CN115281345A - 一种复合益生菌组合物联合二甲基胍治疗ⅱ型糖尿病的用途 - Google Patents
一种复合益生菌组合物联合二甲基胍治疗ⅱ型糖尿病的用途 Download PDFInfo
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Abstract
本发明提供的联合双胍类抗糖尿病药物在制备预防、缓解、辅助治疗或治疗糖尿病的食品、保健品或药物中的用途,所述复合益生菌组合物包括:干酪乳杆菌Zhang(Lactobacillus casei Zhang);乳双歧杆菌V9(Bifidobacterium animalis subsp.lactis V9);植物乳杆菌P‑8(Lactobacillusplantarum P‑8);鼠李糖乳杆菌Probio‑M9(Lactobacillus rhamnosusProbio‑M9);和乳双歧杆菌Probio‑M8(Bifidobacterium lactis Probio‑M8);上述复合益生菌组合物具有预防、缓解、辅助治疗或治疗糖尿病的作用,能够联合二甲双胍协同预防、缓解、辅助治疗或治疗糖尿病,尤其是Ⅱ型糖尿病。
Description
技术领域
本发明涉及益生菌技术领域,具体涉及一种复合益生菌组合物联合二甲基胍治疗Ⅱ型糖尿病的用途。
背景技术
Ⅱ型糖尿病是全世界最为常见的糖尿病类型,占所有糖尿病的90-95%。Ⅱ型糖尿病为非胰岛素依赖型糖尿病,一般发病比较迟缓,常见于成年人、中老年人。Ⅱ型糖尿病的发病率在不断增加,已经到流行的程度,并且在不断年轻化。Ⅱ型糖尿病的诊断标准为:有糖尿病症状并且随机血糖≥11.1mmol/L;空腹血糖≥7.0mmol/L;口服葡萄糖耐量试验时二小时血糖≥11.1mmol/L。Ⅱ型糖尿病可分为肥胖型与非肥胖型。肥胖型患者以胰岛素抵抗为主,病人多肥胖,因胰岛素抵抗,胰岛素敏感性下降,血液中胰岛素增高以补偿其胰岛素抵抗,但相对于病人的高血糖而言,胰岛素分泌仍相对不足。治疗方法一般采用饮食治疗和口服降糖药。非肥胖型患者以胰岛素分泌缺陷为主,临床上需要补充外源性胰岛素。除了胰岛素抵抗的问题,胰腺中的β细胞生产和分泌胰岛素减少。Ⅱ型糖尿病更容易伴发其他疾病,如动脉粥样硬化、冠心病、高血压、肥胖和血脂异常。胰岛素抵抗会加重并可能直接导致这些问题。到目前为止,还无法控制人体的遗传因素。但是,可以通过对环境因素进行干预,降低Ⅱ型糖尿病的患病率。
益生菌已允许用于许多疾病的临床治疗中,通常被定义为当机体从膳食中摄入足够量时,能够调节并改善肠道菌群,对人体健康产生明确益处的一类活性微生物的总称。在《益生菌的科学共识(2020年版)》中要求,益生菌的核心特征是“足够数量、活菌状态和有益健康功能”,因此,选择需要精准和科学。益生菌可直接或间接作用于肠上皮而发挥有益作用,平衡肠道菌群,调节肠道屏障功能和通透性。复合益生菌组合物呈粉末状、颗粒状或块状,而复合益生菌组合物则是将益生菌粉和各原辅料混合后罐装,便于携带和食用。
二甲双胍作为一种双胍类药物,是当前治疗初期Ⅱ型糖尿病的首选药物之一,它具有较好的降低肝脏糖异生及抑制肠道对糖吸收的作用。此外,研究人员发现高脂饮食的肥胖小鼠摄入益生菌后,胰岛素抗性得到改善;饮用益生菌酸奶可显著降低血糖浓度和糖化血红蛋白浓度。目前,还未有益生菌结合二甲双胍协同治疗Ⅱ型糖尿病的相关报道。
发明内容
因此,本发明要解决的技术问题在于提供一种复合益生菌组合物联合双胍类抗糖尿病药物在制备预防、缓解、辅助治疗或治疗糖尿病的食品、保健品或药物中的用途,所述复合益生菌组合物能够联合二甲双胍协同预防、缓解、辅助治疗或治疗糖尿病,尤其是Ⅱ型糖尿病。
为此,本发明提供了如下的技术方案:
一种复合益生菌组合物联合双胍类抗糖尿病药物在制备预防、缓解、辅助治疗或治疗糖尿病的食品、保健品或药物中的用途,所述复合益生菌组合物包括:
干酪乳杆菌Zhang(Lactobacillus casei Zhang),保藏编号为CGMCC No.5469;
乳双歧杆菌V9(Bifidobacterium animalis subsp.lactis V9),保藏编号为CGMCC No.5470;
植物乳杆菌P-8(Lactobacillus plantarum P-8),保藏编号为CGMCC No.6312;
鼠李糖乳杆菌Probio-M9(Lactobacillus rhamnosus Probio-M9),保藏编号为CGMCC No.18639;
乳双歧杆菌Probio-M8(Bifidobacterium lactis Probio-M8),保藏编号为CGMCCNo.18610。
可选的,所述益生菌组合物的总活菌数不低于3.0×1010CFU/g;
可选的,干酪乳杆菌Zhang活菌数不低于50亿,乳双歧杆菌V9活菌数不低于75亿,植物乳杆菌P-8活菌数不低于50亿,鼠李糖乳杆菌Probio-M9活菌数不低于50亿,乳双歧杆菌Probio-M8活菌数不低于75亿。
可选的,每株菌的活菌数不低于6.0×1011CFU/g;
可选的,所述双胍类抗糖尿病药物包括二甲双胍、磷酸西格列汀、利格列汀、吡格列酮、苯乙双胍或丁二胍。
可选的,所述复合益生菌组合物中每株菌的原料包括该株菌的培养物、发酵物或冻干粉中的任意一种;
可选的,每株菌的原料为该株菌的冻干粉。
可选的,所述复合益生菌组合物还包括辅料;
可选的,所述辅料为益生元和/或或膳食纤维;
可选的,所述辅料包括低聚半乳糖、低聚果糖、菊粉、聚葡萄糖和麦芽糖醇中的至少一种;
可选的,所述复合益生菌组合物中,总菌粉量与辅料的质量比为10-15:85-90。
可选的,所述复合益生菌组合物的制备方法包括将含各株菌的原料混合的步骤;
可选的,还包括将含各株菌的原料混合后添加辅料的步骤。
所述的的用途,还具有如下的用途:
(a)在制备发酵剂、发酵制品、益生菌固体饮料或功能性保健制品中的用途;
(b)在制备提高胰岛素分泌、降低血脂、降低血糖、降低糖化血红蛋白含量、降低尿酸含量或改善胰岛功能的食品、保健品或药物中的用途;
(c)在制备预防、缓解、辅助治疗或治疗痛风的食品、保健品或药物中的用途。
可选的,所述糖尿病为2型糖尿病;
可选的,所述缓解糖尿病包括缓解糖尿病患者发病风险;
可选的,为缓解2型糖尿病患者发病风险;
可选的,所述食品包括传统食品、保健食品或辅助治疗型食品组合物。
可选的,所述预防、缓解、辅助治疗或治疗糖尿病包括提高胰岛素分泌、降低血糖、降低糖化血红蛋白含量、降低尿酸含量、降低血脂或改善胰岛功能。
可选的,所述(a)中,所述发酵制品包括豆制品、乳制品或果蔬制品。
一种预防、缓解、辅助治疗或治疗糖尿病的组合物,包括:
权利要求1-9任一项中所述的复合益生菌组合物;和
双胍类抗糖尿病药物;
可选的,所述复合益生菌组合物1-2重量份,双胍类抗糖尿病药物1-2重量份;
可选的,所述复合益生菌组合物2重量份,双胍类抗糖尿病药物1.5重量份;
可选的,所述双胍类抗糖尿病药物包括二甲双胍、磷酸西格列汀、利格列汀、吡格列酮、苯乙双胍或丁二胍。
本发明技术方案,具有如下优点:
1、本发明提供的一种复合益生菌组合物联合双胍类抗糖尿病药物在制备预防、缓解、辅助治疗或治疗糖尿病的食品、保健品或药物中的用途,所述复合益生菌组合物,包括:干酪乳杆菌Zhang(Lactobacillus casei Zhang),保藏编号为CGMCC No.5469;乳双歧杆菌V9(Bifidobacterium animalis subsp.lactis V9),保藏编号为CGMCC No.5470;植物乳杆菌P-8(Lactobacillus plantarum P-8),保藏编号为CGMCC No.6312;鼠李糖乳杆菌Probio-M9(Lactobacillus rhamnosus Probio-M9),保藏编号为CGMCC No.18639;和乳双歧杆菌Probio-M8(Bifidobacterium lactis Probio-M8),保藏编号为CGMCC No.18610;上述复合益生菌组合物联合双胍类抗糖尿病药物具有协同预防、缓解、辅助治疗或治疗糖尿病的作用,尤其是Ⅱ型糖尿病。
进一步的,本发明所述复合益生菌组合物中,干酪乳杆菌Zhang、乳双歧杆菌V9、植物乳杆菌P-8、鼠李糖乳杆菌Probio-M9和乳双歧杆菌Probio-M8具有良好的肠道定植能力。
进一步的,上述复合益生菌组合物能够联合二甲双胍协同预防、缓解、辅助治疗或治疗痛风。
2、本发明提供的一种复合益生菌组合物,所述益生菌组合物的总活菌数不低于3.0×1010CFU/g,每株菌的活菌数不低于6.0×1011CFU/g;在上述活菌数条件下,本发明提供的一种复合益生菌组合物具有调节肠道菌群、防止腹泻和便秘、增强免疫力等有益效果。
3、本发明提供的一种复合益生菌组合物联合双胍类抗糖尿病药物具有制备预防、缓解、辅助治疗或治疗糖尿病或痛风的食品或药物中的用途。
附图说明
为了更清楚地说明本发明具体实施方式或现有技术中的技术方案,下面将对具体实施方式或现有技术描述中所需要使用的附图作简单地介绍,显而易见地,下面描述中的附图是本发明的一些实施方式,对于本领域普通技术人员来讲,在不付出创造性劳动的前提下,还可以根据这些附图获得其他的附图。
图1是本发明实验例中血糖理化指标变化实验中益生菌组与安慰剂组0个月(0M)、3个月(3M)的血液中糖化血红蛋白含量变化;图中**表示p<0.01,具有显著的差异;
图2是本发明实验例中尿酸含量变化实验中益生菌组与安慰剂组0个月、3个月的血液中尿酸含量变化变化;图中**表示p<0.01,具有显著的差异;
图3是本发明实验例中尿酸含量变化实验中益生菌组与安慰剂组0个月、3个月血液中尿酸含量变化;
图4是本发明实验例中脂类理化指标变化实验中益生菌组与安慰剂组0个月、3个月的血液中血清中高密度低密度脂蛋白(HDL-CH)变化;
图5是本发明实验例中血糖与糖耐量分析实验中益生菌组与安慰剂组0个月、3个月的血液中空腹血糖、0.5h血糖、1h血糖、2h血糖、3h血糖含量变化。
图6是本发明实验例中胰岛素相关指标变化实验中益生菌组与安慰剂组口服葡萄糖耐受量试验胰岛素曲线。
具体实施方式
提供下述实施例是为了更好地进一步理解本发明,并不局限于所述最佳实施方式,不对本发明的内容和保护范围构成限制,任何人在本发明的启示下或是将本发明与其他现有技术的特征进行组合而得出的任何与本发明相同或相近似的产品,均落在本发明的保护范围之内。
实施例中未注明具体实验步骤或条件者,按照本领域内的文献所描述的常规实验步骤的操作或条件即可进行。所用试剂或仪器未注明生产厂商者,均为可以通过市购获得的常规试剂产品。
干酪乳杆菌Zhang(Lactobacillus casei Zhang)是2002年分离自内蒙古大草原自然发酵酸马奶中的1株具有多种益生功能的益生菌,是我国第1株完成全基因组测序的益生菌,已于2011年11月18日,保藏在中国微生物菌种保藏管理委员会普通微生物中心,保藏地址北京市朝阳区北辰西路1号院3号,保藏编号为:CGMCC No.5469。试验研究发现:L.casei Zhang干预可加速脂肪酸氧化从而起到降血脂的作用。临床循证研究表明L.caseiZhang增加了血液中抗炎因子水平,增强对流感病毒的免疫应答,菌群分析结果表明可使老年人肠道菌群年轻化。
乳双歧杆菌V9(Bifidobacterium animalis subsp.lactis V9)是2005年分离自健康蒙古族儿童肠道的1株益生菌,于2011年11月18日,保藏在中国微生物菌种保藏管理委员会普通微生物中心,保藏地址北京市朝阳区北辰西路1号院3号,保藏编号为:CGMCCNo.5470。基因组学研究发现该菌株发生重组、突变几率极小,遗传稳定。试验研究表明:B.lactis V9对肠道致病菌具有显著的拮抗作用,可提高肠道抗致病菌感染的能力、显著提高腹泻康复率,可有效治疗腹泻、可使人体肠道菌群结构健康化。
植物乳杆菌P-8(Lactobacillus plantarum P-8)是2005年分离自内蒙古巴彦淖尔市乌拉特中旗草原上牧民家庭自然发酵酸牛乳样品的1株具有优良益生特性的植物乳杆菌。已于2012年06月28日,保藏在中国微生物菌种保藏管理委员会普通微生物中心,保藏地址北京市朝阳区北辰西路1号院3号,保藏编号为:CGMCC No.6312。试验研究表明:L.plantarum P-8具有优异的耐受胃酸、肠液和胆盐能力、具有良好的稳定性。可改善脂质代谢,降低血脂,提高机体的免疫功能,还可缓解焦虑,改善认知能力。
鼠李糖乳杆菌Probio-M9(Lactobacillus rhamnosus Probio-M9)于2017年分离自健康妇女母乳。已于2019年10月8日,保藏在中国微生物菌种保藏管理委员会普通微生物中心,保藏地址北京市朝阳区北辰西路1号院3号,保藏编号为:CGMCC No.18639。具有调节肠道菌群稳态,抗肿瘤活性。
乳双歧杆菌Probio-M8(Bifidobacterium lactis Probio-M8)于2017年分离自健康妇女母乳。已于2019年10月08日,保藏在中国微生物菌种保藏管理委员会普通微生物中心,保藏地址北京市朝阳区北辰西路1号院3号,保藏编号为:CGMCC No.18610。具有调节肠道菌群稳态,缓解过敏,改善睡眠等功能。
下述实施例中各益生菌菌粉的制备方法,包括如下步骤:
1)菌种的活化:将-40℃冷冻保存的菌株(干酪乳杆菌Zhang、乳双歧杆菌V9、植物乳杆菌P-8、鼠李糖乳杆菌Probio-M9和乳双歧杆菌Probio-M8)分别接种于121℃、15min灭菌后对应的液体培养基中,37℃厌氧培养18-24h,如此传代培养1-2次得到活化菌种;乳酸菌(干酪乳杆菌Zhang、植物乳杆菌P-8、鼠李糖乳杆菌Probio-M9)对应的液体培养基为MRS液体培养基,双歧杆菌(乳双歧杆菌V9和和乳双歧杆菌Probio-M8)对应的液体培养基为TPY液体培养基。
2)优化培养基的配制:
将优化培养基各成分按比例配制,混合均匀后调pH值为6.5,121℃下灭菌15min;
双歧杆菌(乳双歧杆菌V9和乳双歧杆菌Probio-M8)优化培养基组成如下:乳糖12.0Kg,牛肉膏7.0Kg,酵母粉7.0Kg,酪蛋白胨12.0Kg,大豆蛋白胨7.0Kg,KH2PO4 4.0Kg,K2HPO4 1.0Kg,MgSO4 0.05Kg,吐温-800.15Kg,L-半胱氨酸盐酸盐0.7Kg,碳酸钙1.2Kg,蒸馏水1000L。
乳酸菌(干酪乳杆菌Zhang、植物乳杆菌P-8、鼠李糖乳杆菌Probio-M9)优化培养基组成如下:蔗糖23.5Kg,乳糖12.0Kg,大豆蛋白胨15.0Kg,酵母粉5.0Kg,酵母胨12Kg,Na2HPO321.0Kg,柠檬酸2.0Kg,MgSO4·7H2O0.6Kg,MnSO4·5H2O 0.3Kg,吐温-80 1.0Kg,L-半胱氨酸盐酸盐0.3Kg,蒸馏水1000L。
3)种子液的制备:
取步骤1)中活化好的各个菌种分别接种于2)中配制的优化培养基中,37℃厌氧培养至pH值为4.5-4.8时停止;
4)接种与发酵:
将步骤3)的种子液,按1‰接种于2)中配制的优化培养基中,在控制的发酵条件下发酵18h;
发酵条件控制为:第一阶段:发酵前期30℃恒温培养,自然发酵至pH为5.0;第二阶段:再调整发酵温度为37℃恒温培养,并控制pH保持6.0,保持厌氧发酵。第一阶段和第二阶段总共的发酵时间为18h。
上述过程中通过流加中和剂的方法控制pH,其中中和剂是NaOH。
其中厌氧条件通过每两个小时通氮气一次的方法实现。
5)终止发酵
当菌体产酸停止时终止发酵,得到各菌株的高密度发酵液,发酵液活菌数达到2×1010cfu/ml以上。
其中可根据pH不再降低,中和剂流加停止来判断产酸是否停止。
6)冷冻干燥
a.菌体浓缩:高密度发酵液经12000g离心浓缩菌体;
b.添加保护剂:菌体浓缩液添加3-8体积倍数的保护剂溶液;保护剂溶液组成如下:脱脂乳10-15Kg,乳糖8-12Kg,维生素C1-2Kg,谷氨酸钠1-2Kg,蒸馏水1000L。
c.干燥:将上述添加保护剂后的菌悬液经冷冻干燥得到冻干菌粉,各株益生菌的菌粉中活菌数均达到6.0×1011cfu/g以上。
实施例1
一种复合益生菌组合物,配方:
干酪乳杆菌Zhang菌粉8.4mg;
乳双歧杆菌V9菌粉12.5mg;
植物乳杆菌P-8菌粉8.4mg;
鼠李糖乳杆菌Probio-M9菌粉8.4mg;
乳双歧杆菌Probio-M8菌粉12.5mg;
辅料低聚半乳糖,451.8mg。
上述复合益生菌组合物的制备方法,按照配方称取每株菌的冻干粉,混合均匀,然后加入辅料,混合均匀。
实施例2
一种复合益生菌组合物,配方:
干酪乳杆菌Zhang菌粉1g;
乳双歧杆菌V9菌粉1g;
植物乳杆菌P-8菌粉1g;
鼠李糖乳杆菌Probio-M9菌粉1g;
乳双歧杆菌Probio-M8菌粉1g;
辅料聚葡萄糖,28.3g。
上述复合益生菌组合物的制备方法,按照配方称取每株菌的冻干粉,混合均匀,然后加入辅料,混合均匀。
实施例3
一种复合益生菌组合物,配方:
干酪乳杆菌Zhang菌粉1g;
乳双歧杆菌V9菌粉1g;
植物乳杆菌P-8菌粉1g;
鼠李糖乳杆菌Probio-M9菌粉1g;
乳双歧杆菌Probio-M8菌粉1g;
辅料低聚半乳糖,35g。
上述复合益生菌组合物的制备方法,按照配方称取每株菌的冻干粉,混合均匀,然后加入辅料,混合均匀。
实施例4一种预防、缓解、辅助治疗或治疗糖尿病的组合物
一种复合益生菌组合物,配方:实施例1的复合益生菌组合物2g,二甲双胍1.5g。
实施例5一种预防、缓解、辅助治疗或治疗糖尿病的组合物
一种复合益生菌组合物,配方:实施例2的复合益生菌组合物1g,丁二胍2g。
实施例6一种预防、缓解、辅助治疗或治疗糖尿病的组合物
一种复合益生菌组合物,配方:实施例3的复合益生菌组合物2g,吡格列酮1g。
实验例
1实验方法
1.1样品
复合益生菌组合物:实施例1制备的复合益生菌组合物。
二甲双胍:格华止。
安慰剂:将实施例1中的菌粉替换为麦芽糊精,其他条件不变制备得到的组合物。
试验检测样本为采集志愿者的血液样本。
1.2试验分组
复合益生菌组合物联合二甲双胍临床试验采用随机、双盲、安慰剂对照试验。试验共招募Ⅱ型糖尿病患者48人,采用随机分组方式,分为益生菌组(27人)和安慰剂组(21人)。
受试人群:受试者应为18-70周岁,男女不限,符合以下任意一项或者同时满足两项:甘油三酯≥1.8mmol/L,总胆固醇≥5.7mmol/L。未曾使用且短期内不计划使用降脂药物治疗。
入选标准:只有当受试者符合以下所有标准,才适合入组本研究。
1.男性或女性均可,年龄在18-70周岁之间;
2.BMI(Body Mass Indx)在24kg/m2-30kg/m2之间;
3.男性腰围≥90cm,女性腰围≥85cm;
4.入组前1月未使用抗生素;
5.无慢性胃肠道疾病史;
6.同意参加此研究,并签署书面知情同意书;
7.新发现或既往有II型糖尿病症患者均可,无其他并发症,未使用过降糖药物治疗(II型糖尿病的诊断标准需要以空腹血糖或餐后血糖为依据,或根据随机血糖和糖化血红蛋白。检查需要在同一天监控两次以上。如果空腹血糖超过7.0mmol/L,餐后血糖超过11.1mmol/L,随机血糖超过11.1mmol/L,糖化血红蛋白超过6.5%,可诊断为II型糖尿病。);
排除标准:若受试者符合以下任一条者,则不能入选:
1.处于妊娠期、哺乳期或者6个月内计划妊娠的妇女;
2.肝功能不全者:谷丙转氨酶及谷草转氨酶≥正常值高限2倍及以上者;
3.肾功能不全者:肾小球滤过率≤90ml/min/1.72m2;
4.高血压,且使用2种以上降压药物治疗血压仍高于160/100mmHg者;
5.心功能不全者;
6.患有贫血或者其他血液病者;
7.有乳酸菌及其制品过敏史或高敏体质者;
8.筛选前3个月内接受过其他药物研究者;
益生菌组(A组):给药剂量为复合益生菌组合物(2g/天)和二甲双胍(格华止,1.5g/天);
安慰剂组(B组):给药剂量为安慰剂(2g/天)和二甲双胍(格华止,1.5g/天)。
给药方式为口服。
给药时间为3个月。
1.3本发明益生菌组合物对各指标的调节作用
1.3.1血糖理化指标变化
诊断糖尿病的主要指标:空腹血糖和糖化血红蛋白。上述指标的检测方法:采集各组患者在第0个月(第0天未服药)和治疗3个月(第90天)后的血液,使用血糖仪检测空腹血糖与糖化血红蛋白。血糖浓度越高,糖化血红蛋白的相对百分率越高。
空腹血糖结果如图1所示,治疗3个月后益生菌组患者的空腹血糖均显著降低,相比第0个月具有显著性差异(P=0.0077**),而安慰剂组治疗3个月后的患者的空腹血糖相比第0个月不具有显著性差异(P=0.45)。
糖化血红蛋白结果如图2所示,治疗3个月后益生菌组患者的糖化血红蛋白均显著降低,相比第0个月具有显著性差异(P<0.001**),而安慰剂组治疗3个月后的患者的糖化血红蛋白相比第0个月不具有显著性差异(P=0.87)。
1.3.2尿酸含量变化
研究表明尿酸浓度升高可增加糖尿病肾病的发病风险。上述尿酸指标的检测方法:在检查前,禁止剧烈运动,保持良好的饮食和作息,检查时:即先排出一部分尿弃去,以冲掉留在尿道口及前尿道的细菌,然后将中段尿留取送检。收集各组患者在第0个月(第0天未服药)和治疗3个月(第90天)后的尿液,用酸碱测定仪测定。
尿酸含量检测结果如图3所示,益生菌组尿酸在治疗后有所下降,安慰剂组有所上升。
1.3.3脂类理化指标变化
检测指标:血清中高密度和低密度脂蛋白(HDL-CH)。上述指标的检测方法:采集各组患者在第0个月(第0天未服药)和治疗3个月(第90天)后的血液,加入低密度脂蛋白胆固醇的抑制剂,将低密度和极低密度部分隐藏起来,直接测定高密度部分的胆固醇含量,在510nm波长处测定吸光度值,计算其含量。低密度脂蛋白能与磷钨酸-镁和聚乙二醇复合剂作用产生沉淀,用分散剂可使沉淀颗粒细小均一,在630nm波长处测定吸光度值,计算其含量。
结果如图4所示,治疗3个月后,益生菌组的血清中高密度和低密度脂蛋白(HDL-CH)有上升趋势,而安慰剂组则呈现上升趋势。
1.3.4血糖分析结果
分别测定了试验开始与结束时益生菌组与安慰剂组志愿者空腹血糖、服用葡萄糖(口服含75g无水葡萄糖的水溶液,儿童按每公斤体重1.75g计算,总量不超过75g)后0.5h血糖、服用葡萄糖后1h血糖、服用葡萄糖后2h血糖、服用葡萄糖后3h血糖含量。上述指标的检测方法:空腹血糖指在隔夜空腹(至少8~10小时未进任何食物,饮水除外)后,早餐前采的血,检测各组患者在第0个月(第0天未服药)和治疗3个月(第90天)的空腹血糖、服用葡萄糖后0.5h血糖、服用葡萄糖后1h血糖、服用葡萄糖后2h血糖、服用葡萄糖后3h血糖含量。
结果如图5所示,益生菌组患者空腹血糖有微显著降低趋势。两组在服用葡萄糖后,血糖含量在1h时达到峰值,随后下降。
1.3.5胰岛素相关指标变化
检测指标:胰岛素分泌总量、胰岛素抵抗指数、胰岛素β细胞功能指数。上述指标的检测方法:给各组患者口服含75g无水葡萄糖的水溶液,然后分别于0.5、1.0、1.5、2.0小时采血,测其血糖变化,以观察病人耐受葡萄糖的能力,是公认的诊断糖尿病的金标准。在血糖异常增高但尚未达到糖尿病诊断标准时,可采用该试验明确是否为糖尿病。
胰岛素分泌总量的测试方法(胰岛素水平测定方法):采用酶联免疫试剂盒测定,方法见说明书(赛默飞)。
胰岛素抵抗指数的计算公式:空腹血糖水平(FPG,mmol/L)×空腹胰岛素水平(FINS,mIU/L)/22.5。空腹血糖水平的测试同1.3.4血糖分析结果,空腹胰岛素水平的测试方法:采用酶联免疫试剂盒测定,方法见说明书(赛默飞)。
胰岛β细胞功能指数的计算公式:20×空腹胰岛素水平(FINS,mIU/L)/(空腹血糖水平(FPG,mmol/L)-3.5)。
健康人的胰岛素抵抗指数应该小于2.69,如果超过这个数值,提示有胰岛素抵抗的可能性。而胰岛素抵抗则是因为机体不能有效的利用胰岛素,导致体内胰岛素的代偿性升高。
胰岛素分泌总量检测结果如图6所示,OGTT(口服葡萄糖耐量试验)胰岛素曲线下面积(AUCins):益生菌组AUCins=141.84;安慰剂组AUCins=108.18。益生菌组的OGTT胰岛素曲线下面积显著上升,安慰剂组则相反。因此,益生菌组胰岛素分泌总量高于安慰剂组。
胰岛素抵抗指数、胰岛素β细胞功能指数的结果如表1所示,胰岛素β细胞功能指数:益生菌组胰岛素β细胞功能指数高于安慰剂组,且治疗3个月后,益生菌组胰岛素β细胞功能指数显著上升。胰岛素抵抗指数:益生菌组胰岛素抵抗指数高于安慰剂组。
表1胰岛素抵抗指数、胰岛素β细胞功能指数的结果
综合地,本发明复合益生菌组合物联合二甲双胍能够提高胰岛素分泌,改善胰岛功能,显著降糖化血红蛋白,空腹血糖,降低糖尿病肾病发病风险。
显然,上述实施例仅仅是为清楚地说明所作的举例,而并非对实施方式的限定。对于所属领域的普通技术人员来说,在上述说明的基础上还可以做出其它不同形式的变化或变动。这里无需也无法对所有的实施方式予以穷举。而由此所引伸出的显而易见的变化或变动仍处于本发明创造的保护范围之中。
Claims (10)
1.一种复合益生菌组合物联合双胍类抗糖尿病药物在制备预防、缓解、辅助治疗或治疗糖尿病的食品、保健品或药物中的用途,所述复合益生菌组合物包括:
干酪乳杆菌Zhang(Lactobacillus casei Zhang),保藏编号为CGMCC No.5469;
乳双歧杆菌V9(Bifidobacterium animalis subsp.lactis V9),保藏编号为CGMCCNo.5470;
植物乳杆菌P-8(Lactobacillus plantarum P-8),保藏编号为CGMCC No.6312;
鼠李糖乳杆菌Probio-M9(Lactobacillus rhamnosus Probio-M9),保藏编号为CGMCCNo.18639;
乳双歧杆菌Probio-M8(Bifidobacterium lactis Probio-M8),保藏编号为CGMCCNo.18610。
2.根据权利要求1所述的用途,其特征在于,所述益生菌组合物的总活菌数不低于3.0×1010CFU/g;
可选的,干酪乳杆菌Zhang活菌数不低于50亿,乳双歧杆菌V9活菌数不低于75亿,植物乳杆菌P-8活菌数不低于50亿,鼠李糖乳杆菌Probio-M9活菌数不低于50亿,乳双歧杆菌Probio-M8活菌数不低于75亿。
可选的,每株菌的活菌数不低于6.0×1011CFU/g;
可选的,所述双胍类抗糖尿病药物包括二甲双胍、磷酸西格列汀、利格列汀、吡格列酮、苯乙双胍或丁二胍。
3.根据权利要求1或2所述的用途,其特征在于,所述复合益生菌组合物中每株菌的原料包括该株菌的培养物、发酵物或冻干粉中的任意一种;
可选的,每株菌的原料为该株菌的冻干粉。
4.根据权利要求1或2所述的用途,其特征在于,所述复合益生菌组合物还包括辅料;
可选的,所述辅料为益生元和/或或膳食纤维;
可选的,所述辅料包括低聚半乳糖、低聚果糖、菊粉、聚葡萄糖和麦芽糖醇中的至少一种;
可选的,所述复合益生菌组合物中,总菌粉量与辅料的质量比为10-15:85-90。
5.权利要求1-4任一项所述的的用途,其特征在于,所述复合益生菌组合物的制备方法包括将含各株菌的原料混合的步骤;
可选的,还包括将含各株菌的原料混合后添加辅料的步骤。
6.权利要求1-5任一项所述的的用途,还具有如下的用途:
(a)在制备发酵剂、发酵制品、益生菌固体饮料或功能性保健制品中的用途;
(b)在制备提高胰岛素分泌、降低血脂、降低血糖、降低糖化血红蛋白含量、降低尿酸含量或改善胰岛功能的食品、保健品或药物中的用途;
(c)在制备预防、缓解、辅助治疗或治疗痛风的食品、保健品或药物中的用途。
7.根据权利要求1-6任一项所述的用途,其特征在于,所述糖尿病为2型糖尿病;
可选的,所述缓解糖尿病包括缓解糖尿病患者发病风险;
可选的,为缓解2型糖尿病患者发病风险;
可选的,所述食品包括传统食品、保健食品或辅助治疗型食品组合物。
8.根据权利要求1-7任一项所述的用途,其特征在于,所述预防、缓解、辅助治疗或治疗糖尿病包括提高胰岛素分泌、降低血糖、降低糖化血红蛋白含量、降低尿酸含量、降低血脂或改善胰岛功能。
9.根据权利要求6所述的用途,其特征在于,所述(a)中,所述发酵制品包括豆制品、乳制品或果蔬制品。
10.一种预防、缓解、辅助治疗或治疗糖尿病的组合物,其特征在于,包括:
权利要求1-9任一项中所述的复合益生菌组合物;和
双胍类抗糖尿病药物;
可选的,所述复合益生菌组合物1-2重量份,双胍类抗糖尿病药物1-2重量份;
可选的,所述复合益生菌组合物2重量份,双胍类抗糖尿病药物1.5重量份;
可选的,所述双胍类抗糖尿病药物包括二甲双胍、磷酸西格列汀、利格列汀、吡格列酮、苯乙双胍或丁二胍。
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CN116731905A (zh) * | 2022-11-30 | 2023-09-12 | 越用越好(上海)生物科技有限公司 | 一种益生菌组合物及其应用 |
CN116731905B (zh) * | 2022-11-30 | 2024-02-09 | 越用越好(上海)生物科技有限公司 | 一种益生菌组合物及其应用 |
CN117821343A (zh) * | 2024-03-05 | 2024-04-05 | 微康益生菌(苏州)股份有限公司 | 一种调节血糖代谢的复合益生菌及其应用 |
CN117821343B (zh) * | 2024-03-05 | 2024-05-14 | 微康益生菌(苏州)股份有限公司 | 一种调节血糖代谢的复合益生菌及其应用 |
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