别优选为0.001~0.01质量%。
在饮食品中也优选含有活性肽以及婴儿双歧杆菌和/或短双歧杆菌。婴儿双歧杆菌和/或短双歧杆菌相对于活性肽的量,与本发明药剂中记载的相同。
实施例
以下,使用实施例进一步具体说明本发明,但本发明并不受这些实施例的任何限定。
[实施例1]
委托Toray Research Center Inc.化学合成具有前述式(1)的结构的本发明肽(以下,有时记载为“活性肽1”)、以及前述式(2)的来源于人乳铁蛋白的肽(以下,有时记载为“人乳铁蛋白肽”)。合成的各个肽的纯度均为95%以上。另外,牛乳铁蛋白使用通过日本特开昭63-152400号公报、实施例8所述的方法制造的物质(纯度96%以上)。
用HCl水溶液将9.375μM的各肽水溶液的pH调节为pH6.5,使用0.22μm的膜滤器进行过滤除菌。将这些肽溶液用稀释水稀释,得到9.375μM、3.125μM、0.9375μM和0.3125μM的样品溶液。稀释水使用用HCl溶液将纯水调节为pH6.5、在115℃下进行15分钟灭菌而成的稀释水。
对于上述各肽,如下评价双歧杆菌增殖促进活性。
试验中使用的双歧杆菌如下。这些菌株可以通过ATCC((American TypeCulture Collection,http://www.atcc.org/)获得。
婴儿双歧杆菌(Bifidobacterium infantis)ATCC15697T
短双歧杆菌(Bifidobacterium breve)ATCC15700T
两歧双歧杆菌(Bifidobacterium bifidum)ATCC29521T
将用10%脱脂奶培养基冷冻保存的各菌株的菌液100μL添加至MRS液体培养基3mL中,37℃下厌氧培养16小时。将这些培养液100μL添加至MRS液体培养基3mL中。MRS液体培养基如下调制:将Difco乳酸菌MRS肉汤(BD公司,“Difco”为Difco Laboratories Incorporated.的注册商标)5.5g和L-半胱氨酸单盐酸盐、单水合物(Wako Pure Chemical Industries,Co.,Ltd.制)50mg溶解于纯水中以成为100mL,用HCl水溶液调节为pH6.5,在115℃下灭菌15分钟。另外,使用Difco乳酸菌MRS肉汤11g和L-半胱氨酸单盐酸盐、单水合物100mg,除此以外,与上述同样地调制2倍浓度的浓缩培养基。
上述培养液用MRS液体培养基稀释以使波长630nm下的浊度成为0.8。进而,将该稀释液用MRS液体培养基稀释100倍。将该稀释液称为1%培养稀释液。
在96孔板(FALCON353072)中将前述2倍浓缩培养基100μL、样品溶液或稀释水80μL以及1%培养稀释液(接种量0.1%)或者MRS液体培养基20μL(接种量0%)混合,37℃下进行16小时厌氧培养。混合液中的肽的终浓度为3.75μM、1.25μM、0.375μM、0.125μM或0μM。
培养后对于各培养液,测定波长630nm下的浊度,用下述式子算出增殖促进率(%)。
增殖促进率(%)=(ODS1-ODS0)/(ODC1-ODC0)×100-100
ODS1:样品浓度3.75~0.125μM,接种量0.1%时16小时后的浊度
ODS0:样品浓度3.75~0.125μM,接种量0%时16小时后的浊度
ODC1:样品浓度0μM,接种量0.1%时16小时后的浊度
ODC0:样品浓度0μM,接种量0%时16小时后的浊度
将结果示于表1。
[表1]
对于婴儿双歧杆菌和短双歧杆菌,本发明的活性肽1与牛乳铁蛋白和人乳铁蛋白肽相比较表现出显著的增殖促进效果。
然而,活性肽1对于两歧双歧杆菌并没有表现出增殖促进效果。
牛乳铁蛋白的分子量为约8万、人乳铁蛋白肽的分子量为5757.7,与此相对,活性肽1的分子量为2673.1(分别为约1/30、约1/2),可以期待少量就有高的效果。
[实施例2]
委托Toray Research Center Inc.化学合成具有前述式(2)和(3)所示的结构的本发明肽(以下,分别记载为“活性肽2、活性肽3”)。
对于上述各肽,与实施例1同样地,评价双歧杆菌增殖促进活性。将结果示于表2。
[表2]
对于婴儿双歧杆菌和短双歧杆菌,本发明的活性肽2和3均表现出显著的增殖促进效果。
产业上的可利用性
本发明的增殖促进剂对于婴儿双歧杆菌和短双歧杆菌具有增殖促进作用,所以通过摄取本发明的增殖促进剂,能够形成这些细菌占优势的肠内环境。作为本发明的增殖促进剂的有效成分的肽来源于乳蛋白质,可以期待安全性。
另外,除了婴幼儿以外,包含本发明的增殖促进剂以及婴儿双歧杆菌和/或短双歧杆菌的组合物,由于能够以提高这些细菌所具有的功能的形式摄取,所以能够用作药品或饮食品等。
Claims (9)
1.一种选自婴儿双歧杆菌(Bifidobacterium infantis)和短双歧杆菌(Bifidobacterium breve)的细菌的增殖促进剂,含有肽二聚体作为有效成分,所述肽二聚体由具有序列号1所示的氨基酸序列的肽和具有序列号2~4的任意者所示的氨基酸序列的肽构成,并且各个肽中的半胱氨酸残基通过二硫键而结合。
2.根据权利要求1所述的增殖促进剂,其中,所述肽二聚体由具有序列号1所示的氨基酸序列的肽和具有序列号2所示的氨基酸序列的肽构成。
3.根据权利要求1所述的增殖促进剂,其中,所述肽二聚体由具有序列号1所示的氨基酸序列的肽和具有序列号3所示的氨基酸序列的肽构成。
4.根据权利要求1所述的增殖促进剂,其中,所述肽二聚体由具有序列号1所示的氨基酸序列的肽和具有序列号4所示的氨基酸序列的肽构成。
5.一种选自婴儿双歧杆菌(Bifidobacterium infantis)和短双歧杆菌(Bifidobacterium breve)的细菌的增殖促进用组合物,其包含权利要求1~4的任一项所述的增殖促进剂和选自婴儿双歧杆菌和短双歧杆菌的细菌。
6.根据权利要求5所述的组合物,其中,所述组合物为药品。
7.根据权利要求5所述的组合物,其中,所述组合物为饮食品。
8.一种肽在用于促进选自婴儿双歧杆菌(Bifidobacterium infantis)和短双歧杆菌(Bifidobacterium breve)的细菌的增殖中的应用,
所述肽为肽二聚体,由具有序列号1所示的氨基酸序列的肽和具有序列号2~4的任意者所示的氨基酸序列的肽构成,并且各个肽中的半胱氨酸残基通过二硫键而结合。
9.一种促进动物中的选自婴儿双歧杆菌(Bifidobacterium infantis)和短双歧杆菌(Bifidobacterium breve)的细菌的增殖的方法,包括对该动物投与肽,
所述肽为肽二聚体,由具有序列号1所示的氨基酸序列的肽和具有序列号2~4的任意者所示的氨基酸序列的肽构成,并且各个肽中的半胱氨酸残基通过二硫键而结合。
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CN107889886A (zh) * | 2017-12-14 | 2018-04-10 | 光明乳业股份有限公司 | 一种制备含有双歧杆菌发酵乳的方法及该发酵乳 |
WO2018181069A1 (ja) * | 2017-03-28 | 2018-10-04 | 森永乳業株式会社 | オピオイドペプチド分解用組成物 |
CN108697773A (zh) * | 2016-02-18 | 2018-10-23 | 天野酶制品株式会社 | 肠内菌群改善剂 |
CN114026218A (zh) * | 2019-06-25 | 2022-02-08 | 株式会社益力多本社 | 双歧杆菌属细菌的增殖促进方法 |
CN116076728A (zh) * | 2023-04-07 | 2023-05-09 | 黑龙江飞鹤乳业有限公司北京分公司 | 促进双歧杆菌生长的组合物 |
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WO2018174938A1 (en) | 2017-03-23 | 2018-09-27 | Virun, Inc. | Stable dry powders and emulsions containing probiotics and mucoadhesive protein |
TWI792375B (zh) * | 2021-06-30 | 2023-02-11 | 肌活麗學創研所股份有限公司 | 乳鐵蛋白的衍生胜肽及其促進及/或增加油脂生成的用途 |
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CN108697773A (zh) * | 2016-02-18 | 2018-10-23 | 天野酶制品株式会社 | 肠内菌群改善剂 |
CN108697773B (zh) * | 2016-02-18 | 2022-11-22 | 天野酶制品株式会社 | 肠内菌群改善剂 |
WO2018181069A1 (ja) * | 2017-03-28 | 2018-10-04 | 森永乳業株式会社 | オピオイドペプチド分解用組成物 |
CN107889886A (zh) * | 2017-12-14 | 2018-04-10 | 光明乳业股份有限公司 | 一种制备含有双歧杆菌发酵乳的方法及该发酵乳 |
CN114026218A (zh) * | 2019-06-25 | 2022-02-08 | 株式会社益力多本社 | 双歧杆菌属细菌的增殖促进方法 |
CN116076728A (zh) * | 2023-04-07 | 2023-05-09 | 黑龙江飞鹤乳业有限公司北京分公司 | 促进双歧杆菌生长的组合物 |
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