US20140322172A1 - Lipid metabolism and/or sugar metabolism improver containing lactic acid bacterium or treatment product thereof - Google Patents
Lipid metabolism and/or sugar metabolism improver containing lactic acid bacterium or treatment product thereof Download PDFInfo
- Publication number
- US20140322172A1 US20140322172A1 US14/363,150 US201214363150A US2014322172A1 US 20140322172 A1 US20140322172 A1 US 20140322172A1 US 201214363150 A US201214363150 A US 201214363150A US 2014322172 A1 US2014322172 A1 US 2014322172A1
- Authority
- US
- United States
- Prior art keywords
- strain
- bacterial cell
- lipid metabolism
- lactobacillus
- metabolism
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 230000037356 lipid metabolism Effects 0.000 title claims abstract description 122
- 230000004060 metabolic process Effects 0.000 title claims abstract description 121
- 241000894006 Bacteria Species 0.000 title claims abstract description 51
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 title description 88
- 239000004310 lactic acid Substances 0.000 title description 44
- 235000014655 lactic acid Nutrition 0.000 title description 44
- 210000004027 cell Anatomy 0.000 claims abstract description 167
- 230000001580 bacterial effect Effects 0.000 claims abstract description 157
- 230000000694 effects Effects 0.000 claims abstract description 91
- 235000013305 food Nutrition 0.000 claims abstract description 83
- 235000013361 beverage Nutrition 0.000 claims abstract description 75
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 claims abstract description 43
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 claims abstract description 43
- 239000000203 mixture Substances 0.000 claims abstract description 31
- 241000186660 Lactobacillus Species 0.000 claims abstract description 21
- 229940039696 lactobacillus Drugs 0.000 claims abstract description 21
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 19
- 241000186000 Bifidobacterium Species 0.000 claims abstract description 17
- 239000004480 active ingredient Substances 0.000 claims abstract description 15
- 241000186713 Lactobacillus amylovorus Species 0.000 claims description 60
- 102000023984 PPAR alpha Human genes 0.000 claims description 42
- 108091008725 peroxisome proliferator-activated receptors alpha Proteins 0.000 claims description 42
- 102000000536 PPAR gamma Human genes 0.000 claims description 36
- 108010016731 PPAR gamma Proteins 0.000 claims description 36
- 238000000034 method Methods 0.000 claims description 29
- 241000186606 Lactobacillus gasseri Species 0.000 claims description 25
- 239000013641 positive control Substances 0.000 claims description 23
- 238000004519 manufacturing process Methods 0.000 claims description 22
- 210000001596 intra-abdominal fat Anatomy 0.000 claims description 21
- 239000013642 negative control Substances 0.000 claims description 20
- 238000003556 assay Methods 0.000 claims description 19
- 239000003446 ligand Substances 0.000 claims description 13
- 241000186012 Bifidobacterium breve Species 0.000 claims description 11
- 241000186015 Bifidobacterium longum subsp. infantis Species 0.000 claims description 11
- 230000009471 action Effects 0.000 claims description 11
- 229940004120 bifidobacterium infantis Drugs 0.000 claims description 11
- 210000004003 subcutaneous fat Anatomy 0.000 claims description 10
- 241000186018 Bifidobacterium adolescentis Species 0.000 claims description 9
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 9
- 235000013376 functional food Nutrition 0.000 claims description 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
- 235000013402 health food Nutrition 0.000 claims description 7
- 229940079593 drug Drugs 0.000 claims description 6
- 208000030159 metabolic disease Diseases 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 5
- 235000013373 food additive Nutrition 0.000 claims description 4
- 239000002778 food additive Substances 0.000 claims description 4
- 238000009825 accumulation Methods 0.000 claims description 3
- 244000005700 microbiome Species 0.000 abstract description 2
- 239000000047 product Substances 0.000 description 62
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 33
- 239000002609 medium Substances 0.000 description 27
- -1 and the like Chemical class 0.000 description 24
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
- 201000010099 disease Diseases 0.000 description 19
- 239000000284 extract Substances 0.000 description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 230000004913 activation Effects 0.000 description 16
- 239000003925 fat Substances 0.000 description 16
- 238000002360 preparation method Methods 0.000 description 16
- 239000000843 powder Substances 0.000 description 15
- 208000035475 disorder Diseases 0.000 description 14
- 235000019197 fats Nutrition 0.000 description 14
- 238000011534 incubation Methods 0.000 description 11
- 239000012124 Opti-MEM Substances 0.000 description 10
- 239000000654 additive Substances 0.000 description 10
- 235000012000 cholesterol Nutrition 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 208000001145 Metabolic Syndrome Diseases 0.000 description 9
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 9
- 239000007788 liquid Substances 0.000 description 9
- 241000894007 species Species 0.000 description 9
- 239000003826 tablet Substances 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 8
- 230000037396 body weight Effects 0.000 description 8
- 239000002775 capsule Substances 0.000 description 8
- 230000001976 improved effect Effects 0.000 description 8
- 238000005259 measurement Methods 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 102000011690 Adiponectin Human genes 0.000 description 7
- 108010076365 Adiponectin Proteins 0.000 description 7
- 108010023302 HDL Cholesterol Proteins 0.000 description 7
- 210000000577 adipose tissue Anatomy 0.000 description 7
- 235000005911 diet Nutrition 0.000 description 7
- 235000014113 dietary fatty acids Nutrition 0.000 description 7
- 239000000194 fatty acid Substances 0.000 description 7
- 229930195729 fatty acid Natural products 0.000 description 7
- 239000003960 organic solvent Substances 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 108010010234 HDL Lipoproteins Proteins 0.000 description 6
- 230000037213 diet Effects 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 6
- 239000000796 flavoring agent Substances 0.000 description 6
- 235000019634 flavors Nutrition 0.000 description 6
- 230000036541 health Effects 0.000 description 6
- 235000009200 high fat diet Nutrition 0.000 description 6
- 239000004615 ingredient Substances 0.000 description 6
- 238000010172 mouse model Methods 0.000 description 6
- 238000000926 separation method Methods 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
- 241001608472 Bifidobacterium longum Species 0.000 description 5
- 229940009291 bifidobacterium longum Drugs 0.000 description 5
- 230000006378 damage Effects 0.000 description 5
- 235000003599 food sweetener Nutrition 0.000 description 5
- 239000002304 perfume Substances 0.000 description 5
- 239000003765 sweetening agent Substances 0.000 description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 239000004375 Dextrin Substances 0.000 description 4
- 229920001353 Dextrin Polymers 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- 206010022489 Insulin Resistance Diseases 0.000 description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- 108010028554 LDL Cholesterol Proteins 0.000 description 4
- 238000008214 LDL Cholesterol Methods 0.000 description 4
- 240000001929 Lactobacillus brevis Species 0.000 description 4
- 235000013957 Lactobacillus brevis Nutrition 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 208000008589 Obesity Diseases 0.000 description 4
- 244000057717 Streptococcus lactis Species 0.000 description 4
- 235000014897 Streptococcus lactis Nutrition 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 239000003086 colorant Substances 0.000 description 4
- 238000002591 computed tomography Methods 0.000 description 4
- 235000019425 dextrin Nutrition 0.000 description 4
- 150000004665 fatty acids Chemical class 0.000 description 4
- 235000020510 functional beverage Nutrition 0.000 description 4
- 108020001507 fusion proteins Proteins 0.000 description 4
- 102000037865 fusion proteins Human genes 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 201000001421 hyperglycemia Diseases 0.000 description 4
- 235000015097 nutrients Nutrition 0.000 description 4
- 235000020824 obesity Nutrition 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 238000012545 processing Methods 0.000 description 4
- 230000001737 promoting effect Effects 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 239000003381 stabilizer Substances 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- 239000006188 syrup Substances 0.000 description 4
- 235000020357 syrup Nutrition 0.000 description 4
- 238000001890 transfection Methods 0.000 description 4
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 4
- 239000011782 vitamin Substances 0.000 description 4
- 235000013343 vitamin Nutrition 0.000 description 4
- 229930003231 vitamin Natural products 0.000 description 4
- 229940088594 vitamin Drugs 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
- 206010003210 Arteriosclerosis Diseases 0.000 description 3
- 241000186016 Bifidobacterium bifidum Species 0.000 description 3
- 241000186011 Bifidobacterium catenulatum Species 0.000 description 3
- 108010076119 Caseins Proteins 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 208000031226 Hyperlipidaemia Diseases 0.000 description 3
- 241000218492 Lactobacillus crispatus Species 0.000 description 3
- 241000186673 Lactobacillus delbrueckii Species 0.000 description 3
- 241000509544 Lactobacillus gallinarum Species 0.000 description 3
- 240000002605 Lactobacillus helveticus Species 0.000 description 3
- 235000013967 Lactobacillus helveticus Nutrition 0.000 description 3
- 241001468157 Lactobacillus johnsonii Species 0.000 description 3
- 241000186605 Lactobacillus paracasei Species 0.000 description 3
- 240000006024 Lactobacillus plantarum Species 0.000 description 3
- 235000013965 Lactobacillus plantarum Nutrition 0.000 description 3
- 241000186869 Lactobacillus salivarius Species 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 229940080774 Peroxisome proliferator-activated receptor gamma agonist Drugs 0.000 description 3
- 244000299461 Theobroma cacao Species 0.000 description 3
- 210000001789 adipocyte Anatomy 0.000 description 3
- 239000000556 agonist Substances 0.000 description 3
- 230000001270 agonistic effect Effects 0.000 description 3
- 208000011775 arteriosclerosis disease Diseases 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- 229940002008 bifidobacterium bifidum Drugs 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 3
- 239000005018 casein Substances 0.000 description 3
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 3
- 235000021240 caseins Nutrition 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 235000009508 confectionery Nutrition 0.000 description 3
- 235000013325 dietary fiber Nutrition 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229940125542 dual agonist Drugs 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 230000000977 initiatory effect Effects 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- 229940054346 lactobacillus helveticus Drugs 0.000 description 3
- 229940072205 lactobacillus plantarum Drugs 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 239000000463 material Substances 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
- 239000011707 mineral Substances 0.000 description 3
- 235000010755 mineral Nutrition 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 229940127557 pharmaceutical product Drugs 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 235000013772 propylene glycol Nutrition 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000013589 supplement Substances 0.000 description 3
- 235000013616 tea Nutrition 0.000 description 3
- 239000000230 xanthan gum Substances 0.000 description 3
- 229920001285 xanthan gum Polymers 0.000 description 3
- 235000010493 xanthan gum Nutrition 0.000 description 3
- 229940082509 xanthan gum Drugs 0.000 description 3
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- 108020004465 16S ribosomal RNA Proteins 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 101100245381 Caenorhabditis elegans pbs-6 gene Proteins 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 241000282552 Chlorocebus aethiops Species 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- 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 2
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 208000032928 Dyslipidaemia Diseases 0.000 description 2
- 241000194032 Enterococcus faecalis Species 0.000 description 2
- PLUBXMRUUVWRLT-UHFFFAOYSA-N Ethyl methanesulfonate Chemical compound CCOS(C)(=O)=O PLUBXMRUUVWRLT-UHFFFAOYSA-N 0.000 description 2
- 208000004930 Fatty Liver Diseases 0.000 description 2
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 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 2
- 108010068370 Glutens Proteins 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 240000001046 Lactobacillus acidophilus Species 0.000 description 2
- 235000013956 Lactobacillus acidophilus Nutrition 0.000 description 2
- 241000186679 Lactobacillus buchneri Species 0.000 description 2
- 241001643449 Lactobacillus parakefiri Species 0.000 description 2
- 241000192129 Leuconostoc lactis Species 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- DATAGRPVKZEWHA-YFKPBYRVSA-N N(5)-ethyl-L-glutamine Chemical compound CCNC(=O)CC[C@H]([NH3+])C([O-])=O DATAGRPVKZEWHA-YFKPBYRVSA-N 0.000 description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 241000242739 Renilla Species 0.000 description 2
- 108700008625 Reporter Genes Proteins 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 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 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 244000269722 Thea sinensis Species 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- 241000238583 Vargula hilgendorfii Species 0.000 description 2
- 229930003268 Vitamin C Natural products 0.000 description 2
- 108010046377 Whey Proteins Proteins 0.000 description 2
- 102000007544 Whey Proteins Human genes 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- QCWXUUIWCKQGHC-UHFFFAOYSA-N Zirconium Chemical compound [Zr] QCWXUUIWCKQGHC-UHFFFAOYSA-N 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 239000000205 acacia gum Substances 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- MBMBGCFOFBJSGT-KUBAVDMBSA-N all-cis-docosa-4,7,10,13,16,19-hexaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCC(O)=O MBMBGCFOFBJSGT-KUBAVDMBSA-N 0.000 description 2
- 230000001399 anti-metabolic effect Effects 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000036760 body temperature Effects 0.000 description 2
- 235000014121 butter Nutrition 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 235000014171 carbonated beverage Nutrition 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 235000005687 corn oil Nutrition 0.000 description 2
- 239000002285 corn oil Substances 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 229940099112 cornstarch Drugs 0.000 description 2
- CVSVTCORWBXHQV-UHFFFAOYSA-N creatine Chemical compound NC(=[NH2+])N(C)CC([O-])=O CVSVTCORWBXHQV-UHFFFAOYSA-N 0.000 description 2
- 210000004748 cultured cell Anatomy 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 229940032049 enterococcus faecalis Drugs 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 239000013613 expression plasmid Substances 0.000 description 2
- 229940125753 fibrate Drugs 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229960002949 fluorouracil Drugs 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 235000015203 fruit juice Nutrition 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 235000021312 gluten Nutrition 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 229940039695 lactobacillus acidophilus Drugs 0.000 description 2
- 108020001756 ligand binding domains Proteins 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 244000144972 livestock Species 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 2
- 238000004020 luminiscence type Methods 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 235000020124 milk-based beverage Nutrition 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 239000006872 mrs medium Substances 0.000 description 2
- 239000003471 mutagenic agent Substances 0.000 description 2
- 231100000707 mutagenic chemical Toxicity 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000012454 non-polar solvent Substances 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 230000035764 nutrition Effects 0.000 description 2
- 235000016709 nutrition Nutrition 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 229920001542 oligosaccharide Polymers 0.000 description 2
- 150000002482 oligosaccharides Chemical class 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000003002 pH adjusting agent Substances 0.000 description 2
- 229920001277 pectin Polymers 0.000 description 2
- 239000001814 pectin Substances 0.000 description 2
- 235000010987 pectin Nutrition 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 230000008092 positive effect Effects 0.000 description 2
- 238000011533 pre-incubation Methods 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 150000005846 sugar alcohols Polymers 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 235000019640 taste Nutrition 0.000 description 2
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 2
- 229960001641 troglitazone Drugs 0.000 description 2
- GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 235000019154 vitamin C Nutrition 0.000 description 2
- 239000011718 vitamin C Substances 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- 235000013618 yogurt Nutrition 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 229910052726 zirconium Inorganic materials 0.000 description 2
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 1
- SPVFQMYEUKTCJQ-UHFFFAOYSA-N (4-nitrophenyl)methylarsonic acid Chemical compound O[As](O)(=O)CC1=CC=C([N+]([O-])=O)C=C1 SPVFQMYEUKTCJQ-UHFFFAOYSA-N 0.000 description 1
- DRCWOKJLSQUJPZ-DZGCQCFKSA-N (4ar,9as)-n-ethyl-1,4,9,9a-tetrahydrofluoren-4a-amine Chemical compound C1C2=CC=CC=C2[C@]2(NCC)[C@H]1CC=CC2 DRCWOKJLSQUJPZ-DZGCQCFKSA-N 0.000 description 1
- 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
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- 239000001763 2-hydroxyethyl(trimethyl)azanium Substances 0.000 description 1
- SEBVWSLCNXRBEA-UHFFFAOYSA-N 2-oxidanylpropanoic acid Chemical compound CC(O)C(O)=O.CC(O)C(O)=O.CC(O)C(O)=O SEBVWSLCNXRBEA-UHFFFAOYSA-N 0.000 description 1
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 1
- 208000022309 Alcoholic Liver disease Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 239000000592 Artificial Cell Substances 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 241001134770 Bifidobacterium animalis Species 0.000 description 1
- 241000901050 Bifidobacterium animalis subsp. lactis Species 0.000 description 1
- 241000186153 Bifidobacterium magnum Species 0.000 description 1
- 241001134772 Bifidobacterium pseudocatenulatum Species 0.000 description 1
- 241000186148 Bifidobacterium pseudolongum Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 206010007572 Cardiac hypertrophy Diseases 0.000 description 1
- 208000006029 Cardiomegaly Diseases 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 235000019743 Choline chloride Nutrition 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 241000777300 Congiopodidae Species 0.000 description 1
- 241000938605 Crocodylia Species 0.000 description 1
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
- UYUXSRADSPPKRZ-UHFFFAOYSA-N D-glucuronic acid gamma-lactone Natural products O=CC(O)C1OC(=O)C(O)C1O UYUXSRADSPPKRZ-UHFFFAOYSA-N 0.000 description 1
- UYUXSRADSPPKRZ-SKNVOMKLSA-N D-glucurono-6,3-lactone Chemical compound O=C[C@H](O)[C@H]1OC(=O)[C@@H](O)[C@H]1O UYUXSRADSPPKRZ-SKNVOMKLSA-N 0.000 description 1
- 238000007900 DNA-DNA hybridization Methods 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 208000002249 Diabetes Complications Diseases 0.000 description 1
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 description 1
- AANLCWYVVNBGEE-IDIVVRGQSA-L Disodium inosinate Chemical compound [Na+].[Na+].O[C@@H]1[C@H](O)[C@@H](COP([O-])([O-])=O)O[C@H]1N1C(NC=NC2=O)=C2N=C1 AANLCWYVVNBGEE-IDIVVRGQSA-L 0.000 description 1
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
- 239000004131 EU approved raising agent Substances 0.000 description 1
- 239000004278 EU approved seasoning Substances 0.000 description 1
- 241001632410 Eleutherococcus senticosus Species 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- 244000119461 Garcinia xanthochymus Species 0.000 description 1
- 235000000885 Garcinia xanthochymus Nutrition 0.000 description 1
- 240000001972 Gardenia jasminoides Species 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 239000000899 Gutta-Percha Substances 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 229920002488 Hemicellulose Polymers 0.000 description 1
- 101001008429 Homo sapiens Nucleobindin-2 Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- 244000199866 Lactobacillus casei Species 0.000 description 1
- 235000013958 Lactobacillus casei Nutrition 0.000 description 1
- 241000186842 Lactobacillus coryniformis Species 0.000 description 1
- 241000186840 Lactobacillus fermentum Species 0.000 description 1
- 241001468190 Lactobacillus homohiochii Species 0.000 description 1
- 241001561398 Lactobacillus jensenii Species 0.000 description 1
- 241000186604 Lactobacillus reuteri Species 0.000 description 1
- 241000218588 Lactobacillus rhamnosus Species 0.000 description 1
- 241000577554 Lactobacillus zeae Species 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229920000057 Mannan Polymers 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- VZUNGTLZRAYYDE-UHFFFAOYSA-N N-methyl-N'-nitro-N-nitrosoguanidine Chemical compound O=NN(C)C(=N)N[N+]([O-])=O VZUNGTLZRAYYDE-UHFFFAOYSA-N 0.000 description 1
- 102100027441 Nucleobindin-2 Human genes 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 240000000342 Palaquium gutta Species 0.000 description 1
- 241000282577 Pan troglodytes Species 0.000 description 1
- 240000004371 Panax ginseng Species 0.000 description 1
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 1
- 235000003140 Panax quinquefolius Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 108010009736 Protein Hydrolysates Proteins 0.000 description 1
- 235000019485 Safflower oil Nutrition 0.000 description 1
- 241001125046 Sardina pilchardus Species 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 235000006468 Thea sinensis Nutrition 0.000 description 1
- 235000009470 Theobroma cacao Nutrition 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 239000005862 Whey Substances 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 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
- 230000003187 abdominal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- JAZBEHYOTPTENJ-JLNKQSITSA-N all-cis-5,8,11,14,17-icosapentaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O JAZBEHYOTPTENJ-JLNKQSITSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- 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
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 235000020244 animal milk Nutrition 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000002518 antifoaming agent Substances 0.000 description 1
- 235000015197 apple juice Nutrition 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229940069768 asian ginseng extract Drugs 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 235000013527 bean curd Nutrition 0.000 description 1
- 230000003796 beauty Effects 0.000 description 1
- 235000015278 beef Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 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 1
- 229940118852 bifidobacterium animalis Drugs 0.000 description 1
- 229940009289 bifidobacterium lactis Drugs 0.000 description 1
- 235000015895 biscuits Nutrition 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 235000021152 breakfast Nutrition 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- 235000012970 cakes Nutrition 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 229960002504 capsaicin Drugs 0.000 description 1
- 235000017663 capsaicin Nutrition 0.000 description 1
- ZICNYIDDNJYKCP-SOFGYWHQSA-N capsiate Chemical compound COC1=CC(COC(=O)CCCC\C=C\C(C)C)=CC=C1O ZICNYIDDNJYKCP-SOFGYWHQSA-N 0.000 description 1
- 229960004203 carnitine Drugs 0.000 description 1
- 235000015190 carrot juice Nutrition 0.000 description 1
- 108010079058 casein hydrolysate Proteins 0.000 description 1
- 150000001765 catechin Chemical class 0.000 description 1
- ADRVNXBAWSRFAJ-UHFFFAOYSA-N catechin Natural products OC1Cc2cc(O)cc(O)c2OC1c3ccc(O)c(O)c3 ADRVNXBAWSRFAJ-UHFFFAOYSA-N 0.000 description 1
- 235000005487 catechin Nutrition 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- SGMZJAMFUVOLNK-UHFFFAOYSA-M choline chloride Chemical compound [Cl-].C[N+](C)(C)CCO SGMZJAMFUVOLNK-UHFFFAOYSA-M 0.000 description 1
- 229960003178 choline chloride Drugs 0.000 description 1
- KXKPYJOVDUMHGS-OSRGNVMNSA-N chondroitin sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](OS(O)(=O)=O)[C@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](C(O)=O)O1 KXKPYJOVDUMHGS-OSRGNVMNSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 235000017471 coenzyme Q10 Nutrition 0.000 description 1
- ACTIUHUUMQJHFO-UPTCCGCDSA-N coenzyme Q10 Chemical compound COC1=C(OC)C(=O)C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UPTCCGCDSA-N 0.000 description 1
- 235000020152 coffee milk drink Nutrition 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 235000020940 control diet Nutrition 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 235000014510 cooky Nutrition 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229960003624 creatine Drugs 0.000 description 1
- 239000006046 creatine Substances 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 235000015140 cultured milk Nutrition 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 235000011950 custard Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 229960003067 cystine Drugs 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 description 1
- 235000013890 disodium inosinate Nutrition 0.000 description 1
- 229940090949 docosahexaenoic acid Drugs 0.000 description 1
- 235000020669 docosahexaenoic acid Nutrition 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 235000015071 dressings Nutrition 0.000 description 1
- 238000002036 drum drying Methods 0.000 description 1
- 229960005135 eicosapentaenoic acid Drugs 0.000 description 1
- 235000020673 eicosapentaenoic acid Nutrition 0.000 description 1
- JAZBEHYOTPTENJ-UHFFFAOYSA-N eicosapentaenoic acid Natural products CCC=CCC=CCC=CCC=CCC=CCCCC(O)=O JAZBEHYOTPTENJ-UHFFFAOYSA-N 0.000 description 1
- 230000003028 elevating effect Effects 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 229940007062 eucalyptus extract Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 235000021121 fermented vegetables Nutrition 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 235000010855 food raising agent Nutrition 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- FTSSQIKWUOOEGC-RULYVFMPSA-N fructooligosaccharide Chemical compound OC[C@H]1O[C@@](CO)(OC[C@@]2(OC[C@@]3(OC[C@@]4(OC[C@@]5(OC[C@@]6(OC[C@@]7(OC[C@@]8(OC[C@@]9(OC[C@@]%10(OC[C@@]%11(O[C@H]%12O[C@H](CO)[C@@H](O)[C@H](O)[C@H]%12O)O[C@H](CO)[C@@H](O)[C@@H]%11O)O[C@H](CO)[C@@H](O)[C@@H]%10O)O[C@H](CO)[C@@H](O)[C@@H]9O)O[C@H](CO)[C@@H](O)[C@@H]8O)O[C@H](CO)[C@@H](O)[C@@H]7O)O[C@H](CO)[C@@H](O)[C@@H]6O)O[C@H](CO)[C@@H](O)[C@@H]5O)O[C@H](CO)[C@@H](O)[C@@H]4O)O[C@H](CO)[C@@H](O)[C@@H]3O)O[C@H](CO)[C@@H](O)[C@@H]2O)[C@@H](O)[C@@H]1O FTSSQIKWUOOEGC-RULYVFMPSA-N 0.000 description 1
- 229940107187 fructooligosaccharide Drugs 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 229940002508 ginger extract Drugs 0.000 description 1
- 235000020708 ginger extract Nutrition 0.000 description 1
- 235000008434 ginseng Nutrition 0.000 description 1
- 235000020710 ginseng extract Nutrition 0.000 description 1
- 229950002441 glucurolactone Drugs 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 235000019674 grape juice Nutrition 0.000 description 1
- 235000009569 green tea Nutrition 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229920000588 gutta-percha Polymers 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 208000006575 hypertriglyceridemia Diseases 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008274 jelly Substances 0.000 description 1
- 229940017800 lactobacillus casei Drugs 0.000 description 1
- 229940012969 lactobacillus fermentum Drugs 0.000 description 1
- 229940001882 lactobacillus reuteri Drugs 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 235000021056 liquid food Nutrition 0.000 description 1
- 239000006402 liver broth Substances 0.000 description 1
- 229940083747 low-ceiling diuretics xanthine derivative Drugs 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 235000013310 margarine Nutrition 0.000 description 1
- 239000003264 margarine Substances 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 239000008268 mayonnaise Substances 0.000 description 1
- 235000010746 mayonnaise Nutrition 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 230000006371 metabolic abnormality Effects 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 235000013379 molasses Nutrition 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 230000003505 mutagenic effect Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 235000012149 noodles Nutrition 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 235000014593 oils and fats Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 235000020333 oolong tea Nutrition 0.000 description 1
- 125000001477 organic nitrogen group Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 235000015927 pasta Nutrition 0.000 description 1
- 238000009304 pastoral farming Methods 0.000 description 1
- 235000020733 paullinia cupana extract Nutrition 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 235000013997 pineapple juice Nutrition 0.000 description 1
- 229960005095 pioglitazone Drugs 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- YLLIGHVCTUPGEH-UHFFFAOYSA-M potassium;ethanol;hydroxide Chemical compound [OH-].[K+].CCO YLLIGHVCTUPGEH-UHFFFAOYSA-M 0.000 description 1
- 235000013324 preserved food Nutrition 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 239000003531 protein hydrolysate Substances 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229940109850 royal jelly Drugs 0.000 description 1
- 235000005713 safflower oil Nutrition 0.000 description 1
- 239000003813 safflower oil Substances 0.000 description 1
- 235000019512 sardine Nutrition 0.000 description 1
- 235000015067 sauces Nutrition 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- JAOZKJMVYIWLKU-UHFFFAOYSA-N sodium 7-hydroxy-8-[(4-sulfonaphthalen-1-yl)diazenyl]naphthalene-1,3-disulfonic acid Chemical compound C1=CC=C2C(=C1)C(=CC=C2S(=O)(=O)O)N=NC3=C(C=CC4=CC(=CC(=C43)S(=O)(=O)O)S(=O)(=O)O)O.[Na+] JAOZKJMVYIWLKU-UHFFFAOYSA-N 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- NRHMKIHPTBHXPF-TUJRSCDTSA-M sodium cholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 NRHMKIHPTBHXPF-TUJRSCDTSA-M 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 235000019830 sodium polyphosphate Nutrition 0.000 description 1
- 235000014214 soft drink Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000011496 sports drink Nutrition 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000012414 sterilization procedure Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003760 tallow Substances 0.000 description 1
- 229960003080 taurine Drugs 0.000 description 1
- 229940026510 theanine Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- DZLNHFMRPBPULJ-UHFFFAOYSA-N thioproline Chemical class OC(=O)C1CSCN1 DZLNHFMRPBPULJ-UHFFFAOYSA-N 0.000 description 1
- 235000015193 tomato juice Nutrition 0.000 description 1
- 108091008023 transcriptional regulators Proteins 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000009777 vacuum freeze-drying Methods 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 239000006200 vaporizer Substances 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 235000015192 vegetable juice Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 229940046001 vitamin b complex Drugs 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 235000021119 whey protein Nutrition 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
Images
Classifications
-
- 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
-
- A23L1/3014—
-
- 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
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
- A23L2/52—Adding ingredients
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/745—Bifidobacteria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
- C12N1/205—Bacterial isolates
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2400/00—Lactic or propionic acid bacteria
- A23V2400/11—Lactobacillus
- A23V2400/115—Amylovorus
-
- 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
- A23V2400/145—Gasseri
-
- 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
Definitions
- the present invention relates to a lipid metabolism and/or sugar metabolism improver comprising a bacterial cell of the genus Lactobacillus or the genus Bifidobacterium or a treated product thereof having a high ability to activate Peroxisome Proliferator Activated Receptors (PPARs) ⁇ and ⁇ , which are deeply involved with metabolic syndrome.
- the present invention also relates to a functional food or a pharmaceutical composition comprising such a lipid metabolism and/or sugar metabolism improver for treating or preventing diseases or disorders associated with the lipid metabolism and sugar metabolism.
- Metabolic syndrome is defined as multiplex conditions of visceral fat type obesity in combination with hyperlipidemia, hyperglycemia, hypertension, and the like, and has a high risk of developing arteriosclerotic diseases.
- PPARs associated with the lipid and sugar metabolisms are attracting attentions.
- PPARs are nuclear transcriptional regulators.
- PPAR ⁇ that is highly expressed mostly in the liver and small intestine causes fat burning by promoting the ⁇ oxidation of fatty acids and also exhibits the action of promoting HDL cholesterol production.
- PPAR ⁇ highly expressed mostly in fat tissues, improves the insulin resistance by regulating the fat cell differentiation in the fatty tissues, suppressing the secretion of an inflammation factor TNF- ⁇ from fat cells, and promoting the secretion of adiponectin.
- a fibrate preparation which is a PPAR ⁇ ligand agent and a thiazolidin derivative which is a PPAR ⁇ ligand agent are known as pharmaceutical products for activating PPARs, but adverse effects thereof are concerned when taken for an extended period of time.
- Patent Documents 1 to 4 it is documented that bacterial cells of lactic acid bacteria or Bifidobacteria and cultured products thereof (culture broth, culture supernatant, concentrated products thereof, and the like) are effective for improving the lipid metabolism, for example, reducing blood cholesterol, reducing body fat or visceral fat, or the like.
- Patent Documents 1 to 4 they did not activate PPARs or did not have satisfactory effects.
- Patent Document 5 an organic solvent extract of a lactic acid bacterium activates PPAR (Patent Document 5) but this was only to show the activity of PPAR ⁇ , and the effect thereof was not sufficient, either.
- Non Patent Document 1 the activity of liver PPAR ⁇ in a model mouse with alcoholic liver disease was examined when Lactobacillus brevis SBC8803 strain was administered to the mouse, and, as a result, the activation remained unchanged (Non Patent Document 1), and it is documented when a mixture of a plurality of lactic acid bacteria was administered to a steatohepatitis model which was on a high fat diet, the PPAR ⁇ activity whose expression had been reduced due to the high fat diet was recovered (Non Patent Document 2), but no descriptions regarding PPAR ⁇ are found.
- a material capable of activating both PPAR ⁇ and PPAR ⁇ is desired.
- An object of the present invention is to provide a means which has a highly agonistic activation of both PPAR ⁇ and PPAR ⁇ and is effective and safe for improving both lipid metabolism and/or sugar metabolism.
- Another object of the present invention is to provide a means for treating or preventing diseases or disorders associated with lipid metabolism disorders and/or sugar metabolism disorders.
- the present inventors carried out extensive studies to solve the above problems and have now accidentally found that a plurality of lactic acid bacteria strains or Bifidobacteria strains, which strongly activate both PPAR ⁇ and PPAR ⁇ .
- Lactobacillus amylovorus CP1563 strain has now been found as the highly active strains.
- the present invention encompasses the following embodiments.
- PPAR peroxisome proliferator activated receptor
- PPAR peroxisome proliferator activated receptor
- bacterial cell or the treated product thereof according to any one of the above (1) to (3), wherein the bacterial cell is the CP1563 strain (Accession Number FERM BP-11255) or CP1562 strain (Accession Number FERM BP-11379) or a mutant or bred strain thereof, or a mutant or bred strain of CP2305 strain (Accession Number FERM BP-11331).
- a lipid metabolism and/or sugar metabolism improver comprising, as an active ingredient, a bacterial cell, a treated product thereof, or a mixture thereof having dual-agonistic activities on a peroxisome proliferator activated receptor (PPAR) ⁇ and a peroxisome proliferator activated receptor (PPAR) ⁇ , wherein the bacterial cell is preferably selected from the genus Lactobacillus and the genus Bifidobacterium.
- PPAR peroxisome proliferator activated receptor
- PPAR peroxisome proliferator activated receptor
- a lipid metabolism and/or sugar metabolism improver comprising, as an active ingredient, a bacterial cell selected from bacteria belonging to the genus Lactobacillus and the genus Bifidobacterium , a treated product thereof, or a mixture thereof having dual-agonistic activities on a peroxisome proliferator activated receptor (PPAR) ⁇ and a peroxisome proliferator activated receptor (PPAR) ⁇ .
- a peroxisome proliferator activated receptor PPAR
- PPAR peroxisome proliferator activated receptor
- the bacterial cell is Lactobacillus amylovorus CP1563 strain (Accession Number FERM BP-11255) or Lactobacillus amylovorus CP1562 strain (Accession Number FERM BP-11379) or Lactobacillus gasseri CP2305 strain (Accession Number FERM BP-11331), or a mutant or bred strain thereof.
- the lipid metabolism and/or sugar metabolism improver according to any one of the above (6) to (11), which further comprises a carrier or an excipient used for foods or beverages or pharmaceutical drugs.
- a food or beverage comprising the lipid metabolism and/or sugar metabolism improver according to any one of the above (6) to (12) as a food additive.
- a pharmaceutical composition for use in preventing, improving, or treating a lipid metabolism disorder and/or sugar metabolism disorder comprising as an active ingredient the lipid metabolism and/or sugar metabolism improver according to any one of the above (6) to (12).
- a process for producing a food or beverage having a lipid metabolism and/or sugar metabolism improving effect comprising adding the lipid metabolism and/or sugar metabolism improver according to any one of the above (6) to (12) to a food or beverage.
- Lactobacillus amylovorus CP1563 strain (Accession Number FERM BP-11255), Lactobacillus amylovorus CP1562 strain (Accession Number FERM BP-11379), Lactobacillus gasseri CP2305 strain (Accession Number FERM BP-11331), or a mutant or bred strain thereof, a treated product thereof, or a mixture thereof in the production of the lipid metabolism and/or sugar metabolism improver according to any one of the above (6) to (12).
- Lactobacillus amylovorus CP1563 strain (Accession Number FERM BP-11255) or Lactobacillus amylovorus CP1562 strain (Accession Number FERM BP-11379), or a mutant or bred strain thereof, or a mutant or bred strain of Lactobacillus gasseri CP2305 strain (Accession Number FERM BP-11331) for use in imparting a lipid metabolism and sugar metabolism improving effect.
- Lactobacillus amylovorus CP1563 strain (Accession Number FERM BP-11255) or Lactobacillus amylovorus CP1562 strain (Accession Number FERM BP-11379) or a mutant or bred strain thereof, or a mutant or bred strain of Lactobacillus gasseri CP2305 strain (Accession Number FERM BP-11331).
- the present invention encompasses the contents described in the specifications and/or drawings of Japanese Patent Application Nos. 2011-268313 and 2012-067187, to which the present application claims priority.
- bacterial cells such as Lactobacillus amylovorus, Lactobacillus gasseri , or the like, comprising Lactobacillus amylovorus CP1563 strain, Lactobacillus amylovorus CP1562 strain, Lactobacillus gasseri CP2305 strain, and the like, or a treated product thereof, which have dual-agonist activities to both PPAR ⁇ and PPAR ⁇ , are taken, fat burning and HDL cholesterol production are promoted and the lipid metabolism is improved by strong activation of PPAR ⁇ , and further the sugar metabolism and the insulin resistance are improved by activation of PPAR ⁇ , whereby the metabolic syndrome can be prevented or improved.
- bacterial cells such as Lactobacillus amylovorus, Lactobacillus gasseri , or the like, comprising Lactobacillus amylovorus CP1563 strain, Lactobacillus amylovorus CP1562 strain, Lactobacillus gasseri CP2305 strain, and the like
- FIG. 1 is a graph showing a dose dependent effect (on HDL-cholesterol) of a lactic acid bacterium in diet induced obese model. * and ** show the statistical significance.
- FIG. 2 is a graph showing a dose dependent effect (on arteriosclerotic index) of a lactic acid bacterium in diet induced obese model. ** shows the statistical significance.
- FIG. 3 is a graph showing an antimetabolic syndrome effect of a lactic acid bacterium in diet induced obese model.
- A is for HDL-cholesterol
- B is for LDL-cholesterol
- C is for triglyceride
- D is for arteriosclerotic index
- E is for high molecular adiponectin
- F is for visceral fat weight, respectively.
- *, **, *** and + show the statistical significance.
- FIG. 4 is a graph showing the fat metabolism improving effect when the disrupted cells of Lactobacillus amylovorus CP1563 strain were administered to healthy human volunteers.
- the comparative control did not contain the disrupted cells of CP1563 strain.
- the influences to or effects on A: body weight, B: body fat ratio, C: BMI, D: body temperature, E: subcutaneous fat, and F: visceral fat, respectively, are shown.
- the present invention provides a fat metabolism and/or sugar metabolism improver comprising, as an active ingredient, preferably a bacterial cell of a lactic acid producing bacterium, more preferably a bacterial cell selected from the genus Lactobacillus and the genus Bifidobacterium , a treated product thereof, or a mixture thereof having dual-agonist activities to peroxisome proliferator activated receptor (PPAR) ⁇ and peroxisome proliferator activated receptor (PPAR) ⁇ .
- PPAR peroxisome proliferator activated receptor
- PPAR peroxisome proliferator activated receptor
- the present invention also provides the above-mentioned bacterial cell or treated product thereof as described below.
- the “PPAR ⁇ agonist activity” used herein promotes the fat burning and the HDL cholesterol production and improves the fat metabolism.
- diseases such as hyperlipidemia, dyslipidemia, obesity, hypercholesterolemia, hypertriglyceridemia, arteriosclerosis, inflammatory symptoms, and the like, can be prevented, improved or treated.
- the “PPAR ⁇ agonist activity” used herein suppresses the secretion of the inflammation factor TNF- ⁇ from fat tissues and promotes the secretion of adiponectin, thereby improving both of the insulin resistance and the sugar metabolism.
- diseases such as hyperglycemia, non-insulin-dependent diabetes mellitus, arteriosclerosis, cardiac hypertrophy, ischemic heart disease, or the like, can be prevented, improved or treated.
- the fat metabolism and/or sugar metabolism improver of the present invention is also effective for preventing, improving or treating so-called the metabolic syndrome including obesity and diabetes by having both PPAR ⁇ agonist activity and PPAR ⁇ agonist activity.
- the PPAR ⁇ agonist activity in the lipid metabolism and/or sugar metabolism improver of the present invention is a positive activity of typically 70 or more, preferably 80 or more, further preferably 90 or more, most preferably 100 or more, for example, 110 or more, 120 or more, 130 or more, or 140 or more, relative to negative control activity of 0 and positive control activity of 100 as measured by PPAR ⁇ reporter assay (see Examples later).
- the negative control activity of 0 and positive control activity of 100 as measured by PPAR ⁇ reporter assay used herein is defined in Definition 1 to be described later.
- the PPAR ⁇ agonist activity in the lipid metabolism and/or sugar metabolism improver of the present invention is a positive activity of exceeding 0, for example, 2 or more, 4 or more, 5 or more, preferably 10 or more, 20 or more, further preferably 30 or more, 35 or more, most preferably 40 or more, relative to negative control activity of 0 and positive control activity of 100 as measured by PPAR ⁇ reporter assay (see Examples later).
- the negative control activity of 0 and positive control activity of 100 as measured by PPAR ⁇ reporter assay used in the present invention is defined in Definition 2 to be described later.
- the bacterial cell having the dual-agonistic activities to PPAR ⁇ and PPAR ⁇ is a bacterial cell selected from bacteria belonging to the genus Lactobacillus and the genus Bifidobacterium , a treated product thereof, or a mixture thereof.
- Such a bacterial cell includes, but is not limited to, Lactobacillus amylovorus, Lactobacillus gasseri, Bifidobacterium infantis, Bifidobacterium adolescentis, Bifidobacterium breve, Bifidobacterium bifidum, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium lactis, Bifidobacterium animalis, Bifidobacterium pseudolongum, Bifidobacterium magnum, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus paracasei, Lactobacillus rhamnosus, Lactobacillus helveticus, Lactobacillus fermentum, Lactobacillus brevis, Lactobacillus plantarum, Lactobacillus salivarius, Lactobacillus reuteri, Lactobacillus johnsonii
- Preferable cell strains are Lactobacillus amylovorus strains (e.g., CP1563 strain; Accession Number FERM BP-11255, CP1562 strain; Accession Number FERM BP-11379), Lactobacillus gasseri strains (e.g., CP2305 strain; Accession Number FERM BP-11331), Bifidobacterium infantis strains, Bifidobacterium breve strains, or mutants or bred strains thereof, and most preferable strains are CP1563 strain (Accession Number FERM BP-11255) or mutants or bred strains thereof.
- CP1563 strain accesion Number FERM BP-11255
- Lactobacillus amylovorus CP1563 strain and Lactobacillus amylovorus CP1562 strain are lactic acid bacteria derived from the human intestinal tract. These bacterial strains or treated products thereof are validated to have the fat metabolism and/or sugar metabolism improving action in Examples later, and available from the National Institute of Advanced Industrial Science and Technology, International Patent Organism Depositary (1-1-1 Higashi, Tsukuba, Ibaraki, Tsukuba Central 6, 305-8566 Japan).
- the lactic acid producing bacteria usable in the present invention preferably bacterial species selected from the genus Lactobacillus and the genus Bifidobacterium , can be grown and recovered by incubating under typically employed conditions using media commonly used for incubating bacterial species such as Lactobacillus (a lactic acid bacterium) and Bifidobacterium.
- a culture medium typically contains a carbon source, a nitrogen source, inorganic salts, and the like, and may be a natural medium or synthetic medium as long as it can efficiently incubate the above bacterial species.
- the usable carbon source include lactose, glucose, sucrose, fructose, galactose, molasses, and the like
- examples of the usable nitrogen source include organic nitrogen-containing products such as casein hydrolysate, whey protein hydrolysate, soy protein hydrolysate, yeast extract, meat extract, and the like.
- the inorganic salts include phosphate, sodium, potassium, magnesium, manganese, iron, zinc, and the like.
- suitable media for culturing lactic acid bacteria include MRS liquid medium, GAM medium, BL medium, Briggs Liver Broth, animal milk, skim milk, milk whey, and the like.
- sterilized MRS medium can be used.
- a medium composed only of food materials and food additives can also be prepared and used.
- tomato juice, carrot juice, other vegetable juices, or apple juice, pineapple juice, grape juice, or the like can also be used.
- the incubation is carried out under anaerobic conditions at 20° C. to 50° C., preferably 25° C. to 42° C., more preferably about 37° C.
- the temperature condition can be adjusted using an incubator, mantle heater, jacket, or the like.
- the anaerobic condition refers to an environment of low oxygen at which the bacterium can grow, and the anaerobic condition can be achieved by, for example, using an anaerobic chamber, anaerobic box or a sealed container or bag containing an oxygen absorber, or simply sealing a culture container.
- the culture mode is stationary culture, shaking culture, tank culture, or the like.
- the incubation time is not limited but may be, for example, 3 hours to 96 hours.
- the medium pH at the time of initiating incubation is preferably maintained, for example, from 4.0 to 8.0.
- Lactobacillus amylovorus CP1563 strain and Lactobacillus amylovorus CP1562 strain are used as lactic acid bacteria, they may be inoculated in food grade media for lactic acid bacteria and incubated at about 37° C. overnight (for about 18 hours).
- the obtained cultured product of a lactic acid bacterium may be used without further treatment, or may be roughly purified as necessary by the centrifugal separation and/or the solid liquid separation or sterilization procedure by filtration, or the like, may be carried out.
- the lactic acid bacteria used in the present invention may be either wet bacterial cell or dry bacterial cell.
- these bacterial cells are stationarily cultured in MRS medium until the logarithmic growth phase, subsequently washed in sterilized physiological saline or sterilized water, and treated with 50 to 500 ⁇ g/ml of a mutagen such as N-methyl-N′-nitro-N-Nitrosoguanidine (NTG) at 30 to 37° C. for 30 to 60 minutes in the same sterilized physiological saline or sterilized water to obtain a mutant strain.
- a mutagen such as N-methyl-N′-nitro-N-Nitrosoguanidine (NTG)
- EMS ethylmethane sulfonate
- fluorouracil 5 -FU
- Taxonomically the microbiological characteristics of an obtained bacterial strain can be verified by, for example, examining the homology of a 16S rRNA gene nucleotide sequence, examining the DNA-DNA homology by DNA-DNA hybridization with the standard strain, examining the sugar utilizing properties, or the like.
- Examples of the treated product of a bacterial cell used herein include, but are not limited to, destructed products of a bacterial cell extracts of a bacterial cell, dried products, frozen products, water-dispersed products, emulsified products, or the like, thereof.
- the destructed products of a bacterial cell are those obtained by the destruction treatment such as disrupting (in this case a bacterial cell disrupted product is obtained), grinding, enzymatically treating, chemically treating, dissolving, or the like, and the form of the destructed product of a bacterial cell is not limited to a specific one as long as the bacterial cell has dual-agonistic activities to peroxisome proliferator activated receptor (PPAR) ⁇ and peroxisome proliferator activated receptor (PPAR) ⁇ .
- PPAR peroxisome proliferator activated receptor
- PPAR peroxisome proliferator activated receptor
- the destruction of bacterial cell can be carried out, using techniques and devices known in the art, by, for example, physical disruption, enzymatic dissolution treatment, or the like.
- the physical disruption may be carried out in either wet mode (processed in the form of bacterial cell suspension) or dry mode (processed in the form of bacterial cell powder), and can be carried out by stirring using a homogenizer, ball mill, bead mill, DYNO-mill, Planetary mill, or the like; by compressing using a jet mill, French press, cell disruptor, or the like; or by filtering using a filter.
- the cell wall of bacterial cell can be destructed using an enzyme such as lysozyme, or the like.
- the bacterial cell is disrupted by treating a suspension of a lactic acid bacterium 1 to 7 times (e.g., 3 to 5 times) in a known DYNO-MILL cell disruptor (DYNO-MILL disrupting device, or the like), using glass beads, at a circumferential speed of 10.0 to 20.0 m/s (e.g., about 14.0 m/s) and a processing flow rate of 0.1 to 10 L/10 min (e.g., about 1 L/10 min) at a disrupting tank temperature of 10 to 30° C. (e.g., about 15° C.).
- DYNO-MILL disrupting device DYNO-MILL disrupting device, or the like
- the bacterial cell is disrupted by, for example, treating a suspension of a lactic acid bacterium 1 to 30 times (e.g., 10 times) in a known wet jet mill cell disruptor (JN20 Nano Jet Pal, or the like) at a discharge pressure of 50 to 1000 MPa (e.g., 270 MPa) and a processing flow rate of 50 to 1000 (e.g., 300) ml/min.
- a suspension of a lactic acid bacterium 1 to 30 times e.g., 10 times
- JN20 Nano Jet Pal JN20 Nano Jet Pal, or the like
- the bacterial cell can also be disrupted by treating lactic acid bacterium cell powder in a known dry planetary mill cell disruptor (GOT5 Galaxy 5, or the like) in the presence of various balls (e.g., 10 mm zirconium ball, 5 mm zirconium ball, 1 mm aluminum ball) at a rotation number of 50 to 10,000 rpm (e.g., 240 rpm, 190 rpm, 110 rpm) for 30 minutes to 20 hours (e.g., 5 to 10 hours).
- various balls e.g., 10 mm zirconium ball, 5 mm zirconium ball, 1 mm aluminum ball
- the bacterial cell may also be disrupted by treating lactic acid bacterium cell powder 1 to 10 times (e.g., 1 time) in a known dry jet mill cell disruptor (Jet O-mizer, or the like) at a supplying rate of 0.01 to 10000 g/min (e.g., 0.5 g/min) and a discharge pressure of 1 to 1000 kg/cm 2 (e.g., 6 kg/cm 2 ).
- a dry jet mill cell disruptor Jet O-mizer, or the like
- the disrupted product of a bacterial cell still shows the effect even when the bacterial cell has just a hall, but it is desirable to prepare the disrupted product so that the average major axis of destructed bacterial cells is 90% or less of before the destruction treatment.
- the average major axis of destructed bacterial cells may sometimes be close to 0%.
- the bacterial cell can be destructed so that the average major axis of destructed bacterial cells in the disrupted product is 90% or less, preferably 80% or less, 70% or less, 60% or less, or 50% or less, more preferably 40% or less, 30% or less, or 20% or less, of before the disruption.
- the bacterial cell and/or the disrupted product thereof can be dried to form a powder product or a granulated product.
- Specific drying methods include, but are not particularly limited to, spray-drying, drum drying, vacuum drying, freeze-drying, and the like, and these methods may be employed alone or in combination. At this time, a commonly used carrier or excipient may be added where needed.
- the bacterial cell extract can be obtained by extraction treatment of the bacterial cell or the disrupted product thereof with water, an organic solvent or a mixed solvent, optionally in combination, and recovering a fraction containing the active ingredient having the agonistic activities to PPAR ⁇ and PPAR ⁇ .
- the organic solvent is a polar solvent, nonpolar solvent, or a mixed solvent thereof
- the polar solvent include alcohols such as methanol, ethanol, and propanol, acetone, acetonitrile, dioxane, DMSO, DMF, and the like
- examples of the nonpolar solvent include ethers such as diethyl ether, hydrocarbons such as hexane, heptane, and the like, alkyl halides such as dichloromethane, chloroform, and the like.
- the active ingredient of the present invention may have a property which is easily extracted by a nonpolar organic solvent such as diethyl ether, or the like, and may be partially extracted also by a polar organic solvent such as ethanol, acetonitrile, DMSO, or the like.
- a nonpolar organic solvent such as diethyl ether, or the like
- a polar organic solvent such as ethanol, acetonitrile, DMSO, or the like.
- the fact that the extract has the agonistic activities to PPAR ⁇ and PPAR ⁇ can be confirmed by known assay techniques such as PPAR ⁇ reporter assay, PPAR ⁇ reporter assay, and the like, as described in Examples later.
- the bacterial cell extract of the present invention also encompasses concentrated products or residues obtained by concentrating using a vaporizer such as an evaporator, or the like, preferably those obtained by removing the solvent.
- a component or a fraction having the lipid metabolism and sugar metabolism improving actions may be purified from the above disrupted product of the bacterial cell using a known separation and purification method.
- the separation and purification method include the method which utilizes solubility such as salt precipitation, organic solvent precipitation, and the like; the method which utilizes the molecular weight difference such as dialysis, ultrafiltration, gel filtration, and the like; the method which utilizes the electric charge difference such as ion exchange chromatography and the like; the method which utilizes the specific bonding such as affinity chromatography and the like; the method which utilizes the hydrophobicity such as hydrophobic chromatography, reversed phase chromatography, and the like; and these methods can be used alone or in combination of two or more methods.
- the thus obtained bacterial cell disrupted product, bacterial cell extract, or active ingredient containing fraction can be prepared as the lipid metabolism and/or sugar metabolism improver without further treatment or in combination with a carrier or excipient used for foods or beverages or pharmaceutical drugs.
- additives such as a disintegrator, binder, wetting agent, stabilizer, buffer, lubricant, preservative, surfactant, sweetener, flavor, perfume, acidulant, coloring agent, or the like, may be contained.
- the dosage form is not limited and can be tablets, capsules, granules, powders, dusts, syrups, dry syrups, solutions, suspensions, emulsifiers, or the like.
- the above bacterial cell or treated products thereof contained in the lipid metabolism and/or sugar metabolism improver of the present invention are produced from the number of bacterial cells corresponding to, but not limited to, for example, about 10 5 cells/g to about 10 14 cells/g, preferably about 10 8 cells/g to about 10 12 cell/g as the number of bacterial cell before treatment.
- the lipid metabolism and/or sugar metabolism improver of the present invention comprises, as the active ingredient, the bacterial cell or the treated product thereof as described above, and the bacterial cell or the treated product thereof may be those obtained from one or a plurality of bacterial species.
- the present invention also provides, the use of CP1563 strain (Accession Number FERM BP-11255), CP1562 strain (Accession Number FERM BP-11379), CP2305 strain (Accession Number FERM BP-11331), or a mutant or bred strain thereof, a treated product thereof, or a mixture thereof, for use in the production of the lipid metabolism and/or sugar metabolism improver of the present invention.
- the present invention further provides CP1563 strain (Accession Number FERM BP-11255) or CP1562 strain (Accession Number FERM BP-11379), or a mutant or bred strain thereof, which imparts the lipid metabolism and sugar metabolism improving effects.
- FERM BP-11255 pertinent to the present invention is the accession number for Lactobacillus amylovorus CP1563 strain internationally deposited with the National Institute of Advanced Industrial Science and Technology, International Patent Organism Depositary (1-1-1 Higashi, Tsukuba, Ibaraki, Tsukuba Central 6 (305-8566 Japan)) on May 25, 2010 under the Budapest Treaty
- “FERM BP-11379” is the accession number for Lactobacillus amylovorus CP1562 strain internationally deposited with the same Organism Depositary on Apr. 22, 2011 under the Budapest Treaty
- “FERM BP-11331” is the accession number for Lactobacillus gasseri CP2305 strain internationally deposited with the same Organism Depositary on Sep. 11, 2007 under the Budapest Treaty.
- the present invention further provides a food or beverage which comprises the lipid metabolism and/or sugar metabolism improver of the present invention as a food additive.
- the food or beverage is a functional food or health food for use in improving the lipid metabolism and/or sugar metabolism.
- the present invention further provides a process for producing a food or beverage having the lipid metabolism and/or sugar metabolism improving effects, which process comprises adding the lipid metabolism and/or sugar metabolism improver of the present invention to a food or beverage.
- the present invention further provides a pharmaceutical composition for use in preventing, improving, or treating lipid metabolism disorders and sugar metabolism disorders, comprising the lipid metabolism and/or sugar metabolism improver of the present invention as the active ingredient.
- the lipid metabolism improver obtained as described above is continuously taken, the improving effects on lipid metabolism and sugar metabolism are expected to be achieved and hence the improver can be used for treating or preventing the diseases or disorders associated with the lipid metabolism and sugar metabolism.
- the lipid metabolism and/or sugar metabolism improver can be used by adding to foods and beverages, pharmaceutical products, or the like.
- the form of a pharmaceutical composition or a food or beverage is not limited and may be, for example, oral preparations such as tablets, capsules, granules, powders, dusts, syrups, dry syrups, solutions, suspensions, inhalants, or the like, enteral preparations such as suppositories or the like, preparation forms such as drops, injections, or the like. Of these, the oral preparations are preferable.
- the solution preparations such as solutions, suspensions, or the like, may be a preparation which is dissolved or suspended in water or other suitable medium immediately before taken, and the tablets and granules may have the surface coated by a well-known method.
- the lipid metabolism improver of the present invention may be formulated into a preparation with the controlled release such as sustained release preparations, delayed release preparations, immediate release preparations, or the like using a technique known in the art.
- Such a form can be produced in accordance with a routine method by adding, to the ingredients described above, additives commonly used such as an excipient, disintegrator, binder, wetting agent, stabilizer, buffer, lubricant, preservative, surfactant, sweetener, flavor, perfume, acidulant, coloring agent, or the like, depending on the preparation (or dosage) form.
- additives commonly used such as an excipient, disintegrator, binder, wetting agent, stabilizer, buffer, lubricant, preservative, surfactant, sweetener, flavor, perfume, acidulant, coloring agent, or the like, depending on the preparation (or dosage) form.
- pharmaceutically acceptable carriers or additives can be added.
- Examples of the pharmaceutically acceptable carriers and additives include water, pharmaceutically acceptable organic solvents, collagen, polyvinyl alcohols, polyvinylpyrrolidone, carboxy vinyl polymers, sodium alginate, water-soluble dextran, water-soluble dextrin, sodium carboxymethyl starch, pectin, xanthan gum, gum arabic, casein, gelatin, agar, glycerol, propylene glycol, polyethylene glycol, petrolatum, paraffin, stearyl alcohol, stearic acid, human serum albumin, mannitol, sorbitol, lactose, surfactants acceptable as pharmaceutical additives, as well as artificial cell structures such as liposome, and the like.
- the content of the lipid metabolism and/or sugar metabolism improver in the pharmaceutical composition or the food or beverage is not particularly limited as long as it imparts the improving effects of lipid metabolism and sugar metabolism, and is, depending on the preparation (or dosage) form, typically within the range of 0.0001 to 99% by mass, preferably 0.001 to 80% by mass, more preferably 0.001 to 75% by mass, in terms of the above bacterial cell or the treated product thereof, and it is desirable to prepare the improver into a form enabling control of a daily dose so that the suitable dose of active ingredient can be taken.
- the bacterial cell or treated products thereof contained in the lipid metabolism and/or sugar metabolism improver of the present invention are those produced from the number of bacterial cells corresponding to, but not limited to, for example, about 10 5 cells/g to about 10 12 cells/g, preferably about 10 8 cells/g to about 10 12 cell/g, as the number of bacterial cell before treatment.
- lipid metabolism improver and/or sugar metabolism improver can be added to or contained in the lipid metabolism and/or sugar metabolism improver of the present invention.
- the other lipid metabolism improver includes, but is not limited to, lipid depressants (e.g., statin drugs, fibrate drugs, eicosapentaenoic acid, docosahexaenoic acid, and the like), and vitamins (e.g., nicotinic acid, vitamin E, and the like).
- the other sugar metabolism improver includes, but is not limited to, pioglitazone and the like.
- the pharmaceutical composition or the food or beverage of the present invention may also contain various additives and other various substances used in the production thereof.
- a substance and additive include various oils and fats (e.g., vegetable oils such as soybean oil, corn oil, safflower oil, olive oil, and the like, animal fats and oils such as beef tallow, sardine oil, and the like), crude drugs (e.g., royal jelly, ginseng, and the like), amino acids (e.g., glutamine, cysteine, leucine, arginine, and the like), polyhydric alcohols (e.g., ethylene glycol, polyethylene glycol, propylene glycol, glycerol, and sugar alcohols including sorbitol, erythritol, xylitol, maltitol, mannitol, and the like), natural polymers (e.g., gum arabic, agar, water-soluble corn fiber, gelatin, xanthan gum, casein, gluten or
- the lipid metabolism and/or sugar metabolism improver of the present invention may contain, as functional ingredients or additives other than the above active ingredients, for example, taurine, glutathione, carnitine, creatine, coenzyme Q, glucuronic acid, glucuronolactone, capsicium extract, ginger extract, cacao extract, guarana extract, garcinia extracts, theanine, ⁇ -aminobutyric acid, capsaicin, capsiate, various organic acids, flavonoids, polyfenols, catechins, xanthine derivatives, non-digestible oligosaccharides such as fructooligosaccharide, and the like, polyvinylpyrrolidone, and the like.
- functional ingredients or additives other than the above active ingredients, for example, taurine, glutathione, carnitine, creatine, coenzyme Q, glucuronic acid, glucuronolactone, capsicium extract, ginger extract, cacao extract, guaran
- the subjects (or patients) who are administered with or ingests the lipid metabolism improver and the pharmaceutical composition or food or beverage comprising the improver of the present invention are vertebrates, in particular, mammals such as human, primates (e.g., monkey, chimpanzee, and the like), livestock animals (e.g., cow, horse, pig, sheep, and the like), companion animals (e.g., dog, cat, and the like), experimental animals (e.g., mouse, rat, and the like), and further reptiles and birds, preferably human.
- mammals such as human, primates (e.g., monkey, chimpanzee, and the like), livestock animals (e.g., cow, horse, pig, sheep, and the like), companion animals (e.g., dog, cat, and the like), experimental animals (e.g., mouse, rat, and the like), and further reptiles and birds, preferably human.
- the dose or intake amount of the lipid metabolism and/or sugar metabolism improver of the present invention varies depending on the subject's age and body weight, administration or intake route, dose or intake frequency, severity of the lipid metabolism disorder or the like, and can be changed in a wide range by the discretion of a person skilled in the art to achieve the intended actions.
- the bacterial cell or the treated product thereof contained in the lipid metabolism and/or sugar metabolism improver is desirably administered in an amount of typically about 10 6 cells to about 10 12 cells, preferably about 10 7 cells to about 10 11 cells, per kg of body weight when represented by the bacterial cell amount before treatment.
- the lipid metabolism and/or sugar metabolism improver, the pharmaceutical composition, and the food or beverage of the present invention are very safe and the intake amount can be increased.
- the daily intake amount may be taken once, or in several divided times.
- the frequency of administration or intake is not particularly limited and can suitably be selected in accordance with various conditions such as administration or intake route, subject's age and body weight, the severity of lipid metabolism disorder or sugar metabolism disorder, the presence of disease or disorder onset caused by the lipid metabolism disorder or sugar metabolism disorder, intended effects (treatment, prevention, or the like), and the like.
- the administration or intake route of the lipid metabolism and/or sugar metabolism improver, the pharmaceutical composition, and the food or beverage of the present invention includes, but is not particularly limited to, oral administration or intake, or parenteral administration (e.g., intrarectal, subcutaneous, intramuscular, and intravenous administrations), and the like, preferably oral administration or intake.
- oral administration or intake or parenteral administration (e.g., intrarectal, subcutaneous, intramuscular, and intravenous administrations), and the like, preferably oral administration or intake.
- the lipid metabolism and/or sugar metabolism improver, the pharmaceutical composition, and the food or beverage of the present invention have the actions of reducing a subject's lipid in blood, promoting the metabolisms of subcutaneous fat and/or visceral fat, and suppressing the body weight gain, as the lipid metabolism improver.
- the lipid metabolism improver, the pharmaceutical composition, and the food or beverage of the present invention have the effects of normalizing the lipid metabolism by reducing a subject's total cholesterol, LDL-cholesterol, triglyceride, arteriosclerotic index and/or visceral fat, and/or elevating HDL-cholesterol and/or adiponectin.
- the lipid metabolism and/or sugar metabolism improver, the pharmaceutical composition, and the food or beverage of the present invention have the actions of preventing, improving, or treating diseases such as hyperglycemia, noninsulin dependent diabetes mellitus, or the like by improving the insulin resistance, as the sugar metabolism improver.
- the lipid metabolism and/or sugar metabolism improver, the pharmaceutical composition, and the food or beverage of the present invention show good preventive, improving and therapeutic effects on the diseases or disorders associated with the lipid metabolism and sugar metabolism. In addition, they are very safe and easily taken continuously for an extended period of time.
- the term “diseases or disorders associated with the lipid metabolism” refers to diseases, disorders, symptoms or syndromes caused by the lipid metabolism abnormality.
- diseases or disorders associated with the lipid metabolism include, but are not limited to, arteriosclerosis, hyperlipidemia, steatohepatitis, obesity, metabolic syndrome, circulatory system diseases (e.g., myocardial infarction, cerebral infarction, and the like).
- diabetes mellitus such as dyslipidemia, hypertension, endodermal impairment, inflammatory atherosclerosis, and the like in addition to non-insulin-dependent diabetes mellitus and hyperglycemia.
- the food or beverage of the present invention contains the lipid metabolism and/or sugar metabolism improver as described above.
- the food or beverage encompasses beverages.
- the food or beverage comprising the lipid metabolism and/or sugar metabolism improver of the present invention encompasses all foods or beverages to which the above lipid metabolism and/or sugar metabolism improver can be added, in addition to the health foods or beverages, functional foods or beverages, foods or beverages for specified health use, and the like, which enhance health by the lipid metabolism improving action and sugar metabolism improving action.
- the “functional food or beverage” of the present invention means a food or beverage having a certain function on the living body, and encompasses the so-called health foods or beverages in general such as foods and beverages with health claims including foods and beverages for specified health use (including qualified “foods for specified health use”) and foods and beverages with nutrient function claims, foods or beverages for special dietary uses, nutrition supplement foods or beverages, health supplement foods or beverages, supplements (e.g., those in various forms such as tablets, coated tablets, sugar coated tablets, capsules, solutions, or the like), food or beverage for beauty (e.g., diet food or beverage, and the like), and the like.
- the functional food or beverage of the present invention also encompasses the health foods or beverages to which the health claim based on the food standard by the Codex (the Joint FAO/WHO Food Standards Commission) is applicable.
- foods or beverages include liquid foods such as intertubular enteral nutrients and the like; health foods or beverages and nutrition supplement foods or beverages in the form of preparation forms such as tablet candies, tablets, chewable tablets, dusts, powders, capsules, granules, drinks, and the like; tea drinks such as green teas, oolong tea, English teas, and the like; drinks such as soft drinks, jelly beverages, sports drinks, milk beverages, carbonated drinks, vegetable drinks, fruit juice drinks, fermented vegetable drinks, fermented fruit juice drinks, fermented milk beverages (yogurts and the like), lactic acid bacterial beverages, milk-based drinks (coffee-flavored milk, fruit-flavored milk, and the like), powder drinks, cocoa drinks, milk as well as purified water, and the like: spreads such as butter, jams, Furikake (dried food sprinkles), margarine, and the like; mayonnaise, shortening, custard cream, dressings, breads, rice, noodles, pastas, misosoup, soybean curd, yogurt
- the food or beverage of the present invention can contain other food materials used in the production of the food or beverage, various nutrients, various vitamins, minerals, dietary fibers, various additives (e.g., taste components, sweeteners, acidulants such as organic acids, stabilizers, flavors) or the like, in addition to the above lipid metabolism and/or sugar metabolism improver, and can be produced in accordance with a routine method.
- various additives e.g., taste components, sweeteners, acidulants such as organic acids, stabilizers, flavors
- the addition amount of lipid metabolism and/or sugar metabolism improver can suitably be determined by those skilled in the art in consideration with the preparation form and required flavors or textures of the food or beverage.
- the addition amount of the lipid metabolism and/or sugar metabolism improver is suitable when the total amount of the bacterial cell or the treated product thereof to be added to the lipid metabolism and/or sugar metabolism improver is typically 0.0001 to 99% by mass, preferably 0.001 to 80% by mass, more preferably 0.001 to 75% by mass, when represented by the bacterial cell amount before treatment.
- the lipid metabolism and/or sugar metabolism improver of the present invention is very safe and hence the addition amount to the food or beverage can further be increased.
- the improver into a form enabling control of a daily dose so that the desirable intake amount of the lipid metabolism and/or sugar metabolism improver can be consumed.
- a prevention method and improving method for the diseases or disorders associated with the lipid metabolism and/or sugar metabolism using the food or beverage of the present invention are provided, when the food or beverage of the present invention is consumed in the form which enables control of the desirable intake amount of the lipid metabolism and/or sugar metabolism improver of the present invention.
- the lipid metabolism and/or sugar metabolism improver of the present invention may be contained in foods or beverages by any suitable method available to those skilled in the art.
- the lipid metabolism and/or sugar metabolism improver of the present invention is formulated into a liquid, gel, solid, powder or granular preparation, and subsequently added to a food or beverage.
- the lipid metabolism and/or sugar metabolism improver of the present invention may be directly mixed with or dissolved in raw materials of the food or beverage.
- the lipid metabolism and/or sugar metabolism improver of the present invention may be coated on, covered over, infiltrated into, or sprayed onto a food or beverage.
- the lipid metabolism and/or sugar metabolism improver of the present invention may be homogeneously dispersed or unevenly distributed in a food or beverage.
- a capsule comprising the lipid metabolism and/or sugar metabolism improver of the present invention may be prepared.
- the lipid metabolism and/or sugar metabolism improver of the present invention may be enveloped with an edible film, edible coating agent, or the like. Further, the lipid metabolism and/or sugar metabolism improver of the present invention may be molded to the shape of tablets or the like after adding a suitable excipient or the like.
- the food or beverage comprising the lipid metabolism and/or sugar metabolism improver of the present invention may further be processed, and such a processed product is also encompassed in the scope of the present invention.
- additives routinely used in foods and beverages may be used in the production of the food or beverage of the present invention.
- the additives include, but are not limited to, color formers (sodium nitrite and the like), coloring agents (gardenia pigment, red 102 , and the like), perfumes (orange perfume and the like), sweeteners (stevia, aspartame, and the like), preservatives (sodium acetate, sorbic acid, and the like), emulsifiers (sodium chondroitin sulfate, propylene glycol fatty acid esters, and the like), antioxidants (disodium EDTA, vitamin C, and the like), pH adjusting agents (citric acid and the like), synthetic seasonings (sodium inosinate and the like), thickeners (xanthan gum and the like), raising agents (calcium carbonate and the like), defoaming agents (calcium phosphate), and the like, binders (sodium polyphosphate and the like), nutri
- the food or beverage of the present invention has the lipid metabolism and sugar metabolism improving actions, and thus has good preventing and improving actions on the diseases or disorders associated with the lipid metabolism and sugar metabolism and is very safe without concerns of adverse effects. Further, the lipid metabolism and/or sugar metabolism improver of the present invention has good flavor and does not affect flavors of any foods or drinks when added to various foods or drinks, and thr this reason the obtained food or beverage can be easily taken continuously for an extended period of time and expected to have good preventing and improving effects on the diseases or disorders associated with the lipid metabolism.
- lipid metabolism and/or sugar metabolism improver of the present invention can be added not only to foods or drinks for human consumption but also to feeds for livestock, racehorses, companion animals, and the like.
- feeds for livestock, racehorses, companion animals, and the like are equally applicable to the feed, since the feed is substantially the same as the food or beverage except that it is for other than human consumption.
- the cell strain of each lactic acid bacterium was inoculated from frozen stocks onto plate medium, and then the pre-preincubation, preincubation and main incubation were carried out (5 ml ⁇ 40 ml ⁇ 2 L) using liquid medium.
- Table 1 shows the bacterial species, bacterial strains, medium and incubation temperatures used. Additionally, the inoculum concentration was 1% of each liquid medium weight and the incubation was carried out for 18 hours (see Table 2 for the medium used and incubation temperatures).
- the culture was centrifuged at 12000 g at 10° C. for 7 minutes, and the supernatant was removed. Ion exchange water was added, the culture was centrifuged in the same manner, and the freeze-dried bacterial cell was dispersed using a mill (TESCOM), thereby obtaining a bacterial cell powder.
- TESCOM freeze-dried bacterial cell powder
- Two g of the bacterial cell powder was suspended in 500 ml of a 0.5 mol/l potassium hydroxide-ethanol solution (KANTO KAGAKU) and then disrupted ultrasonically for 2 minutes (power output 40%, max 750 W, probe-type, VC-750 (TOKYO RIKAKIKAI CO., LTD.)).
- the treated solution was transferred to a 500 ml wide mouthed medium bottle with a red cap (heat resistance, SANSYO), which was then hermetically closed.
- the bottle was heated in boiling water at 100° C. for 1 hour in the stationary state, and then cooled in running water.
- Concentrated hydrochloric acid WAKO PURE CHEMICAL INDUSTRY, Ltd. was added to the cooled bacterial solution to adjust pH to be 2 or less.
- the liquid part was concentrated to about 50 ml in a water bath at 40° C. using a rotary evaporator (NVC-2100, TOKYO RIKAKIKAI CO., LTD.).
- the concentrated liquid was divided into two equal amounts, respectively placed in a 50 ml glass centrifuge tube (AGC Techno Glass, Co., Ltd.), diethyl ether (Wako Pure Chemical Industry, Ltd.) of the equal amount was added thereto and stirred for 1 hour using a shaker (200 rpm/min, R-30, TIETECH Co., Ltd.), thereby separating and collecting the upper layer.
- the same procedure was carried out 4 times in total, and the fraction separated and collected was dried to solidify using a rotary evaporator.
- the fraction was thoroughly dried to solidify by spraying nitrogen gas, then dissolved in 500 ⁇ L of a special grade DMSO (WAKO PURE CHEMICAL INDUSTRY, Ltd.) and preserved at ⁇ 80° C. in a brown vial (cold resistance, SANSYO).
- DMSO a special grade DMSO
- the fatty acid concentration in diethyl ether was measured using NEFA C-Test Wako (WAKO PURE CHEMICAL INDUSTRY, Ltd.).
- Cultured cell CV-1 derived from the kidney of an African green monkey was prepared to a concentration of 5 ⁇ 10 4 cells/ml, suspended in DMEM medium containing 10% (v/v) FBS (SIGMA), and cultured at 37° C. for 24 hours under 5% CO 2 in air (v/v) in a concentration of 500 ⁇ L/well using a flat 24-well plate (Corning). Twenty four hours later, 80 to 90% confluence was microscopically confirmed to have reached, and subsequently the transfection was carried out by the following procedure.
- Plasmid pM-PPAR ⁇ 0.16 which comprises a DNA fragment encoding a chimeric protein comprising PPAR ⁇ ligand binding domain (derived from human) and GAL-4DNA binding domain (derived from yeast), and p4xUASg-tk-luc 0.16 ⁇ g, which is a luc (derived from sea-firefly) reporter gene plasmid designed to receive expression control by the above chimeric protein, and pRL-CMV 0.016 ⁇ g, which is a luc (derived from Renilla) expression plasmid having a viral expression promoter with a fixed expression amount in cells, were added to 25 ⁇ l of the reduced serum medium Opti-MEM (Invitrogen) and mixed, to which 4 ⁇ l of PLUS Reagent (Invitrogen) was added and allowed to stand at room temperature for 15 minutes.
- Opti-MEM Invitrogen
- Lipofectamine Reagent (Invitrogen) 1 ⁇ l and Opti-MEM 25 ⁇ l were added thereto, allowed to stand at room temperature for 15 minutes, and subsequently Opti-MEM 200 ⁇ l was added thereto.
- the obtained solution 250 ⁇ l was added to the cultured CV-1 cell washed with Opti-MEM and incubated at 37° C. for 3 hours. After incubation, the medium was discarded and 1 ml of DMEM medium containing 10% (v/v) FBS was added.
- Evaluation samples were prepared as follows. The diethyl ether extract of each lactic acid bacterium was diluted with Opti-MEM so that the final concentration of DMSO is 0.1%. GW7647 (SIGMA) was used as the positive control and DMSO was used as the negative control of the PPAR ⁇ ligand. The concentration of the lactic acid bacterium extract sample was 2.5 ⁇ M (in terms of fatty acid), and the concentration of GW7647 was 10 nM, at the time of assay.
- the cryopreserved sample 30 ⁇ L was added to a 96-well white microplate (PerkinElmer), and the luminescence intensities (590 nm and 645 nm) were measured using Dual-GloTM Luciferase Assay System (Promega), whereby the PPAR ⁇ ligand ability was measured.
- the activity is shown in the relative value when the negative control is 0 and the positive control is 100.
- the PPAR ⁇ activity value is 70 or more, more preferably 80 or more, 90 or more, 95 or more, 100 or more, 120 or more, 140 or more.
- NCI9040 strain having the highest activity in Patent Document 5 Japanese Patent Publication (Kokai) No. 2007-284360 shows only about 67% activation ability compared with that of Lactobacillus amylovorus CP1563 strain.
- Cultured cell CV-1 derived from the kidney of an African green monkey was prepared to a concentration of 5 ⁇ 10 4 cells/ml, suspended in DMEM medium containing 10% (v/v) FRS (SIGMA), and cultured at 37° C. for 24 hours under 5% CO 2 in air (v/v) in a concentration of 500 ⁇ L/well using a flat 24-well plate (Corning). Twenty four hours later, 80 to 90% confluence was microscopically confirmed to have reached and subsequently the transfection was carried out by the following procedure.
- Plasmid pM-PPAR ⁇ 0.16 ⁇ g which comprises a DNA fragment encoding a chimeric protein comprising PPAR ⁇ ligand binding domain (derived from human) and GAL-4DNA binding domain (derived from yeast), and p4xUASg-tk-luc 0.16 ⁇ g, which is a luc (derived from sea-firefly) reporter gene plasmid designed to receive expression control by the above chimeric protein, and pRL-CMV 0.016 ⁇ g, which is a luc (derived from Renilla) expression plasmid having a viral expression promoter with a fixed expression amount in cells, were added to 25 ⁇ l of reduced serum media Opti-MEM (Invitrogen) and mixed, to which 4 ⁇ l of PLUS Reagent (Invitrogen) was added and allowed to stand at room temperature for 15 minutes.
- Opti-MEM Invitrogen
- PLUS Reagent Invitrogen
- Opti-MEM 200 ⁇ l was added thereto.
- the obtained solution 250 ⁇ l was added to the cultured CV-1 cell washed with Opti-MEM and incubated at 37° C. for 3 hours. After incubation, the medium was discarded and 1 ml of DMEM medium containing 10% (v/v) FBS was added.
- Samples to be evaluated were prepared as follows. Of the lactic acid bacteria strains listed in Table 1, diethyl ether extracts of Lactobacillus amylovorus CP1563 strain, Bifidobacterium infantis No. 23 strain, Bifidobacterium breve No. 22 strain, Lactobacillus gasseri CP2305 strain, Bifidobacterium adolescentis No. 20 strain, Bifidobacterium catenulatum No. 24 strain, Lactococcus lactis No. 14 strain and Bifidobacterium longum No. 21 strain, which were 8 bacterium strains having the comparatively high PPAR ⁇ activation ability, were diluted with Opti-MEM so that the final concentration of DMSO was 0.1%.
- Troglitazone (Wako Pure Chemical Industry, Ltd.) was used as the positive control and DMSO was used as the negative control of the PPAR ⁇ ligand.
- the concentration of lactic acid bacterium extract sample was 2.5 ⁇ M (in terms of fatty acid) and the concentration of Troglitazone was 1 nM, at the time of assay.
- the cryopreserved sample 30 ⁇ L was added to a 96-well white microplate (PerkinElmer), and the luminescence intensities (590 nm and 645 nm) were measured using Dual-GloTM Luciferase Assay System (Promega), whereby the PPAR ⁇ ligand ability was measured.
- the activity is shown in the relative value when the negative control is 0 and the positive control is 100.
- Lactoccus lactis No. 14 strain some bacterial strains with a comparatively high PPAR ⁇ activity do not have the PPAR ⁇ activity. Accordingly, the fact that some bacteria such as Lactobacillus amylovorus CP1563 strain according to the present invention activate both PPAR ⁇ and PPAR ⁇ is a remarkable finding.
- Lactobacillus amylovorus CP1563 strain was taken and isolated from human feces. The bacterial species was identified by the 16S rDNA nucleotide sequence analysis and phenotype observation.
- the lactic acid bacterium was incubated at 37° C. for 18 hours using self-prepared food grade lactic acid bacterium medium and collected by centrifugal separation. After washing with deionized water and collecting, the cells were suspended again in a suitable amount of water and sterilized at 90° C. The sterilized suspension was disrupted using a DYNO-MILL under the following conditions.
- DYNO-MILL disruptor Multi-lab 0.6L, SHINMARU ENTERPRISES CORPORATION
- Circumferential speed 14.0 m/s
- Disrupting tank temperature 15° C.
- the average major axis of destructed bacterial cells in the lactic acid bacterium suspension was reduced to 68% of before treatment (2.77 ⁇ 1.89 ⁇ m) by the above disruption (or destruction) treatment. After disruption, the suspension was freeze-dried, thereby obtaining a disrupted lactic acid bacterium freeze-dried powder.
- the ingredients were mixed in the amounts indicated in Table 4 to produce lactic acid bacterium containing high fat diets.
- mice C57BL/6 male mice (5 weeks of age) were fed with the high fat diet (control diet) prepared as above for 1 week before examination and used as obese model mice. Subsequently, the mice were fed with the Lactobacillus amylovorus CP1563 strain disrupted bacterial cell containing high fat diet (containing 0%, 0.25%, 0.5% or 1.0%, by weight) for 6 weeks. The mice were kept by the pair feeding method to adjust the food intake amount of each group to be equal. Blood samples were collected at the completion of experiment, and HDL cholesterol value was measured to investigate the effect of lactic acid bacteria. In addition, the arteriosclerotic index was determined by the following formula:
- Arteriosclerotic index (total cholesterol ⁇ HDL cholesterol) ⁇ HDL cholesterol
- FIG. 1 HDL-cholesterol
- FIG. 2 arteriosclerotic index
- the above obese model mice were fed with the Lactobacillus amylovorus CP1563 strain disrupted bacterial cell containing high fat diet (containing 0% or 1%, by weight) for 3 months. Then, the obese model mice were measured for HDL-cholesterol, LDL-cholesterol, triglyceride, arteriosclerotic index, high molecular adiponectin, and visceral fat weight.
- CP1563 strain was cultured at 37° C. for 18 hours using self-prepared food grade lactic acid bacterium medium and collected by the filter concentration.
- the concentrated liquid was sterilized at 90° C. and freeze-dried, thereby obtaining a lactic acid bacterium freeze-dried powder.
- the bacterial cell was disrupted using a planetary ball mill under the following conditions.
- Circumferential speed 14.0 m/s
- the CP1563 strain disrupted bacterial cell whose average major axis was reduced to 47% of before treatment (2.77 ⁇ 1.30 ⁇ m) was obtained by the above disruption (destruction) treatment.
- Diagnose and physical examination were carried out 0, 8 and 12 weeks later from the intake, and the fat measurement by a CT scan was carried out 0 and 12 weeks later from the intake.
- FIGS. 4 , A to F The results are shown in FIGS. 4 , A to F.
- the body weight and BMI were significantly reduced when compared with before the intake by the administration of CP1563 strain disrupted bacterial cell, and the body fat rate and BMI were significantly reduced compared with the control groups ( FIGS. 4B , 4 C).
- the body temperature was significantly reduced and suppressed when compared with the control groups ( FIG. 4D ).
- FIG. 4E the subcutaneous fat area was significantly reduced when compared with before initiating the intake by the administration of the CP1563 strain disrupted bacterial cell.
- the bacterial cells described herein can be used as the bacterial cell to produce the composition for improving the lipid metabolism and/or sugar metabolism. Further, it is confirmed that the bacterial cells described herein can be used as the bacterial cell to produce the composition for improving or preventing the lipid metabolism and/or sugar metabolism.
- the bacterial cells described herein can be used as the bacterial cell to produce the composition for reducing the subcutaneous fat and/or visceral fat, and can be used as the bacterial cell to produce the composition for preventing the subcutaneous accumulation of fat and/or visceral fat.
- Tanita body fat analyzer TBF-310 was used for the measurement.
- CT scanner system (CT-W450) of Hitachi Medical Corporation was used.
- the lipid metabolism and/or sugar metabolism improver of the present invention can improve the lipid metabolism and/or sugar metabolism on the human test, and is hence useful for preventing, improving or treating the diseases or disorders associated with such metabolism abnormalities.
- the present invention provides the lactic acid bacterium, Lactobacillus amylovorus CP1563 strain, which has not only high PPAR ⁇ activation ability but also high PPAR ⁇ activation ability.
- the lactic acid bacteria of the present invention promote the fat burning by the PPAR ⁇ activation and increase the expression of adiponectin, which is a beneficial factor secreted from the fat cells by the PPAR ⁇ activation, and thus they can be used for preventing or treating various diseases or disorders. Consequently, the present invention is useful in the fields of pharmaceutical products, food or beverages, livestock farming, and the like.
- FERM BP-11255 is the accession number for Lactobacillus amylovorus CP1563 strain internationally deposited with the National Institute of Advanced Industrial Science and Technology, International Patent Organism Depositary (1-1-1 Higashi, Tsukuba, Ibaraki, Tsukuba Central 6 (305-8566 Japan)) on May 25, 2010 under the Budapest Treaty,
- FERM BP-11379 is the accession number for Lactobacillus amylovorus CP1562 strain internationally deposited with the National Institute of Advanced Industrial Science and Technology, International Patent Organism Depositary (1-1-1 Higashi, Tsukuba, Ibaraki, Tsukuba Central 6 (305-8566 Japan)) on Apr. 22, 2011 under the Budapest Treaty, and
- FERM BP-11331 is the accession number for Lactobacillus gasseri CP2305 strain internationally deposited with the National Institute of Advanced Industrial Science and Technology, International Patent Organism Depositary (1-1-1 Higashi, Tsukuba, Ibaraki, Tsukuba Central 6 (305-8566 Japan)) on Sep. 11, 2007 under the Budapest Treaty.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Microbiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Mycology (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Diabetes (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Polymers & Plastics (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- Tropical Medicine & Parasitology (AREA)
- Virology (AREA)
- General Engineering & Computer Science (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Cardiology (AREA)
- Child & Adolescent Psychology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2011268313 | 2011-12-07 | ||
JP2011-268313 | 2011-12-07 | ||
JP2012-067187 | 2012-03-23 | ||
JP2012067187 | 2012-03-23 | ||
PCT/JP2012/081597 WO2013084971A1 (fr) | 2011-12-07 | 2012-12-06 | Stimulant du metabolisme des lipides et/ou du metabolisme du sucre contenant une bacterie d'acide lactique ou produit de traitement associe |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2012/081597 A-371-Of-International WO2013084971A1 (fr) | 2011-12-07 | 2012-12-06 | Stimulant du metabolisme des lipides et/ou du metabolisme du sucre contenant une bacterie d'acide lactique ou produit de traitement associe |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US15/408,722 Division US10245291B2 (en) | 2011-12-07 | 2017-01-18 | Lipid metabolism and/or sugar metabolism improver containing lactic acid bacterium or treatment product thereof |
Publications (1)
Publication Number | Publication Date |
---|---|
US20140322172A1 true US20140322172A1 (en) | 2014-10-30 |
Family
ID=48574329
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US14/363,150 Abandoned US20140322172A1 (en) | 2011-12-07 | 2012-12-06 | Lipid metabolism and/or sugar metabolism improver containing lactic acid bacterium or treatment product thereof |
US15/408,722 Active US10245291B2 (en) | 2011-12-07 | 2017-01-18 | Lipid metabolism and/or sugar metabolism improver containing lactic acid bacterium or treatment product thereof |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US15/408,722 Active US10245291B2 (en) | 2011-12-07 | 2017-01-18 | Lipid metabolism and/or sugar metabolism improver containing lactic acid bacterium or treatment product thereof |
Country Status (11)
Country | Link |
---|---|
US (2) | US20140322172A1 (fr) |
EP (1) | EP2789340A4 (fr) |
JP (3) | JP5690416B2 (fr) |
KR (2) | KR20150000867A (fr) |
CN (1) | CN104010648A (fr) |
AU (1) | AU2012349340B2 (fr) |
CA (1) | CA2861533C (fr) |
MY (1) | MY172363A (fr) |
PH (1) | PH12014501254A1 (fr) |
SG (2) | SG11201402993XA (fr) |
WO (1) | WO2013084971A1 (fr) |
Families Citing this family (24)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013084971A1 (fr) * | 2011-12-07 | 2013-06-13 | カルピス株式会社 | Stimulant du metabolisme des lipides et/ou du metabolisme du sucre contenant une bacterie d'acide lactique ou produit de traitement associe |
WO2013130773A2 (fr) | 2012-02-29 | 2013-09-06 | Ethicon Endo-Surgery, Inc. | Compositions de microbiota et leurs procédés associés |
WO2014077365A1 (fr) * | 2012-11-16 | 2014-05-22 | カルピス株式会社 | Agent soulageant les troubles intestinaux induits par le stress comprenant une souche spécifique de lactobacillus gasseri ou produit de traitement associé |
EP3016511B1 (fr) * | 2013-07-02 | 2019-10-09 | Austrianova Singapore Pte Ltd. | Procédé de lyophilisation de cellules encapsulées, compositions convenant à la congélation de cellules encapsulées, et utilisation de telles compositions |
JP6557605B2 (ja) * | 2013-11-07 | 2019-08-07 | サントリーホールディングス株式会社 | 乳酸菌を含む腸管バリア機能亢進剤 |
EP3165599A4 (fr) * | 2014-05-29 | 2017-12-27 | Nitto Pharmaceutical Industries, Ltd. | Nouvelle bactérie d'acide lactique et composition comprenant cette bactérie d'acide lactique |
EP3881680A1 (fr) | 2014-10-31 | 2021-09-22 | Pendulum Therapeutics, Inc. | Procédés et compositions se rapportant à un traitement microbien de troubles |
JP5703513B1 (ja) * | 2014-11-05 | 2015-04-22 | 沖縄ハム総合食品株式会社 | 新規乳酸菌株及びその乳酸菌株による発酵組成物及び醗酵エキス |
BR112018001187B1 (pt) | 2015-07-20 | 2022-02-15 | Quorum Innovations, Llc | Composição bacteriana, seus usos, método para melhorar condição de pele e método para desinfecção de uma superfície |
JP2017108679A (ja) * | 2015-12-16 | 2017-06-22 | 株式会社 オヴァールリエゾン | チョコレート菓子 |
JP6961339B2 (ja) * | 2015-12-18 | 2021-11-05 | アサヒ飲料株式会社 | 微生物菌体含有飲料 |
EP3479837B1 (fr) * | 2016-06-30 | 2023-09-06 | Asahi Group Holdings, Ltd. | Composition améliorant l'anémie rénale |
JP6923883B2 (ja) * | 2016-06-30 | 2021-08-25 | アサヒグループホールディングス株式会社 | 栄養状態改善に使用するための組成物 |
EP3675882A4 (fr) | 2017-08-30 | 2021-07-28 | Pendulum Therapeutics, Inc. | Methodes et compositions pour le traitement de troubles associés au microbiome |
KR101935762B1 (ko) * | 2018-08-25 | 2019-01-04 | 김민재 | 동물 투약 보조용 조성물 및 이의 제조방법 |
JP6480630B1 (ja) * | 2018-09-26 | 2019-03-13 | アサヒグループホールディングス株式会社 | 脂肪蓄積抑制剤および血中脂質改善剤 |
CN109666615B (zh) * | 2019-02-20 | 2021-03-19 | 无限极(中国)有限公司 | 一种益生菌组合物及其应用 |
IL288799B1 (en) * | 2019-06-11 | 2024-04-01 | Advance Pharmaceutical Inc | Superoxide soluble fiber components |
KR102229090B1 (ko) * | 2019-07-26 | 2021-03-19 | (주)성운파마코피아 | 락토바실러스 가세리 swpm102를 포함하는 허혈성 뇌질환의 예방, 개선 또는 치료용 조성물 |
JP7364390B2 (ja) * | 2019-08-19 | 2023-10-18 | 株式会社明治 | 糖代謝改善用組成物 |
KR102271528B1 (ko) * | 2020-01-03 | 2021-07-02 | 경희대학교 산학협력단 | 유산균 파쇄체로 코팅된 스테비아 분말을 포함하는 비만 또는 당뇨 예방 및 치료용 조성물 |
CN111235058B (zh) * | 2020-02-20 | 2022-11-15 | 江苏微康生物科技有限公司 | 一种具有修复紫外损伤、缓解炎症、预防皮肤光老化作用的短双歧杆菌及其制备方法和应用 |
KR102128098B1 (ko) * | 2020-03-23 | 2020-06-30 | 주식회사 종근당바이오 | 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주, 및 이를 포함하는 비알코올성 지방간의 예방, 개선, 또는 치료용 조성물 |
KR102257130B1 (ko) * | 2020-06-16 | 2021-05-28 | 주식회사 엠디헬스케어 | 락토바실러스 파라카세이 유래 소포를 포함하는 신경질환 또는 정신질환 예방 또는 치료용 조성물 |
Family Cites Families (22)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS61109729A (ja) | 1984-11-05 | 1986-05-28 | Advance Res & Dev Co Ltd | コレステロ−ル低下剤 |
JPS61271223A (ja) * | 1985-05-24 | 1986-12-01 | Biofuerumin Seiyaku Kk | 血中脂質改善剤 |
JP3359827B2 (ja) * | 1996-10-29 | 2002-12-24 | 株式会社ヤクルト本社 | 脂質代謝改善剤及びそれを含有する食品 |
EP0856259B1 (fr) | 1996-12-23 | 1998-08-12 | SITIA-YOMO S.p.A. | Composition pour l'usage dans l'alimentation comprenant de bactéries vivantes lactiques lyophisées |
JP3777296B2 (ja) | 2000-09-04 | 2006-05-24 | 明治製菓株式会社 | 乳酸菌によるコレステロールの低減若しくは除去方法 |
JP2003306436A (ja) | 2002-02-15 | 2003-10-28 | Snow Brand Milk Prod Co Ltd | 血清コレステロール上昇抑制剤 |
AU2003256419A1 (en) * | 2002-08-21 | 2004-03-11 | Merck & Co., Inc. | Combination therapy using a dual ppar alpha/gamma agonist and an angiotensin ii type i receptor antagonist |
JP2007504285A (ja) * | 2003-01-17 | 2007-03-01 | メルク エンド カムパニー インコーポレーテッド | N−シクロヘキシルアミノカルボニルベンゼンスルホンアミド誘導体 |
JP5025930B2 (ja) * | 2005-09-13 | 2012-09-12 | 株式会社桃屋 | ラクトバチルス・プランタラムの菌体を有効成分とする体脂肪率低減剤 |
JP4336992B2 (ja) | 2006-01-20 | 2009-09-30 | 日清食品ホールディングス株式会社 | 血中コレステロール低減作用を有する新規乳酸菌 |
JP2007284260A (ja) * | 2006-04-12 | 2007-11-01 | Sumco Techxiv株式会社 | シリコン単結晶の製造方法 |
JP2007284360A (ja) | 2006-04-13 | 2007-11-01 | Mitsukan Group Honsha:Kk | 乳酸菌由来のppar依存的遺伝子転写活性化組成物 |
JP5314421B2 (ja) * | 2006-05-31 | 2013-10-16 | 株式会社明治 | 免疫調節活性の高い乳酸菌の培養法 |
JP5247012B2 (ja) | 2006-07-25 | 2013-07-24 | 雪印メグミルク株式会社 | 脂肪肝抑制剤 |
ITMI20062363A1 (it) * | 2006-12-06 | 2008-06-07 | Aat Advanced Analytical Technology | Ceppi di lattobacilli probiotici che persistono nell'intestino e ne modulano i recettori di mucosa |
JP2008214253A (ja) * | 2007-03-02 | 2008-09-18 | Snow Brand Milk Prod Co Ltd | 内臓脂肪減少剤 |
EP2506863A4 (fr) * | 2009-12-04 | 2013-07-17 | Technologie Biolactis Inc | Procédé de régulation de ppar, voies en rapport avec l'obésité et leur impact métabolique connexe |
WO2011155518A1 (fr) * | 2010-06-08 | 2011-12-15 | カルピス株式会社 | Agent améliorant le métabolisme des lipides |
JP2012067187A (ja) | 2010-09-24 | 2012-04-05 | Riso Kagaku Corp | 非水系インクジェットインク |
WO2013084971A1 (fr) * | 2011-12-07 | 2013-06-13 | カルピス株式会社 | Stimulant du metabolisme des lipides et/ou du metabolisme du sucre contenant une bacterie d'acide lactique ou produit de traitement associe |
WO2014077365A1 (fr) | 2012-11-16 | 2014-05-22 | カルピス株式会社 | Agent soulageant les troubles intestinaux induits par le stress comprenant une souche spécifique de lactobacillus gasseri ou produit de traitement associé |
JP2014165231A (ja) * | 2013-02-22 | 2014-09-08 | Fujitsu Ltd | 電子部品ユニット及び固定構造 |
-
2012
- 2012-12-06 WO PCT/JP2012/081597 patent/WO2013084971A1/fr active Application Filing
- 2012-12-06 MY MYPI2014001658A patent/MY172363A/en unknown
- 2012-12-06 KR KR1020147018122A patent/KR20150000867A/ko active Search and Examination
- 2012-12-06 JP JP2013548286A patent/JP5690416B2/ja active Active
- 2012-12-06 SG SG11201402993XA patent/SG11201402993XA/en unknown
- 2012-12-06 AU AU2012349340A patent/AU2012349340B2/en active Active
- 2012-12-06 EP EP12855562.0A patent/EP2789340A4/fr not_active Withdrawn
- 2012-12-06 US US14/363,150 patent/US20140322172A1/en not_active Abandoned
- 2012-12-06 KR KR1020177024273A patent/KR101809695B1/ko active IP Right Grant
- 2012-12-06 CA CA2861533A patent/CA2861533C/fr active Active
- 2012-12-06 SG SG10201609078TA patent/SG10201609078TA/en unknown
- 2012-12-06 CN CN201280059978.4A patent/CN104010648A/zh active Pending
-
2014
- 2014-06-04 PH PH12014501254A patent/PH12014501254A1/en unknown
- 2014-08-14 JP JP2014165231A patent/JP5690435B2/ja active Active
-
2015
- 2015-01-30 JP JP2015017278A patent/JP6165185B2/ja active Active
-
2017
- 2017-01-18 US US15/408,722 patent/US10245291B2/en active Active
Non-Patent Citations (4)
Title |
---|
Kondo et al. Biosci. Biotechnol. Biochem., 2010, 74(8):1656-1661. * |
Namba et al. Infection and Innunity, 1981, 31(2):580-583. * |
Temmerman et al. Applied and Environmental Microbiology, 2003, 220-226. * |
Tursi et al. Int J Colorectal Dis., 2007, 22:1103-1108. * |
Also Published As
Publication number | Publication date |
---|---|
PH12014501254A1 (en) | 2014-09-08 |
JP2014237705A (ja) | 2014-12-18 |
WO2013084971A1 (fr) | 2013-06-13 |
KR101809695B1 (ko) | 2017-12-15 |
MY172363A (en) | 2019-11-21 |
AU2012349340B2 (en) | 2015-11-05 |
JP2015108010A (ja) | 2015-06-11 |
JPWO2013084971A1 (ja) | 2015-04-27 |
EP2789340A4 (fr) | 2015-07-22 |
AU2012349340A1 (en) | 2014-07-24 |
EP2789340A1 (fr) | 2014-10-15 |
US10245291B2 (en) | 2019-04-02 |
US20170119828A1 (en) | 2017-05-04 |
SG11201402993XA (en) | 2014-09-26 |
CA2861533A1 (fr) | 2013-06-13 |
JP5690435B2 (ja) | 2015-03-25 |
KR20150000867A (ko) | 2015-01-05 |
SG10201609078TA (en) | 2016-12-29 |
KR20170104629A (ko) | 2017-09-15 |
JP5690416B2 (ja) | 2015-03-25 |
CA2861533C (fr) | 2020-07-14 |
CN104010648A (zh) | 2014-08-27 |
JP6165185B2 (ja) | 2017-07-19 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US10245291B2 (en) | Lipid metabolism and/or sugar metabolism improver containing lactic acid bacterium or treatment product thereof | |
US9468657B2 (en) | Lactic acid bacterium agent for improving lipid metabolism | |
JP5923238B2 (ja) | 迷走神経活性化剤 | |
EP2478910B1 (fr) | Agent anti-obésité, aliment ou boisson anti-obésité, agent d'amélioration de tolérance au glucose et aliment ou boisson pour l'amélioration de la tolérance au glucose | |
EP3479837B1 (fr) | Composition améliorant l'anémie rénale | |
JP6923883B2 (ja) | 栄養状態改善に使用するための組成物 | |
JP5950993B2 (ja) | 迷走神経活性化剤 | |
EP3479836B1 (fr) | Composition facilitant la régénération du cartilage | |
JP7430312B2 (ja) | 腸内短鎖脂肪酸産生促進用組成物及びこれを含む飲食品 | |
AU2015201076B2 (en) | Lipid metabolism-improving agent |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AS | Assignment |
Owner name: CALPIS CO., LTD., JAPAN Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:NAKAMURA, FUTOSHI;ASHIDA, NOBUHISA;ISHIDA, YU;AND OTHERS;SIGNING DATES FROM 20140507 TO 20140509;REEL/FRAME:033039/0872 |
|
AS | Assignment |
Owner name: ASAHI GROUP HOLDINGS, LTD., JAPAN Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:CALPIS CO., LTD.;REEL/FRAME:037501/0292 Effective date: 20151231 |
|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |