CN113637606A - 一种后生元和噬菌体复配的微生物组合制剂、制备方法及其应用 - Google Patents
一种后生元和噬菌体复配的微生物组合制剂、制备方法及其应用 Download PDFInfo
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Abstract
本发明提供一种后生元和噬菌体复配的微生物组合制剂,包括后生元和噬菌体;后生元可以有效抑制有害菌生物膜的生长能力及活性,解除了生物膜对有害菌的保护,从而为噬菌体侵染有害菌打开了快速通道。有害菌被消灭后,有益菌恢复对病灶上皮细胞的占位,并在后生元的作用下实现快速定植、增殖,从而达到微生态菌群的平衡。另外,根据申请人的进一步研究,再复配益生菌后,其代谢产物可以进一步抑制生物膜的形成。因此使得噬菌体侵染有害菌的速率更快、效果更好。
Description
技术领域
本发明提高一种微生物组合制剂、制备方法及其应用,属于微生物应用技术领域。
背景技术
人体的体表皮肤和与外界相通的口腔、上呼吸道、肠道、泌尿生殖道等粘膜及其腔道寄居着不同种类和数量的微生物,寄生物在正常情况下与宿主相安无事、互相适应,而且各种微生物之间也相互制约而保持一个彼此共存的状态。人体的消化道、上呼吸道、皮肤、尿道、外生殖器、眼结膜与外耳道,都存在微生态菌群。
近年来,越来越多的人认识到人体菌群的重要性。以肠道菌群微生态为例,肠胃道健康与否与人体的多种慢性疾病是有关联的。肠道的健康又与肠道菌群的平衡相辅相成。肠道菌群的平衡则取决于多种因素,如饮食偏好、压力大小、抗生素使用以及其他生活***衡的状态。由此可见人体健康与肠道健康息息相关,而肠道菌群的平衡则是肠道健康的重要决定性因素。
益生菌制剂是常见的用于感染性肠炎、或有外来细菌式侵袭导致肠内菌群失衡的治疗方法。据Transparency Market Research研究显示,美国的益生菌、益生元和其他消化酸类产品市场达到了$68.8billion,在2022年甚至能达到$83.5billion。常见的益生菌制剂有双歧杆菌活菌制剂、枯草芽孢杆菌活菌制剂等。市场上有一种名为益生菌制剂的产品,其成分为NCFM、乳双歧杆菌BI-04、鼠李糖杆菌LR-32等,具有肠道保护的功效。这些益生菌制剂可以调理肠道微生态,促进肠道平衡的恢复。但是花费的时间较长,并不能即可缓解呕吐腹泻等症状造成的不适。也不能作为日常肠道健康维护所采取的方式。
服用抗生素(细菌性抗生素)也是一种常用的缓解肠胃不适时的治疗方法,但是抗生素的服用可能导致人体多处菌群微生态的失衡,目前已渐渐减少此种处理方式的应用。
由于具有较强的杀菌能力,噬菌体作为一种抗细菌感染制剂被使用。中国专利CN106754751A公开了一种肠出血性大肠杆菌噬菌体及其应用,对EHEC具有高效杀菌能力;中国专利CN106754751A一种肠出血性大肠杆菌噬菌体及其应用,该噬菌体菌株保藏号为CCTCC NO:M 2016539,于2016年9月29日保藏于中国武汉大学中国典型培养物保藏中心,分类命名为肠出血性大肠杆菌噬菌体vB_ECM_MIE,Entero-hemorrhagicEscherichia coliO157:H7 phage vB_ECM_MIE;对EHEC具有高效杀菌能力。虽然采用噬菌体可以起到很好的裂解有害菌的作用,但其无法快速的恢复病灶的微生态菌群的平衡。
发明内容
本发明为了解决现有技术中存在的上述缺陷和不足,提供了一种微生物组合制剂、制备方法及其应用,该组合物不但可以快速有效的解决细菌性感染问题,而且还可以帮助恢复原生微生态菌群的平衡。
为解决上述技术问题,本发明提供了如下技术方案:一种后生元和噬菌体复配的微生物组合制剂,包括后生元和噬菌体;所述后生元包括灭活益生菌及益生菌的代谢产物;所述噬菌体对致病细菌具有实质性裂解能力、且为非毒性,所述噬菌体为单株噬菌体或多株噬菌体的混合物。采用上述技术方案,后生元和噬菌体协同作用,具有更好的抑菌或杀菌效果。同时,后生元还可以促进原生菌群的生长,帮助机体内的微生态恢复平衡。
进一步,所述噬菌体为大肠杆菌属噬菌体、埃希氏菌属噬菌体、沙门氏菌属噬菌体、爱德华菌属噬菌体、枸橼酸菌属噬菌体、志贺氏菌属噬菌体、克雷伯菌属噬菌体、沙雷菌属噬菌体、变形杆菌属噬菌体、假单胞菌属噬菌体、克雷伯氏菌属噬菌体、丛毛单胞菌属噬菌体、短波单胞菌属噬菌体、不动杆菌属噬菌体、黄杆菌属噬菌体、威克斯菌属噬菌体、金色单胞菌属噬菌体、黄色单胞菌属噬菌体、弧菌属噬菌体、气单胞菌属噬菌体、葡萄球菌属噬菌体、草绿色链球菌属噬菌体、β溶血链球菌属噬菌体、咽峡炎链球菌属噬菌体、肺炎链球菌属噬菌体、李斯特菌属噬菌体、弯曲杆菌属噬菌体、马拉色菌属噬菌体、丙酸杆菌属噬菌体、动弯杆菌属噬菌体、***属噬菌体、厌氧消化链球菌属噬菌体、加德诺菌属噬菌体中的一种或多种组合;
进一步,所述噬菌体为大肠杆菌噬菌体、阪崎肠杆菌噬菌体、埃希氏菌噬菌体、肺炎克雷伯菌噬菌体、沙门氏菌噬菌体、异型枸橼酸杆菌、志贺氏菌噬菌体、铜绿假单胞菌噬菌体、溶血不动杆菌噬菌体、脑膜败血性黄杆菌噬菌体、动物溃疡威克斯菌噬菌体、浅黄假单胞菌噬菌体、霍乱弧菌噬菌体、副溶血弧菌噬菌体、溶藻弧菌噬菌体、创伤弧菌噬菌体、金黄色葡萄球菌噬菌体、化脓性链球菌噬菌体、咽峡炎链球菌噬菌体、肺炎链球菌、李斯特菌噬菌体、弯曲杆菌噬菌体、合轴马拉色菌噬菌体、痤疮丙酸杆菌噬菌体、动弯杆菌噬菌体、***噬菌体及加德诺菌噬菌体中的一种或多种组合。
其中,大肠杆菌噬菌体可以选自Esc-COP-4(KCTC 12663BP)、Esc-CHP-1(KCTC12660BP)、Esc-CHP-2(KCTC 12661BP)、Esc-COP-1(KCTC 12662B)、Esc-COP-9(KCTC13131BP)、Esc-COP-7(KCTC 13130BP)、CCTCC NO:M 2016539、LL5、LH01、T4D、LL12;阪崎肠杆菌噬菌体可以选自SK1(CGMCC No.3741)、SK2(、CGMCC No.3742)、SK3(CGMCC No.3743)、SK4(CGMCC No.3744)、SK5(CGMCC No.3745)、EspYZU05(CCTCC NO:M 2016716);埃希氏菌噬菌体可以选自BP539、BP700、BP753、BP814、BP953、BP954、BP970、BP1002、BP1151、BP1155、BP1168、BP1176、BP1197、BP1226、BP1229;肺炎克雷伯菌噬菌体可以选自为RDP-KP-20004(CGMCC No.21407)、RDP-KP-20005(CGMCC No.21408)、vB_KpnM_hel(CCTCC No:M2015760);沙门氏菌噬菌体可以选自CCTCC NO:M2014429、STP4-a(CCTCC NO:M2014145);志贺氏菌噬菌体可以选自CCTCC NO:M209029、SGF3(CGMCC No.20294)、SSE1(CGMCC No.18853);铜绿假单胞菌噬菌体可以选自Pse-AEP-3(KCTC13165BP)、Pse-AEP-4(KCTC13166BP)、vB_PaeM_QKL1(CGMCC No.13381)、RDP-PA-20001(CGMCC No.21410);霍乱弧菌噬菌体可以选自vB-VchS-PR02(CGMCC NO.18861);副溶血弧菌噬菌体可以选自VppYZU84(CCTCC M 2020242)、Vib-PAP-5(KCTC 13029BP)、Vib-PAP-2(KCTC 12910BP)、Vib-PAP-4(KCTC 13168BP)、Vib-PAP-7(KCTC 13247BP);溶藻弧菌噬菌体可以选自ValB1 MD(CCTCC M 2019290)、ValB1 HC(CCTCC M 2019291)、VAP7(CCTCC NO:M 2018767)、VAP21(CCTCC NO:M 2018768)、VAP9(CCTCC NO:M 2018766);金黄色葡萄球菌噬菌体可以选自qdsa002(CCTCC M 2015554)、BP-13(CCTCC NO:M 2015142)、BP-13A(CCTCC M 2016535)、BP-14(CCTCC NO:M 2015143)、BP-39(CCTCC NO:M 2015144)、CCTCC M 2011409;李斯特菌噬菌体可以选自LipG2-5(CCTCC M2010003)、CCTCC NO:M 2018644、CCTCC NO:M 2018645;痤疮丙酸杆菌噬菌体可以选自PA6(NCIMB:41332)、1874(NCIMB:41334)、1878(NCIMB:41333)、1905(NCIMB:41335)、1894(NCIMB:41349)、103609(NCIMB:41350)、103672(NCIMB:41351)。
进一步,灭活益生菌的方式可以为现有技术中任意方式,如加热、紫外辐照、化学处理等;灭活益生菌可以进行处理,如研磨、破碎或冷冻干燥处理等;后生元则为灭活益生菌和及其代谢产物的混合物。上述技术方案中,所述后生元为乳酸杆菌属、双歧杆菌属、链球菌属、乳球菌属、明串球菌属、丙酸杆菌属、片球菌属、葡萄球菌属、芽孢杆菌属、克鲁维酵母菌属中的一种或两种以上组合;优选地,所述后生元为熟酸乳杆菌、干酪乳杆菌、卷曲乳杆菌、德氏乳杆菌、发酵乳杆菌、格氏乳杆菌、瑞士乳杆菌、约氏乳杆菌、副干酪乳杆菌、植物乳杆菌、罗伊氏乳杆菌、鼠李糖乳杆菌、唾液乳杆菌、清酒乳杆菌、弯曲乳杆菌、加氏乳杆菌、嗜热链球菌、乳酸乳球菌乳酸亚种、乳酸乳球菌乳脂亚种、乳酸乳球菌双乙酰亚种、肠膜明串珠菌肠膜亚种、费氏丙酸杆菌谢氏亚种、产丙酸丙酸杆菌、乳酸片球菌、戊糖片球菌、小牛葡萄球菌、木糖葡萄球菌、肉葡萄球菌、凝结芽孢杆菌、枯草芽孢杆中的一种或几种组合;更优地,所述后生元为瑞士乳杆菌、干酪乳杆菌、加氏乳杆菌、副干酪乳杆菌、植物乳杆菌、鼠李糖乳杆菌、卷曲乳杆菌、唾液乳杆菌、嗜酸乳杆菌、短乳杆菌、保加利亚乳杆菌、发酵乳杆菌、罗伊氏乳杆菌、乳酸双歧杆菌、短双歧杆菌、两歧双歧杆菌、婴儿双歧杆菌、长双歧杆菌、嗜热链球菌、戊糖片球菌、凝结芽孢杆菌中的一种或两种以上组合。
其中,瑞士乳杆菌可以选自Lactobacillus helveticus HA-122;副干酪乳杆菌可以选自Lactobacillus paracasei HA-108、Lactobacillus paracasei MCC1849;植物乳杆菌可以选自Lactobacillus plantarum HA-119、Lactobacillus plantarum L-137、Lactobacillus plantarum K-1、Lactobacillus plantarum K-2、Lactobacillusplantarum SNK、植物乳杆菌LP226;鼠李糖乳杆菌可以选自Lactobacillus rhamnosus HA-111;嗜热链球菌可以选自Str.thermophilus HA-110;卷曲乳杆菌可以选自KT-11;干酪乳杆菌可以选自Lactobacillus casei 327;凝结芽孢杆菌可以选自B.coagulans GBI-30;戊糖片球菌可以选自Pediococcus pentosaceus NB 17;长双歧杆菌可以选自Bifidobacterium longum 108。本文中在未标明的情况下:
“植物乳杆菌HA-119”表示为植物乳杆菌HA-119后生元;
“植物乳杆菌L-137”表示为植物乳杆菌L-137后生元;
“植物乳杆菌K-1”表示为植物乳杆菌K-1后生元;
“植物乳杆菌K-2”表示为植物乳杆菌K-2后生元;
“植物乳杆菌SNK”表示为植物乳杆菌SNK后生元;
“植物乳杆菌LP226”表示为植物乳杆菌LP226后生元;
“瑞士乳杆菌HA-122”表示为瑞士乳杆菌HA-122后生元;
“副干酪乳杆菌HA-108”表示为副干酪乳杆菌HA-108后生元;
“副干酪乳杆菌MCC1849”表示为副干酪乳杆菌MCC1849后生元;
“鼠李糖乳杆菌HA-111”表示为鼠李糖乳杆菌HA-111后生元;
“嗜热链球菌HA-110”表示为嗜热链球菌HA-110后生元;
“卷曲乳杆菌KT-11”表示为卷曲乳杆菌KT-11后生元;
“干酪乳杆菌327”表示为干酪乳杆菌327后生元;
“凝结芽孢杆菌GBI-30”表示为凝结芽孢杆菌GBI-30后生元;
“戊糖片球菌NB 17”表示为戊糖片球菌NB 17后生元;
“长双歧杆菌108”表示为长双歧杆菌108后生元。
后生元和噬菌体的用量为:后生元中灭活益生菌菌体数与噬菌体菌体数的比例为1:100-100:1,优选地,为1:99、5:95、10:90、20:80、30:70、40:60、50:50、60:40、70:30、80:20、90:10、95:5、或99:1。
或者,后生元与噬菌体的用量比例为0.25mg:108pfu(pfu为噬斑形成单位)噬菌体至1000mg:108pfu噬菌体;进一步的,为0.5mg:108pfu噬菌体、1mg:108pfu噬菌体、5mg:108pfu噬菌体、10mg:108pfu噬菌体、50mg:108pfu噬菌体、100mg:108pfu噬菌体、200mg:108pfu噬菌体、500mg:108pfu噬菌体、800mg:108pfu噬菌体、或1000mg:108pfu噬菌体。
或者,后生元与噬菌体的用量为:后生元的量为0.25-1000mg,噬菌体的量为0.1-1000mg;进一步的,后生元的量为0.5-800mg,噬菌体的量为0.5-800mg;进一步的,后生元的量为1-500mg,噬菌体的量为1-500mg;进一步的,后生元的量为5-200mg,噬菌体的量为5-200mg;进一步的,后生元的量为10-100mg,噬菌体的量为10-100mg;进一步的,后生元的量为50-80mg,噬菌体的量为50-80mg。
或者,后生元与噬菌体的用量比例为0.1亿:108pfu噬菌体至1000亿:108pfu噬菌体。进一步,为1亿:108pfu噬菌体、5亿:108pfu噬菌体、10亿:108pfu噬菌体、50亿:108pfu噬菌体、100亿:108pfu噬菌体、200亿:108pfu噬菌体、500亿:108pfu噬菌体、800亿:108pfu噬菌体、或1000亿:108pfu噬菌体。其中后生元的数量为灭活益生菌死菌体数量,死菌体的数量由生产该后生元的益生菌活菌数、活菌密度进行检测推算确定。
作为更优的技术方案,所述组合物还包括益生菌或/和益生元。益生菌作为外源菌的补给,可以协助快速恢复机体内的微生态菌群平衡;益生元为外源和内源益生菌提供营养,其目的也是快速恢复有益菌群的微生态平衡。
进一步,所述益生菌为乳酸杆菌属、双歧杆菌属、链球菌属、乳球菌属、明串球菌属、丙酸杆菌属、片球菌属、葡萄球菌属、芽孢杆菌属、克鲁维酵母菌属中的一种或两种以上组合;优选地,所述益生菌为熟酸乳杆菌、干酪乳杆菌、卷曲乳杆菌、德氏乳杆菌、发酵乳杆菌、格氏乳杆菌、瑞士乳杆菌、约氏乳杆菌、副干酪乳杆菌、植物乳杆菌、罗伊氏乳杆菌、鼠李糖乳杆菌、唾液乳杆菌、清酒乳杆菌、弯曲乳杆菌、加氏乳杆菌、嗜热链球菌、乳酸乳球菌乳酸亚种、乳酸乳球菌乳脂亚种、乳酸乳球菌双乙酰亚种、肠膜明串珠菌肠膜亚种、费氏丙酸杆菌谢氏亚种、产丙酸丙酸杆菌、乳酸片球菌、戊糖片球菌、小牛葡萄球菌、木糖葡萄球菌、肉葡萄球菌、凝结芽孢杆菌、枯草芽孢杆中的一种或几种组合;更优地,所述益生菌为瑞士乳杆菌、干酪乳杆菌、加氏乳杆菌、副干酪乳杆菌、植物乳杆菌、鼠李糖乳杆菌、卷曲乳杆菌、唾液乳杆菌、嗜酸乳杆菌、短乳杆菌、保加利亚乳杆菌、发酵乳杆菌、罗伊氏乳杆菌、乳酸双歧杆菌、短双歧杆菌、两歧双歧杆菌、婴儿双歧杆菌、长双歧杆菌、嗜热链球菌、戊糖片球菌、凝结芽孢杆菌中的一种或两种以上组合;或/和,所述益生元为短链脂肪酸、乳铁蛋白、低聚果糖、低聚木糖、低聚乳糖、菊粉、乳果糖、洋蓟、菊苣、燕麦、大麦、豆科植物、大蒜、橄榄菜、豆类或草药中的一种或两种以上组合。
益生菌的用量为:后生元中灭活益生菌菌体数与益生菌菌体数的比例为1:100-100:1,优选地,为1:99、5:95、10:90、20:80、30:70、40:60、50:50、60:40、70:30、80:20、90:10、95:5、或99:1。
或者,后生元与益生菌的用量比例为0.25mg:100亿至1000mg:100亿;进一步的,为0.5mg:100亿益生菌、1mg:100亿益生菌、5mg:100亿益生菌、10mg:100亿益生菌、50mg:100亿益生菌、100mg:100亿益生菌、200mg:100亿益生菌、500:100亿益生菌、800mg:100亿益生菌、或1000mg:100亿益生菌。
或者,后生元与益生菌的用量比例为0.1亿:100亿益生菌至1000亿:100亿益生菌。进一步,为1亿:100亿益生菌、5亿:100亿益生菌、10亿:100亿益生菌、50亿:100亿益生菌、100亿:100亿益生菌、200亿:100亿益生菌、500亿:100亿益生菌、800亿:100亿益生菌、或1000亿:100亿益生菌。
本发明还提供一种产品,该产品包含上述的微生物组合制剂以及辅料。该产品中,后生元的量为0.1亿/g-1000亿/g,噬菌体的量为104pfu/g-1010pfu/g;进一步,后生元的量为10亿/g-800亿/g,噬菌体的量为106pfu/g-109pfu/g;更进一步,后生元的量为50亿/g-200亿/g,噬菌体的量为107pfu/g-109pfu/g;更进一步,后生元的量为100亿/g-150亿/g,噬菌体的量为107pfu/g-108pfu/g。
或者,该产品中,后生元的量为0.1亿/ml-1000亿/ml,噬菌体的量为104pfu/ml-1010pfu/ml;进一步,后生元的量为10亿/ml-800亿/ml,噬菌体的量为106pfu/ml-109pfu/ml;更进一步,后生元的量为50亿/ml-200亿/ml,噬菌体的量为107pfu/ml-109pfu/ml;更进一步,后生元的量为100亿/ml-150亿/ml,噬菌体的量为107pfu/ml-108pfu/ml。
本发明中,该产品可以为各种剂型,包括但不限于粉剂、栓剂、固体饮料、硬胶囊、软胶囊、软饮料、多层硬胶囊、溶豆、冻干粉、奶豆、巧克力、夹心软糖、夹心巧克力、茶饮料、冷萃咖啡、湿巾、膏剂、霜剂、液体剂、乳剂、凝胶、固体剂。
本发明还提供了将上述产品或微生物组合制剂在制备治疗细菌感染性疾病的医药品、食品或动物食品、营养品、保健品或补充剂、日化用品、化妆品、洗护用品、消毒用品中的应用。
其中,细菌性感染包括但不限于人类或动物中由细菌感染引起的肠胃***疾病、泌尿***疾病、生殖***疾病、呼吸道疾病和皮肤类疾病。
本发明还提供了一种产品的制备方法,具体步骤为:将后生元悬液与噬菌体液混合、添加或不添加辅料,成型、包装成品;其中,将后生元悬液与噬菌体液混合与添加辅料部分先后顺序,或者混合与添加辅料同时进行;
优选地,对辅料进行预处理,使辅料符合剂型要求后再与后生元悬液和噬菌体液的混合物混合,获得剂型后包装成品;或者,将辅料与后生元悬液和噬菌体液的混合物混合后,进行处理获得符合剂型要求的出产品后,成型、包装成品。
本发明提供的微生物组合物制剂可以快速缓解机体内的细菌感染,恢复有益菌对病灶上皮细胞的占位,并在后生元的作用下实现快速定植、增殖,从而达到微生态菌群的平衡,从而帮助机体内微生态平衡的恢复。
附图说明
图1本发明组合物制剂对大肠杆菌处于初始定植期的抑制情况;
图2本发明组合物制剂对大肠杆菌处于成熟期的抑制情况;
图3本发明之不同后生元对大肠杆菌生物膜生长能力的影响;
图4本发明之不同后生元对金黄色葡萄球菌生物膜生长能力的影响;
图5本发明之不同后生元对白色念珠菌生物膜生长能力的影响;
图6本发明之不同后生元对白色念珠菌处于初始定期生物膜活性的影响;
图7本发明之不同后生元对白色念珠菌处于成熟期生物膜活性的影响。
具体实施方式
下面结合具体实施例对本发明作进一步描述。以下实施例仅用于更加清楚地说明本发明的技术方案,而不能以此来限制本发明的保护范围。
下面结合实施例对本发明专利进一步说明。
噬菌体是一种感染细菌(吃细菌的病毒)、真菌、放线菌、螺旋体等微生物的病毒,对宿主具有高度专一性。噬菌体一般分为两种:一种是能在宿主细菌内复制增殖,从而产生组多子代噬菌体,然后裂解细菌,称为烈性或毒性噬菌体;这种噬菌体在侵染细菌后,能够将细菌杀死,但对机体没有毒性。因此,噬菌体作为抗生素的替代品也逐渐被医学上认可。专利US5688501公开了一种采用具有特异性裂解或非裂解性噬菌体治疗细菌性感染的疾病的方法;专利US4957686也公开了采用噬菌体改善口腔内细菌感染的情况。上述报道虽然在短时间内可以缓解细菌感染,但由细菌感染的机体内的微生态失衡并不能得到很好的控制。且,感染细菌在机体内定植,由于细菌菌落表面生物膜的存在,会严重影响噬菌体对细菌的清除作用。
根据本申请人长期的研究成果显示:1.后生元能够促进益生菌生长的作用,该研究成果已向国家知识产权局申请发明专利(申请号为:202110026795.3),本申请不再赘述。因此将后生元与噬菌体复配可以很好的解决上述问题。2.后生元可以有效抑制有害菌生物膜的生长能力及活性。生物膜是指微生物为适应周围环境,粘附于生命或非生命的介质表面,并被自身分泌的胞外基质包裹而形成的一种稳定复杂的三维网状结构。据相关报道显示,细菌生物膜是引起细菌持续性感染的致病机制,且大多数临床感染病例都是与生物膜的形成有关。噬菌体在侵染细菌过程中,细菌生物膜会阻碍侵染过程。因此,后生元抑制生物膜的生长能力及活性,为噬菌体侵染细菌打开了通道。下面以具体实施例具体说明上述研发结论。
实验例:
1.实验材料和实验设备
1.1主要试剂:LB培养基、无菌水、肉汤培养基等
1.2主要设备:电子天平(梅特勒-托利多仪器(上海)有限公司)、蒸汽灭菌锅(山东博科科学仪器有限公司)、明美显微镜+电脑(广州市明美光电技术有限公司)、超声波清洗仪(昆山超声波仪器有限公司)、pH仪(梅特勒-托利多仪器(上海)有限公司)、高速离心机(上海卢湘仪离心机仪器有限公司)、恒温摇床(山东博科科学仪器有限公司)、医用冷藏冷冻冰箱(Haier)、加热磁力搅拌机(上海恒一科学仪器有限公司)、电热恒温培养箱(上海恒一科学仪器有限公司)、微量移液器(eppendorf等实验设备)。
2.实验方法:
以下实例中,供试菌株为市场购买获得,该供试菌种处于公开状态,科研工作者可以向相关单位索取。
2.1益生菌/有害菌的复苏和培养:取适量样品,用无菌水稀释10倍,8000rpm均质2min。将制成的样品菌液于合适的培养基上进行涂布,于合适的温度下培养48-72h。将活化后的平板至于冰箱保存,用于后续实验使用。其中不同菌属益生菌的培养条件如下:
双歧杆菌:常用培养基为PYG、MRS,培养温度为36℃,厌氧培养;
乳酸菌:常用培养基为MRS、改良MC,培养温度为36℃,厌氧培养;
嗜热链球菌:常用培养基为MRS、改良MC,培养温度为36℃,需氧培养;
2.2噬菌体的培养:将于噬菌体对应的宿主细胞液体过夜培养。噬菌体样品,用无菌水进行稀释,稀释10倍。将1ml宿主细胞液和100ul噬菌体液混匀,静置15min使其感染。将混合液加入5ml冷却45℃的0.7%琼脂培养基中,混合均匀,立刻倒入含有2%的培养基平板表面,铺平。带平板凝固后移至培养箱中,培养8-24h。
按照上述步骤同时制作不含噬菌体的对照平板。
将含有噬菌体的平板于-20℃条件下放置4-5h,冷冻后取出解冻。将解冻后产生的液体移入离心管中,以10000rpm离心10分钟以沉淀寄主细菌。将上清液移至新管中,以0.22μm孔径之过滤器(filter)去除残余菌体,即能得到不含寄主细菌的噬菌体原液。
2.3微生物组合制剂抑制有害菌定植试验
大肠杆菌分组:将活化后的大肠杆菌平板取出,挑取大肠杆菌单菌落接种于LB液体培养基平板中,37℃培养:A组.培养24小时获得生物膜为初期定植阶段大肠杆菌;B组培养48小时获得生物膜为成熟阶段的大肠杆菌。
处理液分组:将处理液加入5ml冷却为45℃的0.7%琼脂培养基中,混合均匀,然后分别倒入A组和B组各大肠杆菌平板表面,铺平。待凝固后移植培养箱中,过夜培养后对平板上大肠杆菌噬菌体菌斑进行计数(大肠杆菌噬菌体菌斑数量越多,对大肠杆菌的抑制效果越好),结果如图1-2所示。其中,处理液分组情况如下:
实验组1:50ul大肠杆菌噬菌体Esc-COP-4噬菌体液(109cpu)
实验组2:1ml后生元悬液(1mg/ml)+50ul大肠杆菌噬菌体Esc-COP-4噬菌体液(109cpu)
实验组3:1ml后生元悬液(1mg/ml)+1ml益生菌液(OD=0.6)+50ul大肠杆菌噬菌体Esc-COP-4噬菌体液(105cpu)
实验组4:1ml后生元悬液(1mg/ml)+1ml益生菌液(OD=0.6)+50ul大肠杆菌噬菌体Esc-COP-4噬菌体液(109cpu)
空白对照:2.5mL PBS溶液。
上述中,益生菌采用后生元对应的活菌菌株。
如图1-2所示,在大肠杆菌的不同生长阶段,不同菌株的后生元悬液与大肠杆菌噬菌体复配后处理大肠杆菌,大肠杆菌噬菌体菌斑数均有显著的提高,即说明其均对大肠杆菌表现出了很好的抑制效果。具体分析如下:
1.大肠杆菌处于初始定植阶段:实验组1和实验组2对大肠杆菌均表现出了很好抑制效果,但,实验组2的抑制效果比实验组1的抑制效果明显,即不同菌株的后生元悬液分别与大肠杆菌噬菌体复配后对大肠杆菌的抑制效果相比单独大肠杆菌噬菌体对大肠杆菌的抑制效果具有明显的差异。其中,植物乳杆菌HA-119与大肠杆菌噬菌体复配后对大肠杆菌的抑制效果与大肠杆菌噬菌体单独作用大肠杆菌的抑制效果相比差异性最明显,卷曲乳杆菌KT-11、鼠李糖乳杆菌HA-111也具有较为明显的差异性。
2.大肠杆菌成熟期:实验组1和实验组2对大肠杆菌均表现出了很好抑制效果,但,实验组2的抑制效果比实验组1的抑制效果明显,即不同菌株的后生元悬液分别与大肠杆菌噬菌体复配后对大肠杆菌的抑制效果相比单独大肠杆菌噬菌体对大肠杆菌的抑制效果具有明显的差异。其中,植物乳杆菌HA-119与大肠杆菌噬菌体复配后对大肠杆菌的抑制效果与大肠杆菌噬菌体单独作用大肠杆菌的抑制效果相比差异性最明显,卷曲乳杆菌KT-11、鼠李糖乳杆菌HA-111和副干酪乳杆菌HA-108也具有较为明显的差异性。
后生元与噬菌体复配对大肠杆菌的抑制效果比噬菌体单独作用的抑制效果较好,有可能是后生元首先打破了大肠杆菌生物膜的保护,从而使得噬菌体可以快速作用于大肠杆菌,从而形成更多的噬菌斑。这是由于后生元所包含的成分,如磷壁酸、胞外多糖蛋白等能够抑制大肠杆菌生物膜的形成和活性,从而为噬菌体发挥其侵染大肠杆菌的功效打开了一条通路,解除了生物膜对大肠杆菌的保护作用,从而有利于噬菌体发挥作用。
根据申请人的进一步研究发现,在微生物组合制剂中添加益生菌后,对大肠杆菌的抑制效果更好。因此,申请人将后生元对应的活菌菌株和后生元一起与噬菌体复配,考察了其对大肠杆菌的抑制情况,结果如图1中实验组3和实验组4所示。从图1中可以看出,加入益生菌后,相比实验组1和实验组2,实验组3和实验组4对大肠杆菌的抑制效果明显提高。其中植物乳杆菌和卷曲乳杆菌在大肠杆菌生物膜初始定植期和成熟期均有很好抑制作用;瑞士乳杆菌、嗜热链球菌在生物膜成熟期对大肠杆菌具有很好的抑制作用。申请人认为,加入益生菌后,其代谢产物可以进一步抑制生物膜的形成。因此使得噬菌体侵染大肠杆菌的速率更快,并呈现出噬菌体噬菌斑数量最多,即对大肠杆菌的抑制效果最好。
为了验证后生元对有害菌生物膜的影响,申请人利用不同菌株的后生元考察了其对有害菌生物膜生长能力以及在有害菌不同的生长时期对生物膜活性的影响,具体如实验2.4和实验2.5所述。
2.4后生元抑制有害菌生物膜生长能力试验
将活化后的有害菌平板取出,挑取有害菌单菌落接种于LB液体培养基中,37℃过夜培养。8000rpm 4℃离心5min,收集菌体,用PBS洗涤两次,再用RPMI-1640液体培养基调整其菌液浓度为106CFU/mL。在96孔板中添加100μL有害菌菌液和100μL后生元混悬液(1mg/mL),以MRS培养基作为空白对照。将孔板置于37℃培养48h。培养后,用PBS轻柔洗涤3次,每孔添加100μL 0.1%结晶紫,染色20min,弃去结晶紫,用PBS清洗3次,每孔添加100μL95%乙醇,用酶标仪测量570nm处的吸光度。结果如图3-5所示。
从图3-5结果可以看出,针对有害菌大肠杆菌、金黄色葡萄球菌和白色念珠菌,不同菌株的后生元对有害菌生物膜的生长能力均具有一定的抑制作用,但抑制程度各不相同。其中,对大肠杆菌的抑制效果最好,白色念珠菌的抑制效果相比大肠杆菌较差。这有可能与不同有害菌的致病能力有关。因为,生物膜是微生物接触到宿主或物体表面后所形成的,由于生物膜的存在,使得膜内的细菌比悬浮细菌具有更强的抗药性、毒力及致病性。因此,对于白色念珠菌生物膜生长能力的抑制效果相比大肠杆菌和金黄色葡萄球菌的抑制效果较差。不同的后生元对同一有害菌菌的抑制效果也是不同的:1.对于大肠杆菌,所选10种后生元均具有很好的抑制效果,其中,卷曲乳杆菌KT-11的抑制效果最好。2.对于金黄色葡萄球菌,副干酪乳杆菌HA-108、植物乳杆菌L-137和HA-119和卷曲乳杆菌KT-11的抑制效果较好。嗜热链球菌HA-110、凝结芽孢杆菌GBI-30、戊糖片球菌NB17和长双歧杆菌108的抑制效果较差。3.对于白色念珠菌,副干酪乳杆菌HA-108、植物乳杆菌L-137和HA-119和鼠李糖乳杆菌HA-111对生物膜的生长能力均表现出了很好抑制效果。
2.5后生元悬液抑制有害菌生物膜活性的试验
将活化后的白色念珠菌平板取出,挑取白色念珠菌单菌落接种于YPD液体培养基中,37℃过夜培养。取100μL白色念珠菌悬液液于96孔板中,37℃80rpm摇床培养3h,弃去孔中的培养液,用PBS清洗轻柔清洗3次。每组平行设置3个。
a.在初始定植阶段:将用PBS清洗轻柔清洗3次的96孔板,每孔加入200μL RPMI-1640液体培养基和100μL后生元悬液(1mg/mL),37℃培养24h,以加入200μL RPMI-1640液体培养基的液体作为空白对照。
b.在成熟阶段:将用PBS清洗3次的96孔板,每孔添加200μL RPMI-1640液体培养基,继续培养24h。培养完成后,用PBS清洗3次。每孔加入100μL后生元悬液(1mg/mL),37℃培养24h,以加入200μL RPMI-1640液体培养基液体作为空白对照。
将上述处理后的96孔板,弃去上清液,PBS清洗3次,每孔分别加入90μLXTT(二甲氧唑黄)(浓度为0.75mg/mL)和10μL PMS(N-甲基吩嗪硫酸甲酯)(浓度为0.32mg/mL),避光培养3h,于酶标仪测量492nm处的吸光度值,结果如图6-7所示。
由图6-7可以看出,无论是初始定植期还是成熟期,后生元悬液对白色念珠菌的生物膜活性均具有抑制作用。其中,植物乳杆菌L-137和HA-199在白色念珠菌的初始定植期和成熟期均对其生物膜的活性表现出很好的抑制作用。在初始定植期,卷曲乳杆菌KT-11也表现出很好的抑制效果。
综上,通过申请人的研究发现,后生元可以有效抑制有害菌生物膜的生长能力及活性,解除了生物膜对有害菌的保护,从而为噬菌体侵染有害菌打开了快速通道。有害菌被消灭后,有益菌恢复对病灶上皮细胞的占位,并在后生元的作用下实现快速定植、增殖,从而达到微生态菌群的平衡。另外,根据申请人的进一步研究,再复配益生菌后,其代谢产物可以进一步抑制生物膜的形成。因此使得噬菌体侵染有害菌的速率更快、效果更好。
以上已以较佳实施例公布了本发明,然其并非用以限制本发明,凡采取等同替换或等效变换的方案所获得的技术方案,均落在本发明的保护范围内。
Claims (10)
1.一种后生元和噬菌体复配的微生物组合制剂,其特征在于:包括后生元和噬菌体;所述后生元包括灭活益生菌;所述噬菌体对致病细菌具实质性裂解能力,所述噬菌体为单株噬菌体或多株噬菌体的混合物。
2.根据权利要求1所述的后生元和噬菌体复配的微生物组合制剂,其特征在于:所述噬菌体为大肠杆菌属噬菌体、埃希氏菌属噬菌体、沙门氏菌属噬菌体、爱德华菌属噬菌体、枸橼酸菌属噬菌体、志贺氏菌属噬菌体、克雷伯菌属噬菌体、沙雷菌属噬菌体、变形杆菌属噬菌体、假单胞菌属噬菌体、克雷伯氏菌属噬菌体、丛毛单胞菌属噬菌体、短波单胞菌属噬菌体、不动杆菌属噬菌体、黄杆菌属噬菌体、威克斯菌属噬菌体、金色单胞菌属噬菌体、黄色单胞菌属噬菌体、弧菌属噬菌体、气单胞菌属噬菌体、葡萄球菌属噬菌体、草绿色链球菌属噬菌体、β溶血链球菌属噬菌体、咽峡炎链球菌属噬菌体、肺炎链球菌属噬菌体、李斯特菌属噬菌体、弯曲杆菌属噬菌体、马拉色菌属噬菌体、丙酸杆菌属噬菌体、动弯杆菌属噬菌体、***属噬菌体、厌氧消化链球菌属噬菌体、加德诺菌属噬菌体中的一种或多种组合;
或/和
所述后生元为乳酸杆菌属、双歧杆菌属、链球菌属、乳球菌属、明串球菌属、丙酸杆菌属、片球菌属、葡萄球菌属、芽孢杆菌属、克鲁维酵母菌属中的一种或两种以上组合;优选地,所述后生元为熟酸乳杆菌、干酪乳杆菌、卷曲乳杆菌、德氏乳杆菌、发酵乳杆菌、格氏乳杆菌、瑞士乳杆菌、约氏乳杆菌、副干酪乳杆菌、植物乳杆菌、罗伊氏乳杆菌、鼠李糖乳杆菌、唾液乳杆菌、清酒乳杆菌、弯曲乳杆菌、加氏乳杆菌、嗜热链球菌、乳酸乳球菌乳酸亚种、乳酸乳球菌乳脂亚种、乳酸乳球菌双乙酰亚种、肠膜明串珠菌肠膜亚种、费氏丙酸杆菌谢氏亚种、产丙酸丙酸杆菌、乳酸片球菌、戊糖片球菌、小牛葡萄球菌、木糖葡萄球菌、肉葡萄球菌、凝结芽孢杆菌、枯草芽孢杆中的一种或几种组合;更优地,所述后生元为瑞士乳杆菌、干酪乳杆菌、加氏乳杆菌、副干酪乳杆菌、植物乳杆菌、鼠李糖乳杆菌、卷曲乳杆菌、唾液乳杆菌、嗜酸乳杆菌、短乳杆菌、保加利亚乳杆菌、发酵乳杆菌、罗伊氏乳杆菌、乳酸双歧杆菌、短双歧杆菌、两歧双歧杆菌、婴儿双歧杆菌、长双歧杆菌、嗜热链球菌、戊糖片球菌、凝结芽孢杆菌中的一种或两种以上组合。
3.根据权利要求2所述的后生元和噬菌体复配的微生物组合制剂,其特征在于:所述噬菌体为大肠杆菌噬菌体、阪崎肠杆菌噬菌体、埃希氏菌噬菌体、肺炎克雷伯菌噬菌体、沙门氏菌噬菌体、异型枸橼酸杆菌、志贺氏菌噬菌体、铜绿假单胞菌噬菌体、溶血不动杆菌噬菌体、脑膜败血性黄杆菌噬菌体、动物溃疡威克斯菌噬菌体、浅黄假单胞菌噬菌体、霍乱弧菌噬菌体、副溶血弧菌噬菌体、溶藻弧菌噬菌体、创伤弧菌噬菌体、金黄色葡萄球菌噬菌体、化脓性链球菌噬菌体、咽峡炎链球菌噬菌体、肺炎链球菌、李斯特菌噬菌体、弯曲杆菌噬菌体、合轴马拉色菌噬菌体、痤疮丙酸杆菌噬菌体、动弯杆菌噬菌体、***噬菌体及加德诺菌噬菌体中的一种或多种组合。
4.根据权利要求1所述的后生元和噬菌体复配的微生物组合制剂,其特征在于:所述组合物还包括益生菌或/和益生元。
5.根据权利要求4所述的后生元和噬菌体复配的微生物组合制剂,其特征在于:所述益生菌为乳酸杆菌属、双歧杆菌属、链球菌属、乳球菌属、明串球菌属、丙酸杆菌属、片球菌属、葡萄球菌属、芽孢杆菌属、克鲁维酵母菌属中的一种或两种以上组合;
优选地,所述益生菌为熟酸乳杆菌、干酪乳杆菌、卷曲乳杆菌、德氏乳杆菌、发酵乳杆菌、格氏乳杆菌、瑞士乳杆菌、约氏乳杆菌、副干酪乳杆菌、植物乳杆菌、罗伊氏乳杆菌、鼠李糖乳杆菌、唾液乳杆菌、清酒乳杆菌、弯曲乳杆菌、加氏乳杆菌、嗜热链球菌、乳酸乳球菌乳酸亚种、乳酸乳球菌乳脂亚种、乳酸乳球菌双乙酰亚种、肠膜明串珠菌肠膜亚种、费氏丙酸杆菌谢氏亚种、产丙酸丙酸杆菌、乳酸片球菌、戊糖片球菌、小牛葡萄球菌、木糖葡萄球菌、肉葡萄球菌、凝结芽孢杆菌、枯草芽孢杆中的一种或几种组合;
更优地,所述后生元为瑞士乳杆菌、干酪乳杆菌、加氏乳杆菌、副干酪乳杆菌、植物乳杆菌、鼠李糖乳杆菌、卷曲乳杆菌、唾液乳杆菌、嗜酸乳杆菌、短乳杆菌、保加利亚乳杆菌、发酵乳杆菌、罗伊氏乳杆菌、乳酸双歧杆菌、短双歧杆菌、两歧双歧杆菌、婴儿双歧杆菌、长双歧杆菌、嗜热链球菌、戊糖片球菌、凝结芽孢杆菌中的一种或两种以上组合;
或/和
所述益生元为短链脂肪酸、乳铁蛋白、低聚果糖、低聚木糖、低聚乳糖、菊粉、乳果糖、洋蓟、菊苣、燕麦、大麦、豆科植物、大蒜、橄榄菜、豆类或草药中的一种或两种以上组合。
6.一种产品,其特征在于:包含权利要求1-5任一项所述的微生物组合制剂以及辅料。
7.根据权利要求6所述的产品,其特征在于:该产品的剂型为粉剂、栓剂、固体饮料、硬胶囊、软胶囊、软饮料、多层硬胶囊、溶豆、冻干粉、奶豆、巧克力、夹心软糖、夹心巧克力、茶饮料、冷萃咖啡、湿巾、膏剂、霜剂、液体剂、乳剂、凝胶、固体剂。
8.权利要求6所述的产品和权利要求1-5任一项所述的微生物组合制剂在制备治疗细菌感染性疾病的医药品、食品或动物食品、营养品、保健品或补充剂、日化用品、化妆品、洗护用品、消毒用品中的应用。
9.根据权利要求8所述的应用,其特征在于:所述细菌感染性疾病包括人类或动物中由细菌感染引起的肠胃***疾病、泌尿***疾病、生殖***疾病、呼吸道疾病和皮肤类疾病。
10.一种产品的制备方法,其特征在于:将后生元悬液与噬菌体液混合、添加或不添加辅料,成型、包装成品;其中,将后生元悬液与噬菌体液混合与添加辅料部分先后顺序,或者混合与添加辅料同时进行;
优选地,对辅料进行预处理,使辅料符合剂型要求后再与后生元悬液和噬菌体液的混合物混合,获得剂型后包装成品;或者,将辅料与后生元悬液和噬菌体液的混合物混合后,进行处理获得符合剂型要求的出产品后,成型、包装成品。
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Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114651915A (zh) * | 2022-04-20 | 2022-06-24 | 湖北凯利特生物科技有限公司 | 一种提高免疫促进生长的后生元、制备方法及应用 |
CN115569229A (zh) * | 2022-08-30 | 2023-01-06 | 中南大学湘雅三医院 | 搭载多种后生元成分的皮肤软组织保护材料及其制备方法 |
CN116019224A (zh) * | 2023-01-05 | 2023-04-28 | 青岛农业大学 | 一种具有防腐和肠胃调节功能的后生元、其制备方法及应用 |
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Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20150079040A1 (en) * | 2012-04-13 | 2015-03-19 | The University Of Manchester | Probiotic bacteria |
US20150297648A1 (en) * | 2012-10-30 | 2015-10-22 | Deerland Enzymes, Inc. | Prebiotic compositions comprising one or more types of bacteriophage |
CN106307549A (zh) * | 2016-08-17 | 2017-01-11 | 江苏微康生物科技有限公司 | 灭活型乳酸菌微生态制剂及其制备方法和应用 |
CN107812018A (zh) * | 2017-11-13 | 2018-03-20 | 浙江禾健生营养食品有限公司 | 一种灭活益生菌制品、制备方法及其应用 |
WO2019035737A1 (ru) * | 2017-08-17 | 2019-02-21 | Павел Павлович НЕСМИЯНОВ | Композиция и способ ее применения в лечении иммунных заболеваний |
US20200215131A1 (en) * | 2017-05-24 | 2020-07-09 | Viktor Veniaminovich Tets | Methods for treating and preventing diseases |
CN111789132A (zh) * | 2020-07-04 | 2020-10-20 | 菲吉乐科(南京)生物科技有限公司 | 一种新型复合制剂及其在细菌性病害中的应用 |
CN111904923A (zh) * | 2020-08-11 | 2020-11-10 | 江苏华能药业有限公司 | 一种益生菌和后生元组合物套装 |
CN111925995A (zh) * | 2020-07-04 | 2020-11-13 | 菲吉乐科(南京)生物科技有限公司 | 一种噬菌体与益生菌耦合发酵的微生态制剂及制备方法 |
WO2021072543A1 (en) * | 2019-10-18 | 2021-04-22 | University Of Ottawa | Probiotic compositions and methods |
-
2021
- 2021-08-10 CN CN202110912517.8A patent/CN113637606A/zh active Pending
Patent Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20150079040A1 (en) * | 2012-04-13 | 2015-03-19 | The University Of Manchester | Probiotic bacteria |
US20150297648A1 (en) * | 2012-10-30 | 2015-10-22 | Deerland Enzymes, Inc. | Prebiotic compositions comprising one or more types of bacteriophage |
CN106307549A (zh) * | 2016-08-17 | 2017-01-11 | 江苏微康生物科技有限公司 | 灭活型乳酸菌微生态制剂及其制备方法和应用 |
US20200215131A1 (en) * | 2017-05-24 | 2020-07-09 | Viktor Veniaminovich Tets | Methods for treating and preventing diseases |
WO2019035737A1 (ru) * | 2017-08-17 | 2019-02-21 | Павел Павлович НЕСМИЯНОВ | Композиция и способ ее применения в лечении иммунных заболеваний |
CN107812018A (zh) * | 2017-11-13 | 2018-03-20 | 浙江禾健生营养食品有限公司 | 一种灭活益生菌制品、制备方法及其应用 |
WO2021072543A1 (en) * | 2019-10-18 | 2021-04-22 | University Of Ottawa | Probiotic compositions and methods |
CN111789132A (zh) * | 2020-07-04 | 2020-10-20 | 菲吉乐科(南京)生物科技有限公司 | 一种新型复合制剂及其在细菌性病害中的应用 |
CN111925995A (zh) * | 2020-07-04 | 2020-11-13 | 菲吉乐科(南京)生物科技有限公司 | 一种噬菌体与益生菌耦合发酵的微生态制剂及制备方法 |
CN111904923A (zh) * | 2020-08-11 | 2020-11-10 | 江苏华能药业有限公司 | 一种益生菌和后生元组合物套装 |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114651915A (zh) * | 2022-04-20 | 2022-06-24 | 湖北凯利特生物科技有限公司 | 一种提高免疫促进生长的后生元、制备方法及应用 |
CN114651915B (zh) * | 2022-04-20 | 2023-12-19 | 湖北凯利特生物科技有限公司 | 一种用于制备提高免疫力促进生长的后生元的方法及应用 |
CN115569229A (zh) * | 2022-08-30 | 2023-01-06 | 中南大学湘雅三医院 | 搭载多种后生元成分的皮肤软组织保护材料及其制备方法 |
CN115569229B (zh) * | 2022-08-30 | 2023-12-22 | 中南大学湘雅三医院 | 搭载多种后生元成分的皮肤软组织保护材料及其制备方法 |
CN116019224A (zh) * | 2023-01-05 | 2023-04-28 | 青岛农业大学 | 一种具有防腐和肠胃调节功能的后生元、其制备方法及应用 |
CN116218719A (zh) * | 2023-01-05 | 2023-06-06 | 青岛农业大学 | 一种抗mrsa后生元、其制备方法及应用 |
CN116019224B (zh) * | 2023-01-05 | 2024-04-09 | 青岛农业大学 | 一种具有防腐和肠胃调节功能的后生元、其制备方法及应用 |
CN116326715A (zh) * | 2023-02-07 | 2023-06-27 | 青岛元达生物科技有限公司 | 具有改善便秘和防腐功能的后生元、其制备方法及应用 |
CN116138462A (zh) * | 2023-03-29 | 2023-05-23 | 杭州知零生物科技有限公司 | 一种增强抵抗力的后生元组合物及其制备方法 |
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