TWI696465B - 新穎乳酸菌及其用途 - Google Patents
新穎乳酸菌及其用途 Download PDFInfo
- Publication number
- TWI696465B TWI696465B TW107118302A TW107118302A TWI696465B TW I696465 B TWI696465 B TW I696465B TW 107118302 A TW107118302 A TW 107118302A TW 107118302 A TW107118302 A TW 107118302A TW I696465 B TWI696465 B TW I696465B
- Authority
- TW
- Taiwan
- Prior art keywords
- lactobacillus
- lactic acid
- acid bacteria
- composition
- ijh
- Prior art date
Links
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 title claims abstract description 366
- 241000894006 Bacteria Species 0.000 title claims abstract description 194
- 239000004310 lactic acid Substances 0.000 title claims abstract description 183
- 235000014655 lactic acid Nutrition 0.000 title claims abstract description 183
- 235000013305 food Nutrition 0.000 claims abstract description 60
- 235000013361 beverage Nutrition 0.000 claims abstract description 54
- 108010003272 Hyaluronate lyase Proteins 0.000 claims abstract description 21
- 102000001974 Hyaluronidases Human genes 0.000 claims abstract description 21
- 229960002773 hyaluronidase Drugs 0.000 claims abstract description 21
- 239000002537 cosmetic Substances 0.000 claims abstract description 18
- 230000006378 damage Effects 0.000 claims abstract description 17
- 230000003266 anti-allergic effect Effects 0.000 claims abstract description 16
- 239000000203 mixture Substances 0.000 claims description 103
- 241000186605 Lactobacillus paracasei Species 0.000 claims description 56
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 41
- 239000008194 pharmaceutical composition Substances 0.000 claims description 18
- 239000013589 supplement Substances 0.000 claims description 11
- 235000013376 functional food Nutrition 0.000 claims description 9
- 235000021107 fermented food Nutrition 0.000 claims description 8
- 208000027418 Wounds and injury Diseases 0.000 claims description 4
- 208000014674 injury Diseases 0.000 claims description 4
- 229920001282 polysaccharide Polymers 0.000 abstract description 111
- 239000005017 polysaccharide Substances 0.000 abstract description 111
- 230000007935 neutral effect Effects 0.000 abstract description 45
- 230000000694 effects Effects 0.000 abstract description 36
- 238000000338 in vitro Methods 0.000 abstract description 30
- 229950006780 n-acetylglucosamine Drugs 0.000 abstract description 16
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 abstract description 14
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 abstract description 14
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 abstract description 14
- 230000002075 anti-alcohol Effects 0.000 abstract description 9
- 230000005764 inhibitory process Effects 0.000 abstract description 8
- 239000003814 drug Substances 0.000 abstract description 7
- -1 feed Substances 0.000 abstract description 5
- 150000004676 glycans Chemical class 0.000 abstract 3
- 150000004804 polysaccharides Chemical class 0.000 description 106
- 108090000623 proteins and genes Proteins 0.000 description 50
- 241000186660 Lactobacillus Species 0.000 description 47
- 239000007788 liquid Substances 0.000 description 37
- 229940039696 lactobacillus Drugs 0.000 description 36
- 235000018102 proteins Nutrition 0.000 description 32
- 102000004169 proteins and genes Human genes 0.000 description 32
- 239000002609 medium Substances 0.000 description 30
- 238000000034 method Methods 0.000 description 27
- 239000000243 solution Substances 0.000 description 27
- 239000002253 acid Substances 0.000 description 23
- 238000012360 testing method Methods 0.000 description 23
- 238000004519 manufacturing process Methods 0.000 description 20
- 108020004414 DNA Proteins 0.000 description 17
- 241000699670 Mus sp. Species 0.000 description 15
- 238000000926 separation method Methods 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 13
- 206010019728 Hepatitis alcoholic Diseases 0.000 description 12
- 208000002353 alcoholic hepatitis Diseases 0.000 description 12
- 230000002401 inhibitory effect Effects 0.000 description 12
- 230000001580 bacterial effect Effects 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- 239000000843 powder Substances 0.000 description 11
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 10
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 10
- 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 10
- 239000008103 glucose Substances 0.000 description 10
- 239000002244 precipitate Substances 0.000 description 10
- 210000002966 serum Anatomy 0.000 description 10
- 235000000346 sugar Nutrition 0.000 description 10
- 102000004190 Enzymes Human genes 0.000 description 9
- 108090000790 Enzymes Proteins 0.000 description 9
- 101100290389 Schizosaccharomyces pombe (strain 972 / ATCC 24843) ceg1 gene Proteins 0.000 description 9
- 238000012258 culturing Methods 0.000 description 9
- 229940088598 enzyme Drugs 0.000 description 9
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 8
- 108010082126 Alanine transaminase Proteins 0.000 description 8
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 8
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 8
- 238000005481 NMR spectroscopy Methods 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- BJRNKVDFDLYUGJ-RMPHRYRLSA-N hydroquinone O-beta-D-glucopyranoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC=C(O)C=C1 BJRNKVDFDLYUGJ-RMPHRYRLSA-N 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 7
- 239000006071 cream Substances 0.000 description 7
- 238000000855 fermentation Methods 0.000 description 7
- 230000004151 fermentation Effects 0.000 description 7
- 108091008053 gene clusters Proteins 0.000 description 7
- 238000002156 mixing Methods 0.000 description 7
- 239000006872 mrs medium Substances 0.000 description 7
- 230000035755 proliferation Effects 0.000 description 7
- 235000002639 sodium chloride Nutrition 0.000 description 7
- 238000010998 test method Methods 0.000 description 7
- 235000013311 vegetables Nutrition 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 102000016938 Catalase Human genes 0.000 description 6
- 108010053835 Catalase Proteins 0.000 description 6
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 6
- 102000003855 L-lactate dehydrogenase Human genes 0.000 description 6
- 108700023483 L-lactate dehydrogenases Proteins 0.000 description 6
- 244000199885 Lactobacillus bulgaricus Species 0.000 description 6
- 235000013960 Lactobacillus bulgaricus Nutrition 0.000 description 6
- 102000002704 Leucyl aminopeptidase Human genes 0.000 description 6
- 108010004098 Leucyl aminopeptidase Proteins 0.000 description 6
- 108090001060 Lipase Proteins 0.000 description 6
- 102000004882 Lipase Human genes 0.000 description 6
- 239000004367 Lipase Substances 0.000 description 6
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 210000000941 bile Anatomy 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- XLJMAIOERFSOGZ-UHFFFAOYSA-N cyanic acid Chemical compound OC#N XLJMAIOERFSOGZ-UHFFFAOYSA-N 0.000 description 6
- 235000013572 fruit purees Nutrition 0.000 description 6
- 239000001963 growth medium Substances 0.000 description 6
- 235000019421 lipase Nutrition 0.000 description 6
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 235000013399 edible fruits Nutrition 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 210000004051 gastric juice Anatomy 0.000 description 5
- 238000002955 isolation Methods 0.000 description 5
- 235000012054 meals Nutrition 0.000 description 5
- 239000006041 probiotic Substances 0.000 description 5
- 235000018291 probiotics Nutrition 0.000 description 5
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 5
- 239000011550 stock solution Substances 0.000 description 5
- 150000008163 sugars Chemical class 0.000 description 5
- 230000002087 whitening effect Effects 0.000 description 5
- 108020004465 16S ribosomal RNA Proteins 0.000 description 4
- 241000251468 Actinopterygii Species 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 108700023372 Glycosyltransferases Proteins 0.000 description 4
- 240000006024 Lactobacillus plantarum Species 0.000 description 4
- 235000013965 Lactobacillus plantarum Nutrition 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 108700026244 Open Reading Frames Proteins 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 229960000271 arbutin Drugs 0.000 description 4
- 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 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 235000015140 cultured milk Nutrition 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 229940004208 lactobacillus bulgaricus Drugs 0.000 description 4
- 229940072205 lactobacillus plantarum Drugs 0.000 description 4
- 238000010172 mouse model Methods 0.000 description 4
- 235000016709 nutrition Nutrition 0.000 description 4
- 230000008520 organization Effects 0.000 description 4
- BJRNKVDFDLYUGJ-UHFFFAOYSA-N p-hydroxyphenyl beta-D-alloside Natural products OC1C(O)C(O)C(CO)OC1OC1=CC=C(O)C=C1 BJRNKVDFDLYUGJ-UHFFFAOYSA-N 0.000 description 4
- 230000002062 proliferating effect Effects 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 235000011888 snacks Nutrition 0.000 description 4
- 210000002784 stomach Anatomy 0.000 description 4
- 238000003860 storage Methods 0.000 description 4
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 229920001817 Agar Polymers 0.000 description 3
- 102000002322 Egg Proteins Human genes 0.000 description 3
- 108010000912 Egg Proteins Proteins 0.000 description 3
- 240000001046 Lactobacillus acidophilus Species 0.000 description 3
- 235000013956 Lactobacillus acidophilus Nutrition 0.000 description 3
- 241000186673 Lactobacillus delbrueckii Species 0.000 description 3
- 241001647418 Lactobacillus paralimentarius Species 0.000 description 3
- 241000186604 Lactobacillus reuteri Species 0.000 description 3
- 108010014251 Muramidase Proteins 0.000 description 3
- 102000016943 Muramidase Human genes 0.000 description 3
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 239000008272 agar Substances 0.000 description 3
- 239000003613 bile acid Substances 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 210000002421 cell wall Anatomy 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 235000013339 cereals Nutrition 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 235000009508 confectionery Nutrition 0.000 description 3
- 238000012136 culture method Methods 0.000 description 3
- 230000008260 defense mechanism Effects 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 229910052742 iron Inorganic materials 0.000 description 3
- 229940039695 lactobacillus acidophilus Drugs 0.000 description 3
- 239000004325 lysozyme Substances 0.000 description 3
- 229960000274 lysozyme Drugs 0.000 description 3
- 235000010335 lysozyme Nutrition 0.000 description 3
- 235000013336 milk Nutrition 0.000 description 3
- 239000008267 milk Substances 0.000 description 3
- 210000004080 milk Anatomy 0.000 description 3
- 230000035764 nutrition Effects 0.000 description 3
- OQUKIQWCVTZJAF-UHFFFAOYSA-N phenol;sulfuric acid Chemical compound OS(O)(=O)=O.OC1=CC=CC=C1 OQUKIQWCVTZJAF-UHFFFAOYSA-N 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 239000007974 sodium acetate buffer Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 101150068642 wzb gene Proteins 0.000 description 3
- WQZGKKKJIJFFOK-SVZMEOIVSA-N (+)-Galactose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-SVZMEOIVSA-N 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 2
- XUCIJNAGGSZNQT-JHSLDZJXSA-N (R)-amygdalin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](O[C@@H](C#N)C=2C=CC=CC=2)O1 XUCIJNAGGSZNQT-JHSLDZJXSA-N 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 241000304886 Bacilli Species 0.000 description 2
- 241000193830 Bacillus <bacterium> Species 0.000 description 2
- 241000186000 Bifidobacterium Species 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 241001635320 Desemzia Species 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 229920002444 Exopolysaccharide Polymers 0.000 description 2
- 229930091371 Fructose Natural products 0.000 description 2
- 239000005715 Fructose Substances 0.000 description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 2
- 241000287828 Gallus gallus Species 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 241000489238 Lactobacillus camelliae Species 0.000 description 2
- 244000199866 Lactobacillus casei Species 0.000 description 2
- 235000013958 Lactobacillus casei Nutrition 0.000 description 2
- 241001147746 Lactobacillus delbrueckii subsp. lactis Species 0.000 description 2
- 241000370757 Lactobacillus fuchuensis Species 0.000 description 2
- 241000186684 Lactobacillus pentosus Species 0.000 description 2
- 241000218588 Lactobacillus rhamnosus Species 0.000 description 2
- 241000186869 Lactobacillus salivarius Species 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 241000192001 Pediococcus Species 0.000 description 2
- 241000191996 Pediococcus pentosaceus Species 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 238000012300 Sequence Analysis Methods 0.000 description 2
- 102000004338 Transferrin Human genes 0.000 description 2
- 108090000901 Transferrin Proteins 0.000 description 2
- 241000202221 Weissella Species 0.000 description 2
- 239000005862 Whey Substances 0.000 description 2
- 102000007544 Whey Proteins Human genes 0.000 description 2
- 108010046377 Whey Proteins Proteins 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 230000007815 allergy Effects 0.000 description 2
- 229940089837 amygdalin Drugs 0.000 description 2
- YZLOSXFCSIDECK-UHFFFAOYSA-N amygdalin Natural products OCC1OC(OCC2OC(O)C(O)C(O)C2O)C(O)C(O)C1OC(C#N)c3ccccc3 YZLOSXFCSIDECK-UHFFFAOYSA-N 0.000 description 2
- 238000005349 anion exchange Methods 0.000 description 2
- 238000005571 anion exchange chromatography Methods 0.000 description 2
- 230000000721 bacterilogical effect Effects 0.000 description 2
- 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 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000001851 biosynthetic effect Effects 0.000 description 2
- 235000008429 bread Nutrition 0.000 description 2
- ZCCIPPOKBCJFDN-UHFFFAOYSA-N calcium nitrate Chemical compound [Ca+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ZCCIPPOKBCJFDN-UHFFFAOYSA-N 0.000 description 2
- 229940041514 candida albicans extract Drugs 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 235000013330 chicken meat Nutrition 0.000 description 2
- 230000001332 colony forming effect Effects 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 230000003750 conditioning effect Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 210000002969 egg yolk Anatomy 0.000 description 2
- 235000013345 egg yolk Nutrition 0.000 description 2
- 235000013601 eggs Nutrition 0.000 description 2
- YGHHWSRCTPQFFC-UHFFFAOYSA-N eucalyptosin A Natural products OC1C(O)C(O)C(CO)OC1OC1C(OC(C#N)C=2C=CC=CC=2)OC(CO)C(O)C1O YGHHWSRCTPQFFC-UHFFFAOYSA-N 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 208000010706 fatty liver disease Diseases 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 229920002674 hyaluronan Polymers 0.000 description 2
- 229960003160 hyaluronic acid Drugs 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 229940017800 lactobacillus casei Drugs 0.000 description 2
- 229940001882 lactobacillus reuteri Drugs 0.000 description 2
- 238000009630 liquid culture Methods 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 235000013372 meat Nutrition 0.000 description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
- 150000002772 monosaccharides Chemical class 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- 210000002706 plastid Anatomy 0.000 description 2
- 230000001376 precipitating effect Effects 0.000 description 2
- 230000000529 probiotic effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- HEBKCHPVOIAQTA-ZXFHETKHSA-N ribitol Chemical compound OC[C@H](O)[C@H](O)[C@H](O)CO HEBKCHPVOIAQTA-ZXFHETKHSA-N 0.000 description 2
- 238000007789 sealing Methods 0.000 description 2
- 238000011218 seed culture Methods 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 231100000240 steatosis hepatitis Toxicity 0.000 description 2
- 238000012916 structural analysis Methods 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 239000011573 trace mineral Substances 0.000 description 2
- 235000013619 trace mineral Nutrition 0.000 description 2
- 239000012581 transferrin Substances 0.000 description 2
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- 238000000108 ultra-filtration Methods 0.000 description 2
- 239000012138 yeast extract Substances 0.000 description 2
- 235000013618 yogurt Nutrition 0.000 description 2
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 description 1
- PUMZXCBVHLCWQG-UHFFFAOYSA-N 1-(4-Hydroxyphenyl)-2-aminoethanol hydrochloride Chemical compound [Cl-].[NH3+]CC(O)C1=CC=C(O)C=C1 PUMZXCBVHLCWQG-UHFFFAOYSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- PAWQVTBBRAZDMG-UHFFFAOYSA-N 2-(3-bromo-2-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1F PAWQVTBBRAZDMG-UHFFFAOYSA-N 0.000 description 1
- BGNGWHSBYQYVRX-UHFFFAOYSA-N 4-(dimethylamino)benzaldehyde Chemical compound CN(C)C1=CC=C(C=O)C=C1 BGNGWHSBYQYVRX-UHFFFAOYSA-N 0.000 description 1
- QCVGEOXPDFCNHA-UHFFFAOYSA-N 5,5-dimethyl-2,4-dioxo-1,3-oxazolidine-3-carboxamide Chemical compound CC1(C)OC(=O)N(C(N)=O)C1=O QCVGEOXPDFCNHA-UHFFFAOYSA-N 0.000 description 1
- 241000201860 Abiotrophia Species 0.000 description 1
- 208000007082 Alcoholic Fatty Liver Diseases 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- 241000422409 Alkalibacterium Species 0.000 description 1
- 241000193818 Atopobium Species 0.000 description 1
- 241000193836 Atopobium rimae Species 0.000 description 1
- 241001136151 Atopostipes Species 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 241000053357 Bavariicoccus Species 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241000206594 Carnobacterium Species 0.000 description 1
- 108010059892 Cellulase Proteins 0.000 description 1
- 241000283153 Cetacea Species 0.000 description 1
- 241000819038 Chichester Species 0.000 description 1
- 241000725101 Clea Species 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- GUBGYTABKSRVRQ-CUHNMECISA-N D-Cellobiose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-CUHNMECISA-N 0.000 description 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
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 102000016911 Deoxyribonucleases Human genes 0.000 description 1
- 108010053770 Deoxyribonucleases Proteins 0.000 description 1
- 241001430190 Eggerthia catenaformis Species 0.000 description 1
- 108010067770 Endopeptidase K Proteins 0.000 description 1
- 241000194033 Enterococcus Species 0.000 description 1
- 208000004930 Fatty Liver Diseases 0.000 description 1
- 206010016262 Fatty liver alcoholic Diseases 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 235000019733 Fish meal Nutrition 0.000 description 1
- 241000551711 Fructobacillus Species 0.000 description 1
- 208000007882 Gastritis Diseases 0.000 description 1
- 240000004409 Gaultheria antipoda Species 0.000 description 1
- 235000012446 Gaultheria antipoda Nutrition 0.000 description 1
- 235000007270 Gaultheria hispida Nutrition 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 102000051366 Glycosyltransferases Human genes 0.000 description 1
- BIVBRWYINDPWKA-VLQRKCJKSA-L Glycyrrhizinate dipotassium Chemical compound [K+].[K+].O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@H]1CC[C@]2(C)[C@H]3C(=O)C=C4[C@@H]5C[C@](C)(CC[C@@]5(CC[C@@]4(C)[C@]3(C)CC[C@H]2C1(C)C)C)C(O)=O)C([O-])=O)[C@@H]1O[C@H](C([O-])=O)[C@@H](O)[C@H](O)[C@H]1O BIVBRWYINDPWKA-VLQRKCJKSA-L 0.000 description 1
- 241000235796 Granulicatella Species 0.000 description 1
- 206010019708 Hepatic steatosis Diseases 0.000 description 1
- 240000005979 Hordeum vulgare Species 0.000 description 1
- 235000007340 Hordeum vulgare Nutrition 0.000 description 1
- 241001267420 Isobaculum Species 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- 241000186778 Kandleria vitulina Species 0.000 description 1
- LKDRXBCSQODPBY-AMVSKUEXSA-N L-(-)-Sorbose Chemical compound OCC1(O)OC[C@H](O)[C@@H](O)[C@@H]1O LKDRXBCSQODPBY-AMVSKUEXSA-N 0.000 description 1
- SHZGCJCMOBCMKK-JFNONXLTSA-N L-rhamnopyranose Chemical compound C[C@@H]1OC(O)[C@H](O)[C@H](O)[C@H]1O SHZGCJCMOBCMKK-JFNONXLTSA-N 0.000 description 1
- PNNNRSAQSRJVSB-UHFFFAOYSA-N L-rhamnose Natural products CC(O)C(O)C(O)C(O)C=O PNNNRSAQSRJVSB-UHFFFAOYSA-N 0.000 description 1
- 241000186717 Lactobacillus acetotolerans Species 0.000 description 1
- 241000110061 Lactobacillus acidifarinae Species 0.000 description 1
- 241000028630 Lactobacillus acidipiscis Species 0.000 description 1
- 241000186716 Lactobacillus agilis Species 0.000 description 1
- 241001507052 Lactobacillus algidus Species 0.000 description 1
- 241000186715 Lactobacillus alimentarius Species 0.000 description 1
- 241001647783 Lactobacillus amylolyticus Species 0.000 description 1
- 241000186714 Lactobacillus amylophilus Species 0.000 description 1
- 241000168643 Lactobacillus amylotrophicus Species 0.000 description 1
- 241000186713 Lactobacillus amylovorus Species 0.000 description 1
- 241000186712 Lactobacillus animalis Species 0.000 description 1
- 241000316282 Lactobacillus antri Species 0.000 description 1
- 241000954248 Lactobacillus apodemi Species 0.000 description 1
- 241000861652 Lactobacillus aquaticus Species 0.000 description 1
- 241000186723 Lactobacillus bifermentans Species 0.000 description 1
- 240000001929 Lactobacillus brevis Species 0.000 description 1
- 235000013957 Lactobacillus brevis Nutrition 0.000 description 1
- 241000186679 Lactobacillus buchneri Species 0.000 description 1
- 241000208559 Lactobacillus cacaonum Species 0.000 description 1
- 241000902616 Lactobacillus ceti Species 0.000 description 1
- 241001061980 Lactobacillus coleohominis Species 0.000 description 1
- 241001468197 Lactobacillus collinoides Species 0.000 description 1
- 241000838743 Lactobacillus concavus Species 0.000 description 1
- 241000186842 Lactobacillus coryniformis Species 0.000 description 1
- 241000218492 Lactobacillus crispatus Species 0.000 description 1
- 241000861211 Lactobacillus crustorum Species 0.000 description 1
- 241001134659 Lactobacillus curvatus Species 0.000 description 1
- 241001647786 Lactobacillus delbrueckii subsp. delbrueckii Species 0.000 description 1
- 241001060359 Lactobacillus delbrueckii subsp. indicus Species 0.000 description 1
- 241000500356 Lactobacillus dextrinicus Species 0.000 description 1
- 241000790171 Lactobacillus diolivorans Species 0.000 description 1
- 241000976279 Lactobacillus equi Species 0.000 description 1
- 241001026944 Lactobacillus equigenerosi Species 0.000 description 1
- 241000208558 Lactobacillus fabifermentans Species 0.000 description 1
- 241000831741 Lactobacillus farraginis Species 0.000 description 1
- 241000186840 Lactobacillus fermentum Species 0.000 description 1
- 241000015236 Lactobacillus fornicalis Species 0.000 description 1
- 241000186839 Lactobacillus fructivorans Species 0.000 description 1
- 241001493843 Lactobacillus frumenti Species 0.000 description 1
- 241000509544 Lactobacillus gallinarum Species 0.000 description 1
- 241000186606 Lactobacillus gasseri Species 0.000 description 1
- 241000316283 Lactobacillus gastricus Species 0.000 description 1
- 241000950383 Lactobacillus ghanensis Species 0.000 description 1
- 241000866684 Lactobacillus graminis Species 0.000 description 1
- 241000111368 Lactobacillus hammesii Species 0.000 description 1
- 241000383778 Lactobacillus hamsteri Species 0.000 description 1
- 241000925032 Lactobacillus harbinensis Species 0.000 description 1
- 241000914114 Lactobacillus hayakitensis Species 0.000 description 1
- 240000002605 Lactobacillus helveticus Species 0.000 description 1
- 235000013967 Lactobacillus helveticus Nutrition 0.000 description 1
- 241000186685 Lactobacillus hilgardii Species 0.000 description 1
- 241001468190 Lactobacillus homohiochii Species 0.000 description 1
- 241001195326 Lactobacillus hordei Species 0.000 description 1
- 241001324870 Lactobacillus iners Species 0.000 description 1
- 241001343376 Lactobacillus ingluviei Species 0.000 description 1
- 241001640457 Lactobacillus intestinalis Species 0.000 description 1
- 241001561398 Lactobacillus jensenii Species 0.000 description 1
- 241001468157 Lactobacillus johnsonii Species 0.000 description 1
- 241000316281 Lactobacillus kalixensis Species 0.000 description 1
- 241000108055 Lactobacillus kefiranofaciens Species 0.000 description 1
- 241001468191 Lactobacillus kefiri Species 0.000 description 1
- 241000191683 Lactobacillus kisonensis Species 0.000 description 1
- 241000674808 Lactobacillus kitasatonis Species 0.000 description 1
- 241001339775 Lactobacillus kunkeei Species 0.000 description 1
- 241001134654 Lactobacillus leichmannii Species 0.000 description 1
- 241000520745 Lactobacillus lindneri Species 0.000 description 1
- 241000751214 Lactobacillus malefermentans Species 0.000 description 1
- 241000186851 Lactobacillus mali Species 0.000 description 1
- 241000016642 Lactobacillus manihotivorans Species 0.000 description 1
- 241000414465 Lactobacillus mindensis Species 0.000 description 1
- 241000394636 Lactobacillus mucosae Species 0.000 description 1
- 241000186871 Lactobacillus murinus Species 0.000 description 1
- 241001635183 Lactobacillus nagelii Species 0.000 description 1
- 241000468580 Lactobacillus namurensis Species 0.000 description 1
- 241000938545 Lactobacillus nantensis Species 0.000 description 1
- 241001097694 Lactobacillus nodensis Species 0.000 description 1
- 241001150383 Lactobacillus oligofermentans Species 0.000 description 1
- 241000186784 Lactobacillus oris Species 0.000 description 1
- 241000191684 Lactobacillus otakiensis Species 0.000 description 1
- 241000216456 Lactobacillus panis Species 0.000 description 1
- 241000692795 Lactobacillus pantheris Species 0.000 description 1
- 241001105994 Lactobacillus parabrevis Species 0.000 description 1
- 241001643453 Lactobacillus parabuchneri Species 0.000 description 1
- 241000972176 Lactobacillus paracollinoides Species 0.000 description 1
- 241000831743 Lactobacillus parafarraginis Species 0.000 description 1
- 241001643449 Lactobacillus parakefiri Species 0.000 description 1
- 241000866650 Lactobacillus paraplantarum Species 0.000 description 1
- 241001448603 Lactobacillus perolens Species 0.000 description 1
- 241001495404 Lactobacillus pontis Species 0.000 description 1
- 241000220680 Lactobacillus psittaci Species 0.000 description 1
- 241000191682 Lactobacillus rapi Species 0.000 description 1
- 241000692139 Lactobacillus rennini Species 0.000 description 1
- 241000602084 Lactobacillus rossiae Species 0.000 description 1
- 241000186870 Lactobacillus ruminis Species 0.000 description 1
- 241000318646 Lactobacillus saerimneri Species 0.000 description 1
- 241000186612 Lactobacillus sakei Species 0.000 description 1
- 241000186868 Lactobacillus sanfranciscensis Species 0.000 description 1
- 235000013864 Lactobacillus sanfrancisco Nutrition 0.000 description 1
- 241001424195 Lactobacillus satsumensis Species 0.000 description 1
- 241000915257 Lactobacillus secaliphilus Species 0.000 description 1
- 241000024101 Lactobacillus senmaizukei Species 0.000 description 1
- 241000186867 Lactobacillus sharpeae Species 0.000 description 1
- 241000755777 Lactobacillus siliginis Species 0.000 description 1
- 241001599932 Lactobacillus spicheri Species 0.000 description 1
- 241001643448 Lactobacillus suebicus Species 0.000 description 1
- 241000191665 Lactobacillus sunkii Species 0.000 description 1
- 241000390527 Lactobacillus taiwanensis Species 0.000 description 1
- 241000489237 Lactobacillus thailandensis Species 0.000 description 1
- 241000692136 Lactobacillus tucceti Species 0.000 description 1
- 241000316280 Lactobacillus ultunensis Species 0.000 description 1
- 241000908018 Lactobacillus uvarum Species 0.000 description 1
- 241000751212 Lactobacillus vaccinostercus Species 0.000 description 1
- 241000186783 Lactobacillus vaginalis Species 0.000 description 1
- 241001456524 Lactobacillus versmoldensis Species 0.000 description 1
- 241000692127 Lactobacillus vini Species 0.000 description 1
- 241000577554 Lactobacillus zeae Species 0.000 description 1
- 241000110060 Lactobacillus zymae Species 0.000 description 1
- 241000194036 Lactococcus Species 0.000 description 1
- 241000907998 Lactovum Species 0.000 description 1
- 241000192132 Leuconostoc Species 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 239000005913 Maltodextrin Substances 0.000 description 1
- 229920002774 Maltodextrin Polymers 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 229910021380 Manganese Chloride Inorganic materials 0.000 description 1
- GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001423782 Marinilactibacillus Species 0.000 description 1
- 241001468189 Melissococcus Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000202223 Oenococcus Species 0.000 description 1
- 241000927544 Olsenella Species 0.000 description 1
- 241000282372 Panthera onca Species 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 241000398992 Pilibacter Species 0.000 description 1
- 108010059820 Polygalacturonase Proteins 0.000 description 1
- 108010009736 Protein Hydrolysates Proteins 0.000 description 1
- 241000287530 Psittaciformes Species 0.000 description 1
- 108090000783 Renin Proteins 0.000 description 1
- 102100028255 Renin Human genes 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- NGFMICBWJRZIBI-JZRPKSSGSA-N Salicin Natural products O([C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@H](CO)O1)c1c(CO)cccc1 NGFMICBWJRZIBI-JZRPKSSGSA-N 0.000 description 1
- 229920002385 Sodium hyaluronate Polymers 0.000 description 1
- 235000019764 Soybean Meal Nutrition 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 244000057717 Streptococcus lactis Species 0.000 description 1
- 235000014897 Streptococcus lactis Nutrition 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
- 229930006000 Sucrose Natural products 0.000 description 1
- 241000500334 Tetragenococcus Species 0.000 description 1
- 102000008579 Transposases Human genes 0.000 description 1
- 108010020764 Transposases Proteins 0.000 description 1
- 241001635318 Trichococcus Species 0.000 description 1
- 241000207194 Vagococcus Species 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 229920001284 acidic polysaccharide Polymers 0.000 description 1
- 150000004805 acidic polysaccharides Chemical class 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 208000026594 alcoholic fatty liver disease Diseases 0.000 description 1
- 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 1
- NGFMICBWJRZIBI-UHFFFAOYSA-N alpha-salicin Natural products OC1C(O)C(O)C(CO)OC1OC1=CC=CC=C1CO NGFMICBWJRZIBI-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000003796 beauty Effects 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000010876 biochemical test Methods 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 235000015895 biscuits Nutrition 0.000 description 1
- 229940036811 bone meal Drugs 0.000 description 1
- 239000002374 bone meal Substances 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 235000019577 caloric intake Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- 229960004203 carnitine Drugs 0.000 description 1
- 229940106157 cellulase Drugs 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 230000009920 chelation Effects 0.000 description 1
- 229940112822 chewing gum Drugs 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 239000008294 cold cream Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 238000009500 colour coating Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 229920002055 compound 48/80 Polymers 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000000490 cosmetic additive Substances 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 230000001877 deodorizing effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 229940101029 dipotassium glycyrrhizinate Drugs 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 235000014103 egg white Nutrition 0.000 description 1
- 210000000969 egg white Anatomy 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 108010093305 exopolygalacturonase Proteins 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 239000011790 ferrous sulphate Substances 0.000 description 1
- 235000003891 ferrous sulphate Nutrition 0.000 description 1
- 239000004467 fishmeal Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 235000015203 fruit juice Nutrition 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000012239 gene modification Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 230000005017 genetic modification Effects 0.000 description 1
- 235000013617 genetically modified food Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 235000013402 health food Nutrition 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 231100000753 hepatic injury Toxicity 0.000 description 1
- 235000012907 honey Nutrition 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 230000004957 immunoregulator effect Effects 0.000 description 1
- 229960001438 immunostimulant agent Drugs 0.000 description 1
- 239000003022 immunostimulating agent Substances 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000019734 interleukin-12 production Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 1
- 229910000359 iron(II) sulfate Inorganic materials 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 235000015141 kefir Nutrition 0.000 description 1
- 235000021109 kimchi Nutrition 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 229940012969 lactobacillus fermentum Drugs 0.000 description 1
- 229940054346 lactobacillus helveticus Drugs 0.000 description 1
- 239000006356 lactobacillus kefiranofaciens Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000009115 maintenance therapy Methods 0.000 description 1
- 229940035034 maltodextrin Drugs 0.000 description 1
- 239000011565 manganese chloride Substances 0.000 description 1
- 235000002867 manganese chloride Nutrition 0.000 description 1
- 229940099607 manganese chloride Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 235000020124 milk-based beverage Nutrition 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 235000013379 molasses Nutrition 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 150000002823 nitrates Chemical class 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
- 235000015097 nutrients Nutrition 0.000 description 1
- 229960001576 octopamine Drugs 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 235000016046 other dairy product Nutrition 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 239000013630 prepared media Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 235000002020 sage Nutrition 0.000 description 1
- NGFMICBWJRZIBI-UJPOAAIJSA-N salicin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC=CC=C1CO NGFMICBWJRZIBI-UJPOAAIJSA-N 0.000 description 1
- 229940120668 salicin Drugs 0.000 description 1
- 230000009291 secondary effect Effects 0.000 description 1
- 239000004460 silage Substances 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000010378 sodium ascorbate Nutrition 0.000 description 1
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 1
- 229960005055 sodium ascorbate Drugs 0.000 description 1
- 229940010747 sodium hyaluronate Drugs 0.000 description 1
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 1
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 235000019614 sour taste Nutrition 0.000 description 1
- 239000004455 soybean meal Substances 0.000 description 1
- 235000011496 sports drink Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 235000019640 taste Nutrition 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- WUUHFRRPHJEEKV-UHFFFAOYSA-N tripotassium borate Chemical compound [K+].[K+].[K+].[O-]B([O-])[O-] WUUHFRRPHJEEKV-UHFFFAOYSA-N 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 239000008256 whipped cream Substances 0.000 description 1
- 235000008924 yoghurt drink Nutrition 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
- C12N1/205—Bacterial isolates
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K10/00—Animal feeding-stuffs
- A23K10/10—Animal feeding-stuffs obtained by microbiological or biochemical processes
- A23K10/16—Addition of microorganisms or extracts thereof, e.g. single-cell proteins, to feeding-stuff compositions
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K10/00—Animal feeding-stuffs
- A23K10/10—Animal feeding-stuffs obtained by microbiological or biochemical processes
- A23K10/16—Addition of microorganisms or extracts thereof, e.g. single-cell proteins, to feeding-stuff compositions
- A23K10/18—Addition of microorganisms or extracts thereof, e.g. single-cell proteins, to feeding-stuff compositions of live microorganisms
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/163—Sugars; Polysaccharides
-
- 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
- A23L19/00—Products from fruits or vegetables; Preparation or treatment thereof
- A23L19/09—Mashed or comminuted products, e.g. pulp, purée, sauce, or products made therefrom, e.g. snacks
-
- 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
- A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/99—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from microorganisms other than algae or fungi, e.g. protozoa or bacteria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P19/00—Preparation of compounds containing saccharide radicals
- C12P19/04—Polysaccharides, i.e. compounds containing more than five saccharide radicals attached to each other by glycosidic bonds
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P19/00—Preparation of compounds containing saccharide radicals
- C12P19/26—Preparation of nitrogen-containing carbohydrates
- C12P19/28—N-glycosides
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
- C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
- C12Y302/01035—Hyaluronoglucosaminidase (3.2.1.35), i.e. hyaluronidase
-
- 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
- A23V2400/165—Paracasei
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- C12R2001/00—Microorganisms ; Processes using microorganisms
- C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
- C12R2001/225—Lactobacillus
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Polymers & Plastics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- General Engineering & Computer Science (AREA)
- Food Science & Technology (AREA)
- Mycology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Tropical Medicine & Parasitology (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Husbandry (AREA)
- Virology (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Birds (AREA)
- Dermatology (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
本發明之新穎乳酸菌可產生中性多醣作為菌體外多醣,該中性多醣具有N-乙醯葡萄糖胺藉α-1,6鍵而連結之結構,該乳酸菌可得自無花果且具有抑制玻尿酸酶之活性及抗酒精傷害活性等,對於發揮抗過敏效果及抗酒精傷害效果等之飲食品、醫藥品、飼料、化妝品等甚是有用。
Description
本發明有關一種新穎乳酸菌及其用途。更詳言之,則本發明有關一種新穎乳酸菌以及含有該乳酸菌且可發揮抗過敏效果等之飲食品組成物、醫藥組成物等組成物,該乳酸菌可產生中性多醣作為菌體外多醣,且該中性多醣具有N-乙醯葡萄糖胺藉α-1,6鍵而連結之結構。
背景技術
乳酸菌係將葡萄糖等碳水化合物發酵來獲得能量並生成多量乳酸之一群細菌,為非病原性且非芽孢形成性之革蘭氏陽性菌。乳酸菌自古供用於調製優格、起司等發酵食品,若以適切量投予則對於宿主之健康照護而言可發揮有益之效果,因此也被視為益生菌而廣泛使用。
作為益生菌而具有效果之乳酸菌舉例來說已知有:對血清脂質具有效果之胚芽乳酸桿菌(Lactobacillus plantarum)MA2菌株(非專利文獻1);及,具有膽固醇減低作用之胚芽乳酸桿菌(Lactobacillus plantarum)PH04菌株(非專利文獻2)等。此外,就源自植物之乳酸菌而言,具有改善脂肪肝與抑制體內脂肪蓄積效果之戊糖片球菌(Pediococcus pentosaceus)LP28株(非專利文獻3)等也已為人所知。
就屬於副乾酪乳酸桿菌(Lactobacillus paracasei)之乳酸菌株而言,也有具抗過敏作用之Lactobacillus paracasei K71菌株(專利文獻1)、具抗流感病毒活性之Lactobacillus paracasei MCC1375菌株(專利文獻2)、可使介白素-12生產活性化之Lactobacillus paracasei KW3110菌株(非專利文獻4)等為所人知。
已知有數種乳酸菌株會產生有益於維持與提升人體健康之生理活性物質的菌體外多醣(exopolysaccharide)。已顯示乳酸菌所產生之菌體外多醣可發揮免疫調節機能及抗胃炎作用(非專利文獻5及6)。此外,屬於Lactobacillus paracasei之乳酸菌所產生之菌體外多醣也已為人所知,已有報告指出Lactobacillus paracasei DG菌株可產生富含鼠李糖之菌體外多醣(非專利文獻7),Lactobacillus paracasei KB28菌株則可產生富含葡萄糖之菌體外多醣(非專利文獻8)。也有報告指出Lactobacillus paracasei 34-1菌株會產生由D-半乳糖、2-乙醯胺-2-去氧-D-半乳糖及sn-丙三醇3-磷酸酯構成之菌體外多醣(非專利文獻9)。
[專利文獻1]國際公開第WO2009/131208號
[專利文獻2]國際公開第WO2012/133827號
[非專利文獻1]Appl. Microbiol. Biotechnol., 84, 341-347(2009)
[非專利文獻2]Int. J. Food Microbiol., 113, 358-361 (2007)
[非專利文獻3]PLoS One e30696(2012)
[非專利文獻4]Biosci. Biotechnol. Biochem., 73, 1561-1565
[非專利文獻5]Carbohydr. Polym., 124, 292-301(2015)
[非專利文獻6]Biol. Pharm. Bull., 17, 1012-1017(1994)
[非專利文獻7]Appl. Environ. Microbiol., 83, e02702-16 (2107)
[非專利文獻8]J. Microbiol. Biotechnol., 21, 1174-1178 (2011)
[非專利文獻9]Carbohdr. Res., 285, 129-139(1996)
於此種背景技術下,乃期望進一步開發可用作新穎益生菌之有用新穎乳酸菌。因此,本發明之課題即在於提供一種新穎乳酸菌及其用途,該乳酸菌可期待作為新穎之益生菌,且可有效作為飲食品組成物、醫藥組成物等組成物之有效成分。
本案發明人以開發出可用作新穎益生菌之
有用新穎乳酸菌為目的並進行精心探討,結果發現可從無花果獲得一種可產生完全未見於習知乳酸菌之新穎中性多醣的乳酸菌,該中性多醣具有N-乙醯葡萄糖胺藉α-1,6鍵而連結之結構,並基於該知識見解進一步反覆研究而完成了本案發明。
於本發明之一局面中,本發明關於一種乳酸菌,其可產生中性多醣作為菌體外多醣,且該中性多醣具有N-乙醯葡萄糖胺藉α-1,6鍵而連結之結構。
乳酸菌以屬於乳酸桿菌(Lactobacillus)之乳酸菌為宜,屬於副乾酪乳酸桿菌(Lactobacillus paracasei)之乳酸菌尤佳。此外,本發明之乳酸菌以源自無花果之乳酸菌為宜,其中以Lactobacillus paracasei IJH-SONE68菌株(寄存編號NITE BP-02242)或與其同等之乳酸菌尤佳。
此外,此一乳酸菌所產生之中性多醣尤其具有玻尿酸酶抑制活性。
於本發明之另一局面中,本發明關於一種含有該等乳酸菌之組成物。
組成物以飲食品組成物為宜,且飲食品以飲料、機能性食品、發酵食品或補充劑(supplement)為佳。此外,該組成物以醫藥組成物、飼料組成物及化妝品組成物為佳。
該等組成物宜供用於抑制玻尿酸酶、抗過敏或抗酒精傷害等。
由於本發明之乳酸菌作為菌體外多醣而產
生之中性多醣等之多醣會顯示出抑制玻尿酸酶(即令玻尿酸發生水解之酵素)的活性,本發明之乳酸菌可有效作為發揮抗過敏效果等之飲食品、補充劑、醫藥品及飼料。此外,由於本發明之乳酸菌對於酒精性肝炎誘發模式小鼠具有減少酒精傷害檢測指標之血清中AST(天門冬胺酸轉胺酶)、ALT(丙胺酸轉胺酶)、ALP(鹼性磷酸酶)等之效果,可有效作為抗酒精傷害用之飲食品或醫藥品。
進一步來說,由於本發明之乳酸菌對於胃酸及膽酸具有高度耐性,可有效作為在人類消化管中發揮效能之飲食品、補充劑及醫藥品以及哺乳動物、家畜類、寵物等之飼料。
此外,由於本發明之乳酸菌即使在使用蛋白之培養基中也能發揮強烈之增殖能力,對於存在於蛋白中之溶菌酶(分解細菌細胞壁之酵素)及運鐵蛋白(具有藉螯合作用來阻礙細菌利用鐵質的作用)等之防禦機制甚強,即使從此層面來看,本發明之乳酸菌也可有效用作飲食品或醫藥品。
此外,本發明之乳酸菌具有具下述特徵之同化能力,即:無法同化一旦被分解即有可能產生氰酸之苦杏仁苷及可抑制黑色素產生而被稱頌美白效果之熊果苷。更進一步來說,如同上述,由於即使在使用蛋白之培養基中也能發揮強烈增殖能力,舉例來說,與蛋白等共同製成化妝品亦可有效使用。
圖1為本發明所分離並鑑定之Lactobacillus paracasei IJH-SONE68菌株之顯微鏡照片。圖1之(A)為革蘭氏染色顯微鏡照片,(B)為掃描型電子顯微鏡(SEM)照片。
圖2為Lactobacillus paracasei IJH-SONE68菌株之菌體外多醣體利用陰離子交換層析法(TOYOPEARL DEAE-650M樹脂(TOSOH CORPORATION))之分離輪廓。以0mM~500mM梯度濃度之NaCl(虛線)使菌體外多醣體溶出,再藉酚硫酸法於490nm下監測各分液中之菌體外多醣(直線)。
圖3顯示:將以陰離子交換管柱層析法純化Lactobacillus paracasei IJH-SONE68菌株之菌體外多醣體所得菌體外中性多醣施行質子-NMR及碳-NMR所獲得之各NMR輪廓。圖3之(A)為質子-NMR之NMR輪廓,(B)為碳-NMR之NMR輪廓。
圖4顯示源自NMR輪廓之菌體外中性多醣之結構解析結果。數值表示NMR之化學位移植。劃底線之數值表示碳NMR之值,未劃底線之數值表示質子NMR之值。由該結構解析結果明確得知,Lactobacillus paracasei IJH-SONE68菌株之菌體外中性多醣具有N-乙醯葡萄糖胺藉α-1,6鍵而連結之結構。亦即,可知其為在α-N-乙醯葡萄糖胺之1位上進一步鍵結有α-N-乙醯葡萄糖胺之6位的成列結構。
圖5為已命名為Lactobacillus paracasei IJH-SONE68菌株之基因組DNA之pce1簇及pce2簇的菌體外多醣生合成基因簇組織圖。
圖6中(A)顯示Lactobacillus paracasei IJH-SONE68菌株、ATCC 334菌株及JCM 8130T菌株等三株乳酸菌間之基因組重組圖,(B)為Lactobacillus paracasei IJH-SONE68菌株之pce1基因簇與JCM 8130T菌株之基因簇的對應情況。
圖7為圖表,顯示Lactobacillus paracasei IJH-SONE68菌株對酒精性肝炎誘發模式小鼠之血清中AST(天門冬胺酸轉胺酶)的影響。
圖8為圖表,顯示Lactobacillus paracasei IJH-SONE68菌株對酒精性肝炎誘發模式小鼠之血清中ALT(丙胺酸轉胺酶)的影響。
圖9為圖表,顯示Lactobacillus paracasei IJH-SONE68菌株對酒精性肝炎誘發模式小鼠之血清中ALP(鹼性磷酸酶)的影響。
圖10為圖表,顯示Lactobacillus paracasei IJH-SONE68菌株對酒精性肝炎誘發模式小鼠之血清中LDH(乳酸脫氫酶)的影響。
圖11為圖表,顯示Lactobacillus paracasei IJH-SONE68菌株對酒精性肝炎誘發模式小鼠之血清中LAP(白胺酸胺肽酶)的影響。
圖12為圖表,顯示Lactobacillus paracasei IJH-SONE68菌株對酒精性肝炎誘發模式小鼠之血清中LIP(脂酶)的影響。
圖13顯示以使用蛋白之培養基來培養Lactobacillus paracasei IJH-SONE68菌株之結果。培養後,僅在SONE68菌株觀察到混濁。
圖14顯示將Lactobacillus paracasei IJH-SONE68菌株以蛋白中添加有葡萄糖及鹽滷原液之培養基進行培養之結果。培養後,僅在SONE68菌株觀察到顯著增殖。
用以實施發明之形態
以下就本發明之乳酸菌及其用途予以詳盡說明。
1.本發明之乳酸菌
本發明之乳酸菌係一產生中性多醣作為菌體外多醣的乳酸菌,該中性多醣具有N-乙醯葡萄糖胺藉α-1,6鍵而連結之結構的。產生具N-乙醯葡萄糖胺藉α-1,6鍵而連結之結構的中性多醣來作為菌體外多醣之乳酸菌迄今未為人所知,而是由本發明首先發現者。本發明之乳酸菌只要是可產生具此種特定結構之中性多醣的乳酸菌即可,可為任一乳酸菌,且不限於特定之乳酸菌。
本發明之乳酸菌可舉例如屬於乳酸桿菌(Lactobacillus)屬、白念珠菌(Leuconostoc)屬、鏈球菌(Streptococcus)屬、片球菌(Pediococcus)屬、蜜蜂球菌(Melissococcus)屬、腸球菌(Enterococcus)屬、毛髮球
菌(Trichococcus)屬、乳酸球菌(Lactococcus)屬、肉品桿菌(Carnobacterium)屬、徘徊球菌(Vagococcus)屬、四聯球菌(Tetragenococcus)屬、阿托波菌(Atopobium)屬、魏斯氏菌(Weissella)屬、酒球菌(Oenococcus)屬、貧養菌(Abiotrophia)屬、德庫菌(Desemzia)屬、副乳桿菌(Paralactobacillus)屬、顆粒鏈菌(Granulicatella)屬、鹼桿菌(Alkalibacterium)屬、歐魯森氏菌(Olsenella)屬、棍狀菌(Isobaculum)屬、海生乳桿菌(Marinilactibacillus)屬、阿托波葉柄菌(Atopostipes)屬、乳卵形菌(Lactovum)屬、茅形細菌(Pilibacter)屬、果糖桿菌(Fructobacillus)屬、Lacticigemium屬、巴伐利亞菌(Bavariicoccus)屬及雙歧桿菌(Bifidobacterium)屬等之乳酸菌。其等之中仍以屬於乳酸桿菌屬之乳酸菌為佳。
屬於乳酸桿菌屬之乳酸菌可舉例如副乾酪乳酸桿菌(Lactobacillus paracasei)、耐酸乳酸桿菌(Lactobacillus acetotolerans)、酸麵乳酸桿菌(Lactobacillus acidifarinae)、馬里乳酸桿菌(Lactobacillus acidipiscis)、嗜酸乳酸桿菌(Lactobacillus acidophilus)、敏捷乳酸桿菌(Lactobacillus agilis)、低溫乳酸桿菌(Lactobacillus algidus)、消化乳酸桿菌(Lactobacillus alimentarius)、解澱粉乳酸桿菌(Lactobacillus amylolyticus)、嗜澱粉乳酸桿菌(Lactobacillus amylophilus)、發酵澱粉乳酸桿
菌(Lactobacillus amylotrophicus)、噬澱粉乳酸桿菌(Lactobacillus amylovorus)、動物乳酸桿菌(Lactobacillus animalis)、胃竇乳酸桿菌(Lactobacillus antri)、田鼠乳酸桿菌(Lactobacillus apodemi)、Lactobacillus aquaticus、鳥類乳酸桿菌(Lactobacillus aviaries)、雙發酵乳酸桿菌(Lactobacillus bifermentans)、巴博乳酸桿菌(Lactobacillus bobalius)、短乳酸桿菌(Lactobacillus brevis)、布氏乳酸桿菌(Lactobacillus buchneri)、Lactobacillus cacaonum、茶葉乳酸桿菌(Lactobacillus camelliae)、多毛乳酸桿菌(Lactobacillus capilatus)、乾酪乳酸桿菌(Lactobacillus casei)、鏈狀乳酸桿菌(Lactobacillus catenaformis)、鯨乳酸桿菌(Lactobacillus ceti)、Lactobacillus coleohominis、丘狀乳酸桿菌(Lactobacillus collinoides)、複合乳酸桿菌(Lactobacillus composti)、弧形乳酸桿菌(Lactobacillus concavus)、棒狀乳酸桿菌(Lactobacillus coryniformis)、卷曲乳酸桿菌(Lactobacillus crispatus)、麵包乳酸桿菌(Lactobacillus crustorum)、彎曲乳酸桿菌(Lactobacillus curvatus)、德氏乳酸桿菌保加利亞亞種(Lactobacillus delbrueckii subsp.bulgaricus)、德氏乳酸桿菌德氏亞種(Lactobacillus delbrueckii subsp.delbrueckii)、德氏乳酸桿菌indicus亞種(Lactobacillus delbrueckii subsp.indicus)、德氏
乳酸桿菌乳酸亞種(Lactobacillus delbrueckii subsp.lactis)、糊精乳酸桿菌(Lactobacillus dextrinicus)、Lactobacillus diolivorans、馬乳酸桿菌(Lactobacillus equi)、同代乳酸桿菌(Lactobacillus equigenerosi)、Lactobacillus fabifermentans、香腸乳酸桿菌(Lactobacillus farciminis)、穀糠乳酸桿菌(Lactobacillus farraginis)、發酵乳酸桿菌(Lactobacillus fermentum)、近莖軸乳酸桿菌(Lactobacillus fornicalis)、食果糖乳酸桿菌(Lactobacillus fructivorans)、穀物乳酸桿菌(Lactobacillus frumenti)、府中乳酸桿菌(Lactobacillus fuchuensis)、母雞乳酸桿菌(Lactobacillus gallinarum)、加氏乳酸桿菌(Lactobacillus gasseri)、胃乳酸桿菌(Lactobacillus gastricus)、甘氏乳酸桿菌(Lactobacillus ghanensis)、草乳酸桿菌(Lactobacillus graminis)、黑氏乳酸桿菌(Lactobacillus hammesii)、倉鼠乳酸桿菌(Lactobacillus hamsteri)、哈爾濱乳酸桿菌(Lactobacillus harbinensis)、Lactobacillus hayakitensis、瑞士乳酸桿菌(Lactobacillus helveticus)、希氏乳酸桿菌(Lactobacillus hilgardii)、同型腐酒乳酸桿菌(Lactobacillus homohiochii)、大麥乳酸桿菌(Lactobacillus hordei)、惰性乳酸桿菌(Lactobacillus iners)、果囊乳酸桿菌(Lactobacillus ingluviei)、腸乳酸桿菌(Lactobacillus intestinalis)、詹
氏乳酸桿菌(Lactobacillus jensenii)、約氏乳酸桿菌(Lactobacillus johnsonii)、卡利克斯鎮乳酸桿菌(Lactobacillus kalixensis)、產馬乳酒乳酸桿菌(Lactobacillus kefiranofaciens)、高加索酸奶粒乳酸桿菌(Lactobacillus kefiri)、韓國泡菜乳酸桿菌(Lactobacillus kimchii)、Lactobacillus kisonensis、北里乳酸桿菌(Lactobacillus kitasatonis)、昆氏乳酸桿菌(Lactobacillus kunkeei)、萊氏乳酸桿菌(Lactobacillus leichmannii)、林氏乳酸桿菌(Lactobacillus lindneri)、壞發酵乳酸桿菌(Lactobacillus malefermentans)、馬利乳酸桿菌(Lactobacillus mali)、食木薯乳酸桿菌(Lactobacillus manihotivorans)、明登乳酸桿菌(Lactobacillus mindensis)、黏膜乳酸桿菌(Lactobacillus mucosae)、鼠乳酸桿菌(Lactobacillus murinus)、內氏乳酸桿菌(Lactobacillus nagelii)、那慕爾乳酸桿菌(Lactobacillus namurensis)、南特港乳酸桿菌(Lactobacillus nantensis)、諾登西斯乳酸桿菌(Lactobacillus nodensis)、寡發酵乳酸桿菌(Lactobacillus oligofermentans)、口乳酸桿菌(Lactobacillus oris)、大瀧乳酸桿菌(Lactobacillus otakiensis)、麵包乳酸桿菌(Lactobacillus panis)、美洲虎乳酸桿菌(Lactobacillus pantheris)、副短乳酸桿菌(Lactobacillus parabrevis)、類布氏乳酸桿菌(Lactobacillus parabuchneri)、類丘狀菌落乳酸桿菌
(Lactobacillus paracollinoides)、類穀糠乳酸桿菌(Lactobacillus parafarraginis)、類高加索酸奶乳酸桿菌(Lactobacillus parakefiri)、類消化乳桿菌(Lactobacillus paralimentarius)、類植物乳酸桿菌(Lactobacillus paraplantarum)、戊糖乳酸桿菌(Lactobacillus pentosus)、惡味乳酸桿菌(Lactobacillus perolens)、植物乳酸桿菌(Lactobacillus plantarum)、橋乳酸桿菌(Lactobacillus pontis)、鸚鵡乳酸桿菌(Lactobacillus psittaci)、Lactobacillus rapi、蛋白原酶乳酸桿菌(Lactobacillus rennini)、路氏乳酸桿菌(Lactobacillus reuteri)、鼠李糖乳酸桿菌(Lactobacillus rhamnosus)、齦溝乳酸桿菌(Lactobacillus rimae)、羅氏乳酸桿菌(Lactobacillus rossiae)、瘤胃乳酸桿菌(Lactobacillus ruminis)、神話豬乳酸桿菌(Lactobacillus saerimneri)、清酒乳酸桿菌(Lactobacillus sakei)、唾液乳酸桿菌(Lactobacillus salivarius)、舊金山乳酸桿菌(Lactobacillus sanfranciscensis)、紅條乳酸桿菌(Lactobacillus satsumensis)、嗜黑麥乳酸桿菌(Lactobacillus secaliphilus)、千枚漬乳酸桿菌(Lactobacillus senmaizukei)、沙氏乳酸桿菌(Lactobacillus sharpeae)、白麵粉乳酸桿菌(Lactobacillus siliginis)、斯比氏乳酸桿菌(Lactobacillus spicheri)、斯瓦比乳酸桿菌(Lactobacillus suebicus)、Lactobacillus sunkii、
Lactobacillus susicola、台灣乳酸桿菌(Lactobacillus taiwanensis)、泰國乳酸桿菌(Lactobacillus thailandensis)、Lactobacillus tucceti、厄爾那拉乳酸桿菌(Lactobacillus ultunensis)、Lactobacillus uvarum、牛糞乳酸桿菌(Lactobacillus vaccinostercus)、陰道乳酸桿菌(Lactobacillus vaginalis)、文氏乳酸桿菌(Lactobacillus versmoldensis)、酒乳酸桿菌(Lactobacillus vini)、犢牛乳酸桿菌(Lactobacillus vitulinus)、玉米乳酸桿菌(Lactobacillus zeae)、老麵乳酸桿菌(Lactobacillus zymae)等。此等之中仍以副乾酪乳酸桿菌為佳。
該等乳酸菌中,本發明之乳酸菌以源自無花果之乳酸菌為佳。具體來說,藉由本發明而從無花果葉分離並鑑定產生中性多醣作為菌體外多醣之乳酸菌Lactobacillus paracasei IJH-SONE68菌株,該中性多醣具有N-乙醯葡萄糖胺藉α-1,6鍵而連結之結構。該菌株係於2016年4月19日以寄存編號NITE P-02242於獨立行政法人製品評價技術基盤機構專利微生物中心(〒292-0818日本國千葉縣木更津市上總鎌足2-5-8 122號室)進行國內寄存,之後移管為遵照布達佩斯條約之國際寄存,並於2017年5月26日賦予國際寄存編號為NITE BP-02242。
從無花果葉分離並鑑定之Lactobacillus paracasei IJH-SONE68菌株係如圖1之照片所示,為過
氧化氫酶陰性之革蘭氏陽性桿菌,且具有白色菌落形成性,並具有視條件而定之雜乳酸發酵特性的菌學性質。進一步來說,具有產生多醣體之能力,尤其是具有N-乙醯葡萄糖胺藉α-1,6鍵而連結之結構的中性多醣。
該中性多醣係如後述實施例4所載,可藉陰離子交換層析法將得自Lactobacillus paracasei IJH-SONE68菌株培養物之多醣體進行分離純化來製得。從圖3所示質子-NMR及碳-NMR之NMR輪廓,可明確得知該中性多醣具有N-乙醯葡萄糖胺藉α-1,6鍵而連結之結構。
此外,如後述實施例3之表1所示,Lactobacillus paracasei IJH-SONE68菌株對糖類具有同化能力。與其他Lactobacillus paracasei相較,特別是具有具下述特徵之醣類同化能力,即:不會同化一旦分解即有可能產生氰酸之苦杏仁苷以及會阻礙黑色素而被稱頌美白效果之熊果苷。
從Lactobacillus paracasei IJH-SONE68菌株之全基因組序列解析,預測Lactobacillus paracasei IJH-SONE68菌株之基因組DNA係由GC含量46.37%之3,084,917bp所構成,且結構基因數為2,963個。進一步來說,顯示出Lactobacillus paracasei IJH-SONE68菌株具有2個質體,且其中一個至少為51kb另一個為45,267bp尺寸。與其他乳酸菌相較,Lactobacillus paracasei IJH-SONE68菌株具有較大之基因組尺寸及結構基因數。
此外,於Lactobacillus paracasei IJH-SONE68菌株之基因組DNA序列中發現2個菌體外多醣生合成基因簇,將其中一個23kb之簇命名為pce1簇,另一個28kb之簇則命名為pce2簇。接著,由於從pce2簇中命名為pce2J之1個醣基轉移酶基因推定出的蛋白質與可見於已知β-1,6-N-乙醯基葡萄糖胺基轉移酶之pfam02485模體或區域(Genes Dev.,1993 Mar;7(3):468-478及J.Biol.Chem.,1999 Jan 29;274(5):3215-3221)具有相同之模體或區域,暗示pce2簇中之編碼該蛋白質之結構基因與中性多醣之生合成相關。
於本發明中,與Lactobacillus paracasei IJH-SONE68菌株同等之乳酸菌也包含在本發明之乳酸菌中。於此,所謂同等之乳酸菌意指下述乳酸菌:屬於Lactobacillus paracasei且具有產生中性多醣之能力,該中性多醣具有N-乙醯葡萄糖胺藉α-1,6鍵而連結之結構。此外,所謂同等之乳酸菌意指下述菌株:屬於副乾酪乳酸桿菌,其16S rDNA基因之鹼基序列與Lactobacillus paracasei IJH-SONE68菌株之16S rDNA基因之序列編號3的鹼基序列具有98%以上(宜99%以上,更宜100%)之相同性,並且宜具有與Lactobacillus paracasei IJH-SONE68菌株相同之菌學性質及/或相同之糖類同化能力。此外,所謂同等之乳酸菌意指下述菌株:屬於副乾酪乳酸桿菌且具有與Lactobacillus paracasei
IJH-SONE68菌株所具抗過敏作用、抗酒精傷害作用、耐酸性等生物活性相同之生物活性。
舉例來說,此等同等之乳酸菌可藉由對Lactobacillus paracasei IJH-SONE68菌株進行突變、基因改造等一般之突變處理技術來獲得,此外,亦可為藉選擇Lactobacillus paracasei IJH-SONE68菌株之自然突變菌株等並育種而成之菌株。
2.本發明乳酸菌之取得及增殖
本發明之乳酸菌可藉下述方式取得:與後述實施例4所載Lactobacillus paracasei IJH-SONE68菌株所產生之多醣體的分離純化相同,將乳酸菌所產生之菌體外多醣分離,並調查該多醣是否為具有N-乙醯葡萄糖胺藉α-1,6鍵而連結之結構的中性多醣。
本發明之乳酸菌可藉由培養其等而使其輕易增殖。培養方法只要是可使乳酸菌增殖之培養方法即可,不限於特定培養方法,可直接採用一般培養乳酸菌所使用之方法,或者視需要予以適度修正使用。舉例來說,培養溫度通常為25~50℃即可,且宜為35~42℃。培養可於嗜氧條件及厭氧條件中之任一條件下進行皆可,尤宜在厭氧條件下進行,例如,可一邊使適當濃度之二氧化碳氣體及氮氣等厭氧性氣體通氣一邊進行培養。此外,亦可於液體靜置培養等之嗜微氧條件下進行培養。
培養乳酸菌之培養基並未特別受限,可將一般用於培養乳酸菌之培養基視需要予以適當修正使用。
亦即,舉例來說,碳源可視同化性而使用半乳糖、葡萄糖、果糖、甘露糖、山梨糖、甘露醇、柳苷、纖維雙醣、麥芽糖、蔗糖、繭蜜糖、澱粉水解物、廢糖蜜等醣類。就氮源而言,例如可使用氨、硫酸銨、氯化銨、硝酸銨等銨鹽類及硝酸鹽類。此外,就無機鹽類而言,例如可使用氯化鈉、氯化鉀、磷酸鉀、硫酸鎂、氯化鈣、硝酸鈣、氯化錳、硫酸亞鐵等。此外,亦可使用蛋白腖、酒粕、乳清(whey)、大豆粉、脫脂大豆粕、肉萃、酵母萃等有機成分。又,就已調製完成之培養基而言,舉例來說可適用MRS培養基或其修正培養基。
乳酸菌可直接使用培養後所得培養物,亦可將所得培養液予以稀釋或濃縮使用,也可使用回收自培養物之菌體。此外,在不損及本發明效果之前提下,也可於培養後進行加熱及冷凍乾燥等各種追加操作。追加操作以活菌生存率高者為宜。又本發明之乳酸菌可為活菌亦可為死菌,也可為活菌及死菌二者。死菌亦可為破碎物。
3.本發明乳酸菌之用途
本發明之乳酸菌作為菌體外多醣來產生之中性多醣及酸性多醣等之多醣體會顯示出抑制玻尿酸酶(即令玻尿酸水解之酵素)之活性。本發明之乳酸菌對於酒精性肝炎誘發模式小鼠具有使酒精傷害檢測指標之血清中AST(天門冬胺酸轉胺酶)等減少之效果。本發明之乳酸菌對於胃酸及膽酸具有高度耐性。此外,由於本發明之乳酸菌即使在使用蛋白之培養基中亦可發揮強烈之增殖能力,對於存在於蛋
白中之溶菌酶(分解細菌細胞壁之酵素)及運鐵蛋白(具有藉螯合作用來妨礙細菌利用鐵質之作用)等之生物防衛機制甚強。
如同上述,由於本發明之乳酸菌可發揮各種生物活性而具有生理學特徵,可廣泛用作飲食品組成物、醫藥組成物、飼料組成物及化妝品組成物等各種組成物之有效成分。舉例來說,可用作玻尿酸酶抑制用、抗過敏用或抗酒精傷害用飲食品組成物、醫藥組成物或飼料組成物之有效成分。此外,本發明之乳酸菌也可與蛋白等共同用作化妝品組成物之有效成分。
本發明之醫藥組成物只要含有本發明之乳酸菌即不特別受限。本發明之醫藥組成物一般係將本發明之乳酸菌摻合到生理上可接受之液體或固體製劑載體並製劑化後予以使用。
本發明之醫藥組成物之劑形並未特別受限,具體來說可例示如錠劑、丸劑、粉劑、液劑、懸浮劑、乳劑、顆粒劑、膠囊劑、糖漿劑、栓劑、注射劑、軟膏劑、貼劑、點眼劑及點鼻劑等。製劑化時,製劑載體可使用一般使用之賦形劑、結合劑、崩解劑、潤滑劑、安定劑、矯味矯臭劑、稀釋劑、界面活性劑或注射劑用溶劑等添加劑。
本發明之醫藥組成物之製劑中,乳酸菌含量可視劑形、用法、對象年齡、性別、疾病種類、疾病程度、及其他條件等予以適度設定,通常宜在1×106~1×1012cfu/g或1×106~1×1012cfu/ml範圍內,更宜
在1×107~1×1011cfu/g或1×107~1×1011cfu/ml範圍內。乳酸菌為死菌時,cfu/g或cfu/ml可替換為個細胞/g或個細胞/ml。
在不損及本發明效果之前提下,可視用途將本發明之乳酸菌與其他有效成分(諸如免疫賦活劑等)適切併用。
本發明之醫藥組成物的投予時期並未特別受限,可視施用對象來適當選擇投予時期。此外,亦可作預防性投予,也可用於維持治療法。投予形態宜視製劑形態、投予對象之年齡、性別、其他條件、投予對象之症狀程度等來適當決定。本發明之醫藥組成物在任一狀況下皆可1天1次或分為多數次投予,此外,也可隔數天或數週投予1次。
舉例來說,本發明之醫藥組成物可用於降低投予對象之過敏情況。此外,本發明之醫藥組成物可使用於治療、緩和或預防諸如酒精性肝傷害、酒精成癮症、酒精性肝炎及脂肪肝等。
包含本發明乳酸菌之飲食品組成物之飲食品只要含有乳酸菌即不特別受限,飲食品可例示如:清涼飲料、碳酸飲料、營養飲料、果汁飲料、乳酸菌飲料等飲料;該等飲料之濃縮原液、調製用粉末等;冰淇淋、雪果霜、刨冰等冰製點心;糖果、膠質糖、穀物片、口香糖、硬糖、樹膠、巧克力、糖果錠、零食、餅乾、果凍、果醬、鮮奶油及烘焙點心等點心類;加工乳、乳飲料、發酵乳、優酪飲品、奶油等乳製品;麵包;經腸營養食品、流
質食品、育兒用奶粉、運動飲料;蔬果泥(Purée)等食品;其他機能性食品等。此外,飲食品亦可為補充劑(supplement),例如,可為顆粒狀、粉末狀、錠狀補充劑。為補充劑時,可在每日用餐量及攝取卡路里上不受其他食品影響地攝取乳酸菌。
如上所述之飲食品可藉由在飲食品原料中添加乳酸菌來製造,或者,可與一般飲食品同樣地製造。乳酸菌之添加可在飲食品製程之任一階段進行。也可經所添加之乳酸菌的發酵步驟後再製造飲食品。此種飲食品可舉如乳酸菌飲料、發酵乳等發酵食品等。
食品或飲料之原料可使用一般用於飲料及食品之原料。製得之飲食品可經口攝取。
本發明之飲食品包含用以製造飲食品之原料及食品添加物等,在飲食品之製程中或製造後添加至飲食品之物。舉例來說,本發明之乳酸菌可用作發酵乳製造用菌元。此外,亦可於已製出之發酵乳中後續添加本發明之乳酸菌。
飲食品組成物中之乳酸菌含量可視飲食品之態樣來適當設定,一般而言,於飲食品中,宜在1×106~1×1012cfu/g或1×106~1×1012cfu/ml範圍內,更宜在1×107~1×1011cfu/g或1×107~1×1011cfu/ml範圍內。乳酸菌為死菌時,cfu/g或cfu/ml可替代為個細胞/g或個細胞/ml。
包含本發明乳酸菌之飲食品組成物可使用
在利用抗過敏效果及抗酒精傷害效果之各種用途上。
包含本發明乳酸菌之飲食品可作為已標示其用途之飲食品來製造、販賣。此種飲食品可作「過敏改善用」、「酒精傷害改善用」等之標示。除此之外,若是用以表示藉此種改善效果而副次產生之效果的標示,也可使用而毋須贅言。於此,所謂「標示」意指:用以使需要者知悉上述用途之所有行為,只要是可使人想到或類推上述用途之標示,則無論標示目的、標示內容、標示對象物及媒體等何如,皆該當於「標示」。然而,宜以可使需要者直接認識上述用途之表現方式來標示。
具體來說,可例示如在本發明飲食品之商品或商品包裝上標示上述用途,尤宜標示在包裝、容器、商品目錄、手冊、POP等販賣現場之宣傳材料、其他文件等。此外,就標示而言,舉例來說可例示如健康食品、機能性食品、經腸營養食品、特別用途食品、營養機能食品、類藥品(quasi drug)及特定保健用食品等。
包含本發明乳酸菌之飼料組成物之飼料可舉如寵物食品、家畜飼料、飼育魚飼料等。此種飼料可於一般飼料諸如穀類、粕類、糠類、魚粉、骨粉、油脂類、脫脂奶粉、乳清(whey)、鹽滷、礦物質飼料、酵母類等中混入乳酸菌來製造。此外,舉例來說,可如青貯料時般,經所添加之乳酸菌所致發酵步驟後再製造飼料。所製造之飼料可經口頭投予一般哺乳動物、家畜類、飼育魚類、寵物等。此外,飼育魚類時,也可採用將添加有本發
明乳酸菌之發酵物撒於養魚場之方法。
飼料組成物中之乳酸菌含量可視飼料態樣及投予對象來適當設定,但宜在1×106~1×1012cfu/g或1×106~1×1012cfu/ml範圍內,更宜在1×107~1×1011cfu/g或1×107~1×1011cfu/ml範圍內。乳酸菌為死菌時,cfu/g或cfu/ml可替代為個細胞/g或個細胞/ml。
包含本發明乳酸菌之飼料組成物可使用在利用諸如抗過敏效果之各種用途上。
包含本發明乳酸菌之化妝品組成物之化妝品可舉例如:肥皂、沐浴乳、卸妝乳、洗面乳等洗浄用品;化妝水(lotion)、雪花膏(vanishing cream)、冷霜、潤膚霜(emollient cream)、按摩霜等乳霜;乳液及美容液等。
就包含本發明乳酸菌之化妝品組成物而言,舉例來說,宜使用以下述方式製得之乳酸發酵蛋白:於將雞等鳥類之蛋打破並分離蛋黃所得液狀蛋白中添加本發明之乳酸菌並使其發酵。此種乳酸發酵宜使用一般用作營養源之葡萄糖等並視需要添加酵母萃等發酵促進物質來使其發酵。乳酸發酵蛋白之形態可視所摻合之化妝品而定,可舉如液狀、粉末狀、霜狀、膏狀、凍狀等。
舉例來說,用於本發明之化妝品組成物之乳酸菌含量以換算為乳酸發酵蛋白乾燥物計,通常為0.001重量%以上,更宜為0.01重量%以上。
包含本發明乳酸菌之化妝品組成物可使用於利用諸如抗過敏效果之各種用途上。此外,亦可用作顯示出美白效果及保濕效果之化妝品。
以下藉實施例來進一步詳盡說明本發明,蛋本發明不受此等實施例所侷限。
實施例1
乳酸菌之分離及鑑定
1.乳酸菌樣本之分離
選擇無花果(品種「豐蜜姬」)之葉、莖及果實,使用已殺菌之鑷子與剪刀使其細破片化至2~3mm後,於已滅菌之裝有MRS液體培養基之試管中分別裝入5~6個細片,於28℃及37℃下靜置培養至乳酸菌之標準培養基即MRS培養基發生混濁(增殖)。亦即,至可目視到乳酸菌候補菌株增殖為止需要2~4天。
將上述乳酸菌候補菌株之各培養液的一部分以拋棄式接種環劃線塗菌於MRS洋菜培養基上後進行靜置培養。形成於洋菜培養基上之菌落中,將「顏色、光澤、形狀不同者」全部拾取,再於新鮮之MRS洋菜培養基上進行劃線塗菌來純化菌落。
對於經純化之各菌落,為了驗證有無過氧化氫酶之產生而進行H2O2測試。此係一用以觀察菌體暴露於10% H2O2溶液時若過氧化氫酶存在即會生成氧的現象有無發生的試驗法。亦即,乳酸菌不會產生過氧化氫酶。
從無花果嘗試探索分離之結果,從以無花果葉作為分離源之物中成功獲得顯示過氧化氫酶陰性之乳酸菌候補菌株1株。
2.分離菌株之鑑定
將上述乳酸菌候補菌株另以MRS液體培養基培養,並利用離心分離取得菌體。以細胞壁溶解酵素處理後,使用DNAzol試劑抽提出基因組DNA。
按照計載於Lane,D.J.(1991).16S/23S rRNA sequencing.In Nucleic Acid Techniques in Bacterial Systematics、pp.115-175.Edited by E.Stackebrandt & M.Goodfellow.Chichester:Wiley之方法,以基因組DNA為模板,藉由使用27f引子(5'-AGAGTTTGATCCTGGCTCAG-3')(序列表之序列編號1)與1525r引子(5'-AAAGGAGGTGATCCAGCC-3')(序列表之序列編號2)之PCR反應,使16S rDNA部分擴增,並以NucleoSpin Gel and PCR Clean-up kit(MACHEREY-NAGEL GmbH & Co.KG製)自瓊脂糖凝膠回收目的斷片。用以決定鹼基序列之dye terminator法所致序列反應係以Big Dye Terminator Cycle Sequencing FS Ready Reaction Kit ver.3.1(ThermoFisher Scientific社製)進行,並以ABI PRISM 3130xl Genetic Analyzer(ThermoFisher Scientific社製)解析。解析出之16S rDNA的鹼基序列具有序列表之序列編號3的鹼基序列。對該鹼基序列以BLAST program進
行相同性檢索,並藉由與DNA data bank(DDBJ/EMBL/GenBank)之資料庫比較來進行分離菌株之分類學鑑定。
將分離自無花果葉之乳酸菌候補菌株命名為IJH-SONE68菌株,由於其與已登記在DNA data bank(DDBJ/EMBL/GenBank)之「Lactobacillus paracasei R094」之菌株且鹼基序列之accession編號為「NR_025880」的鹼基序列100%一致,而鑑定為Lactobacillus paracasei。
該菌株係於2016年4月19日以寄存編號NITE P-02242進行國內寄存於獨立行政法人製品評價技術基盤機構專利微生物中心(〒292-0818日本國千葉縣木更津市上總鎌足2-5-8 122號室),之後移管為遵照布達佩斯條約之國際寄存,並於2017年5月26日賦予國際寄存編號為NITE BP-02242。
3.基因組DNA之序列分析
針對源自IJH-SONE68菌株之基因組DNA,以使用P6聚合酶及C4 chemistry(P6C4)之單一分子實時(SMRT)Cell,藉PacBio RS II(Pacific Biosciences、Menlo Park、CA、U.S.A.)進行基因組DNA定序。使用g-TUBE套組(Covaris、Woburn、MA、U.S.A.)將已純化之基因組DNA試料切斷為斷片。接著,使用AMPure PB套組(Pacific Biosciences)將切斷之斷片純化。使用PacBio DNA模板調製套組1.0(Pacific Biosciences)及PacBio DNA/Polymerase Binding Kit P6(Pacific
Biosciences),建構DNA庫。以Blue Pippin(Sage Science、Beverly、MA、U.S.A.)去除較短之斷片,接著於PacBio SMRT平台上將純化DNA庫定序。以分級基因組拚接製程(HGAP)程序(Nat.Methods,10,563-56933)進行重頭拚接(De novo assembly),將所得全基因組片段重疊組(contig)以微生物基因組註解管線(MiGAP)進行註解(第20屆國際基因組資訊學研討會,海報與軟體展示(橫濱),S001-1-2;The 20th International Conference on Genome Informatics(GIW2009)Poster and Software Demonstrations(Yokohama),S001-1-2)。
4.基因組DNA序列分析結果
決定IJH-SONE68菌株之全基因組序列,結果,基因組DNA由GC含量46.37%之3,084,917bp構成,結構基因數以MiGAP預測為2,963個。進一步來說,序列結果顯示,IJH-SONE68菌株含2個質體,其中一個至少為51kbp,另一個為45,267bp之尺寸。與其他乳酸菌相較,IJH-SONE68菌株具有較大之基因組尺寸及結構基因數。
實施例2
經分離鑑定之乳酸菌的菌學性質
經分離鑑定之上述乳酸菌IJH-SONE68菌株係如圖1之照片所示,為過氧化氫酶陰性之革蘭氏陽性桿菌,且具白色菌落形成性並具有視條件而定之雜乳酸發酵特性的菌學性質。
實施例3
經分離鑑定之乳酸菌的醣類同化能力
1.同化能力之試驗方法
藉下述試驗方法,就IJH-SONE68菌株對49種醣類之同化能力進行調查。
將IJH-SONE68菌株以MRS液體培養基靜置培養至增殖穩定期。將離心分離所得菌體以適量之懸浮介質(suspension medium,bioMérieux公司製)洗淨後,最後懸浮於2mL之suspension medium。將其一部分添加到5mL之suspension medium中,求出麥式(McFarland)濁度為2之量(n)。接著,於API 50 CHL培養基(bioMérieux公司製)中加入2n菌液,將其分注到API 50 CHL套組(bioMérieux公司製,各孔底分別塗附了49種醣)之各孔中。最後覆上礦物油層,安裝於已裝有滅菌水之托盤中。於37℃下培養48小時後,觀察各孔中之色調變化,藉此判定有無同化能力。
2.同化能力之試驗結果
IJH-SONE68菌株對49種醣類之同化能力調查結果係如表1所示。表1中一併顯示了對專利公開公報所載其他Lactobacillus paracasei使用相同套組調查而得之同化能力。
由表1結果可知,IJH-SONE68菌株與其他Lactobacillus paracasei相較,無法同化且不分解一旦分解即有可能產生氰酸之苦杏仁苷、以及會抑制黑色素產生而被稱頌美白效果之熊果苷,因此具優異安全性,用作化妝品添加劑時可謂具優異美白效果。此外,相較於其他Lactobacillus paracasei無法同化D-核糖醇而可同化D-松二糖,IJH-SONE68菌株也具有可同化D-核糖醇而無法同化D-松二糖之特徵。
實施例4
1.IJH-SONE68菌株所產生之多醣體的分離純化
以下述方式將IJH-SONE68菌株所產生之菌體外多醣予以分離純化。
將IJH-SONE68菌株以MRS液體培養基靜置培養至增殖穩定期。將該培養液5mL用作種培養液,植菌至5L之多醣體產生用半合成培養基(其組成後述)後,於37℃下靜置培養120小時。將培養液冷卻至4℃後,使培養液上清中所含蛋白質改質,為了在後續步驟中以沉澱物形式去除,添加202.5mL之100%三氯乙酸水溶液,混合後靜置30分鐘。藉離心分離去除沉澱物,於回收之上清液中加入等量丙酮並混合後,使其於4℃下靜置一夜,藉此使IJH-SONE68菌株所產生之多醣體沉澱。以離心分離回收沉澱物後,以250mL之70%乙醇進行沉澱物之洗淨。使沉澱物風乾後,添加75mL之50mM Tris-HCl緩衝液(pH 8.0)並混合1小時,藉此使沉澱物溶解。藉離心分離去除
不溶性之夾雜物後,對所回收之上清液分別添加750μL之1mg/mL DNase溶液(Worthington公司)及1mg/mL RNase溶液(Nacalai Tesque公司),於37℃下使其反應8小時。接著,添加750μL之2mg/mL proteinase K溶液(和光純藥工業社製),於37℃下使其反應16小時。使反應後之溶液冷卻至4℃後,使所添加之各酵素改質,為了以後續之離心分離將其作為沉澱物去除,而添加8.75mL之100%三氯乙酸水溶液並混合,於4℃下靜置1小時。以離心分離去除沉澱物,對所得上清液添加262.5mL之100%乙醇,確實混合後藉離心分離將IJH-SONE68菌株所產生之多醣體作為沉澱物回收。以50mL之70%乙醇洗淨沉澱物後使其風乾,添加適量(約25mL)純水並於4℃下靜置一夜,藉此使多醣體溶解。溶解後之多醣體樣本係使用10,000MWCO之超過濾單元(Merck公司),一邊將溶劑替換為純水,一邊去除所回收樣本中之單糖類等小分子,而製得經純化之多醣體樣本。
將已純化之多醣體樣本施用到已預先以50mM Tris-HCl緩衝液(pH8.0)平衡化且填充有TOYOPEARL DEAE-650M樹脂(TOSOH CORPORATION)之開放管柱(2.5×22cm),進行用以分離純化中性多醣分液與酸性多醣分液之管柱作業。溶液使用相同之緩衝液,流速以1mL/min固定。此外,溶出液每6mL回收到不同的試管。首先,從一開始至240分鐘的期間,以相同緩衝液使其溶出(試管編號1-40)。接著,從
240分鐘之時間點至600分鐘之時間點為止,製作出使用相同緩衝液之0-500mM NaCl的濃度梯度並持續溶出(試管編號41-100)。茲將管柱分離圖譜顯示於圖2。對溶出至試管之全部樣本以酚硫酸法(後述)確認多醣體之存在後,將對應試管內之溶液分別統整為中性多醣分液、酸性多醣分液。各分液使用10,000MWCO之超過濾單元,一邊將溶劑替換為純水,一邊去除所回收樣本中之單糖類等小分子。
藉由上述而分離純化出中性多醣分液及酸性多醣分液作為IJH-SONE68菌株所產生之菌體外多醣。
多醣體產生用半合成培養基係將記載於Kimmel SA、Roberts RF.Development of a growth medium suitable for exopolysaccharide production by Lactobacillus delbrueckii ssp.bulgaricus RR.Int.J.Food Microbiol.,40,87-92(1998)之培養基變更如下。
微量元素溶液(Trace element Soln.)係載於Kets EPW,Galinski EA,de Bont JAM.Carnitine:a novel compatible solute in Lactobacillus plantarum.Arch.Microbiol.,192,243-248(1994),其組成如下。
酚硫酸法(DuBois M,Gilles KA,Hamilton JK,Rebers PA,Smith F.,Colorimetric method for determination of sugars and related substances.,Anal.Chem.,28,350-356(1956))
將30μL之對象樣本與等量之5w/v%酚水溶液混合後,添加150μL之濃硫酸使其混合並開始反應。10分鐘後立刻予以冰冷使反應停止。藉由測定反應液於490nm下之吸光度來測定糖類濃度。另,濃度之決定係使用以葡萄糖作為標準品進行相同實驗所製出之檢量線。
2.菌體外多醣之分析
將上述經陰離子交換管柱層析法(TOYOPEARL DEAE-650M樹脂(TOSOH CORPORATION))而純化之菌體外中性多醣施行質子-NMR及碳-NMR,並將所得各NMR輪廓顯示於圖3。茲將得自此等NMR輪廓之菌體外中性多醣之結構解析結果顯示於圖4。
由該構造解析結果,明確得知IJH-SONE68菌株所產生之菌體外中性多醣具有N-乙醯葡萄糖胺藉α-1,6鍵而連結之結構。
3.IJH-SONE68菌株之菌體外多醣生合成基因簇之解析
基於實施例1所載IJH-SONE68菌株之基因組配列的註解,在基因組DNA上找出2個菌體外多醣生合成基因簇(圖5)。其中一個23kb之簇命名為pce1簇,該pce1簇係由18個開放閱讀框(ORF(pce1A~R))構成,該等開放閱讀框包含編碼機能不明之蛋白質的基因。另一個28kb之簇命名為pce2簇,該pce2簇包含12個完整之ORF與3個縮短(truncated)ORF(pce2A~O)。進一步來說,於pce2簇上找出12個轉位酶相關基因。
就編碼菌體外多醣之生合成所必須之蛋白質的基因而言,編碼作為股長因子發揮作用之蛋白質-酪胺酸磷酸酶Wzb的wzb基因(Yother J.Annu.Rev.Microbiol.,65,563-581(2011))未在pce1簇上找出。另一方面,pce2簇上不存在與催化醣聚合最初步驟之引導醣基轉移酶(van Kranenburg R,Vos HR,van Swam II,Kleerebezem M,de Vos WM.,J.Bacteriol.,1999 Oct;181(20):6347-6353)顯示出相同性的基因。
製作出IJH-SONE68菌株、ATCC 334菌株(Makarova,K.et.al,Proc.Natl.Acad.Sci.U.S.A.,103(42),15611-15616(2006))及JCM 8130T菌株(Toh,H.et.al,PLoS ONE 8,e75073(2013))等三株乳酸菌間之基因組再重組圖(圖6)。由該圖可知,pce2簇區域在IJH-SONE68菌株上具特異性。另一方面,對pce1簇顯示出相同性之基因簇雖未見於ATCC334菌株之基因組,但存在於JCM8130T菌株。
基於上述相同性檢索,於pce1簇及pce2簇上見到分別與wzb基因及導引醣基轉移酶基因相同之基因。因IJH-SONE68菌株之基因組DNA上未找到其他之簇等,可以想見菌體外多醣之生合成所需基因係以pce1簇與pce2簇相互彌補完成。實際上,pce1簇與pce2簇僅隔34kb。
由於從pce2簇中命名為pce2J之1個醣基轉移酶基因推定出的蛋白質與可見於已知β-1,6-N-乙醯基葡萄糖胺基轉移酶之pfam02485模體或區域(Genes Dev.,1993 Mar;7(3):468-478及J.Biol.Chem.,1999 Jan 29;274(5):3215-3221)具有相同之模體或區域,暗示pce2簇中之編碼該蛋白質之結構基因與中性多醣之生合成相關。實際上,pce2簇與ATCC 334菌株及JCM 8130T菌株相較下,在IJH-SONE68株基因組上具特異性,可想見具新穎結構之中性多醣係由pce2簇而生合成。
實施例5
IJH-SONE68菌株所產生之菌體外多醣體之玻尿酸酶活性抑制
調查實施例4所得IJH-SONE68菌株所產生之菌體外多醣即包含中性多醣分液及酸性多醣分液之多醣樣本、以及中性多醣分液及酸性多醣分液的玻尿酸酶活性抑制情況。
1.試驗方法
對包含實施例4所得含中性多醣分液及酸性多醣分液之多醣體樣本、從中性多醣分液及酸性多醣分液調整為任意濃度之多醣的水溶液10μL,添加5μL之玻尿酸酶溶液(MP Biomedicals社,4mg/mL、100mM乙酸鈉緩衝液(pH 4.0)),於37℃下培養20分鐘。之後,添加10μL酵素活性化溶液(0.5mg/ml Compound 48/80(MP Biomedicals公司),3.75mg CaC12‧2H2O、100mM乙酸鈉緩衝液(pH 4.0)),再次於37℃下培養20分鐘。接著,添加25μL之玻尿酸鈉溶液(和光純藥工業社,0.8mg/mL、100mM乙酸鈉緩衝液(pH 4.0)),進一步於37℃下使其反應40分鐘。反應後,添加10μL之0.4M NaOH水溶液以使反應停止。接著添加10μL之100mM硼酸鉀緩衝液(pH10.0)後於100℃下加熱3分鐘,立刻令其冰冷。將反應液40μL與200μL之p-DMAB溶液(後述)混合,於37℃下使其反應20分鐘後,測定585nm下之吸光度。作為對照組,亦同樣調製不含玻尿酸酶溶液之反應液並進行實驗。
多醣體樣本之酵素活性抑制率係以下式求出。
抑制率(%)=100-(S/C)×100
於該式中,C為不含樣本時之酵素活性,S為含樣本時之酵素活性。此外,有關多醣體樣本之IC50值,則於取得多數使含有濃度變化之數據後,繪圖成X軸取多醣體樣本濃度且Y軸取抑制率之圖表,並以下列近似式求出。
[數學式1]
Y=α/(1+βe-γX)
式中,α、β及γ表示常數。
p-DMAB溶液(Fujitani N、Sakai S、Yamaguchi Y、Takenaka H.Inhibitory effects of microalgae on the activation of hyaluronidase.J.Appl.Phycol.,13,489-492(2001))
將10×儲備溶液(5g之對二甲胺基苯甲醛、6ml之10M HCl、44ml之乙酸)在剛要使用前以乙酸稀釋並調製出p-DMAB溶液。
2.試驗結果
茲將所得對玻尿酸酶之活性抑制試驗結果顯示於表2。
由表2之結果可明顯得知,IJH-SONE68菌株所產生之菌體外多醣的多醣體樣本(含中性多醣分液及酸性多醣分液)、中性多醣分液及酸性多醣分液顯示出甚高之玻尿酸酶抑制活性。尤其是多醣體樣本及中性多醣分液顯示出與具抗炎症作用之甘草酸二鉀相同程度之玻尿酸酶抑制活性。
實施例6
IJH-SONE68菌株之耐酸性特性
為了調查IJH-SONE68菌株之耐酸性特性而進行了對人工胃液及人工膽汁之耐酸性試驗。
1.對人工胃液之耐酸性試驗
(1)試驗方法
人工胃液使用日本藥典崩解試驗第一液(pH1.2)及日本藥典崩解試驗第二液(pH6.8)(皆為和光純藥工業社製)來調製。調製出含有0.04w/v%胃蛋白酶(1:10000,和光純藥工業社製)且pH3.0之人工胃液,接種一定量之經MRS液體培養基靜置培養至穩定狀態之IJH-SONE68菌株的種培養液後,計數1、3、5小時後之活菌數。以接種時間點之活菌數為100%,求出生存率。另,計測活菌數時,將經過各時間後之溶液的一部分適當分階稀釋,使用添加BCP之平板計數洋菜培養基(日水製藥社)使其混釋培養(37℃,厭氧,數天),計數所產生之菌落數藉此算出存在該稀釋液中之活菌數。同時,也針對Lactobacillus bulgaricus B-5b(http://www.gene.affrc.go.jp/databases-micro_search_detail.php?maff=401001)進行試驗。
(2)試驗結果
將所得耐酸性試驗結果顯示於表3。
由表3之結果可明顯看出,IJH-SONE68菌株相較於Lactobacillus bulgaricus B-5b,對於人工胃液具有高耐酸性特性。
2.對人工膽汁之耐酸性試驗
(1)試驗方法
調製出含0.1、0.2、0.3w/v%膽汁粉末(和光純藥工業社製)之MRS液體培養基,接種經MRS液體培養基靜置培養至穩定狀態之IJH-SONE68菌株的種培養液0.1v/v%,於37℃下進行24小時靜置培養。培養結束後,以不含膽汁粉之粉末之MRS培養基的菌體濁度(O.D.600nm)為100%,算出含各濃度膽汁粉末之MRS培養基之菌體濁度比率。同時,也針對Lactobacillus acidophilus L-54(日本乳業技術協會提供)及Lactobacillus bulgaricus B-5b進行試驗。
(2)試驗結果
將所得耐酸性試驗結果示於表4。
從表4之結可明顯看出,IJH-SONE68菌株相較於Lactobacillus acidophilus L-54及Lactobacillus bulgaricus B-5b,對人工膽汁具有高耐酸性。
實施例7
IJH-SONE68菌株對酒精傷害之效果
為了調查IJH-SONE68菌株對酒精傷害之效果,就IJH-SONE68菌株對酒精性肝炎誘發模式小鼠之影響予以探討。
1.試驗方法
使具有酒精嗜好性之C57BL/6J系雄性小鼠(CLEA Japan,Inc.,8週齡)攝取含乙醇飼料6週以製作酒精性肝炎誘發模式小鼠,並觀察其間有無攝取乳酸菌所造成之影響。具體來說,於飼育期間中,依小鼠飼餌之差異分為以下3組((1)~(3)),且於飼育開始6週後進行採血。
1):陽性對照組(僅有含乙醇飼料L10016)
2):陰性對照組(僅有不含乙醇飼料L10015)
3):IJH-SONE68菌株投予組(含乙醇飼料L10016+乳酸菌活菌體)
含乙醇飼料L10016:
即將使用前,於Pre-Mix L10016A(Research Diet公司)中混合水及乙醇來調製。
不含乙醇飼料L10015:
即將使用前,於Pre-Mix L10016A(Research Diet公司)中混合水及麥芽糊精來調製。
另,小鼠購入7週齡者,每組5隻,為了進行1週馴化,預先以普通餌食(Oriental Yeast Co.,Ltd.製,MF)飼育後供予實驗。飼育係於廣島大学霞校區內之霞動物實驗設施進行,此外,飼育期間中濕度維持40-60%,氣溫維持20-26℃,以每12小時切換照明之ON/OFF的環境來進行。各隻小鼠之識別係藉由將尾部以動物標記(室町器械社製)分色塗佈來進行(以紅、藍、綠、黃、無著色來區別)。
試驗餌食係將經MRS培養基培養並洗淨之各乳酸菌株混入乙醇飼料者。實驗中,餌食係將裝入給餌容器者每天更換並令其自由攝取。另,完全不給予包含水在內之其他食餌。此外,也就餌食之殘餘量進行計測。從開始飼育至經過6週後,藉吸入異氟醚及腹腔內投予戊巴比妥使小鼠安樂死並進行採血。將自血液回收之血清於-80℃下冷凍保存。進行血液生化學檢測,測定酒精傷害檢測指標之血清中AST(天門冬胺酸轉胺酶)、ALT(丙胺酸轉胺酶)、ALP(鹼性磷酸酶)、LDH(乳酸脫氫酶)、LAP(白胺酸胺肽酶)及LIP(脂酶)之值。各測定值之統計
解析係以SPSS 17.0(SPSS Japan)進行。
2.試驗結果
就陽性對照組(PC)、陰性對照組(NC)及IJH-SONE68菌株投予組(SONE68)之AST、ALT、ALP、LDH、LAP及LIP的各測定值(IU/L)顯示於圖7~12之圖表。從圖7~12之圖表可知,IJH-SONE68菌株使得AST、ALT、ALP、LDH、LAP及LIP之值較陽性對照組(PC)更為減少,而對酒精傷害具有優異之預防改善效果。
實施例8
IJH-SONE68菌株對蔬果泥之應用
茲將IJH-SONE68菌株應用於由無花果果實、酒粕等構成之蔬果泥之例顯示如下。
將無花果果實切分為適當大小,添加相對重量為1.0(w/w)%之纖維素酶「Onozuka」3S、0.5(w/w)%之果膠酶3S、0.5(w/w)%之抗壞血酸鈉、2.0(w/w)%之酒粕(釀造副產物)粉末及100(w/w)%純水,使用完整萃取(Marugoto extract)裝置(東洋高壓公司製),在50℃、100MPa之條件下進行24小時處理。具體來說,預先將必要量之已藉菜刀分割成大致均等1/4尺寸之無花果果實投入處理用調理袋(Hybri-Bag,Cosmo-Bio Co.,Ltd.製),於其中添加已使上述試劑全部溶解之水溶液後,僅可能去除氣泡,並以封口機(Polysealer,AS ONE Corporation製)將其密封。將密封後之袋放入完整萃取裝置(2L型,東洋高壓公司製),於
上述條件下進行處理。另,培養前於潔淨台(SANYO公司製)內以無菌方式將調理袋開封(以經酒精滅菌處理之剪刀),再以無菌方式將內容物移到預先以高壓滅菌機(TOMY SEIKO Co,Ltd.製)進行過滅菌處理之容器( ,AS ONE Corporation製)。
對於調製出之蔬果泥,將預先使用MRS培養基於37℃下進行2-3天種培養之Lactobacillus paracasei IJH-SONE68菌株的菌體懸浮液添加至相當於1(v/v)%之量,於37℃下進行靜置培養48小時。具體來說,先將已分別分注10mL至附螺栓之試管中的MRS培養基(Merck公司製)以118℃、15分鐘之條件進行高壓滅菌,再於潔淨台內以-80℃冷凍保存之IJH-SONE68菌株之菌液儲備於其中進行植菌。密栓後,利用培養器於37℃下以於試管架維持直立的方式培養2-3天。培養後,使其顛倒混合至培養液之混濁呈均勻為止,再於潔淨台內將內容物移至15mL容積之離心管(Nunc公司製)。藉離心分離(Eppendorf公司製)使菌體沉澱後,於潔淨台內丟棄培養液上清,同時添加蔬果泥10mL份,密栓後以Vortex Machine(Scientific Industries公司製)使沉澱之菌體再懸浮。之後,於潔淨台內對蔬果泥添加必要量之菌體懸浮蔬果泥,密栓後以培養器(大和科學社製)於37℃下以維持瓶身直立的方式進行培養2-3天。
以上所得蔬果泥與未加菌體懸浮液所得之蔬果泥相較,添加酸味而獲得良好之食感與風味。
實施例9
使用蛋白培養基之培養
使用蛋白培養基培養IJH-SONE68菌株,並調查其增殖狀況。
1.蛋白培養基之調製及培養
(1).方法
於潔淨台中將連殼一起經乙醇輕微消毒之雞蛋打破,分離為蛋黃與蛋白,僅取蛋白部分。蛋白分取至50mL容積之錐形管,進行渦流攪拌製成均勻黏度後,以平均量分注到其他管中供培養用。
將種培養之IJH-SONE68菌株之乳酸菌培養液以無菌方式植菌到各管中使最終濃度為1v/v%,進行靜置培養。同樣地,使用其他乳酸菌之戊糖片球菌(Pediococcus pentosaceus)(LP28菌株)進行培養。
(2).結果
將培養結果示於圖13。從圖13可得知,IJH-SONE68菌株之乳酸菌在使用蛋白之培養基中增殖非常多。
2.於蛋白中添加有葡萄糖及鹽滷原液之培養基的調製及培養
(1).方法
以上述1之方法進行培養時,於蛋白中添加葡萄糖使最終濃度為1w/v%,並進一步添加鹽滷原液(組成:Na+:92mg;Ca2+:3,500mg;Mg2+:6,400mg;及K+:2,300mg)使最終濃度同樣成為1v/v%並進行培養。具體來說,於乳
酸菌培養前,分別以無菌方式添加蛋白1/10容量之已進行過濾滅菌處理之10w/v%葡萄糖水溶液及蛋白1/100容量之同樣已進行過濾滅菌之鹽滷原液,並進行培養。
(2).結果
將培養結果顯示於圖14。從圖14可知,IJH-SONE68菌株之乳酸菌在於蛋白中添加有葡萄糖及鹽滷原液之培養基中顯著增殖。
由此等結果可知,IJH-SONE68菌株之乳酸菌即使在使用蛋白之培養基中亦能發揮強烈增殖能力,因此對於存在於蛋白中之溶菌酶(分解細菌細胞壁之酵素)及運鐵蛋白(具有藉螯合作用來阻礙細菌利用鐵質的作用)等之生物防禦機制甚強。
由上述詳細說明可清楚得知,若依本發明,可提供下列之發明。
[1]一種乳酸菌,會產生中性多醣作為菌體外多醣,且該中性多醣具有N-乙醯葡萄糖胺藉α-1,6鍵而連結之結構。
[2]如上述[1]之乳酸菌,其中乳酸菌係屬於乳酸桿菌(Lactobacillus)屬之乳酸菌。
[3]如上述[1]或[2]之乳酸菌,其中乳酸菌係屬於副乾酪乳酸桿菌(Lactobacillus paracasei)之乳酸菌。
[4]如上述[1]至[3]中任一項之乳酸菌,其中乳酸菌為源自無花果之乳酸菌。
[5]如上述[1]至[4]中任一項之乳酸菌,其中乳酸菌為Lactobacillus paracasei IJH-SONE68菌株(寄存編號NITE BP-02242)或與其同等之乳酸菌。
[6]如上述[1]至[5]中任一項之乳酸菌,其中中性多醣具有玻尿酸酶活性抑制活性。
[7]一種組成物,含有如上述[1]至[6]中任一項之乳酸菌。
[8]如上述[7]之組成物,其中組成物為飲食品組成物。
[9]如上述[8]之組成物,其中飲食品為飲料、機能性食品、發酵食品或補充劑。
[10]如上述[7]之組成物,其中組成物為醫藥組成物。
[11]如上述[7]之組成物,其中組成物為飼料組成物。
[12]如上述[7]之組成物,其中組成物為化妝品組成物。
[13]如上述[7]至[12]中任一項之組成物,其係用以抑制玻尿酸酶者。
[14]如上述[7]至[12]中任一項之組成物,其係用以抗過敏者。
[15]如上述[7]至[12]中任一項之組成物,其係用以抗酒精傷害者。
[16]一種如上述[1]至[6]中任一項之乳酸菌的用途,其係用作組成物之有效成分。
[17]如上述[16]之用途,其中組成物為飲食品組成物。
[18]如上述[17]之用途,其中飲食品為飲料、機能性食品、發酵食品或補充劑。
[19]如上述[16]之用途,其中組成物為醫藥組成物。
[20]如上述[16]之用途,其中組成物為飼料組成物。
[21]如上述[16]之用途,其中組成物為化妝品組成物。
[22]如上述[16]至[21]中任一項之用途,其中組成物係用以抑制玻尿酸酶之組成物。
[23]如上述[16]至[21]中任一項之用途,其中組成物係用以抗過敏之組成物。
[24]如上述[16]至[21]中任一項之用途,其中組成物係用以抗酒精傷害之組成物。
[25]一種組成物之製造方法,包含:將如上述[1]至[6]中任一項之乳酸菌與其他成分混合。
[26]如上述[25]之製造方法,其中組成物為飲食品組成物。
[27]如上述[26]之製造方法,其中飲食品為飲料、機能性食品、發酵食品或補充劑。
[28]如上述[25]之製造方法,其中組成物為醫藥組成物。
[29]如上述[25]之製造方法,其中組成物為飼料組成物。
[30]如上述[25]之製造方法,其中組成物為化妝品組成物。
[31]如上述[25]至[30]中任一項之製造方法,其中組成物係用以抑制玻尿酸酶之組成物。
[32]如上述[25]至[30]中任一項之製造方法,其中組成物係用以抗過敏之組成物。
[33]如上述[25]至[30]中任一項之製造方法,其中組成物係用以抗酒精傷害之組成物。
[34]一種施用方法,係將如上述[1]至[6]中任一項之乳酸菌施用於有其必要之對象的方法,包含:將含有如上述[1]至[6]中任一項之乳酸菌的組成物施用於對象。
[35]如上述[34]之施用方法,其中組成物為飲食品組成物。
[36]如上述[35]之施用方法,其中飲食品為飲料、機能性食品、發酵食品或補充劑。
[37]如上述[34]之施用方法,其中組成物為醫藥組成物。
[38]如上述[34]之施用方法,其中組成物為飼料組成物。
[39]如上述[34]之施用方法,其中組成物為化妝品組成物。
[40]如上述[34]至[39]中任一項之施用方法,其係對對象發揮玻尿酸酶抑制作用。
[41]如上述[34]至[39]中任一項之施用方法,其係對對象發揮抗過敏作用。
[42]如上述[34]至[39]中任一項之施用方法,其係對對象發揮抗酒精傷害之作用。
如以上詳細說明,本發明之乳酸菌可產生發揮玻尿酸酶抑制活性而顯示出抗過敏效果之菌體外多醣,此外,顯示出抗酒精傷害效果。進一步來說,本發明之乳酸菌對胃酸及膽酸具高度耐性,即使在使用蛋白之培養基中也能發揮強烈增殖能力。因此,本發明之乳酸菌可用作飲食品、醫藥品、飼料、化妝品等之有效成分。
JP日本 獨立行政法人製品評價技術基盤機構專利微生物中心 2017年5月19日 NITE BP-02242
(無)
Claims (10)
- 一種乳酸菌,係副乾酪乳酸桿菌(Lactobacillus paracasei)IJH-SONE68菌株(寄存編號NITE BP-02242)。
- 一種組成物,含有如請求項1之乳酸菌。
- 如請求項2之組成物,其中組成物為飲食品組成物。
- 如請求項3之組成物,其中飲食品為飲料、機能性食品、發酵食品或補充劑(supplement)。
- 如請求項2之組成物,其中組成物為醫藥組成物。
- 如請求項2之組成物,其中組成物為飼料組成物。
- 如請求項2之組成物,其中組成物為化妝品組成物。
- 如請求項2至7中任一項之組成物,其係用以抑制玻尿酸酶者。
- 如請求項2至7中任一項之組成物,其係用以抗過敏者。
- 如請求項2至5中任一項之組成物,其係用以抗酒精傷害者。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2017114171 | 2017-06-09 | ||
JP2017-114171 | 2017-06-09 |
Publications (2)
Publication Number | Publication Date |
---|---|
TW201902500A TW201902500A (zh) | 2019-01-16 |
TWI696465B true TWI696465B (zh) | 2020-06-21 |
Family
ID=64567287
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
TW107118302A TWI696465B (zh) | 2017-06-09 | 2018-05-29 | 新穎乳酸菌及其用途 |
Country Status (11)
Country | Link |
---|---|
US (1) | US11447740B2 (zh) |
EP (1) | EP3483259A4 (zh) |
JP (1) | JP6523580B2 (zh) |
KR (1) | KR102313677B1 (zh) |
CN (1) | CN110741073A (zh) |
AU (1) | AU2018281511B2 (zh) |
BR (1) | BR112019000069A2 (zh) |
CA (1) | CA3032572C (zh) |
NZ (1) | NZ750188A (zh) |
TW (1) | TWI696465B (zh) |
WO (1) | WO2018225556A1 (zh) |
Families Citing this family (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TWI746955B (zh) * | 2018-04-25 | 2021-11-21 | 日商曾根農場股份有限公司 | 第i型過敏用組成物 |
TWI727293B (zh) * | 2018-04-25 | 2021-05-11 | 日商曾根農場股份有限公司 | 第iv型過敏用組成物 |
TWI739078B (zh) * | 2018-04-25 | 2021-09-11 | 日商曾根農場股份有限公司 | 脂肪累積抑制用組成物 |
CN109468247B (zh) * | 2018-11-27 | 2021-06-01 | 宜宾五粮液股份有限公司 | 耐乙醇、耐高温及高产乳酸的耐酸乳杆菌及其用途 |
CN112481148A (zh) * | 2019-08-22 | 2021-03-12 | 丰华生物科技股份有限公司 | 用于美白功效的含乳酸菌发酵物的组合物及其用途 |
TWI715177B (zh) * | 2019-08-30 | 2021-01-01 | 葡萄王生技股份有限公司 | 鼠李糖乳桿菌gklc1、組合物及其改善酒精性肝損傷、胃損傷及/或腸損傷之用途 |
KR20220080075A (ko) * | 2019-10-11 | 2022-06-14 | 고쿠리츠 다이가꾸 호우진 시즈오까 다이가꾸 | 니코틴아미드 리보시드를 산생하는 유산균, 및 니코틴아미드 모노뉴클레오티드 및 니코틴아미드 리보시드를 산생하는 유산균 |
JP7195714B2 (ja) * | 2020-10-19 | 2022-12-26 | 曽根ファーム株式会社 | 炎症性腸疾患用組成物 |
TWI788633B (zh) * | 2019-12-11 | 2023-01-01 | 臺灣菸酒股份有限公司 | 新穎乳酸菌用於製備嘌呤化合物降解劑之用途 |
CN111662850B (zh) * | 2020-07-10 | 2022-03-15 | 江南大学 | 一株能够缓解酒精性肠道损伤的副干酪乳杆菌及其应用 |
TWI770595B (zh) * | 2020-08-27 | 2022-07-11 | 臺灣菸酒股份有限公司 | 乳酸菌用於治療或預防肝臟損傷相關疾病之用途 |
KR102453319B1 (ko) * | 2021-08-09 | 2022-10-12 | 주식회사 한국화장품제조 | 락토바실러스 쿤키 Hankook-001 균주를 이용한 항산화, 항염, 미백, 항주름용 발효추출물 및 그 제조 방법, 그 발효추출물을 포함하는 항산화, 항염, 미백, 항주름용 화장료 조성물 |
CN113755403A (zh) * | 2021-10-12 | 2021-12-07 | 浙江省农业科学院 | 一种产胞外多糖的戊糖乳杆菌及其发酵工艺和应用 |
TWI785854B (zh) * | 2021-10-21 | 2022-12-01 | 領航生技股份有限公司 | 一種生產玻尿酸之乳酸菌株、其用途以及組合物 |
JPWO2023106376A1 (zh) * | 2021-12-09 | 2023-06-15 | ||
KR102701254B1 (ko) * | 2021-12-14 | 2024-09-03 | 주식회사 엘지생활건강 | 신규한 락토바실러스 프룩티보란스 균주 및 이의 용도 |
CN114277085B (zh) * | 2021-12-27 | 2024-04-30 | 烟台欣和企业食品有限公司 | 一种区分过氧化乳杆菌与干酪类乳杆菌的检测方法 |
CN115612634B (zh) * | 2022-06-13 | 2023-12-08 | 湖北至正天辰生物科技有限公司 | 一株分离的黑氏乳杆菌及其发酵的昆虫蛋白及应用 |
CN115895948B (zh) * | 2022-10-24 | 2024-08-02 | 浙江一鸣食品股份有限公司 | 一种高效抑制霉菌生长的副干酪乳杆菌及其培养方法和应用 |
CN116814464B (zh) * | 2023-03-13 | 2024-02-02 | 广东悦创生物科技有限公司 | 一株发酵粘液乳杆菌jf5及其在制备减脂和助消化食品药品中的应用 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20110150838A1 (en) * | 2009-12-23 | 2011-06-23 | Lytone Enterprise, Inc. | Lactobacillus paracasei strain lt12 as immunity regulatory agent |
US20140377238A1 (en) * | 2011-06-20 | 2014-12-25 | H.J. Heinz Company | Probiotic compositions and methods |
Family Cites Families (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040023361A1 (en) * | 1997-10-17 | 2004-02-05 | Nestec S.A. | Lactic acid bacteria producing polysaccharide similar to those in human milk and corresponding gene |
JP2006298779A (ja) * | 2005-04-15 | 2006-11-02 | Kanehide Bio Kk | 乳酸菌培養により得られる抗アレルギー剤 |
CN101314620B (zh) * | 2007-05-29 | 2010-07-14 | 光明乳业股份有限公司 | 一种干酪乳杆菌胞外多糖的单一多糖及其制备方法和应用 |
FR2930264B1 (fr) | 2008-04-18 | 2013-02-22 | Gervais Danone Sa | Nouvelle souche de lactobacillus paracasei subsp. paracasei dotee de proprietes antimicrobiennes et immunomodulatrices. |
US8361481B2 (en) | 2008-04-25 | 2013-01-29 | Kameda Seika Co., Ltd. | Lactic acid bacterium having anti-allergic activity and pharmaceutical composition |
JP2010252641A (ja) * | 2009-04-22 | 2010-11-11 | Mitsubishi Rayon Co Ltd | 乳酸菌由来多糖類の製造方法 |
WO2012133827A1 (ja) | 2011-03-31 | 2012-10-04 | 森永乳業株式会社 | 新規乳酸菌、並びに新規乳酸菌を含有する医薬、飲食品、及び飼料 |
KR101869498B1 (ko) | 2011-04-08 | 2018-06-22 | 시에이치알. 한센 에이/에스 | 시너지적 항균 효과 |
EP2791367B1 (en) * | 2011-12-16 | 2019-04-24 | Inbiose N.V. | Mutant microorganisms to synthesize colanic acid, mannosylated and/or fucosylated oligosaccharides |
KR101371648B1 (ko) | 2012-02-10 | 2014-03-07 | 매일유업주식회사 | 알코올 분해능이 우수한 락토바실러스 브레비스 및 그를 함유하는 조성물 |
EA034173B1 (ru) | 2012-04-09 | 2020-01-14 | Кр. Хансен А/С | Противогрибковая композиция, содержащая штамм lactobacillus paracasei |
US9161957B2 (en) | 2012-08-03 | 2015-10-20 | Life Well Lived, Llc | Compositions and methods for reducing blood alcohol content |
CN113684233A (zh) * | 2014-06-27 | 2021-11-23 | 格礼卡姆股份公司 | 寡糖的制备 |
JP5629841B1 (ja) * | 2014-08-06 | 2014-11-26 | 大高酵素株式会社 | 発酵化粧料の製造方法及び乳酸菌菌株 |
-
2018
- 2018-05-28 CN CN201880003581.0A patent/CN110741073A/zh active Pending
- 2018-05-28 NZ NZ750188A patent/NZ750188A/en unknown
- 2018-05-28 WO PCT/JP2018/020333 patent/WO2018225556A1/ja unknown
- 2018-05-28 EP EP18812929.0A patent/EP3483259A4/en not_active Ceased
- 2018-05-28 AU AU2018281511A patent/AU2018281511B2/en active Active
- 2018-05-28 CA CA3032572A patent/CA3032572C/en active Active
- 2018-05-28 JP JP2018562385A patent/JP6523580B2/ja active Active
- 2018-05-28 US US16/317,397 patent/US11447740B2/en active Active
- 2018-05-28 KR KR1020197004371A patent/KR102313677B1/ko active IP Right Grant
- 2018-05-28 BR BR112019000069A patent/BR112019000069A2/pt not_active IP Right Cessation
- 2018-05-29 TW TW107118302A patent/TWI696465B/zh active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20110150838A1 (en) * | 2009-12-23 | 2011-06-23 | Lytone Enterprise, Inc. | Lactobacillus paracasei strain lt12 as immunity regulatory agent |
US20140377238A1 (en) * | 2011-06-20 | 2014-12-25 | H.J. Heinz Company | Probiotic compositions and methods |
Non-Patent Citations (4)
Title |
---|
GenBank accession no: /01 Hee et. Al. "Exopolysaccharide-Overproducing Lactobacillus paracasei KB28 Induces Cytokines in Mouse Peritoneal Macrophages via Modulation of NF-κB and MAPKs" J. Microbiol. Biotechnol. (2011), 21(11), 1174–1178 Panthavee et. al., "Characterization of Exopolysaccharides Produced by Thermophilic Lactic Acid Bacteria Isolated from Tropical Fruits of Thailand" Biol. Pharm. Bull. 40, 621–629 (2017) (Published: May 01, 2017) * |
GenBank accession no: CP007122 2014/10/01 |
Hee et. Al. "Exopolysaccharide-Overproducing Lactobacillus paracasei KB28 Induces Cytokines in Mouse Peritoneal Macrophages via Modulation of NF-κB and MAPKs" J. Microbiol. Biotechnol. (2011), 21(11), 1174–1178 |
Panthavee et. al., "Characterization of Exopolysaccharides Produced by Thermophilic Lactic Acid Bacteria Isolated from Tropical Fruits of Thailand" Biol. Pharm. Bull. 40, 621–629 (2017) (Published: May 01, 2017) |
Also Published As
Publication number | Publication date |
---|---|
US11447740B2 (en) | 2022-09-20 |
JP6523580B2 (ja) | 2019-06-05 |
EP3483259A4 (en) | 2019-10-09 |
CN110741073A (zh) | 2020-01-31 |
WO2018225556A1 (ja) | 2018-12-13 |
JPWO2018225556A1 (ja) | 2019-06-27 |
BR112019000069A2 (pt) | 2019-12-17 |
KR20190111890A (ko) | 2019-10-02 |
AU2018281511B2 (en) | 2020-04-16 |
CA3032572C (en) | 2020-04-21 |
EP3483259A1 (en) | 2019-05-15 |
AU2018281511A1 (en) | 2019-01-17 |
NZ750188A (en) | 2022-04-29 |
TW201902500A (zh) | 2019-01-16 |
KR102313677B1 (ko) | 2021-10-18 |
CA3032572A1 (en) | 2018-12-13 |
US20190390289A1 (en) | 2019-12-26 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
TWI696465B (zh) | 新穎乳酸菌及其用途 | |
TWI713850B (zh) | 乳酸菌之菌體外多醣及其用途 | |
TWI689585B (zh) | 新穎乳酸菌株及包含新穎乳酸菌株之免疫賦活劑 | |
CN107208040B (zh) | 乳酸菌、来源于该乳酸菌的天然免疫活化剂、感染症预防治疗剂和饮食品 | |
TWI739078B (zh) | 脂肪累積抑制用組成物 | |
JP6679202B2 (ja) | Iv型アレルギー用組成物 | |
CN111212575A (zh) | 肌肉增量用组合物 | |
TWI746955B (zh) | 第i型過敏用組成物 | |
CN103562381B (zh) | 缺失d-乳酸产生并且具有改进的贮藏期限的约氏乳杆菌菌株cncm i-1225的衍生物 |