JP6053466B2 - ストレス性下痢の抑制剤 - Google Patents
ストレス性下痢の抑制剤 Download PDFInfo
- Publication number
- JP6053466B2 JP6053466B2 JP2012252422A JP2012252422A JP6053466B2 JP 6053466 B2 JP6053466 B2 JP 6053466B2 JP 2012252422 A JP2012252422 A JP 2012252422A JP 2012252422 A JP2012252422 A JP 2012252422A JP 6053466 B2 JP6053466 B2 JP 6053466B2
- Authority
- JP
- Japan
- Prior art keywords
- strain
- stress
- diarrhea
- cell
- inhibitor according
- 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
- 206010012735 Diarrhoea Diseases 0.000 title claims description 68
- 239000003112 inhibitor Substances 0.000 title claims description 34
- 241000186606 Lactobacillus gasseri Species 0.000 claims description 35
- 230000000694 effects Effects 0.000 claims description 32
- 241001465754 Metazoa Species 0.000 claims description 24
- 230000000813 microbial effect Effects 0.000 claims description 23
- 230000028327 secretion Effects 0.000 claims description 19
- 235000015140 cultured milk Nutrition 0.000 claims description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
- 239000004480 active ingredient Substances 0.000 claims description 14
- 230000001629 suppression Effects 0.000 claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 235000013305 food Nutrition 0.000 claims description 10
- 230000002401 inhibitory effect Effects 0.000 claims description 10
- 230000001734 parasympathetic effect Effects 0.000 claims description 10
- 108010062745 Chloride Channels Proteins 0.000 claims description 9
- 102000011045 Chloride Channels Human genes 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 9
- 210000001072 colon Anatomy 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 210000001035 gastrointestinal tract Anatomy 0.000 claims description 5
- 210000004197 pelvis Anatomy 0.000 claims 1
- 210000004027 cell Anatomy 0.000 description 63
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 40
- 241000894006 Bacteria Species 0.000 description 34
- 238000011282 treatment Methods 0.000 description 26
- 239000000047 product Substances 0.000 description 22
- 208000024891 symptom Diseases 0.000 description 22
- 239000004310 lactic acid Substances 0.000 description 20
- 235000014655 lactic acid Nutrition 0.000 description 20
- 102100021752 Corticoliberin Human genes 0.000 description 14
- 239000000055 Corticotropin-Releasing Hormone Substances 0.000 description 14
- 230000001954 sterilising effect Effects 0.000 description 13
- 241000700159 Rattus Species 0.000 description 12
- 239000000843 powder Substances 0.000 description 12
- 239000002609 medium Substances 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
- 239000003085 diluting agent Substances 0.000 description 10
- 208000002551 irritable bowel syndrome Diseases 0.000 description 10
- 239000007788 liquid Substances 0.000 description 10
- 239000000546 pharmaceutical excipient Substances 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 238000004659 sterilization and disinfection Methods 0.000 description 10
- 239000000654 additive Substances 0.000 description 9
- 238000000855 fermentation Methods 0.000 description 9
- 230000004151 fermentation Effects 0.000 description 9
- 235000013373 food additive Nutrition 0.000 description 9
- 239000002778 food additive Substances 0.000 description 9
- 235000013376 functional food Nutrition 0.000 description 9
- -1 glycerin fatty acid ester Chemical class 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 230000009471 action Effects 0.000 description 8
- 150000002500 ions Chemical class 0.000 description 8
- 239000000902 placebo Substances 0.000 description 8
- 229940068196 placebo Drugs 0.000 description 8
- 235000019730 animal feed additive Nutrition 0.000 description 7
- 230000001580 bacterial effect Effects 0.000 description 7
- 238000012258 culturing Methods 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 210000005036 nerve Anatomy 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 240000001046 Lactobacillus acidophilus Species 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- 210000002429 large intestine Anatomy 0.000 description 6
- 230000002265 prevention Effects 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 208000018522 Gastrointestinal disease Diseases 0.000 description 5
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 5
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 5
- 210000004921 distal colon Anatomy 0.000 description 5
- 239000000839 emulsion Substances 0.000 description 5
- 239000000796 flavoring agent Substances 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- 230000008991 intestinal motility Effects 0.000 description 5
- 230000037427 ion transport Effects 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 239000013642 negative control Substances 0.000 description 5
- 239000008188 pellet Substances 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 101000957724 Catostomus commersonii Corticoliberin-1 Proteins 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- MCMNRKCIXSYSNV-UHFFFAOYSA-N Zirconium dioxide Chemical compound O=[Zr]=O MCMNRKCIXSYSNV-UHFFFAOYSA-N 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 239000003086 colorant Substances 0.000 description 4
- 235000005911 diet Nutrition 0.000 description 4
- 230000037213 diet Effects 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 229940088598 enzyme Drugs 0.000 description 4
- 230000008035 nerve activity Effects 0.000 description 4
- 230000007383 nerve stimulation Effects 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 241000233866 Fungi Species 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241000186660 Lactobacillus Species 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 230000000996 additive effect Effects 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 239000003899 bactericide agent Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000003995 emulsifying agent Substances 0.000 description 3
- 235000013355 food flavoring agent Nutrition 0.000 description 3
- 235000003599 food sweetener Nutrition 0.000 description 3
- 230000014509 gene expression Effects 0.000 description 3
- 230000000968 intestinal effect Effects 0.000 description 3
- 210000000936 intestine Anatomy 0.000 description 3
- 210000004731 jugular vein Anatomy 0.000 description 3
- 229940039696 lactobacillus Drugs 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 235000013336 milk Nutrition 0.000 description 3
- 239000008267 milk Substances 0.000 description 3
- 210000004080 milk Anatomy 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 239000002438 stress hormone Substances 0.000 description 3
- 239000003765 sweetening agent Substances 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241001134772 Bifidobacterium pseudocatenulatum Species 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
- 206010009900 Colitis ulcerative Diseases 0.000 description 2
- 239000004278 EU approved seasoning Substances 0.000 description 2
- 241000283086 Equidae Species 0.000 description 2
- 241000186673 Lactobacillus delbrueckii Species 0.000 description 2
- 241001407640 Lactobacillus kefiranofaciens subsp. kefirgranum Species 0.000 description 2
- 241000186605 Lactobacillus paracasei Species 0.000 description 2
- 240000006024 Lactobacillus plantarum Species 0.000 description 2
- 235000013965 Lactobacillus plantarum Nutrition 0.000 description 2
- 241000218588 Lactobacillus rhamnosus Species 0.000 description 2
- 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 2
- 241000031670 Saccharopolyspora thermophila Species 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 201000006704 Ulcerative Colitis Diseases 0.000 description 2
- 102000007544 Whey Proteins Human genes 0.000 description 2
- 108010046377 Whey Proteins Proteins 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 230000005784 autoimmunity Effects 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000005018 casein Substances 0.000 description 2
- 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 2
- 235000021240 caseins Nutrition 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000000741 diarrhetic effect Effects 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 235000011194 food seasoning agent Nutrition 0.000 description 2
- 235000020510 functional beverage Nutrition 0.000 description 2
- 239000000417 fungicide Substances 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000003871 intestinal function Effects 0.000 description 2
- 229940072205 lactobacillus plantarum Drugs 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 230000002906 microbiologic effect Effects 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 210000004877 mucosa Anatomy 0.000 description 2
- 201000006417 multiple sclerosis Diseases 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 239000006041 probiotic Substances 0.000 description 2
- 230000000529 probiotic effect Effects 0.000 description 2
- 235000018291 probiotics Nutrition 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 239000003531 protein hydrolysate Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 235000020183 skimmed milk Nutrition 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000000230 xanthan gum Substances 0.000 description 2
- 235000010493 xanthan gum Nutrition 0.000 description 2
- 229920001285 xanthan gum Polymers 0.000 description 2
- 229940082509 xanthan gum Drugs 0.000 description 2
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- 101150007969 ADORA1 gene Proteins 0.000 description 1
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 101150061984 Adcy5 gene Proteins 0.000 description 1
- 101710128948 Adenosine receptor A1 Proteins 0.000 description 1
- 102100033346 Adenosine receptor A1 Human genes 0.000 description 1
- 102100032161 Adenylate cyclase type 5 Human genes 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 102000004881 Angiotensinogen Human genes 0.000 description 1
- 102100033394 Angiotensinogen Human genes 0.000 description 1
- 108090001067 Angiotensinogen Proteins 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 102100023995 Beta-nerve growth factor Human genes 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- 108010022152 Corticotropin-Releasing Hormone Proteins 0.000 description 1
- 208000011231 Crohn disease Diseases 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
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 description 1
- AANLCWYVVNBGEE-IDIVVRGQSA-L Disodium inosinate Chemical compound [Na+].[Na+].O[C@@H]1[C@H](O)[C@@H](COP([O-])([O-])=O)O[C@H]1N1C(NC=NC2=O)=C2N=C1 AANLCWYVVNBGEE-IDIVVRGQSA-L 0.000 description 1
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 241000490229 Eucephalus Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 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 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 241000590002 Helicobacter pylori Species 0.000 description 1
- 101000775478 Homo sapiens Adenylate cyclase type 5 Proteins 0.000 description 1
- 101000732617 Homo sapiens Angiotensinogen Proteins 0.000 description 1
- 101001111439 Homo sapiens Beta-nerve growth factor Proteins 0.000 description 1
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 1
- 101001076292 Homo sapiens Insulin-like growth factor II Proteins 0.000 description 1
- 101000945751 Homo sapiens Leukocyte cell-derived chemotaxin-2 Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 101150088952 IGF1 gene Proteins 0.000 description 1
- 101150002416 Igf2 gene Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 1
- 102100025947 Insulin-like growth factor II Human genes 0.000 description 1
- 241000186840 Lactobacillus fermentum Species 0.000 description 1
- 102000010445 Lactoferrin Human genes 0.000 description 1
- 108010063045 Lactoferrin Proteins 0.000 description 1
- 102100034762 Leukocyte cell-derived chemotaxin-2 Human genes 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- 206010029719 Nonspecific reaction Diseases 0.000 description 1
- 229940123973 Oxygen scavenger Drugs 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 241000286209 Phasianidae Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 238000011530 RNeasy Mini Kit Methods 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 108010073771 Soybean Proteins Proteins 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 239000005862 Whey Substances 0.000 description 1
- 229920002494 Zein Polymers 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- IYKJEILNJZQJPU-UHFFFAOYSA-N acetic acid;butanedioic acid Chemical compound CC(O)=O.OC(=O)CCC(O)=O IYKJEILNJZQJPU-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 229940124415 agent for irritable bowel syndrome Drugs 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 235000020244 animal milk Nutrition 0.000 description 1
- 230000002180 anti-stress Effects 0.000 description 1
- 239000002518 antifoaming agent Substances 0.000 description 1
- 239000000164 antipsychotic agent Substances 0.000 description 1
- 229940005529 antipsychotics Drugs 0.000 description 1
- 239000003699 antiulcer agent Substances 0.000 description 1
- 230000004596 appetite loss Effects 0.000 description 1
- 230000000721 bacterilogical effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 210000005056 cell body Anatomy 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- KXKPYJOVDUMHGS-OSRGNVMNSA-N chondroitin sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](OS(O)(=O)=O)[C@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](C(O)=O)O1 KXKPYJOVDUMHGS-OSRGNVMNSA-N 0.000 description 1
- 230000000112 colonic effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 235000013325 dietary fiber Nutrition 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 208000010643 digestive system disease Diseases 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- PXEDJBXQKAGXNJ-QTNFYWBSSA-L disodium L-glutamate Chemical compound [Na+].[Na+].[O-]C(=O)[C@@H](N)CCC([O-])=O PXEDJBXQKAGXNJ-QTNFYWBSSA-L 0.000 description 1
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 description 1
- 235000013890 disodium inosinate Nutrition 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000002036 drum drying Methods 0.000 description 1
- 208000000718 duodenal ulcer Diseases 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000010304 firing Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 244000005709 gut microbiome Species 0.000 description 1
- 229940037467 helicobacter pylori Drugs 0.000 description 1
- 208000035861 hematochezia Diseases 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
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 229960003943 hypromellose Drugs 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 229940068935 insulin-like growth factor 2 Drugs 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000001678 irradiating effect Effects 0.000 description 1
- CSSYQJWUGATIHM-IKGCZBKSSA-N l-phenylalanyl-l-lysyl-l-cysteinyl-l-arginyl-l-arginyl-l-tryptophyl-l-glutaminyl-l-tryptophyl-l-arginyl-l-methionyl-l-lysyl-l-lysyl-l-leucylglycyl-l-alanyl-l-prolyl-l-seryl-l-isoleucyl-l-threonyl-l-cysteinyl-l-valyl-l-arginyl-l-arginyl-l-alanyl-l-phenylal Chemical compound C([C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 CSSYQJWUGATIHM-IKGCZBKSSA-N 0.000 description 1
- 229940004311 lactobacillus casei rhamnosus Drugs 0.000 description 1
- 229940012969 lactobacillus fermentum Drugs 0.000 description 1
- 235000021242 lactoferrin Nutrition 0.000 description 1
- 229940078795 lactoferrin Drugs 0.000 description 1
- 239000008141 laxative Substances 0.000 description 1
- 229940125722 laxative agent Drugs 0.000 description 1
- 239000006402 liver broth Substances 0.000 description 1
- 235000021266 loss of appetite Nutrition 0.000 description 1
- 208000019017 loss of appetite Diseases 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 210000001809 melena Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 235000013379 molasses Nutrition 0.000 description 1
- 235000013923 monosodium glutamate Nutrition 0.000 description 1
- 239000006872 mrs medium Substances 0.000 description 1
- 239000003471 mutagenic agent Substances 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 125000001477 organic nitrogen group Chemical group 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 235000020200 pasteurised milk Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 235000008476 powdered milk Nutrition 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 235000020185 raw untreated milk Nutrition 0.000 description 1
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000002356 single layer Substances 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
- 229940073490 sodium glutamate Drugs 0.000 description 1
- 235000019830 sodium polyphosphate Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000013322 soy milk Nutrition 0.000 description 1
- 229940001941 soy protein Drugs 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000000470 submucous plexus Anatomy 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000001040 synthetic pigment Substances 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000009777 vacuum freeze-drying Methods 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 235000021119 whey protein Nutrition 0.000 description 1
- 239000005019 zein Substances 0.000 description 1
- 229940093612 zein Drugs 0.000 description 1
Images
Landscapes
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Description
(1) ラクトバチルス・ガセリCP2305株(FERM BP-11331)、その菌体処理物、或いはそれらの混合物、を有効成分として含有することを特徴とする、ストレス性下痢の抑制剤。
(2) 前記CP2305株が、生菌体又は殺菌体である、上記(1)に記載の抑制剤。
(4) ストレスによる骨盤(副交感)神経活動の抑制を阻害する作用を有する、上記(1)〜(3)のいずれかに記載の抑制剤。
(6) 上記(1)〜(5)のいずれかに記載の抑制剤を動物飼料成分と配合して、ストレス性下痢抑制効果を有する動物飼料を製造することを含む、動物飼料の製造方法。
(8) 上記(1)〜(5)のいずれかに記載の抑制剤を含有する食品添加剤又は動物飼料添加剤。
(9) 上記(1)〜(5)のいずれかに記載の抑制剤を食品用の担体、賦形剤又は希釈剤と混合し、場合により食品添加物をさらに混合して、ストレス性下痢抑制効果を有する機能性飲食品を製造することを含む、機能性飲食品の製造方法。
(11) 上記(1)〜(5)のいずれかに記載の抑制剤と、薬学的に許容されうる担体、賦形剤又は希釈剤とを含む、ストレス性下痢を予防、抑制又は治療するための医薬組成物。
<ストレス性下痢の抑制剤>
本発明は、第1の態様により、ラクトバチルス・ガセリCP2305株(FERM BP-11331)(以下、単に「CP2305株」とも称する。)、その菌体処理物、或いはその混合物、を有効成分として含有することを特徴とする、被験体のストレス性下痢の抑制剤を提供する。
CP2305株は、生菌体又は殺菌体のいずれでもよい。
本発明は、第2の態様により、上記抑制剤を含有する食品添加剤又は動物飼料添加剤を提供する。
本発明はさらに、ラクトバチルス・ガセリCP2305株(FERM BP-11331)、その菌体処理物、或いはその混合物、を有効成分として含有することを特徴とする、被験体のストレス性下痢、とりわけ下痢型ストレス性腸障害のストレス性下痢、を予防、抑制(軽減)又は治療するための医薬組成物を提供する。
好ましい投与法は、経口投与又は坐剤投与である。
SD雄ラット(4週齢、日本チャールス・リバー社製)を12時間毎の明暗周期下(8時より12時間点灯)で1週間飼育後、試験菌体配合餌を以下のように3週間自由摂取させた。
a)餌は、オリエンタル酵母株式会社のCRF-1粉末餌を使用した。
b)上記餌(CRF−1)25gに対し、菌数2.0×1010個が含まれる試験菌体の凍結乾燥粉末を配合(餌CRF-1:25gに対し、凍結乾燥粉末0.25g)し、試験菌体配合餌とした。
c)試験菌体配合餌を3週間自由摂取させた。
d)この試験による菌体摂食量はおおよそ2.0×1010個/日と推定された。
e)各群19匹に摂取させた。
3週間後、CRF(Corticotropin Releasing Factor、アナスペック社製、USA)溶液を125μg/kg腹腔内投与し、ストレス性下痢を誘発させ、CRF投与後の100分間の糞便状況を以下に記載する下痢スコアにて評価し、試験菌体のストレス性下痢抑制を評価した。
(a)CRF投与後の100分間の糞便を10分間隔で10回採取する。
(b)各回で採取した糞便の重量をg単位で測定する(各回の糞便重量(i値))。
(c)各回で採取した糞便について、糞便の水分状況及び形状から図8に示す糞便スコア基準により、各回の糞便スコアとして数値化する(各回の糞便スコア(ii値))
(d)各回の糞便重量(i値)×各回の糞便スコア(ii値)を求める。
(e)各回で求めた、糞便重量(i値)×糞便スコア(ii値)の10回分の総和を「下痢スコア」と定義する。
(f)これによって、CRF投与後100分間の糞便状況を評価した。
比較対象とした公知寄託菌株A菌体の結果は、CP2305株と同菌数投与した結果である。また、市販生菌製剤Bの結果は、ヒト1日分の摂取用量の重量をラットの体重換算で、単位体重あたり同量となるよう投与した結果である(図2)。公知寄託菌株A(L. gasseri)及び市販生菌製剤B(L. acidophilus 含む)ではストレス性下痢が抑制されず、CP2305株(生菌体)のみ有意なストレス性下痢の抑制を確認した(図2)。
さらにまた、CRF投与4時間後に解剖を実施し、結腸組織をISOGEN(ニッポンジーン)およびRNeasy Mini Kit(Qiagen,USA)にて総RNAを抽出後、遺伝子発現をRat whole genome ver. 3 (G4847B,Agilent,USA) で網羅的に解析を行った。その結果、プラセボ群でCRF投与後に増加するクロライド・チャネル関連遺伝子を、CP2305株投与群では抑制することを確認した(図3)。従って、CP2305株はクロライドチャネルを抑制し、水分の移動を制御していると考えられる。
SDラット(体重380〜400g、日本SLC社製)を麻酔後、断頭、放血屠殺し、解剖学的基準により遠位結腸(distal colon)を摘出し、実態顕微鏡下で輪走筋および縦走筋層を剥離し、粘膜下神経叢を含む粘膜−粘膜下神経叢標本を作製した。標本を測定面積0.64cm2のUssing chamber(CHM2, WPI, FL, USA)に装着し、標本の粘膜側−漿膜側間に生じる電位差及び短絡電流short-circuit current(ISC)を測定した。1分間に3秒間10mVのコマンドパルスを組織に与え、短絡電流の変化量から膜コンダクタンス(Gt)を算出した。basel ISC およびGtが安定したところで粘膜下神経に電気刺激(25V, duration of 0.5ms, 5Hz, 120s)を行い組織の状態を確認した。その後、試験乳酸菌の菌体または発酵乳の希釈溶液(500μg/ml)を粘膜側に投与し、ISCおよびGtの変化を測定し、神経刺激誘発により発生するCl−/HCO3 −分泌に対する試験物質の影響を評価した。
さらに、ラット大腸(遠位結腸)の神経刺激誘発のイオン輸送に及ぼす菌体のみの影響を評価するために、各種乳酸菌の殺菌体を調製し、投与した結果、CP2305株殺菌体は、公知寄託菌株A(L. gasseri)殺菌体及びL. acidophilus殺菌体と比較し、有意にイオン分泌を顕著に抑制し、下痢抑制に強く寄与していることが示唆された(図5)。
SD系雄ラット(4週齢、株式会社紀和動物製)を12時間毎の明暗周期下(8時より12時間点灯)で1週間飼育後、CP2305株配合餌もしくは未配合対照粉餌を3週間自由摂食させた。実験当日はラットを3時間絶食させた後、ウレタン麻酔し、頚静脈に静脈投与用のカニューレを挿入し、その後、下部大腸を神経支配する骨盤(副交感)神経を銀電極で吊上げ、その電気活動を測定した。測定値が安定した時期にCRF溶液(1μg/kg)を頚静脈投与し骨盤神経の電気活動(PNA)の変化を電気生理学的に測定した。データは5分間毎の5秒あたりの発火頻度の平均値にて解析し、頚静脈投与直前の値(0分値)を100%として百分率で示した。その結果、ストレスホルモン(CRF)投与することで、ラット大腸を神経支配する骨盤(副交感)神経活動が抑制されることを確認した。更にはCP2305株の投与がストレス誘発の骨盤(副交感)神経抑制を阻害することを確認した(図7)。従って、CP2305株の投与により、ストレス時の腸管機能が正常に保たれるものと考えられる。
Claims (10)
- ラクトバチルス・ガセリCP2305株(FERM BP-11331)若しくはその派生株、その菌体処理物、或いはそれらの混合物、を有効成分として含有することを特徴とする、健常人のストレス性下痢の抑制剤。
- 前記CP2305株若しくはその派生株が、生菌体又は殺菌体である、請求項1に記載の抑制剤。
- ストレスによる骨盤(副交感)神経活動の抑制を阻害するための、請求項1又は2に記載の抑制剤。
- 大腸クロライドチャネルを抑制することによって水分分泌を抑制するための、請求項1〜3のいずれか1項に記載の抑制剤。
- ラクトバチルス・ガセリCP2305株(FERM BP-11331)若しくはその派生株、その菌体処理物、或いはそれらの混合物、を有効成分として含有することを特徴とする、腸管での水分過剰分泌抑制剤。
- 前記CP2305株若しくはその派生株が、生菌体又は殺菌体である、請求項5に記載の抑制剤。
- 大腸クロライドチャネルを抑制することによって水分分泌を抑制するための、請求項5又は6に記載の抑制剤。
- 健常人のストレス性腸障害を抑制するための、請求項1〜7のいずれか1項に記載の抑制剤。
- 菌体処理物が、乾燥菌体、破壊菌体、破砕菌体又は発酵乳である、請求項1〜8のいずれか1項に記載の抑制剤。
- 飲食品、動物飼料又は医薬組成物である、請求項1〜9のいずれか1項に記載の抑制剤。
Priority Applications (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2012252422A JP6053466B2 (ja) | 2012-11-16 | 2012-11-16 | ストレス性下痢の抑制剤 |
PCT/JP2013/080930 WO2014077365A1 (ja) | 2012-11-16 | 2013-11-15 | 特定のラクトバチルス・ガセリ株又はその処理物を含有するストレス性腸障害の軽減剤 |
CA2890507A CA2890507A1 (en) | 2012-11-16 | 2013-11-15 | Agent for alleviating stress-induced bowel disorder containing specific lactobacillus gasseri strain or treated product threof |
BR112015010978A BR112015010978A2 (pt) | 2012-11-16 | 2013-11-15 | agente para alívio de distúrbio intestinal induzido por estresse contendo cepa de lactobacillus gasseri específica ou produto tratado da mesma |
CN201380059938.4A CN104797265A (zh) | 2012-11-16 | 2013-11-15 | 含有特定的加氏乳杆菌株或其处理物的压力性肠紊乱的减轻剂 |
EP13854909.2A EP2923704B1 (en) | 2012-11-16 | 2013-11-15 | Stress-induced bowel disorder-relieving agent comprising specific lactobacillus gasseri strain or treatment product thereof |
US14/443,089 US20150283187A1 (en) | 2012-11-16 | 2013-11-15 | Agent for alleviating stress-induced bowel disorder containing specific lactobacillus gasseri strain or treated product thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2012252422A JP6053466B2 (ja) | 2012-11-16 | 2012-11-16 | ストレス性下痢の抑制剤 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2014101282A JP2014101282A (ja) | 2014-06-05 |
JP2014101282A5 JP2014101282A5 (ja) | 2015-07-30 |
JP6053466B2 true JP6053466B2 (ja) | 2016-12-27 |
Family
ID=51024139
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012252422A Active JP6053466B2 (ja) | 2012-11-16 | 2012-11-16 | ストレス性下痢の抑制剤 |
Country Status (1)
Country | Link |
---|---|
JP (1) | JP6053466B2 (ja) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2014101288A (ja) * | 2012-11-16 | 2014-06-05 | Calpis Co Ltd | ストレス性腸障害の抑制剤 |
AU2017287989B2 (en) * | 2016-06-30 | 2024-03-14 | Asahi Group Holdings, Ltd. | Composition for use in improvement of nutritional state |
US11376287B2 (en) | 2016-10-20 | 2022-07-05 | Biofermin Pharmaceutical Co., Ltd. | Agent acting on transcellular ion transporter in intestinal tract, agent for activating chloride channel, agent for preventing or treating renal disease, or agent for promoting defecation |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP4853986B2 (ja) * | 2001-09-20 | 2012-01-11 | 雪印メグミルク株式会社 | 炎症性腸疾患及び過敏性腸症候群の予防・治療剤 |
JP3648233B2 (ja) * | 2003-04-08 | 2005-05-18 | 明治飼糧株式会社 | 飼料組成物 |
JP5923238B2 (ja) * | 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 | 迷走神経活性化剤 |
JP5681533B2 (ja) * | 2011-03-14 | 2015-03-11 | ビオフェルミン製薬株式会社 | 消化管痛の予防又は軽減剤 |
JP2014101288A (ja) * | 2012-11-16 | 2014-06-05 | Calpis Co Ltd | ストレス性腸障害の抑制剤 |
-
2012
- 2012-11-16 JP JP2012252422A patent/JP6053466B2/ja active Active
Also Published As
Publication number | Publication date |
---|---|
JP2014101282A (ja) | 2014-06-05 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2014077365A1 (ja) | 特定のラクトバチルス・ガセリ株又はその処理物を含有するストレス性腸障害の軽減剤 | |
KR101279852B1 (ko) | 골다공증 예방 또는 치료용 조성물 | |
US9468657B2 (en) | Lactic acid bacterium agent for improving lipid metabolism | |
JP6165185B2 (ja) | 乳酸菌又はその処理物を含む脂質代謝及び/又は糖代謝改善剤 | |
KR101473058B1 (ko) | 과민성 대장 증후군 예방 또는 치료용 조성물 | |
US7214370B2 (en) | Prebiotic and preservative uses of oil-emulsified probiotic encapsulations | |
US8846082B2 (en) | Probiotic and preservative uses of oil-emulsified probiotic encapsulations | |
KR101618391B1 (ko) | 높은 옥살산 분해능을 갖는 유산균 | |
KR102146429B1 (ko) | 비피도박테리움 아니말리스 아종 아니말리스 균주 | |
KR101228035B1 (ko) | 신규한 유산균 및 이를 포함하는 당뇨병 예방 및 치료용 조성물 | |
US11376289B2 (en) | Composition and uses thereof | |
JP6214162B2 (ja) | 新規の低温耐性ラクトバチルス・ガセリ株 | |
JP6923883B2 (ja) | 栄養状態改善に使用するための組成物 | |
JP6894097B2 (ja) | 腎性貧血改善用組成物 | |
JP3648233B2 (ja) | 飼料組成物 | |
KR101656208B1 (ko) | 염증 질환 예방 또는 치료용 조성물 | |
US11058733B2 (en) | Active substances of Bifidobacterium lactis GKK2, composition comprising the same and method of promoting longevity using the same | |
JP2023033532A (ja) | 骨格筋遅筋化用組成物 | |
JP6053466B2 (ja) | ストレス性下痢の抑制剤 | |
KR20210143723A (ko) | 내장 통증의 예방 및/또는 치료를 위한 락토콕커스 락티스 균주 | |
JP2014101288A (ja) | ストレス性腸障害の抑制剤 | |
Guo et al. | Comparative evaluation of three Lactobacilli with strain-specific activities for rats when supplied in drinking water | |
AU2015201076B2 (en) | Lipid metabolism-improving agent | |
CN114410547A (zh) | 一株能促进5-htp分泌及缓解抑郁的戊糖乳杆菌lpq1及其应用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20141217 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150616 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20151109 |
|
A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20160129 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20160816 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20161012 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20161101 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20161129 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6053466 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |