CN110538200A - 用于改善肾病及抑制发炎的乳酸菌菌株的医药组合物及食品组合物 - Google Patents
用于改善肾病及抑制发炎的乳酸菌菌株的医药组合物及食品组合物 Download PDFInfo
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Abstract
本发明提供一种用于改善肾病及抑制发炎的包含乳酸菌菌株的医药组合物及食品组合物,其包含经分离的乳酸菌菌株,该乳酸菌菌株选自以下群组中的至少一种或任意组合:保藏编号为CGMCC No.15212的长双歧杆菌婴儿亚种(Bifidobacterium longum subsp.infantis)BLI‑02菌株、保藏编号为CGMCC No.15210的嗜酸乳杆菌(Lactobacillus acidophilus)TYCA06菌株以及保藏编号为CGMCC No.15211的两歧双歧杆菌(Bifidobacterium bifidum)VDD088菌株。
Description
【技术领域】
本发明涉及一种医药组合物及食品组合物,特别是一种用于改善肾病和/或抑制发炎的包含乳酸菌菌株的医药组合物及食品组合物。
【背景技术】
随着饮食习惯的改变,现代人罹患慢性肾脏病的人数已逐年攀升,而初期罹患慢性肾脏病的患者虽然可能有蛋白尿及血尿的症状,但只要肾脏功能大抵还正常,透过实时的治疗及饮食控制仍可减缓病情继续恶化。然而,重症的肾脏病患者则恐需要透过长期的血液透析治疗方能维持生命,其治疗的过程常会造成患者的不适,且亦产生庞大的经济压力。
一般的食用乳酸菌常见用于调整肠道健康的效果,目前有发现乳酸菌稳定肠道菌群的功效可能有助于改善慢性肾脏病,然并无特定的菌株被确认。而乳酸菌对身体健康的功能在于菌株(strain)的特异性而非菌种(species),此种对于人身健康有特殊功效的菌株称为功能性益生菌(Guidelines for the evaluation of probiotics in food;Reportof joint FAO/WHO working group on drafting guidelines for the evaluation ofprobiotics in food;London Ontario,Canada April 30 and May 1,2002:1-7)。因此,开发具有改善肾脏病的功能性益生菌是目前需努力的目标。
【发明内容】
本发明提供一种用于改善肾病及抑制发炎的包含乳酸菌菌株的医药组合物及食品组合物,其可降低血尿素氮(BUN)、血清肌酸酐(CRE)及尿液白蛋白(Urine ALB),改善肾脏纤维化的状况,以及抑制肾脏发炎反应,进而缓解肾脏病的病程。
本发明一实施例提供一种用于改善肾病和/或抑制发炎的包含乳酸菌菌株的医药组合物,其包含经分离的乳酸菌菌株以及医药上可接受的赋形剂或稀释剂。该乳酸菌菌株选自以下群组中的至少一种或其任意组合:保藏编号为CGMCC No.15212的长双歧杆菌婴儿亚种(Bifidobacterium longum subsp.infantis)BLI-02菌株、保藏编号为CGMCCNo.15210的嗜酸乳杆菌(Lactobacillus acidophilus)TYCA06菌株以及保藏编号为CGMCCNo.15211的两歧双歧杆菌(Bifidobacterium bifidum)VDD088菌株。
本发明另一实施例提供一种用于改善肾病和/或抑制发炎的包含乳酸菌菌株的食品组合物,其包含经分离的乳酸菌菌株以及生理上可接受的赋形剂或稀释剂。该乳酸菌菌株选自以下群组中的至少一种或其任意组合:保藏编号为CGMCC No.15212的长双歧杆菌婴儿亚种(Bifidobacterium longum subsp.infantis)BLI-02菌株、保藏编号为CGMCCNo.15210的嗜酸乳杆菌(Lactobacillus acidophilus)TYCA06菌株以及保藏编号为CGMCCNo.15211的两歧双歧杆菌(Bifidobacterium bifidum)VDD088菌株。
以下藉由具体实施例配合所附的图式详加说明,当更容易了解本发明的目的、技术内容、特点及其所达成的功效。
【附图说明】
图1为各组别小鼠血压影响的比较图。
图2为各组别小鼠进食量的比较图。
图3为各组别小鼠体重的比较图。
图4A为各组别小鼠肾脏重量的比较图。
图4B为各组别小鼠肾脏外观的比较图。
图5A及图5B为各组别小鼠血浆生化检测结果比较图。
图6为各组别小鼠尿蛋白分析结果比较图。
图7及图8为各组别小鼠肾脏组织染色切片示意图。
【具体实施方式】
以下将详述本发明的各个实施例,并配合图式作为例示。除了这些详细说明之外,本发明亦可广泛地施行于其它的实施例中,任何所述实施例的轻易替代、修改、等效变化都包含在本发明范围内,并以申请专利范围为准。在说明书的描述中,为了使读者对本发明有较完整的了解,提供了许多特定细节;然而,本发明可能在省略部分或全部特定细节的前提下,仍可实施。此外,众所周知的步骤或组件并未描述于细节中,以避免对本发明形成不必要的限制。图式中相同或类似的组件将以相同或类似符号来表示。特别注意的是,图式仅为示意之用,并非代表组件实际的尺寸或数量,有些细节可能未完全绘出,以求图式简洁。
本发明所述乳酸菌菌株的冷冻干燥培养物已于2018年1月15日保藏于中国微生物菌种保藏管理委员会普通微生物中心(CGMCC,北京市朝阳区北辰西路1号院3号,中国科学院微生物研究所,100101)。保藏的详细资料如以下表1所示。
表1:乳酸菌菌株的保藏资料
菌株名 | 分类 | 保藏编号 | 保藏日期 |
BLI-02 | 长双歧杆菌婴儿亚种 | CGMCC No.15212 | 2018年1月15日 |
TYCA06 | 嗜酸乳杆菌 | CGMCC No.15210 | 2018年1月15日 |
VDD088 | 两歧双歧杆菌 | CGMCC No.15211 | 2018年1月15日 |
根据本发明的一个实施例,提供一种用于改善肾病及抑制发炎包含乳酸菌菌株的医药组合物,其包含经分离的乳酸菌菌株以及医药上可接受的赋形剂或稀释剂。该乳酸菌菌株选自以下群组中的至少一种或其任意组合:保藏编号为CGMCC No.15212的长双歧杆菌婴儿亚种(Bifidobacterium longum subsp.infantis)BLI-02菌株、保藏编号为CGMCCNo.15210的嗜酸乳杆菌(Lactobacillus acidophilus)TYCA06菌株以及保藏编号为CGMCCNo.15211的两歧双歧杆菌(Bifidobacterium bifidum)VDD088菌株。其中,乳酸菌菌株可为具有活性的菌株或去活性菌株。乳酸菌菌株的数量可为106 CFU至1010 CFU,较佳地,本发明的医药组合物及食品组合物中的乳酸菌菌株数量可为107 CFU至109 CFU。
根据本发明另一实施例,提供一种用于改善肾病和/或抑制发炎的包含乳酸菌菌株的食品组合物,其包含经分离的乳酸菌菌株及生理上可接受的赋形剂或稀释剂。乳酸菌菌株选自以下群组中的至少一种或其任意组合:保藏编号为CGMCC No.15212的长双歧杆菌婴儿亚种(Bifidobacterium longum subsp.infantis)BLI-02菌株、保藏编号为CGMCCNo.15210的嗜酸乳杆菌(Lactobacillus acidophilus)TYCA06菌株以及保藏编号为CGMCCNo.15211的两歧双歧杆菌(Bifidobacterium bifidum)VDD088菌株。其中,乳酸菌菌株可为具有活性的菌株或去活性菌株。其中,乳酸菌菌株数量可为106 CFU至1010CFU。
于食品组合物的实施例中,生理上可接受的赋形剂或稀释剂可为一食品,举例而言,食品可包含但不限于乳制饮品、茶、咖啡、或其组合,其中乳制饮品可包含发酵乳、优格、奶酪或乳粉。于医药组合物的实施例中,医药组合物可包含口服剂型,其可为锭剂、胶囊、溶液剂或粉剂等。
以下,将以多个实施例说明本发明的含乳酸菌菌株的医药组合物及食品组合物改善肾病及抑制发炎的功效。
实施例1:用于改善肾病及抗发炎的乳酸菌的形态学以及一般性质
根据16S rDNA序列分析以及API细菌鉴定系统分析结果来确认菌株在分类学上的特征。上述菌株在形态学及一般性质上的特征详细列于以下表2。
表2:乳酸菌菌株的形态学及一般性质特征
为了进一步分析菌株改善肾病及抑制发炎的能力,以腺嘌呤(Adenine)诱发慢性肾脏病(chronic kidney disease,CKD)的小鼠进行实验,实验步骤如下所列:
1.提供6~8周龄雄性SPF级C57BL/6小鼠,将其分为四组,如以下表3所示:
表3
乳酸菌菌株选自以下群组中的至少一种或其任意组合:保藏编号为CGMCC No.15212的长双歧杆菌婴儿亚种(Bifidobacterium longum subsp.infantis)BLI-02菌株、保藏编号为CGMCC No.15210的嗜酸乳杆菌(Lactobacillus acidophilus)TYCA06菌株以及保藏编号为CGMCC No.15211的两歧双歧杆菌(Bifidobacterium bifidum)VDD088菌株。
2.试验前先秤量各小鼠体重,试验期间每周测量一次小鼠体重及食物摄取量。
3.上述四组小鼠饲养6周后进行牺牲,牺牲前一天先测定小鼠血压、采集血液并收集尿液以进行血浆生化检测及尿蛋白分析。牺牲时取出小鼠肾脏以评估肾脏组织状况。
4.各项实验数据以mean±SEM来表示,并以Student’s t-test测定是否达到生物统计上的显著意义。如p值小于0.05则为具有显著差异。(*p<0.05;**p<0.01;***p<0.001)。
较佳地,在本发明的乳酸菌菌株中所含的菌数比例较佳可为:TYCA06:BLI02:VDD88=3:4:3,将以此菌数比例进行小鼠实验。然本发明并不以此为限制,可依需求而调整乳酸菌菌株的比例,举例而言,乳酸菌菌株所含的菌数比例可为TYCA06:BLI02:VDD88=10:0:0、或TYCA06:BLI02:VDD88=0:10:0、或TYCA06:BLI02:VDD88=0:0:10。
以下,将搭配图式说明实验结果。请参阅图1,其是各组小鼠的血压比较图。一般来说,当肾脏阻塞时会造成血压升高的现象,因此血压的高低表现也是评估肾脏病状况有无改善的表征之一。由图1可了解,比较组的血压数据明显高于对照组,显示喂食0.2%腺嘌呤确实会造成血压升高的状况。然而,在有给予本发明乳酸菌菌株的组别中,小鼠的血压有下降的趋势,且给予高剂量的组别血压下降的趋势更为明显,显示给予本发明乳酸菌菌株的小鼠肾脏阻塞的情况确实有减缓,且具有剂量依赖性(dose dependent)。而图2为各组别小鼠每周的摄食量,并无明显差异。
图3为各组别小鼠的体重的比较图,其中,在有喂食0.2%腺嘌呤的组别中,给予本发明乳酸菌菌株的组别(实施例1及实施例2)体重皆有上升,且给予较高剂量的本发明乳酸菌菌株的组别(实施例2)其体重范围与对照组一致。罹患肾脏病的个体因其身体代谢异常,因此常有体重减轻的现象,在本实施例中可发现给予本发明乳酸菌菌株的小鼠的体重有恢复的情况,且具有剂量依赖性(dose dependent),显示本发明乳酸菌菌株对于肾脏健康的恢复具备显著影响。
接着,进行各组别小鼠的肾脏功能评估,一般来说,肾脏功能评估包含检测肾脏大小、重量、血液中尿素氮(BUN)与血清肌酸酐(creatinine)含量、以及尿蛋白分析。
请参阅图4A,相较于比较组,实施例2的小鼠肾脏重量有明显上升的趋势;另外,可由肾脏表面平滑度及形状的完整度来评估肾脏的状态,请参阅图4B,(a)部分为对照组小鼠的肾脏、(b)部分为比较组小鼠的肾脏、(c)部分为实施例1小鼠的肾脏、(d)部分为实施例2小鼠的肾脏。可发现比较组的小鼠肾脏外观较不平整且略为萎缩,而实施例1及实施例2的小鼠肾脏外观平滑度高且完整,与对照组的差异不大。由上述可了解,本发明乳酸菌菌株对于肾脏的修复有所帮助。
而有关于血液中BUN与肌酸酐含量的分析,请参阅图5A及5B。使用干式生化分析仪FUJI DRI-CHEM 4000i进行分析。比较组小鼠血液中BUN与肌酸酐含量相较于对照组皆明有显升高,而实施例1及实施例2的小鼠血液中BUN与肌酸酐含量皆有下降的趋势,且是下降至接近对照组的含量,显示本发明乳酸菌菌株有助于肾脏功能的恢复。
此外,有关尿蛋白的分析,是于96孔盘中分别将标准溶液和尿液检体各取10μl加入,然后加入已稀释好的Bio-rad染料200μl,震荡摇晃5分钟,以595nm波长测定吸光值。根据标准品与吸光值所显示的标准曲线,经过回归运算后得到的公式,可用内插法来推算尿液中白蛋白的浓度。请参阅图6。一般来说,罹患慢性肾炎的患者由于肾脏廓清率下降的缘故,其尿白蛋白会有偏高的现象。然而,在本试验中,比较组、实施例1及实施例2的动物造症模式为急性肾炎模式,是因阻塞性发炎而导致肾脏发炎,因此尿白蛋白会因阻塞而降低。如图6所示,实施例2的小鼠尿中的白蛋白含量明显地恢复至与对照组相似,显示本发明乳酸菌菌株有助于改善因肾脏发炎所导致的尿白蛋白异常现象,且具有剂量依赖性。
此外,在医学上来说,“慢性肾脏病”常见是因为肾脏长期的发炎(如:感染、免疫复合体伤害、炎症反应)而造成受损,导致其结构或功能产生病变,因此,若能抑制肾脏发炎的状况,应可达到改善肾病症状或减缓肾脏病病程的功效。接着,将进一步了解本发明医药组合物对于抑制发炎的效果,请参阅图7,其是为各组别小鼠的肾脏组织染色切片图(H&Estain、MT stain)。取小鼠左肾2mm厚度泡中性福尔马林固定,并利用苏木酸和伊红染色(hematoxylin and eosin stain,H&E stain)来进行染色切片。其中,(a)部分为对照组小鼠的肾脏组织染色切片、(b)部分为比较组小鼠的肾脏组织染色切片、(c)部分为实施例1小鼠的肾脏组织染色切片、(d)部分为实施例2小鼠的肾脏组织染色切片。由图7可发现,比较组的小鼠肾脏有大量的免疫细胞浸润的情况,而实施例1及实施例2的小鼠肾脏中免疫细胞浸润的程度则逐渐与对照组相似。一般来说,发炎反应是表示活体组织对于外来或内在因素造成伤害所引起的保护性免疫作用,当发炎程度趋于严重时,则免疫细胞浸润的情况就会越加明显。而上述图7的结果可了解,实施例1及实施例2的小鼠免疫细胞浸润的状况相较于比较组的小鼠为低,显见其发炎的状况获得改善或抑制。
另外一方面,当肾脏长期处于发炎反应时,会使其组织产生纤维化的情况,于此,将利用MT stain观察各组别小鼠肾脏组织切片纤维化情形。请参阅图8,其中,(a)部分为对照组小鼠的肾脏组织切片、(b)部分为比较组小鼠的肾脏组织切片、(c)部分为实施例1小鼠的肾脏组织切片、(d)部分为实施例2小鼠的肾脏组织切片。可发现,比较组的小鼠肾脏纤维化的情况较为严重,而实施例1及实施例2的小鼠肾脏组织纤维化的程度则逐渐与对照组相似,与比较组的纤维化程度差异甚大,尤其是实施例2中给予较高剂量乳酸菌菌株的组别差异更为显著。
由上述可了解,本发明含乳酸菌菌株的医药组合物及食品组合物具有改善肾病及抑制发炎的功效,其具有降低罹患肾病个体的血尿素氮(BUN)、血清肌酸酐(CRE)及尿液白蛋白(Urine ALB)的功效,并能改善肾脏纤维化的情况,更具有抑制肾脏发炎反应的效果,进而达到缓解慢性肾脏病的病程的目的。
以上所述实施例仅是为说明本发明的技术思想及特点,其目的在使熟习此项技艺之人士能够了解本发明的内容并据以实施,当不能以之限定本发明的专利范围,即大凡依本发明所揭示的精神所作的均等变化或修饰,仍应涵盖在本发明的专利范围内。
Claims (10)
1.一种含乳酸菌菌株的医药组合物,用以改善肾病和/或抑制发炎,其特征在于,包含:
经分离的乳酸菌菌株,该乳酸菌菌株选自以下群组中的至少一种或其任意组合:保藏编号为CGMCC No.15212的长双歧杆菌婴儿亚种(Bifidobacterium longumsubsp.infantis)BLI-02菌株、保藏编号为CGMCC No.15210的嗜酸乳杆菌(Lactobacillusacidophilus)TYCA06菌株以及保藏编号为CGMCC No.15211的两歧双歧杆菌(Bifidobacterium bifidum)VDD088菌株;以及
医药上可接受的赋形剂或稀释剂。
2.如权利要求1所述的含乳酸菌菌株的医药组合物,其特征在于,该乳酸菌菌株为具有活性的菌株。
3.如权利要求1所述的含乳酸菌菌株的医药组合物,其特征在于,该乳酸菌菌株为去活性的菌株。
4.如权利要求1所述的含乳酸菌菌株的医药组合物,其特征在于,该乳酸菌菌株的数量为106CFU至1010CFU。
5.一种含乳酸菌菌株的食品组合物,用以改善肾病和/或抑制发炎,包含:
经分离的乳酸菌菌株,该乳酸菌菌株选自以下群组中的至少一种或其任意组合:保藏编号为CGMCC No.15212的长双歧杆菌婴儿亚种(Bifidobacterium longumsubsp.infantis)BLI-02菌株、保藏编号为CGMCC No.15210的嗜酸乳杆菌(Lactobacillusacidophilus)TYCA06菌株以及保藏编号为CGMCC No.15211的两歧双歧杆菌(Bifidobacterium bifidum)VDD088菌株;以及
生理上可接受的赋形剂或稀释剂。
6.如权利要求5所述的含乳酸菌菌株的食品组合物,其特征在于,该乳酸菌菌株为具有活性的菌株。
7.如权利要求5所述的含乳酸菌菌株的食品组合物,其特征在于,该乳酸菌菌株为去活性的菌株。
8.如权利要求5所述的含乳酸菌菌株的食品组合物,其特征在于,该乳酸菌菌株的数量为106CFU至1010CFU。
9.选自以下的乳酸菌菌株:
保藏编号为CGMCC No.15212的长双歧杆菌婴儿亚种(Bifidobacterium longumsubsp.infantis)BLI-02菌株;
保藏编号为CGMCC No.15210的嗜酸乳杆菌(Lactobacillus acidophilus)TYCA06菌株;和
保藏编号为CGMCC No.15211的两歧双歧杆菌(Bifidobacterium bifidum)VDD088菌株。
10.选自以下的乳酸菌菌株中的任意一种或多种在制备改善肾病和/或抑制发炎用的医药组合物或食品组合物中的应用:
保藏编号为CGMCC No.15212的长双歧杆菌婴儿亚种(Bifidobacterium longumsubsp.infantis)BLI-02菌株;
保藏编号为CGMCC No.15210的嗜酸乳杆菌(Lactobacillus acidophilus)TYCA06菌株;和
保藏编号为CGMCC No.15211的两歧双歧杆菌(Bifidobacterium bifidum)VDD088菌株。
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CN112007052A (zh) * | 2020-09-22 | 2020-12-01 | 上海泓商生物科技有限公司 | 护肾益生菌组合物 |
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CN115247138B (zh) * | 2021-04-28 | 2023-05-26 | 锦乔生物科技有限公司 | 具减少脂肪与提升运动表现的乳酸菌组合物及其用途 |
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US10993973B2 (en) | 2021-05-04 |
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US20190358273A1 (en) | 2019-11-28 |
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