WO2015056770A1 - 新規乳酸菌、新規乳酸菌を有効成分とする自然免疫活性化剤、及び新規乳酸菌を含有する飲食品 - Google Patents
新規乳酸菌、新規乳酸菌を有効成分とする自然免疫活性化剤、及び新規乳酸菌を含有する飲食品 Download PDFInfo
- Publication number
- WO2015056770A1 WO2015056770A1 PCT/JP2014/077652 JP2014077652W WO2015056770A1 WO 2015056770 A1 WO2015056770 A1 WO 2015056770A1 JP 2014077652 W JP2014077652 W JP 2014077652W WO 2015056770 A1 WO2015056770 A1 WO 2015056770A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- lactic acid
- acid bacterium
- food
- innate immunity
- bacterium
- Prior art date
Links
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 title claims abstract description 206
- 241000894006 Bacteria Species 0.000 title claims abstract description 134
- 239000004310 lactic acid Substances 0.000 title claims abstract description 103
- 235000014655 lactic acid Nutrition 0.000 title claims abstract description 103
- 235000013305 food Nutrition 0.000 title claims abstract description 44
- 239000004480 active ingredient Substances 0.000 title claims abstract description 18
- 229960001438 immunostimulant agent Drugs 0.000 title abstract 3
- 239000003022 immunostimulating agent Substances 0.000 title abstract 3
- 230000003308 immunostimulating effect Effects 0.000 title abstract 3
- 241000191967 Staphylococcus aureus Species 0.000 claims abstract description 23
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 claims abstract description 22
- 229960003085 meticillin Drugs 0.000 claims abstract description 22
- 244000005700 microbiome Species 0.000 claims abstract description 15
- 241000194036 Lactococcus Species 0.000 claims abstract description 13
- 241000589517 Pseudomonas aeruginosa Species 0.000 claims abstract description 13
- 238000011156 evaluation Methods 0.000 claims abstract description 8
- 101000852852 Homo sapiens Innate immunity activator protein Proteins 0.000 claims description 35
- 102100036724 Innate immunity activator protein Human genes 0.000 claims description 35
- 230000015788 innate immune response Effects 0.000 claims description 33
- 235000015140 cultured milk Nutrition 0.000 claims description 25
- 238000000034 method Methods 0.000 claims description 23
- 108020004465 16S ribosomal RNA Proteins 0.000 claims description 15
- 230000008569 process Effects 0.000 claims description 13
- 241000194033 Enterococcus Species 0.000 claims description 10
- 235000013336 milk Nutrition 0.000 claims description 6
- 239000008267 milk Substances 0.000 claims description 6
- 210000004080 milk Anatomy 0.000 claims description 6
- 239000012141 concentrate Substances 0.000 claims description 4
- 239000000284 extract Substances 0.000 claims description 4
- 235000013618 yogurt Nutrition 0.000 abstract description 38
- 241000520134 Enterococcus mundtii Species 0.000 abstract 1
- 239000000047 product Substances 0.000 description 53
- 241000255789 Bombyx mori Species 0.000 description 24
- 230000004913 activation Effects 0.000 description 22
- 230000000694 effects Effects 0.000 description 16
- 238000004519 manufacturing process Methods 0.000 description 15
- 239000000843 powder Substances 0.000 description 15
- 238000002360 preparation method Methods 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 239000002609 medium Substances 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 244000057717 Streptococcus lactis Species 0.000 description 10
- 230000000529 probiotic effect Effects 0.000 description 10
- 235000014897 Streptococcus lactis Nutrition 0.000 description 9
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 9
- 235000013361 beverage Nutrition 0.000 description 9
- 208000015181 infectious disease Diseases 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 8
- 239000000306 component Substances 0.000 description 7
- 235000002639 sodium chloride Nutrition 0.000 description 7
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 6
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 6
- 229920002472 Starch Polymers 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 6
- 239000000796 flavoring agent Substances 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 235000019698 starch Nutrition 0.000 description 6
- 239000008107 starch Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 208000032536 Pseudomonas Infections Diseases 0.000 description 5
- 241001240958 Pseudomonas aeruginosa PAO1 Species 0.000 description 5
- 239000012190 activator Substances 0.000 description 5
- 235000005911 diet Nutrition 0.000 description 5
- 230000037213 diet Effects 0.000 description 5
- 230000000968 intestinal effect Effects 0.000 description 5
- 230000004118 muscle contraction Effects 0.000 description 5
- 235000021590 normal diet Nutrition 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 239000003381 stabilizer Substances 0.000 description 5
- 229960004793 sucrose Drugs 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 244000298697 Actinidia deliciosa Species 0.000 description 4
- 235000009436 Actinidia deliciosa Nutrition 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 241000233866 Fungi Species 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
- 229930006000 Sucrose Natural products 0.000 description 4
- PYMYPHUHKUWMLA-LMVFSUKVSA-N aldehydo-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 4
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 4
- LFYJSSARVMHQJB-QIXNEVBVSA-N bakuchiol Chemical compound CC(C)=CCC[C@@](C)(C=C)\C=C\C1=CC=C(O)C=C1 LFYJSSARVMHQJB-QIXNEVBVSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 238000012136 culture method Methods 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 235000013355 food flavoring agent Nutrition 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- BJRNKVDFDLYUGJ-RMPHRYRLSA-N hydroquinone O-beta-D-glucopyranoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC=C(O)C=C1 BJRNKVDFDLYUGJ-RMPHRYRLSA-N 0.000 description 4
- 230000008076 immune mechanism Effects 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 4
- -1 patches Substances 0.000 description 4
- 230000001954 sterilising effect Effects 0.000 description 4
- 238000004659 sterilization and disinfection Methods 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 229920001817 Agar Polymers 0.000 description 3
- WQZGKKKJIJFFOK-SVZMEOIVSA-N D-(+)-Galactose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-SVZMEOIVSA-N 0.000 description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Natural products OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- PNNNRSAQSRJVSB-UHFFFAOYSA-N L-rhamnose Natural products CC(O)C(O)C(O)C(O)C=O PNNNRSAQSRJVSB-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 230000003213 activating effect Effects 0.000 description 3
- 239000008272 agar Substances 0.000 description 3
- 235000010419 agar Nutrition 0.000 description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 229910000019 calcium carbonate Inorganic materials 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 235000008504 concentrate Nutrition 0.000 description 3
- 235000013365 dairy product Nutrition 0.000 description 3
- 210000004443 dendritic cell Anatomy 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 235000013399 edible fruits Nutrition 0.000 description 3
- 238000000855 fermentation Methods 0.000 description 3
- 230000004151 fermentation Effects 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 230000036039 immunity Effects 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000002773 nucleotide Substances 0.000 description 3
- 125000003729 nucleotide group Chemical group 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 2
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- XUCIJNAGGSZNQT-JHSLDZJXSA-N (R)-amygdalin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](O[C@@H](C#N)C=2C=CC=CC=2)O1 XUCIJNAGGSZNQT-JHSLDZJXSA-N 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 2
- PMNLUUOXGOOLSP-UHFFFAOYSA-N 2-mercaptopropanoic acid Chemical compound CC(S)C(O)=O PMNLUUOXGOOLSP-UHFFFAOYSA-N 0.000 description 2
- PLXMOAALOJOTIY-FPTXNFDTSA-N Aesculin Natural products OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](O)[C@H]1Oc2cc3C=CC(=O)Oc3cc2O PLXMOAALOJOTIY-FPTXNFDTSA-N 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 238000010356 CRISPR-Cas9 genome editing Methods 0.000 description 2
- WNBCMONIPIJTSB-BGNCJLHMSA-N Cichoriin Natural products O([C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1)c1c(O)cc2c(OC(=O)C=C2)c1 WNBCMONIPIJTSB-BGNCJLHMSA-N 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- GUBGYTABKSRVRQ-UHFFFAOYSA-N D-Cellobiose Natural products OCC1OC(OC2C(O)C(O)C(O)OC2CO)C(O)C(O)C1O GUBGYTABKSRVRQ-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-CUHNMECISA-N D-Cellobiose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-CUHNMECISA-N 0.000 description 2
- RFSUNEUAIZKAJO-VRPWFDPXSA-N D-Fructose Natural products OC[C@H]1OC(O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-VRPWFDPXSA-N 0.000 description 2
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 2
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
- LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 2
- 240000001929 Lactobacillus brevis Species 0.000 description 2
- 235000013957 Lactobacillus brevis Nutrition 0.000 description 2
- 108090001060 Lipase Proteins 0.000 description 2
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 2
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 2
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- DKXNBNKWCZZMJT-UHFFFAOYSA-N O4-alpha-D-Mannopyranosyl-D-mannose Natural products O=CC(O)C(O)C(C(O)CO)OC1OC(CO)C(O)C(O)C1O DKXNBNKWCZZMJT-UHFFFAOYSA-N 0.000 description 2
- AYRXSINWFIIFAE-UHFFFAOYSA-N O6-alpha-D-Galactopyranosyl-D-galactose Natural products OCC1OC(OCC(O)C(O)C(O)C(O)C=O)C(O)C(O)C1O AYRXSINWFIIFAE-UHFFFAOYSA-N 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- NGFMICBWJRZIBI-JZRPKSSGSA-N Salicin Natural products O([C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@H](CO)O1)c1c(CO)cccc1 NGFMICBWJRZIBI-JZRPKSSGSA-N 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 244000269722 Thea sinensis Species 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 2
- NGFMICBWJRZIBI-UHFFFAOYSA-N alpha-salicin Natural products OC1C(O)C(O)C(CO)OC1OC1=CC=CC=C1CO NGFMICBWJRZIBI-UHFFFAOYSA-N 0.000 description 2
- 229940089837 amygdalin Drugs 0.000 description 2
- YZLOSXFCSIDECK-UHFFFAOYSA-N amygdalin Natural products OCC1OC(OCC2OC(O)C(O)C(O)C2O)C(O)C(O)C1OC(C#N)c3ccccc3 YZLOSXFCSIDECK-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 229960000271 arbutin Drugs 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000006172 buffering agent Substances 0.000 description 2
- 235000010216 calcium carbonate Nutrition 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 229960003067 cystine Drugs 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- XHCADAYNFIFUHF-TVKJYDDYSA-N esculin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC(C(=C1)O)=CC2=C1OC(=O)C=C2 XHCADAYNFIFUHF-TVKJYDDYSA-N 0.000 description 2
- 229940093496 esculin Drugs 0.000 description 2
- AWRMZKLXZLNBBK-UHFFFAOYSA-N esculin Natural products OC1OC(COc2cc3C=CC(=O)Oc3cc2O)C(O)C(O)C1O AWRMZKLXZLNBBK-UHFFFAOYSA-N 0.000 description 2
- YGHHWSRCTPQFFC-UHFFFAOYSA-N eucalyptosin A Natural products OC1C(O)C(O)C(CO)OC1OC1C(OC(C#N)C=2C=CC=CC=2)OC(CO)C(O)C1O YGHHWSRCTPQFFC-UHFFFAOYSA-N 0.000 description 2
- 235000021107 fermented food Nutrition 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 229940050410 gluconate Drugs 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 230000005934 immune activation Effects 0.000 description 2
- 230000036737 immune function Effects 0.000 description 2
- 230000008105 immune reaction Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 230000011542 interferon-beta production Effects 0.000 description 2
- 239000003589 local anesthetic agent Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229960002160 maltose Drugs 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000004899 motility Effects 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 229950006780 n-acetylglucosamine Drugs 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- BJRNKVDFDLYUGJ-UHFFFAOYSA-N p-hydroxyphenyl beta-D-alloside Natural products OC1C(O)C(O)C(CO)OC1OC1=CC=C(O)C=C1 BJRNKVDFDLYUGJ-UHFFFAOYSA-N 0.000 description 2
- 239000003002 pH adjusting agent Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 230000001766 physiological effect Effects 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- 239000006041 probiotic Substances 0.000 description 2
- 235000018291 probiotics Nutrition 0.000 description 2
- NGFMICBWJRZIBI-UJPOAAIJSA-N salicin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC=CC=C1CO NGFMICBWJRZIBI-UJPOAAIJSA-N 0.000 description 2
- 229940120668 salicin Drugs 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 235000013311 vegetables Nutrition 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- GZCWLCBFPRFLKL-UHFFFAOYSA-N 1-prop-2-ynoxypropan-2-ol Chemical compound CC(O)COCC#C GZCWLCBFPRFLKL-UHFFFAOYSA-N 0.000 description 1
- VBUYCZFBVCCYFD-JJYYJPOSSA-N 2-dehydro-D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C(=O)C(O)=O VBUYCZFBVCCYFD-JJYYJPOSSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 108010051457 Acid Phosphatase Proteins 0.000 description 1
- 102000013563 Acid Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 102100026189 Beta-galactosidase Human genes 0.000 description 1
- 101710180684 Beta-hexosaminidase Proteins 0.000 description 1
- 101710124976 Beta-hexosaminidase A Proteins 0.000 description 1
- 241000186000 Bifidobacterium Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 102100035882 Catalase Human genes 0.000 description 1
- 108010053835 Catalase Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 240000007154 Coffea arabica Species 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 206010011409 Cross infection Diseases 0.000 description 1
- HEBKCHPVOIAQTA-NGQZWQHPSA-N D-Arabitol Natural products OC[C@H](O)C(O)[C@H](O)CO HEBKCHPVOIAQTA-NGQZWQHPSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- QWIZNVHXZXRPDR-UHFFFAOYSA-N D-melezitose Natural products O1C(CO)C(O)C(O)C(O)C1OC1C(O)C(CO)OC1(CO)OC1OC(CO)C(O)C(O)C1O QWIZNVHXZXRPDR-UHFFFAOYSA-N 0.000 description 1
- SRBFZHDQGSBBOR-SOOFDHNKSA-N D-ribopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@@H]1O SRBFZHDQGSBBOR-SOOFDHNKSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 239000004278 EU approved seasoning Substances 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 102000053187 Glucuronidase Human genes 0.000 description 1
- 108010060309 Glucuronidase Proteins 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 1
- 101000831496 Homo sapiens Toll-like receptor 3 Proteins 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- LKDRXBCSQODPBY-AMVSKUEXSA-N L-(-)-Sorbose Chemical compound OCC1(O)OC[C@H](O)[C@@H](O)[C@@H]1O LKDRXBCSQODPBY-AMVSKUEXSA-N 0.000 description 1
- SHZGCJCMOBCMKK-PQMKYFCFSA-N L-Fucose Natural products C[C@H]1O[C@H](O)[C@@H](O)[C@@H](O)[C@@H]1O SHZGCJCMOBCMKK-PQMKYFCFSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 241000186660 Lactobacillus Species 0.000 description 1
- 244000199885 Lactobacillus bulgaricus Species 0.000 description 1
- 235000013960 Lactobacillus bulgaricus Nutrition 0.000 description 1
- 244000199866 Lactobacillus casei Species 0.000 description 1
- 235000013958 Lactobacillus casei Nutrition 0.000 description 1
- 235000013471 Lactococcus lactis subsp hordniae Nutrition 0.000 description 1
- 235000009191 Lactococcus lactis subsp lactis Il1403 Nutrition 0.000 description 1
- 241001183079 Lactococcus lactis subsp. hordniae Species 0.000 description 1
- 241000432051 Lactococcus lactis subsp. lactis Il1403 Species 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 239000004367 Lipase Substances 0.000 description 1
- 102000004882 Lipase Human genes 0.000 description 1
- 102100024295 Maltase-glucoamylase Human genes 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
- 101150026476 PAO1 gene Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- HCBIBCJNVBAKAB-UHFFFAOYSA-N Procaine hydrochloride Chemical compound Cl.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 HCBIBCJNVBAKAB-UHFFFAOYSA-N 0.000 description 1
- 102100030122 Protein O-GlcNAcase Human genes 0.000 description 1
- 101710081801 Protein O-GlcNAcase Proteins 0.000 description 1
- 101710199095 Putative beta-hexosaminidase Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- 108010060818 Toll-Like Receptor 9 Proteins 0.000 description 1
- 102100024324 Toll-like receptor 3 Human genes 0.000 description 1
- 102100033117 Toll-like receptor 9 Human genes 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- BZHJMEDXRYGGRV-UHFFFAOYSA-N Vinyl chloride Chemical compound ClC=C BZHJMEDXRYGGRV-UHFFFAOYSA-N 0.000 description 1
- 229930003451 Vitamin B1 Natural products 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- PYMYPHUHKUWMLA-WISUUJSJSA-N aldehydo-L-xylose Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WISUUJSJSA-N 0.000 description 1
- 229930195726 aldehydo-L-xylose Natural products 0.000 description 1
- 102000005840 alpha-Galactosidase Human genes 0.000 description 1
- 108010030291 alpha-Galactosidase Proteins 0.000 description 1
- 108010028144 alpha-Glucosidases Proteins 0.000 description 1
- 102000012086 alpha-L-Fucosidase Human genes 0.000 description 1
- 108010061314 alpha-L-Fucosidase Proteins 0.000 description 1
- 102000019199 alpha-Mannosidase Human genes 0.000 description 1
- 108010012864 alpha-Mannosidase Proteins 0.000 description 1
- 108010027597 alpha-chymotrypsin Proteins 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 102000006995 beta-Glucosidase Human genes 0.000 description 1
- 108010047754 beta-Glucosidase Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- VBICKXHEKHSIBG-UHFFFAOYSA-N beta-monoglyceryl stearate Natural products CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000015895 biscuits Nutrition 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229910021538 borax Inorganic materials 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001722 carbon compounds Chemical class 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 239000007765 cera alba Substances 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 150000001868 cobalt Chemical class 0.000 description 1
- 235000016213 coffee Nutrition 0.000 description 1
- 235000013353 coffee beverage Nutrition 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- 230000008260 defense mechanism Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- QYDYPVFESGNLHU-UHFFFAOYSA-N elaidic acid methyl ester Natural products CCCCCCCCC=CCCCCCCCC(=O)OC QYDYPVFESGNLHU-UHFFFAOYSA-N 0.000 description 1
- 230000022912 endospore formation Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 210000003495 flagella Anatomy 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 235000013376 functional food Nutrition 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- DLRVVLDZNNYCBX-CQUJWQHSSA-N gentiobiose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)C(O)O1 DLRVVLDZNNYCBX-CQUJWQHSSA-N 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 235000009569 green tea Nutrition 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 235000013402 health food Nutrition 0.000 description 1
- 239000001341 hydroxy propyl starch Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 235000013828 hydroxypropyl starch Nutrition 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 229960000367 inositol Drugs 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 150000002505 iron Chemical class 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008274 jelly Substances 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 229940039696 lactobacillus Drugs 0.000 description 1
- 229940004208 lactobacillus bulgaricus Drugs 0.000 description 1
- 229940017800 lactobacillus casei Drugs 0.000 description 1
- 239000010699 lard oil Substances 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 229960004393 lidocaine hydrochloride Drugs 0.000 description 1
- YECIFGHRMFEPJK-UHFFFAOYSA-N lidocaine hydrochloride monohydrate Chemical compound O.[Cl-].CC[NH+](CC)CC(=O)NC1=C(C)C=CC=C1C YECIFGHRMFEPJK-UHFFFAOYSA-N 0.000 description 1
- 235000019421 lipase Nutrition 0.000 description 1
- 238000009630 liquid culture Methods 0.000 description 1
- 235000021056 liquid food Nutrition 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000012533 medium component Substances 0.000 description 1
- DLRVVLDZNNYCBX-ABXHMFFYSA-N melibiose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)C(O)O1 DLRVVLDZNNYCBX-ABXHMFFYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- QYDYPVFESGNLHU-KHPPLWFESA-N methyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC QYDYPVFESGNLHU-KHPPLWFESA-N 0.000 description 1
- 229940073769 methyl oleate Drugs 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 235000013379 molasses Nutrition 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 239000006872 mrs medium Substances 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229910017464 nitrogen compound Inorganic materials 0.000 description 1
- 150000002830 nitrogen compounds Chemical class 0.000 description 1
- 239000004745 nonwoven fabric Substances 0.000 description 1
- 235000012149 noodles Nutrition 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 229940100688 oral solution Drugs 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000012858 packaging process Methods 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 229940023462 paste product Drugs 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000013630 prepared media Substances 0.000 description 1
- 229960001309 procaine hydrochloride Drugs 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 235000020374 simple syrup Nutrition 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000004328 sodium tetraborate Substances 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- 235000014214 soft drink Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 235000013616 tea Nutrition 0.000 description 1
- 229960003495 thiamine Drugs 0.000 description 1
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 239000012929 tonicity agent Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- RULSWEULPANCDV-PIXUTMIVSA-N turanose Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](C(=O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O RULSWEULPANCDV-PIXUTMIVSA-N 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 239000000273 veterinary drug Substances 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 239000011691 vitamin B1 Substances 0.000 description 1
- 235000010374 vitamin B1 Nutrition 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 239000002759 woven fabric Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- 210000004340 zona pellucida Anatomy 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING THEREOF
- A23C9/00—Milk preparations; Milk powder or milk powder preparations
- A23C9/12—Fermented milk preparations; Treatment using microorganisms or enzymes
- A23C9/123—Fermented milk preparations; Treatment using microorganisms or enzymes using only microorganisms of the genus lactobacteriaceae; Yoghurt
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
- C12N1/205—Bacterial isolates
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/324—Foods, ingredients or supplements having a functional effect on health having an effect on the immune system
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2400/00—Lactic or propionic acid bacteria
- A23V2400/21—Streptococcus, lactococcus
- A23V2400/231—Lactis
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- C12R2001/00—Microorganisms ; Processes using microorganisms
- C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
- C12R2001/46—Streptococcus ; Enterococcus; Lactococcus
Definitions
- the present invention relates to a novel lactic acid bacterium, an innate immune activator containing the novel lactic acid bacterium as an active ingredient, and a food or drink containing the novel lactic acid bacterium.
- Lactic acid bacteria have long been used for fermented foods and are industrially used for the production of food, pharmaceuticals and probiotics. Lactic acid bacteria are characterized by Gram-positive, catalase-negative, no endospore formation and no motility.
- Lactococcus lactis (L. lactis) is a non-pathogenic gram-positive lactic acid bacterium that does not belong to the human intestinal flora and does not form colonies in the oral cavity or intestinal tract. In addition, the entire genome has been decoded, and genetics, vector systems, and gene expression systems have been analyzed. Recently, recombinant L. It has been reported that lactis is used for in situ synthesis and in vivo delivery of cytokines and specific antigens through the intestinal epidermis of animals (Non-Patent Documents 1 to 4).
- innate immune reaction In the innate immune reaction, it is known that immune cells such as dendritic cells and macrophages produce cytokines in response to innate immune activators derived from bacteria and viruses, and subsequent immune reactions occur.
- the innate immunity mechanism is an infection defense mechanism common to living organisms, and is characterized by a non-specific reaction and a quick reaction that effectively functions against many infection sources. Even in higher vertebrates such as humans, nonspecific innate immunity is more important than acquired immunity specific to the source of infection from the viewpoint of early infection resistance, prevention of cancer and lifestyle-related diseases, and tissue repair. Seems to occupy a more important position.
- Patent Document 1 a method capable of easily measuring the innate immune activation reaction in silkworms.
- Patent Document 2 a model of pathogenic microorganism infection for an organism having an acquired immune mechanism using an organism having only an innate immune mechanism.
- innate immunity mechanisms cause various diseases, and therefore, innate immunity activators and food / beverages that activate innate immunity that can regulate such innate immunity mechanisms as desired. Development is desired.
- Non-patent Document 6 Double-stranded RNA is thought to be formed by the CRISPR-Cas9 pathway. CRISPR-Cas9 is not found from the genomic base sequence of lactis. However, L. In lactis, there is a report that CpG DNA activates IFN ⁇ production of dendritic cells via the TLR9 pathway (Non-patent Document 7).
- An object of the present invention is to provide a lactic acid bacterium having high innate immunity activation ability, and an innate immunity activator comprising as an active ingredient the lactic acid bacterium, a killed bacterium of the lactic acid bacterium, or a processed product of the lactic acid bacterium, and
- An object of the present invention is to provide a food or drink containing the lactic acid bacteria or the innate immunity activator.
- lactic acid bacteria having innate immunity activation ability have been analyzed by analysis of their properties and analysis of the 16S rRNA base sequence, etc. (It may be abbreviated in some cases).
- the present invention provides a lactic acid bacterium belonging to the genus Lactococcus having a receipt number of NITE ABP-01694 in the Patent Microorganism Deposit Center (NPMD) of the National Institute for Product Evaluation and Technology (NITE). .
- NPMD Patent Microorganism Deposit Center
- NITE National Institute for Product Evaluation and Technology
- the present invention also provides an innate immunity activator comprising as an active ingredient a lactic acid bacterium belonging to the genus Lactococcus deposited under the receipt number NITE ABP-01694, a killed bacterium of the lactic acid bacterium, or a processed product of the lactic acid bacterium.
- the processed product of lactic acid bacteria is a culture of lactic acid bacteria; a concentrate; a paste product; a dry product such as a spray-dried product, a freeze-dried product, a vacuum-dried product, or a drum-dried product; a liquefied product; a diluted product; And an innate immunity activator characterized in that it is at least one processed product selected from the group consisting of a product and an extract from the culture.
- this embodiment is referred to as “embodiment 2”.
- the present invention also provides a food or drink containing a lactic acid bacterium belonging to the genus Lactococcus deposited under the receipt number NITE ABP-01694, and also provides a food or drink containing the above innate immunity activator. To do. Moreover, the food / beverage products manufactured using the process fermented using this lactic acid bacteria are provided. Hereinafter, this aspect of the invention is referred to as "Aspect 3".
- the present invention also relates to a fermented milk containing a lactic acid bacterium belonging to the genus Lactococcus deposited under the receipt number NITE ABP-01694.
- the fermented milk comprises methicillin-sensitive S. aureus, methicillin-resistant S. aureus, Pseudomonas aeruginosa.
- the present invention provides fermented milk having resistance to at least one bacterium selected from the group consisting of bacterium and Enterococcus mundidi.
- this embodiment is referred to as “embodiment 4”.
- the novel lactic acid bacterium which has a higher innate immunity activation ability than the lactic acid bacterium known until now can be provided. Furthermore, the innate immunity activator which uses this lactic acid bacterium as an active ingredient, and the food-drinks containing this lactic acid bacterium or this innate immunity activator can be provided.
- MSSA methicillin-sensitive Staphylococcus aureus
- MRSA methicillin-resistant Staphylococcus aureus
- Pseudomonas aeruginosa Enterococcus mundidi by edible lactic acid bacteria or fermented milk containing lactic acid bacteria of the present invention
- High resistance to at least one bacterium selected from These bacteria are causative bacteria that cause nosocomial infections, and by using the fermented milk, infection by these bacteria can be prevented or treated.
- (1) shows the result of eating a diet containing 11 / 19-B1 yogurt, and ( ⁇ ) shows the result of eating a normal diet.
- (1) shows the result of eating a diet containing 11 / 19-B1 yogurt (A) or 11 / 19-B1 live bacteria powder (B), and ( ⁇ ) shows the result of eating a normal diet.
- A) It is the graph which showed the change of the probiotic effect by changing the quantity of 11 / 19-B1 yogurt contained in a bait.
- B) is a graph showing the correlation of LD 50 for yoghurt intake and Pseudomonas aeruginosa.
- Aspect 1 of the present invention is a lactic acid bacterium belonging to the genus Lactococcus having a receipt number of NITE ABP-01694 in the Patent Microorganism Deposit Center (NPMD) of the National Institute of Technology and Evaluation (NITE).
- NPMD Patent Microorganism Deposit Center
- This 11 / 19-B1 strain is a Gram-positive bacilli, has no flagella, and has no motility. This strain was isolated using fruit as a source of separation.
- Physiological properties The physiological and chemical taxonomic properties of this 11 / 19-B1 strain are as follows. (1) Attitude toward oxygen: Anaerobic (2) Catalase:- (3) Alkaline phosphatase:- (4) Esterase:- (5) Esterase lipase:- (6) Lipase:- (7) Leucine allylamidase:- (8) Valine allylamidase:- (9) Cystine allylamidase:- (10) Trypsin:- (11) ⁇ -chymotrypsin:- (12) Acid phosphatase: + (13) Naphthol-AS-BI-phosphohumanlorase: + (14) ⁇ -Galactosidase:- (15) ⁇ -galactosidase:- (16) ⁇ -glucuronidase:- (17) ⁇ -Glucosidase:- (18) ⁇ -Glucosidase:- (19) N-acetyl- ⁇ -glucosaminidas
- the analysis results of 11 / 19-B1 strain on 16S rRNA used as an index for molecular biological phylogeny are as follows. As a result of amplification of the base sequence of the 16S rRNA region from the genomic DNA of the 11 / 19-B1 strain by PCR and analysis by a sequencer, 16S rRNA excluding some bases on the 5 ′ end side and 3 ′ end side The base sequence corresponding to almost the entire length of was found. This base sequence is shown in SEQ ID NO: 1 in the sequence listing. Since the base sequence of SEQ ID NO: 1 in the sequence listing is not the full length of 16S rRNA, it was designated as a 16S rRNA “region”.
- the nucleotide sequence of the 16S rRNA region of the 11 / 19-B1 strain was found to be Lactococcus lactis subsp. lactis IL1403, Lactococcus lactis subsp. hordniae NCDO 2181, Lactococcus lactis subsp.
- the base sequence (NR_103918, NR_040956, NR_040955) of lactis NCDO 604 strain and a homology of 99% were shown. However, it is different from the 11 / 19-B1 strain because it is not completely consistent.
- the properties of the above 11 / 19-B1 strain were compared with the classification according to Bergey's Manual of Systematic Bacteriology, vol.3, 1989, and the contents of other documents, and further 16S rRNA. As a result of comprehensive determination in consideration of the analysis results, the 11 / 19-B1 strain was determined to be a microorganism belonging to the genus Lactococcus.
- the 11 / 19-B1 strain was judged to be a novel microbial strain.
- 11 / 19-B1 strain is a patent microorganism deposit of 2-5-8 Kazusa Kamashishi, Kisarazu City, Chiba Prefecture, National Institute of Technology and Evaluation (hereinafter abbreviated as “NITE”) It is a microorganism deposited domestically at the Center (NPMD) and deposited under the deposit number: NITE P-01694 (deposit date: August 20, 2013). “11 / 19-B1” will then be submitted to the original microorganism application center (NPMD) of Kazusa Kamashichi 2-5-8, Kisarazu City, Chiba Prefecture, and the National Institute of Technology and Evaluation (NITE). Application for transfer from domestic deposit (original deposit date: August 20, 2013) to deposit under the Budapest Treaty (reception date: October 15, 2014, receipt number “NITE ABP-01694”) ").
- the 11 / 19-B1 strain may not be within the range of the physiological properties shown above. Needless to say, such “mutation” includes both natural and artificial mutations.
- the culture method of 11 / 19-B1 strain is described below.
- the culture method of the 11 / 19-B1 strain may be performed according to a general culture method performed for microorganisms belonging to the genus Lactococcus.
- the culture is preferably performed under anaerobic conditions.
- Examples of the carbon source in the medium include L-arabinose, D-ribose, D-xylose, D-galactose, D-mannose, D-mannitol, N-acetylglucosamine, amygdalin, arbutin, esculin, salicin, D-cellobiose
- Organic carbon compounds such as D-maltose, D-lactose, D-trehalose, gentiobiose, gluconate, D-glucose, D-fructose, sucrose, molasses, starch syrup, and fats and oils are used as the nitrogen source.
- Organic / inorganic nitrogen compounds such as casein, peptone, yeast extract, dry yeast, germ, soybean powder, urea, amino acid, ammonium salt can be used.
- inorganic salts such as sodium salt, potassium salt, calcium salt, magnesium salt, phosphate, iron salt, copper salt, zinc salt, cobalt salt and the like are appropriately added as necessary.
- a growth promoting substance such as biotin, vitamin B1, cystine, methyl oleate, lard oil or the like in terms of increasing the production amount of the target product.
- antifoamers such as a silicone oil and surfactant.
- the prepared medium for example, an MRS medium, a GAM medium or the like is preferably used.
- the culture conditions may be according to the general culture conditions performed for the microorganisms of the genus Lactococcus as described above. If it is a liquid culture method, stationary culture is desirable. If it is a small scale, you may use the stationary culture method by the glass bottle with a lid
- the culture temperature is preferably maintained between 25 ° C. and 37 ° C., more preferably around 37 ° C.
- the culture pH is preferably performed in the vicinity of 7.
- the culture period is a factor that varies depending on the composition of the medium used, the culture temperature, etc. In the case of the 11 / 19-B1 strain, it is usually sufficient for a short period of about 12 to 48 hours, preferably about 12 to 24 hours. A certain amount of objects can be secured.
- Aspect 2 of the present invention is an innate immunity activator comprising as an active ingredient the lactic acid bacterium of aspect 1, the dead bacterium of the lactic acid bacterium, or the processed product of the lactic acid bacterium,
- the above processed products of lactic acid bacteria are lactic acid bacteria cultures, concentrates, pasted products, spray-dried products, freeze-dried products, vacuum-dried products, drum-dried products, etc., liquefied products, diluted products, crushed products, and sterilized products.
- an innate immunity activator characterized by being at least one processed product selected from the group consisting of an extract from the culture. That is, Aspect 2 of the present invention is an innate immunity activator comprising as an active ingredient the lactic acid bacteria of Aspect 1, the killed bacteria of the lactic acid bacteria, or the processed product of the lactic acid bacteria.
- the innate immunity activator of the present invention can contain the lactic acid bacteria of aspect 1 in various states.
- lactic acid bacteria suspensions, lactic acid bacteria cultures (cells, culture supernatant (including medium components)) Can be mentioned.
- the innate immunity activator of the present invention may include the lactic acid bacterium of aspect 1 as it is, or may be included as a lactic acid bacterium treated product obtained by subjecting the lactic acid bacterium of aspect 1 to some kind of treatment.
- Specific examples of the treated product of lactic acid bacteria used in the innate immunity activator of the present invention include, for example, a culture of lactic acid bacteria; a concentrate; a paste; a spray-dried product, a freeze-dried product, a vacuum-dried product, and a drum-dried product.
- a dried product such as a product; a liquefied product; a diluted product; a crushed product; a sterilized processed product; an extract from the culture product;
- lactic acid bacteria viable cells, wet bacteria, dry bacteria and the like can be used as appropriate.
- the killed bacteria which performed sterilization ie, heat sterilization process, radiation sterilization process, crushing process, etc. may be sufficient.
- the content of the lactic acid bacterium, the killed lactic acid bacterium, and the processed product of the lactic acid bacterium, which is an active ingredient in the innate immunity activator of the present invention, with respect to the entire innate immunity activator is not particularly limited, depending on the purpose.
- the total amount of lactic acid bacteria, dead bacteria of the lactic acid bacteria, and processed products of the lactic acid bacteria can be 0.001 to 100 parts by mass when the total amount of the innate immunity activator is 100 parts by mass. It is preferable to blend in an amount of 0.01 to 99 parts by mass, particularly preferably 0.1 to 95 parts by mass, and still more preferably 1 to 90 parts by mass.
- any one of the active ingredients may be used alone, or two or more of them may be used in combination.
- the content ratio of each active ingredient in the innate immunity activator when two or more are used in combination is not particularly limited and can be appropriately selected according to the purpose.
- the innate immunity activator of the present invention can also be added to pharmaceuticals and / or foods and drinks having biological standards such as milk powder, and various pharmaceuticals regardless of the form of the pharmaceuticals and / or foods and drinks. And / or can be applied to food and drink.
- the innate immunity activator of the present invention can contain “other components” in addition to lactic acid bacteria, killed bacteria of the lactic acid bacteria, and processed products of the lactic acid bacteria, which are active ingredients.
- the “other components” in the innate immunity activator are not particularly limited and can be appropriately selected according to the purpose within a range not impairing the effects of the present invention.
- carrier There is no restriction
- carrier For example, according to the dosage form etc. which are mentioned later, it can select suitably.
- the content of the “other components” in the innate immunity activator is not particularly limited and can be appropriately selected according to the purpose.
- a dosage form of the innate immunity activation agent of this invention can select suitably according to the desired administration method as mentioned later.
- oral solids tablettes, coated tablets, granules, powders, capsules, etc.
- oral liquids internal solutions, syrups, elixirs, etc.
- injections solvents, suspensions, etc.
- Ointments patches, gels, creams, powders for external use, sprays, inhalation sprays and the like.
- Examples of the oral solid preparation include, for example, excipients and further additives such as binders, disintegrants, lubricants, colorants, flavoring and flavoring agents as necessary, in addition to the active ingredients.
- Examples of the excipient include lactose, sucrose, sodium chloride, glucose, starch, calcium carbonate, kaolin, microcrystalline cellulose, silicic acid and the like.
- Examples of the binder include water, ethanol, propanol, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethylcellulose, hydroxypropylcellulose, hydroxypropyl starch, methylcellulose, ethylcellulose, shellac, calcium phosphate, polyvinylpyrrolidone and the like. It is done.
- Examples of the disintegrant include dry starch, sodium alginate, agar powder, sodium bicarbonate, calcium carbonate, sodium lauryl sulfate, stearic acid monoglyceride, and lactose.
- Examples of the lubricant include purified talc, stearate, borax, and polyethylene glycol.
- Examples of the colorant include titanium oxide and iron oxide.
- Examples of the flavoring / flavoring agent include sucrose, orange peel, citric acid, tartaric acid and the like.
- the oral solution can be produced by a conventional method, for example, by adding additives such as a flavoring / flavoring agent, a buffering agent, and a stabilizer to the active ingredient.
- additives such as a flavoring / flavoring agent, a buffering agent, and a stabilizer
- the flavoring / flavoring agent include sucrose, orange peel, citric acid, tartaric acid and the like.
- the buffer include sodium citrate.
- the stabilizer include tragacanth, gum arabic, and gelatin.
- a pH adjuster, a buffer, a stabilizer, a tonicity agent, a local anesthetic, etc. are added to the active ingredient, and subcutaneous, intramuscular, intravenous use are performed by a conventional method.
- Etc. can be manufactured.
- the pH adjusting agent and the buffering agent include sodium citrate, sodium acetate, sodium phosphate and the like.
- the stabilizer include sodium pyrosulfite, EDTA, thioglycolic acid, thiolactic acid, and the like.
- the isotonic agent include sodium chloride and glucose.
- the local anesthetic include procaine hydrochloride and lidocaine hydrochloride.
- a known base, stabilizer, wetting agent, preservative and the like may be blended with the active ingredient and mixed by a conventional method.
- the base include liquid paraffin, white petrolatum, white beeswax, octyldodecyl alcohol, and paraffin.
- the preservative include methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, and the like.
- a cream, gel, paste or the like as the ointment can be applied to a known support by a conventional method.
- the support include woven fabric, nonwoven fabric, soft vinyl chloride, polyethylene, polyurethane and other films made of cotton, suf, and chemical fibers, and foam sheets.
- the innate immunity activator of the present invention is, for example, an individual who requires activation of the innate immune mechanism (for example, an individual who needs to maintain health or recover from fatigue; needs prevention or treatment of cancer or lifestyle-related diseases) Individual; individuals infected with bacteria, fungi, viruses, etc .; etc.).
- mice There are no particular restrictions on the animal to which the innate immunity activator of the present invention is administered.
- animals For example, humans; mice; rats; monkeys; horses; domestic animals such as cows, pigs, goats and chickens; And the like.
- the method for administering the innate immunity activator is not particularly limited, and can be appropriately selected according to, for example, the dosage form of the innate immunity activator. Oral administration, intraperitoneal administration, blood Injection, intestinal injection and the like.
- the dose of the innate immunity activator is not particularly limited and may be appropriately selected depending on the age, weight, desired degree of effect, etc. of the individual to be administered.
- the daily dose is preferably from 1 mg to 30 g, more preferably from 10 mg to 10 g, particularly preferably from 100 mg to 3 g as the amount of the active ingredient.
- Aspect 3 of the present invention is a food or drink containing the lactic acid bacterium of the present invention or the innate immunity activator of the present invention.
- the content of the lactic acid bacterium or the innate immunity activator in the food or drink containing the lactic acid bacterium or the innate immunity activator (hereinafter sometimes abbreviated as “the food or drink of the present invention”) is not particularly limited. Depending on the purpose and the form (type) of the food or drink, it can be selected as appropriate. When the whole food and drink is 100 parts by mass, the total amount of the innate immune activator is 0.001 to 100.
- the content is preferably in parts by mass, more preferably 0.01 to 100 parts by mass, and particularly preferably 0.1 to 100 parts by mass.
- any one of lactic acid bacteria and innate immunity activators may be used alone, or two or more may be used in combination.
- the food / beverage products of aspect 3 of this invention have an innate immunity activation effect.
- the food and beverage product of the present invention can further contain “other components”.
- the ⁇ other ingredients '' are not particularly limited and can be appropriately selected according to the purpose within a range not impairing the effects of the present invention.
- various food raw materials are mentioned.
- the content of “other components” is not particularly limited and can be appropriately selected depending on the purpose.
- confectionery such as jelly, a candy, chocolate, a biscuit
- taste drinks such as green tea, tea, coffee, a soft drink
- Dairy products such as fermented milk, yogurt and ice cream
- Vegetable and fruit processed products such as vegetable drinks, fruit drinks and jams
- Liquid foods such as soup; Grain processed products such as breads and noodles; Various seasonings; etc. Is mentioned.
- dairy products such as yogurt and fermented milk are preferred.
- a manufacturing method of these food / beverage products For example, according to the manufacturing method of various normal food / beverage products, it can manufacture suitably.
- the food and drink may be manufactured as oral solid preparations such as tablets, granules and capsules, or oral liquid preparations such as internal use liquid preparations and syrup preparations.
- the method for producing the oral solid preparation and oral liquid preparation is not particularly limited and can be appropriately selected according to the purpose.
- the preparation can be produced in accordance with the method for producing the oral solid preparation or oral liquid preparation described above. it can.
- the foods and drinks are considered to be particularly useful as functional foods, health foods and the like for the purpose of activating the innate immune mechanism.
- the 11 / 19-B1 strain is a novel lactic acid bacterium that has been artificially isolated from kiwifruit. Other than kiwifruit, the 11 / 19-B1 strain does not exist in an isolated form in nature. Therefore, the artificially isolated 11 / 19-B1 strain is not a substance that exists in nature. Therefore, neither the innate immunity activator containing the 11 / 19-B1 strain nor the food or drink containing the 11 / 19-B1 strain correspond to natural products. In the natural environment, the 11 / 19-B1 strain is not in contact with milk, and the strain is not present as a food or drink, so the fermented milk and food or drink of the present invention existed in nature. Therefore, none of these are natural products.
- the production method can be carried out by methods well known to those skilled in the art. If it is an expert, the process which mixes the microbial cell or processed material of the lactic acid bacteria of this invention with another component, a formation process, a sterilization process, a fermentation process, a baking process, a drying process, a cooling process, a granulation process, a packaging process, etc. Can be combined as appropriate to produce the desired food or drink.
- the lactic acid bacteria of this invention when using the lactic acid bacteria of this invention for manufacture of various fermented milk, it can manufacture using a method well-known to those skilled in the art.
- a food or drink manufactured using the process of adding a required amount of the lactic acid bacteria of the present invention as dead bacteria to fermented milk, or a food or drink manufactured using the process of fermenting using the lactic acid bacteria of the present invention as a lactic acid bacteria starter Can be mentioned.
- the fermentation can be performed under the same conditions as the culture conditions of the lactic acid bacteria of the present invention.
- Aspect 4 of the present invention is a fermented milk containing the lactic acid bacterium of the present invention, wherein the fermented milk is a group consisting of methicillin-sensitive Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Enterococcus mundidi. It is fermented milk characterized by having resistance to at least one bacterium selected from.
- Fermented milk is a dairy product obtained by fermenting milk such as cows with lactic acid bacteria or yeast, and examples thereof include yogurt.
- Fermented milk containing the lactic acid bacterium of the present invention is methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MSA), Staphylococcus aureus (MSA). It is shown in the results of Examples 4 to 6 that the bacterium and Enterococcus munditi are resistant to any fungus.
- MSSA methicillin-sensitive Staphylococcus aureus
- MSA methicillin-resistant Staphylococcus aureus
- MSA Staphylococcus aureus
- the subject of vaccination with fermented milk is a person who is ingested in the sense of increasing resistance to various infectious diseases, and those who have various infectious diseases are also limited to those with a decrease in innate immune function. Without being used, it can be used for those who have most diseases for the purpose of activating the systemic innate immune function. Furthermore, it can be applied to animals in various forms such as feed and veterinary drugs.
- the fermented milk is preferably used for prevention or treatment of infection caused by methicillin-sensitive Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Enterococcus mundidi, particularly for prevention or treatment of Pseudomonas aeruginosa infection. It is preferable to be used.
- the “11 / 19-B1 strain” used in the examples is isolated from kiwifruit as described above. Deposited as Lactococcus lactis 11 / 19-B1 strain belonging to Lactococcus lactis, Patent Evaluation Microorganism Depositary (NPMD), Kazusa Kamashitsu City, Kisarazu City, Chiba Prefecture (Accession number: NITE P-01694, Deposit date: August 20, 2013). “11 / 19-B1” will then be submitted to the original microorganism application center (NPMD) of Kazusa Kamashichi 2-5-8, Kisarazu City, Chiba Prefecture, and the National Institute of Technology and Evaluation (NITE). Application for transfer from domestic deposit (original deposit date: August 20, 2013) to deposit under the Budapest Treaty (reception date: October 15, 2014, receipt number “NITE ABP-01694”) ").
- Example 1 ⁇ Measurement of innate immunity activation activity> The 11 / 19-B1 strain cultured overnight in GAM medium is sterilized at 121 ° C for 20 minutes, then 50 ⁇ L is injected into a decapitation muscle specimen of a 5-year-old silkworm, and the innate immune activation activity is measured by slowing muscle contraction did. Measurement of innate immunity activation activity by slowing muscle contraction is performed by Ishii K., Hamamoto H., Kamimura M., Sekimizu K., J. Biol. Chem. Jan. 25; 283 (4): 2185-91 (2008) ).
- Comparative Example 1 The cultured Lactobacillus bulgaricus OLL1073 strain cultured overnight in GAM medium was sterilized at 121 ° C. for 20 minutes, and 50 ⁇ L was injected into a decapitated silkworm, and the innate immunity activation activity was measured by muscle contraction.
- Comparative Example 2 The cultured Lactobacillus casei strain YIT9029 cultured overnight in GAM medium was sterilized at 121 ° C. for 20 minutes, and 50 ⁇ L was injected into a decapitated silkworm, and the innate immunity activation activity was measured by muscle contraction.
- Example 1 The results of Example 1 and Comparative Examples 1 to 3 are shown in Table 1.
- C value 0.15 is defined as 1 (U) unit.
- the lactic acid bacteria of Comparative Examples 1 to 3 are lactic acid bacteria that are actually used in the production of commercially available fermented milk. As shown in Table 1, it was found that the lactic acid bacteria of Example 1 had higher innate immunity activation ability than Comparative Examples 1 to 3. Since the 11 / 19-B1 strain and its killed bacteria have a high ability to activate innate immunity, the 11 / 19-B1 strain is a producer of “food and drinks such as fermented milk” that activates innate immunity. It was suggested that it was promising.
- the 11 / 19-B1 strain has many similarities to the existing Lactococcus lactis in terms of sugar fermentability and chemical properties, and Lactococcus lactis sspssp in the analysis by bacteria 944 strain api web v5.1 database (Sysmex Biomelieu). It is completely different in that it shows 77.2% identity with lactis 1 and 21.9% identity with Lactobacillus brevis 1. This is a significant difference from existing strains. The possibility of Lactobacillus brevis is excluded because the gram-stained image of the 11 / 19-B1 strain is a gram-positive cocci. Therefore, from the above results, the 11 / 19-B1 strain was determined to be a novel microorganism belonging to the genus Lactococcus.
- Example 2 ⁇ Manufacture of innate immunity activation agent> ⁇ Tablet >> The cultured 11 / 19-B1 strain was sterilized at 121 ° C. for 20 minutes and then concentrated. After uniformly mixing the concentrated culture solution of 11 / 19-B1 strain 20.0 mg, lactose 40 mg, starch 20 mg, and low-substituted hydroxypropylcellulose 5 mg, hydroxypropylmethylcellulose 8 mass% aqueous solution was used as a binder. Granules for tableting were produced by a wet granulation method. To this, 0.5 mg to 1 mg of magnesium stearate necessary for providing lubricity was added, and then tableted using a tableting machine to obtain tablets.
- ⁇ Liquid 10.0 mg of the concentrated culture solution of 11 / 19-B1 strain was dissolved in 10 mL of a 2% by mass 2-hydroxypropyl- ⁇ -cyclodextrin aqueous solution to prepare an injection solution.
- Example 3 Manufacture of fermented milk> The milk was sterilized at 95 ° C. for 5 minutes, cooled to 40 ° C., and 0.001 part by mass of 11 / 19-B1 strain was added. And it fermented at 37 degreeC and 72 hours, and fermented milk was obtained. After cooling this fermented milk at 10 degrees C or less, the flavor and physical property were confirmed. As a result, both flavor and physical properties were extremely good.
- Example 4 Provides ⁇ Probiotic effect of 11 / 19-B1 yogurt>
- antibacterial activity was not observed in the culture solution of the 11 / 19-B1 strain, the culture supernatant, and the yogurt produced using the 11 / 19-B1 strain (not shown).
- the probiotic effect of yogurt produced using the 11 / 19-B1 strain was verified.
- ⁇ Verification method The silkworms were infected with a diet containing 11 / 19-B1 yogurt or a normal diet as a control overnight, and then the silkworms were infected with the fungus. Artificial feed silk mate 2S (Nippon Agricultural Industries) was used as a normal bait.
- the “bait containing 11 / 19-B1 yogurt” is a bait obtained by mixing 11 / 19-B1 yogurt with normal bait.
- the total number of silkworms per group was 7, and the viability was determined 2 days after inoculation with Pseudomonas aeruginosa or methicillin-sensitive Staphylococcus aureus, and the LD 50 (50% half lethal dose) was calculated from the survival curve.
- FIG. 1 the vertical axis represents the survival rate (Survival%), and the horizontal axis represents the dose dependency of bacteria in the survival rate 2 days after infection (OD 600 ).
- Example 5 Comparison of effects of 11 / 19-B1 yogurt and 11 / 19-B1 live powder in silkworm Pseudomonas aeruginosa infection model> Next, we examined the factors that showed a strong effect when infected with Pseudomonas aeruginosa.
- the 11 / 19-B1 strain was cultured on a 10-liter scale to produce viable powder.
- the produced viable powder is abbreviated as “11 / 19-B1 viable powder”.
- Example 4 In the same manner as in Example 4, a feed containing 11 / 19-B1 yogurt (8 ⁇ 10 7 cfu / g, 0.5 g / individual), 11 / 19-B1 live bacteria powder (4 ⁇ 10 8 cfu / g) g, 0.1 g / individual) or normal food was given to the silkworm overnight, and then the silkworm was infected with P. aeruginosa PAO1. The results are shown in FIG.
- Example 6 ⁇ Relationship between 11 / 19-B1 yogurt intake and LD 50 in a silkworm Pseudomonas aeruginosa infection model>
- the bait containing 6% by mass, 11% by mass, 20% by mass, and 33% by mass of 11 / 19-B1 yogurt with respect to the entire diet, or a normal diet as a control was given to silkworms overnight, and the silkworms were infected with P. aeruginosa PAO1.
- FIG. 4B is a graph showing the correlation between the amount of yogurt food intake and the LD 50 of (P. aeruginosa PAO1).
- the vertical axis represents the LD 50 ratio ((LD 50 value when feeding containing 11 / 19-B1 yogurt) / (normal feeding without 11 / 19-B1 yogurt). LD 50 value))), and the horizontal axis represents the ratio (mass%) of yogurt to the whole bait.
- the novel lactic acid bacterium of the present invention has high innate immunity activation ability. Therefore, the innate immunity activation agent or food / beverage product which activates innate immunity using the lactic acid bacteria of this invention can be provided, and it can use widely in the food industry, the pharmaceutical industry, etc.
- SEQ ID NO: 1 is a base sequence corresponding to almost the entire length of 16S rRNA of an unknown strain belonging to the genus Lactococcus.
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Wood Science & Technology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Biotechnology (AREA)
- Zoology (AREA)
- Mycology (AREA)
- Polymers & Plastics (AREA)
- Food Science & Technology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Biomedical Technology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Virology (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Nutrition Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
Description
ヒト等の高等な脊椎動物においても、感染初期の抵抗性、癌や生活習慣病の予防、組織修復等の観点からは、感染源に特異的な獲得免疫よりも、非特異的な自然免疫の方がより重要な位置を占めていると考えられる。
以下、この発明の態様を「態様1」とする。
以下、この発明の態様を「態様2」とする。
以下、この発明の態様を「態様3」とする。
以下、この発明の態様を「態様4」とする。
更には、該乳酸菌を有効成分とする自然免疫活性化剤、及び、該乳酸菌又は該自然免疫活性化剤を含有する飲食品を提供することができる。
これらの菌は院内感染を引き起こす原因菌であり、該発酵乳を食用することにより、これらの菌による感染を予防又は治療することができる。
本発明の態様1は、独立行政法人製品評価技術基盤機構(NITE)の特許微生物寄託センター(NPMD)における受領番号がNITE ABP-01694であるラクトコッカス(Lactococcus)属に属する乳酸菌である。
形態:本11/19-B1株は、グラム陽性の桿菌であり、鞭毛は認められず、運動性がない。本株は、果実を分離源として分離された。
(1)GAM及びMRS寒天培地上では白色のコロニーを形成する。拡散性の色素は認められない。
(2)炭酸カルシウム入りMRS寒天培地上では乳酸の生成に伴う透明帯の形成が認められる。
(1)酸素に対する態度:嫌気的
(2)カタラーゼ:-
(3)アルカリフォスファターゼ:-
(4)エステラーゼ:-
(5)エステラーゼリパーゼ:-
(6)リパーゼ:-
(7)ロイシンアリルアミダーゼ:-
(8)バリンアリルアミダーゼ:-
(9)シスチンアリルアミダーゼ:-
(10)トリプシン:-
(11)α-キモトリプシン:-
(12)酸性フォスファターゼ:+
(13)ナフトール-AS-BI-フォスフォヒトロラーゼ:+
(14)α-ガラクトシダーゼ:-
(15)β-ガラクトシダーゼ:-
(16)β-グルクロニダーゼ:-
(17)α-グルコシダーゼ:-
(18)β-グルコシダーゼ:-
(19)N-アセチル-β-グルコサミニダーゼ:-
(20)α-マンノシダーゼ:-
(21)α-フコシダーゼ:-
グリセロール(Glycerol):-
エリトリトール(Erythritol):-
D-アラビノース(D-Arabinose):-
L-アラビノース(L-Arabinose):+
D-リボース(D-Ribose):+
D-キシロース(D-Xylose):+
L-キシロース(L-Xylose):-
D-アドニトール(D-Adonitol):-
メチル-β-D-キシロピラノサイド(methyl-β-D-xylopyranoside):-
D-ガラクトース(D-Galactose):±
D-グルコース(D-Glucose):+
D-フルクトース(D-Fructose):+
D-マンノース(D-Mannose):+
L-ソルボース(D-Sorbose):-
L-ラムノース(L-Rhamnose):-
ズルシトール(Dulcitol):-
イノシトール(Inositol):-
D-マンニトール(D-Mannitol):+
D-ソルビトール(D-Sorbitol):-
メチル-α-D-マンノピラノサイド(methyl-α-D-mannopyranoside):-
メチル-α-D-グルコピラノサイド(methyl-α-D-glucopyranoside):-
N-アセチルグルコサミン(N-Acetyl glucosamine):+
アミグダリン(Amygdalin):±
アルブチン(Arbutin):+
エスクリン(Esculin):+
サリシン(Salicin):+
D-セロビオース(D-Cellobiose):-
D-マルトース(D-Maltose):+
D-ラクトース(D-Lactose):+
D-メリビオース(D-Melibiose):-
D-スクロース(D-Sucrose):+
D-トレハロース(D-Trehalose):+
インスリン(Insulin):-
D-メレジトース(D-Melezitose):-
D-ラフィノース(D-Raffinose):-
スターチ(Starch):-
グリコーゲン(Glycogen):-
キシリトール(Xylitol):-
ゲンチオビオース(Gentiobiose):+
D-ツラノース(D-Turanose):-
D-リキソース(D-Lyxose):-
D-タガトース(D-Tagatose):-
D-フコース(D-Fucose):-
L-フコース(L-Fucose):-
D-アラビトール(D-Arabitol):-
L-アラビトール(L-Arabitol):-
グルコネート(Gluconate):±
2-ケト-グルコネート(2-Keto-gluconate):-
5-ケト-グルコネート(5-Keto-gluconate):-
11/19-B1株のゲノムDNAから、PCRにより、16S rRNA領域の塩基配列を増幅し、シーケンサーによる解析を行った結果、5’末端側、3’末端側のいくつかの塩基を除く16S rRNAのほぼ全長に当たる塩基配列が見出された。この塩基配列を配列表の配列番号1に示す。配列表の配列番号1の塩基配列は、16S rRNAの全長ではないため、16S rRNA「領域」とした。
この塩基配列をNCBIのBLASTで相同性検索を行ったところ、11/19-B1株の16S rRNA領域の塩基配列は、ラクトコッカス属であるLactococcus lactis subsp.lactis IL1403、Lactococcus lactis subsp.hordniae NCDO 2181、Lactococcus lactis subsp.lactis NCDO 604株の塩基配列(NR_103918,NR_040956,NR_040955)と相同率99%を示した。しかしながら、完全には一致していないので、11/19-B1株とは異なるものである。
「11/19-B1」は、その後、千葉県木更津市かずさ鎌足2-5-8、独立行政法人製品評価技術基盤機構(NITE)の特許微生物寄託センター(NPMD)に、原寄託申請書を提出して、国内寄託(原寄託日:2013年8月20日)から、ブタペスト条約に基づく寄託への移管申請を行った(受領日:2014年10月15日、受領番号「NITE ABP-01694」)。
培養は嫌気条件下で行うことが好ましい。培地中の炭素源としては、例えば、L-アラビノース、D-リボース、D-キシロース、D-ガラクトース、D-マンノース、D-マンニトール、N-アセチルグルコサミン、アミグダリン、アルブチン、エスクリン、サリシン、D-セロビオース、D-マルトース、D-ラクトース、D-トレハロース、ゲンチオビオース、グルコネート、D-グルコース、D-フラクトース、シュクロース、糖蜜、水飴、油脂類等の有機炭素化合物が用いられ、窒素源としては、肉エキス、カゼイン、ペプトン、酵母エキス、乾燥酵母、胚芽、大豆粉、尿素、アミノ酸、アンモニウム塩等の有機・無機窒素化合物を用いることができる。
また、塩類は、ナトリウム塩、カリウム塩、カルシウム塩、マグネシウム塩、リン酸塩、鉄塩、銅塩、亜鉛塩、コバルト塩等の無機塩類を必要に応じて適宜添加する。更に、ビオチン、ビタミンB1、シスチン、オレイン酸メチル、ラード油等の生育促進物質を添加することが、目的物の産生量を増加させる点で好ましい。
また、シリコン油、界面活性剤等の消泡剤を添加してもよい。調製済みの培地としては、例えば、MRS培地、GAM培地等を用いることが好ましい。
本発明の態様2は、態様1の乳酸菌、該乳酸菌の死菌、又は、該乳酸菌の処理物を有効成分とする自然免疫活性化剤であって、
上記乳酸菌の処理物は、乳酸菌の培養物、濃縮物、ペースト化物、噴霧乾燥物、凍結乾燥物、真空乾燥物、ドラム乾燥物等の乾燥物、液状化物、希釈物、破砕物、殺菌加工物及び該培養物からの抽出物よりなる群から選ばれる少なくとも1つの処理物であることを特徴とする自然免疫活性化剤である。
すなわち、本発明の態様2は、態様1の乳酸菌、該乳酸菌の死菌、又は、該乳酸菌の処理物を有効成分とする自然免疫活性化剤である。
本発明の自然免疫活性化剤に用いられる乳酸菌の処理物としては、具体的には、例えば、乳酸菌の培養物;濃縮物;ペースト化物;噴霧乾燥物、凍結乾燥物、真空乾燥物、ドラム乾燥物等の乾燥物;液状化物;希釈物;破砕物;殺菌加工物;該培養物からの抽出物;等が挙げられる。
また、殺菌、すなわち、加熱殺菌処理、放射線殺菌処理、破砕処理等を施した死菌であってもよい。
かかる担体としては、特に制限はなく、例えば、後述する剤型等に応じて適宜選択することができる。また、前記自然免疫活性化剤中の前記「その他の成分」の含有量としても、特に制限はなく、目的に応じて適宜選択することができる。
具体的には、例えば、経口固形剤(錠剤、被覆錠剤、顆粒剤、散剤、カプセル剤等)、経口液剤(内服液剤、シロップ剤、エリキシル剤等)、注射剤(溶剤、懸濁剤等)、軟膏剤、貼付剤、ゲル剤、クリーム剤、外用散剤、スプレー剤、吸入散布剤等が挙げられる。
前記賦形剤としては、例えば、乳糖、白糖、塩化ナトリウム、ブドウ糖、デンプン、炭酸カルシウム、カオリン、微結晶セルロース、珪酸等が挙げられる。
前記結合剤としては、例えば、水、エタノール、プロパノール、単シロップ、ブドウ糖液、デンプン液、ゼラチン液、カルボキシメチルセルロース、ヒドロキシプロピルセルロース、ヒドロキシプロピルスターチ、メチルセルロース、エチルセルロース、シェラック、リン酸カルシウム、ポリビニルピロリドン等が挙げられる。
前記崩壊剤としては、例えば、乾燥デンプン、アルギン酸ナトリウム、カンテン末、炭酸水素ナトリウム、炭酸カルシウム、ラウリル硫酸ナトリウム、ステアリン酸モノグリセリド、乳糖等が挙げられる。
前記滑沢剤としては、例えば、精製タルク、ステアリン酸塩、ホウ砂、ポリエチレングリコール等が挙げられる。
前記着色剤としては、例えば、酸化チタン、酸化鉄等が挙げられる。
前記矯味・矯臭剤としては、例えば、白糖、橙皮、クエン酸、酒石酸等が挙げられる。
前記矯味・矯臭剤としては、例えば、白糖、橙皮、クエン酸、酒石酸等が挙げられる。前記緩衝剤としては、例えば、クエン酸ナトリウム等が挙げられる。前記安定化剤としては、例えば、トラガント、アラビアゴム、ゼラチン等が挙げられる。
前記pH調節剤及び前記緩衝剤としては、例えば、クエン酸ナトリウム、酢酸ナトリウム、リン酸ナトリウム等が挙げられる。前記安定化剤としては、例えば、ピロ亜硫酸ナトリウム、EDTA、チオグリコール酸、チオ乳酸等が挙げられる。前記等張化剤としては、例えば、塩化ナトリウム、ブドウ糖等が挙げられる。前記局所麻酔剤としては、例えば、塩酸プロカイン、塩酸リドカイン等が挙げられる。
前記基剤としては、例えば、流動パラフィン、白色ワセリン、サラシミツロウ、オクチルドデシルアルコール、パラフィン等が挙げられる。前記保存剤としては、例えば、パラオキシ安息香酸メチル、パラオキシ安息香酸エチル、パラオキシ安息香酸プロピル等が挙げられる。
また、前記自然免疫活性化剤の投与量としては、特に制限はなく、投与対象である個体の年齢、体重、所望の効果の程度等に応じて適宜選択することができるが、例えば、成人への1日の投与量は、有効成分の量として、1mg~30gが好ましく、10mg~10gがより好ましく、100mg~3gが特に好ましい。
また、前記自然免疫活性化剤の投与時期としても、特に制限はなく、目的に応じて適宜選択することができ、例えば、予防的に投与されてもよいし、治療的に投与されてもよい。
本発明の態様3は、上記本発明の乳酸菌又は上記本発明の自然免疫活性化剤を含有する飲食品である。
本発明の飲食品は、本発明の態様2の自然免疫活性化剤に加えて、更に、「その他の成分」を含有することができる。
これらの飲食品の製造方法としては、特に制限はなく、例えば、通常の各種飲食品の製造方法に応じて、適宜製造することができる。
況や、自然界では、上記11/19-B1株と乳とが接触することはなく、上記菌株が飲食品として存在することもないので、本発明の発酵乳と飲食品は自然界に存在していたことはなく、従ってこれらは何れも自然産物には該当しない。
乳酸菌スターターとして本発明の乳酸菌を用いて発酵を行う場合、本発明の乳酸菌の培養条件と同様の条件等で行うことができる。
本発明の態様4は、上記本発明の乳酸菌を含有する発酵乳であり、該発酵乳は、メチシリン感受性黄色ブドウ球菌、メチシリン耐性黄色ブドウ球菌、緑膿菌、及び、エンテロコッカス・ムンディディからなる群から選ばれる少なくとも1つの菌に対して抵抗性を有することを特徴とする発酵乳である。
上記発酵乳は、メチシリン感受性黄色ブドウ球菌、メチシリン耐性黄色ブドウ球菌、緑膿菌、及び、エンテロコッカス・ムンディディによる感染の予防又は治療に用いられることが好ましく、特に緑膿菌感染の予防又は治療に用いられることが好ましい。
「11/19-B1」は、その後、千葉県木更津市かずさ鎌足2-5-8、独立行政法人製品評価技術基盤機構(NITE)の特許微生物寄託センター(NPMD)に、原寄託申請書を提出して、国内寄託(原寄託日:2013年8月20日)から、ブタペスト条約に基づく寄託への移管申請を行った(受領日:2014年10月15日、受領番号「NITE ABP-01694」)。
<自然免疫活性化活性の測定>
GAM培地で一晩培養した11/19-B1株を、121℃、20分で滅菌処理後、50μLを5齢カイコの断頭筋肉標本に注射し、緩行性筋収縮により自然免疫活性化活性を測定した。
緩行性筋収縮による自然免疫活性化活性の測定は、Ishii K.,Hamamoto H., Kamimura M., Sekimizu K., J.Biol.Chem. Jan.25;283(4):2185-91(2008)に記載の方法に従って行った。
すなわち、5齢カイコの断頭筋肉標本に、上記試料0.05mLを血液内投与し、C値が最大となったとき(約10分後)に体長を測定して、注射前の体長から注射後の体長を引き算し、その値を注射前の体長で割り算した値であるC値(Contraction Value)を測定した。
GAM培地で一晩培養した培養したラクトバチルス・ブルガリクス OLL1073株を、121℃、20分で滅菌処理後、50μLを断頭カイコに注射し、筋収縮により自然免疫活性化活性を測定した。
GAM培地で一晩培養した培養したラクトバチルス・カゼイ YIT9029株を、121℃、20分で滅菌処理後、50μLを断頭カイコに注射し、筋収縮により自然免疫活性化活性を測定した。
GAM培地で一晩培養した培養したラクトコッカス・ラクティス JCM5805株を、121℃、20分で滅菌処理後、50μLを断頭カイコに注射し、筋収縮により自然免疫活性化活性を測定した。
表1に示されるように、実施例1の乳酸菌は、比較例1~3に比べてより高い自然免疫活性化能を有することが分かった。
11/19-B1株、及び、その死菌は、自然免疫活性化能が高いことから、11/19-B1株は、自然免疫を活性化させる「発酵乳等の飲食品」の生産菌として有望であることが示唆された。
<16S rRNA解析>
11/19-B1株の16S rDNAの塩基をゲノムDNAからPCR法によって増幅し、増幅できたDNA断片についてシーケンサーによって解析し、5’末端側、3’末端側のいくつかの塩基を除く配列番号1に示すほぼ16S rRNA領域全長に相当する塩基配列を決定した。
この塩基配列を元に、NCBIのBLASTを用いて既存の菌株との相同性検索を行った。その結果、11/19-B1株は、既存のLactococcus lactis IL1403株と99%の相同性を示したことから、ラクトコッカス(Lactococcus)属に属する微生物であると考えられた。
11/19-B1株は、糖の発酵能と化学的性質について既存のLactococcus lactisに相似する点が多く、細菌944株のapi web v5.1 database(シスメックス・ビオメリュー)による解析では、Lactococcus lactis ssp lactis 1と77.2%の同一性を示し、Lactobacillus brevis 1と21.9%の同一性を示した点で全く異なっている。この点は、既存の菌株との大きな相違点である。尚、Lactobacillus brevisである可能性は11/19-B1株のグラム染色像がグラム陽性球菌であることから排除される。よって、以上の結果から、11/19-B1株は、ラクトコッカス(Lactococcus)属に属する新規な微生物であると判定した。
<自然免疫活性化剤の製造>
<<錠剤>>
培養した11/19-B1株を、121℃、20分で滅菌処理後、濃縮した。該濃縮させた11/19-B1株の培養液20.0mg、ラクトース40mg、デンプン20mg、及び、低置換度ヒドロキシプロピルセルロース5mgを均一に混合した後、ヒドロキシプロピルメチルセルロース8質量%水溶液を結合剤として湿式造粒法で打錠用顆粒を製造した。これに、滑沢性を与えるのに必要なステアリン酸マグネシウムを0.5mg~1mg加えてから打錠機を用いて打錠し、錠剤とした。
上記濃縮させた11/19-B1株の培養液10.0mgを、2質量%の2-ヒドロキシプロピル-β-サイクロデキストリン水溶液10mLに溶解し、注射用液剤とした。
<発酵乳の製造>
牛乳を95℃で5分間殺菌した後、40℃に冷却し、11/19-B1株を0.001質量部加えた。そして、37℃、72時間で発酵して、発酵乳を得た。該発酵乳を10℃以下で冷却してから、風味と物性を確認した。
その結果、風味と物性は何れも極めて良好であった。
<11/19-B1ヨーグルトのプロバイオティクス効果>
生体外の実験では、11/19-B1株の培養液、培養上清、及び、11/19-B1株を用いて製造されたヨーグルトには抗菌活性が見られなかった(図示せず)。
11/19-B1株を用いて製造されたヨーグルトのプロバイオティクス効果(生菌を利用して腸内バランスを改善し、抵抗力や免疫力を高める効果)を検証した。
LB培地で一晩培養した緑膿菌(Pseudomonas aeruginosa PAO1)又はメチシリン感受性黄色ブドウ球菌(Staphylococcus aureus MSSA1)の培養液を、滅菌した0.9質量%NaCl溶液で希釈し、5齢2日目のカイコ幼虫(平均体重2g)に50μLずつ血液内注射した。
乳酸菌(11/19-B1株)末50mgを生理食塩水(滅菌済み0.9質量%NaCl溶液)1mLに懸濁し、懸濁液50μLを、0.267質量%グルコース及び0.025質量%カザミノ酸を含む牛乳200mL中に混ぜ、滅菌したガラス瓶中で、37℃、3日間保温した。以下、作製したヨーグルトを、「11/19-B1ヨーグルト」と略記する。
11/19-B1ヨーグルトを含有する餌、又は、対照として通常の餌をカイコに一晩与えた後、カイコに菌を感染させた。通常の餌として、人工飼料シルクメイト2S(日本農産工業)を用いた。ここで、「11/19-B1ヨーグルトを含有する餌」とは、通常の餌に、11/19-B1ヨーグルトを混合させた餌である。
1群当たりのカイコの総数は7匹とし、緑膿菌又はメチシリン感受性黄色ブドウ球菌の接種2日後に生死を判定し、生存曲線からLD50(50%半数致死量)を算出した。ネガティブコントロールには0.9質量%NaCl溶液を用いた。結果を図1に示す。
図1中、縦軸は生存率(Survival%)、横軸は感染2日後の生存率における菌の用量依存性を表す(OD600)。
<カイコ緑膿菌感染モデルでの11/19-B1ヨーグルト及び11/19-B1生菌粉末の効果の比較>
次に、緑膿菌を感染させたときに強い効果を示した要因を検証した。
10リットルスケールで11/19-B1株を培養し、生菌粉末を作製した。以下、作製した生菌粉末を、「11/19-B1生菌粉末」と略記する。
実施例4と同様の手法により、11/19-B1ヨーグルト(8×107 cfu/g、0.5g/個体)を含有する餌、11/19-B1生菌粉末(4×108 cfu/g、0.1g/個体)を含有する餌、又は、通常の餌をカイコに一晩与えた後、カイコに緑膿菌(P.aeruginosa PAO1)を感染させた。
結果を図3及び表2に示す。
また、11/19-B1ヨーグルト及び11/19-B1生菌粉末は同等の効果であったから、11/19-B1による緑膿菌感染死の予防効果は、菌自体に含まれる成分によるプロバイオティクス効果であるものではないかと示唆された。
<カイコ緑膿菌感染モデルでの11/19-B1ヨーグルト摂取量とLD50との相関性>
実施例4と同様の手法により、餌全体に対して、11/19-B1ヨーグルトを6質量%、11質量%、20質量%、33質量%をそれぞれ含有する餌、又は、対照として通常の餌をカイコに一晩与えた後、カイコに緑膿菌(P.aeruginosa PAO1)を感染させた。
Claims (9)
- 独立行政法人製品評価技術基盤機構(NITE)の特許微生物寄託センター(NPMD)における受領番号がNITE ABP-01694であるラクトコッカス(Lactococcus)属に属する乳酸菌。
- 請求項1に記載の乳酸菌又はその自然的若しくは人工的に変異した乳酸菌であって、自然免疫活性化能を有する乳酸菌。
- 配列表の配列番号1で示される16S rRNA領域の塩基配列を有する請求項1又は請求項2に記載の乳酸菌。
- 請求項1ないし請求項3の何れかの請求項に記載の乳酸菌、該乳酸菌の死菌、又は、該乳酸菌の処理物を有効成分とする自然免疫活性化剤であって、
上記乳酸菌の処理物は、乳酸菌の培養物、濃縮物、ペースト化物、乾燥物、液状化物、希釈物、破砕物、殺菌加工物、及び、該培養物からの抽出物よりなる群から選ばれる少なくとも1つの処理物であることを特徴とする自然免疫活性化剤。 - 請求項1ないし請求項3の何れかの請求項に記載の乳酸菌を含有する飲食品。
- 請求項4に記載の自然免疫活性化剤を含有する飲食品。
- 請求項1ないし請求項3の何れかの請求項に記載の乳酸菌を用いて発酵する工程を用いて製造された飲食品。
- 上記飲食品が発酵乳である請求項7に記載の飲食品。
- 請求項1ないし請求項3の何れかの請求項に記載の乳酸菌を含有する発酵乳であり、
該発酵乳は、メチシリン感受性黄色ブドウ球菌、メチシリン耐性黄色ブドウ球菌、緑膿菌、及び、エンテロコッカス・ムンディディからなる群から選ばれる少なくとも1つの菌に対して抵抗性を有することを特徴とする発酵乳。
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201480054895.5A CN105637084B (zh) | 2013-10-17 | 2014-10-17 | 新型乳酸菌、以新型乳酸菌作为有效成分的天然免疫活化剂以及含有新型乳酸菌的饮食品 |
KR1020167009994A KR102267879B1 (ko) | 2013-10-17 | 2014-10-17 | 신규 유산균, 신규 유산균을 유효 성분으로 하는 자연 면역 활성화제, 및 신규 유산균을 함유하는 음식품 |
JP2015542676A JP6505018B2 (ja) | 2013-10-17 | 2014-10-17 | 新規乳酸菌、新規乳酸菌を有効成分とする自然免疫活性化剤、及び新規乳酸菌を含有する飲食品 |
HK16107430.5A HK1219501A1 (zh) | 2013-10-17 | 2016-06-26 | 新型乳酸菌、以新型乳酸菌作為有效成分的天然免疫活化劑以及含有新型乳酸菌的飲食品 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2013216517 | 2013-10-17 | ||
JP2013-216517 | 2013-10-17 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2015056770A1 true WO2015056770A1 (ja) | 2015-04-23 |
Family
ID=52828209
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2014/077652 WO2015056770A1 (ja) | 2013-10-17 | 2014-10-17 | 新規乳酸菌、新規乳酸菌を有効成分とする自然免疫活性化剤、及び新規乳酸菌を含有する飲食品 |
Country Status (5)
Country | Link |
---|---|
JP (1) | JP6505018B2 (ja) |
KR (1) | KR102267879B1 (ja) |
CN (1) | CN105637084B (ja) |
HK (1) | HK1219501A1 (ja) |
WO (1) | WO2015056770A1 (ja) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2018034203A1 (ja) * | 2016-08-16 | 2018-02-22 | 株式会社ゲノム創薬研究所 | 新規乳酸菌、新規乳酸菌を有効成分として含有する自然免疫活性化剤、及び新規乳酸菌を含有する飲食品 |
JP2018033334A (ja) * | 2016-08-30 | 2018-03-08 | 株式会社ゲノム創薬研究所 | 野菜又は果物ジュース中の糖濃度を減少させる方法、及び該方法を用いる乳酸菌含有野菜又は果物ジュースの製造方法 |
WO2018045534A1 (zh) * | 2016-09-08 | 2018-03-15 | 潍坊华英生物科技有限公司 | 一种增强免疫功能的静脉注射剂 |
JP2019071879A (ja) * | 2017-10-11 | 2019-05-16 | 株式会社ゲノム創薬研究所 | 乳酸醗酵ニンジンの製造方法 |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2016125861A1 (ja) * | 2015-02-06 | 2016-08-11 | 株式会社ゲノム創薬研究所 | 乳酸菌、該乳酸菌由来の自然免疫活性化剤、感染症予防治療剤及び飲食品 |
CN107802659B (zh) * | 2016-09-08 | 2020-08-25 | 潍坊华英生物科技有限公司 | 一种增强免疫功能的静脉注射剂 |
WO2020204615A1 (ko) * | 2019-04-05 | 2020-10-08 | 에스케이바이오랜드 주식회사 | 용암해수 유래 천연 미네랄 코팅 프로바이오틱스의 제조방법 및 이를 이용한 용암해수 유래 천연 미네랄 코팅 프로바이오틱스 |
KR102154254B1 (ko) * | 2020-04-29 | 2020-09-09 | (주)녹십자웰빙 | 우수한 면역기능 증진 효과를 갖는 신규한 유산균 및 이를 포함하는 식품조성물, 건강기능성 식품 조성물 및 프로바이오틱스 |
CN114196586B (zh) * | 2021-12-20 | 2023-04-11 | 郑州大学 | 一株蒙氏肠球菌及其在发酵中草药中的应用 |
Citations (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH11281625A (ja) * | 1998-03-31 | 1999-10-15 | Matsushita Electric Ind Co Ltd | 青果物の熟度測定方法 |
JP2002293780A (ja) * | 2001-03-30 | 2002-10-09 | Sakamoto Koryo Kk | キウイカテキン及びキウイカテキンの製造方法 |
JP2003047462A (ja) * | 2001-08-07 | 2003-02-18 | Yotsuba Nyugyo Kk | ケフィア粒から分離したラクトコッカス属乳酸菌とそれを用いた食品の製造法 |
JP2003088362A (ja) * | 2001-09-17 | 2003-03-25 | National Agricultural Research Organization | 免疫賦活に有用なラクトコッカス属乳酸菌 |
JP2006149320A (ja) * | 2004-11-30 | 2006-06-15 | Sato Corp | 食品開封シール |
JP2007006769A (ja) * | 2005-06-30 | 2007-01-18 | Asahi Breweries Ltd | 新規乳酸菌及び新規乳酸菌を利用した飲料 |
JP2007259729A (ja) * | 2006-03-28 | 2007-10-11 | Yotsuba Nyugyo Kk | 免疫賦活作用を有するラクトコッカス属乳酸菌と粘稠性ラクトコッカス属乳酸菌並びにこれらを併用した粘稠性を有する発酵乳の製造方法 |
JP2007327964A (ja) * | 2000-05-11 | 2007-12-20 | Genome Soyaku Kenkyusho:Kk | 獲得免疫機構を有する生物に感染する病原微生物に対し抗菌活性を有する化合物を自然免疫機構のみを有する生物を利用してスクリーニングする方法、および該抗菌活性を自然免疫機構のみを有する生物を利用して評価する方法 |
JP2008154534A (ja) * | 2006-12-25 | 2008-07-10 | Bio Tec Japan:Kk | 乳酸菌発酵米ぬかの製造方法 |
WO2008126905A1 (ja) * | 2007-04-10 | 2008-10-23 | Genome Pharmaceuticals Institute Co., Ltd. | 自然免疫機構を活性化/抑制する作用を有する物質の評価方法及びスクリーニング方法、並びに、自然免疫機構を活性化/抑制するための薬剤、食品及びそれらの製造方法 |
WO2011115114A1 (ja) * | 2010-03-19 | 2011-09-22 | 株式会社ヤクルト本社 | ラクトバチルス・プランタラムに属する新規乳酸菌およびその利用 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008126905A (ja) | 2006-11-22 | 2008-06-05 | Toyota Motor Corp | 車窓透過率制御装置 |
KR101010537B1 (ko) * | 2010-03-24 | 2011-01-24 | 주식회사 누림 | 신규한 락토바실러스 klf01 및 락토코커스 klc02 종과 이를 이용한 식물병 방제용 조성물 |
KR101599769B1 (ko) * | 2012-08-10 | 2016-03-04 | 한국생명공학연구원 | 신규한 락토코쿠스 종 균주 및 이의 용도 |
-
2014
- 2014-10-17 CN CN201480054895.5A patent/CN105637084B/zh active Active
- 2014-10-17 WO PCT/JP2014/077652 patent/WO2015056770A1/ja active Application Filing
- 2014-10-17 JP JP2015542676A patent/JP6505018B2/ja active Active
- 2014-10-17 KR KR1020167009994A patent/KR102267879B1/ko active IP Right Grant
-
2016
- 2016-06-26 HK HK16107430.5A patent/HK1219501A1/zh unknown
Patent Citations (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH11281625A (ja) * | 1998-03-31 | 1999-10-15 | Matsushita Electric Ind Co Ltd | 青果物の熟度測定方法 |
JP2007327964A (ja) * | 2000-05-11 | 2007-12-20 | Genome Soyaku Kenkyusho:Kk | 獲得免疫機構を有する生物に感染する病原微生物に対し抗菌活性を有する化合物を自然免疫機構のみを有する生物を利用してスクリーニングする方法、および該抗菌活性を自然免疫機構のみを有する生物を利用して評価する方法 |
JP2002293780A (ja) * | 2001-03-30 | 2002-10-09 | Sakamoto Koryo Kk | キウイカテキン及びキウイカテキンの製造方法 |
JP2003047462A (ja) * | 2001-08-07 | 2003-02-18 | Yotsuba Nyugyo Kk | ケフィア粒から分離したラクトコッカス属乳酸菌とそれを用いた食品の製造法 |
JP2003088362A (ja) * | 2001-09-17 | 2003-03-25 | National Agricultural Research Organization | 免疫賦活に有用なラクトコッカス属乳酸菌 |
JP2006149320A (ja) * | 2004-11-30 | 2006-06-15 | Sato Corp | 食品開封シール |
JP2007006769A (ja) * | 2005-06-30 | 2007-01-18 | Asahi Breweries Ltd | 新規乳酸菌及び新規乳酸菌を利用した飲料 |
JP2007259729A (ja) * | 2006-03-28 | 2007-10-11 | Yotsuba Nyugyo Kk | 免疫賦活作用を有するラクトコッカス属乳酸菌と粘稠性ラクトコッカス属乳酸菌並びにこれらを併用した粘稠性を有する発酵乳の製造方法 |
JP2008154534A (ja) * | 2006-12-25 | 2008-07-10 | Bio Tec Japan:Kk | 乳酸菌発酵米ぬかの製造方法 |
WO2008126905A1 (ja) * | 2007-04-10 | 2008-10-23 | Genome Pharmaceuticals Institute Co., Ltd. | 自然免疫機構を活性化/抑制する作用を有する物質の評価方法及びスクリーニング方法、並びに、自然免疫機構を活性化/抑制するための薬剤、食品及びそれらの製造方法 |
WO2011115114A1 (ja) * | 2010-03-19 | 2011-09-22 | 株式会社ヤクルト本社 | ラクトバチルス・プランタラムに属する新規乳酸菌およびその利用 |
Non-Patent Citations (7)
Title |
---|
"Kiwi Nyusankin Yogurt Todai Kyoju ra Kaihatsu Men'ekiryoku Up = Fukushima", YOMIURI SHINBUN, 30 May 2014 (2014-05-30) * |
"Shizen Men'eki Kasseikano ga Takai Nyusankin + Fukushima-Ken San Gyunyu Yogurt Tanjo/ Tohoku Kyodo Nyugyo ga Hanbai Net de Raigetsu kara", THE JAPAN AGRICULTURAL NEWS, 27 November 2014 (2014-11-27) * |
"Tohoku Kyodo Nyugyo ga Shinseihin Yogurt Kaihatsu Todai Daigakuin Kyoju to Kyodo de", FUKUSHIMA MINPOSHA FACEBOOK, 29 May 2014 (2014-05-29), Retrieved from the Internet <URL:https://www.facebook.com/permalink.php?story_fbid=771541649543298&id=187705544593581> [retrieved on 20150109] * |
DATABASE GENBANK 10 April 2011 (2011-04-10), accession no. Q721275 * |
DATABASE GENBANK 5 August 2009 (2009-08-05), accession no. Q337868 * |
ISHII, K. ET AL.: "Activation of the silkworm cytokine by bacterial and fungal cell wall components via a reactive oxygen Species- triggered mechanism", J. BIOL. CHEM., vol. 283, no. 4, 2008, pages 2185 - 2191, XP008117802, doi:10.1074/jbc.M705480200 * |
SATOSHI NISHIDA: "Shizen Men'eki o Kasseika suru Nyusankin ni yoru Kansensho Yobo", DAI 62 KAI THE JAPANESE ASSOCIATION FOR INFECTIOUS DISEASES HIGASHINIHON CHIHOKAI GAKUJUTSU SHUKAI, DAI 60 KAI JAPANESE SOCIETY OF CHEMOTHERAPY HIGASHINIHON SHIBU SOKAI GODO GAKKAI PROGRAM SHOROKUSHU, vol. 76, 7 October 2013 (2013-10-07), pages 8 - 4 * |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2018034203A1 (ja) * | 2016-08-16 | 2018-02-22 | 株式会社ゲノム創薬研究所 | 新規乳酸菌、新規乳酸菌を有効成分として含有する自然免疫活性化剤、及び新規乳酸菌を含有する飲食品 |
JP2018033334A (ja) * | 2016-08-30 | 2018-03-08 | 株式会社ゲノム創薬研究所 | 野菜又は果物ジュース中の糖濃度を減少させる方法、及び該方法を用いる乳酸菌含有野菜又は果物ジュースの製造方法 |
WO2018045534A1 (zh) * | 2016-09-08 | 2018-03-15 | 潍坊华英生物科技有限公司 | 一种增强免疫功能的静脉注射剂 |
RU2746084C2 (ru) * | 2016-09-08 | 2021-04-06 | Вэйфан Хуаин Байотекнолоджи Ко., Лтд. | Состав для внутривенных инъекций, предназначенный для повышения иммунитета |
US11213555B2 (en) | 2016-09-08 | 2022-01-04 | Weifang Huaying Biotechnology Co., Ltd. | Intravenous injection for enhancing immune function |
JP2019071879A (ja) * | 2017-10-11 | 2019-05-16 | 株式会社ゲノム創薬研究所 | 乳酸醗酵ニンジンの製造方法 |
JP7267536B2 (ja) | 2017-10-11 | 2023-05-02 | 株式会社ゲノム創薬研究所 | 乳酸醗酵ニンジンの製造方法 |
Also Published As
Publication number | Publication date |
---|---|
HK1219501A1 (zh) | 2017-04-07 |
KR20160060676A (ko) | 2016-05-30 |
KR102267879B1 (ko) | 2021-06-21 |
CN105637084B (zh) | 2019-08-06 |
JPWO2015056770A1 (ja) | 2017-03-09 |
JP6505018B2 (ja) | 2019-04-24 |
CN105637084A (zh) | 2016-06-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6505018B2 (ja) | 新規乳酸菌、新規乳酸菌を有効成分とする自然免疫活性化剤、及び新規乳酸菌を含有する飲食品 | |
US10653730B2 (en) | Lactic acid bacterium, drug, food or drink, and feed which contain the lactic acid bacterium | |
JP6594911B2 (ja) | 乳酸菌、該乳酸菌由来の自然免疫活性化剤、感染症予防治療剤及び飲食品 | |
US11241463B2 (en) | Lactic acid bacterium, drug, food or drink, and feed which contain the lactic acid bacterium | |
JP7090288B2 (ja) | 新規乳酸菌、新規乳酸菌を有効成分として含有する自然免疫活性化剤、及び新規乳酸菌を含有する飲食品 | |
JP7054111B2 (ja) | 乳酸菌、該乳酸菌由来の血糖低下剤、糖尿病治療薬、及び飲食品 | |
JP6675703B1 (ja) | 乳酸菌、該乳酸菌由来の自然免疫活性化剤、感染症予防・治療薬及び飲食品 | |
JP7261867B2 (ja) | 骨格筋遅筋化用組成物 | |
JP6588509B2 (ja) | 乳酸菌を有効成分として含有する抗真菌剤 | |
WO2024090414A1 (ja) | 乳酸菌、該乳酸菌由来の自然免疫活性化剤及び該乳酸菌を含有する食品 | |
WO2024090415A1 (ja) | 乳酸菌、該乳酸菌由来の自然免疫活性化剤及び該乳酸菌を含有する食品 | |
WO2024090413A1 (ja) | 乳酸菌、該乳酸菌由来の自然免疫活性化剤及び該乳酸菌を含有する食品 | |
RU2412239C2 (ru) | ШТАММ Lactobacillus fermentum Z, ИСПОЛЬЗУЕМЫЙ ДЛЯ ПРОИЗВОДСТВА ПРОБИОТИЧЕСКИХ МОЛОЧНОКИСЛЫХ ПРОДУКТОВ | |
WO2022185419A1 (ja) | 新規乳酸菌株、及び新規乳酸菌株を含有する組成物 | |
Avci et al. | Determination of fundamental probiotic properties of Lactobacillus strains isolated from Turkish local yogurt | |
Spagna et al. | Angela Ribbera |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 14854288 Country of ref document: EP Kind code of ref document: A1 |
|
ENP | Entry into the national phase |
Ref document number: 2015542676 Country of ref document: JP Kind code of ref document: A |
|
ENP | Entry into the national phase |
Ref document number: 20167009994 Country of ref document: KR Kind code of ref document: A |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 14854288 Country of ref document: EP Kind code of ref document: A1 |