JPH09227391A - Suppressant for cytolytic activity in alimentary canal - Google Patents
Suppressant for cytolytic activity in alimentary canalInfo
- Publication number
- JPH09227391A JPH09227391A JP8041263A JP4126396A JPH09227391A JP H09227391 A JPH09227391 A JP H09227391A JP 8041263 A JP8041263 A JP 8041263A JP 4126396 A JP4126396 A JP 4126396A JP H09227391 A JPH09227391 A JP H09227391A
- Authority
- JP
- Japan
- Prior art keywords
- bifidobacterium
- cells
- cytolytic activity
- microorganism belonging
- alimentary canal
- 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.)
- Granted
Links
- 230000001461 cytolytic effect Effects 0.000 title claims abstract description 24
- 244000005700 microbiome Species 0.000 claims abstract description 18
- 235000013305 food Nutrition 0.000 claims abstract description 8
- 239000004480 active ingredient Substances 0.000 claims abstract description 7
- 239000003814 drug Substances 0.000 claims abstract description 7
- 230000000813 microbial effect Effects 0.000 claims abstract description 6
- 210000001035 gastrointestinal tract Anatomy 0.000 claims description 13
- 230000000694 effects Effects 0.000 claims description 6
- 230000000968 intestinal effect Effects 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 241000186000 Bifidobacterium Species 0.000 abstract description 23
- 239000001963 growth medium Substances 0.000 abstract description 3
- 238000012258 culturing Methods 0.000 abstract description 2
- 238000002156 mixing Methods 0.000 abstract 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 32
- 210000004027 cell Anatomy 0.000 description 31
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 26
- 239000011780 sodium chloride Substances 0.000 description 16
- 239000000243 solution Substances 0.000 description 16
- 239000011575 calcium Substances 0.000 description 14
- 229910052791 calcium Inorganic materials 0.000 description 13
- 229910052742 iron Inorganic materials 0.000 description 13
- 241001608472 Bifidobacterium longum Species 0.000 description 9
- 229940009291 bifidobacterium longum Drugs 0.000 description 9
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 8
- 210000003743 erythrocyte Anatomy 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 210000004347 intestinal mucosa Anatomy 0.000 description 7
- 229910021642 ultra pure water Inorganic materials 0.000 description 7
- 239000012498 ultrapure water Substances 0.000 description 7
- 235000005911 diet Nutrition 0.000 description 6
- 230000037213 diet Effects 0.000 description 6
- 230000002550 fecal effect Effects 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 241000186015 Bifidobacterium longum subsp. infantis Species 0.000 description 5
- 206010009944 Colon cancer Diseases 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 229940004120 bifidobacterium infantis Drugs 0.000 description 5
- 210000003608 fece Anatomy 0.000 description 5
- 241000186012 Bifidobacterium breve Species 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 229930006000 Sucrose Natural products 0.000 description 4
- 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 4
- 239000003613 bile acid Substances 0.000 description 4
- 235000014113 dietary fatty acids Nutrition 0.000 description 4
- 235000019197 fats Nutrition 0.000 description 4
- 239000000194 fatty acid Substances 0.000 description 4
- 229930195729 fatty acid Natural products 0.000 description 4
- 150000004665 fatty acids Chemical class 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- WLDRFJDGKMTPPV-UHFFFAOYSA-N 1,2-dimethylhydrazine dihydrochloride Chemical compound Cl.Cl.CNNC WLDRFJDGKMTPPV-UHFFFAOYSA-N 0.000 description 3
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
- 241000186016 Bifidobacterium bifidum Species 0.000 description 3
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 3
- 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 229940002008 bifidobacterium bifidum Drugs 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
- 230000002401 inhibitory effect Effects 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 239000002002 slurry Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 241000186018 Bifidobacterium adolescentis Species 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 239000007995 HEPES buffer Substances 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
- 241001465754 Metazoa Species 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 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 2
- 239000008187 granular material Substances 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 230000002101 lytic effect Effects 0.000 description 2
- 235000012054 meals Nutrition 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 239000011812 mixed powder Substances 0.000 description 2
- 235000013923 monosodium glutamate Nutrition 0.000 description 2
- 235000016709 nutrition Nutrition 0.000 description 2
- 230000035764 nutrition Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 239000011833 salt mixture Substances 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229940073490 sodium glutamate Drugs 0.000 description 2
- 235000014214 soft drink Nutrition 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 150000003722 vitamin derivatives Chemical class 0.000 description 2
- RBCOYOYDYNXAFA-UHFFFAOYSA-L (5-hydroxy-4,6-dimethylpyridin-3-yl)methyl phosphate Chemical compound CC1=NC=C(COP([O-])([O-])=O)C(C)=C1O RBCOYOYDYNXAFA-UHFFFAOYSA-L 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 108010076119 Caseins Proteins 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 239000011665 D-biotin Substances 0.000 description 1
- 235000000638 D-biotin Nutrition 0.000 description 1
- 239000004470 DL Methionine Substances 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 206010018910 Haemolysis Diseases 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 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
- MJVAVZPDRWSRRC-UHFFFAOYSA-N Menadione Chemical compound C1=CC=C2C(=O)C(C)=CC(=O)C2=C1 MJVAVZPDRWSRRC-UHFFFAOYSA-N 0.000 description 1
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 235000021068 Western diet Nutrition 0.000 description 1
- FMRLDPWIRHBCCC-UHFFFAOYSA-L Zinc carbonate Chemical compound [Zn+2].[O-]C([O-])=O FMRLDPWIRHBCCC-UHFFFAOYSA-L 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000005273 aeration Methods 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229940037003 alum Drugs 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 235000015197 apple juice Nutrition 0.000 description 1
- 229940054333 biotin 2 mg Drugs 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000037396 body weight Effects 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
- FAPWYRCQGJNNSJ-UBKPKTQASA-L calcium D-pantothenic acid Chemical compound [Ca+2].OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O.OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O FAPWYRCQGJNNSJ-UBKPKTQASA-L 0.000 description 1
- XAAHAAMILDNBPS-UHFFFAOYSA-L calcium hydrogenphosphate dihydrate Chemical compound O.O.[Ca+2].OP([O-])([O-])=O XAAHAAMILDNBPS-UHFFFAOYSA-L 0.000 description 1
- 229960002079 calcium pantothenate Drugs 0.000 description 1
- 235000019577 caloric intake Nutrition 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 239000002775 capsule 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
- 210000005056 cell body Anatomy 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229960004874 choline bitartrate Drugs 0.000 description 1
- QWJSAWXRUVVRLH-UHFFFAOYSA-M choline bitartrate Chemical compound C[N+](C)(C)CCO.OC(=O)C(O)C(O)C([O-])=O QWJSAWXRUVVRLH-UHFFFAOYSA-M 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- FDJOLVPMNUYSCM-UVKKECPRSA-L cobalt(3+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2,7, Chemical compound [Co+3].N#[C-].C1([C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)[N-]\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O FDJOLVPMNUYSCM-UVKKECPRSA-L 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 229940116318 copper carbonate Drugs 0.000 description 1
- 229910000009 copper(II) carbonate Inorganic materials 0.000 description 1
- GEZOTWYUIKXWOA-UHFFFAOYSA-L copper;carbonate Chemical compound [Cu+2].[O-]C([O-])=O GEZOTWYUIKXWOA-UHFFFAOYSA-L 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000002577 cryoprotective agent Substances 0.000 description 1
- 235000015140 cultured milk Nutrition 0.000 description 1
- 235000019854 cupric carbonate Nutrition 0.000 description 1
- 239000011646 cupric carbonate Substances 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 235000006694 eating habits Nutrition 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 235000019985 fermented beverage Nutrition 0.000 description 1
- 229940106305 folic acid 20 mg Drugs 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 235000015203 fruit juice Nutrition 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000021552 granulated sugar Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- SURQXAFEQWPFPV-UHFFFAOYSA-L iron(2+) sulfate heptahydrate Chemical compound O.O.O.O.O.O.O.[Fe+2].[O-]S([O-])(=O)=O SURQXAFEQWPFPV-UHFFFAOYSA-L 0.000 description 1
- 235000021027 japanese diet Nutrition 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 238000002350 laparotomy Methods 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- SCVOEYLBXCPATR-UHFFFAOYSA-L manganese(II) sulfate pentahydrate Chemical compound O.O.O.O.O.[Mn+2].[O-]S([O-])(=O)=O SCVOEYLBXCPATR-UHFFFAOYSA-L 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- FFEARJCKVFRZRR-UHFFFAOYSA-N methionine Chemical compound CSCCC(N)C(O)=O FFEARJCKVFRZRR-UHFFFAOYSA-N 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 235000006109 methionine Nutrition 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
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 235000021590 normal diet Nutrition 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- JLKDVMWYMMLWTI-UHFFFAOYSA-M potassium iodate Chemical compound [K+].[O-]I(=O)=O JLKDVMWYMMLWTI-UHFFFAOYSA-M 0.000 description 1
- 239000001230 potassium iodate Substances 0.000 description 1
- 235000006666 potassium iodate Nutrition 0.000 description 1
- 229940093930 potassium iodate Drugs 0.000 description 1
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 1
- 229910052939 potassium sulfate Inorganic materials 0.000 description 1
- 239000001120 potassium sulphate Substances 0.000 description 1
- 235000011151 potassium sulphates Nutrition 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 108010009004 proteose-peptone Proteins 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229960005055 sodium ascorbate Drugs 0.000 description 1
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- JZRWCGZRTZMZEH-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
- 235000004416 zinc carbonate Nutrition 0.000 description 1
- 239000011667 zinc carbonate Substances 0.000 description 1
- 229910000010 zinc carbonate Inorganic materials 0.000 description 1
Landscapes
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、ビフィドバクテリ
ウム(Bifidobacterium) 属に属する微生物の菌体を有効
成分とする腸管内での細胞溶解活性抑制剤に関する。ま
た、本発明は、ビフィドバクテリウム(Bifidobacteriu
m) 属に属する微生物の菌体を配合して腸管内での細胞
溶解活性抑制作用を賦与した医薬又は飲食品に関する。TECHNICAL FIELD The present invention relates to an agent for suppressing cytolytic activity in the intestinal tract, which comprises, as an active ingredient, cells of a microorganism belonging to the genus Bifidobacterium . The present invention also relates to Bifidobacteriu
m ) The present invention relates to a drug, food or drink, which has been mixed with the cells of a microorganism belonging to the genus to impart a cytolytic activity-suppressing action in the intestinal tract.
【０００２】[0002]
【従来の技術】従来の日本型の食事は、人間にとって理
想的な食事に近いことから世界的に注目されてきてい
る。しかし、近年、日本人の食事は、従来の日本型から
西洋型へと変化してきており、そのことが問題視されて
きている。つまり、西洋型の食事は、一般的に肉や脂肪
が多く、野菜や穀物が少ない高脂肪・低カルシウムであ
るからである。2. Description of the Related Art Conventional Japanese-style meals have received worldwide attention because they are close to ideal meals for humans. However, in recent years, the Japanese diet has been changing from the traditional Japanese style to the Western style, which has been regarded as a problem. In other words, the western diet is high in fat and low in calcium, which is generally high in meat and fat and low in vegetables and grains.
【０００３】先に Lapreらは、高脂肪・低カルシウムの
食事を摂取すると腸管の内容物に含まれる水溶性の胆汁
酸と脂肪酸が共に増加し、この水溶性の胆汁酸と脂肪酸
が界面活性剤として作用するので、腸粘膜を構成する細
胞を破壊すると報告している(Lapre,J.A., De Vries,H.
T., Termont,D.S.M.L., Kleibeuker,J.H., De Vries,E.
G.E. and Van der Meer,R., Cancer Research, vol.53,
pp.248-253, 1993)。なお、 Lapreらは、水溶性の胆汁
酸と脂肪酸の作用について、赤血球の溶血反応を利用し
た細胞溶解活性を測定することにより評価している。[0003] First, Lapre et al. Increased both water-soluble bile acids and fatty acids contained in the contents of the intestinal tract when a high-fat and low-calcium diet was ingested, and these water-soluble bile acids and fatty acids were surfactants. It has been reported that it destroys the cells that make up the intestinal mucosa (Lapre, JA, De Vries, H.
T., Termont, DSML, Kleibeuker, JH, De Vries, E.
GE and Van der Meer, R., Cancer Research, vol.53,
pp.248-253, 1993). Lapre et al. Evaluated the action of water-soluble bile acids and fatty acids by measuring the cytolytic activity using the hemolytic reaction of red blood cells.
【０００４】また、遺伝的素因により大腸癌を発病する
リスクの高い人々においては、高脂肪・低カルシウムの
食事を取り続けることにより腸粘膜の損傷が起こり、大
腸癌を発病するリスクがさらに高まる恐れがあることが
報告されている(Lipkin,M.,Blattner,W.E., Fraumeni,
J.F.Jr., Lynch,H.T., Deschner,E. and Winawer,S.,Ca
ncer Research, vol.43, pp.1899-1904, 1983; Newmar
k,H.L., Lipkin,M. and Maheshwari,N., Journal of Na
tional Cancer Institute, vol.82, pp.491-496, 199
0)。In addition, in people who are at high risk of developing colorectal cancer due to genetic predisposition, there is a risk that the intestinal mucosa may be damaged by continuing to eat a high-fat, low-calcium diet, further increasing the risk of developing colorectal cancer. It has been reported (Lipkin, M., Blattner, WE, Fraumeni,
JFJr., Lynch, HT, Deschner, E. And Winawer, S., Ca
ncer Research, vol.43, pp.1899-1904, 1983; Newmar
k, HL, Lipkin, M. and Maheshwari, N., Journal of Na
tional Cancer Institute, vol.82, pp.491-496, 199
0).
【０００５】このように、高脂肪・低カルシウムの食事
を取ると、腸管の内容物に含まれる水溶性の胆汁酸と脂
肪酸が増加し、腸粘膜が損傷を受け易い腸内環境を誘発
することになる。As described above, when a high-fat, low-calcium diet is taken, the amount of water-soluble bile acids and fatty acids contained in the contents of the intestinal tract is increased, which induces an intestinal environment in which the intestinal mucosa is easily damaged. become.
【０００６】一方、高脂肪・低カルシウムの食事に起因
する腸粘膜の損傷は、カルシウムを大量に経口摂取する
ことにより緩和されることが、前述した Lapreらの報告
から知られている。しかし、その有効なカルシウムの摂
取量は、一日当たり 1,422mgであり、成人一日当りのカ
ルシウム所要量といわれる 600mgの２倍以上を必要とす
るものである。したがって、大量のカルシウムを通常の
食事で摂取し続けるということは困難であり、腸粘膜を
保護するにはカルシウム製剤等に頼らざるを得ないとい
う問題があった。On the other hand, it is known from the above-mentioned report of Lapre et al. That the damage to the intestinal mucosa caused by a high-fat, low-calcium diet can be alleviated by ingesting a large amount of calcium. However, the effective intake of calcium is 1,422 mg per day, which is more than twice as much as 600 mg, which is said to be the daily calcium requirement for adults. Therefore, it is difficult to keep ingesting a large amount of calcium in a normal diet, and there is a problem that a calcium preparation or the like must be used to protect the intestinal mucosa.
【０００７】[0007]
【発明が解決しようとする課題】本発明者らは、上記の
現状を鑑み、食生活を大きく変えることなく、安全に腸
粘膜を保護することができる安価な食品素材を求めて鋭
意研究を進めていたところ、従来より食用として使用さ
れ、安全性が立証されている微生物であるビフィドバク
テリウム・ロンガム(Bifidobacterium longum) の菌体
が腸管内での細胞溶解活性を抑制する作用を有すること
を見出した。そして、ビフィドバクテリウム(Bifidobac
terium) 属に属する微生物であるビフィドバクテリウム
・アドレスセンティス(Bifidobacterium adolescenti
s) 、ビフィドバクテリウム・インファンティス(Bifido
bacterium infantis) 、ビフィドバクテリウム・ビフ
ィダム(Bifidobacterium bifidum)及びビフィドバクテ
リウム・ブレベ(Bifidobacterium breve)の菌体も同様
に腸管内での細胞溶解活性を抑制する作用を有すること
を見出し、本発明を完成するに至った。したがって、本
発明は、ビフィドバクテリウム(Bifidobacterium) 属に
属する微生物の菌体を有効成分とする腸管内細胞溶解活
性抑制剤に関する。また、本発明は、ビフィドバクテリ
ウム(Bifidobacterium) 属に属する微生物の菌体を配合
して腸管内での細胞溶解活性抑制作用を賦与した医薬又
は飲食品に関する。SUMMARY OF THE INVENTION In view of the above situation, the present inventors have conducted earnest research in search of an inexpensive food material capable of safely protecting the intestinal mucosa without significantly changing their eating habits. However, it has been confirmed that the cells of Bifidobacterium longum , which is a microorganism that has been used for food and whose safety has been proved, has an action of suppressing the cytolytic activity in the intestinal tract. I found it. And Bifidobac
terium ) is a microorganism belonging to the genus Bifidobacterium adolescenti
s ), Bifidobacterium infantis (Bifido
bacterium infantis), Bifidobacterium Biff <br/> Idamu (Bifidobacterium bifidum) and have an effect of inhibiting cytolytic activity in Bifidobacterium Burebe (Bifidobacterium breve) intestinal bacteria also similarly The present invention has been completed and the present invention has been completed. Therefore, the present invention relates to an agent for suppressing intestinal cytolytic activity containing a bacterial cell of a microorganism belonging to the genus Bifidobacterium as an active ingredient. The present invention also relates to a medicine or a food or drink in which cells of a microorganism belonging to the genus Bifidobacterium are mixed to impart a cytolytic activity suppressing action in the intestinal tract.
【０００８】[0008]
【課題を解決するための手段】本発明で有効成分として
使用するビフィドバクテリウム(Bifidobacterium) 属に
属する微生物は、発酵乳等のスターターとして使用され
ており、腸管に定着して感染や腐敗の防止、下痢の予防
等に役立っていることが知られている。The microorganisms belonging to the genus Bifidobacterium used as an active ingredient in the present invention are used as a starter for fermented milk and the like, and colonize the intestinal tract to prevent infection and putrefaction. It is known to be useful for prevention and prevention of diarrhea.
【０００９】このビフィドバクテリウム(Bifidobacteri
um) 属に属する微生物の菌体は、例えば、培養基として
合成培地等を使用し、嫌気的条件下で培養した後、遠心
分離等の処理により生菌体を回収し、そのまま利用する
こともできるし、また、この生菌体を洗浄した後、凍結
乾燥等の処理により乾燥菌体として利用することもでき
る。[0009] This Bifidobacteri
The cells of microorganisms belonging to the genus um ) can be used as they are, for example, after culturing under anaerobic conditions using a synthetic medium or the like as a culture medium, and then collecting the viable cells by a treatment such as centrifugation. Alternatively, after the living cells are washed, they can be used as dried cells by a treatment such as freeze-drying.
【００１０】なお、本発明で有効成分として使用するこ
とのできるビフィドバクテリウム(Bifidobacterium) 属
に属する微生物としては、ビフィドバクテリウム・ロン
ガム(Bifidobacterium longum) 、ビフィドバクテリウ
ム・アドレスセンティス(Bifidobacterium adolescent
is) 、ビフィドバクテリウム・インファンティス(Bifid
obacterium infantis) 、ビフィドバクテリウム・ビフ
ィダム(Bifidobacterium bifidum)、ビフィドバクテリ
ウム・ブレベ(Bifidobacterium breve)等を例示するこ
とができる。[0010] As the Bifidobacterium (Bifidobacterium) microorganism belonging to the genus which can be used as an active ingredient in the present invention, Bifidobacterium Ron <br/> gum (Bifidobacterium longum) Bifidobacterium・ Address Sentis (Bifidobacterium adolescent
is ), Bifidobacteria infantis (Bifid
obacterium infantis ), Bifidobacterium bifidum , Bifidobacterium breve, and the like.
【００１１】[0011]
【発明の実施の形態】上記のようにして得られたビフィ
ドバクテリウム(Bifidobacterium) 属に属する微生物の
菌体は、そのまま使用しても良いし、あるいは、乳糖等
の賦形剤を加え、粉剤、錠剤、丸剤、カプセル剤、顆粒
剤等の医薬としても良い。また、各種飲食品、例えば、
清涼飲料水、果汁飲料、発酵飲料、ゼリー、アイスクリ
ーム、ガム、キャンディー等に配合して使用することも
できる。DETAILED DESCRIPTION OF THE INVENTION Cells of a microorganism belonging to Bifidobacterium (Bifidobacterium) genus obtained as described above, it may be used, or an excipient such as lactose is added, The medicine may be a powder, tablets, pills, capsules, granules and the like. Also, various food and drink, for example,
It can also be used by being mixed with soft drinks, fruit juice drinks, fermented drinks, jellies, ice creams, gums, candies and the like.
【００１２】なお、ビフィドバクテリウム(Bifidobacte
rium) 属に属する微生物の菌体に腸管内での細胞溶解活
性抑制作用を発揮させるには、成人の場合、一日当たり
乾燥菌体重量として0.5g〜5gを摂取する必要がある。以
下に実施例を示し、本発明を詳しく説明する。 Bifidobacte
In order for the cells of the microorganism belonging to the genus rium ) to exert the cytolytic activity-suppressing activity in the intestinal tract, it is necessary for adults to ingest 0.5 g to 5 g of dry cell weight per day. Hereinafter, the present invention will be described in detail with reference to Examples.
【００１３】[0013]
【実施例１】表１に組成を示した培地12リットルに、同
様の培地で前培養したビフィドバクテリウム・ロンガム
(Bifidobacterium longum) SBT-2928 (FERM P-10657)
を５重量％接種した後、37℃で16時間、嫌気的条件下で
循環培養して、菌体を増殖させた。なお、この培養は、
6Nアンモニア溶液を断続的に添加することによりpHが6.
5となるよう調整しながら行った。Example 1 Bifidobacterium longum pre-cultured in 12 liters of the medium whose composition is shown in Table 1 in the same medium
(Bifidobacterium longum ) SBT-2928 (FERM P-10657)
After inoculating 5% by weight of the bacterium, the cells were cultivated at 37 ° C. for 16 hours under anaerobic conditions in a circulating culture to grow the cells. In addition, this culture is
The pH was adjusted to 6.by the intermittent addition of 6N ammonia solution.
The adjustment was made so that it became 5.
【００１４】[0014]
【表１】 ─────────────────────────────── プロテオースペプトン（雪印乳業製） 10 (g/リットル) 酵母エキス粉末（アサヒビール薬品製） 10 Ｄ−グルコース 10 リン酸水素二カリウム 5 リン酸二水素カリウム 1 Ｌ−アスコルビン酸ナトリウム 1 ───────────────────────────────[Table 1] ─────────────────────────────── Proteose Peptone (Snow Brand Milk Products Co., Ltd.) 10 (g / l) Yeast Extract powder (manufactured by Asahi Breweries) 10 D-Glucose 10 Dipotassium hydrogen phosphate 5 Potassium dihydrogen phosphate 1 L-Sodium ascorbate 1 ─────────────────── ─────────────
【００１５】培養終了後、この培養液に 0.9％塩化ナト
リウム溶液60リットルを通液して菌体を洗浄し、限外濾
過膜処理して溶液が７リットルとなるまで濃縮した後、
遠心分離(8,000×g 、15分間、４℃) し菌体及び菌体を
含んだスラリーを回収した。そして、菌体を含んだスラ
リーには凍結保護剤として最終濃度１％のグルタミン酸
ナトリウムと最終濃度５％のショ糖を添加し、溶解し
た。そして、菌体とグルタミン酸ナトリウムとショ糖を
溶解したスラリーとを混合し、凍結乾燥した後、粉砕し
てビフィドバクテリウム・ロンガム(Bifidobacterium
longum) の菌体80g を得た。なお、この菌体中の生菌数
は３×1011cfu/g であった。After the completion of the culture, 60 liters of 0.9% sodium chloride solution was passed through this culture medium to wash the cells, which was subjected to ultrafiltration membrane treatment and concentrated until the solution reached 7 liters.
The cells and the slurry containing the cells were collected by centrifugation (8,000 xg, 15 minutes, 4 ° C). Then, sodium glutamate with a final concentration of 1% and sucrose with a final concentration of 5% were added as a cryoprotective agent to the slurry containing the cells and dissolved. Then, the bacterial cells, a slurry in which sodium glutamate and sucrose are dissolved are mixed, freeze-dried, and then pulverized to produce Bifidobacterium longum (Bifidobacterium longum ).
80 g of longum ) cells were obtained. The viable cell count in this cell was 3 × 10 11 cfu / g.
【００１６】[0016]
【実施例２】実施例１と同様の条件で、ビフィドバクテ
リウム・アドレスセンティス(Bifidobacterium adoles
centis) JCM-7046、ビフィドバクテリウム・インファン
ティス(Bifidobacterium infantis) JCM-1210、ビフィ
ドバクテリウム・ビフィダム(Bifidobacterium bifidu
m) JCM-7004 及びビフィドバクテリウム・ブレベ(Bifid
obacterium breve) JCM-7016 を培養し、同様に処理し
て各菌体を得た。Example 2 Under the same conditions as in Example 1, Bifidobacterium adoles
centis ) JCM-7046, Bifidobacterium infantis JCM-1210, Bifidobacterium bifidu
m) JCM-7004 and Bifidobacterium Burebe (Bifid
obacterium breve) JCM-7016 was cultured and treated in the same manner to obtain each microbial cell.
【００１７】[0017]
【試験例１】実施例１及び２で得られたビフィドバクテ
リウム(Bifidobacterium) 属に属する微生物の各菌体を
使用し、動物実験により、腸管内での細胞溶解活性抑制
作用を調べた。[Test Example 1] Using the respective cells of a microorganism belonging to Bifidobacterium (Bifidobacterium) Genus obtained in Example 1 and 2, by animal experiments, was examined cytolytic activity inhibitory effect in the intestinal tract.
【００１８】１，２−ジメチルヒドラジン・２塩酸を体
重１kg当たり40mgとなるよう調整して８週齢のWistar系
雄ラット16匹に皮下注射した。なお、実験動物に１，２
−ジメチルヒドラジン・２塩酸を注射すると大腸癌を発
病し易い遺伝的素因が誘導される。そして、これらのラ
ットを群間において体重が等しくなるように配慮しなが
ら１群８匹の２群に分け、表２に示した飼料を15日間自
由摂取させると共に、イオン交換水も自由摂取させた。
なお、対照飼料及び本発明飼料に配合した脂肪は標準飼
料(American Institute of Nutrition: Journal of Nut
rition, vol.107, pp.1340-1348, 1977)の４倍であり、
対照飼料及び本発明飼料に配合したカルシウムは標準飼
料の 1/5であって、高脂肪・低カルシウムとなってい
る。1,2-Dimethylhydrazine dihydrochloride was adjusted to 40 mg / kg body weight and subcutaneously injected into 16 8-week-old Wistar male rats. In addition, 1, 2
-Injection of dimethylhydrazine dihydrochloride induces a genetic predisposition to develop colon cancer. Then, these rats were divided into two groups of 8 animals in consideration of equal weights among the groups, and the diet shown in Table 2 was freely taken for 15 days, and ion-exchanged water was also freely taken. .
The fat mixed in the control feed and the feed of the present invention is a standard feed (American Institute of Nutrition: Journal of Nut
rition, vol.107, pp.1340-1348, 1977),
The calcium added to the control feed and the feed of the present invention is 1/5 of that of the standard feed, and has high fat and low calcium.
【００１９】そして、15日間の飼育期間中、各群共に体
重増加量及び摂取カロリーに有意差は認められなかっ
た。During the 15-day breeding period, no significant difference was observed in the weight gain and the calorie intake in each group.
【００２０】[0020]
【表２】 ──────────────────────────────────── 対照飼料 本発明飼料 ──────────────────────────────────── カゼイン 20 (重量％) 20 (重量％) ココナツ油 18 18 コーン油 2 2 グルコース 50 49 実施例１及び２で得られた各菌体 − 1 セルロース 5 5 塩類混合 3.5 3.5 ビタミン混合 1 1 ＤＬ−メチオニン 0.3 0.3 重酒石酸コリン 0.2 0.2 ────────────────────────────────────[Table 2] ──────────────────────────────────── Control feed The feed of the present invention ───── ─────────────────────────────── Casein 20 (wt%) 20 (wt%) Coconut oil 18 18 Corn oil 2 2 Glucose 50 49 Cell bodies 1 obtained in Examples 1 and 2-1 Cellulose 55 Salt mixture 3.5 3.5 Vitamin mixture 11 DL-methionine 0.3 0.3 Choline bitartrate 0.2 0.2 ───────────── ────────────────────────
【００２１】また、飼料に配合した塩類混合の組成を表
３に、ビタミン混合の組成を表４にそれぞれ示す。Table 3 shows the composition of the salt mixture added to the feed, and Table 4 shows the composition of the vitamin mixture.
【００２２】[0022]
【表３】 ─────────────────────────── リン酸水素カルシウム・２水和物 12.3 (重量％) 塩化ナトリウム 7.4 塩化カリウム 7.7 炭酸水素カリウム 10.0 硫酸カリウム 5.2 酸化マグネシウム 2.4 硫酸マンガン・５水和物 0.73 硫酸第一鉄・７水和物 0.51 炭酸亜鉛 0.16 炭酸水酸化第二銅・１水和物 0.03 セレン酸ナトリウム・５水和物 0.001 ヨウ素酸カリウム 0.001 クロムミョウバン 0.055 ──────────────────────────────────── ショ糖で全量を 100％とした。[Table 3] ─────────────────────────── Calcium hydrogen phosphate dihydrate 12.3 (wt%) Sodium chloride 7.4 Potassium chloride 7.7 Potassium hydrogen carbonate 10.0 Potassium sulphate 5.2 Magnesium oxide 2.4 Manganese sulphate pentahydrate 0.73 Ferrous sulphate heptahydrate 0.51 Zinc carbonate 0.16 Cupric carbonate hydroxide monohydrate 0.03 Sodium selenate-5 water Japanese 0.001 Potassium iodate 0.001 Chromium alum 0.055 ───────────────────────────────────── Sucrose Was set to 100%.
【００２３】[0023]
【表４】 ────────────────────── ビタミンＥ・アセテート 750IU/100g ビタミンＫ3 5mg/100g ビタミンＢ1 60mg/100g ビタミンＢ2 60mg/100g ビタミンＢ6 70mg/100g ビタミンＢ12 0.1mg/100g Ｄ−ビオチン 2mg/100g 葉酸 20mg/100g パントテン酸カルシウム 160mg/100g ニコチン酸 300mg/100g ────────────────────── ショ糖で全量を100gとした。[Table 4] ────────────────────── Vitamin E / acetate 750IU / 100g Vitamin K 3 5mg / 100g Vitamin B 1 60mg / 100g Vitamin B 2 60mg / 100g Vitamin B 6 70mg / 100g Vitamin B 12 0.1mg / 100g D-Biotin 2mg / 100g Folic Acid 20mg / 100g Calcium Pantothenate 160mg / 100g Nicotinic Acid 300mg / 100g ──────────────── ─────── Sucrose was used to make the total amount 100g.
【００２４】飼料摂取を開始して11〜14日目に、糞を定
量的に回収し、凍結乾燥した後、粉砕した。そして、こ
の粉砕した糞1.2gに超純水 3.6mlを加えてペースト状に
し、37℃で１時間加温した後、遠心分離 (15,000×g 、
10分間) して水溶性画分を分離、回収し、この水溶性画
分の細胞溶解活性を測定した。On the 11th to 14th day after the start of feeding, the feces were quantitatively collected, freeze-dried and then pulverized. Then, 3.6 ml of ultrapure water was added to 1.2 g of the crushed feces to form a paste, which was heated at 37 ° C for 1 hour and then centrifuged (15,000 xg,
After 10 minutes), the water-soluble fraction was separated and collected, and the cytolytic activity of this water-soluble fraction was measured.
【００２５】また、飼育が終了したラットはエーテル麻
酔下で解剖し、大腸遠位部の内容物を回収し、凍結乾燥
して水分（％）を測定した。The rats which had been raised were dissected under ether anesthesia, the contents of the distal part of the large intestine were collected, freeze-dried and the water content (%) was measured.
【００２６】一方、13週齢Wistar系雄ラット１匹をエー
テル麻酔下で開腹し、後大静脈より血液５mlを回収し、
ヘパリン処理した後、遠心分離(1,000×g 、10分間、４
℃)し、上清とバフィコートをパスツールピペットで除
去して残渣を赤血球画分とした。次に、この赤血球画分
に３倍体積量のＮ−２−ヒドロキシエチルピペラジン−
Ｎ’−２−エタンスルホン酸（ＨＥＰＥＳ）緩衝液(pH
7.4、1.5mM ＨＥＰＥＳ及び 0.9％塩化ナトリウム含有)
を添加し、赤血球膜を壊さないよう良く撹拌した後、
遠心分離(1,000×g 、10分間、４℃) し、上層とバフィ
コートを除去するという操作を４回繰り返し、赤血球を
洗浄した。そして、このようにして得られた赤血球に３
倍体積量の 0.9％塩化ナトリウム溶液を添加、混合し、
糞の水溶性画分の細胞溶解活性を測定する際に使用し
た。On the other hand, one 13-week-old Wistar male rat was subjected to laparotomy under ether anesthesia, and 5 ml of blood was collected from the posterior vena cava.
After heparinization, centrifuge (1,000 × g, 10 minutes, 4
C.) and the supernatant and buffy coat were removed with a Pasteur pipette, and the residue was used as the red blood cell fraction. Next, this erythrocyte fraction was mixed with 3-fold volume of N-2-hydroxyethylpiperazine-
N'-2-ethanesulfonic acid (HEPES) buffer (pH
(Contains 7.4, 1.5 mM HEPES and 0.9% sodium chloride)
After adding and stirring well to avoid breaking the red blood cell membrane,
The operation of centrifuging (1,000 × g, 10 minutes, 4 ° C.) and removing the upper layer and buffy coat was repeated 4 times to wash red blood cells. Then, the red blood cells thus obtained have 3
Add and mix double volume of 0.9% sodium chloride solution,
It was used in measuring the cytolytic activity of the fecal water-soluble fraction.
【００２７】糞の水溶性画分の細胞溶解活性を測定する
に際しては、以下のような検体を調製して使用した。 検体１ 糞の水溶性画分 40μl ＋ 0.9％塩化ナトリウム溶液 120μl 検体２ 糞の水溶性画分 80μl ＋ 0.9％塩化ナトリウム溶液 80μl 検体３ 糞の水溶性画分 120μl ＋ 0.9％塩化ナトリウム溶液 40μl 検体４ 糞の水溶性画分 160μl ＋ 0.9％塩化ナトリウム溶液 ０μl 標準検体１ 超純水 ０μl ＋ 0.9％塩化ナトリウム溶液 160μl 標準検体２ 超純水 40μl ＋ 0.9％塩化ナトリウム溶液 120μl 標準検体３ 超純水 80μl ＋ 0.9％塩化ナトリウム溶液 80μl 標準検体４ 超純水 120μl ＋ 0.9％塩化ナトリウム溶液 40μl 標準検体５ 超純水 160μl ＋ 0.9％塩化ナトリウム溶液 ０μl When measuring the cytolytic activity of the water-soluble fraction of feces, the following specimens were prepared and used. Specimen 1 Fecal water-soluble fraction 40 μl + 0.9% sodium chloride solution 120 μl Specimen 2 Fecal water-soluble fraction 80 μl + 0.9% sodium chloride solution 80 μl Specimen 3 Fecal water-soluble fraction 120 μl + 0.9% sodium chloride solution 40 μl Specimen 4 Water-soluble fraction of feces 160 μl + 0.9% sodium chloride solution 0 μl Standard sample 1 ultrapure water 0 μl + 0.9% sodium chloride solution 160 μl Standard sample 2 Ultrapure water 40 μl + 0.9% sodium chloride solution 120 μl Standard sample 3 Ultrapure water 80 μl + 0.9% sodium chloride solution 80 μl Standard sample 4 ultrapure water 120 μl + 0.9% sodium chloride solution 40 μl Standard sample 5 ultrapure water 160 μl + 0.9% sodium chloride solution 0 μl
【００２８】まず、検体１〜４に 0.9％塩化ナトリウム
溶液に混合した赤血球40μl を添加した後、１分間に 1
00回のストロークで振とうしながら37℃で２時間加温し
た。また、検体ブランクとして、糞の水溶性画分 160μ
l と 0.9％塩化ナトリウム溶液40μl を混合したものを
同様に加温した。さらに、標準検体１〜５に 0.9％塩化
ナトリウム溶液に混合した赤血球40μl を添加した後、
同様に加温した。First, 40 μl of erythrocytes mixed with 0.9% sodium chloride solution was added to each of the samples 1 to 4 and then 1 minute per minute.
The mixture was heated at 37 ° C for 2 hours while shaking with 00 strokes. In addition, as a sample blank, the water-soluble fraction of feces 160μ
The mixture of 1 and 40 μl of 0.9% sodium chloride solution was similarly heated. Furthermore, after adding 40 μl of red blood cells mixed with 0.9% sodium chloride solution to the standard samples 1 to 5,
It heated similarly.
【００２９】この加温した検体１〜４、検体ブランク及
び標準検体１〜５をそれぞれ遠心分離 (10,000×g 、５
分間) し、上清を回収した後、この上清 150μl に超純
水６mlを添加し、原子吸光分析機（日立製作所製、180-
80型）で鉄濃度を測定した。The heated samples 1 to 4, the sample blank and the standard samples 1 to 5 were centrifuged (10,000 xg, 5
After collecting the supernatant, add 6 ml of ultrapure water to 150 μl of this supernatant, and use an atomic absorption spectrometer (Hitachi, 180-
The iron concentration was measured by 80 type).
【００３０】そして、以下のような計算により細胞溶解
活性を算出した。 （１）次式により、標準検体１〜５の鉄濃度から標準の
面積を求めた。 標準の面積=(B-A)×1/2 +((B-A)+(C-A))×1/2 +((C-A)+
(D-A))×1/2 +((D-A)+(E-A))×1/2 標準検体１の鉄濃度 (μg/ml) ： A 標準検体２の鉄濃度 (μg/ml) ： B 標準検体３の鉄濃度 (μg/ml) ： C 標準検体４の鉄濃度 (μg/ml) ： D 標準検体５の鉄濃度 (μg/ml) ： EThen, the cytolytic activity was calculated by the following calculation. (1) The standard area was calculated from the iron concentrations of the standard samples 1 to 5 by the following formula. Standard area = (BA) × 1/2 + ((BA) + (CA)) × 1/2 + ((CA) +
(DA)) × 1/2 + ((DA) + (EA)) × 1/2 Standard sample 1 iron concentration (μg / ml): A Standard sample 2 iron concentration (μg / ml): B Standard sample Iron concentration of 3 (μg / ml): C Iron concentration of standard sample 4 (μg / ml): D Iron concentration of standard sample 5 (μg / ml): E
【００３１】（２）次式により、検体１〜４及び検体ブ
ランクの鉄濃度から検体の面積を求めた。 検体の面積=(F-J/4)×1/2 +((F-J/4)+(G-J/2))×1/2 +
((G-J/2)+(H-3J/4)) ×1/2 +((H-3J/4)+(I-J)) ×1/2 検体１の鉄濃度 (μg/ml) ： F 検体２の鉄濃度 (μg/ml) ： G 検体３の鉄濃度 (μg/ml) ： H 検体４の鉄濃度 (μg/ml) ： I 検体ブランクの鉄濃度 (μg/ml) ： J(2) The area of the sample was obtained from the iron concentrations of the samples 1 to 4 and the sample blank by the following equation. Area of sample = (FJ / 4) × 1/2 + ((FJ / 4) + (GJ / 2)) × 1/2 +
((GJ / 2) + (H-3J / 4)) × 1/2 + ((H-3J / 4) + (IJ)) × 1/2 Iron concentration of sample 1 (μg / ml): F sample 2 Iron concentration (μg / ml): G Specimen 3 iron concentration (μg / ml): H Specimen 4 iron concentration (μg / ml): I Specimen blank iron concentration (μg / ml): J
【００３２】（３）次式により、糞の水溶性画分の細胞
溶解活性を求めた。 細胞溶解活性(%)=検体の面積× 100×３×(100／（各群
の大腸内容物の平均水分含量(%)-1)／標準の面積 その結果を表５に示す。(3) The cytolytic activity of the fecal water-soluble fraction was determined by the following formula. Cell lytic activity (%) = area of sample × 100 × 3 × (100 / (average water content (%)-1 of colon contents of each group-1) / standard area) The results are shown in Table 5.
【００３３】[0033]
【表５】 ──────────────────────────────────── 細胞溶解活性 ──────────────────────────────────── 対照群 151±24（％） ビフィドバクテリウム・ロンガム投与群 87±19* ビフィドバクテリウム・アドレスセンティス投与群 90±22* ビフィドバクテリウム・インファンティス投与群 89±15* ビフィドバクテリウム・ビフィダム投与群 92±20* ビフィドバクテリウム・ブレベ投与群 85±18* ──────────────────────────────────── 数値は平均値±標準誤差を示す * 対照群との間に有意差あり（危険率５％以下）[Table 5] ──────────────────────────────────── Cell lytic activity ─────── ───────────────────────────── Control group 151 ± 24 (%) Bifidobacterium longum administration group 87 ± 19 * Fidobacterium addressentis administration group 90 ± 22 * Bifidobacterium infantis administration group 89 ± 15 * Bifidobacterium bifidum administration group 92 ± 20 * Bifidobacterium breve administration group 85 ± 18 * ──────────────────────────────────── Values are mean ± standard error * There is a significant difference (danger rate of 5% or less)
【００３４】本発明の有効成分であるビフィドバクテリ
ウム(Bifidobacterium) 属に属する微生物の各菌体は、
１，２−ジメチルヒドラジン・２塩酸を注射することに
より大腸癌を発病し易い遺伝的素因を誘導し、さらに高
脂肪・低カルシウム飼料を摂取させたラットから***さ
れる糞の水溶性画分の細胞溶解活性を対照群に比べ有意
に低下させることが判った。Each of the bacterial cells of the microorganism belonging to the genus Bifidobacterium, which is the active ingredient of the present invention, is
Injecting 1,2-dimethylhydrazine dihydrochloride induces a genetic predisposition to develop colorectal cancer, and the fecal water-soluble fraction excreted from rats fed a high-fat, low-calcium diet It was found that the cytolytic activity was significantly reduced compared to the control group.
【００３５】[0035]
【実施例３】実施例１で得られたビフィドバクテリウム
・ロンガム(Bifidobacterium longum) の菌体 40gに乳
糖900gとコーンスターチ574gを加え、Ｖ型混合機で混合
し、混合粉末を得た。そして、ヒドロキシプロピルセル
ロース 16gに滅菌精製水 150mlを加えて撹拌し溶解した
溶液とこの混合粉末とを双軸練合機で練合し、押し出し
造粒機で造粒した後、通気乾燥機を使用して60℃で30分
間乾燥することにより整粒し、腸管内での細胞溶解活性
抑制作用を賦与した顆粒状薬剤1,480gを製造した。Example 3 To 40 g of Bifidobacterium longum cells obtained in Example 1, 900 g of lactose and 574 g of corn starch were added and mixed with a V-type mixer to obtain a mixed powder. Then, add 150 ml of sterilized purified water to 16 g of hydroxypropyl cellulose, stir and dissolve the solution and the mixed powder with a twin-screw kneader, and after granulating with an extrusion granulator, use an aeration dryer. Then, the granules were sized by drying at 60 ° C. for 30 minutes to prepare 1,480 g of a granular drug having an inhibitory effect on the cytolytic activity in the intestinal tract.
【００３６】[0036]
【実施例４】実施例１で得られたビフィドバクテリウム
・ロンガム(Bifidobacterium longum) の菌体500g、リ
ンゴ冷凍濃縮果汁25kg、グラニュー糖92kg、リンゴ酸
2.5kg、クエン酸 0.5kg、アップルアロマ３kg及びエッ
センス１kgに水 900kgを加えて混合し溶解することによ
り、腸管内での細胞溶解活性抑制作用を賦与した清涼飲
料 1,000kgを製造した。Example 4 500 g of Bifidobacterium longum cells obtained in Example 1, 25 kg of frozen apple juice concentrate, 92 kg of granulated sugar, malic acid
2.5 kg, 0.5 kg of citric acid, 3 kg of apple aroma and 1 kg of essence were mixed with 900 kg of water and dissolved to produce 1,000 kg of a soft drink having a cytolytic activity suppressing effect in the intestinal tract.
【００３７】[0037]
【発明の効果】ビフィドバクテリウム(Bifidobacteriu
m) 属に属する微生物の菌体は、腸管内での細胞溶解活
性抑制作用を有するので、結果的に腸粘膜を保護する効
果を発揮し、大腸癌等の発病を予防することが期待され
る。EFFECT OF THE INVENTION Bifidobacteriu
Since the cells of the microorganism belonging to the genus m ) have a cytolytic activity-suppressing action in the intestinal tract, they are expected to exert an effect of protecting the intestinal mucosa and prevent the onset of colon cancer, etc. as a result. .
Claims (2)
m) 属に属する微生物の菌体を有効成分とする腸管内細
胞溶解活性抑制剤。1. Bifidobacteriu
m ) An agent for suppressing intestinal cytolytic activity containing a microbial cell belonging to the genus as an active ingredient.
m) 属に属する微生物の菌体を配合して腸管内での細胞
溶解活性抑制作用を賦与した医薬又は飲食品。2. Bifidobacteriu
m ) A drug or food or drink in which cells of a microorganism belonging to the genus are mixed to impart a cytolytic activity suppressing effect in the intestinal tract.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP04126396A JP4852681B2 (en) | 1996-02-28 | 1996-02-28 | Intestinal cytolytic activity inhibitor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP04126396A JP4852681B2 (en) | 1996-02-28 | 1996-02-28 | Intestinal cytolytic activity inhibitor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH09227391A true JPH09227391A (en) | 1997-09-02 |
| JP4852681B2 JP4852681B2 (en) | 2012-01-11 |
Family
ID=12603573
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP04126396A Expired - Fee Related JP4852681B2 (en) | 1996-02-28 | 1996-02-28 | Intestinal cytolytic activity inhibitor |
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| Country | Link |
|---|---|
| JP (1) | JP4852681B2 (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002053472A (en) * | 2000-05-31 | 2002-02-19 | Yakult Honsha Co Ltd | Lipid peroxidation inhibitor |
| JP2006516405A (en) * | 2003-01-31 | 2006-07-06 | プロビ エービー | Novel Bifidobacterium strain having glutamine-producing ability |
| JP2012180288A (en) * | 2011-02-28 | 2012-09-20 | Morinaga Milk Ind Co Ltd | Antimicrobial agent |
| WO2018136617A3 (en) * | 2017-01-18 | 2018-08-23 | Evelo Biosciences, Inc. | Bacteria for treating cancer |
-
1996
- 1996-02-28 JP JP04126396A patent/JP4852681B2/en not_active Expired - Fee Related
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002053472A (en) * | 2000-05-31 | 2002-02-19 | Yakult Honsha Co Ltd | Lipid peroxidation inhibitor |
| JP4624574B2 (en) * | 2000-05-31 | 2011-02-02 | 株式会社ヤクルト本社 | Lipid peroxidation inhibitor |
| JP2006516405A (en) * | 2003-01-31 | 2006-07-06 | プロビ エービー | Novel Bifidobacterium strain having glutamine-producing ability |
| JP2012180288A (en) * | 2011-02-28 | 2012-09-20 | Morinaga Milk Ind Co Ltd | Antimicrobial agent |
| WO2018136617A3 (en) * | 2017-01-18 | 2018-08-23 | Evelo Biosciences, Inc. | Bacteria for treating cancer |
Also Published As
| Publication number | Publication date |
|---|---|
| JP4852681B2 (en) | 2012-01-11 |
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