CN116925960B - 一株能够利用普鲁兰多糖的凝结魏茨曼氏菌及其应用 - Google Patents
一株能够利用普鲁兰多糖的凝结魏茨曼氏菌及其应用 Download PDFInfo
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Abstract
本发明涉及一株能够利用普鲁兰多糖的凝结魏茨曼氏菌及其应用,属于微生物应用技术领域,具体提供了一种凝结魏茨曼氏菌(Weizmannia coagulans)菌株,已于2023年3月6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,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.26756;所述凝结魏茨曼氏菌菌株在制备治疗便秘药物中的应用;以及一种组合物,包括所述凝结魏茨曼氏菌和普鲁兰多糖;所述组合物在制备治疗便秘药物中的应用;本发明提供的凝结魏茨曼氏菌有治疗便秘的作用效果,并且结合普鲁兰多糖共同治疗便秘有非常理想的效果,治疗周期较短。
Description
技术领域
本发明属于微生物医药应用技术领域,具体涉及一株能够利用普鲁兰多糖的凝结魏茨曼氏菌及其应用。
背景技术
普鲁兰多糖是一种由出芽短梗霉发酵所产生的类似葡聚糖、黄原胶的胞外水溶性粘质多糖,该多糖是由α-1,4糖苷键连接的麦芽三糖重复单位经α-1,6糖苷键聚合而成的直链状多糖,分子量2万~200万,聚合度100~5000。普鲁兰多糖的成膜性、阻气性、可塑性、粘性均较强,并且具有易溶于水、无毒无害、无色无味等优良特性。
凝结魏茨曼氏菌(Weizmannia coagulans),细胞呈杆状,革兰氏阳性菌,它能够很好的调节肠道菌群,和其他益生菌相比它可以耐胃酸顺利进入肠道,促进双歧杆菌、乳杆菌等益生菌生长;凝结魏茨曼氏菌在肠道繁殖的过程中还会分泌淀粉酶和蛋白酶,促进机体对营养物质的消化和吸收;其产生的B族维生素、氨基酸、短链脂肪酸等物质能刺激肠道蠕动,增加粪便湿度,起到通便的效果,另外,凝结魏茨曼氏菌在肠道内定居后还能产生大量抑制有害菌的凝固素(Coagulin)和L(+)乳酸等抑菌物质,因此,对胃肠道炎症也有一定的治疗作用。
人体内没有能水解a-1,6糖苷键的消化酶,所以普鲁兰多糖是非消化吸收性碳水化合物不被肠吸收,因此普鲁兰多糖多用于低热量健康食品的生产,而开发出更多普鲁兰多糖的益生效果尤为重要。同时,该多糖有良好的水溶性和吸湿性又用作食品品质改良剂和增稠剂。最近发现普鲁兰多糖还具有使双歧杆菌增殖和治疗便秘的作用,事实上,对普鲁兰多糖的生物活性功能方面的研究还是很少。
芽孢杆菌属可以产普鲁兰酶,普鲁兰酶属淀粉酶类,能够专一性切开支链淀粉分支点中的α-1,6糖苷键,切下整个分支结构,形成直链淀粉。其分解支链的特性决定了普鲁兰酶在食品工业中的广泛应用,已成为淀粉酶制剂中一个很有前途的新品种,在食品加工领域具有广阔的开发和应用前景。
而芽孢杆菌利用普鲁兰多糖,使得普鲁兰多糖被分解,一方面为肠道菌群提供营养,有利于益生菌的增殖,也为肠道增添了芽孢杆菌的数量,增强肠道健康;另一方面凝结魏茨曼氏菌利用普鲁兰多糖在治疗便秘方面有重要意义,其具有更多更好的功用性,在开发功能食品、治疗疾病方面有着巨大的潜力。
凝结魏茨曼氏菌通常对于便秘有效,但不会即刻见效。若患者服时间过短,便秘可能不会出现明显改善,现有技术中芽孢杆菌虽具有治疗便秘的作用,但是存在治疗周期、并且还需补充其他益生菌均衡肠道才能达到更好治疗效果的局限性等,现有技术中凝结魏茨曼氏菌治疗小鼠便秘的周期一般为3-4周,治疗周期较长。凝结魏茨曼氏菌治疗便秘的主要作用机制,在于芽孢杆菌属于人体有益菌,进入肠道以后可以调节肠道菌群之间的平衡,有利于机体增加有益菌。而益生菌还有其它较多复杂的机制,目前临床还并不明确,如果患者服用益生菌治疗便秘,有可能还需要多种有益菌补充并达到一定的时间。凝结魏茨曼氏菌治疗便秘的好处在于其属于益生菌,对人体没有不良反应。但是长期服用益生菌可能有一定的副作用和依赖性。并且在现有技术中还未有以普鲁兰多糖为唯一碳源生长的芽孢杆菌的报道。
中国专利文献CN111004733A(申请号:201910188239.9)公开了一种具有缓解便秘功能的凝结芽孢杆菌复合微生态制剂,该发明提供的复合微生态制剂包括下列重量份的原料:凝结芽孢杆菌0.01-0.1份,低聚果糖4-6份,低聚半乳糖4-6份,菊粉10-13份,其中凝结芽孢杆菌的芽孢含量不低于1010cfu/g,该专利文献公开的技术方案与本发明完全不同。
中国专利文献CN114480218A(申请号:202210245396.0)公开了一种改善便秘的凝结芽孢杆菌及其应用,该专利文献公开凝结芽孢杆菌与本发明的不同,并且作用效果也不同。
发明内容
针对现有技术的不足,本发明提供了一株能够利用普鲁兰多糖的凝结魏茨曼氏菌及其应用。
本发明的技术方案如下:
一种凝结魏茨曼氏菌(Weizmannia coagulans)菌株,已于2023年3月6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,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.26756。
上述凝结魏茨曼氏菌(Weizmannia coagulans)菌株在制备治疗便秘药物中的应用。
根据本发明优选的,上述应用中,所述药物含有一种或多种药学上可接受的载体或辅剂。
进一步优选的,上述应用中,所述的辅剂为缓释剂、赋形剂、填充剂、粘合剂、湿润剂、崩解剂、吸促进剂、表面活性剂或润滑剂中的至少一种。
根据本发明优选的,上述应用中,所述药物的剂型为胶囊、丸剂、片剂、口服液、颗粒剂或注射剂。
一种组合物,包括上述凝结魏茨曼氏菌(Weizmannia coagulans)和普鲁兰多糖。
上述组合物在制备治疗便秘药物中的应用。
根据本发明优选的,上述组合物在制备治疗便秘药物中的应用,所述药物含有一种或多种药学上可接受的载体或辅剂。
进一步优选的,上述组合物在制备治疗便秘药物中的应用,所述的辅剂为缓释剂、赋形剂、填充剂、粘合剂、湿润剂、崩解剂、吸促进剂、表面活性剂或润滑剂中的至少一种。
根据本发明优选的,上述组合物在制备治疗便秘药物中的应用,所述药物的剂型为胶囊、丸剂、片剂、口服液、颗粒剂或注射剂。
本发明的有益效果如下:
1、本发明提供了一株凝结魏茨曼氏菌能以普鲁兰多糖为唯一碳源生长,并且生长良好。
2、本发明提供的凝结魏茨曼氏菌有治疗便秘的作用效果,并且结合普鲁兰多糖共同治疗便秘有非常理想的效果,治疗周期较短,治疗4天便秘症状能够得到非常明显的改善,更具有时效性,并且经普鲁兰多糖和凝结魏茨曼氏菌的结合治疗后,小鼠肠道推进速率高达95.37%,对便秘的治疗效果明显。
附图说明
图1为凝结魏茨曼氏菌CGMCC No.26756在不同糖为唯一碳源的CDM培养基中的生长曲线图。
图2为三株凝结魏茨曼氏菌在普鲁兰多糖为唯一碳源的CDM培养基生长曲线图;
图中:凝结魏茨曼氏菌为凝结魏茨曼氏菌CGMCC No.26756。
图3为小鼠肠道推进速率图。
具体实施方式
下面通过具体实施例对本发明作进一步阐述,但保护范围不限于此。
实施例中未详加说明的均按本领域现有技术。
主要材料的具体来源如下:
凝结魏茨曼氏菌CGMCC No.26756从山东济南、泡菜中分离获得。
凝结魏茨曼氏菌176从山东济南、泡菜中分离获得。
凝结魏茨曼氏菌222从山东济南、土壤中分离获得。
普鲁兰多糖购自生工生物工程(上海)股份有限公司。
实施例1
一种凝结魏茨曼氏菌菌株的筛选,包括如下步骤:
(1)配制筛选培养基-限定化学成分培养基CDM,培养基配方每升组分包括:乙酸钠5g,磷酸二氢钾3g,磷酸氢二钾3g,七水硫酸镁0.2g,四水硫酸锰0.05g,七水硫酸亚铁0.02g,丙氨酸0.1g,精氨酸0.1g,天冬氨酸0.2g,半胱氨酸0.2g,谷氨酰胺0.2g,谷氨酸0.2g,甘氨酸0.1g,组氨酸0.1g,异亮氨酸0.1g,亮氨酸0.1g,赖氨酸0.1g,苯丙氨酸0.1g,甲硫氨酸0.1g,脯氨酸0.1g,丝氨酸0.1g,苏氨酸0.1g,色氨酸0.1g,酪氨酸0.1g,缬氨酸0.1g,烟酸VB3 0.001g,泛酸VB5 0.001g,吡哆醛VB6 0.002g,核黄素VB2 0.001g,对氨基苯甲酸0.01g,叶酸0.001g,氰钴胺VB12 0.001g,D-生物素0.01g,硫胺素0.01g,肌苷0.01g,腺嘌呤0.01g,黄嘌呤0.01g,尿嘧啶0.01g,胸腺嘧啶0.01g,余量水;作为基础培养基,设置三种条件:a.不添加任何碳源的CDM培养基,即基础培养基,记为阴性对照培养基;b.添加质量分数1%普鲁兰多糖为唯一碳源的CDM培养基,记为实验培养基;c.添加质量分数1%葡萄糖为唯一碳源的CDM培养基记为阳性对照培养基。
(2)从泡菜中分离得到凝结魏茨曼氏菌(Weizmannia coagulans)菌株。
(3)所筛选得到的凝结魏茨曼氏菌(Weizmannia coagulans)菌株,已于2023年3月6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,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.26756。
(4)所述凝结魏茨曼氏菌CGMCC No.26756具有凝结魏茨曼氏菌的典型特征,即细胞呈杆状,革兰氏阳性菌,端生芽孢,无鞭毛;分解糖类生成L-乳酸,为同型乳酸发酵菌;其菌落为不透明白色,边缘呈不规则圆形,表面凸出,显微镜下细胞呈杆状。
(5)所述凝结魏茨曼氏菌CGMCC No.26756的最适生长温度为45℃,最适pH为7.0。
(6)所述凝结魏茨曼氏菌CGMCC No.26756分别在步骤(1)的三种条件培养基中,45℃、200r/min摇动培养50h,生长曲线如图1所示。所述凝结魏茨曼氏菌CGMCC No.26756在以普鲁兰多糖为唯一碳源的CDM培养基45℃摇动培养36小时后,菌体的密度达到OD600 4.85,培养基的pH值变为4.7,见图1。
(7)将本发明的凝结魏茨曼氏菌CGMCC No.26756 16SrDNA与相关凝结魏茨曼氏菌菌株的16SrDNA比较,具有99.85%相似性,但不完全相同,说明本发明的菌株具有原创性。
实验例1
利用凝结魏茨曼氏菌176、凝结魏茨曼氏菌222和凝结魏茨曼氏菌CGMCC No.26756分别以普鲁兰多糖为唯一碳源的CDM培养基中培养,所述培养基为实施例1中的实验培养基,培养条件同实施例1中凝结魏茨曼氏菌CGMCC No.26756的培养条件,生长曲线如图2所示。
培养期间,凝结魏茨曼氏菌CGMCC No.26756OD600最高达4.82,而凝结魏茨曼氏菌176、凝结魏茨曼氏菌222的OD600最高仅为1.36、0.70,且在各个时间段,凝结魏茨曼氏菌CGMCCNo.26756生长状况均优于凝结魏茨曼氏菌176和凝结魏茨曼氏菌222。说明凝结魏茨曼氏菌CGMCC No.26756与其他菌株相比能够很好地利用普鲁兰多糖,且具有特异性。
实施例2
建立由盐酸洛哌丁胺(loperamide hydrochloride)诱导的功能性便秘小鼠模型。
小鼠选择雄性C57BL/KsJ-db/db(6周龄,n=48),适应性饲养1周后,除正常组外,功能性便秘组通过口服强饲法连续5天给予0.25mL盐酸洛哌丁胺混悬液(1mg/mL),每日2次,建立功能性便秘小鼠模型。
选取建模成功小鼠42只,随机分为7组,每组6只,分为模型组、阳性对照组、实验组1、实验组2、实验组3、实验组4、实验组5。另外选取健康小鼠6只作为正常组。各给药组于造模完成后分别通过灌胃喂养8天,模型组和正常组给予等量生理盐水,具体如下:
正常组(NC):0.25mL/d生理盐水;
模型组(Mod):0.25mL/d生理盐水;
阳性对照组(Met):0.25mL/d,200mg/mL比沙可啶;
实验组1(P):0.25mL/d,200mg/mL普鲁兰多糖;
实验组2(BC):0.25mL/d,109CFU/mL凝结魏茨曼氏菌CGMCC No.26756细胞悬液;
实验组3(BC176):0.25mL/d,109CFU/mL凝结魏茨曼氏菌176细胞悬液
实验组4(P+BC):0.125mL/d,200mg/mL普鲁兰多糖+0.125mL/d,109CFU/mL凝结魏茨曼氏菌CGMCC No.26756细胞悬液;
实验组5(P+BC176):0.125mL/d,200mg/mL普鲁兰多糖+0.125mL/d,109CFU/mL凝结魏茨曼氏菌176细胞悬液;
小鼠造模成功后,在治疗期间每隔2天收集一次当天的粪便颗粒并称重,小鼠粪便颗粒重量变化如表1所示。
表1不同分组对小鼠粪便颗粒重量的影响
由表1可知,与正常对照组相比,盐酸洛哌丁胺诱导的功能性便秘小鼠的粪便颗粒重量明显降低。治疗期间,正常对照组小鼠的粪便颗粒重量几乎不变,其余各组小鼠的粪便颗粒重量均有所增加。到第4天,与模型组相比,阳性对照组、实验组2和实验组4小鼠的粪便颗粒重量均明显增加,其中实验组4增加最为明显,即普鲁兰多糖和凝结魏茨曼氏菌CGMCCNo.26756细胞悬液混合使用治疗小鼠便秘效果最好,其作用优于单独使用凝结魏茨曼氏菌CGMCC No.26756。其中实验组2、实验组4的小鼠粪便颗粒重量明显大于实验组3、实验组5,说明本发明筛选的凝结魏茨曼氏菌CGMCC No.26756在治疗便秘方面效果明显优于凝结魏茨曼氏菌176。并且对比现有技术,本发明对便秘的治疗效果更好更具时效性。
计算小鼠粪便颗粒的含水量。在8天的实验周期内,每隔2天收集一次当天的粪便颗粒,并称重后将粪便颗粒在70℃干燥炉中干燥,直到粪便颗粒的重量恒定。根据湿粪和干粪重量之间的差异计算粪便含水量,如下所示:粪便含水量(%)=100%×(湿重-干重)/湿重。小鼠粪便颗粒含水量的变化如表2所示:
表2不同分组对小鼠粪便颗粒含水量变化的影响
如表2所示,治疗期间,各给药组小鼠粪便颗粒含水量均有明显增加,在治疗4天时,各给药组小鼠粪便颗粒含水量趋于稳定。其中治疗效果:实验组4>实验组2>阳性对照组>实验组5>实验组3。实验组4小鼠的粪便颗粒含水量达到16.09%高于阳性对照组的10.97%,说明普鲁兰多糖和凝结魏茨曼氏菌CGMCC No.26756细胞悬液混合使用4天,其对便秘会有良好的治疗效果。治疗4天时,实验组3的小鼠粪便颗粒含水量为10.08%,明显低于实验组2的13.98%;与此同时,实验组5的小鼠粪便颗粒含水量仅为10.96%,远远低于实验组4的16.09%。对比说明本发明筛选的凝结魏茨曼氏菌CGMCC No.26756在治疗便秘方面效果远远好于凝结魏茨曼氏菌176。并且对比现有技术,本发明使用普鲁兰多糖和凝结魏茨曼氏菌CGMCC No.26756细胞悬液混合治疗,其对便秘的治疗效果更好更具时效性。
肠道推进速率的测定在实验期结束时进行,将各组小鼠禁食过夜(16小时)以排空其肠道内容物。每只小鼠口服强饲0.25mL活性炭悬浮液,20分钟后麻醉处死。迅速打开小鼠的腹腔,解剖从幽门到肛门的整个肠道。小鼠肠道推进速率计算为D=L2/L1×100%,其中L1为拉直无张力后的肠道全长,L2为活性炭在肠道内的运动长度。
如图3所示,各组小鼠相较于模型组其肠道推进率都有所增加。实验组1和实验组2的肠道推进率小于实验组4,说明普鲁兰多糖和凝结魏茨曼氏菌CGMCC No.26756结合使用治疗便秘的效果要好于普鲁兰多糖、凝结魏茨曼氏菌CGMCC No.26756的单独作用效果,二者起到了一定的协同作用。实验组3肠道推进率为78.02%,低于实验组2的肠道推进率91.21%;实验组5的肠道推进率为84.37%,明显低于实验组4的95.37%。说明本发明筛选的凝结魏茨曼氏菌CGMCC No.26756在治疗便秘方面效果明显优于凝结魏茨曼氏菌176。且对比现有技术,实验组4的治疗效果最佳。
本发明提供了一株凝结魏茨曼氏菌CGMCC No.26756能以普鲁兰多糖为唯一碳源生长,并且生长良好。本发明提供的凝结魏茨曼氏菌有治疗便秘的作用效果,结合普鲁兰多糖共同治疗便秘有非常理想的效果,并且治疗周期较短,治疗4天便秘症状能够得到非常明显的改善,更具有时效性,并且经普鲁兰多糖和凝结魏茨曼氏菌的结合治疗后,小鼠肠道推进速率高达95.37%,对便秘的治疗效果明显。
Claims (10)
1.一种凝结魏茨曼氏菌(Weizmannia coagulans)菌株,已于2023年3月6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,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.26756。
2.权利要求1所述凝结魏茨曼氏菌(Weizmannia coagulans)菌株在制备治疗便秘药物中的应用。
3.如权利要求2所述的应用,其特征在于,所述药物含有一种或多种药学上可接受的载体或辅剂。
4.如权利要求3所述的应用,其特征在于,所述的辅剂为填充剂、粘合剂、湿润剂、崩解剂、表面活性剂或润滑剂中的至少一种。
5.如权利要求2所述的应用,其特征在于,所述药物的剂型为胶囊、丸剂、片剂、口服液、颗粒剂或注射剂。
6.一种组合物,其特征在于,包括权利要求1所述的凝结魏茨曼氏菌(Weizmannia coagulans)和普鲁兰多糖。
7.权利要求6所述组合物在制备治疗便秘药物中的应用。
8.如权利要求7所述的应用,其特征在于,所述药物含有一种或多种药学上可接受的载体或辅剂。
9.如权利要求8所述的应用,其特征在于,所述的辅剂为填充剂、粘合剂、湿润剂、崩解剂、表面活性剂或润滑剂中的至少一种。
10.如权利要求7所述的应用,其特征在于,所述药物的剂型为胶囊、丸剂、片剂、口服液、颗粒剂或注射剂。
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Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111004733A (zh) * | 2019-03-13 | 2020-04-14 | 江南大学 | 一种具有缓解便秘功能的凝结芽孢杆菌复合微生态制剂 |
CN111254088A (zh) * | 2019-12-30 | 2020-06-09 | 杭州保安康生物技术有限公司 | 一种凝结芽孢杆菌菌株及其应用 |
CN111603489A (zh) * | 2020-05-28 | 2020-09-01 | 武汉微康益生菌研究院有限公司 | 一种改善便秘的菌剂及其制备方法 |
CN112029674A (zh) * | 2020-02-12 | 2020-12-04 | 善恩康生物科技(苏州)有限公司 | 改善肠道微生态缓解便秘的凝结芽孢杆菌bc01及应用 |
CN114480218A (zh) * | 2022-03-14 | 2022-05-13 | 善恩康生物科技(苏州)有限公司 | 一种改善便秘的凝结芽孢杆菌及其应用 |
JP2022150437A (ja) * | 2021-03-26 | 2022-10-07 | 三菱ケミカル株式会社 | 皮膚状態改善剤及び皮膚粘弾性改善剤 |
CN115322931A (zh) * | 2022-08-19 | 2022-11-11 | 华南农业大学 | 一株能够抑制α-葡萄糖苷酶和/或α-淀粉酶活性的凝结魏兹曼杆菌及其应用 |
JP2023023981A (ja) * | 2021-08-06 | 2023-02-16 | 三菱ケミカル株式会社 | 生体内のIgAとIFN-γ産生を促進する乳酸菌製剤及び経口組成物 |
-
2023
- 2023-06-05 CN CN202310665808.0A patent/CN116925960B/zh active Active
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111004733A (zh) * | 2019-03-13 | 2020-04-14 | 江南大学 | 一种具有缓解便秘功能的凝结芽孢杆菌复合微生态制剂 |
CN111254088A (zh) * | 2019-12-30 | 2020-06-09 | 杭州保安康生物技术有限公司 | 一种凝结芽孢杆菌菌株及其应用 |
CN112029674A (zh) * | 2020-02-12 | 2020-12-04 | 善恩康生物科技(苏州)有限公司 | 改善肠道微生态缓解便秘的凝结芽孢杆菌bc01及应用 |
CN111603489A (zh) * | 2020-05-28 | 2020-09-01 | 武汉微康益生菌研究院有限公司 | 一种改善便秘的菌剂及其制备方法 |
JP2022150437A (ja) * | 2021-03-26 | 2022-10-07 | 三菱ケミカル株式会社 | 皮膚状態改善剤及び皮膚粘弾性改善剤 |
JP2023023981A (ja) * | 2021-08-06 | 2023-02-16 | 三菱ケミカル株式会社 | 生体内のIgAとIFN-γ産生を促進する乳酸菌製剤及び経口組成物 |
CN114480218A (zh) * | 2022-03-14 | 2022-05-13 | 善恩康生物科技(苏州)有限公司 | 一种改善便秘的凝结芽孢杆菌及其应用 |
CN115322931A (zh) * | 2022-08-19 | 2022-11-11 | 华南农业大学 | 一株能够抑制α-葡萄糖苷酶和/或α-淀粉酶活性的凝结魏兹曼杆菌及其应用 |
Non-Patent Citations (1)
Title |
---|
加味增液汤联合凝结芽孢杆菌活菌片治疗小儿功能性便秘(肠燥津亏证)的疗效观察;拓晓萍等;海南医学;第34卷(第01期);第54-58页 * |
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