JP2021101645A - Composition for regulating immune balance - Google Patents
Composition for regulating immune balance Download PDFInfo
- Publication number
- JP2021101645A JP2021101645A JP2019234183A JP2019234183A JP2021101645A JP 2021101645 A JP2021101645 A JP 2021101645A JP 2019234183 A JP2019234183 A JP 2019234183A JP 2019234183 A JP2019234183 A JP 2019234183A JP 2021101645 A JP2021101645 A JP 2021101645A
- Authority
- JP
- Japan
- Prior art keywords
- lactic acid
- composition
- production
- immune balance
- eps
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 77
- 230000001105 regulatory effect Effects 0.000 title claims abstract description 24
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims abstract description 128
- 241000894006 Bacteria Species 0.000 claims abstract description 66
- 229920002444 Exopolysaccharide Polymers 0.000 claims abstract description 64
- 239000004310 lactic acid Substances 0.000 claims abstract description 64
- 235000014655 lactic acid Nutrition 0.000 claims abstract description 64
- 238000004519 manufacturing process Methods 0.000 claims abstract description 35
- 102100037850 Interferon gamma Human genes 0.000 claims abstract description 23
- 108010074328 Interferon-gamma Proteins 0.000 claims abstract description 23
- 108090000978 Interleukin-4 Proteins 0.000 claims abstract description 21
- 230000001965 increasing effect Effects 0.000 claims abstract description 18
- 102000003814 Interleukin-10 Human genes 0.000 claims abstract description 17
- 108090000174 Interleukin-10 Proteins 0.000 claims abstract description 17
- 239000004480 active ingredient Substances 0.000 claims abstract description 16
- 102000013691 Interleukin-17 Human genes 0.000 claims description 26
- 108050003558 Interleukin-17 Proteins 0.000 claims description 26
- 235000015140 cultured milk Nutrition 0.000 claims description 11
- 241000186660 Lactobacillus Species 0.000 claims description 10
- 229940039696 lactobacillus Drugs 0.000 claims description 10
- 230000033228 biological regulation Effects 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 6
- 230000024949 interleukin-17 production Effects 0.000 abstract description 4
- 239000000126 substance Substances 0.000 abstract description 4
- 239000000463 material Substances 0.000 abstract 1
- 235000013305 food Nutrition 0.000 description 33
- 239000000047 product Substances 0.000 description 18
- 229920001282 polysaccharide Polymers 0.000 description 12
- 239000005017 polysaccharide Substances 0.000 description 12
- 150000004804 polysaccharides Chemical class 0.000 description 12
- 239000000427 antigen Substances 0.000 description 10
- 102000036639 antigens Human genes 0.000 description 10
- 108091007433 antigens Proteins 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 10
- 102000004127 Cytokines Human genes 0.000 description 9
- 108090000695 Cytokines Proteins 0.000 description 9
- 239000007788 liquid Substances 0.000 description 9
- 239000003826 tablet Substances 0.000 description 8
- 208000023275 Autoimmune disease Diseases 0.000 description 7
- 206010047115 Vasculitis Diseases 0.000 description 7
- 235000013361 beverage Nutrition 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 108090000765 processed proteins & peptides Proteins 0.000 description 7
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 230000002708 enhancing effect Effects 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 241000186673 Lactobacillus delbrueckii Species 0.000 description 5
- 230000009471 action Effects 0.000 description 5
- 238000000855 fermentation Methods 0.000 description 5
- 230000004151 fermentation Effects 0.000 description 5
- 235000013376 functional food Nutrition 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 102000004388 Interleukin-4 Human genes 0.000 description 4
- 208000026935 allergic disease Diseases 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 201000001981 dermatomyositis Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 235000013402 health food Nutrition 0.000 description 4
- 235000013336 milk Nutrition 0.000 description 4
- 239000008267 milk Substances 0.000 description 4
- 210000004080 milk Anatomy 0.000 description 4
- -1 pH regulators Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 241000894007 species Species 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 241000186000 Bifidobacterium Species 0.000 description 3
- 241000792859 Enema Species 0.000 description 3
- 208000009386 Experimental Arthritis Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000000654 additive Substances 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
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 235000008504 concentrate Nutrition 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 235000013365 dairy product Nutrition 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 235000015872 dietary supplement Nutrition 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000007920 enema Substances 0.000 description 3
- 229940095399 enema Drugs 0.000 description 3
- 230000037406 food intake Effects 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 230000028993 immune response Effects 0.000 description 3
- 208000026278 immune system disease Diseases 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 238000002372 labelling Methods 0.000 description 3
- 235000012054 meals Nutrition 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 235000016709 nutrition Nutrition 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 239000013589 supplement Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 235000013618 yogurt Nutrition 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- GUBGYTABKSRVRQ-PICCSMPSSA-N D-Maltose 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-PICCSMPSSA-N 0.000 description 2
- 239000004375 Dextrin Substances 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 2
- 206010014950 Eosinophilia Diseases 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 241000700721 Hepatitis B virus Species 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 241000186605 Lactobacillus paracasei Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 201000004681 Psoriasis Diseases 0.000 description 2
- 241000194020 Streptococcus thermophilus Species 0.000 description 2
- 238000000692 Student's t-test Methods 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 2
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 235000019425 dextrin Nutrition 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000002554 disease preventive effect Effects 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 235000015897 energy drink Nutrition 0.000 description 2
- 239000003889 eye drop Substances 0.000 description 2
- 229940012356 eye drops Drugs 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 229930182830 galactose Natural products 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 210000002443 helper t lymphocyte Anatomy 0.000 description 2
- 238000002649 immunization Methods 0.000 description 2
- 230000003053 immunization Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 235000021056 liquid food Nutrition 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 239000006072 paste Substances 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 208000005987 polymyositis Diseases 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 239000012264 purified product Substances 0.000 description 2
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 2
- 235000021067 refined food Nutrition 0.000 description 2
- 206010048628 rheumatoid vasculitis Diseases 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 235000014347 soups Nutrition 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 210000004989 spleen cell Anatomy 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 239000007940 sugar coated tablet Substances 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 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 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-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
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- PVXPPJIGRGXGCY-DJHAAKORSA-N 6-O-alpha-D-glucopyranosyl-alpha-D-fructofuranose 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@](O)(CO)O1 PVXPPJIGRGXGCY-DJHAAKORSA-N 0.000 description 1
- XGWFJBFNAQHLEF-UHFFFAOYSA-N 9-anthroic acid Chemical compound C1=CC=C2C(C(=O)O)=C(C=CC=C3)C3=CC2=C1 XGWFJBFNAQHLEF-UHFFFAOYSA-N 0.000 description 1
- 208000007815 Acquired Hyperostosis Syndrome Diseases 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 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 1
- 208000003343 Antiphospholipid Syndrome Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010003267 Arthritis reactive Diseases 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 241000304886 Bacilli Species 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 241000186016 Bifidobacterium bifidum Species 0.000 description 1
- 241000131482 Bifidobacterium sp. Species 0.000 description 1
- 238000011746 C57BL/6J (JAX™ mouse strain) Methods 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 208000005024 Castleman disease Diseases 0.000 description 1
- 208000034103 Castleman-Kojima disease Diseases 0.000 description 1
- 102000016938 Catalase Human genes 0.000 description 1
- 108010053835 Catalase Proteins 0.000 description 1
- 241001478240 Coccus Species 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-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
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-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
- 229920002307 Dextran Polymers 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 238000008157 ELISA kit Methods 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
- 206010016717 Fistula Diseases 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- 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 1
- 241000233866 Fungi Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 208000007514 Herpes zoster Diseases 0.000 description 1
- 229920000869 Homopolysaccharide Polymers 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 101800000324 Immunoglobulin A1 protease translocator Proteins 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 206010059176 Juvenile idiopathic arthritis Diseases 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-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
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-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
- 241000194035 Lactococcus lactis Species 0.000 description 1
- 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 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 208000005384 Pneumocystis Pneumonia Diseases 0.000 description 1
- 206010073755 Pneumocystis jirovecii pneumonia Diseases 0.000 description 1
- 206010065159 Polychondritis Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 208000002200 Respiratory Hypersensitivity Diseases 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 1
- 201000004854 SAPHO syndrome Diseases 0.000 description 1
- 206010039509 Scab Diseases 0.000 description 1
- 206010062164 Seronegative arthritis Diseases 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 201000002661 Spondylitis Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- 235000014897 Streptococcus lactis Nutrition 0.000 description 1
- 239000004376 Sucralose Substances 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 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 1
- 208000004732 Systemic Vasculitis Diseases 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 230000030429 T-helper 17 type immune response Effects 0.000 description 1
- 208000012169 TAFRO syndrome Diseases 0.000 description 1
- 210000004241 Th2 cell Anatomy 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products 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-WSWWMNSNSA-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
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- 229930003451 Vitamin B1 Natural products 0.000 description 1
- 229930003779 Vitamin B12 Natural products 0.000 description 1
- 229930003471 Vitamin B2 Natural products 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 229930003448 Vitamin K 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
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000001785 acacia senegal l. willd gum Substances 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229920001284 acidic polysaccharide Polymers 0.000 description 1
- 150000004805 acidic polysaccharides Chemical class 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 230000010085 airway hyperresponsiveness Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 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 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003367 anti-collagen effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 206010003230 arteritis Diseases 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 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 1
- 230000003796 beauty Effects 0.000 description 1
- 229940002008 bifidobacterium bifidum Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 150000001615 biotins Chemical class 0.000 description 1
- 235000015895 biscuits Nutrition 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 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
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- FDJOLVPMNUYSCM-WZHZPDAFSA-L cobalt(3+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+3].N#[C-].N([C@@H]([C@]1(C)[N-]\C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C(\C)/C1=N/C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C\C1=N\C([C@H](C1(C)C)CCC(N)=O)=C/1C)[C@@H]2CC(N)=O)=C\1[C@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]1[C@@H](O)[C@@H](N2C3=CC(C)=C(C)C=C3N=C2)O[C@@H]1CO FDJOLVPMNUYSCM-WZHZPDAFSA-L 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 235000012495 crackers Nutrition 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000008260 defense mechanism Effects 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 235000013325 dietary fiber Nutrition 0.000 description 1
- 238000007598 dipping method Methods 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 239000003221 ear drop Substances 0.000 description 1
- 229940047652 ear drops Drugs 0.000 description 1
- 239000007938 effervescent tablet Substances 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- 238000012869 ethanol precipitation Methods 0.000 description 1
- CKSJXOVLXUMMFF-UHFFFAOYSA-N exalamide Chemical compound CCCCCCOC1=CC=CC=C1C(N)=O CKSJXOVLXUMMFF-UHFFFAOYSA-N 0.000 description 1
- 229950010333 exalamide Drugs 0.000 description 1
- 238000009207 exercise therapy Methods 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000003890 fistula Effects 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 235000013611 frozen food Nutrition 0.000 description 1
- 235000015203 fruit juice Nutrition 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000004727 humoral immunity Effects 0.000 description 1
- 208000013403 hyperactivity Diseases 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 230000005934 immune activation Effects 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000008629 immune suppression Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000031261 interleukin-10 production Effects 0.000 description 1
- 230000017307 interleukin-4 production Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- 235000014705 isoleucine Nutrition 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008274 jelly Substances 0.000 description 1
- 201000002215 juvenile rheumatoid arthritis Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000005772 leucine Nutrition 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 206010063344 microscopic polyangiitis Diseases 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 150000002814 niacins Chemical class 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 230000000474 nursing effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940069265 ophthalmic ointment Drugs 0.000 description 1
- 239000006191 orally-disintegrating tablet Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 150000002948 pantothenic acids Chemical class 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 235000013550 pizza Nutrition 0.000 description 1
- 201000000317 pneumocystosis Diseases 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 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
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 208000002815 pulmonary hypertension Diseases 0.000 description 1
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 235000020185 raw untreated milk Nutrition 0.000 description 1
- 208000002574 reactive arthritis Diseases 0.000 description 1
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 210000003289 regulatory T cell Anatomy 0.000 description 1
- 230000000552 rheumatic effect Effects 0.000 description 1
- 229960002477 riboflavin Drugs 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 235000020183 skimmed milk 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
- 239000007901 soft capsule Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 210000004988 splenocyte Anatomy 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 235000019408 sucralose Nutrition 0.000 description 1
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000019635 sulfation Effects 0.000 description 1
- 238000005670 sulfation reaction Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000009885 systemic effect Effects 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
- 230000001256 tonic effect Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 229940074410 trehalose Drugs 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 235000014393 valine Nutrition 0.000 description 1
- 229940099259 vaseline Drugs 0.000 description 1
- 235000015192 vegetable juice Nutrition 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 235000010374 vitamin B1 Nutrition 0.000 description 1
- 239000011691 vitamin B1 Substances 0.000 description 1
- 235000019163 vitamin B12 Nutrition 0.000 description 1
- 239000011715 vitamin B12 Substances 0.000 description 1
- 235000019164 vitamin B2 Nutrition 0.000 description 1
- 239000011716 vitamin B2 Substances 0.000 description 1
- 235000019158 vitamin B6 Nutrition 0.000 description 1
- 239000011726 vitamin B6 Substances 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 235000019168 vitamin K Nutrition 0.000 description 1
- 239000011712 vitamin K Substances 0.000 description 1
- 150000003721 vitamin K derivatives Chemical class 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 229940011671 vitamin b6 Drugs 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- 229940046010 vitamin k Drugs 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
-
- 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
- A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
-
- 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
- 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
-
- 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
- A23V2400/00—Lactic or propionic acid bacteria
- A23V2400/11—Lactobacillus
- A23V2400/123—Bulgaricus
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Mycology (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Polymers & Plastics (AREA)
- Food Science & Technology (AREA)
- Nutrition Science (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Dairy Products (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
Description
本発明は、免疫バランスを調節するための、乳酸菌の培養物を含有する組成物に関する。 The present invention relates to a composition containing a culture of lactic acid bacteria for regulating the immune balance.
抗原を認識したヘルパーＴ細胞（Ｔｈ）は、いくつかのサイトカインを細胞外に大量に分泌することで、周囲の免疫反応を特定の方向へと導く役割を持つ。これらのＴｈにはいくつかの種類が存在する。 Helper T cells (Th) that recognize the antigen have a role of guiding the surrounding immune response in a specific direction by secreting a large amount of some cytokines extracellularly. There are several types of these Ths.
例えば、Ｔｈ１は主にＩＦＮ−γを分泌することで、免疫反応を細胞性免疫が強まる方向へと導く。具体的には、ＩＦＮ−γで刺激されたマクロファージは病原体を活発に貪食し、また細胞傷害性Ｔ細胞やＮＫ細胞などを活性化して細胞傷害活性を高める。Ｔｈ２細胞は、ＩＬ−４等を放出し、抗体産生を高める体液性免疫を亢進することで感染防御に寄与する。Ｔｒｅｇは、活性化することで炎症性疾患やアレルギーなどを引き起こす過剰な免疫反応にブレーキをかける。Ｔｈ１７は比較的新しく見つかったＴｈの一種であり、ＩＬ−１７等のサイトカインを分泌する。ＩＬ−１７は炎症性サイトカインの１種であり、その亢進は自己免疫疾患の病態形成に関与していると考えられている。Ｔｈ１７による免疫反応は細胞外細菌及び真菌からの防御機構として働く一方で、その過剰亢進は関節リウマチ、炎症性腸疾患、多発性硬化症、乾癬などの自己免疫疾患に深く関与していることが明らかになっている。 For example, Th1 mainly secretes IFN-γ to guide the immune response in the direction of strengthening cell-mediated immunity. Specifically, macrophages stimulated with IFN-γ actively phagocytose pathogens and activate cytotoxic T cells, NK cells, and the like to enhance cytotoxic activity. Th2 cells contribute to infection defense by releasing IL-4 and the like and enhancing humoral immunity that enhances antibody production. Tregs brake excessive immune responses that, when activated, cause inflammatory diseases, allergies, and the like. Th17 is a relatively newly discovered type of Th that secretes cytokines such as IL-17. IL-17 is a type of inflammatory cytokine, and its enhancement is considered to be involved in the pathogenesis of autoimmune diseases. While the Th17 immune response acts as a defense mechanism against extracellular bacteria and fungi, its hyperactivity is deeply involved in autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, and psoriasis. It has become clear.
そのため、各Ｔｈは、それぞれが産生するサイトカインによって互いの働きを抑制しあっており、正常状態において特定のＴｈの働きが亢進しないような仕組みがある。このような免疫の活性化／抑制の適切なバランス（免疫バランス）の維持は、自然および獲得免疫系の生理的機能にとって、非常に重要である。この均衡が崩れると、自己免疫疾患、過敏症、免疫不全などの免疫系疾患につながる。 Therefore, each Th suppresses each other's action by the cytokine produced by each, and there is a mechanism that the action of a specific Th is not enhanced in a normal state. Maintaining such an appropriate balance of immune activation / suppression (immune balance) is very important for the physiological function of the natural and acquired immune system. This imbalance leads to immune system disorders such as autoimmune diseases, hypersensitivity, and immunodeficiency.
アレルギー疾患や自己免疫疾患の克服を目的に、免疫制御機構を適正に機能させることに関し、いくつかの報告がある（特許文献１〜３）。また、乳酸菌に関連したものとして、特許文献４は、ラクトバチルス・パラカゼイKW3110株及びビフィドバクテリウム・ビフィダムYIT4007株の培養物の加熱後凍結乾燥物の組み合わせを経口摂取することにより、アレルギー疾患モデルマウスにおいて、肺胞への好酸球の浸潤の割合が有意に低下し、またpenh（メサコリン吸入に対する気道抵抗（気道過敏性））が低下したとの実験結果、およびコラーゲン誘導性関節炎モデルマウスにおいて抗コラーゲン抗体価が低下し、また関節炎を抑制する傾向が見られたとの実験結果に基づき、(A)ラクトバチルス・パラカゼイ（Lactobacillus paracasei）の菌体及び/又はその処理物と、(B)ビフィドバクテリウム（Bifidobacterium）属の細菌の菌体及び/又はその処理物とを含有することを特徴とする免疫バランス調節用組成物を提案する。特許文献５は、乳酸菌Streptococcus thermophilusの特定の株の培養物の殺菌後凍結乾燥物を添加することにより、TGF-βおよびIL-6で刺激したマウス脾臓細胞を用いた試験において、IFN-γの産生が促進され、かつIL-17の産生が抑制されたとの実験結果に基づき、特定の乳酸菌Streptococcus thermophilusを、IL-17産生抑制の有効成分として含有する医薬又は飲食品を提案する。特許文献６は、加熱殺菌したビフィドバクテリウム・エスピーＣＦＢ１株を培地に加えることにより、ＴＧＦ−βおよびＩＬ−６で刺激したマウス脾臓細胞において、ＩＬ−１７の産生が抑制されたとの実験結果、およびＩＦＮ−γの産生が上昇し、かつＩＬ−４の産生が減少したとの実験結果に基づき、特定のビフィドバクテリウム属微生物を含有し、ＩＬ−１７の産生を抑制し、好ましくはＩＦＮ−γの産生を促進し、かつ、ＩＬ−４の産生を抑制する飲食品を提案する。
There are several reports on the proper functioning of the immune control mechanism for the purpose of overcoming allergic diseases and autoimmune diseases (Patent Documents 1 to 3). Further, as related to lactic acid bacteria,
一方、乳酸菌は、その醗酵過程で種々の物質を産生するが、その一つが菌体外多糖（Exopolysaccharides; ＥＰＳ）である。出願人は、Lactobacillus delbrueckii subsp. bulgaricus OLL 1073 R-1株の培養物の凍結乾燥粉末の経口投与により、慢性関節リウマチの動物実験モデルにおいて、ＣＩＡ（Collagen-Induced Arthritis）発症率と炎症重篤度の両者とも約１／５に減少したとの実験結果に基づき、ガラクトースとグルコースを構成糖とし且つリンを含有する多糖類生産性を有する乳酸菌、該乳酸菌含有物、その処理物の少なくともひとつを含有してなることを特徴とする自己免疫疾患予防組成物を提案した（特許文献７）。 On the other hand, lactic acid bacteria produce various substances in the fermentation process, one of which is exopolysaccharides (EPS). Applicants received oral administration of lyophilized powder of a culture of Lactobacillus delbrueckii subsp. Bulgaricus OLL 1073 R-1 strain to CIA (Collagen-Induced Arthritis) incidence and inflammatory severity in an animal experimental model of rheumatoid arthritis. Based on the experimental results that both of them were reduced to about 1/5, lactic acid bacteria having polysaccharide productivity containing galactose and glucose as constituent sugars and containing phosphorus, the lactic acid bacteria-containing product, and at least one of the treated products thereof were contained. We have proposed an autoimmune disease preventive composition characterized by the above (Patent Document 7).
免疫バランスの十分な調節という観点からは、Ｔｈ１、Ｔｈ２、およびＴｒｅｇからなる群より選択されるいずれかの働きを亢進させるが、Ｔｈ１７の働きは亢進しないことが望ましい。また、食経験のある物質を有効成分とし、免疫バランスの調節ができる組成物があれば望ましいことはいうまでもない。 From the viewpoint of sufficient regulation of immune balance, it is desirable that the function of any one selected from the group consisting of Th1, Th2, and Treg is enhanced, but the function of Th17 is not enhanced. Needless to say, it is desirable to have a composition that can regulate the immune balance by using a substance having eating experience as an active ingredient.
本発明者らは、Lactobacillus delbrueckii subsp. bulgaricus OLL1073R-1で発酵したヨーグルト、または該乳酸菌により産生される菌体外多糖（Exopolysaccharide：ＥＰＳ）の機能について研究してきた。その中で、今般、ＥＰＳに新たな機能を発見し、当該機能に基づき、ＥＰＳが免疫バランスの調節において有用に使用できることを見出し、本発明を完成した。 The present inventors have studied the function of yogurt fermented with Lactobacillus delbrueckii subsp. Bulgaricus OLL1073R-1 or exopolysaccharide (EPS) produced by the lactic acid bacterium. Among them, we have recently discovered a new function in EPS, found that EPS can be usefully used in the regulation of immune balance based on the function, and completed the present invention.
本発明は、以下を提供する。
［１］ 乳酸菌の菌体外多糖を有効成分として含む、免疫バランスを調節するための組成物。
［２］ 免疫バランスを調節することが、ＩＬ−１７の産生を維持することを含む、１に記載の組成物。
［３］ 免疫バランスを調節することが、ＩＦＮ−γ、ＩＬ−４、およびＩＬ−１０からなる群より選択されるいずれかの産生を増加させ、ＩＬ−１７の産生を維持することを含む、１または２に記載の組成物。
［４］ 免疫バランスを調節することが、Ｔｈ１７の働きを維持することを含む、１から３のいずれか１項に記載の組成物。
［５］ 免疫バランスを調節することが、Ｔｈ１、Ｔｈ２、およびＴｒｅｇからなる群より選択されるいずれかの働きを亢進し、Ｔｈ１７の働きを維持することを含む、１から４のいずれか１項に記載の組成物。
［６］ 乳酸菌が、ラクトバチルス属に分類されるものである、１から５のいずれか１項に記載の組成物。
［７］ 乳酸菌が、ラクトバチルス・デルブルッキー・サブスピーシーズ・ブルガリクスに分類されるものである、１から６のいずれか１項に記載の組成物。
［８］ 菌体外多糖を発酵乳として含む、１から７のいずれか１項に記載の組成物。
［９］ 乳酸菌の菌体外多糖を対象に投与することを含む、対象における免疫バランスを調節する方法（ヒトに対する医療行為を除く。）。
The present invention provides:
[1] A composition for regulating immune balance, which comprises an extracellular polysaccharide of lactic acid bacteria as an active ingredient.
[2] The composition according to 1, wherein regulating the immune balance comprises maintaining the production of IL-17.
[3] Modulating the immune balance comprises increasing the production of any one selected from the group consisting of IFN-γ, IL-4, and IL-10 and maintaining the production of IL-17. The composition according to 1 or 2.
[4] The composition according to any one of 1 to 3, which comprises regulating the immune balance to maintain the function of Th17.
[5] Any one of 1 to 4 including that regulating the immune balance enhances the action of any one selected from the group consisting of Th1, Th2, and Treg and maintains the action of Th17. The composition according to.
[6] The composition according to any one of 1 to 5, wherein the lactic acid bacterium is classified into the genus Lactobacillus.
[7] The composition according to any one of 1 to 6, wherein the lactic acid bacterium is classified into Lactobacillus delbrucky subspecies bulgaricus.
[8] The composition according to any one of 1 to 7, which contains exopolysaccharide as fermented milk.
[9] A method for regulating the immune balance in a subject, including administration of exopolysaccharide of lactic acid bacteria to the subject (excluding medical practice for humans).
また、本発明は、以下も提供する。
［１０］ 免疫バランスを調節するための組成物の製造における、乳酸菌の菌体外多糖の使用。
［１１］ ＩＦＮ−γ、ＩＬ−４、およびＩＬ−１０からなる群より選択されるいずれかの産生を増加させ、ＩＬ−１７の産生を維持するための組成物の製造における、乳酸菌の菌体外多糖の使用。
［１２］ 免疫バランスを調節するための方法における使用のための、乳酸菌の菌体外多糖または乳酸菌の菌体外多糖を含む組成物。
［１３］ ＩＦＮ−γ、ＩＬ−４、およびＩＬ−１０からなる群より選択されるいずれかの産生を増加させ、ＩＬ−１７の産生を維持する方法における使用のための、乳酸菌の菌体外多糖または乳酸菌の菌体外多糖を含む組成物。
［１４］ 乳酸菌の菌体外多糖または乳酸菌の菌体外多糖を含む組成物を対象に投与することを含む、対象における免疫バランスを調節する方法。
［１５］ 乳酸菌の菌体外多糖または乳酸菌の菌体外多糖を含む組成物を対象に投与することを含む、対象におけるＩＦＮ−γ、ＩＬ−４、およびＩＬ−１０からなる群より選択されるいずれかの産生を増加させ、ＩＬ−１７の産生を維持するための方法。
The present invention also provides the following.
[10] Use of exopolysaccharides of lactic acid bacteria in the production of compositions for regulating immune balance.
[11] Lactic acid bacteria cells in the production of a composition for increasing the production of any one selected from the group consisting of IFN-γ, IL-4, and IL-10 and maintaining the production of IL-17. Use of exopolysaccharide.
[12] A composition comprising an exopolysaccharide of a lactic acid bacterium or an exopolysaccharide of a lactic acid bacterium for use in a method for regulating an immune balance.
[13] Extracellular lactic acid bacteria for use in methods of increasing production of any one selected from the group consisting of IFN-γ, IL-4, and IL-10 and maintaining production of IL-17. A composition containing a polysaccharide or an extracellular polysaccharide of a lactic acid bacterium.
[14] A method for regulating an immune balance in a subject, which comprises administering to the subject an extracellular polysaccharide of lactic acid bacteria or a composition containing an extracellular polysaccharide of lactic acid bacteria.
[15] Selected from the group consisting of IFN-γ, IL-4, and IL-10 in a subject, which comprises administering to the subject an extracellular polysaccharide of lactic acid bacteria or a composition containing an extracellular polysaccharide of lactic acid bacteria. A method for increasing the production of either and maintaining the production of IL-17.
本発明に拠れば、Ｔｈ１７の働きを亢進させずに、Ｔｈ１、Ｔｈ２、およびＴｒｅｇからなる群より選択されるいずれかの働きを亢進させることができ、これにより、対象において、免疫バランスが調節されうる。
また本発明に拠れば、ＩＬ−１７の分泌を増加させずに、ＩＦＮ−γ、ＩＬ−４、およびＩＬ−１０からなる群より選択されるいずれかの分泌を促進させることができ、これにより、対象において免疫バランスが調節されうる。
According to the present invention, it is possible to enhance the function of any one selected from the group consisting of Th1, Th2, and Treg without enhancing the function of Th17, whereby the immune balance is regulated in the subject. sell.
Further, according to the present invention, it is possible to promote the secretion of any one selected from the group consisting of IFN-γ, IL-4, and IL-10 without increasing the secretion of IL-17. , The immune balance can be regulated in the subject.
以下、本発明を詳細に説明する。
本発明は、乳酸菌が産生する菌体外多糖（ＥＰＳ）を有効成分とする組成物に関する。より詳細には、ＥＰＳを有効成分とし、免疫バランスを調節するための組成物に関する。
Hereinafter, the present invention will be described in detail.
The present invention relates to a composition containing extracellular polysaccharide (EPS) produced by lactic acid bacteria as an active ingredient. More specifically, it relates to a composition containing EPS as an active ingredient for regulating immune balance.
［有効成分］
本発明の組成物は、有効成分として乳酸菌のＥＰＳを含む。乳酸菌とは、ブドウ糖を資化して対糖収率で５０％以上の乳酸を生産する微生物の総称で、生理学的性質としてグラム陽性菌の球菌または桿菌で、運動性なし、多くの場合胞子形成能なし（バシラス・コアギュランスのように胞子形成能のある乳酸菌もある。）、カタラーゼ陰性などの特徴を有しているものである。乳酸菌は古来、発酵乳等を介して世界各地で食されており、極めて安全性の高い微生物といえる。乳酸菌は、複数の属に分類される。本発明の組成物に含まれる乳酸菌のＥＰＳは、好ましくはラクトバチルス（Lactobacillus）属に分類されるラクトバチルス属乳酸菌により産生されたものである。
[Active ingredient]
The composition of the present invention contains EPS of lactic acid bacteria as an active ingredient. Lactic acid bacteria are a general term for microorganisms that assimilate glucose to produce lactic acid of 50% or more in terms of sugar yield. They are gram-positive cocci or bacilli as physiological properties, and have no motility and often have spore-forming ability. None (some lactic acid bacteria have the ability to form spores, such as Bacillus coccus), and they have characteristics such as catalase negative. Lactic acid bacteria have been eaten all over the world through fermented milk since ancient times, and can be said to be extremely safe microorganisms. Lactic acid bacteria are classified into multiple genera. The EPS of the lactic acid bacterium contained in the composition of the present invention is preferably produced by a lactic acid bacterium of the genus Lactobacillus, which is classified into the genus Lactobacillus.
本発明の組成物に用いられるＥＰＳは、目的の効果を有する限り、特に限定されない。乳酸菌が産生するＥＰＳは、構造的に、ホモ多糖であるものとヘテロ多糖であるもの（例えば、ガラクトースとグルコースから構成されるもの）に分類され、リン酸化や硫酸化などの修飾を受けている場合もあるが、いずれも本発明の組成物の有効成分として用いることができる。好ましいＥＰＳの例の一つは、中性多糖体、および中性多糖体にリン酸基が付加した酸性多糖体の少なくとも一方を含むものである。このようなＥＰＳは、ラクトバチルス・デルブルッキー・サブスピーシーズ・ブルガリクス（Lactobacillus delbrueckii subsp. bulgaricus）や、ラクトコッカス・ラクティス・サブスピーシーズ・クレモリス（Lactococcus lactis subsp. cremoris）などによって産生されることが知られている。本発明に用いられるＥＰＳは、一種でもよく、２種以上の組み合わせであってもよい。 The EPS used in the composition of the present invention is not particularly limited as long as it has the desired effect. EPS produced by lactic acid bacteria is structurally classified into homopolysaccharides and heteropolysaccharides (for example, those composed of galactose and glucose), and has undergone modifications such as phosphorylation and sulfation. In some cases, any of them can be used as an active ingredient of the composition of the present invention. One of the preferred examples of EPS is one that contains at least one of a neutral polysaccharide and an acidic polysaccharide in which a phosphate group is added to the neutral polysaccharide. It is known that such EPS is produced by Lactobacillus delbrueckii subsp. Bulgaricus and Lactococcus lactis subsp. Cremoris. Has been done. The EPS used in the present invention may be one type or a combination of two or more types.
本発明の組成物に用いられる特に好ましいＥＰＳを産生する乳酸菌の例は、ラクトバチルス属乳酸菌である。ラクトバチルス属乳酸菌としては、例えば、ブルガリクス種、カゼイ種、アシドフィルス種、プランタラム種などが挙げられる。これらのラクトバチルス属乳酸菌の中でも、本発明では、ラクトバチルス・デルブルッキー・サブスピーシーズ・ブルガリクス（Lactobacillus delbrueckii subsp. bulgaricus）（ブルガリクス菌とも称する）に分類されるものであることがより好ましい。特に好ましい態様においては、乳酸菌は、ラクトバチルス・デルブルッキー・サブスピーシーズ・ブルガリクスＯＬＬ１０７３ Ｒ−１菌（受託番号：ＦＥＲＭ ＢＰ−１０７４１）（「ブルガリクス菌Ｒ−１株」と称することがある。）である。すなわち、本発明の組成物に用いられるＥＰＳの特に好ましい例の一つは、ブルガリクス菌Ｒ−１株が産生するＥＰＳである。 An example of a particularly preferred EPS-producing lactic acid bacterium used in the compositions of the present invention is Lactobacillus lactic acid bacterium. Examples of Lactobacillus lactic acid bacteria include Bulgaricus species, Casei species, Acidophilus species, Plantalum species and the like. Among these Lactobacillus lactic acid bacteria, in the present invention, it is more preferable that they are classified into Lactobacillus delbrueckii subsp. Bulgaricus (also referred to as Bulgaricus bacterium). In a particularly preferred embodiment, the lactic acid bacterium may be referred to as Lactobacillus delbrucky Subspecies Bulgaricus OLL1073 R-1 bacterium (accession number: FERM BP-10741) ("Bulgaricus bacterium R-1 strain". ). That is, one of the particularly preferable examples of EPS used in the composition of the present invention is EPS produced by the Bulgaricus R-1 strain.
ブルガリクス菌Ｒ−１株は、独立行政法人製品評価技術基盤機構特許生物寄託センター（ＩＰＯＤ，ＮＩＴＥ）（日本国千葉県木更津市かずさ鎌足２−５−８ １２０号室）にブタペスト条約に基づき、国際寄託されている（寄託者：株式会社 明治、寄託日：２００６年１１月２９日、受託番号：ＦＥＲＭ ＢＰ−１０７４１）。 The Bulgaris bacterium R-1 strain was sent to the Patent Organism Depositary Center (IPOD, NITE) (Kazusakamatari Room 2-5-8 120, Kisarazu City, Chiba Prefecture, Japan) based on the Butapest Convention. It has been deposited internationally (Depositor: Meiji Co., Ltd., Deposit date: November 29, 2006, Deposit number: FERM BP-10741).
本発明の組成物に含まれる乳酸菌のＥＰＳは、乳酸菌発酵物として含まれていてもよい。乳酸菌発酵物には、乳酸菌による発酵物自体のほか、その処理物が含まれる。乳酸菌発酵物自体には、例えば発酵乳（具体的には、ヨーグルト等）が含まれる。処理物には、例えば、粗精製物、精製物、発酵物をろ過、遠心分離、または膜分離で除菌して得られた培養濾液や培養上清液、培養濾液・培養上清液を濃縮した濃縮物、濃縮物の乾燥物が含まれる。 The EPS of lactic acid bacteria contained in the composition of the present invention may be contained as a fermented product of lactic acid bacteria. The fermented product of lactic acid bacteria includes the fermented product itself by lactic acid bacteria and the processed product thereof. The fermented lactic acid bacterium itself contains, for example, fermented milk (specifically, yogurt or the like). For the treated product, for example, a culture filtrate, a culture supernatant, or a culture filtrate / culture supernatant obtained by sterilizing a crude product, a purified product, or a fermented product by filtration, centrifugation, or membrane separation is concentrated. Concentrates and dried concentrates are included.
乳酸菌のＥＰＳの調製方法は従来技術を利用することができ、より詳細な条件が必要な場合は、本明細書の実施例等を参照することができる。また、乳酸菌のＥＰＳを乳酸菌発酵物として調製する場合は、ＥＰＳを産生する乳酸菌をスターターとして原料乳に添加し、発酵させ、ＥＰＳを発酵物中に産生させることで、ＥＰＳを含む発酵乳が製造できる。発酵の際の条件、例えば、原料乳、発酵温度、発酵時間は、用いる乳酸菌がＥＰＳを産生することができれば特に制限されず、当業者であれば、適宜設定することができる。 Conventional techniques can be used for preparing EPS of lactic acid bacteria, and examples of the present specification can be referred to when more detailed conditions are required. When the EPS of lactic acid bacteria is prepared as a fermented product of lactic acid bacteria, the fermented milk containing EPS is produced by adding the lactic acid bacteria that produce EPS to the raw material milk as a starter and fermenting the EPS to produce EPS in the fermented product. it can. Fermentation conditions, such as raw milk, fermentation temperature, and fermentation time, are not particularly limited as long as the lactic acid bacteria used can produce EPS, and can be appropriately set by those skilled in the art.
［用途］
本発明の組成物は、免疫バランスを調節するために用いることができる。
[Use]
The compositions of the present invention can be used to regulate the immune balance.
本発明でいう免疫バランスの調節は、ＩＬ−１７の産生を維持すること、またはＩＦＮ−γ、ＩＬ−４、およびＩＬ−１０からなる群より選択されるいずれかの産生を増加させることを含む。免疫バランスの調節は、好ましくはＩＬ−１７の産生を維持し、かつＩＦＮ−γ、ＩＬ−４、およびＩＬ−１０からなる群より選択される少なくとも一つの産生を増加させることを含み、より好ましくはＩＬ−１７の産生を維持し、かつＩＦＮ−γ、ＩＬ−４、およびＩＬ−１０の産生を増加させることを含む。 The regulation of immune balance as used in the present invention includes maintaining the production of IL-17 or increasing the production of any one selected from the group consisting of IFN-γ, IL-4, and IL-10. .. Modulation of the immune balance preferably comprises maintaining the production of IL-17 and increasing the production of at least one selected from the group consisting of IFN-γ, IL-4, and IL-10, more preferably. Includes maintaining IL-17 production and increasing IFN-γ, IL-4, and IL-10 production.
サイトカインの産生に関し、「維持（する）」とは、増加も減少もしないことをいう。維持するといえるか否か、また増加させるといえるか否かは、当業者であれば適宜判断できる。 With respect to cytokine production, "maintaining" means neither increasing nor decreasing. Those skilled in the art can appropriately determine whether or not it can be said to be maintained and whether or not it can be said to be increased.
例えば、次のように判断することができる：
評価しようとする成分を投与する群と投与しない群それぞれについて、目的のサイトカインの産生量について測定する。そして投与の有無で有意差検定を行い、Ｐ値が有意水準（典型的には０．０５）を下回ったときに差がある（「増加させる」、等）と判断することができる。
また両群について平均値を求め、平均値の差が比較的小さいとき、例えば２０％以下、好ましくは１０％以下であるときに、「維持する」と判断することができる。または投与の有無で有意差検定を行い、Ｐ値が比較的大きいとき、例えば、０．５以上、好ましくは０．６以上、より好ましくは０．７以上、さらに好ましくは０．８以上のときに、「維持する」と判断することができる。
For example, we can determine:
The amount of the target cytokine produced is measured for each of the group to which the component to be evaluated is administered and the group to which the component to be evaluated is not administered. Then, a significance test is performed depending on the presence or absence of administration, and it can be determined that there is a difference (“increase”, etc.) when the P value falls below the significance level (typically 0.05).
Further, the average value is obtained for both groups, and when the difference between the average values is relatively small, for example, 20% or less, preferably 10% or less, it can be determined to "maintain". Alternatively, a significant difference test is performed with or without administration, and when the P value is relatively large, for example, 0.5 or more, preferably 0.6 or more, more preferably 0.7 or more, still more preferably 0.8 or more. In addition, it can be judged to "maintain".
本発明でいう免疫バランスの調節とはまた、Ｔｈ１７の働きを維持すること、またはＴｈ１、Ｔｈ２、およびＴｒｅｇからなる群より選択されるいずれかの働きを亢進させることを含む。免疫バランスの調節は、好ましくはＴｈ１７の働きを維持し、かつＴｈ１、Ｔｈ２、およびＴｒｅｇからなる群より選択される少なくとも一つの働きを亢進させることを含み、より好ましくはＴｈ１７の働きを維持し、かつＴｈ１、Ｔｈ２、およびＴｒｅｇの働きを亢進させることを含む。 The regulation of immune balance as used in the present invention also includes maintaining the function of Th17 or enhancing the function of any one selected from the group consisting of Th1, Th2, and Treg. Regulation of immune balance preferably comprises maintaining Th17 activity and enhancing at least one activity selected from the group consisting of Th1, Th2, and Treg, more preferably maintaining Th17 activity. And it includes enhancing the action of Th1, Th2, and Treg.
ヘルパーＴ細胞の働きに関し、「維持（する）」とは、亢進させないことをいう。維持するといえるか否か、また亢進させるといえるか否かは、目的のＴ細胞が産生するサイトカインの産生量を分析することにより判断することができる。 Regarding the function of helper T cells, "maintaining" means not enhancing. Whether or not it can be said to be maintained and whether or not it can be said to be enhanced can be determined by analyzing the amount of cytokine produced by the target T cell.
本発明の組成物によるＩＦＮ−γ、ＩＬ−４、およびＩＬ−１０の産生の増加、ならびにＩＬ−１７の産生の維持は、脾臓において確認できる。ＩＦＮ−γ、ＩＬ−４、ＩＬ−１０、およびＩＬ−１７の産生量は、例えば、末梢血において分析することができ、また末梢血から得たＴ細胞を適切な方法によって刺激することにより増加する程度を分析することにより、評価できる。ＩＦＮ−γ、ＩＬ−４、ＩＬ−１０、およびＩＬ−１７の分析に際しては、市販のキット用いて分析できる。 Increased production of IFN-γ, IL-4, and IL-10 and maintenance of IL-17 production by the compositions of the present invention can be confirmed in the spleen. Production of IFN-γ, IL-4, IL-10, and IL-17 can be analyzed, for example, in peripheral blood and can be increased by stimulating T cells from peripheral blood in an appropriate manner. It can be evaluated by analyzing the degree of doing. IFN-γ, IL-4, IL-10, and IL-17 can be analyzed using commercially available kits.
分析とは、分析対象分子の、存在の有無、および存在する場合はその程度（量）のいずれかを測定することをいう。 Analysis refers to measuring either the presence or absence of a molecule to be analyzed and, if so, its degree (amount).
本発明の組成物は、免疫バランスの調節が、感染症やがんの処置のための他の療法と一緒に行われる場合であっても、用いることができる。そのような他の療法には、薬物による療法、手術、放射線治療、他の免疫療法（例えば、サイトカイン療法、免疫賦活剤の投与、免疫細胞移植、等）、健康食品やサプリメントの摂取、運動療法等がある。 The compositions of the present invention can be used even when the regulation of immune balance is performed in conjunction with other therapies for the treatment of infections and cancers. Such other therapies include drug therapy, surgery, radiation therapy, other immunotherapies (eg, cytokine therapy, administration of immunostimulators, immune cell transplantation, etc.), intake of health foods and supplements, exercise therapy. And so on.
本発明の組成物により免疫バランスが調節されることで、各種の免疫疾患の発症リスクが低減され、また治療が期待できる。免疫疾患の例は、関節リウマチとその類縁疾患（例えば、関節リウマチ、悪性関節リウマチ/リウマトイド血管炎、リウマチ性多発筋痛症、RS3PE症候群、変形性手関節症）、脊椎関節炎（例えば、強直性脊椎炎、乾癬性関節炎、SAPHO症候群、反応性関節炎）、（自己免疫疾患（例えば、全身性エリテマトーデス、全身性強皮症、多発性筋炎・皮膚筋炎、筋無症候性皮膚筋炎、混合性結合組織病、シェーグレン症候群、抗リン脂質抗体症候群）、 ベーチェット病、成人スティル病、再発性多発軟骨炎、キャッスルマン病、TAFRO症候群、血管炎症候群（例えば、高安動脈炎、巨細胞性動脈炎、結節性多発動脈炎、ANCA関連血管炎、顕微鏡的多発血管炎、多発血管炎性肉芽腫症、好酸球性多発血管炎性肉芽腫症、アレルギー疾患（気管支喘息、好酸球増多症、IgG4関連疾患、血管性浮腫）、肺高血圧症、不明熱、骨粗鬆症、感染症（ニューモシスチス肺炎、帯状疱疹）等がある。 By regulating the immune balance with the composition of the present invention, the risk of developing various immune diseases is reduced, and treatment can be expected. Examples of immune disorders include rheumatoid arthritis and related disorders (eg, rheumatoid arthritis, malignant rheumatoid arthritis / rheumatoid vasculitis, rheumatic polymyositis, RS3PE syndrome, dermatomyositis deformans), dermatomyositis (eg, tonic). Spondylitis, psoriasis vasculitis, SAPHO syndrome, reactive arthritis), (autoimmune diseases (eg, systemic erythematosus, systemic vasculitis, polymyositis / dermatomyositis, myonsymptomatic dermatomyositis, mixed connective tissue) Diseases, Schegren's syndrome, antiphospholipid antibody syndrome), Bechet's disease, adult Still's disease, recurrent polychondritis, Castleman's disease, TAFRO syndrome, vasculitis syndrome (eg, hyperan arteritis, giant cell artitis, nodular) Polyarteritis, ANCA-related vasculitis, microscopic polyangiitis, polyangiitis granulomatosis, eosinophilia polyangiitis granulomatosis, allergic diseases (bronchial asthma, eosinophilia, IgG4-related) Diseases, vasculitis), pulmonary hypertension, unknown fever, osteoporosis, infectious diseases (pneumocystis pneumonia, herpes zoster), etc.
本発明の組成物の一態様は、自己免疫疾患予防組成物を除いた、免疫バランスを調節するための組成物、およびＩＦＮ−γ、ＩＬ−４、およびＩＬ−１０からなる群より選択されるいずれかの産生を増加させ、ＩＬ−１７の産生を維持するための組成物である。
ものである。
One aspect of the composition of the present invention is selected from the composition for regulating immune balance, excluding the autoimmune disease preventive composition, and the group consisting of IFN-γ, IL-4, and IL-10. A composition for increasing the production of either and maintaining the production of IL-17.
It is a thing.
［組成物］
（食品組成物等）
本発明の組成物は、食品組成物または医薬組成物とすることができる。食品および医薬品は、特に記載した場合を除き、ヒトのためのもののみならず、ヒト以外の動物のためのものを含む。食品は、特に記載した場合を除き、一般食品、機能性食品、栄養組成物を含み、また治療食（治療の目的を果たすもの。医師が食事箋を出し、それに従い栄養士等が作成した献立に基づいて調理されたもの。）、食事療法食、成分調整食、介護食、治療支援用食品を含む。食品は、特に記載した場合を除き、固形物のみならず、液状のもの、例えば飲料、ドリンク剤、流動食、およびスープを含む。機能性食品とは、生体に所定の機能性を付与できる食品をいい、例えば、特定保健用食品（条件付きトクホ［特定保健用食品］を含む）、機能性表示食品、栄養機能食品を含む保健機能食品、特別用途食品、栄養補助食品、健康補助食品、サプリメント（例えば、錠剤、被覆錠、糖衣錠、カプセル、液剤等の各種の剤型のもの）、美容食品（例えば、ダイエット食品）等の、健康食品の全般を包含している。また、本発明において「機能性食品」とは、コーデックス（FAO/WHO合同食品規格委員会）の食品規格に基づく健康強調表示（Health claim）が適用される健康食品を包含している。
[Composition]
(Food composition, etc.)
The composition of the present invention can be a food composition or a pharmaceutical composition. Foods and pharmaceuticals include those for non-human animals as well as those for humans, unless otherwise stated. Unless otherwise specified, foods include general foods, functional foods, nutritional compositions, and therapeutic foods (those that serve the purpose of treatment. Doctors issue meals, and nutritionists, etc. prepare foods accordingly. Includes foods cooked based on), dietary foods, ingredient-adjusted foods, nursing foods, and therapeutic support foods. Foods include not only solids but also liquids such as beverages, energy drinks, liquid foods, and soups, unless otherwise specified. Functional foods are foods that can impart predetermined functionality to living organisms, for example, foods for specified health use (including conditional foods [food for specified health use]), foods with functional claims, and health foods including nutritionally functional foods. Functional foods, special-purpose foods, nutritional supplements, health supplements, supplements (for example, tablets, coated tablets, sugar-coated tablets, capsules, liquids and other various dosage forms), beauty foods (for example, diet foods), etc. It includes all kinds of health foods. Further, in the present invention, the "functional food" includes a health food to which a health claim based on the food standard of Codex (FAO / WHO Joint Food Standards Committee) is applied.
（対象）
本発明の組成物は、免疫バランスの調節が好ましい対象に、摂取させる、または投与するのに適している。このような対象には、乳幼児、子ども、成人（１５歳以上）、中高年者、高齢者（６５歳以上）、病中病後の者、妊婦、産婦、男性、女性が含まれる。
(Target)
The compositions of the present invention are suitable for ingestion or administration to subjects who prefer to regulate their immune balance. Such subjects include infants, children, adults (15 years and older), middle-aged and elderly people (65 years and older), those after illness, pregnant women, pregnant women, men and women.
（投与経路）
本発明の組成物は、種々の経路で投与しうる。投与する経路の例は、経口投与（ＰＯ）、経管栄養（胃瘻、腸瘻）、注腸投与、経皮投与、経粘膜投与、吸入投与、皮膚上投与、吸入投与、注腸投与、腹腔内投与（ＩＰ）、点眼、点耳、経鼻投与、膣内投与、経静脈投与（ＩＶ）、経動脈投与（ＩＡ）、筋肉内投与（ＩＭ）、皮下投与（ＳＣ、ｓｕｂ−Ｑ）、皮内投与（ＩＤ）等である。本発明の組成物は、経腸投与（経口投与、経管栄養、または注腸投与）することが好ましいが、本発明の組成物の有効成分はＥＰＳであるので、乳酸菌または発酵物を有効成分とする場合に比較して、投与経路がより広く選択でき、また投与経路に適した剤型とすることがより容易である。
(Route of administration)
The compositions of the present invention can be administered by various routes. Examples of administration routes include oral administration (PO), tube feeding (gastrostomy, enteral fistula), enema administration, transdermal administration, transmucosal administration, inhalation administration, intradermal administration, inhalation administration, enema administration, Intraperitoneal administration (IP), eye drops, ear drops, nasal administration, intravaginal administration, intravenous administration (IV), transarterial administration (IA), intramuscular administration (IM), subcutaneous administration (SC, sub-Q) , Intradermal administration (ID), etc. The composition of the present invention is preferably administered by intestine (oral administration, tube feeding, or enema administration), but since the active ingredient of the composition of the present invention is EPS, a lactic acid bacterium or a fermented product is used as an active ingredient. In comparison with the case of, the administration route can be selected more widely, and it is easier to obtain a dosage form suitable for the administration route.
（有効成分の含有量・用量）
本発明の組成物における、乳酸菌のＥＰＳの含有量は、目的の効果が発揮される量であればよい。組成物は、その被験体の年齢、体重、症状等の種々の要因を考慮して、その投与量または摂取量を適宜設定することができるが、一日量あたりの乳酸菌のＥＰＳの量は、例えば0.1 mg以上とすることができ、0.6 mg以上とすることが好ましく、1 mg以上とすることがより好ましく、3 mg以上とすることが特に好ましい。一日量あたりのＥＰＳの量の上限値は、下限値がいずれの場合であっても、500 mg以下とすることができ、300 mg以下とすることが好ましく、250 mg以下とすることが特に好ましい。
(Content / dose of active ingredient)
The content of EPS of lactic acid bacteria in the composition of the present invention may be any amount as long as the desired effect is exhibited. The dose or intake of the composition can be appropriately set in consideration of various factors such as the age, body weight, and symptoms of the subject, but the amount of EPS of lactic acid bacteria per day is determined. For example, it can be 0.1 mg or more, preferably 0.6 mg or more, more preferably 1 mg or more, and particularly preferably 3 mg or more. The upper limit of the amount of EPS per daily dose can be 500 mg or less, preferably 300 mg or less, and particularly 250 mg or less, regardless of the lower limit. preferable.
１投与または１食あたり、すなわち一回量あたりの乳酸菌のＥＰＳの量は、例えば0.03 mg以上とすることができ、0.2 mg以上とすることが好ましく、1 mg以上とすることがより好ましい。一回量あたりのＥＰＳの量の上限値は、下限値がいずれの場合であっても、200 mg以下とすることができ、100 mg以下とすることが好ましく、70 mg以下とすることがより好ましく、30 mg以下とすることが特に好ましい。 The amount of EPS of lactic acid bacteria per administration or meal, that is, per dose, can be, for example, 0.03 mg or more, preferably 0.2 mg or more, and more preferably 1 mg or more. The upper limit of the amount of EPS per dose can be 200 mg or less, preferably 100 mg or less, and more preferably 70 mg or less, regardless of the lower limit. It is preferably 30 mg or less, and particularly preferably 30 mg or less.
本発明の組成物における、乳酸菌のＥＰＳを発酵乳のような組成物として用いる場合、組成物としての一日量は、例えば30 g以上とすることができ、50 g以上とすることが好ましく、60 g以上とすることがより好ましく、100 g以上とすることが特に好ましい。発酵乳としての一日量の上限値は、下限値がいずれの場合であっても、例えば1500 g以下とすることができ、1200 g以下とすることが好ましく、900 g以下とすることがより好ましく、600 g以下とすることがより好ましい。 When EPS of lactic acid bacteria in the composition of the present invention is used as a composition such as fermented milk, the daily amount of the composition can be, for example, 30 g or more, preferably 50 g or more. It is more preferably 60 g or more, and particularly preferably 100 g or more. The upper limit of the daily amount of fermented milk can be, for example, 1500 g or less, preferably 1200 g or less, and more preferably 900 g or less, regardless of the lower limit. It is preferably 600 g or less, more preferably 600 g or less.
組成物としての一回量は、例えば10 g以上とすることができ、20 g以上とすることが好ましく、30 g以上とすることがより好ましい。組成物としての一回量の上限値は、下限値がいずれの場合であっても、例えば500 g以下とすることができ、400 g以下とすることが好ましく、200 g以下とすることがより好ましく、125 g以下とすることが特に好ましい。 The single dose of the composition can be, for example, 10 g or more, preferably 20 g or more, and more preferably 30 g or more. Regardless of the lower limit, the upper limit of the single dose of the composition can be, for example, 500 g or less, preferably 400 g or less, and more preferably 200 g or less. It is preferably 125 g or less, and particularly preferably 125 g or less.
組成物は、一日１回の投与・摂取としてもよいし、一日複数回、例えば食事毎の３回の投与としてもよい。組成物は、食経験豊富な乳酸菌のＥＰＳを有効成分としている。そのため、本発明の組成物は、有効成分が食経験の長いＥＰＳであるため、長期間の摂取に適している。そのため繰り返し、または長期間にわたって摂取してもよく、例えば３日以上、好ましくは１週間以上、より好ましくは４週間以上、特に好ましくは１カ月以上、続けて投与・摂取することができる。なおＥＰＳの投与・摂取量を増やしてもＩＬ−１７の産生にはほとんど影響を及ぼさないと考えられる。 The composition may be administered / ingested once a day, or may be administered a plurality of times a day, for example, three times per meal. The composition contains EPS of lactic acid bacteria with abundant eating experience as an active ingredient. Therefore, the composition of the present invention is suitable for long-term ingestion because the active ingredient is EPS having a long eating experience. Therefore, it may be ingested repeatedly or for a long period of time, and can be continuously administered and ingested, for example, for 3 days or more, preferably 1 week or more, more preferably 4 weeks or more, and particularly preferably 1 month or more. It is considered that increasing the administration / intake of EPS has almost no effect on the production of IL-17.
（他の成分、添加剤）
本発明の組成物は、食品または医薬品として許容可能な他の有効成分や栄養成分を含んでいてもよい。そのような成分の例は、アミノ酸類（例えば、リジン、アルギニン、グリシン、アラニン、グルタミン酸、ロイシン、イソロイシン、バリン）、糖質（グルコース、ショ糖、果糖、麦芽糖、トレハロース、エリスリトール、マルチトール、パラチノース、キシリトール、デキストリン）、電解質（例えば、ナトリウム、カリウム、カルシウム、マグネシウム）、ビタミン（例えば、ビタミンＡ、ビタミンＢ１、ビタミンＢ２、ビタミンＢ６、ビタミンＢ１２、ビタミンＣ、ビタミンＤ、ビタミンＥ、ビタミンＫ、ビオチン、葉酸、パントテン酸およびニコチン酸類）、ミネラル（例えば、銅、亜鉛、鉄、コバルト、マンガン）、抗生物質、食物繊維、タンパク質、脂質等である。
(Other ingredients and additives)
The compositions of the present invention may contain other active or nutritional ingredients that are acceptable as foods or pharmaceuticals. Examples of such ingredients are amino acids (eg, lysine, arginine, glycine, alanine, glutamic acid, leucine, isoleucine, valine), sugars (glucose, sucrose, fructose, malt sugar, trehalose, erythritol, maltitol, palatinose). , Xylitol, dextrin), electrolytes (eg sodium, potassium, calcium, magnesium), vitamins (eg vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K, Biotins, folic acid, pantothenic acids and nicotinic acids), minerals (eg copper, zinc, iron, cobalt, manganese), antibiotics, dietary fiber, proteins, lipids and the like.
また組成物は、食品または医薬として許容される添加物をさらに含んでいてもよい。そのような添加物の例は、不活性担体（固体や液体担体）、賦形剤、界面活性剤、結合剤、崩壊剤、滑沢剤、溶解補助剤、懸濁化剤、コーティング剤、着色剤、保存剤、緩衝剤、pH調整剤、乳化剤、安定剤、甘味料、酸化防止剤、香料、酸味料、天然物である。より具体的には、水、他の水性溶媒、製薬上で許容される有機溶媒、コラーゲン、ポリビニルアルコール、ポリビニルピロリドン、カルボキシビニルポリマー、アルギン酸ナトリウム、水溶性デキストラン、水溶性デキストリン、カルボキシメチルスターチナトリウム、ペクチン、キサンタンガム、アラビアゴム、カゼイン、ゼラチン、寒天、グリセリン、プロピレングリコール、ポリエチレングリコール、ワセリン、パラフィン、ステアリルアルコール、ステアリン酸、ヒト血清アルブミン、マンニトール、ソルビトール、ラクトース、スクラロース、ステビア、アスパルテーム、アセスルファムカリウム、クエン酸、乳酸、りんご酸、酒石酸、リン酸、酢酸、果汁、野菜汁等である。 The composition may also further include food or pharmaceutically acceptable additives. Examples of such additives are inert carriers (solid and liquid carriers), excipients, surfactants, binders, disintegrants, lubricants, solubilizers, suspending agents, coatings, colorings. Agents, preservatives, buffers, pH regulators, emulsifiers, stabilizers, sweeteners, antioxidants, fragrances, acidulants, natural products. More specifically, water, other aqueous solvents, pharmaceutically acceptable organic solvents, collagen, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, sodium alginate, water-soluble dextran, water-soluble dextrin, sodium carboxymethyl starch, Pectin, xanthan gum, arabic gum, casein, gelatin, agar, glycerin, propylene glycol, polyethylene glycol, vaseline, paraffin, stearyl alcohol, stearic acid, human serum albumin, mannitol, sorbitol, lactose, sucralose, stevia, aspartame, assesulfam potassium, Citric acid, lactic acid, apple acid, dextrinic acid, phosphoric acid, acetic acid, fruit juice, vegetable juice and the like.
（剤型・形態）
本発明の医薬組成物は、投与経路に応じ、エアゾール剤、液剤、エキス剤（軟エキス剤、乾燥エキス剤）、エリキシル剤、カプセル剤（硬カプセル剤、軟カプセル剤、顆粒剤、丸剤、眼軟膏剤、経皮吸収型製剤懸濁剤・乳剤、坐剤、散剤、酒精剤、錠剤(口腔内崩壊錠、チュアブル錠、発泡錠、即放性錠剤(素錠,裸錠) 、糖衣錠）、シロップ剤、浸剤・煎剤、注射剤、貼付剤、チンキ剤、点眼剤、トローチ剤、軟膏剤、パップ剤、芳香水剤、リニメント剤、リモナーデ剤、流エキス剤、ローション剤等の任意の剤型にすることができる。
(Dosage form / form)
The pharmaceutical composition of the present invention comprises an aerosol agent, a liquid agent, an extract agent (soft extract agent, a dry extract agent), an elixir agent, a capsule agent (hard capsule agent, a soft capsule agent, a granule, a pill, a pill), depending on the administration route. Ophthalmic ointment, transdermal absorption type formulation Suspension / emulsion, suppository, powder, alcohol, tablets (orally disintegrating tablets, chewable tablets, effervescent tablets, immediate release tablets (bare tablets, naked tablets), sugar-coated tablets) , Syrups, dipping / decoctions, injections, patches, tinctures, eye drops, troches, ointments, poultices, aromatic waters, liniments, limonades, flow extracts, lotions, etc. Can be molded.
経口投与に適した剤型としては、錠剤、顆粒剤、散剤、丸剤、カプセル剤等の固形製剤、液剤、懸濁剤、シロップ剤等の液体製剤、ジェル剤、エアロゾル剤等が挙げられる。 Dosage forms suitable for oral administration include solid preparations such as tablets, granules, powders, pills and capsules, liquid preparations such as liquids, suspensions and syrups, gels and aerosols.
本発明の食品組成物は、固体、液体、混合物、懸濁液、粉末、顆粒、ペースト、ゼリー、ゲル、カプセル等の任意の形態に調製されたものであってよい。また、本発明に係る食品組成物は、乳製品、サプリメント、菓子、飲料、ドリンク剤、調味料、加工食品、惣菜、スープ等の任意の形態にすることができる。より具体的には、本発明の組成物は、乳飲料、清涼飲料、乳酸菌飲料、乳性飲料、発酵乳、ヨーグルト、アイスクリーム、タブレット、チョコレート、チーズ、パン、ビスケット、クラッカー、ピッツァクラスト、調製粉乳、液体ミルク、流動食、病者用食品、栄養食品、冷凍食品、加工食品等の形態とすることができ、また飲料や食品に混合して摂取するための、顆粒、粉末、ペースト、濃厚液等の形態とすることができる。 The food composition of the present invention may be prepared in any form such as solid, liquid, mixture, suspension, powder, granule, paste, jelly, gel, capsule and the like. In addition, the food composition according to the present invention can be in any form such as dairy products, supplements, confectionery, beverages, energy drinks, seasonings, processed foods, prepared foods, soups and the like. More specifically, the compositions of the present invention are dairy beverages, soft beverages, lactic acid bacteria beverages, dairy beverages, fermented milk, yogurt, ice cream, tablets, chocolate, cheese, bread, biscuits, crackers, pizza crusts, preparations. It can be in the form of milk powder, liquid milk, liquid foods, foods for the sick, nutritional foods, frozen foods, processed foods, etc., and granules, powders, pastes, and concentrates for mixing with beverages and foods. It can be in the form of a liquid or the like.
（その他）
本発明の組成物の製造において、乳酸菌のＥＰＳの配合の段階は、適宜選択することができる。乳酸菌のＥＰＳの特性を著しく損なわない限り配合の段階は特に制限されない。例えば、ＥＰＳを産生する乳酸菌を培養して得られたＥＰＳを含む培養物やその粗精製物、精製物を、製造工程の様々な段階で、原材料に混合して配合することができる。あるいは、本発明の組成物を発酵乳として実施する場合は、ＥＰＳを含む培養物やその粗精製物、精製物を原材料や発酵後の発酵乳に混合して配合するか、ＥＰＳを産生する乳酸菌をスターターとして原料乳に添加し、発酵させ、ＥＰＳを産生させることで、ＥＰＳを含む発酵乳が製造できる。
(Other)
In the production of the composition of the present invention, the stage of blending EPS of lactic acid bacteria can be appropriately selected. The compounding stage is not particularly limited as long as the EPS characteristics of lactic acid bacteria are not significantly impaired. For example, a culture containing EPS obtained by culturing an EPS-producing lactic acid bacterium, a crude product thereof, and a purified product can be mixed and blended with raw materials at various stages of the production process. Alternatively, when the composition of the present invention is carried out as fermented milk, a culture containing EPS, a crude refined product thereof, or a refined product thereof is mixed with a raw material or fermented milk after fermentation and blended, or a lactic acid bacterium that produces EPS. Is added to the raw material milk as a starter and fermented to produce EPS, whereby fermented milk containing EPS can be produced.
本発明の組成物には、免疫バランスの調節のために用いることができる旨を表示することができ、また特定の対象に対して摂取を薦める旨を表示することができる。表示は、直接的にまたは間接的にすることができ、直接的な表示の例は、製品自体、パッケージ、容器、ラベル、タグ等の有体物への記載であり、間接的な表示の例は、ウェブサイト、店頭、パンフレット、展示会、メディアセミナー等のセミナー、書籍、新聞、雑誌、テレビ、ラジオ、郵送物、電子メール、音声等の、場所または手段による、広告・宣伝活動を含む。 The composition of the present invention can be labeled as being usable for the regulation of immune balance, and can be labeled as being recommended for ingestion by a specific subject. Labeling can be direct or indirect, examples of direct labeling are descriptions on tangible objects such as the product itself, packages, containers, labels, tags, and examples of indirect labeling are. Includes advertising and publicity activities by location or means such as websites, storefronts, pamphlets, exhibitions, media seminars and other seminars, books, newspapers, magazines, television, radio, mailings, e-mail, audio, etc.
以下、実施例を用いて、本発明をさらに具体的に説明する。但し、本発明の技術的範囲は、これら実施例に限定されるものではない。 Hereinafter, the present invention will be described in more detail with reference to Examples. However, the technical scope of the present invention is not limited to these examples.
＜EPS（菌体外多糖体）の調製＞
実施例1においては、10質量%脱脂粉乳培地でLactobacillus delbrueckii subsp. bulgaricus OLL1073R-1を培養して得た培養物中のEPSを精製した。すなわち、37℃で18時間培養した培養物に、終濃度10質量%になるようトリクロロ酢酸を加えて変性タンパク質を除去し、冷エタノールを加えて4℃で2時間静置してEPSを含む沈殿物を得た。これを、透析膜（分画分子量6,000 - 8,000）を用いてMilliQ水に対して透析し、核酸とタンパク質を酵素分解した後、再度エタノール沈殿を行って沈殿物を得た。これをMilliQ水に溶解し、再度透析を行った後に凍結乾燥を行ってEPSを精製した。
<Preparation of EPS (Extracellular polysaccharide)>
In Example 1, EPS in the culture obtained by culturing Lactobacillus delbrueckii subsp. Bulgaricus OLL1073R-1 in 10% by mass skim milk powder medium was purified. That is, trichloroacetic acid was added to the culture cultured at 37 ° C. for 18 hours to remove the denatured protein, cold ethanol was added, and the mixture was allowed to stand at 4 ° C. for 2 hours to precipitate containing EPS. I got something. This was dialyzed against MilliQ water using a dialysis membrane (molecular weight cut off 6,000-8,000), nucleic acids and proteins were enzymatically decomposed, and then ethanol precipitation was performed again to obtain a precipitate. This was dissolved in MilliQ water, dialyzed again, and then freeze-dried to purify EPS.
＜実施例１＞
C57BL/6Jマウス、メス、8週齢(日本チャールスリバー)に対し、ヒトB型肝炎ウイルス抗原ペプチド(I-Ad HBc helper peptide TPPAYRPPNAPIL, MBL)50μgを用いて4匹を免疫した。免疫組成物はComplete Freund's Adjuvant(和光純薬) 50μL、上記抗原ペプチド溶液5μL、PBS 45μLの計100μLを十分にエマルジョン化した後、1匹ずつマウス腹腔内に注射した。免疫後、マウス体内ではヒトB型肝炎ウイルス抗原(以下、HBc)に特異的な各Thが増殖するとともに体内を循環する。
<Example 1>
Four C57BL / 6J mice, females, and 8 weeks old (Charles River Japan) were immunized with 50 μg of human hepatitis B virus antigen peptide (IA d HBc helper peptide TPPAYRPPNAPIL, MBL). The immune composition was fully emulsified with 50 μL of Complete Freund's Adjuvant (Wako Pure Chemical Industries, Ltd.), 5 μL of the above-mentioned antigen peptide solution, and 45 μL of PBS, and then injected into the abdominal cavity of each mouse. After immunization, each Th specific for human hepatitis B virus antigen (hereinafter, HBc) proliferates and circulates in the body of the mouse.
免疫1週間後、マウスを安楽殺した。HBc抗原特異的なTh1、Th2、Th17、Tregを含む脾臓を採取し、4匹の脾細胞をプールして一定の細胞数(5×106cells/ml)で培養した。培養時にHBcペプチドを加えて(10μg/ml)各Thを刺激し、48時間後にHBc抗原ペプチド特異的に産生されたIFN-γ、IL-4、IL-17、IL-10の上清濃度を、BD OptEIA Mouse ELISA Set(Becton, Dickinson and Company)を用いて測定した(IFN-γ、IL-4、IL-10)。IL-17は、IL-17A Mouse Uncoated ELISA Kit (Invitrogen)を用いて測定した。いずれもEPSを培地に添加した(150μg/mL)場合も同様に測定し、EPSを加えない場合と比較した。それぞれについて、平均±SEM, n=8, HBcペプチド刺激時のEPSの有無でstudent's t test検定によりP値を算出した。 One week after immunization, the mice were euthanized. Spleens containing HBc antigen-specific Th1, Th2, Th17, and Treg were collected, and 4 splenocytes were pooled and cultured at a constant cell number (5 × 10 6 cells / ml). HBc peptide was added during culture (10 μg / ml) to stimulate each Th, and 48 hours later, the supernatant concentrations of IFN-γ, IL-4, IL-17, and IL-10 produced specifically for HBc antigen peptide were measured. , BD OptEIA Mouse ELISA Set (Becton, Dickinson and Company) (IFN-γ, IL-4, IL-10). IL-17 was measured using the IL-17A Mouse Uncoated ELISA Kit (Invitrogen). In each case, the measurement was performed in the same manner when EPS was added to the medium (150 μg / mL), and the comparison was made when EPS was not added. For each, the mean ± SEM, n = 8, and the presence or absence of EPS during HBc peptide stimulation were used to calculate the P value by the student's t-test test.
結果、抗原特異的なIFN-γ、IL-4、IL-17、IL-10を確認した。これらはそれぞれTh1、Th2、Th17、Tregから産生されていることが考えられる。培地へEPSを添加すると、IL-17以外のサイトカイン分泌は有意に増加した。しかし、IL-17は変動が無かった。(図1) As a result, antigen-specific IFN-γ, IL-4, IL-17, and IL-10 were confirmed. It is considered that these are produced from Th1, Th2, Th17, and Treg, respectively. Addition of EPS to the medium significantly increased the secretion of cytokines other than IL-17. However, IL-17 did not change. (Figure 1)
このことから、EPSが、Th17を活性化することなく（抑制もせず、適切な発現を維持し続ける）、Th1、Th2、Tregを活性化し、IFN-γ、IL-4、IL-10の産生を促進することを見出した。 From this, EPS activates Th1, Th2, and Treg without activating Th17 (without suppressing it and maintaining proper expression), and produces IFN-γ, IL-4, and IL-10. Found to promote.
Claims (9)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2019234183A JP2021101645A (en) | 2019-12-25 | 2019-12-25 | Composition for regulating immune balance |
| CN202011542027.5A CN113018308A (en) | 2019-12-25 | 2020-12-23 | Composition for regulating immune balance |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2019234183A JP2021101645A (en) | 2019-12-25 | 2019-12-25 | Composition for regulating immune balance |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2021101645A true JP2021101645A (en) | 2021-07-15 |
Family
ID=76459066
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019234183A Pending JP2021101645A (en) | 2019-12-25 | 2019-12-25 | Composition for regulating immune balance |
Country Status (2)
| Country | Link |
|---|---|
| JP (1) | JP2021101645A (en) |
| CN (1) | CN113018308A (en) |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008245576A (en) * | 2007-03-30 | 2008-10-16 | Yotsuba Nyugyo Kk | Lactobacillus expectable to have immunomodulating action and extracellular polysaccharide |
| JP2009256312A (en) * | 2008-03-26 | 2009-11-05 | Fujicco Co Ltd | Immunomodulating composition and food and drink or material for food and drink using the composition |
| JP2010132579A (en) * | 2008-12-02 | 2010-06-17 | Snow Brand Milk Prod Co Ltd | Lactobacillus having immunomodulating function |
| WO2016084029A1 (en) * | 2014-11-26 | 2016-06-02 | Probiotical S.P.A. | Strains of lactobacillus or bifidobacterium for maintaining homeostasis |
| JP6916042B2 (en) * | 2017-06-09 | 2021-08-11 | 株式会社明治 | Composition for promoting antigen-specific interferon gamma production |
| CN109182186B (en) * | 2018-09-19 | 2022-02-01 | 内蒙古大学 | Lactobacillus extracellular polysaccharide and immunologic adjuvant |
-
2019
- 2019-12-25 JP JP2019234183A patent/JP2021101645A/en active Pending
-
2020
- 2020-12-23 CN CN202011542027.5A patent/CN113018308A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CN113018308A (en) | 2021-06-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Arunachalam et al. | Enhancement of natural immune function by dietary consumption of Bifidobacterium lactis (HN019) | |
| WO2022041656A1 (en) | Lactobacillus paracasei 207-27 and application thereof | |
| JP4521687B2 (en) | Probiotics, Propionibacterium ienseni 702 | |
| US9737575B2 (en) | Use of lactic acid bacteria to treat or prevent eczema | |
| WO2022041658A1 (en) | Bifidobacterium breve 207-1 and use thereof | |
| EP1854467B1 (en) | Immunostimulatory composition | |
| KR20160130779A (en) | Sleep quality improver | |
| ES2716973T3 (en) | Lactobacillus rhamnosus RHT-3201 conjugated with polymeric binder polysaccharide and use thereof for the prevention or treatment of atopic diseases | |
| US20100221226A1 (en) | Use of a Bifidobacterium Strain for Preparing a Composition for Preventing and/or Treating Allergic Manifestations | |
| CN111212575A (en) | Composition for muscle building | |
| US20230390348A1 (en) | Composition for enhancing immune checkpoint blockade therapy | |
| CN112351693A (en) | Anti-influenza virus agent for inhibiting severe influenza | |
| TWI476000B (en) | Production of Propionic Acid Bacteria in the Preparation of Preventive Agents for Influenza Infectious Diseases and Induction Promoters for Neutralizing Antibodies | |
| CN108882740A (en) | Fermentating formula object containing indigestible oligosaccharides | |
| WO2018190407A1 (en) | COMPOSITION FOR ACTIVATING Toll-LIKE RECEPTOR 2 | |
| WO2020067422A1 (en) | Composition for activating t cells | |
| WO2018225786A1 (en) | Composition for cellular immune activation | |
| JPH05252900A (en) | Immunopotentiative composition | |
| WO2015046407A1 (en) | Prophylactic agent for immunological diseases | |
| Van de Water et al. | Yogurt and immunity: the health benefits of fermented milk products that contain lactic acid bacteria | |
| WO2011099875A1 (en) | Use of lactic acid bacteria to treat or prevent rhinitis | |
| JP2021101645A (en) | Composition for regulating immune balance | |
| JP2021080187A (en) | Composition for inhibiting viral replication | |
| JP3958456B2 (en) | Functional food and drink with serum lipid improving effect | |
| JP2017197486A (en) | INTERFERON λ INDUCER |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20221215 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20231110 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20231226 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20240220 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20240417 |