JP6664315B2 - Serotonin secretagogue - Google Patents
Serotonin secretagogue Download PDFInfo
- Publication number
- JP6664315B2 JP6664315B2 JP2016248224A JP2016248224A JP6664315B2 JP 6664315 B2 JP6664315 B2 JP 6664315B2 JP 2016248224 A JP2016248224 A JP 2016248224A JP 2016248224 A JP2016248224 A JP 2016248224A JP 6664315 B2 JP6664315 B2 JP 6664315B2
- Authority
- JP
- Japan
- Prior art keywords
- serotonin
- group
- cells
- lactobacillus
- administration
- 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.)
- Active
Links
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 title claims description 146
- 229940076279 serotonin Drugs 0.000 title claims description 72
- 230000000580 secretagogue effect Effects 0.000 title claims description 30
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 78
- 241000894006 Bacteria Species 0.000 claims description 40
- 239000004310 lactic acid Substances 0.000 claims description 39
- 235000014655 lactic acid Nutrition 0.000 claims description 39
- 230000028327 secretion Effects 0.000 claims description 26
- 241000186660 Lactobacillus Species 0.000 claims description 22
- 229940039696 lactobacillus Drugs 0.000 claims description 22
- 230000001737 promoting effect Effects 0.000 claims description 17
- 235000013305 food Nutrition 0.000 claims description 16
- 239000004480 active ingredient Substances 0.000 claims description 13
- 241000192001 Pediococcus Species 0.000 claims description 10
- 240000001929 Lactobacillus brevis Species 0.000 claims description 8
- 235000013957 Lactobacillus brevis Nutrition 0.000 claims description 8
- 239000000654 additive Substances 0.000 claims description 7
- 239000003623 enhancer Substances 0.000 claims description 7
- 150000001875 compounds Chemical class 0.000 claims description 6
- 230000000996 additive effect Effects 0.000 claims description 4
- 241000186679 Lactobacillus buchneri Species 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 241000186604 Lactobacillus reuteri Species 0.000 claims description 2
- 229940001882 lactobacillus reuteri Drugs 0.000 claims description 2
- 230000008326 skin blood flow Effects 0.000 claims description 2
- 244000199866 Lactobacillus casei Species 0.000 claims 1
- 235000013958 Lactobacillus casei Nutrition 0.000 claims 1
- 235000013361 beverage Nutrition 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 229940017800 lactobacillus casei Drugs 0.000 claims 1
- 210000004027 cell Anatomy 0.000 description 99
- 230000000694 effects Effects 0.000 description 62
- 230000001580 bacterial effect Effects 0.000 description 35
- 230000017531 blood circulation Effects 0.000 description 34
- 230000002889 sympathetic effect Effects 0.000 description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
- 210000005036 nerve Anatomy 0.000 description 23
- 230000002496 gastric effect Effects 0.000 description 22
- 210000001367 artery Anatomy 0.000 description 21
- 238000000540 analysis of variance Methods 0.000 description 20
- 230000008035 nerve activity Effects 0.000 description 20
- 238000012360 testing method Methods 0.000 description 18
- 238000005259 measurement Methods 0.000 description 17
- 239000000047 product Substances 0.000 description 17
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 16
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 16
- 239000000843 powder Substances 0.000 description 15
- 230000002708 enhancing effect Effects 0.000 description 14
- 230000036572 transepidermal water loss Effects 0.000 description 14
- 210000001186 vagus nerve Anatomy 0.000 description 14
- 241000700159 Rattus Species 0.000 description 12
- 210000003486 adipose tissue brown Anatomy 0.000 description 12
- 239000003112 inhibitor Substances 0.000 description 12
- 238000000585 Mann–Whitney U test Methods 0.000 description 11
- 238000000034 method Methods 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- 230000001965 increasing effect Effects 0.000 description 10
- 239000002609 medium Substances 0.000 description 10
- 230000003247 decreasing effect Effects 0.000 description 9
- 210000001198 duodenum Anatomy 0.000 description 9
- 239000002504 physiological saline solution Substances 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- MFWNKCLOYSRHCJ-BTTYYORXSA-N granisetron Chemical compound C1=CC=C2C(C(=O)N[C@H]3C[C@H]4CCC[C@@H](C3)N4C)=NN(C)C2=C1 MFWNKCLOYSRHCJ-BTTYYORXSA-N 0.000 description 8
- 229960003727 granisetron Drugs 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 230000002567 autonomic effect Effects 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 230000036760 body temperature Effects 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 210000003491 skin Anatomy 0.000 description 6
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 5
- 230000000968 intestinal effect Effects 0.000 description 5
- 230000033764 rhythmic process Effects 0.000 description 5
- 230000001515 vagal effect Effects 0.000 description 5
- 238000005303 weighing Methods 0.000 description 5
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 241000186000 Bifidobacterium Species 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 241000700157 Rattus norvegicus Species 0.000 description 4
- 239000000306 component Substances 0.000 description 4
- 238000012258 culturing Methods 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 210000001035 gastrointestinal tract Anatomy 0.000 description 4
- 239000003906 humectant Substances 0.000 description 4
- 208000013403 hyperactivity Diseases 0.000 description 4
- 239000002858 neurotransmitter agent Substances 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 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 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 238000010304 firing Methods 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
- 229920000053 polysorbate 80 Polymers 0.000 description 3
- 229910052709 silver Inorganic materials 0.000 description 3
- 239000004332 silver Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 2
- 108020004465 16S ribosomal RNA Proteins 0.000 description 2
- 108091005477 5-HT3 receptors Proteins 0.000 description 2
- 102000035037 5-HT3 receptors Human genes 0.000 description 2
- 206010002091 Anaesthesia Diseases 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
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 2
- 239000004375 Dextrin Substances 0.000 description 2
- 229930091371 Fructose Natural products 0.000 description 2
- 239000005715 Fructose Substances 0.000 description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 241000214517 Lactobacillus casei group Species 0.000 description 2
- 241000186673 Lactobacillus delbrueckii Species 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 229920001214 Polysorbate 60 Polymers 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 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
- 230000037005 anaesthesia Effects 0.000 description 2
- 239000003674 animal food additive Substances 0.000 description 2
- 230000036528 appetite Effects 0.000 description 2
- 235000019789 appetite Nutrition 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 210000003403 autonomic nervous system Anatomy 0.000 description 2
- 210000000467 autonomic pathway Anatomy 0.000 description 2
- 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 2
- 239000011230 binding agent Substances 0.000 description 2
- 229940041514 candida albicans extract Drugs 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 235000019425 dextrin Nutrition 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 235000021107 fermented food Nutrition 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 229940075507 glyceryl monostearate Drugs 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 210000004731 jugular vein Anatomy 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 235000013372 meat Nutrition 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 230000001734 parasympathetic effect Effects 0.000 description 2
- 210000005037 parasympathetic nerve Anatomy 0.000 description 2
- 210000000578 peripheral nerve Anatomy 0.000 description 2
- 230000008855 peristalsis Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 235000019422 polyvinyl alcohol Nutrition 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
- 230000001603 reducing effect Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 210000004927 skin cell Anatomy 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- 210000000689 upper leg Anatomy 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 239000012138 yeast extract Substances 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- 102000049773 5-HT2A Serotonin Receptor Human genes 0.000 description 1
- 108010072564 5-HT2A Serotonin Receptor Proteins 0.000 description 1
- 108091005482 5-HT4 receptors Proteins 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 108010076119 Caseins Proteins 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 235000005956 Cosmos caudatus Nutrition 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 208000013600 Diabetic vascular disease Diseases 0.000 description 1
- 238000011891 EIA kit Methods 0.000 description 1
- 241000792859 Enema 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
- 108010068370 Glutens Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
- 241000186606 Lactobacillus gasseri Species 0.000 description 1
- 241001468157 Lactobacillus johnsonii Species 0.000 description 1
- 240000006024 Lactobacillus plantarum Species 0.000 description 1
- 235000013965 Lactobacillus plantarum Nutrition 0.000 description 1
- 241000186612 Lactobacillus sakei Species 0.000 description 1
- 241000186869 Lactobacillus salivarius Species 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 244000294411 Mirabilis expansa Species 0.000 description 1
- 235000015429 Mirabilis expansa Nutrition 0.000 description 1
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 235000019774 Rice Bran oil Nutrition 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 206010057469 Vascular stenosis Diseases 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000005273 aeration Methods 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 239000003420 antiserotonin agent Substances 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 235000013527 bean curd Nutrition 0.000 description 1
- 230000003796 beauty Effects 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 210000003198 cerebellar cortex Anatomy 0.000 description 1
- 229940082500 cetostearyl alcohol Drugs 0.000 description 1
- 210000003737 chromaffin cell Anatomy 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 235000015140 cultured milk Nutrition 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 201000009101 diabetic angiopathy Diseases 0.000 description 1
- 201000002249 diabetic peripheral angiopathy Diseases 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940095399 enema Drugs 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 235000021323 fish oil Nutrition 0.000 description 1
- 235000015203 fruit juice Nutrition 0.000 description 1
- 235000013376 functional food Nutrition 0.000 description 1
- 235000021312 gluten Nutrition 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 239000006458 gyp medium Substances 0.000 description 1
- 235000013402 health food Nutrition 0.000 description 1
- 231100000753 hepatic injury Toxicity 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 235000012907 honey Nutrition 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- 229960000367 inositol Drugs 0.000 description 1
- 210000002490 intestinal epithelial cell Anatomy 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- FPCCSQOGAWCVBH-UHFFFAOYSA-N ketanserin Chemical compound C1=CC(F)=CC=C1C(=O)C1CCN(CCN2C(C3=CC=CC=C3NC2=O)=O)CC1 FPCCSQOGAWCVBH-UHFFFAOYSA-N 0.000 description 1
- 229940072205 lactobacillus plantarum Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 235000011147 magnesium chloride Nutrition 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229940099596 manganese sulfate Drugs 0.000 description 1
- 239000011702 manganese sulphate Substances 0.000 description 1
- 235000007079 manganese sulphate Nutrition 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
- SQQMAOCOWKFBNP-UHFFFAOYSA-L manganese(II) sulfate Chemical compound [Mn+2].[O-]S([O-])(=O)=O SQQMAOCOWKFBNP-UHFFFAOYSA-L 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 230000006996 mental state Effects 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
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 229960002900 methylcellulose Drugs 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 235000020124 milk-based beverage Nutrition 0.000 description 1
- 235000013536 miso Nutrition 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 235000013379 molasses Nutrition 0.000 description 1
- 229910052750 molybdenum Inorganic materials 0.000 description 1
- 239000011733 molybdenum Substances 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 239000006872 mrs medium Substances 0.000 description 1
- 238000011392 neighbor-joining method Methods 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 235000012149 noodles Nutrition 0.000 description 1
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 239000005426 pharmaceutical component Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 239000008165 rice bran oil Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 210000001991 scapula Anatomy 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 239000002400 serotonin 2A antagonist Substances 0.000 description 1
- 239000003523 serotonin 4 antagonist Substances 0.000 description 1
- 239000003369 serotonin 5-HT3 receptor antagonist Substances 0.000 description 1
- 229940121356 serotonin receptor antagonist Drugs 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 210000002460 smooth muscle Anatomy 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
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000014214 soft drink Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 235000013322 soy milk Nutrition 0.000 description 1
- 235000013555 soy sauce Nutrition 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- -1 troches Substances 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Images
Landscapes
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Description
本発明は、セロトニン分泌促進剤に関する。 The present invention relates to a serotonin secretagogue.
ラクトバチラス・ブレビス（Ｌａｃｔｏｂａｃｉｌｌｕｓ ｂｒｅｖｉｓ）ＳＢＣ８８０３（以下、「ＳＢＬ８８」とも称する。）は、抗アレルギー作用を有すること（特許文献１）、アルコール性肝障害抑制作用を有すること（特許文献２）、腸管保護作用を有すること（特許文献３）が知られている。 Lactobacillus brevis SBC8803 (hereinafter also referred to as “SBL88”) has an antiallergic effect (Patent Document 1), an alcoholic liver injury suppressing effect (Patent Document 2), and an intestinal protective effect. (Patent Document 3) is known.
本発明は、ラクトバチラス・ブレビスＳＢＣ８８０３の新規な用途を提供することを課題とする。 An object of the present invention is to provide a novel use of Lactobacillus brevis SBC8803.
本発明は、ラクトバチラス・デルブリッキィー（Ｌａｃｔｏｂａｃｉｌｌｕｓ ｄｅｌｂｒｕｅｃｋｉｉ）グループに属する乳酸菌以外のラクトバチラス属に属する乳酸菌、及びペディオコッカス（Ｐｅｄｉｏｃｏｃｃｕｓ）属に属する乳酸菌からなる群より選ばれる菌株の菌体又はその処理物を有効成分として含有するセロトニン分泌促進剤を提供する。 The present invention relates to a lactic acid bacterium belonging to the genus Lactobacillus other than a lactic acid bacterium belonging to the group Lactobacillus delbrueckii and a lactic acid bacterium belonging to the genus Pediococcus or a processed product thereof, which is selected from the group consisting of lactic acid bacteria belonging to the genus Pediococcus. And a serotonin secretagogue containing the compound as an active ingredient.
本発明者らは、上記乳酸菌群から選択される菌株の菌体又は菌体処理物は、モノアミン神経伝達物質であるセロトニンの細胞からの分泌を促進する作用を有する、との新規な知見を得た。本発明はこの知見に基づいており、ラクトバチラス・ブレビスＳＢＣ８８０３を含む上記菌株の新規な用途を提供するものである。 The present inventors have obtained a new finding that cells or treated cells of a strain selected from the above lactic acid bacteria group have an action of promoting secretion of serotonin, which is a monoamine neurotransmitter, from cells. Was. The present invention is based on this finding, and provides a novel use of the above strains including Lactobacillus brevis SBC8803.
セロトニンは人の精神面に大きな影響を与える神経伝達物質で、不足すると「うつ病」などの精神疾患に陥り易いといわれている。また、体内セロトニンの約９０％は、腸管に存在している腸クロム親和性細胞（Ｅｎｔｅｒｏｃｈｒｏｍａｆｆｉｎ（ＥＣ）細胞）により産生されおり、腸の蠕動運動等に重要な役割を果たしていると考えられている。従って、セロトニン産生を制御することは、ストレス社会における健康感（生活リズム改善）において、極めて重要である。 Serotonin is a neurotransmitter that has a major effect on the mental state of humans, and it is said that if it is deficient, it will easily lead to mental disorders such as "depression". In addition, about 90% of in vivo serotonin is produced by intestinal chromaffin cells (Enterochromaffin (EC) cells) present in the intestinal tract, and is considered to play an important role in intestinal peristalsis and the like. . Therefore, controlling serotonin production is extremely important for a sense of health (improving life rhythm) in a stressed society.
上記セロトニン分泌促進剤は、ラクトバチラス・ブレビスに属する菌株の菌体又は菌体処理物を有効成分として含有することが好ましく、ラクトバチラス・ブレビスＳＢＣ８８０３の菌体又は菌体処理物を有効成分として含有することがより好ましい。これにより、より一層優れたセロトニン分泌促進作用を奏する。 The above-mentioned serotonin secretagogue preferably contains, as an active ingredient, cells of a strain belonging to Lactobacillus brevis or a processed product thereof, and contains cells or a processed product of Lactobacillus brevis SBC8803 as an active ingredient. Is more preferred. Thereby, a more excellent serotonin secretion promoting effect is exhibited.
なお、ラクトバチラス・ブレビスＳＢＣ８８０３は、２００６年６月２８日に独立行政法人産業技術総合研究所 特許生物寄託センター（日本国茨城県つくば市東１丁目１番地１ 中央第６（郵便番号３０５−８５６６））に寄託された、受託番号がＦＥＲＭ ＢＰ−１０６３２の菌株である。 In addition, Lactobacillus brevis SBC8803 was obtained on June 28, 2006, National Institute of Advanced Industrial Science and Technology, Patent Organism Depositary Center (1-1-1, Higashi, Tsukuba, Ibaraki, Japan, Chuo No. 6 (zip code 305-8566)). Deposited under the accession number FERM BP-10632.
上記セロトニン分泌促進剤は、セロトニンの分泌を介して自律神経に作用し、例えば、胃迷走神経亢進作用、皮膚動脈交感神経抑制作用及び褐色脂肪組織交感神経亢進作用を発揮する。したがって、上記セロトニン分泌促進剤は、自律神経調節剤として使用することもできる。 The above-mentioned serotonin secretagogue acts on autonomic nerves through secretion of serotonin, and exhibits, for example, a gastric vagus nerve enhancing action, a cutaneous artery sympathetic nerve suppressing action, and a brown adipose tissue sympathetic nerve enhancing action. Therefore, the above-mentioned serotonin secretagogue can also be used as an autonomic nervous regulator.
上記セロトニン分泌促進剤は、血流量増加作用（血流促進作用）及び経皮水分蒸散量低下作用（経皮水分蒸散抑制作用）を有しているため、皮膚の保湿度を高めることができ、保湿剤として使用することもできる。また、上記セロトニン分泌促進剤は、血流促進剤として使用することもできる。 Since the above-mentioned serotonin secretagogue has a blood flow increasing action (blood flow promoting action) and a transcutaneous water evaporation decreasing action (transdermal water evaporation suppressing action), it can increase the moisture retention of the skin, It can also be used as a humectant. In addition, the above-mentioned serotonin secretagogue can also be used as a blood flow enhancer.
上記セロトニン分泌促進剤による血流促進効果及び保湿効果は、少なくともその一部はセロトニン分泌促進作用に基づいており、セロトニンの分泌を介して皮膚動脈交感神経が抑制されることにより生じる。 The blood flow-promoting effect and the moisturizing effect of the serotonin secretagogue are based at least in part on the serotonin secretion-promoting effect, and are caused by suppression of the cutaneous artery sympathetic nerve through the secretion of serotonin.
上記菌株は、古くから発酵食品に利用されており、生体への安全性が確立されている。したがって、上記セロトニン分泌促進剤、上記自律神経調節剤、上記保湿剤又は上記血流促進剤は、生体への安全性が高く、長期間継続的に摂取することができるため、医薬品成分、飲食品成分、飲食品添加物、飼料成分、飼料添加物等として使用することができる。また、医薬品、飲食品又は飼料に添加して使用（摂取）することもできる。 The above strain has been used for fermented foods for a long time, and its safety to living organisms has been established. Therefore, the serotonin secretagogue, the autonomic nervous regulator, the humectant or the blood flow enhancer is highly safe for living organisms and can be taken continuously for a long period of time. It can be used as an ingredient, food and drink additive, feed ingredient, feed additive and the like. In addition, it can be used (ingested) by being added to pharmaceuticals, foods and drinks or feeds.
本発明はまた、飲食品の製造における上記セロトニン分泌促進剤、上記自律神経調節剤、上記保湿剤又は上記血流促進剤の使用ということもできる。 The present invention can also be described as the use of the above-mentioned serotonin secretagogue, the above-mentioned autonomic nervous regulator, the above-mentioned humectant or the above-mentioned blood flow enhancer in the production of food and drink.
本発明によれば、生体への安全性が高く、飲食品の成分としても使用可能な新規のセロトニン分泌促進剤が提供される。また、当該セロトニン分泌促進剤を含有する医薬品、飲食品、飲食品添加物等が提供される。 According to the present invention, there is provided a novel serotonin secretagogue which is highly safe for living organisms and can be used as a component of foods and drinks. In addition, pharmaceuticals, foods and drinks, food and drink additives, and the like containing the serotonin secretagogue are provided.
現在のストレス社会においては、生活リズムが乱れ易い状況下にあり、これが体調不良、睡眠障害、疲労、生活習慣病等々に導く要因の１つとなっている。ストレスが続くと交感神経が強く刺激され、血流循環障害が起こり皮膚の状態が悪くなったり、睡眠不足になったりすると言われている。一方、副交感神経活動が抑えられるため、副交感神経の支配下にある消化管では、消化液の分泌が抑制され、蠕動運動も抑制されるので、食欲不振、便秘などの症状が起きる。本発明のセロトニン分泌促進剤は、胃迷走神経の活動を亢進する作用を有するため、整腸効果、並びに便通及び食欲を促進する効果が期待できる。 In the current stressed society, the life rhythm is easily disturbed, and this is one of the factors leading to poor physical condition, sleep disorders, fatigue, lifestyle-related diseases and the like. It is said that if the stress continues, the sympathetic nerve is strongly stimulated, causing a blood circulation disorder, resulting in poor skin condition and lack of sleep. On the other hand, since parasympathetic nerve activity is suppressed, in the digestive tract under the control of the parasympathetic nerve, secretion of digestive juice is suppressed and peristalsis is also suppressed, so that symptoms such as anorexia and constipation occur. Since the serotonin secretagogue of the present invention has an effect of enhancing the activity of the gastric vagus nerve, it can be expected to have an intestinal effect and an effect of promoting bowel movement and appetite.
また、本発明のセロトニン分泌促進剤は、皮膚動脈交感神経の活動を抑制する作用を有しており、皮膚動脈を弛緩させて血流を促進し（血流量増加作用）、皮膚細胞への酸素及び栄養素の供給を高め、経皮水分蒸散量を低下させ（経皮水分蒸散量低下作用）、皮膚の保湿度を高めることができる。これにより、美容効果が期待できる。また、入眠を促進する効果も期待できる。 In addition, the serotonin secretagogue of the present invention has an effect of suppressing the activity of cutaneous artery sympathetic nerves, relaxes cutaneous arteries, promotes blood flow (increases blood flow), and reduces oxygen supply to skin cells. In addition, the supply of nutrients can be increased, the transepidermal water loss can be reduced (a transdermal water loss reduction effect), and the moisture retention of the skin can be increased. Thereby, a beauty effect can be expected. In addition, the effect of promoting sleep onset can be expected.
また、本発明の自律神経調節剤によれば、神経伝達物質であるセロトニンを介して、少なくとも胃迷走神経亢進作用、皮膚動脈交感神経抑制作用及び褐色脂肪組織交感神経亢進作用が奏される。セロトニンによる各臓器の自律神経活動への更なる影響を勘案すれば、健康的な生活リズムの基本となる内臓活動のリズムを維持する効果が期待できる。 In addition, the autonomic nervous regulator of the present invention exerts at least a gastric vagus nerve enhancing effect, a cutaneous artery sympathetic nerve suppressing effect, and a brown adipose tissue sympathetic nerve enhancing effect via serotonin, which is a neurotransmitter. Considering the further effect of serotonin on autonomic nervous activity of each organ, the effect of maintaining the rhythm of internal organs, which is the basis of a healthy living rhythm, can be expected.
本実施形態に係るセロトニン分泌促進剤は、ラクトバチラス・デルブリッキィー（Ｌａｃｔｏｂａｃｉｌｌｕｓ ｄｅｌｂｒｕｅｃｋｉｉ）グループに属する乳酸菌以外のラクトバチラス属に属する乳酸菌、及びペディオコッカス（Ｐｅｄｉｏｃｏｃｃｕｓ）属に属する乳酸菌からなる群（以下、「本実施形態に係る乳酸菌群」ともいう。）より選ばれる菌株の菌体又はその処理物を有効成分として含有する。 The serotonin secretagogue according to the present embodiment is a group consisting of a lactic acid bacterium belonging to the genus Lactobacillus other than a lactic acid bacterium belonging to the Lactobacillus delbrueckii group, and a lactic acid bacterium belonging to the genus Pediococcus (hereinafter, referred to as “Pediococcus”). The lactic acid bacteria group according to the present embodiment is also referred to as "the lactic acid bacteria group."
ラクトバチラス・デルブリッキィーグループに属する乳酸菌とは、ラクトバチラス属に属する乳酸菌、及びペディオコッカス属に属する乳酸菌を１６Ｓ ｒＤＮＡの塩基配列に基づいて近隣結合（Ｎｅｉｇｈｂｏｒ-ｊｏｉｎｉｎｇ）法により系統樹を作成したときに、ラクトバチラス・デルブリッキィーが含まれる系統群に分類される乳酸菌である（図１参照。出典：Ｊａｐａｎｅｓｅ Ｊｏｕｒｎａｌ ｏｆ Ｌａｃｔｉｃ Ａｃｉｄ Ｂａｃｔｅｒｉａ，２００８年，Ｖｏｌ．１９，Ｎｏ．３，ｐｐ．１５４）。本実施形態に係る乳酸菌群は、図１に示すラクトバチラス属及びペディオコッカス属に属する乳酸菌から、図１に示すラクトバチラス・デルブリッキィーグループに属する乳酸菌を除いた乳酸菌からなる群である。 A lactic acid bacterium belonging to the Lactobacillus delbrikii group refers to a lactic acid bacterium belonging to the genus Lactobacillus and a lactic acid bacterium belonging to the genus Pediococcus when a phylogenetic tree is prepared by a neighbor-joining method based on the base sequence of 16S rDNA. Lactobacillus bacterium classified into a family including Lactobacillus delbrickii (see FIG. 1. Source: Japanese Journal of Lactic Acid Bacteria, 2008, Vol. 19, No. 3, pp. 154). The lactic acid bacteria group according to the present embodiment is a group consisting of lactic acid bacteria belonging to the genus Lactobacillus and Pediococcus shown in FIG. 1 and excluding the lactic acid bacteria belonging to the Lactobacillus del Brickii group shown in FIG.
本実施形態に係る乳酸菌群としては、具体的には例えば、ラクトバチラス・ブッヒネリ（ｂｕｃｈｎｅｒｉ）グループに属する乳酸菌、ペディオコッカスグループに属する乳酸菌、ラクトバチラス・アリメンタリウス（ａｌｉｍｅｎｔａｒｉｕｓ）−ラクトバチラス・ファルシミニス（ｆａｒｃｉｍｉｎｉｓ）グループに属する乳酸菌、ラクトバチラス・プランタルム（ｐｌａｎｔａｒｕｍ）グループに属する乳酸菌、ラクトバチラス・ロイテリ（ｒｅｕｔｅｒｉ）グループに属する乳酸菌、ラクトバチラス・カゼイ（ｃａｓｅｉ）グループに属する乳酸菌、ラクトバチラス・サケイ（ｓａｋｅｉ）グループに属する乳酸菌、ラクトバチラス・サリヴァリゥス（ｓａｌｉｖａｒｉｕｓ）グループに属する乳酸菌が挙げられる。 Specific examples of the lactic acid bacteria group according to the present embodiment include, for example, lactic acid bacteria belonging to the Lactobacillus buchneri group, lactic acid bacteria belonging to the Pediococcus group, and Lactobacillus alimentarius-Lactobacillus falciminis. Lactobacillus belonging to the Lactobacillus plantarum group, Lactobacillus belonging to the Lactobacillus reuteri group, Lactobacillus belonging to the Lactobacillus casei group, Lactobacillus belonging to the Lactobacillus casei group, Lactobacillus belonging to the Lactobacillus sakei group, Lactic acid bacteria belonging to the Lactobacillus salivarius group are mentioned.
本実施形態に係る乳酸菌群から選択される菌株としては、セロトニンの分泌がより一層促進されることから、ラクトバチラス・ブッヒネリグループに属する菌株が好ましく、ラクトバチラス・ブレビスに属する菌株がより好ましく、ラクトバチラス・ブレビスＳＢＣ８８０３が更に好ましい。 The strain selected from the lactic acid bacteria group according to the present embodiment is preferably a strain belonging to the Lactobacillus buchneri group, and more preferably a strain belonging to Lactobacillus brevis, because the secretion of serotonin is further promoted. Brevis SBC8803 is more preferred.
本実施形態に係るセロトニン分泌促進剤における菌株は、例えば、自然界から分離可能なもの、又はＡＴＣＣ等の細胞バンクから入手可能なものであってもよい。本実施形態に係るセロトニン分泌促進剤は、本実施形態に係る乳酸菌群より選ばれる菌株の菌体又はその処理物を有効成分とする。上記菌株は１種単独であってもよく、２種以上の組み合わせであってもよい。 The strain in the serotonin secretagogue according to the present embodiment may be, for example, one that can be separated from nature or one that can be obtained from a cell bank such as ATCC. The serotonin secretagogue according to the present embodiment contains, as an active ingredient, cells of a strain selected from the lactic acid bacteria group according to the present embodiment or a processed product thereof. The above strains may be used alone or in combination of two or more.
菌株の菌体は、生菌体及び死菌体のいずれであってもよい。菌体は、生菌体を培養することにより大量に生産することができる。培地は、液体培地及び固体培地のいずれでもよいが、窒素源及び炭素源を含有するものが好ましい。窒素源としては、肉エキス、ペプトン、グルテン、カゼイン、酵母エキス、アミノ酸等を、また、炭素源としては、グルコース、キシロース、フルクトース、イノシトール、マルトース、水アメ、麹汁、デンプン、バカス、フスマ、糖蜜、グリセリン等を用いることができる。また、無機質として、硫酸アンモニウム、リン酸カリウム、塩化マグネシウム、食塩、鉄、マンガン、モリブデン等を添加することができ、更にビタミン等を添加することができる。好適な培地としては、ＭＲＳ培地、ＬＢＳ培地、Ｒｏｇｏｓａ培地、ＷＹＰ培地、ＧＹＰ培地等が挙げられる。 The cells of the strain may be live cells or dead cells. Cells can be produced in large quantities by culturing live cells. The medium may be either a liquid medium or a solid medium, but preferably contains a nitrogen source and a carbon source. As a nitrogen source, meat extract, peptone, gluten, casein, yeast extract, amino acids, etc., and as a carbon source, glucose, xylose, fructose, inositol, maltose, water candy, koji juice, starch, bacas, bran, Molasses, glycerin and the like can be used. As inorganic substances, ammonium sulfate, potassium phosphate, magnesium chloride, salt, iron, manganese, molybdenum, and the like can be added, and vitamins and the like can be further added. Suitable media include MRS medium, LBS medium, Rogosa medium, WYP medium, GYP medium and the like.
生菌体の培養条件は、各乳酸菌に適した条件を採用すればよいが、例えば、培養温度は通常２０〜５０℃、好ましくは２５〜４０℃、より好ましくは３０℃である。培養時間は通常６〜６２時間であり、好ましくは１２〜４８時間であり、より好ましくは１５〜３０時間である。培地のｐＨは通常３〜８、好ましくは４〜７であり、より好ましくは６〜７である。培養はインキュベーター中で行ってもよく、また、培養の際は通気振とうしてもよい。 The culturing conditions for the viable cells may be those suitable for each lactic acid bacterium. For example, the culturing temperature is usually 20 to 50 ° C, preferably 25 to 40 ° C, and more preferably 30 ° C. The culture time is usually 6 to 62 hours, preferably 12 to 48 hours, and more preferably 15 to 30 hours. The pH of the medium is usually 3 to 8, preferably 4 to 7, and more preferably 6 to 7. The culture may be performed in an incubator, and the culture may be performed with aeration and shaking.
菌体の処理物としては、上記菌体（生菌体又は死菌体）に、加熱、加圧、乾燥、粉砕、破壊又は自己溶解等の処理を行って得られる処理物が挙げられる。これらの処理は２種以上を組み合わせてもよい。菌体の処理物としては、例えば、菌体を１００℃以上で数分以上加熱して得られる処理物（例えば、菌体に、１０５〜１２５℃の温度で１０分以上、オートクレーブ処理を施して得られる処理物）、菌体に対して凍結乾燥、噴霧乾燥等を行って得られる処理物、菌体を有機溶媒（アセトン、エタノール等）に接触させて得られる処理物、菌体を酸若しくはアルカリ溶液に接触させて得られる処理物、菌体を酵素的に破砕して得られる処理物、又は菌体を超音波、フレンチプレス等で物理的に破壊して得られる処理物が挙げられる。このような菌体処理物は、未処理菌体（特に生菌体）と比較して、取り扱いが容易な点で好適である。 Examples of the processed product of the cells include a processed product obtained by subjecting the above cells (live cells or dead cells) to treatments such as heating, pressurization, drying, pulverization, destruction, and self-lysis. These processes may be used in combination of two or more. As a treated product of the cells, for example, a treated product obtained by heating the cells at 100 ° C. or more for several minutes or more (for example, subjecting the cells to an autoclave treatment at a temperature of 105 to 125 ° C. for 10 minutes or more) Treated product), a processed product obtained by subjecting cells to freeze-drying, spray-drying, or the like, a processed product obtained by contacting the cells with an organic solvent (acetone, ethanol, etc.), and transforming the cells with acid or A treated product obtained by contacting with an alkaline solution, a treated product obtained by enzymatically crushing cells, or a treated product obtained by physically destroying cells by ultrasonic waves, French press or the like can be used. Such treated cells are preferable in that they are easier to handle than untreated cells (especially live cells).
セロトニンは、５−ヒドロキシトリプタミン（５−ｈｙｄｒｏｘｙｔｒｙｐｔａｍｉｎｅ）とも呼ばれ、モノアミン神経伝達物質の一つである。本実施形態に係るセロトニン分泌促進剤は、セロトニンの分泌を介して自律神経（特に、脳から各臓器へ向かう神経である遠心枝）に作用し、例えば、胃迷走神経亢進作用、皮膚動脈交感神経抑制作用及び褐色脂肪組織交感神経亢進作用を発揮することができるため、自律神経調節剤として使用してもよい。また、本実施形態に係る自律神経調節剤は、生活リズム改善剤として使用することもできる。 Serotonin is also called 5-hydroxytryptamine and is one of monoamine neurotransmitters. The serotonin secretagogue according to the present embodiment acts on the autonomic nerves (particularly, the efferent branch which is a nerve from the brain to each organ) via secretion of serotonin, and includes, for example, a gastric vagus nerve enhancing action, a cutaneous artery sympathetic nerve. Since it can exert an inhibitory action and a brown adipose tissue sympathetic nerve enhancing action, it may be used as an autonomic nervous regulator. Further, the autonomic nervous regulator according to the present embodiment can also be used as a living rhythm improving agent.
本実施形態に係るセロトニン分泌促進剤は、皮膚動脈交感神経抑制作用を介して、皮膚動脈を弛緩させて血流を促進することができるため、血流促進剤として使用することもできる。またこのような作用に基づいているため、本実施形態に係る血流促進剤は、手足の冷え、肩凝り及び糖尿病性血管障害等の血管狭窄症状に対して有効である。 The serotonin secretion enhancer according to the present embodiment can relax the cutaneous artery and promote blood flow through the cutaneous artery sympathetic nerve inhibitory action, and thus can also be used as a blood flow enhancer. Further, based on such an action, the blood flow enhancer according to the present embodiment is effective for vascular stenosis symptoms such as cold limbs, stiff shoulders, and diabetic vascular disorders.
本実施形態に係るセロトニン分泌促進剤は、血流促進作用により、皮膚細胞への酸素及び栄養素の供給を高め、経皮水分蒸散量を低下させ（経皮水分蒸散量低下作用）、皮膚の保湿度を高めることができるため、保湿剤として使用することもできる。 The serotonin secretagogue according to the present embodiment enhances the supply of oxygen and nutrients to skin cells by a blood flow promoting action, reduces transdermal water loss (transdermal water loss reducing action), and moisturizes the skin. Since the degree can be increased, it can be used as a humectant.
本実施形態に係るセロトニン分泌促進剤は、固体（例えば、凍結乾燥させて得られる粉末）、液体（水溶性又は脂溶性の溶液又は懸濁液）、ペースト等のいずれの形状であってもよく、また、散剤、丸剤、顆粒剤、錠剤、シロップ剤、トローチ剤、カプセル剤等のいずれの剤形であってもよい。 The serotonin secretagogue according to the present embodiment may be in any form such as a solid (for example, a powder obtained by freeze-drying), a liquid (a water-soluble or fat-soluble solution or suspension), and a paste. And any dosage form such as powders, pills, granules, tablets, syrups, troches, capsules and the like.
上述の各種製剤は、有効成分である上記菌株の菌体又はその処理物のみからなるものであってもよく、例えば、当該菌株の菌体又はその処理物を上記剤形に成形することによって調製することができる。上述の各種製剤はまた、上記有効成分と、薬学的に許容される添加剤（賦形剤、結合剤、滑沢剤、崩壊剤、乳化剤、界面活性剤、基剤、溶解補助剤、懸濁化剤等）とを混和し、成形することによって調製することもできる。この場合の上記有効成分の含有量は、製剤全量を基準として、０．５〜５０質量％である。 The above-mentioned various preparations may be composed of only the cells of the above-mentioned strain which is an active ingredient or a processed product thereof, for example, prepared by molding the cells of the strain or the processed product thereof into the above-mentioned dosage form. can do. The above-mentioned various preparations may also contain the above-mentioned active ingredient and pharmaceutically acceptable additives (excipient, binder, lubricant, disintegrant, emulsifier, surfactant, base, solubilizer, suspension) And a molding agent. In this case, the content of the active ingredient is 0.5 to 50% by mass based on the total amount of the preparation.
例えば、賦形剤としては、ラクトース、スクロース、デンプン、デキストリン等が挙げられる。結合剤としては、ポリビニルアルコール、アラビアゴム、トラガント、ゼラチン、ヒドロキシプロピルメチルセルロース、ヒドロキシプロピルセルロース、カルボキシメチルセルロースナトリウム、ポリビニルピロリドン等が挙げられる。滑沢剤としては、ステアリン酸マグネシウム、ステアリン酸カルシウム、タルク等が挙げられる。崩壊剤としては、結晶セルロース、寒天、ゼラチン、炭酸カルシウム、炭酸水素ナトリウム、デキストリン等が挙げられる。乳化剤又は界面活性剤としては、Ｔｗｅｅｎ６０、Ｔｗｅｅｎ８０、Ｓｐａｎ８０、モノステアリン酸グリセリン等が挙げられる。基剤としては、セトステアリルアルコール、ラノリン、ポリエチレングリコール、米糠油、魚油（ＤＨＡ、ＥＰＡ等）、オリーブ油等が挙げられる。溶解補助剤としては、ポリエチレングリコール、プロピレングリコール、炭酸ナトリウム、クエン酸ナトリウム、Ｔｗｅｅｎ８０等が挙げられる。懸濁化剤としては、Ｔｗｅｅｎ６０、Ｔｗｅｅｎ８０、Ｓｐａｎ８０、モノステアリン酸グリセリン、ポリビニルアルコール、ポリビニルピロリドン、メチルセルロース、ヒドロキシメチルセルロース、アルギン酸ナトリウム等が挙げられる。
For example, excipients include lactose, sucrose, starch, dextrin and the like. Examples of the binder include polyvinyl alcohol, gum arabic, tragacanth, gelatin, hydroxypropylmethylcellulose, hydroxypropylcellulose, sodium carboxymethylcellulose, and polyvinylpyrrolidone. Lubricants include magnesium stearate, calcium stearate, talc and the like. Disintegrators include crystalline cellulose, agar, gelatin, calcium carbonate, sodium bicarbonate, dextrin and the like. Examples of the emulsifier or the surfactant include
本実施形態に係るセロトニン分泌促進剤は、ヒトに投与しても、非ヒト哺乳動物に投与してもよい。投与量及び投与方法は、投与される個体の状態、年齢等に応じて適宜決定することができる。投与方法（投与経路）としては、例えば、注腸投与、経口投与、経管栄養、経静脈投与が挙げられる。好適な投与方法としては、例えば、経口投与が挙げられる。投与量及び投与方法の一例として、本実施形態に係るセロトニン分泌促進剤を有効成分量が０．５ｍｇ〜５００ｍｇとなる量を１日１回経口で投与する方法を挙げることができる。 The serotonin secretagogue according to the present embodiment may be administered to a human or a non-human mammal. The dose and the administration method can be appropriately determined depending on the condition, age, etc. of the individual to be administered. Examples of the administration method (administration route) include enema administration, oral administration, tube feeding, and intravenous administration. Suitable administration methods include, for example, oral administration. As an example of the dosage and the administration method, there can be mentioned a method in which the serotonin secretagogue according to this embodiment is orally administered once a day in an amount such that the amount of the active ingredient is 0.5 mg to 500 mg.
本実施形態に係るセロトニン分泌促進剤は、医薬品成分、飲食品成分、飲食品添加物、飼料成分、飼料添加物等として使用することができる。 The serotonin secretagogue according to the present embodiment can be used as a pharmaceutical component, a food or drink component, a food or drink additive, a feed component, a feed additive or the like.
例えば、本実施形態に係るセロトニン分泌促進剤は、水、清涼飲料水、果汁飲料、乳飲料、アルコール飲料、パン類、麺類、米類、豆腐、乳製品、醗酵食品、発酵乳、醤油、味噌、菓子類等の飲食品への添加物として使用することができる。これらの飲食品は、当分野で通常使用される他の添加物を更に含有してもよく、そのような添加物としては、例えば、苦味料、香料、リンゴファイバー、大豆ファイバー、肉エキス、黒酢エキス、ゼラチン、コーンスターチ、蜂蜜、動植物油脂；グルコース、フルクトース等の単糖類；スクロース等の二糖類；デキストロース、デンプン等の多糖類；エリスリトール、キシリトール、ソルビトール、マンニトール等の糖アルコール類；ビタミンＣ等のビタミン類、が挙げられる。本実施形態に係るセロトニン分泌促進剤はまた、特定保健用食品、特別用途食品、栄養補助食品、健康食品、機能性食品、病者用食品等の成分として使用することもできる。本実施形態に係るセロトニン分泌促進剤を含有する飲食品は、本実施形態に係る乳酸菌群より選択される菌株で牛乳、脱脂乳、豆乳等を発酵させて得られる発酵物であってもよい。 For example, the serotonin secretagogue according to the present embodiment is water, soft drink, fruit juice drink, milk drink, alcoholic drink, breads, noodles, rice, tofu, dairy products, fermented food, fermented milk, soy sauce, miso , Can be used as an additive to foods and drinks such as confectionery. These foods and drinks may further contain other additives commonly used in the art, such as bitterness, flavoring, apple fiber, soy fiber, meat extract, black Vinegar extract, gelatin, corn starch, honey, animal and vegetable fats and oils; monosaccharides such as glucose and fructose; disaccharides such as sucrose; polysaccharides such as dextrose and starch; sugar alcohols such as erythritol, xylitol, sorbitol, and mannitol; Vitamins. The serotonin secretagogue according to the present embodiment can also be used as a component for foods for specified health use, special use foods, dietary supplements, health foods, functional foods, foods for patients, and the like. The food or drink containing the serotonin secretagogue according to the present embodiment may be a fermented product obtained by fermenting milk, skim milk, soy milk, or the like with a strain selected from the lactic acid bacteria group according to the present embodiment.
以下、実施例等に基づいて本発明をより具体的に説明する。 Hereinafter, the present invention will be described more specifically based on examples and the like.
〔実施例１：ＳＢＬ８８株のセロトニン分泌促進作用〕
＜菌体処理物の調製＞
ＳＢＬ８８株をＭＲＳ液体培地１０ｍＬ中で、１〜２日間、３０℃、静置培養した。培養液を１０，０００ｒｐｍで１０分間遠心分離し、菌体の沈殿を滅菌生理食塩水（１０ｍＬ）で２回洗浄した。得られた菌体は、５ｍＬの滅菌水に懸濁し、凍結乾燥させた。凍結乾燥した菌体を１０ｍｇ／ｍＬになるように滅菌水に懸濁した後、１０５℃で１０分間加熱処理し、菌体溶液を得た。
[Example 1: Serotonin secretion promoting action of SBL88 strain]
<Preparation of treated cells>
The SBL88 strain was statically cultured at 30 ° C. for 1 to 2 days in 10 mL of an MRS liquid medium. The culture was centrifuged at 10,000 rpm for 10 minutes, and the cell precipitate was washed twice with sterile physiological saline (10 mL). The obtained cells were suspended in 5 mL of sterilized water and freeze-dried. The freeze-dried cells were suspended in sterilized water to a concentration of 10 mg / mL, and then heat-treated at 105 ° C for 10 minutes to obtain a cell solution.
＜大腸細胞ＣＯＬＯ−３２０ＤＭの培養＞
ＣＯＬＯ−３２０ＤＭ（ＪＣＲＢ０２２５）は（財）ヒューマンサイエンス振興財団より購入した。１０％ＦＢＳ含有Ｄ’ＭＥＭ培地を使用し、５％ＣＯ２インキュベーター内で、ＣＯＬＯ−３２０ＤＭを３日おきに継代しながら培養した。
<Culture of colon cell COLO-320DM>
COLO-320DM (JCRB0225) was purchased from Human Science Promotion Foundation. Using D'MEM medium containing 10% FBS, COLO-320DM was cultured in a 5% CO 2 incubator while subcultured every three days.
＜ＣＯＬＯ−３２０ＤＭのセロトニン分泌促進アッセイ＞
１０％ＦＢＳ含有Ｄ’ＭＥＭ培地で３日間培養したＣＯＬＯ−３２０ＤＭ培養液を、１，０００ｒｐｍで５分間遠心分離して細胞を回収した。回収した細胞を、約２×１０５ｃｅｌｌｓ／ｍＬとなるように無血清ＲＰＭＩ１６４０培地に懸濁して２４穴マイクロプレートに播種した後（０．５ｍＬ／ウェル）、菌体の濃度が１００質量ｐｐｍとなるように菌体溶液を添加した（１％添加）。５％ＣＯ２インキュベーター内で２時間培養した後、培養液を遠心分離して菌体及び細胞を除去した。得られた上清中のセロトニン濃度を、セロトニンＥＩＡキット（品番９００−１７５、コスモバイオ）を使用して測定した。菌体を添加せずに同様の操作を行った対照（菌体非添加）との比較から、ＳＢＬ８８株のセロトニン分泌促進作用を評価した。
<Serotonin secretion promotion assay of COLO-320DM>
A COLO-320DM culture solution cultured in a D'MEM medium containing 10% FBS for 3 days was centrifuged at 1,000 rpm for 5 minutes to collect cells. The collected cells were suspended in a serum-free RPMI1640 medium to a concentration of about 2 × 10 5 cells / mL and seeded on a 24-well microplate (0.5 mL / well). A bacterial cell solution was added (1% addition). After culturing for 2 hours in a 5% CO 2 incubator, the culture was centrifuged to remove cells and cells. The serotonin concentration in the obtained supernatant was measured using a serotonin EIA kit (Part No. 900-175, Cosmo Bio). The serotonin secretion promoting effect of the SBL88 strain was evaluated by comparison with a control (without adding the cells) in which the same operation was performed without adding the cells.
図２に、セロトニン分泌促進アッセイの結果を示す。図２中、Ｂｌａｎｋは、菌体非添加のウェル中のセロトニン濃度（ｎＭ／ウェル）の測定結果を示す。図２から明らかなように、ＳＢＬ８８株の菌体を添加することによって、ＣＯＬＯ−３２０ＤＭのセロトニン分泌が強く促進された（図２）。すなわち、ＳＢＬ８８株は、セロトニン分泌を促進する作用を有する。 FIG. 2 shows the results of the serotonin secretion promotion assay. In FIG. 2, Blank shows the measurement results of the serotonin concentration (nM / well) in the wells to which no cells were added. As is evident from FIG. 2, the addition of cells of the SBL88 strain strongly promoted the serotonin secretion of COLO-320DM (FIG. 2). That is, the SBL88 strain has an action of promoting serotonin secretion.
〔実施例２：ＳＢＬ８８株の自律神経への作用〕
ＳＢＬ８８株の胃迷走（副交感）神経活動、皮膚動脈交感神経活動及び褐色脂肪組織交感神経活動への作用を解析した。
[Example 2: Action of SBL88 strain on autonomic nervous system]
The effects of the SBL88 strain on gastric vagus (parasympathetic) nerve activity, cutaneous artery sympathetic nerve activity, and brown adipose tissue sympathetic nerve activity were analyzed.
＜菌体処理物の調製＞
ＳＢＬ８８株を培地（マルトース２質量％，酵母エキス１．４質量％，酢酸ナトリウム０．５質量％，硫酸マンガン０．００５質量％，ｐＨ６．５〜７．０）に植菌し、３０℃で１日間静置培養した。得られた培養液（約８×１０８ｃｆｕ／ｍＬ）を、８，０００ｒｐｍで１０分間遠心分離して菌体を回収した。回収した菌体を蒸留水に懸濁し、８，０００ｒｐｍで１０分遠心分離して菌体を回収した。この操作を２度繰り返した後、蒸留水に懸濁した菌体を１０５℃で１０分間加熱処理した後、凍結乾燥して加熱処理菌体粉末を得た。
<Preparation of treated cells>
The SBL88 strain was inoculated into a culture medium (
＜胃迷走神経活動、皮膚動脈交感神経活動及び褐色脂肪組織交感神経活動の測定＞
１２時間毎の明暗周期（８時〜２０時まで点灯）下で、２４℃の恒温動物室にて１週間以上飼育した体重約３００ｇのＷｉｓｔａｒ系雄ラット（約９週齢）を試験に使用した。試験当日は３時間絶食させた後、ウレタン麻酔し、十二指腸に菌体投与用のカニューレを挿入した。その後、胃迷走神経の遠心枝、右大腿部の皮膚動脈交感神経の遠心枝、又は背甲間の褐色脂肪組織交感神経の遠心枝を銀電極で吊り上げて、これらの神経の電気活動を測定した。測定値が落ち着いた段階（１３時頃）でカニューレを使用して、加熱処理菌体粉末の懸濁液１ｍＬ（８×１０７ｃｆｕ／ｍＬ）を十二指腸に投与し、胃迷走神経活動、皮膚動脈交感神経活動又は褐色脂肪組織交感神経活動の変化を測定した。対照として、加熱処理菌体粉末の懸濁液１ｍＬに代えて水１ｍＬを十二指腸に投与し、これらの神経活動の変化を測定した。測定の間、体温維持装置で体温（ラット直腸温）を３５．０±０．５℃に保った。神経活動の測定データは、５分間毎の５秒あたりの発火頻度（ｐｕｌｓｅ／５秒）の平均値をとり、菌体（又は水）投与前５分間の平均値（０分値）を１００％とした百分率で表した。なお、測定データから平均値±標準誤差を計算すると共に、群としての統計学的有意差の検定を、反復測定分散分析（ＡＮＯＶＡ ｗｉｔｈ ｒｅｐｅａｔｅｄ ｍｅａｓｕｒｅｓ）により行った。また、菌体（又は水）投与前（０分）の電気活動の測定値（絶対値）間の統計学的有意差の検定は、マン・ホイットニーのＵ検定（Ｍａｎｎ−Ｗｈｉｔｎｅｙ Ｕ−ｔｅｓｔ）により行った。なお、各群それぞれ３匹のラットを用いた。
<Measurement of gastric vagus nerve activity, cutaneous artery sympathetic nerve activity, and brown adipose tissue sympathetic nerve activity>
Male Wistar rats (approximately 9 weeks old) weighing about 300 g and bred in a constant temperature animal room at 24 ° C. for at least one week under a 12-hour light / dark cycle (lights on from 8:00 to 20:00) were used for the test. . After fasting for 3 hours on the test day, urethane was anesthetized, and a cannula for administration of bacterial cells was inserted into the duodenum. Then, the distal branch of the gastric vagus nerve, the distal branch of the cutaneous artery sympathetic nerve in the right thigh, or the distal branch of the brown adipose tissue sympathetic nerve between the scapulas are lifted with silver electrodes, and the electrical activity of these nerves is measured. did. At the stage when the measured values were settled (around 13:00), 1 mL (8 × 10 7 cfu / mL) of the suspension of the heat-treated bacterial cell powder was administered to the duodenum using a cannula, and gastric vagus nerve activity, cutaneous artery Changes in sympathetic activity or brown adipose tissue sympathetic activity were measured. As a control, 1 mL of water was administered to the duodenum instead of 1 mL of the suspension of the heat-treated microbial cell powder, and the changes in these nerve activities were measured. During the measurement, the body temperature (rat rectal temperature) was maintained at 35.0 ± 0.5 ° C. with a body temperature maintaining device. The measurement data of nerve activity is the average value of the firing frequency (pulse / 5 seconds) per 5 seconds every 5 minutes, and the average value (0 minutes value) of 5 minutes before the administration of the bacteria (or water) is 100%. And expressed as a percentage. The mean ± standard error was calculated from the measured data, and the statistical significance of the group was tested by repeated measures analysis of variance (ANOVA with repeated measures). In addition, the test of the statistically significant difference between the measured values (absolute values) of the electric activity before (0 minute) administration of the bacterial cells (or water) was performed by the Mann-Whitney U test (Mann-Whitney U-test). went. In addition, three rats were used for each group.
図３に、胃迷走神経活動（ｇａｓｔｒｉｃ ｖａｇａｌ ｎｅｒｖｅ ａｃｉｔｉｖｉｔｙ：ＧＶＮＡ）の測定結果を示す。ＳＢＬ８８株の菌体を投与した群（以下「ＳＢＬ８８群」という。）では、投与直後からＧＶＮＡが上昇し続け、投与６０分後には３２５．８％に達した（図３）。一方、対照として水を投与した群（以下「対照群」という。）では、ＧＶＮＡはほとんど変化せず、最低値９７．６％（投与１５分後）及び最高値１１１．８％（投与５５分後）の間でほぼ一定の値を維持した（図３）。 FIG. 3 shows the results of measurement of gastric vagal nerve activity (GVNA). In the group to which the cells of the SBL88 strain were administered (hereinafter, referred to as “SBL88 group”), the GVNA continued to increase immediately after the administration, and reached 325.8% 60 minutes after the administration (FIG. 3). On the other hand, in the group to which water was administered as a control (hereinafter referred to as “control group”), GVNA hardly changed, and the minimum value was 97.6% (15 minutes after administration) and the maximum value was 111.8% (55 minutes after administration). The value was kept almost constant during (after) (FIG. 3).
投与５分後から９０分後までの間のＧＶＮＡを、対照群及びＳＢＬ８８群の２群間で分散分析（ＡＮＯＶＡ）法により統計学的に検討した結果、ＳＢＬ８８群のＧＶＮＡは対照群のＧＶＮＡより有意に（Ｐ＜０．０００５，Ｆ＝３１．０（反復測定分散分析））高かった。また、これら２群の菌体（又は水）投与前（０分）の電気活動は、対照群が１３０±１８、ＳＢＬ８８群が２５３±３２であった。マン・ホイットニーのＵ検定の結果、これら２群の菌体（又は水）投与前（０分）の電気活動には、有意差は認められなかった。 The GVNA from 5 minutes to 90 minutes after administration was statistically examined by the analysis of variance (ANOVA) method between the control group and the SBL88 group. As a result, the GVNA of the SBL88 group was higher than that of the control group. Significantly (P <0.0005, F = 31.0 (repeated measures ANOVA)). The electrical activity of the two groups before the administration of the bacterial cells (or water) (0 min) was 130 ± 18 in the control group and 253 ± 32 in the SBL88 group. As a result of the Mann-Whitney U test, no significant difference was observed in the electrical activity of these two groups before (0 minute) administration of the bacterial cells (or water).
すなわち、ＳＢＬ８８株は胃迷走（副交感）神経の活動を亢進する作用を有する。この胃迷走神経亢進作用により、整腸効果、並びに便通及び食欲を促進する効果が期待できる。 That is, the SBL88 strain has the effect of enhancing the activity of the gastric vagus (parasympathetic) nerve. This gastric vagal hyperactivity can be expected to have an intestinal effect and an effect of promoting bowel movement and appetite.
図４に、皮膚動脈交感神経活動（ｃｕｔａｎｅｏｕｓ ａｒｔｅｒａｌ ｓｙｍｐａｔｈｅｔｉｃ ｎｅｒｖｅ ａｃｉｔｉｖｉｔｙ：ＣＡＳＮＡ）の測定結果を示す。ＳＢＬ８８群は、投与直後ＣＡＳＮＡがやや上昇し、投与５分後に最高値１２４．４％に達したものの、その後はＣＡＳＮＡが低下し続け、投与６０分後には６３．３％に達した（図４）。一方、対照群では、投与２５分後以降ＣＡＳＮＡが徐々に上昇し、投与６０分後には１２２．４％に達した（図４）。 FIG. 4 shows the measurement results of cutaneous arterial sympathetic nerve activity (CASNA). In the SBL88 group, CASNA slightly increased immediately after administration, and reached a maximum of 124.4% 5 minutes after administration, but thereafter CASNA continued to decrease, and reached 63.3% 60 minutes after administration (FIG. 4). ). On the other hand, in the control group, CASNA gradually increased 25 minutes after administration, and reached 122.4% 60 minutes after administration (FIG. 4).
投与５分後から９０分後までの間のＣＡＳＮＡを、対照群及びＳＢＬ８８群の２群間で、ＡＮＯＶＡ法により統計学的に検討した結果、ＳＢＬ８８群のＣＡＳＮＡは対照群のＣＡＳＮＡより有意に（Ｐ＜０．０００５，Ｆ＝２９．０（反復測定分散分析））低かった。また、これら２群の菌体（又は水）投与前（０分）の電気活動は、対照群が３１６±７０、ＳＢＬ８８群が２５０±４であった。マン・ホイットニーのＵ検定の結果、これら２群の菌体（又は水）投与前（０分）の電気活動には、有意差は認められなかった。 As a result of statistically examining the CASNA from 5 minutes to 90 minutes after administration between the control group and the SBL88 group by the ANOVA method, the CASNA of the SBL88 group was significantly more significant than the CASNA of the control group ( P <0.0005, F = 29.0 (repeated analysis of variance)). The electrical activity of these two groups before administration of the bacterial cells (or water) (0 min) was 316 ± 70 in the control group and 250 ± 4 in the SBL88 group. As a result of the Mann-Whitney U test, no significant difference was observed in the electrical activity of these two groups before (0 minute) administration of the bacterial cells (or water).
すなわち、ＳＢＬ８８株は皮膚動脈交感神経の活動を抑制する作用を有する（投与６０分後において、投与前の約６０％にまで神経活動を抑制した）。この皮膚動脈交感神経抑制作用により、皮膚への血流を増加させて皮膚の保湿度を高めるという美容効果、及び入眠を促進する効果が期待できる。 That is, the SBL88 strain has an effect of suppressing the activity of the cutaneous artery sympathetic nerve (60 minutes after administration, the nerve activity was suppressed to about 60% of that before administration). By this cutaneous artery sympathetic nerve-suppressing action, a cosmetic effect of increasing blood flow to the skin to increase the moisture retention of the skin and an effect of promoting sleep onset can be expected.
図５に、褐色脂肪組織交感神経活動（ｂｒｏｗｎ ａｄｉｐｏｓｅ ｔｉｓｓｕｅ ｓｙｍｐａｔｈｅｔｉｃ ｎｅｒｖｅ ａｃｉｔｉｖｉｔｙ：ＢＡＴ−ＳＮＡ）の測定結果を示す。ＳＢＬ８８群は、投与直後からＢＡＴ−ＳＮＡが上昇し続け、投与５５分後には１６７．２％に達した（図５）。一方、対照群では、ＢＡＴ−ＳＮＡはほとんど変化せず、最低値９１．０％（投与１５分後）及び最高値１０１．１％（投与５５分後）の間でほぼ一定の値を維持した（図５）。 FIG. 5 shows the results of measurement of brown adipose tissue sympathetic neural activity (BAT-SNA). In the SBL88 group, BAT-SNA continued to increase immediately after administration, and reached 167.2% 55 minutes after administration (FIG. 5). On the other hand, in the control group, BAT-SNA hardly changed, and maintained a substantially constant value between the minimum value of 91.0% (15 minutes after administration) and the maximum value of 101.1% (55 minutes after administration). (FIG. 5).
投与５分後から９０分後までの間のＢＡＴ−ＳＮＡを、対照群及びＳＢＬ８８群の２群間で、ＡＮＯＶＡ法により統計学的に検討した結果、ＳＢＬ８８群のＢＡＴ−ＳＮＡは対照群のＢＡＴ−ＳＮＡより有意に（Ｐ＜０．０００５，Ｆ＝４８．６（反復測定分散分析））高かった。また、これら２群の菌体（又は水）投与前（０分）の電気活動は、対照群が１８３±１９、ＳＢＬ８８群が２４３±９であった。マン・ホイットニーのＵ検定の結果、これら２群の菌体（又は水）投与前（０分）の電気活動には、有意差は認められなかった。 The BAT-SNA from 5 minutes to 90 minutes after administration was statistically examined by the ANOVA method between the control group and the SBL88 group. As a result, the BAT-SNA of the SBL88 group was found to be BAT of the control group. Significantly (P <0.0005, F = 48.6 (repeated measures analysis of variance)) higher than -SNA. In addition, the electrical activity of these two groups before administration of bacterial cells (or water) (0 minutes) was 183 ± 19 in the control group and 243 ± 9 in the SBL88 group. As a result of the Mann-Whitney U test, no significant difference was observed in the electrical activity of these two groups before (0 minute) administration of the bacterial cells (or water).
すなわち、ＳＢＬ８８株は褐色脂肪組織交感神経の活動を亢進する作用を有する。この褐色脂肪組織交感神経亢進作用により、褐色脂肪組織でのエネルギー消費及び熱産生を高める効果が期待できる。 That is, the SBL88 strain has an action of enhancing the activity of brown adipose tissue sympathetic nerve. The effect of enhancing energy consumption and heat production in brown adipose tissue can be expected by the action of enhancing brown adipose tissue sympathetic nerve.
〔参考例１：胃迷走神経亢進作用に対するセロトニン受容体阻害剤の影響〕
ＳＢＬ８８株の胃迷走神経亢進作用に関して、セロトニン受容体阻害剤による影響を解析した。
[Reference Example 1: Effect of serotonin receptor inhibitor on gastric vagal hyperactivity]
The effect of a serotonin receptor inhibitor on the gastric vagal hyperactivity of the SBL88 strain was analyzed.
＜菌体処理物の調製＞
実施例２と同様にして、ＳＢＬ８８株の加熱処理菌体粉末を得た。
<Preparation of treated cells>
In the same manner as in Example 2, heat-treated bacterial cell powder of SBL88 strain was obtained.
＜セロトニン受容体阻害剤の影響＞
１２時間毎の明暗周期（８時〜２０時まで点灯）下で、２４℃の恒温動物室にて１週間以上飼育した体重約３００ｇのＷｉｓｔａｒ系雄ラット（約９週齢）を試験に使用した。試験当日は３時間絶食させた後、ウレタン麻酔し、十二指腸に菌体投与用のカニューレを挿入した。その後、胃迷走神経の遠心枝を銀電極で吊り上げて、胃迷走神経の電気活動を測定した。測定値が落ち着いた段階（１３時頃）でカニューレを使用して、加熱処理菌体粉末の懸濁液１ｍＬ（８×１０７ｃｆｕ／ｍＬ）を十二指腸に投与した。なお、菌体投与の５分前に、ウレタン麻酔下で、頚静脈にカニューレを挿入し、０．１ｍＬのセロトニン受容体阻害剤（後述のセロトニン受容体アンタゴニスト）溶液、又は当該溶液の溶媒を静脈内に投与した。なお、各群それぞれ１匹のラットを用いた。
<Effect of serotonin receptor inhibitor>
Male Wistar rats (approximately 9 weeks old) weighing about 300 g and bred in a constant temperature animal room at 24 ° C. for at least one week under a 12-hour light / dark cycle (lights on from 8:00 to 20:00) were used for the test. . After fasting for 3 hours on the test day, urethane was anesthetized, and a cannula for administration of bacterial cells was inserted into the duodenum. Thereafter, the efferent branch of the gastric vagus nerve was lifted with a silver electrode, and the electrical activity of the gastric vagus nerve was measured. At the stage when the measured values were settled (around 13:00), 1 mL (8 × 10 7 cfu / mL) of the suspension of the heat-treated bacterial cell powder was administered to the duodenum using a cannula. Five minutes before the administration of the bacterial cells, a cannula was inserted into the jugular vein under urethane anesthesia, and a 0.1 mL serotonin receptor inhibitor (serotonin receptor antagonist described later) solution or a solvent for the solution was injected into the vein. Was administered within. One rat was used for each group.
セロトニン受容体阻害剤：
Ｋｅｔａｎｓｅｒｉｎｅ（シグマ社製，５−ＨＴ２Ａアンタゴニスト：生理食塩水に溶解させ、１０μｇ／ｋｇを静脈投与）
Ｇｒａｎｉｓｅｔｒｏｎ（シグマ社製，５−ＨＴ３アンタゴニスト：生理食塩水に溶解させ、１０μｇ／ｋｇを静脈投与）
ＧＲ１１３８０８（シグマ社製，５−ＨＴ４アンタゴニスト：ジメチルスルホキシド（ＤＭＳＯ）に溶解させ、１０μｇ／ｋｇ及び１００μｇ／ｋｇを静脈投与）
Serotonin receptor inhibitors:
Ketanserine (Sigma, 5-HT2A antagonist: dissolved in physiological saline and intravenously administered at 10 μg / kg)
Granisetron (Sigma, 5-HT3 antagonist: dissolved in physiological saline, and intravenously administered at 10 μg / kg)
GR113808 (Sigma, 5-HT4 antagonist: dissolved in dimethylsulfoxide (DMSO) and intravenously administered at 10 μg / kg and 100 μg / kg)
測定の間、体温維持装置で体温（ラット直腸温）を３５．０±０．５℃に保った。神経活動の測定データは、５分間毎の５秒あたりの発火頻度（ｐｕｌｓｅ／５秒）の平均値をとり、菌体投与前５分間の平均値（０分値）を１００％とした百分率で表した。 During the measurement, the body temperature (rat rectal temperature) was maintained at 35.0 ± 0.5 ° C. with a body temperature maintaining device. The measurement data of the nerve activity was the average value of the firing frequency (pulse / 5 seconds) per 5 seconds every 5 minutes, and the percentage was defined as 100% with the average value (0 minutes value) 5 minutes before the administration of the bacterial cells. expressed.
図６に、胃迷走神経活動（ＧＶＮＡ）の測定結果を示す。セロトニン受容体５−ＨＴ３に対するアンタゴニストであるＧｒａｎｉｓｅｔｒｏｎを直前に投与することで、ＳＢＬ８８株の胃迷走神経亢進作用が顕著に阻害された（図６（Ａ））。また、セロトニン受容体５−ＨＴ４に対するアンタゴニストであるＧＲ１１３８０８を高濃度（１００μｇ／ｋｇ）で投与した場合にも同様に、胃迷走神経亢進作用が阻害された（図６（Ｂ））。この結果は、ＳＢＬ８８株の胃迷走神経亢進作用は、セロトニンを介した作用であることを示している。 FIG. 6 shows the measurement results of gastric vagus nerve activity (GVNA). Immediately before administration of Granisetron, an antagonist to serotonin receptor 5-HT3, markedly inhibited the gastric vagus nerve enhancing effect of SBL88 strain (FIG. 6 (A)). Similarly, when GR113808, which is an antagonist to serotonin receptor 5-HT4, was administered at a high concentration (100 μg / kg), the gastric vagus nerve-enhancing effect was similarly inhibited (FIG. 6 (B)). This result indicates that the gastric vagal hyperactivity of the SBL88 strain is a serotonin-mediated effect.
また、５−ＨＴ３受容体は抹消神経及び最終野で、５−ＨＴ４受容体は海馬及び胃腸管で、５−ＨＴ２Ａ受容体は血小板、平滑筋及び小脳皮質で発現していることが知られている。これらセロトニン受容体の発現部位と、セロトニン受容体阻害剤による胃迷走神経亢進作用の阻害（図６）との関係から、ＳＢＬ８８株の投与により腸管上皮細胞（例：ＥＣ細胞等）がセロトニンを分泌し（ＳＢＬ８８株のセロトニン分泌促進作用）、分泌されたセロトニンにより腸管の末梢神経（５−ＨＴ３受容体）が興奮して脳が刺激を受け、脳から各臓器に繋がる自律神経系へ指令が出されるものと考えられる。 It is known that 5-HT3 receptor is expressed in peripheral nerves and terminal areas, 5-HT4 receptor is expressed in hippocampus and gastrointestinal tract, and 5-HT2A receptor is expressed in platelets, smooth muscle and cerebellar cortex. I have. Due to the relationship between the expression site of these serotonin receptors and the inhibition of gastric vagus nerve enhancing action by serotonin receptor inhibitors (FIG. 6), intestinal epithelial cells (eg, EC cells etc.) secrete serotonin by administration of SBL88 strain. Then, the secreted serotonin excites the peripheral nerves (5-HT3 receptor) of the intestinal tract to stimulate the brain, and the brain issues a command to the autonomic nervous system connected to each organ. It is considered to be.
〔実施例３：他の乳酸菌株によるセロトニン分泌促進作用〕
各種乳酸菌及びビフィズス菌の菌体調製は、実施例１の＜菌体処理物の調製＞と同様に行った。また、それら菌体調製液について、＜ＣＯＬＯ−３２０ＤＭのセロトニン分泌促進アッセイ＞を実施例１と同様に行った。その結果を図７及び８並びに表１及び２に示した。表１及び２中、セロトニン濃度が０．０のものは、測定値が検出限界（３ｎＭ／ウェル以下）以下であったことを意味する。
[Example 3: Serotonin secretion promoting action by other lactic acid bacteria strains]
Preparation of cells of various lactic acid bacteria and bifidobacteria was performed in the same manner as in <Preparation of treated cells> in Example 1. In addition, <Serotonin secretion promotion assay of COLO-320DM> was performed on the cell suspensions in the same manner as in Example 1. The results are shown in FIGS. 7 and 8 and Tables 1 and 2. In Tables 1 and 2, a serotonin concentration of 0.0 means that the measured value was below the detection limit (3 nM / well or less).
図７及び８中の略号と乳酸菌及びビフィズス菌との対応を表１及び２に示す。
ラクトバチラス・デルブリッキィー、ラクトバチラス・アシドフィルス（ａｃｉｄｏｐｈｉｌｕｓ）、ラクトバチラス・ガセリ（ｇａｓｓｅｒｉ）、ラクトバチラス・ジョンソニー（ｊｏｈｎｓｏｎｉｉ）等のラクトバチラス・デルブリッキィーグループに属する乳酸菌等には、セロトニン分泌促進作用は認められなかった（図７）。 Lactobacillus belonging to the Lactobacillus delbrickii, Lactobacillus acidulophilus (acidophilus), Lactobacillus gasseri (gasseri), Lactobacillus johnsonii (johnsonii), and other lactic acid bacteria belonging to the Lactobacillus delbrickii group, etc., do not show a serotonin secretion promoting effect. (FIG. 7).
一方、ラクトバチラス・デルブリッキィーグループに属する乳酸菌以外のラクトバチラス属に属する乳酸菌には、セロトニン分泌促進作用が認められた（図８）。特に、ＳＢＬ８８株は、強いセロトニン分泌促進作用を有していた（図８）。 On the other hand, lactic acid bacteria belonging to the genus Lactobacillus other than the lactic acid bacteria belonging to the Lactobacillus delbrikii group showed a serotonin secretion promoting effect (FIG. 8). In particular, the SBL88 strain had a strong serotonin secretion promoting effect (FIG. 8).
〔実施例４：ＳＢＬ８８株の血流量への作用〕
＜菌体処理物の調製＞
実施例２と同様にして、ＳＢＬ８８株の加熱処理菌体粉末を得た。
[Example 4: Effect on blood flow of SBL88 strain]
<Preparation of treated cells>
In the same manner as in Example 2, heat-treated bacterial cell powder of SBL88 strain was obtained.
＜血流量の測定＞
１２時間毎の明暗周期（８時〜２０時まで点灯）下で、２４℃の恒温動物室にて１週間飼育した体重約３００ｇのＷｉｓｔａｒ系雄ラット（約９週齢）を試験に使用した。試験当日は３時間絶食させた後、ウレタン麻酔し、十二指腸に菌体投与用のカニューレを挿入した。その後、ラットの尾の背部表面の起始部に近い所にレーザー血流計（ＡＬＦ２１、アドバンス社製）のプローブ（径１ｃｍ）を外科用テープで固定し、血流の測定を開始した。測定値が安定した段階でカニューレを使用して、加熱処理菌体粉末の懸濁液１ｍＬ（８×１０７ｃｆｕ／ｍＬ）又は水１ｍＬを十二指腸に投与した。なお、各群それぞれ４匹のラットを用いた。
<Measurement of blood flow>
Male Wistar rats (approximately 9 weeks old) weighing about 300 g and bred in a constant temperature animal room at 24 ° C. for 1 week under a light-dark cycle every 12 hours (light on from 8:00 to 20:00) were used for the test. After fasting for 3 hours on the test day, urethane was anesthetized, and a cannula for administration of bacterial cells was inserted into the duodenum. Thereafter, a probe (diameter: 1 cm) of a laser blood flow meter (ALF21, manufactured by Advance Co., Ltd.) was fixed to the back surface of the tail of the rat near the origin by surgical tape, and measurement of blood flow was started. When the measured value was stabilized, 1 mL of the heat-treated bacterial cell powder suspension (8 × 10 7 cfu / mL) or 1 mL of water was administered to the duodenum using a cannula. In addition, each group used four rats.
血流量のデータはＰｏｗｅｒ−Ｌａｂ ａｎａｌｏｇ−ｔｏ−ｄｉｇｉｔａｌ ｃｏｎｖｅｒｔｅｒを用いて採取した。得られたデータから５分間毎の血流量（ｍＬ／分／組織１００ｇ）の平均値をとり、加熱処理菌体粉末の投与前５分間の平均値（０分値）を１００％とした百分率で表した。なお、測定データから平均値±標準誤差を計算すると共に、群としての統計学的有意差の検定を、反復測定分散分析により行った。また、菌体（又は水）投与前（０分）の血流量の測定値（絶対値）間の統計学的有意差の検定は、マン・ホイットニーのＵ検定により行った。 Blood flow data was collected using a Power-Lab analog-to-digital converter. From the obtained data, the average value of the blood flow rate (mL / min / 100 g of tissue) every 5 minutes was taken, and the average value (0 minute value) for 5 minutes before administration of the heat-treated bacterial cell powder was taken as 100%. expressed. The mean ± standard error was calculated from the measured data, and a test for statistical significance as a group was performed by repeated measures analysis of variance. In addition, a test for a statistically significant difference between measured values (absolute values) of blood flow before (0 minute) administration of bacterial cells (or water) was performed by the Mann-Whitney U test.
図９に、血流量（ラットの尾の皮膚血流量）の測定結果を示す。ＳＢＬ８８株の菌体を投与した群（以下「ＳＢＬ８８群」という。）では、投与直後に血流量がやや上昇し、投与１０分後には最高値の１１４．０％に達した（図９）。その後、血流量は徐々に低下したが、投与６０分後の血流量は９４．８％であった（図９）。一方、対照として水を投与した群（以下「対照群」という。）では、投与直後から血流量が徐々に低下し、投与３０分後には７１．７％にまで減少した。その後、血流量はゆっくりと低下し、投与５５分後には、６７．７％の最低値に達した（図９）。
FIG. 9 shows the measurement results of blood flow (rat skin blood flow at the tail). In the group to which the cells of the SBL88 strain were administered (hereinafter, referred to as “SBL88 group”), the blood flow slightly increased immediately after the administration, and reached 114.0% of the
投与５分後から６０分後までの間の血流量を、対照群及びＳＢＬ８８群の２群間で分散分析（ＡＮＯＶＡ）法により統計学的に検討した結果、ＳＢＬ８８群の血流量は対照群の血流量より有意に（Ｐ＜０．０００５，Ｆ＝１９１（反復測定分散分析））高かった。また、これら２群の菌体（又は水）投与前（０分）の血流量は、対照群が４．５２±０．７［ｍＬ／分／組織１００ｇ］、ＳＢＬ８８群が３．６２±０．５［ｍＬ／分／組織１００ｇ］であった。マン・ホイットニーのＵ検定の結果、これら２群の菌体（又は水）投与前（０分）の血流量には、有意差は認められなかった。 The blood flow from 5 minutes to 60 minutes after administration was statistically examined between the control group and the SBL88 group by analysis of variance (ANOVA). As a result, the blood flow in the SBL88 group was Significantly (P <0.0005, F = 191 (repeated measures analysis of variance)) higher than blood flow. The blood flow of these two groups before administration of bacterial cells (or water) (0 min) was 4.52 ± 0.7 [mL / min / 100 g of tissue] in the control group and 3.62 ± 0 in the SBL88 group. It was 0.5 [mL / min / 100 g of tissue]. As a result of the Mann-Whitney U test, no significant difference was observed in the blood flow before (0 minute) administration of the bacterial cells (or water) in these two groups.
実施例４の結果により、ＳＢＬ８８株による血流量増加作用（血流促進作用）が確認された。 From the results of Example 4, the blood flow increasing effect (blood flow promoting effect) of the SBL88 strain was confirmed.
〔実施例５：ＳＢＬ８８株の経皮水分蒸散量への作用〕
＜菌体処理物の調製＞
実施例２と同様にして、ＳＢＬ８８株の加熱処理菌体粉末を得た。
Example 5: Effect of SBL88 strain on transepidermal water loss
<Preparation of treated cells>
In the same manner as in Example 2, heat-treated bacterial cell powder of SBL88 strain was obtained.
＜経皮水分蒸散量の測定＞
１２時間毎の明暗周期（８時〜２０時まで点灯）下で、２４℃の恒温動物室にて１週間飼育した体重約３００ｇの雄性ＨＷＹヘアレスラットを試験に使用した。試験期間中、ラットには、加熱処理菌体粉末の懸濁液（８×１０７ｃｆｕ／ｍＬ）又は水を自由摂取させた。毎日１３時に、背中の部位における経皮水分蒸散量（ｔｒａｎｓｅｐｉｄｅｒｍａｌ ｗａｔｅｒ ｌｏｓｓ：ＴＥＷＬ）を、ケタミン麻酔下で、ＶａｐｏＭｅｔｅｒ Ｄｅｌｆｉｎｅ，Ｆｉｎｌａｎｄ）を用いて測定した。なお、各群それぞれ５匹のラットを用いた。
<Measurement of transepidermal water loss>
Male HWY hairless rats weighing about 300 g and bred in a constant temperature animal room at 24 ° C. for 1 week under a light-dark cycle every 12 hours (lights on from 8:00 to 20:00) were used for the test. During the test period, rats were allowed to freely receive a suspension of the heat-treated bacterial cell powder (8 × 10 7 cfu / mL) or water. At 13:00 every day, the transepidermal water loss (TEWL) at the site on the back was measured under ketamine anesthesia using VapoMeter Define, Finland. In addition, 5 rats were used for each group.
得られたデータから経皮水分蒸散量の平均値をとり、加熱処理菌体粉末の懸濁液、又は水の自由摂取開始前（０日目）の平均値を１００％とした百分率で表した。なお、測定データから平均値±標準誤差を計算すると共に、群としての統計学的有意差の検定を、反復測定分散分析により行った。また、自由摂取開始前（０日目）の経皮水分蒸散量の測定値（絶対値）間の統計学的有意差の検定は、マン・ホイットニーのＵ検定により行った。 The average value of the transepidermal water loss was obtained from the obtained data and expressed as a percentage with the average value before the start of free intake of water or suspension of the heat-treated microbial cell powder (day 0) as 100%. . The mean ± standard error was calculated from the measured data, and a test for statistical significance as a group was performed by repeated measures analysis of variance. In addition, a test for a statistically significant difference between the measured values (absolute values) of the transdermal water loss before the start of free intake (day 0) was performed by the Mann-Whitney U test.
図１０に、経皮水分蒸散量の測定結果を示す。対照として水を自由摂取させた群（以下「対照群」という。）では、ＴＥＷＬ値はわずかに低下したもののほとんど変化せず、試験開始から３日目の値が９７．３％であった（図１０）。これに対し、ＳＢＬ８８株の菌体懸濁液を自由摂取させた群（以下「ＳＢＬ８８群」という。）では、ＴＥＷＬ値が徐々に低下していき、試験開始から３日目には、７６．４％にまで低下した（図１０）。 FIG. 10 shows the measurement results of the transepidermal water loss. In the group to which water was freely ingested as a control (hereinafter referred to as “control group”), the TEWL value slightly decreased but hardly changed, and the value on the third day from the start of the test was 97.3% ( (FIG. 10). On the other hand, in the group to which the cell suspension of the SBL88 strain was freely ingested (hereinafter referred to as “SBL88 group”), the TEWL value gradually decreased. It decreased to 4% (FIG. 10).
自由摂取開後１日目から３日目までの間のＴＥＷＬ値を、対照群及びＳＢＬ８８群の２群間で分散分析（ＡＮＯＶＡ）法により統計学的に検討した結果、ＳＢＬ８８群のＴＥＷＬ値は対照群のＴＥＷＬの値より有意に（Ｐ＜０．０００５，Ｆ＝４６．１（反復測定分散分析））低かった。また、これら２群の自由摂取開始前（０日目）の経皮水分蒸散量は、対照群が１１．１±０．２［ｇ／ｍ２／時間］、ＳＢＬ８８群が１１．７±０．４［ｇ／ｍ２／時間］であった。マン・ホイットニーのＵ検定の結果、これら２群の自由摂取開始前（０日目）の経皮水分蒸散量には、有意差は認められなかった。 As a result of statistically examining the TEWL value from the first day to the third day after the free intake between the control group and the SBL88 group by the analysis of variance (ANOVA) method, the TEWL value of the SBL88 group was found to be It was significantly (P <0.0005, F = 46.1 (repeated measures analysis of variance)) significantly lower than the TEWL value of the control group. The transepidermal water loss of these two groups before the start of free intake (day 0) was 11.1 ± 0.2 [g / m 2 / hour] in the control group and 11.7 ± 0 in the SBL88 group. 0.4 [g / m 2 / hour]. As a result of the Mann-Whitney U test, there was no significant difference in the transepidermal water loss between these two groups before the start of free intake (day 0).
実施例５の結果により、ＳＢＬ８８株による経皮水分蒸散量低下作用（経皮水分蒸散抑制作用）が確認された。 From the results of Example 5, the effect of reducing the amount of transdermal water evaporation (the effect of suppressing transdermal water evaporation) by the SBL88 strain was confirmed.
〔参考例２：皮膚動脈交感神経抑制作用に対するセロトニン受容体阻害剤の影響〕
ＳＢＬ８８株の皮膚動脈交感神経抑制作用に関して、セロトニン受容体阻害剤による影響を解析した。
[Reference Example 2: Effect of serotonin receptor inhibitor on cutaneous artery sympathetic nerve inhibitory action]
The effect of the serotonin receptor inhibitor on the cutaneous artery sympathetic nerve inhibitory effect of the SBL88 strain was analyzed.
＜菌体処理物の調製＞
実施例２と同様にして、ＳＢＬ８８株の加熱処理菌体粉末を得た。
<Preparation of treated cells>
In the same manner as in Example 2, heat-treated bacterial cell powder of SBL88 strain was obtained.
＜セロトニン受容体阻害剤の影響＞
１２時間毎の明暗周期（８時〜２０時まで点灯）下で、２４℃の恒温動物室にて１週間以上飼育した体重約３００ｇのＷｉｓｔａｒ系雄ラット（約９週齢）を試験に使用した。試験当日は３時間絶食させた後、ウレタン麻酔し、頚静脈及び十二指腸に菌体投与用のカニーレを挿入した。その後、左大腿部の皮膚動脈交感神経の遠心枝を銀電極で吊り上げて、皮膚動脈交感神経の電気活動を測定した。測定値が落ち着いた段階（１３時頃）で、０．１ｍＬのセロトニン受容体阻害剤（上述のＧｒａｎｉｓｅｔｒｏｎ）又は０．１ｍＬの生理食塩水を静脈内に投与した。投与から５分後に加熱処理菌体粉末の懸濁液（８×１０７ｃｆｕ／ｍｌ）を十二指腸に投与した。なお、各群それぞれ３匹のラットを用いた。
<Effect of serotonin receptor inhibitor>
Male Wistar rats (approximately 9 weeks old) weighing about 300 g and bred in a constant temperature animal room at 24 ° C. for at least one week under a 12-hour light / dark cycle (lights on from 8:00 to 20:00) were used for the test. . On the day of the test, the animals were fasted for 3 hours, then anesthetized with urethane, and inserted into the jugular vein and duodenum with cannile for administration of bacterial cells. Thereafter, the distal branch of the cutaneous artery sympathetic nerve on the left thigh was lifted with a silver electrode, and the electrical activity of the cutaneous artery sympathetic nerve was measured. At the stage when the measured values were settled (around 13:00), 0.1 mL of a serotonin receptor inhibitor (Granisetron described above) or 0.1 mL of physiological saline was intravenously administered. Five minutes after the administration, a suspension of the heat-treated bacterial cell powder (8 × 10 7 cfu / ml) was administered to the duodenum. In addition, three rats were used for each group.
測定の間、体温維持装置で体温（ラット直腸温）を３５．０±０．５℃に保った。神経活動のデータは、５分間毎の５秒あたりの発火頻度（ｐｕｌｓｅ／５秒）の平均値をとり、菌体投与前５分間の平均値（０分値）を１００％とした百分率で表した。なお、測定データから平均値±標準誤差を計算すると共に、群としての統計学的有意差の検定を、反復測定分散分析により行った。また、菌体投与前（０分）の電気活動の絶対値の統計学的有意差の検定は、マン・ホイットニーのＵ検定により行った。 During the measurement, the body temperature (rat rectal temperature) was maintained at 35.0 ± 0.5 ° C. with a body temperature maintaining device. The nerve activity data was calculated by taking the average value of the firing frequency (pulse / 5 seconds) per 5 seconds every 5 minutes, and expressed as a percentage with the average value (0 minutes value) of 5 minutes before the administration of the cells as 100%. did. The mean ± standard error was calculated from the measured data, and a test for statistical significance as a group was performed by repeated measures analysis of variance. In addition, the test of the statistically significant difference in the absolute value of the electrical activity before the administration of the bacterial cells (0 minute) was performed by the Mann-Whitney U test.
図１１に、皮膚動脈交感神経活動（ｃｕｔａｎｅｏｕｓ ａｒｔｅｒｉａｌ ｓｙｍｐａｔｈｅｔｉｃ ｎｅｒｖｅ ａｃｔｉｖｉｔｙ：ＣＡＳＮＡ）の測定結果を示す。生理食塩水のみを直前に投与した群（以下、「生理食塩水＋ＳＢＬ８８群」という。）では、菌体投与直後からＣＡＳＮＡは徐々に減少していき、菌体投与５５分後には最低値の５３．５％に達した（図１１）。一方、セロトニン受容体５−ＨＴ３に対するアンタゴニストであるＧｒａｎｉｓｅｔｒｏｎを直前に投与した群（以下、「Ｇｒａｎｉｓｅｔｒｏｎ＋ＳＢＬ８８群」という。）では、ＣＡＳＮＡは、菌体投与１０分後に一時的に９５．８％まで減少したものの、その後は徐々に上昇し、菌体投与６０分後には１２８．１％に達し、ＳＢＬ８８株の皮膚動脈交感神経抑制作用が顕著に阻害された（図１１）。 FIG. 11 shows the results of measurement of cutaneous arterial sympathetic nerve activity (CASNA). In the group to which only physiological saline was administered immediately before (hereinafter referred to as “physiological saline + SBL88 group”), CASNA gradually decreased immediately after the administration of bacterial cells, and the minimum value of 53 minutes after administration of bacterial cells was 53 minutes. 0.5% (FIG. 11). On the other hand, in the group to which Granisetron, an antagonist to serotonin receptor 5-HT3, was administered immediately before (hereinafter, referred to as “Granisetron + SBL88 group”), CASNA was temporarily reduced to 95.8% 10 minutes after bacterial cell administration. However, the concentration gradually increased thereafter and reached 128.1% 60 minutes after the administration of the bacterial cells, thereby markedly inhibiting the cutaneous arterial sympathetic nerve-suppressing effect of the SBL88 strain (FIG. 11).
菌体投与５分後から６０分後までの間のＣＡＳＮＡを、生理食塩水＋ＳＢＬ８８群及びＧｒａｎｉｓｅｔｒｏｎ＋ＳＢＬ８８群の２群間で分散分析法により統計学的に検討した結果、Ｇｒａｎｉｓｅｔｒｏｎ＋ＳＢＬ８８群のＣＡＳＮＡは、生理食塩水＋ＳＢＬ８８群のＣＡＳＮＡより有意に（Ｐ＜０．０００５，Ｆ＝４５．８（反復測定分散分析））高かった。また、これら２群の菌体投与前の電気活動（０分値）は、生理食塩水＋ＳＢＬ８８群が２１１±５３（ｓｐｉｋｅｓ／５秒）、Ｇｒａｎｉｓｅｔｒｏｎ＋ＳＢＬ８８群が２５９±１１（ｓｐｉｋｅｓ／５秒）であった。マン・ホイットニーのＵ検定の結果、これら２群の菌体投与前の電気活動（０分値）には、有意差は認められなかった。 As a result of statistically examining CASNA from 5 minutes to 60 minutes after the administration of the bacterial cells between the two groups of physiological saline + SBL88 group and Granisetron + SBL88 group by the analysis of variance method, CASNA of Granisetron + SBL88 group was found to be physiological saline + It was significantly (P <0.0005, F = 45.8 (repeated analysis of variance)) higher than CASNA in the water + SBL88 group. The electrical activity (0 minute value) of the two groups before administration of the bacterial cells was 211 ± 53 (spikes / 5 seconds) for the physiological saline + SBL88 group, and 259 ± 11 (spikes / 5 seconds) for the Granisetron + SBL88 group. Was. As a result of the Mann-Whitney U test, no significant difference was observed in the electrical activity (0 minute value) of these two groups before administration of the bacterial cells.
この結果は、ＳＢＬ８８株の皮膚動脈交感神経抑制作用は、セロトニンを介した作用であることを示している。 This result indicates that the cutaneous artery sympathetic nerve-suppressing effect of SBL88 strain is a serotonin-mediated effect.
Claims (6)
の化合物を有効成分として含有するものを除く。）。 Lactobacillus Buhhineri (Lactobacillus buchneri) lactic acid bacteria belonging to the group, Pediococcus (Pediococcus) lactic acid bacteria belonging to the group, lactic acid bacteria belonging to the La Kutobachirasu plantarum (plantarum) group, Lactobacillus reuteri (reuteri) lactic acid bacteria belonging to the group and Lactobacillus casei ( casei) cells of the strain selected from the lactic acid bacteria or Ranaru belonging to the group or serotonin secretion promoter containing a processed product thereof as an active ingredient (where the following formula (I):
Excluding those containing the compound as an active ingredient. ).
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2012062127 | 2012-03-19 | ||
| JP2012062127 | 2012-03-19 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012203208A Division JP6067292B2 (en) | 2012-03-19 | 2012-09-14 | Serotonin secretion promoter |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2017061567A JP2017061567A (en) | 2017-03-30 |
| JP6664315B2 true JP6664315B2 (en) | 2020-03-13 |
Family
ID=49594622
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012203208A Active JP6067292B2 (en) | 2012-03-19 | 2012-09-14 | Serotonin secretion promoter |
| JP2016248224A Active JP6664315B2 (en) | 2012-03-19 | 2016-12-21 | Serotonin secretagogue |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012203208A Active JP6067292B2 (en) | 2012-03-19 | 2012-09-14 | Serotonin secretion promoter |
Country Status (1)
| Country | Link |
|---|---|
| JP (2) | JP6067292B2 (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP6671652B2 (en) * | 2013-06-13 | 2020-03-25 | 国立研究開発法人産業技術総合研究所 | Body temperature raising agent |
| JP6353478B2 (en) * | 2016-03-28 | 2018-07-04 | 日清食品ホールディングス株式会社 | Bifidobacteria capable of promoting serotonin secretion |
| JP7130220B2 (en) * | 2016-12-28 | 2022-09-05 | 高梨乳業株式会社 | skin moisturizer |
| JP2018104387A (en) * | 2016-12-28 | 2018-07-05 | 高梨乳業株式会社 | Cutaneous arterial sympatholytic agent |
| JP2020048547A (en) * | 2018-09-03 | 2020-04-02 | イチビキ株式会社 | Lactic acid bacteria, and serotonin secretion promoter |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002171933A (en) * | 2000-12-07 | 2002-06-18 | Ko Gijutsu Kenkyusho:Kk | Kimchi essence health food |
| JP2003081808A (en) * | 2001-09-13 | 2003-03-19 | Taiyo Corp | Humectant and cosmetic composition comprising lactic acid fermentation metabolite |
| DE102004039196B4 (en) * | 2004-08-12 | 2008-07-31 | Dr.Kamprad Kg | New formulation for L-tryptophan |
| EP1806134B1 (en) * | 2004-09-17 | 2012-07-11 | Ajinomoto Co., Inc. | Agent and food for preventing/improving functional digestive disorder |
| JP2006094747A (en) * | 2004-09-29 | 2006-04-13 | Ajinomoto Co Inc | Composition and food/drink each having anti-obesity function |
| KR101106077B1 (en) * | 2006-08-10 | 2012-01-18 | 하우스 웰니스 푸드 코퍼레이션 | Moisturizing agent |
| SG182959A1 (en) * | 2007-03-30 | 2012-08-30 | Suntory Holdings Ltd | Medicinal composition, food or drink having effect of enhancing parasympathetic nervous activity |
| SG186003A1 (en) * | 2007-11-15 | 2012-12-28 | Poonsook Lohajoti | Skin moisturizer, blood circulation promoter, and external preparations for the skin containing the skin moisturizer and the blood circulation promoter |
| JP5488949B2 (en) * | 2008-03-28 | 2014-05-14 | 独立行政法人農業・食品産業技術総合研究機構 | Plasminogen activator |
| EP2123168B1 (en) * | 2008-05-16 | 2011-12-21 | Nestec S.A. | Lactobacillus paracasei and weight control |
| JP5923238B2 (en) * | 2010-07-07 | 2016-05-24 | アサヒグループホールディングス株式会社 | Vagus nerve activator |
| JP5967527B2 (en) * | 2012-06-22 | 2016-08-10 | 国立研究開発法人産業技術総合研究所 | Appetite increase and weight gain inhibitor |
-
2012
- 2012-09-14 JP JP2012203208A patent/JP6067292B2/en active Active
-
2016
- 2016-12-21 JP JP2016248224A patent/JP6664315B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| JP2017061567A (en) | 2017-03-30 |
| JP6067292B2 (en) | 2017-01-25 |
| JP2013224287A (en) | 2013-10-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6664315B2 (en) | Serotonin secretagogue | |
| US8492442B2 (en) | Medicinal composition, food or drink having effect of enhancing parasympathetic nervous activity | |
| EP2123168B1 (en) | Lactobacillus paracasei and weight control | |
| KR20200084817A (en) | Novel Lactobacillus rhamnosus strain for preventing or treating obesity and the use thereof | |
| JPWO2008088008A1 (en) | Gastrointestinal dysfunction prevention and / or treatment agent | |
| EP2821073B1 (en) | Agent for use in improving circadian rhythm sleep disorders | |
| CN113543659A (en) | Composition for preventing, ameliorating or treating neurodegenerative disease comprising Pediococcus exodus | |
| JP5254682B2 (en) | Skin property improving agent for oral intake | |
| JP6471145B2 (en) | Autonomic nerve regulator and diurnal rhythm improving agent for sedation | |
| KR20140142170A (en) | Lactobacillus brevis G-101 and its use | |
| JP5967527B2 (en) | Appetite increase and weight gain inhibitor | |
| AU2017287987A1 (en) | Cartilage regeneration facilitating composition | |
| ES2763874B2 (en) | PHASCOLARCTOBACTERIUM FAECIUM FOR USE IN THE PREVENTION AND TREATMENT OF OBESITY AND ITS COMORBIDITIES | |
| TWI731377B (en) | Use of Lactobacillus brevis ProGA28 and its metabolites for the treatment or improvement of sleep disorders | |
| US20240108665A1 (en) | Composition for preventing, alleviating or treating sleep disorders, containing, as active ingredient, gut microbiota or extracellular vesicles derived therefrom | |
| KR20190068068A (en) | Pediococcus acidilactici AO22 strain with Anti-Obesity Ability and Composition for treatment or improvement or preventing of obesity comprising the same | |
| EP3978075A1 (en) | Walking ability improver | |
| KR20220112192A (en) | Composition for preventing, improving or treating sleep disorder comprising an intestinal microorganism or extracellular vesicles derived therefrom as an effective ingredient | |
| JP6671652B2 (en) | Body temperature raising agent | |
| JP2020048547A (en) | Lactic acid bacteria, and serotonin secretion promoter | |
| KR20230160115A (en) | Prevotella histicola KCOM 4081 | |
| KR20230160116A (en) | Prevotella histicola KCOM 3796 | |
| KR20230160117A (en) | Prevotella histicola KCOM 4227 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20161221 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20161222 |
|
| A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20170125 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20170125 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20170808 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20171006 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20180109 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180404 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20180418 |
|
| A912 | Re-examination (zenchi) completed and case transferred to appeal board |
Free format text: JAPANESE INTERMEDIATE CODE: A912 Effective date: 20180518 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190226 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190724 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20200218 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6664315 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |