CN106661542A - 新型乳酸菌和包含所述乳酸菌的组合物 - Google Patents
新型乳酸菌和包含所述乳酸菌的组合物 Download PDFInfo
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- CN106661542A CN106661542A CN201580028657.1A CN201580028657A CN106661542A CN 106661542 A CN106661542 A CN 106661542A CN 201580028657 A CN201580028657 A CN 201580028657A CN 106661542 A CN106661542 A CN 106661542A
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- acid bacteria
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Abstract
本发明提供一种改善高尿酸血症、脂肪肝和生活方式相关疾病的乳酸菌,以及含有所述乳酸菌的组合物。
Description
技术领域
本发明涉及具有多种功能的短乳杆菌(Lactobacillus brevis),特别是以保藏号为NITE BP-01634进行保藏的短乳杆菌NTM003株,以及含有其的组合物,特别是药物、食品等。
背景技术
高尿酸血症是指由于遗传因素或环境因素导致的尿酸***减少和尿酸生成过多引起的血液中显示高水平的尿酸的状态。已知高尿酸血症引起以痛风,以及肾病、***症等为代表的并发症。据说目前在日本有500万人面临发生痛风的风险,并且发病年龄的峰值变得从过去的50多岁提前到30多岁,高尿酸血症的预防和治疗引起了重视。
高尿酸血症的预防和治疗通过生活指导(消除肥胖、饮食治疗、限制酒精摄入、避免过度运动、减轻压力)和药物治疗的组合来控制血中的尿酸水平来进行。通过生活指导改善生活方式提供了改善高尿酸血症的效果;然而,长期控制生活方式并不容易。当需要药物治疗时,由医生控制血中尿酸水平。当通过生活指导来改善不需要药物的患者的症状时,作为生活指导辅助方法,已经报道了通过对患者口服摄入分解嘌呤体的微生物例如乳酸菌和酵母来分解肠中的嘌呤体,从而减少嘌呤体在体内的吸收等方法(专利文献1)。乳酸菌是一种久已广泛应用于诸如酸奶、泡菜等食品和药物的微生物,即使长期摄入也只有很少的副作用的担心。因此,摄入乳酸菌可以是预防或治疗高尿酸血症的有用方法。
脂肪肝是脂肪在肝脏中过度积累的状态,医学上指在肝脏中在不少于30%的肝细胞中发现脂肪空泡的状态。脂肪肝主要分为酒精性脂肪肝和非酒精性脂肪肝,据称在日本有1200~3600万人患有非酒精性脂肪肝或脂肪性肝炎。非酒精性脂肪肝的原因包括例如:肥胖、糖尿病、高脂血症、营养不良等。脂肪肝几乎不显示主观症状,并且因为已被报道会转化为肝炎、肝硬化和肝癌,因此需要早期治疗。
对于脂肪肝的预防或治疗而言,对于酒精性脂肪肝,减少饮酒和禁酒是最有效的,对于非酒精性脂肪肝,需要通过饮食疗法、运动疗法等改善生活方式。特别地,由糖尿病引起的非酒精性脂肪肝也需要药物治疗。虽然改善生活方式对于预防或治疗脂肪肝是有效的,但是改善不规律的生活方式、不平衡的饮食和缺乏运动并不容易。因此,期望一种安全且无负担的用于支持生活方式的改善的方法。迄今为止,已经公开了利用乳酸菌用于预防和/或抑制脂肪肝而很少担心副作用的药剂(专利文献2)。
然而,上述专利文献中公开的乳酸菌,是各自分别具有血清尿酸水平降低剂或用于预防和/或抑制脂肪肝的药剂的功能的单独的乳酸菌,而尚未有报道一种乳酸菌同时具有改善高尿酸血症和脂肪肝的功能。
现有技术文献
专利文献
专利文献1:WO 2004/112809
专利文献2:JP-A-2011-201801
发明内容
发明要解决的问题
鉴于上述情况,本发明的一个目的在于提供可用于食品和药品的乳酸菌,所述乳酸菌可以预防或治疗高尿酸血症和脂肪肝,以及生活方式相关疾病。同时,本发明的目的在于,提供用于预防和/或治疗高尿酸血症、脂肪肝和生活方式相关疾病的组合物,特别是药物或食品。
解决问题的方法
本发明人为了解决上述问题进行了深入研究,并选择了具有显著高的降解核苷能力的乳酸菌。将所述选择的乳酸菌口服给予以含有嘌呤体的饲料饲养的大鼠,并观察对大鼠的血清尿酸值的影响。此外,观察了当具有比较高的(不低于6.5mg/dL)血液尿酸水平的人摄入含有乳酸菌的胶囊时,对血液尿酸水平的影响。结果,发现了一种显著抑制尿酸水平的升高的新型短乳杆菌NTM003(Lactobacillus brevis NTM003)。进一步,本发明人将上述乳酸菌与高脂饮食一起给予小鼠肥胖模型,并在42天后测量了肝重和肝脏脂质含量。结果发现,与不施用上述乳酸菌的组相比,乳酸菌施用组的肝重显著低,并且肝脂质含量的增加受到抑制。
基于上述发现完成了本发明。
因此,本发明如下:
[1]一种乳酸菌(NITE BP-01634)或其菌体处理物,其中,所述乳酸菌(NITE BP-01634)为短乳杆菌NTM003株。
[2]一种用于抑制或改善血中尿酸值增加的组合物,其包含上述[1]的乳酸菌或其菌体处理物作为活性成分。
[3]一种用于抑制或改善脂肪肝的组合物,其包含上述[1]的乳酸菌或其菌体处理物作为活性成分。
[4]一种抑制或改善生活方式相关疾病的组合物,其包含上述[1]的乳酸菌或其菌体处理物作为活性成分。
[5]根据上述[2]~[4]中任一项所述的组合物,其为药物。
[6]根据上述[2]~[4]中任一项所述的组合物,其为食品。
[7]一种抑制或改善血中尿酸值的增加、脂肪肝或生活方式相关疾病的方法,其包括向受试者施用有效量的乳酸菌(NITE BP-01634)或其菌体处理物,所述乳酸菌(NITE BP-01634)为短乳杆菌NTM003株。
[8]根据上述[7]的方法,其中将所述乳酸菌(NITE BP-01634)或其菌体处理物,以每天1×104~1×1012个细胞或与其相当的量口服给予血中尿酸水平高的患者、脂肪肝患者或生活方式相关疾病患者,所述乳酸菌(NITE BP-01634)为短乳杆菌NTM003株。
发明的效果
在本发明中,发现短乳杆菌NTM003株(NITE BP-01634)(下文中称为本发明的乳酸菌)为现有技术中未知的具有抑制血中尿酸水平升高或改善血中尿酸水平的作用、并且还兼具抑制或改善脂肪肝的作用的乳酸菌。基于上述功能,本发明的乳酸菌由于可以应用于改善或预防生活方式相关疾病,并且可以用在为特别改善当发展时引起痛风和肾病的高尿酸血症、引起肝炎等的脂肪肝的目的的药物、食品等领域中,因此在工业上极其有用。
附图说明
图1显示了由NTM003株进行的核苷降解。
图2显示了由NTM003株进行的核苷降解的时程变化。Ino:肌苷,Hx:次黄嘌呤,Guo:鸟苷,G:鸟嘌呤
图3显示了高尿酸血症大鼠模型中的血清尿酸水平的变化。
图4显示了在人体试验中,摄入NTM003株前后的血中尿酸水平。
图5显示了在人体试验中,摄入NTM003株之前和之后的血液尿酸水平,该患者在施用前显示较高(不小于6.5mg/dL)的尿酸水平。
图6显示了在给予高脂饮食和乳酸菌后直到第42天,肥胖小鼠模型的体重变化。
图7显示了在给予高脂饮食和乳酸菌后直到第42天,肥胖小鼠模型的肝重和肝脏脂质含量。
具体实施方式
下面详细解释本发明。
本发明提供了有效预防或改善高尿酸血症和脂肪肝的短乳杆菌NTM003(Lactobacillus brevis NTM003)株。本发明的乳酸菌于2013年6月11日保藏于日本千叶县木更津市2-5-8Kazusakamatari的独立行政法人制品评价技术基础机构专利微生物保藏中心(Incorporated Administrative Agency National Institute of Technology andEvaluation Patent Microorganisms Depositary)。NTM003株的保藏号为NITE BP-01634。
本发明的乳酸菌可以根据乳酸菌培养的常规方法培养。作为用于培养的培养基,只要能够使本发明的乳酸菌在其中生长即可,没有特别限制,所述乳酸菌可以在乳酸菌培养用培养基(固体培养基、液体培养基等)例如MRS培养基等中培养。培养基可以含有各种维生素(维生素A、维生素B1、维生素B2、维生素B6、维生素C、维生素D、维生素E等及其衍生物)、各种氨基酸(包括天然氨基酸和合成氨基酸)、核酸碱基(嘌呤、嘧啶)、无机盐(MgSO4、MnSO4、FeSO4、NaCl等)等。作为培养条件,可以适当调节培养温度、培养时间和培养基的pH。例如,培养温度通常为30~37℃,优选35~37℃。培养期通常为16小时~3天,优选为1~2天。培养基的pH通常为pH 3~8,优选为pH 4~7。培养可以为静置培养,当培养基是液体培养基时,可以为搅拌培养。此外,培养可以为好氧或厌氧。
本发明的乳酸菌为从油菜花腌菜(菜の花漬け)中分离出来的。
本发明的乳酸菌的真菌学性质如下所示。
(1)细胞形态
杆菌
(2)运动性
无
(3)形成孢子
不形成
(4)琼脂培养基上菌落的肉眼特征
在MRS琼脂培养基上,形成圆形形状的白色菌落
(5)革兰氏染色
阳性
(6)生长温度
在30~37℃生长良好。
本发明的乳酸菌的糖同化性示于表1中。
表1
+:阳性,-:阴性
进一步,本发明的乳酸菌具有SEQ ID No:1所示的16S rRNA。从以上各种性质和特征,利用伯杰氏***细菌学手册(Berge's Manual of Systematic Bacteriology),可鉴定本发明的乳酸菌株为属于短乳杆菌的菌株。
如下述实施例中,在本发明的乳酸菌中,基质溶液中的嘌呤体:肌苷、鸟苷,分别被转换为不同的嘌呤体:次黄嘌呤、鸟嘌呤。嘌呤体为具有嘌呤骨架的化合物,包括:嘌呤核苷酸(腺苷酸、脱氧腺苷酸、鸟苷酸、脱氧鸟苷酸)、嘌呤核苷(腺苷、脱氧腺苷、鸟苷、脱氧鸟苷)、嘌呤碱(腺嘌呤、鸟嘌呤)、含有嘌呤碱的寡核苷酸和多核苷酸等。嘌呤碱构成了核酸、以及各种生物成分如ATP、GTP、cAMP、cGMP、辅酶A、FAD和NAD等,作为这样的生物成分,只要有嘌呤骨架,也都包括在嘌呤体中。
在体内不需要的嘌呤体最终被代谢为尿酸并***。嘌呤体到尿酸的代谢途径是众所周知的,其中AMP由5’-核苷酶变成腺苷,腺苷经过肌苷代谢成次黄嘌呤。GMP由5’-核苷酶变成鸟苷,然后代谢成鸟嘌呤。进一步,次黄嘌呤由黄嘌呤氧化酶代谢成黄嘌呤,而鸟嘌呤由鸟嘌呤脱氨酶代谢成黄嘌呤,最后,黄嘌呤由黄嘌呤氧化酶代谢成尿酸。因此,抑制或改善血中尿酸水平升高的有效手段之一是抑制体内从肠道吸收的嘌呤体的量。据了解,其吸收效率为按照黄嘌呤、鸟嘌呤、鸟苷的顺序依次增加,以及按照次黄嘌呤、肌苷、腺苷的顺序依次增加。
因此,如下述实施例中,试图通过将具有高吸收效率的肌苷和鸟苷,转变为具有低吸收效率的次黄嘌呤和鸟嘌呤来抑制嘌呤体吸收量,将本发明的乳酸菌口服给予大鼠,发现抑制大鼠血清尿酸水平的增加。在另一个实施例中,在口服摄入本发明的乳酸菌的试验中,具有高血中尿酸水平的试验受试者表现出水平明显降低。因此,本发明的乳酸菌为一种新型的乳酸菌,其对血中尿酸水平的增加有抑制或改善作用。
如下提到的另一个实施例,对肥胖和/或糖尿病小鼠模型口服摄入本发明的乳酸菌,抑制了小鼠的肝重和肝脏脂质含量的增加。因此,本发明的乳酸菌是一种对脂肪肝有抑制或改善的作用的新型乳酸菌。
基于本发明的乳酸菌对血中尿酸值升高的抑制或改善效果、脂肪肝的抑制/改善效果,本发明提供了用于抑制或改善血中尿酸值升高、抑制或改善脂肪肝的组合物,其包含本发明的乳酸菌或其菌体处理物作为活性成分(以下简称本发明的组合物)。此外,本发明的组合物也可以应用于抑制/改善生活方式相关的疾病。在本发明中,生活方式相关疾病是指生活方式如饮食习惯、运动习惯、休息、吸烟、饮酒等参与其发病和进展的一组疾病,包括以下疾病如:高尿酸血症、成人肥胖、儿童肥胖、营养不良、厌食症、痛风、高血压、动脉硬化、肾结石、心肌梗死、心绞痛、胃溃疡、肾脏病、脂肪肝、肝炎、肝硬化、肝癌、肺癌、脑卒中、脑梗塞等。
作为本发明组合物中包括的活性成分,可以使用利用离心等收集方法从培养物中分离的本发明的乳酸菌。本发明的乳酸菌的菌体处理物也可以作为本发明的组合物中包括的活性成分。本发明菌体处理物包括经浓缩、干燥、冻干等处理的本发明的乳酸菌。此外,不仅分离的菌体,细菌的破碎产物、和细菌破碎后通过离心去除碎片后的匀浆也可用作本发明的菌体处理物。作为培养物的形态,不仅可以使用根据上述培养条件获得的培养物和用一般用于培养乳酸菌的培养基获得的培养物,也可以使用乳制品等如奶酪、发酵乳、乳酸菌饮料等,本发明的乳酸菌可通过已知的方法分离。
本发明的组合物包括上述本发明的乳酸菌等作为活性成分,可以根据用途适当添加赋形剂、粘合剂、崩解剂、润滑剂等进行配制,并选择形态(固体、液体等)。
作为赋形剂的例子,包括动物和植物油,如豆油、红花油、橄榄油、胚芽油、葵花油、牛油、沙丁鱼油等,多元醇如聚乙二醇、丙二醇、甘油、山梨醇等,作为表面活性剂,如脂肪酸山梨醇酯、蔗糖脂肪酸酯、甘油脂肪酸酯、聚甘油脂肪酸酯等,纯净水、乳糖、淀粉、微晶纤维素、D-甘露醇、卵磷脂、***胶、山梨糖醇溶液、糖溶液等。
作为粘合剂的例子,包括羟丙基甲基纤维素、羟丙基纤维素、明胶、预胶化淀粉、聚乙烯吡咯烷酮、聚乙烯醇等。
作为崩解剂的例子,包括羧甲基纤维素钙、羧甲基纤维素钠、交联羧甲基纤维素钠、交联聚乙烯吡咯烷酮、低取代羟丙基纤维素、玉米淀粉等。
作为润滑剂的例子,包括滑石粉、氢化植物油、蜡、轻质无水硅酸等来自天然存在的物质及其衍生物、硬脂酸、硬脂酸镁、硬脂酸钙、硬脂酸铝等。
本发明的组合物还可以进一步含有甜味剂、着色剂、pH调节剂、香料、多种氨基酸等。此外,固态产品可以通过公知的方法进行包衣。在摄入时,液体可溶解或悬浮在水中或其他合适的介质中。
本发明的组合物提供为例如药物、食品、饲料等,但并不限于这些。
当本发明的组合物用作药物(以下简称本发明的药物)时,本发明的药物的剂型包括:粉剂、颗粒剂、丸剂、软胶囊、硬胶囊、片剂、咀嚼片、快速崩解的片剂、糖浆、液体、悬浮液等。其制备为根据常规方法制备。
用于口服给药的本发明的药物的例子包括固体或液体剂型,特别是片剂(包括糖衣片、膜包衣片)、丸剂、颗粒剂、粉剂、胶囊(包括软胶囊)、糖浆、乳剂、悬浮液等。该组合物通过已知的方法进行生产,可以包含在医药领域通常使用的载体、稀释剂或赋形剂。作为片剂的载体、辅料,使用乳糖、淀粉、蔗糖、硬脂酸镁。
作为用于胃肠外给药的本发明的药物,使用注射剂、栓剂等。注射剂的制备方法,包括将本发明的乳酸菌或本发明菌体处理物,悬浮或乳化于通常用于注射的无菌的水溶液或油溶液中。作为用于注射的水溶液,使用生理盐水、含有葡萄糖或其他助剂的等渗溶液等。作为油溶液,使用芝麻油、大豆油等。用于直肠给药的栓剂,可以通过将本发明的乳酸菌或其菌体处理物与通常用于栓剂的基底混合而制备。
本发明的药物制剂的给药受试者为人或其他恒温动物(如小鼠、大鼠、兔、绵羊、猪、牛、猫、狗、猴、鸡等)。
本发明的药物的剂量取决于给药受试者、目标疾病、症状、给药途径等,当它被用于例如,成人高尿酸血症的抑制/改善时,作为本发明的乳酸菌或其菌体处理物的每日剂量,可以口服或胃肠外给药通常为1×104~1×1012个细胞,优选是1×106~1×1011个细胞,更优选1×108~1×1011个细胞或与其相当的量。可以每天分多次给药。当情况特别严重时,所述剂量可根据症状增加。在本发明的药品用于抑制/改善成人的脂肪肝、或抑制/改善生活方式相关的疾病时,可使用与上述中相似的剂量、给药途径和给药天数。
当本发明的组合物作为食品(以下简称本发明的食品)时,本发明的食品的形式的例子包括:补充剂(粉末、颗粒、软胶囊、硬胶囊、片剂、咀嚼片、快速崩解片剂、糖浆、液体等),饮料(茶饮料、碳酸饮料、乳酸饮料、运动饮料等),甜食(软糖、果冻、口香糖、巧克力、饼干、糖果(candy)等)、油、油脂食品(蛋黄酱、调味汁(dressing)、黄油、奶油、人造黄油等)等。
上述食品在必要时可以包含:各种营养素、各种维生素(维生素A、维生素B1、维生素B2、维生素B6、维生素C、维生素D、维生素E、维生素K等)、多种矿物质(镁、锌、铁、钠、钾、硒等)、膳食纤维、分散剂、稳定剂如乳化剂等,甜味剂、香味成分(柠檬酸、苹果酸等)、香精、蜂王浆、蜂胶、姬松茸(Agaricus)等。
本发明的食物的每日摄入量取决于摄入食物的受试者、目标疾病、症状等,例如,当它被用于抑制/改善成人的高尿酸血症,作为本发明的乳酸菌或其菌体处理物的每日摄入量,可以口服摄入通常为1×104~1×1012个细胞,优选1×106~1×1011个细胞,更优选1×108~1×1011个细胞或与其相当的量。每一天可以摄入多个分割部分。当情况特别严重时,所述剂量可根据症状增加。当摄入本发明的食物用于抑制/改善成人的脂肪肝、或抑制/改善与生活方式相关的疾病时,可使用与上述中相似的摄入量、摄入途径和摄入天数。
实施例
下面通过参考实施例更详细地解释本发明。实施例仅为本发明的示例,不以任何方式限制本发明的范围。
实施例1关于乳酸菌降低尿酸水平的作用的体外试验
将乳酸菌NTM003株接种于MRS培养基15mL(由BD制造),并在37℃培养并收集。将获得的乳酸菌用0.85%氯化钠设置为给定的浊度(OD600=0.1),用作样品溶液。向样品溶液中加入底物溶液(1mL)(肌苷4mM、鸟苷2mM、0.1M的KPB pH 7.0:H2O=1:9),将混合物厌氧进行反应(37℃,120rpm,1小时),用HPLC分析反应混合物。绘制了各分析曲线,测定了反应混合物中包含的核酸的浓度。其结果示于图1。反应1小时后检测不到肌苷和鸟苷,而检测到次黄嘌呤和鸟嘌呤。
进一步,检查了NTM003株的时程变化。乳酸菌的数量与上述样品溶液中相同,而底物溶液增加至5mL。反应混合物在厌氧室中于37℃进行搅拌,每10分钟分取并用HPLC分析。结果示于图2。可以证实伴随底物的减少,得到的产物增加。
实施例2关于乳酸菌降低尿酸水平的作用的体内试验
(制造例1:粉末状乳酸菌的制备和试验溶液的制备)
NTM003株在MRS培养基(600L)(由BD制造)或制备的与MRS培养基的组成相同的培养基(600L)中于37℃进行培养,通过离心收集并冻干。用研磨机粉碎冻干后的菌体,并与马铃薯淀粉混合,得到具有一定浓度的粉末状菌体。作为试验溶液,将上述粉末状乳酸菌(NTM003株)以5.51×109个细胞/mL悬浮在日本药典注射用水中(使用时制备)。
(实验动物的制备)
使用大鼠(Wistar SPF,雄性,7周龄)。对饲养而言,使用铝制丝网底笼,每笼放置一只大鼠。光照时间为12小时/天(7:00至19:00)。
(检疫和驯化)
在搬入后,实验动物驯化(适应)7天。在收到动物时确认健康状况,将不显示异常的动物放置饲养室中,并在除了饲料和试验溶液以外均与下述试验相同的饲养条件和饲养环境下,检疫和适应性养育7天。
(饲料和混合饲料)
使用Oriental Yeast Co.,Ltd.制造的粉末状饲料MF。将氧嗪酸钾(potassiumoxonate)(Sigma-Aldrich Ltd.)以2.5w/w%与粉末状饲料MF混合,作为氧嗪酸钾混合饲料。将氧嗪酸钾以2.5w/w%、RNA(MP biomedical)以1w/w%与粉末状饲料MF混合,作为氧嗪酸钾+RNA混合饲料。
(分组)
分组为对照组、阴性对照组和乳酸菌3组,每组8只动物。试验组的构成示于表2。
表2
(饲养(试验))
如表2所示分组后,从饲喂器分别将氧嗪酸钾混合饲料(对照组)和氧嗪酸钾+RNA混合饲料(阴性对照组、乳酸菌组)自由地给予大鼠8天。向对照组和阴性对照组,每天一次用灌胃针(stomach gavage needle)强制给药日本药典注射用水1mL/只,而向乳酸菌组,每天一次用灌胃针强制给药上述试验溶液1mL/只。血液样本采集的频率为在开始自由摄入混合饲料前、第5天(试验溶液给药后1小时)和第8天(试验溶液给药后1小时)。血液在室温放置不少于30分钟,离心后收集血清。血清冷冻保存。保存的血清使用尿酸C-Test Wako(WakoPure Chemical Industries,Ltd.)进行测量血清中的尿酸浓度。
(试验结果)
经过观察期的9天,一般状态中没有发现异常。各组均表现出良好的体重增加。对照组、阴性对照组和乳酸菌组的饲料摄入量没有显示出差异。血清尿酸水平的结果示于图3。与阴性对照组相比,乳酸菌组中血清尿酸水平的增加被抑制。
实施例3关于乳酸菌降低尿酸水平的作用的人体试验
(试验物质的制备)
将实施例2的制造例1制备的乳酸菌粉,以每粒胶囊2×1010CFU乳酸菌填充入食品明胶硬胶囊中并用作试验品。
(试验受试者)
18名成人男性和女性(20多岁~60多岁)
(试验)
试验受试者每天摄入一粒试验物质胶囊共一个月,在开始摄入前和摄入一个月后收集血液样本。收集到的血液样本由临床试验公司测定了血中尿酸水平。
18名试验受试者的尿酸水平的结果示于图4。此外,在图5中,仅显示了在开始摄入之前表现出较高的(不低于6.5mg/dL)尿酸水平的试验受试者的结果。血中尿酸水平较高的试验受试者的结果显示,摄入前的平均值和摄入后的平均值之间存在P值<0.05的显著差异。也就是说,显示正常尿酸水平的人,其尿酸水平没有显示出变化的趋势,而在表现出较高的尿酸水平的人中,高尿酸血症可以通过摄入乳酸菌粉改善。
实施例4关于乳酸菌抑制脂肪肝的作用的体内试验
使用肥胖和/或糖尿病的模型小鼠KKAy小鼠,对NTM003株的效果进行了评价。将KKAy小鼠(KKAy/TaJcL,雄性,4周龄)用市售的普通饲料(ND)驯化一周,分为如表3所示的两组。
表3
试验组 | 饲料+试验物质 | n |
组1 | HFD60(93%)+HFD60改良饲料(5%)+淀粉(2%) | 8 |
组2 | HFD60(93%)+HFD60改良饲料(5%)+NTM003粉末(2%) | 8 |
(饲料和试验物质)
HFD60购自Orientalbio Co.,Ltd.HFD60改良饲料根据表4所示的组成由Orientalbio Co.,Ltd.制备。作为试验物质,使用了淀粉或NTM003粉末。作为NTM003粉末,将实施例2的制造例1中制备的乳酸菌粉末用淀粉调节至2×1011CFU/g的浓度,并使用所得的粉末状菌体。通过以表3所述的比例捏合各材料,制备了试验组中的组1和组2将要自由摄入的饲料+试验物质。
[表4]
成分 | 量(%) |
乳酪蛋白 | 16.4 |
L-胱氨酸 | 0.25 |
麦芽糖糊精 | 6 |
α-玉米淀粉 | 10.11 |
蔗糖 | 5.5 |
豆油 | 2 |
猪油 | 48.2 |
粉末纤维素 | 6.61 |
AIN-93G-MX | 3.5 |
碳酸钙 | 0.18 |
AIN-93-VM | 1 |
重酒石酸胆碱 | 0.25 |
合计 | 100 |
(饲养(试验))
允许每组自由摄入饲料+试验物质4g/天共42天。
每周测量KKAy小鼠的体重,在第42天尸体解剖,并测量了器官重量、血液生化试验(胆固醇、中性脂肪、游离脂肪酸)和粪便的含水量。体重曲线示于图6,第42天的生化试验等示于表5。肝重和肝脏的脂质含量也示于图7。
[表5]
平均值±标准偏差
Dunnett的多重比较检验(对照组>)*p<0.05
#1内脏脂肪重量为腹股沟单侧的重量
如图7和表5所示,与组1相比,摄入NTM003株乳酸菌作为试验物质的组2显示出肝重显著轻和肝脏脂质含量低,证实了NTM003株的脂肪肝抑制作用。
上述结果显示,短乳杆菌NTM003株(NITE BP-01634)是同时具有高尿酸水平改善效果和脂肪肝抑制作用的新型乳酸菌。
虽然已经通过强调优选的实施例描述了本发明,但是对于本领域技术人员显而易见的是,可以对优选实施例进行修改。在此引用的任何出版物中公开的内容,包括专利和专利申请,通过引用整体并入本文,至其已经在本文中公开的程度。
工业实用性
本发明发现了一种新型乳酸菌株,并阐明了所述乳酸菌株具有改善高尿酸血症和脂肪肝的多种功能。含有所述乳酸菌或其菌体处理物的组合物可以应用于诸如药品和食品等各种领域,因此本发明在工业上极为有用。
本申请基于在日本提交的专利申请No.2004-110912(申请日:2014年5月29日),其内容全部并入本文。
序列表
<110> 日东药品工业株式会社
<120> 新型乳酸菌和包含所述乳酸菌的组合物
<130> 092317
<150> JP 2014-110912
<151> 2014-05-29
<160> 1
<170> PatentIn version 3.5
<210> 1
<211> 1527
<212> DNA
<213> 短乳杆菌(Lactobacillus brevis)
<400> 1
agagtttgat cctggctcag gacgaacgct ggcggcatgc ctaatacatg caagtcgaac 60
gagcttccgt tgaatgacgt gcttgcactg atttcaacaa tgaagcgagt ggcgaactgg 120
tgagtaacac gtgggaaatc tgcccagaag caggggataa cacttggaaa caggtgctaa 180
taccgtataa caacaaaatc cgcatggatt ttgtttgaaa ggtggcttcg gctatcactt 240
ctggatgatc ccgcggcgta ttagttagtt ggtgaggtaa aggcccacca agacgatgat 300
acgtagccga cctgagaggg taatcggcca cattgggact gagacacggc ccaaactcct 360
acgggaggca gcagtaggga atcttccaca atggacgaaa gtctgatgga gcaatgccgc 420
gtgagtgaag aagggtttcg gctcgtaaaa ctctgttgtt aaagaagaac acctttgaga 480
gtaactgttc aagggttgac ggtatttaac cagaaagcca cggctaacta cgtgccagca 540
gccgcggtaa tacgtaggtg gcaagcgttg tccggattta ttgggcgtaa agcgagcgca 600
ggcggttttt taagtctgat gtgaaagcct tcggcttaac cggagaagtg catcggaaac 660
tgggagactt gagtgcagaa gaggacagtg gaactccatg tgtagcggtg gaatgcgtag 720
atatatggaa gaacaccagt ggcgaaggcg gctgtctagt ctgtaactga cgctgaggct 780
cgaaagcatg ggtagcgaac aggattagat accctggtag tccatgccgt aaacgatgag 840
tgctaagtgt tggagggttt ccgcccttca gtgctgcagc taacgcatta agcactccgc 900
ctggggagta cgaccgcaag gttgaaactc aaaggaattg acgggggccc gcacaagcgg 960
tggagcatgt ggtttaattc gaagctacgc gaagaacctt accaggtctt gacatcttct 1020
gccaatctta gagataagac gttcccttcg gggacagaat gacaggtggt gcatggttgt 1080
cgtcagctcg tgtcgtgaga tgttgggtta agtcccgcaa cgagcgcaac ccttattatc 1140
agttgccagc attcagttgg gcactctggt gagactgccg gtgacaaacc ggaggaaggt 1200
ggggatgacg tcaaatcatc atgcccctta tgacctgggc tacacacgtg ctacaatgga 1260
cggtacaacg agttgcgaag tcgtgaggct aagctaatct cttaaagccg ttctcagttc 1320
ggattgtagg ctgcaactcg cctacatgaa gttggaatcg ctagtaatcg cggatcagca 1380
tgccgcggtg aatacgttcc cgggccttgt acacaccgcc cgtcacacca tgagagtttg 1440
taacacccaa agccggtgag ataaccttcg ggagtcagcc gtctaaggtg ggacagatga 1500
ttagggtgaa gtcgtaacaa ggtaacc 1527
Claims (8)
1.一种乳酸菌(NITE BP-01634)或其菌体处理物,其中,所述乳酸菌(NITE BP-01634)为短乳杆菌(Lactobacillus brevis)NTM003株。
2.一种用于抑制或改善血中尿酸值升高的组合物,其包含权利要求1所述的乳酸菌或其菌体处理物作为活性成分。
3.一种用于抑制或改善脂肪肝的组合物,其包含权利要求1所述的乳酸菌或其菌体处理物作为活性成分。
4.一种用于抑制或改善生活方式相关疾病的组合物,其包含权利要求1所述的乳酸菌或其菌体处理物作为活性成分。
5.根据权利要求2~4中任一项所述的组合物,其为药物。
6.根据权利要求2~4中任一项所述的组合物,其为食品。
7.一种抑制或改善血中尿酸值升高、脂肪肝或生活方式相关疾病的方法,其包括向受试者施用有效量的乳酸菌(NITE BP-01634)或其菌体处理物,所述乳酸菌(NITE BP-01634)为短乳杆菌NTM003株。
8.根据权利要求7所述的方法,其中将所述乳酸菌(NITE BP-01634)或其菌体处理物,以每天1×104~1×1012个细胞或与其相当的量口服给药至血中尿酸值高的患者、脂肪肝患者或生活方式相关疾病患者,其中,所述乳酸菌(NITE BP-01634)为短乳杆菌NTM003株。
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Application Number | Priority Date | Filing Date | Title |
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JP2014-110912 | 2014-05-29 | ||
JP2014110912 | 2014-05-29 | ||
PCT/JP2015/002715 WO2015182155A1 (ja) | 2014-05-29 | 2015-05-28 | 新規乳酸菌及び該乳酸菌を含む組成物 |
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CN116536186A (zh) * | 2022-08-22 | 2023-08-04 | 扬州大学 | 一种可发酵大豆低聚糖的短乳杆菌及其应用 |
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CN106754479B (zh) * | 2016-11-24 | 2019-11-08 | 浙江大学宁波理工学院 | 一种弯曲乳杆菌及其应用 |
CN106834162A (zh) * | 2016-12-09 | 2017-06-13 | 大连医科大学 | 可降低血尿酸的短乳杆菌dm9218、基因片段及重组蛋白 |
BE1026084B1 (nl) * | 2018-03-07 | 2019-10-10 | Nutrition Sciences N.V. | Probiotische samenstelling voor gebruik in een voederadditief |
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CN116536186A (zh) * | 2022-08-22 | 2023-08-04 | 扬州大学 | 一种可发酵大豆低聚糖的短乳杆菌及其应用 |
CN116536186B (zh) * | 2022-08-22 | 2023-12-12 | 扬州大学 | 一种可发酵大豆低聚糖的短乳杆菌及其应用 |
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JP6524432B2 (ja) | 2019-06-05 |
EP3165599A4 (en) | 2017-12-27 |
EP3165599A1 (en) | 2017-05-10 |
US20170202890A1 (en) | 2017-07-20 |
CN106661542B (zh) | 2020-07-10 |
WO2015182155A1 (ja) | 2015-12-03 |
JPWO2015182155A1 (ja) | 2017-04-20 |
US10507222B2 (en) | 2019-12-17 |
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